Tipar Colaj nr 4 din 2008 final.qxd

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					                                Notes and Comments

The XVth Romanian National Symposium of

             Main topics:
   Neuroendocrinology of aging people
 Hormones and motivations in adolescence
        Neuroendocrine tumors

        Alba Iulia, 5-7 June 2008

                     “Grigore Coculescu” Grant for Neuroendocrinology

            Tumor cells behaviour could be influenced by HIF variations

Ileana R. Botusan
Molecular Medicine and Surgery Dept., Diabetes and Endocrinology Unit, Karolinska
Institute, and Dept of Endocrinology, "Carol Davila" University, Bucharest, Romania

Pituitary tumors are associated with important morbidity due to compression, hormonal
hypersecretion or secondary hypopituitarism. The angiogenic phenotype of the tumors may
play an important role in tumor behavior. Hypoxia inducible factor (HIF), a transcriptional
factor composed of two subunits (and) plays a key role in angiogenesis, activating
proangiogenic factors, such as VEGF. The HIF subunits are critically regulated by oxygen
but also modulated by growth factors.
Aim. To study how HIF expression relates to and influences tumor behaviour in pituitary
Methods. The effects of hypoxia and different growth factors on HIF- stability and function
were performed in vitro, in rat pituitary GH/PRL secreting GH3 cells. The protein
expression was evaluated by Western blot and the function and translocation by luciferase
assay. Evaluation of the expression of target genes was done by quantitative RT-PCR. We
also performed immunohistochemistry (IHC) on 11 pituitary adenomas (both secreting and
clinically not secreting type) looking for the hormonal expression and also for HIF1 , HIF2
and CD31 expression.
Results. We were able to show that both HIF alpha congeners were increased in the GH3
cell line by low oxygen tension (O2=1%) and also by growth factors: IGF1 (100 ng/ml) and
dopamine (400 µM). The transcription activation potency of HIF was also increased as
assessed by transient hypoxia-inducible reporter gene assay and RT-PCR of its target genes.
The incubation of GH3 cells with dopamine in hypoxia led also to an increased angiogenesis
as assessed by the capacity of tube formation. In vivo, both HIF alpha congeners were
expressed in the pituitary adenomas. HIF-2 expression didn't correlate with the angiogenic
phenotype assessed by CD31 (IHC) or indirect by levels of serum VEGF (ELISA).
Conclusion. HIF- subunits are modulated in pituitary cells by oxygen and growth factors.
HIF- variations influence the tumoral cells behavior with a potential different impact on
tumorigenesis of the two alpha subunits (HIF-1 and HIF-2) .

Acknowledment: The author is grateful to the following contributors to the grant results:
Sergiu Bogdan. Catrina, V. Sunkari, O. Savu, Kerstin Brismar working at the Molecular
Medicine and Surgery Dept., Diabetes and Endocrinology Unit, from Karolinska Institute,
Stockholm, Sweden, and M. Coculescu, Institute of Endocrinology, Bucharest, Romania.

                                        ORAL SHORT COMMUNICATIONS

  New biochemical parameters during aging:                             The effect of small dozes of thyroid hormone for
      implications of the homocysteine                                stimulating concentration and memory in patients
           and folate metabolism                                         with euthyroidism and Hashimoto thyroiditis

Mariana Purice 1, Ioan- Horea Ursu1, Valeria Lungu2,                  Daniela Cristina Staicu, Iolanda Gheorghe, Dumitra
Diana Chiper2, Florin Alexiu1                                         Ion, Dan Pereþianu
1C.I Parhon” Institute of Endocrinology, Bucharest,                    SCM “Povernei”, Bucharest
Romania, 2Horia Hulubei National Institute for Physics and
Nuclear Engineering, Magurele, Bucharest, Romania                     Thyroid hormones (levothyroxine) are involved in the
                                                                      process of aging. Hypothyroidism leads to premature,
Homocysteine (Hcy) exists at a critical biochemical intersection in   early coronarian accidents and depression.
the methionine cycle - between S-adenosylmethionine, the              Aim.To analyze if in normothyroidism, thyroid
indispensable ubiquitous methyl donor, and vitamins B12 and           hormones in small doses could improve the
folic acid. Increase in homocysteine (Hcy) levels is a major          concentration capacity and the memory.
consequence of folate deficiency that may have adverse effects on     Methods. Concentration and memory were analyzed
multiple organ systems during aging. A significant correlation has    semi-quantitatively according to of simple
been found between the risk of Alzheimer's disease and high           questionnaires, emerging from WARS score,
plasma levels of homocysteine, as well as low levels of folic acid,   numbered from 0 (no change) to 3 (very altered item).
and vitamins B6 and B12. Folate deficiency and                        Patients. 254 patients with euthyroidism and
hyperhomocysteinemia are also prevalent in elderly post-stroke        Hashimoto thyroiditis, with age between 20-86 years,
patients. These two conditions are strongly and independently         average: 51.38 (SD=15) years, women = 246 and men
associated with the development of brain atrophy.                     = 8; 2. Patients over 65 years: 54, average: 72 years,
Two groups of patients were studied: 1: 15 elderly post-stroke        min: 65, max: 86, Patients under 65 years: 200,
patients; we found a significantly higher concentration of Hcy        average: 46, min: 3 max: 64. The diagnostic of
(17.90 µmol/L) versus control group (9.32 µmol/L). 2: 25 patients     euthyroidism and Hashimoto thyroiditis was
with moderate hypothyroidism, before levothyroxine treatment;         established on specific hormonal tests (FT4, TSH,
we found moderate hyperhomocysteinemia (>12.0 µmol/L) in              ATPO, echography). As treatment, 25 µg/day
68%, borderline values (10-12 µmol/L) in 20% and only 8% had          levothyroxine was administered. The statistical
normal Hcy levels (<10 µmol/L). Mean serum folate (11.9 ng/ml)        analysis was realized by Student test.
was significantly lower in this group versus control (5.9 ng/ml)      Results. The indexes decreased under low-doses of
(P<0.001).Cholesterol, LDL cholesterol were higher but not            levothyroxine for both investigated components and for
statistically significant. Patients of age between 50-70 had basal    all patient groups: total, under 65 years, and over 65
Hcy higher (15.56 µmol/L) versus hypothyroid patients with age        years. Decreases of indexes suggest amelioration of
between 30-50 (10 µmol/L), p<0.001. For the decade 70-80, we          concentration and of memory. The difference is more
found two time higher values Hcy than for patients between 30-50      important for patients under 65 years vs those over 65
years (19.9 µmol/L versus 10 µmol/L). Serum folate was                years. Levothyroxine, in small doses, 25 µg/day, could
significantly lower (p<0.001) than for the control group (5.81        stimulate, on short and medium terms, the capability of
versus 11.9 ng/ml). After three months of folate therapy associated   concentration and the memory.
with levothyroxine, plasma homocysteine decreased from 14.27          In conclusion, an improvement of memory and
µmol/L to 9.38 µmol/L (p<0.001).                                      concentration was noticed after thyroxine therapy, more
In conclusion, high prevalence of hyperhomocysteinemia in             important at younger ages than at older ones. No side
hypothyroid patients represents an argument to associate folate       effects were observed at such small doses.
supplementation to levothyroxine therapy, especially in patients
with other risk factors for cardiovascular disease. Homocysteine
and folic acid can be considered as predictive markers in aging
                                 ORAL SHORT COMMUNICATIONS

     Evolution of the adrenal incidentalomas                Candidate gene approach in genetics of polycystic
                   in the elderly                              ovary syndrome: one step ahead towards the
                                                             genome-wide scanning in European populations
ML Gheorghiu1,2, R Trifanescu1,2,                 Mara
Mangalagiu2, M Coculescu1,2                                 Attaoua R1, Ait El Mkadem S1, Kaouache S 1, Zouaoui
1 “Carol Davila” University of Medicine and                 S1, Radian S2, Hanzu F2, Gheorghiu M2, Fica S2,
Pharmacy, 2 “C.I. Parhon” Institute of Endocrinology,       Coculescu M2 and Grigorescu F1,2
Bucharest, Romania                                          1 Molecular Endocrinology Laboratory (EA 4188),

                                                            IURC, Montpellier, France,2 “Carol Davila” University
Objective. To investigate the evolution of adrenal          of Medicine and Pharmacy, Bucharest, Romania
incidentalomas diagnosed by imaging in aged patients
(> 60 years old), where they have been considered part
of the age-specific biology, as compared to younger         In the latest decades, the candidate gene approach has
adults.                                                     been extensively used to study genetics of complex
Patients and methods. We reviewed the files of 82           conditions such as the polycystic ovary syndrome
consecutive patients with adrenal incidentalomas,           (PCOS). A technological advance in genotyping
hospitalized in 1992 – 2008: group A has 52 patients with
                                                            allows now to screen the entire genome for SNP
incidentally discovered adrenal masses (age 29 – 78
years, 16 aged); group B has 30 patients with suggestive    (single nucleotide polymorphism) variation and
but non-specific symptoms and no relevant hormonal          through case-control association to detect potential
hypersecretion (age 24 – 73, 8 aged). Evaluation included   new genes. The use of genome wide scanning (GWS)
biochemical blood tests, electrolytes, plasma or urine      implies larger populations and more stringent
metanephrines (MN) and normetanephrines, at least 2         conditions for DNA collections, which were recently
tests evaluating cortisol secretion and adrenal computed
                                                            reviewed by NIH. Since 2002 we have started a DNA
tomography (CT).
Results. In group A, hypersecretion was detected in 4/16    collection of women with PCOS from Central Europe
(25%) of aged patients (1 Cushing’s syndrome (CS), 2        (Romania) and performed association for several
subclinical CS, 1 borderline high MN) and in 5/36           genes of insulin resistance. Among these, the FTO
(13.8%) of adult patients: 3 pheochromocytomas, 1           gene genotyped by rs1421085 (T/C) showed no direct
subclinical CS, 1 borderline high MN), p=NS. Adrenal
                                                            role in PCOS but was strongly associated with obesity,
cancer or metastases were recorded in 1/16 (6.2%) in
aged patients and in 6/36 (16.6%) of adults, p=NS.          metabolic syndrome (P < 0.0001, OR 3.2, 95%CI 1.8-
Patients with malignancies and franc hypersecretion (9      5.7) and glucose intolerance. By contrast, the insulin
from group A) were excluded from subsequent analyses.       receptor (IR) gene, although involved in insulin
Sex rate was similar in aged patients (6 M:16F) and         resistance, was strongly associated with the PCOS (P
adults (13 M:36 F); tumors were more frequently             < 0.003, OR 2.78 95%CI 1.3-5.8) and more influential
bilateral in aged patients 10/22 (45%) vs 9/49 (18%),
                                                            on hyperandrogenism and women infertility. Other
p<0.05. Mean tumor size was 2.6 cm, similar in aged
people (0.5 – 4.2 cm, 22% over 4 cm) and in adults          genes such as VNTR of insulin gene and CAPN10
(0.4–8 cm, 16% over 4 cm). Tumor evolution was similar      showed more variable results. We intend to study
in aged and adult patients, after a mean follow-up of 2.2   PCOS population by increasing the sample size, to
(0.5–5.1) years and 3.4 (0.5–9.1) years, respectively,      extend recruitment to other geographical areas and to
p=NS. Stable tumors were recorded in 21/27 (77%)
                                                            collect more detailed demographic and historical data,
adults and in 11/16 (69%) aged patients, while increases
(0.2-0.8 cm, only in tumors < 4 cm) were recorded in        including ethnic components and thus, to move one
15% of adults and 19% of aged patients.                     step ahead toward GWS applications.
Conclusions. Except for a higher prevalence of bilateral
tumors in aged patients, apparently non-functional
adrenal tumors have similar prevalence of “mute”
hormonal hypersecretion and tumor evolution in aged
patients and in adults; therefore, we recommend a similar
management of these tumors in adult and aged patients.

                                  ORAL SHORT COMMUNICATIONS

    Anxious syndrome, cause or effect of iatrogenic                 Sleep architecture in elderly subjects
                Cushing syndrome?
                                                             D. Niculescu
Carmen Barbu1,2, Liudmila Minea 2, Alina Roman 2,            Department of Endocrinology, “Carol Davila”
Roxana Geantã 3, Simona Fica1,2                              University of Medicine and Pharmacy, Bucharest,
1   „Carol Davila” University of Medicine and Pharmacy,      Romania
2 Endocrinology Department, Elias University Hospital, 3

„N.Gh.Lupu” Clinical Hospital, Bucharest, Romania            Sleep in elderly subjects is altered in both quantity
                                                             (insomnia) and quality (fragmented, abnormal sleep
Cushing syndrome is classically associated with              cycles, lower amplitude cerebral waves).
psychological disturbance such as emotional lability and     Aim. To compare sleep architecture in the elderly (age
anxiety. However, anxiety can determinate an iatrogenic      >60 years) vs. young subjects (age <25 years).
Cushing syndrome when it is associated with chronic use      Methods. Sleep duration and efficiency, sleep stages
of high doses of glucocorticoid treatment. We present a      and arousals were compared in 3 groups: group 1
case of a 30 years old young man B.B. examined in our        consisted of normal elderly subjects (6 women and 2
clinic in 2006 when he accused asthenia, weight increase     men, age 64±2 years, body mass index [BMI]=25±2.3
(30 kg in one year), insomnia, anxiety and panic attacks.    kg/m2, apnea-hypopnea index [AHI] 4.3±2.4 events/h);
Clinical examination showed cushingoid features, muscle      group 2 consisted of obese elderly subjects (4 men,
weakness and high blood pressure. Hormonal evaluation        BMI=38.3±3 kg/m 2, age 66±3 years, AHI=50±14
revealed low cortisol and ACTH serum levels with             events/h and group 3 consisted of normal young subjects
normal abdominal and pituitary TC. Our patient had           (7 women and 3 men, age 22±2 years, BMI=22.4±1
iterative surgery for nasal septal deviation, in 1993 and    kg/m2 AHI = 1.2±07 events /h). Sleep architecture was
2003. After the last intervention, he was treated with       assessed by complete polysomnography recorded
Biorinil (0.05g bethamethasone/ 10 ml solution). He          between 10 pm and 6 am. Sleep and respiratory
declared the use of 0.002 g bethamethasone daily,            disturbances were manually staged according to
equivalent of 16 mg Prednisone daily. In the first day of    standard criteria. ANOVA was used for comparison
hospitalization the patient applied the intranasal dose 15   between groups.
times, and accused subfebrility, asthenia, nausea, and       Results. Total sleep time was 5.4±1.5 hours, 5.3±0.8
headache because of decreased dose. DXA examination          hours and 7.1±0.7 hours in group 1, group 2 and group
showed low BMD ( Z-score= - 3.2 DS) at lumbar spine.         3 respectively (p<0.05 for trend). Sleep efficiency was
We stopped Biorinil treatment and began administration       67.5±18.4%, 66.4±5.8% and 88.5±11.9% in group 1,
of Prednisone 20 mg daily with a low decrease of this        group 2 and group 3 respectively (p<0.05 for trend).
dose combined with intermittent ACTH administration.         Stage 1 sleep was significantly increased in elderly
Clinical evolution was favorable with evident clinical       subjects 12.5±8.9% of total sleep time (TST),
and T-score at DXA examination improvement but with          54.5±20.3% and 5.6±2.1 respectively (p<0.05 for
persistence of low cortisol and ACTH serum levels. Our       trend). Slow wave sleep (% of TST) was 16.5±4.2,
patient uses now 5 mg Prednisone daily. Psychological        3.8±5.5 and 22.4±9.5 respectively (p<0.05 for trend).
examination revealed social anxiety, a psychic disease       Rapid eye movement sleep (% of TST) was 16.2±5.7,
manifested with strong discomfort and fear sensation in      6.1±3 and 19.6±6 respectively (p<0.05 for trend).
any situation when the respective person can be exposed      Arousal index (arousals/h) was also significantly
to the another person evaluation. Our patient had a social   increased in older individuals 25.6±18, 58±17 and
problem of nasal obstruction and use of handkerchief in      7±3.2 respectively (p<0.05 for trend).
public, so he was forced to use frequently the intranasal    Conclusions. Sleep arousals play a role in reduced
treatment with Biorinil.                                     sleep duration and abnormal sleep architecture in the
Conclusion. Although the anxiety is classically              elderly. Sleep apnea syndrome is only partially
described as a consequence of hypercortisolism, in our       responsible for this abnormal sleep architecture.
case the anxiety was the determinant factor for
iatrogenic Cushing syndrome.

                                ORAL SHORT COMMUNICATIONS

Somatostatin analogs effects in endocrine tumors            Polyphenols improve the antioxidant status in
                                                             streptozotocin-induced diabetic rat tissues
Simona Galoiu
Department of Endocrinology, "Carol Davila"               Irina Chis1, Marius-Ionut Ungureanu2, Ramona
University of Medicine and Pharmacy, Bucharest            Simedrea 1 , Adriana Muresan1 , Patricia Suteu2 ,
                                                          Adriana Marton 2, Nicoleta Decea1
Somatostatin analogs have long been used in the           1Department   of Physiology, “Iuliu Hatieganu”
therapy of GH secreting pituitary adenomas and other      University of Medicine and Pharmacy, 2Student,
somatostatin receptor positive neuroendocrine tumors.     Faculty of Medicine, “Iuliu Hatieganu” University of
Aim. To determine the impact on glucose metabolism        Medicine and Pharmacy Cluj-Napoca, Romania
and on the heart of the somatostatin analogs used in
Romania, beside the antisecretory and antiproliferative
                                                          Polyphenols are natural compounds which can express
effects. Patients and methods. 17 patients with active
                                                          beneficial effects in health, but also in chronic
acromegaly treated with long acting somatostatin
analogs, admitted in the Department of                    diseases, such as diabetes mellitus. The aim of our
Neuroendocrinology, Institute of Endocrinology,           study is to assess their effects on the oxidative stress in
Bucharest, since 2005 till 2007. They were evaluated      the tissues of diabetic rats.
by serum GH determination- IRMA (sensitivity 0.02         Materials and methods. Two groups of rats, each one
ng/mL), serum IGF1/upper limit of kit for age and sex     consisting of 10 animals, were used in the study. Diabetes
ratio, serum insulin - RIA (sensitivity 1mU/ml) (n=2      was induced in both groups with Streptozotocin, injected
pt), oral glucose tolerance test (OGTT) with glucose,     in a dose of 50 mg/kg. After diabetes was induced, the
GH and insulin determination, echocardiography and        second group received 100 mg/kg polyphenols, by
computed tomography. Results. 7 patients (3 males),       gavage, for a period of 10 days. At the end of this period,
aged 44 +19 years were treated with lanreotide for 6 +    the markers of oxidative stress were assayed in tissue
3 months after unsuccessful surgery and radiotherapy.
                                                          homogenates: thiobarbituric acid reactive substances
Basal GH decreased to normal values (<2.5 ng/ml) in
                                                          (TBARS), carbonylated proteins and hydrogen donor
5/7 patients, most being after minimum 6 months after
radiotherapy. In 3/7 patients, nadir of GH during         capacity.
OGTT decreased to < 1 ng/ml and IGF1/ upper limit         Results. As compared to group I, the levels of TBARS
for age and sex ratio became <1. Tumor diameters did      and carbonylated proteins showed a significant
not change with >25% in neither of patients.              decrease in group II, while hydrogen donor capacity
Lanreotide treatment did not alter basal and post         was higher in group II than in group I.
OGTT serum glucose and insulin level (before              Conclusion. Oxidative stress is present in the tissues
treatment, 5 patients had normal glucose tolerance, 1     of diabetic rats, but, as far as our study revealed, it can
had secondary diabetes mellitus and 1 had impaired        be     positively      influenced      by    polyphenols
glucose tolerance, the last showing normal glucose        administration, which can create the premises of a
tolerance after 6 months of therapy). After 6 months of   therapy that should prevent tissue lesions in the
long acting therapy, the classic echocardiographic
                                                          evolution of diabetes mellitus.
parameters did not significantly change: the left
ventricular mass index decreased with 5%, with no
significant change of ejection fraction or E/A ratio as
an index of diastolic function. Conclusion. six months
of long acting somatostatin analogs therapy showed
antisecretory effect in 5/7 acromegalic patients,
without altering glucose metabolism, with no effect on
tumor diameters or echocardiographic parameters,
probably due to a short duration of treatment.

                                 ORAL SHORT COMMUNICATIONS

 The role of N3, N6 PUFAs in pathogeny and the               Clinical presentation, evolution and outcome of
    treatment of CNS’s degenerative diseses                        macroprolactinomas in adolescence

G.L. Iamandei, Veronica Mocanu, L. Dram, Veronica           R. Trifanescu 1,2, D. Voicu 1, A. Caraghergheopol 1,2, D.
Luca                                                        Hortopan2, A. Dumitrascu 2, L. Radulescu2, S. Adam1,
                                                            M. Coculescu1,2
Pathophysiology, Iasi, Romania                              1“Carol Davila” University of Medicine and Pharmacy,
                                                            2 “C.I. Parhon” Institute of Endocrinology, Bucharest
There are lot of data concerning PUFAs’ implication in
the expression of some genes, activity of some enzymes,
regulation of ionic channels, neurotransmitters, cellular   Aims. To assess clinical presentation and long-term
junction and regulation of membrane fluidity.               effectiveness of therapies in macroprolactinomas in
One of the reasons for the huge importance of PUFAs is      teenagers.     Patients.     150     patients     with
represented by the crucial role of their dietary intake     macroprolactinomas from the Institute of
and consequently the possibility of directly influencing    Endocrinology, Bucharest, were retrospectively
their effects through the diet.                             reviewed: study group A (n=20, 4M:16F, aged 19.25
Epidemiological studies have shown a reduction of the       ± 1 years) - patients diagnosed under 18 years or
risk for some neurodegenerative diseases in the             presenting with primary amenorrhea; control group B
patients with a high content of omega3-PUFAs in the         (n= 124, 55M:69F, aged 34.9 ± 1 years) - diagnosed
diet and the increase of the prevalence of some
                                                            between 18-65 years; control group C (n= 6, 4M:2F,
diseases (ADHD, AD, schizophrenia, major
depression and dementia) in the patients with low           aged 66.2±0.8 years) - diagnosed after 65 years.
blood      levels    of     omega3-PUFAs;         dietary   Methods. Rapid FIA/chemiluminescence assessed
supplementation with omega3-PUFAs improved some             prolactin levels; computed tomography assessed
of those neurodegenerative diseases’ symptoms.              tumor size. Results. Galactorrhoea was more frequent
Decrease of the membranary PUFAs has been proved            (14/20, 70%) in group A as compared with groups B
to have a direct implication in some immune                 (53/124, 42%) and C (1/6, 16.6%), p= 0.02 (c2 test),
impairments of schizophrenia.                               but this finding may reflect gender heterogeneity of
An important quantitative measurement of PUFAs’             the groups. Prevalence of amenorrhoea, visual defects,
implication in the neurodegenerative diseases’              hypopituitarism was similar in the 3 groups. Pre
pathology is the report omega3-PUFA/omega6-PUFA,            diagnosis period was significantly longer in group C
which has been shown to correlate directly to some
                                                            as compared with groups A and B. Prolactin levels
aspects of serotoninergic and catecholaminergic
transmitting in animal models; decrease of this report in   were similar in group A (2333.1±841.3 ng/mL), group
plasma and in red blood cells’ membrane was                 B (1439.5±218.2 ng/mL) and in group C (2206±913.5
associated with depression in some epidemiological          ng/mL), p=NS (Anova). Maximum tumor diameter
studies. Some studies try to establish a connection         was similar irrespective of patients’ age: 2.3±0.3 cm
among the extension of the occidental food habits –         (group A), 2.7±1.1 cm (group B) and 2.6±0.3 cm
fast-food type diet (replacement of omega3-PUFAs            (group C), p=NS (Anova). Cure rate was 5% (1/20) in
from fish and vegetables by omega6-PUFAs from               group A and 4% in group B (5/124); 12/20 patients
cereal oils) and the raise in the prevalence of some        (60%) were controlled on dopamine agonists in group
cognitive disjunctions.                                     A, 95/124 patients (76.7%) in group B and 6/6 cases
Our experiment with Morris tank involved male               (100%) in group C. Resistance to dopamine agonists
Wistar rats that have been fed normally and n3
                                                            treatment was similar: 7/20 patients (35%) in study
enriched diets, and we studied the improvement of
cognitive function, memory and behavior. The results        group A and 24/124 (29.8%) in control group B,
indicated better results for the rats that were fed         p=NS. Surgery was ineffective in teenagers resistant to
omega3-PUFAs supplemented diets comparatively               medical therapy, but 4 out of 6 teenagers submitted to
with the ones that received normal omega6-PUFAs             radiotherapy normalized their prolactin. Conclusion.
diet, suggesting that the administration of omega3-         Macroprolactinomas showed a similar clinical
PUFAs enriched diets can be used in amelioration of         presentation, outcome and response to medical and
the clinical status of patients with degenerative           combined therapy in teenagers, adult and elderly
diseases and also in the prophylaxis of such diseases.      patients.

                                  ORAL SHORT COMMUNICATIONS

Phenotypical details of polycystic ovary syndrome                   Depression in Craniopharyngiomas
     (PCOS) along the reproductive years
                                                            Virginia Rotarescu2, A. V. Ciurea 1
S.Radian1,2, Monica Gheorghiu1,2, Alice Albu 3, Ileana      1 ”Bagdasar-Arseni” Department of Clinical Hospital,

Botusan2,3, Nicoleta Baculescu 1,2, Simona Fica2,3, M.      2 ”Bagdasar-Arseni” Clinical Hospital, Postgraduate

Coculescu 1,2                                               “Carol Davila”, Univesity of Medicine and Pharmacy
1 Institute of Endocrinology C.I. Parhon,2 Department       Bucharest, Romania
of Endocrinology, C Davila Univ. of Medicine,
3Department of Endocrinology, Elias Emergency               Objective. The purpose of this study was to identify
University Hospital, Bucharest, Romania                     neuropsychological             dysfunctions           in
                                                            craniopharyngiomas and to assess life’s quality in
The clinical presentation of PCOS is variable and           terms of efficiency, efficacy and personal
influences its diagnosis. Aim. To examine the age-          satisfactions.
specific characteristics of phenotypic and biochemical      Material and method. 36 patients, between 5 and 58
parameters in a Romanian PCOS cohort, correlated            years old, were evaluated in three sessions (before
with Rotterdam diagnostic criteria. Patients and            operation, after 6 and 12 months after operation) with
methods. 328 PCOS patients and 159 controls were            Wechsler Intelligence Scale for Children/Wechsler
examined, after informed consent. PCOS patients had         Adult Intelligence Scale, Auditory Learning Test
hormonal assays (total testosterone-T, prolactin, TSH,      (Rey)/ Wechsler Memory Scale. This information was
DHEAS and 17-OH Progesterone), glycemia and                 submitted to a statistic informatics processing (SPSS
insulinemia during OGTT and ovarian ultrasound. In          10.05) which is a describing analysis, with central
controls, basal glycemia, insulinemia and T were            tendency and index of variation, correlations and
obtained. Results. Age was significantly lower in           inferences, to take the variability of the study and
PCOS than in controls (25+/-5.67 vs. 28.3+/-6.3 yrs.        synthesize in the following: socio - demographic,
old), but the proportion of young subjects (<18 yrs.        emotional – cognitive and behavioral factors.
old) was similar (12.1% vs. 8.8%) (All parameters are       Results. Neuropsychological assessments show
mean+/-SD). The two groups were not significantly           unaltered IQ at an individual level. Intracranial-
different for BMI, obesity (41.4% vs. 49%) or fasting       hypertension and the localization of the tumor
glycemia. Basal insulinemia and HOMA-IR index               determine attention deficits. The extensive localization
(3.2+/-2.4 vs. 2.4+/-1.7) were significantly higher in      of the tumor shows the deficit of a mental control and
PCOS than in controls. Only acne out of all diagnostic      apathy. Tumor relapse determines psychological
signs was more frequent in young than in adult PCOS         dysfunctions in attention, memory and orientation.
(58.3% vs. 30.7%, p<0.001). Young patients were             The depression depends on the patient’s age and it is
leaner than adult PCOS (BMI=25.65+/-6.3 vs. 28.1+/-         installed at different moments, according to tumor
6.8kg/m2, p=0.024), but had similar HOMA-IR values          relapse.
and incidence of acanthosis nigricans. HOMA-IR              Conclusions. Patient quality of life is dependent on
residuals for BMI were significantly higher in young        tumor localization. Psychological reinsertion is
patients than in adult PCOS (p<0.005). Despite this, 2-     affected by memory dysfunctions, medium intensity of
hour glycemia was higher in adult PCOS (p=0.014).           depression and decrease of the Ego strength. A good
This could be due to age-dependent beta-cell                rehabilitation was recorded for 50% of the patients –
dysfunction in PCOS. Conclusions. Except for a              those who benefit of a psychological preparatory
higher frequency of acne, clinical diagnostic criteria      counseling.
are not different in young PCOS patients. Insulin-
resistance is more severe in this age group, but this has
no impact on glucose homeostasis.

                                 ORAL SHORT COMMUNICATIONS

    Convulsion-endocrine etiology in children               The relationship between thyroid hormones level
                                                              and eating behavior disorders in a group of
Luminita Beldean1, Elena Bouleanu2                                       severely obese patients
1“Lucian Blaga” University, Sibiu, Faculty of
Medicine, 2 Faculty of Psychology                          Anca Sirbu 1,2, Ludmila Minea2, Claudia Lenghen 2,
                                                           Simona Fica 1,2
                                                           1Carol Davila University of Medicine and Pharmacy,
Convulsion is one of major emergencies in children.
Endocrine etiology of convulsions is rare but a correct    2Elias   University Hospital, Bucharest
diagnostic is important for a proper treatment.
Aim. To debate cause of late diagnostic in endocrine       Background. Eating behavior is modulated by the
convulsion in children and to identify common aspects      interrelation between TRH secreting neurons, hunger
in clinical and laboratory tests for diagnostic in         and satiety centers from arcuate nucleus and leptin
hypoparathyroidism cases from Sibiu.                       actions, for which each of these neuronal populations
                                                           express receptors. The aim of our study was to
Methods and materials. Four children with
                                                           evaluate the prevalence of eating disorders in a group
convulsions caused by hypoparathyroidism (now they
                                                           of severely obese patients and to investigate if there is
are 20-22 years old). Clinical data, personal and          a relation between serum levels of TSH, fT4, T3 and
familial history, laboratory tests and other               leptin and the presence of eating disorders.
investigations were considered.                            Patients and methods. Clinical (BMI, blood
Results. Convulsions with different characteristics-       pressure) and biochemical parameters (fasting glucose
one child had only night convulsion, other two cases       and insulin, plasma TSH, fT4, T3, leptin-ELISA, basal
had short tonic or tonico-clonic convulsion in day         cortisol and after 1 mg dexametasone inhibition test)
time, one presented only parestesy. All cases              were recorded in 69 severely obese patients (BMI>35
presented irritability, agitation at age of early          kg/m2). All patients completed the Edinburgh BITE
childhood. Two cases presented complications:              questionnaire to assess the frequency and the intensity
calcification of anterior pole of eyes. Laboratory data:   of eating disorders. A score below 12 points was
                                                           considered normal, between 13 and 23- inadequate
low calcaemia (different level), slightly high
                                                           eating behavior (EB) and above 24- bulimia nervosa
phosphatemia, low parathormone. Diagnostic: clinical
                                                           (BN). Results. 58% of our patients had inadequate
sign was observed in early childhood but the               EB, 6% had features of bulimia nervosa and only 36%
diagnostic of hypoparathyroidism was done 5-15 years       had normal EB. We considered the group of patients
later.                                                     with normal eating behavior and those with abnormal
Discussion. Late etiologic diagnostic of convulsion in     (inadequate or BN) and found no significant
all four children studied is related with incomplete       difference between the two groups regarding BMI,
laboratory tests. All cases had hypocalcaemia but it       waist circumference, cholesterol or triglycerides level,
was considered due to dietary deficiency so                HTA prevalence, fasting glycemia or HOMA-IR.
phosphatemia, and parathormone were not checked.           Patients BITE scores were positively correlated with
Conclusions. Etiological diagnostic and correct            T3 level (r=0.436, p<0.05) and negatively correlated
treatment were late in all four children with              with fT4/T3 (r=-0.56, p<0.01). Patients with abnormal
                                                           EB had higher levels of plasma T3 and lower fT4/T3
hypoparathyroidism. This shows the necessity of a
                                                           ratio. Leptin levels were positively correlated with
careful evaluation in all cases with history of
                                                           BITE scores (r=0.56, p<0.05). We found no relation
convulsion, parestesy associated with hypocalcaemia.       between plasma cortisol levels(basal or after inhibition
                                                           test) and EB. Conclusions. Severely obese patients
                                                           with abnormal EB had higher levels of leptin and T3
                                                           and a lower fT4/T3 ratio. Higher T3 levels may
                                                           explain the lack of BMI difference between these high
                                                           caloric ingesters and obese patients without eating

        Informative abstracts not available                          Plenary Lectures:
   for the following oral short communications:              Neuroendocrinology of Ageing People

  Atypical forms of thyrotoxicosis in the elderly                Neuroendocrinology of Ageing

H Ursu                                                M. Coculescu
Institute of Endocrinology, Bucharest                 “Carol Davila” University of Medicine and Pharmacy,
                                                      “C.I.Parhon” Institute of Endocrinology
     Morenian classical psychodrama and its
        advantages in the group therapy               The theories of ageing involve brain neuroendocrine
                                                      structures, together with some endocrine glands, such
Diana Iamandescu
                                                      as the pituitary and the thyroid, as a trigger of ageing
Romanian Association for Psychodrama                  process aside the stochastic processes as are the
                                                      diffuse cell necrosis and cell apoptosis due to the
     PCOS in adolescent girls - psychological         stress oxidation, telomer shortage, genetic program,
        disturbances and quality of life              etc. There are several interesting problems binding the
                                                      neuroendocrinology with the gerontology: the
                                                      involvment of some hormones, such as insulin/IGF1 in
C. Preda, L. Leustean, C. Cristea, C. Gaspar, M.      the longevity mechanisms;the physiological changes
Turiceanu, C. Vulpoi, E. Zbranca                      of hormone production over 65 years of age (GH,
Univ. of Medicine and Pharmacy “Gr. T. Popa” Iasi     DHEA, testosterone); some comorbidity related to age
                                                      like sleep disturbances in relation to the metabolic
   Vitamin D deficiency and immune status in          syndrome, and especially the tumorigenesis in some
                                                      vital endocrine glands such as the adrenals; and how to
            institutionalized elderly
                                                      use the hormones, neurohormones and analogues in
                                                      anti-ageing therapy. There are consistent data that
V. Mocanu, F. Zugun, R. Haliga, R. Costan, V. Luca,   mutation of the genes of IGF1 and IGF1-receptor
C. Galesanu                                           increases the lifespan in lower species from worms to
Univ. of Medicine and Pharmacy “Gr. T. Popa” Iasi     insects and mice. The KO mice for GH-receptor gene
                                                      (equivalent to Laron syndrome) showed an increased
                                                      lifespan. However, TH genome complexity increases
                                                      toward humans and the impact of candidate genes on
                                                      lifespan becomes smaller.Surprinsingly, in human
                                                      hypopituitarism the longevity is shorter as well as the
                                                      serum levels of IGF1; however, in acromegaly the
                                                      lifespan is also shorter, and the serum level of IGF1 is
                                                      high. The deficiency of GH, testosterone (A.D.A.M.
                                                      syndrome) and DHEA in ageing people is well known.
                                                      However, the serum levels of thyroid hormones is
                                                      similar at various ages, although in myxedema the
                                                      ageing process is accelerated. The sleep duration,
                                                      especially sleep deprivation, is related to the risk for
                                                      obesity and diabetes.The sleep duration is also shorter
                                                      in aged people. In our series (109 subjects ,50 women,
                                                      59 men; age 58±13 years) the CPAP therapy used in
                                                      patients with sleep apnea decreased the sleepness time
                                                      and was associated with an increase in body weight.
                                                      Also our series (n= 53) confirms that the incidence of
                                                      the nonfunctioning, benign, adrenal tumors is related to
                                                      the age, as a characteristic of the biology of ageing, a
                                                      fact which was not noticed in pituitary incidentalomas
                                                      (n=183). The use of this data in anti-ageing therapy has
                                                      not been well established yet, but it is promising.
                                          PLENARY LECTURES

    Controversies in hormonal anti-aging therapy               Endocrine cognitive correlations in women aging

Carmen Georgescu, I. Coman, Georgeta Hazi,                 Olga Ianas1, Dana Manda 1, Susana Vladoiu1, Roxana
Gh. Dragotoiu, Ileana Duncea                               Rosca1, Oana Popa1, Sabina Oros1, Oltea Joja 1,
Department of Endocrinology, Department of Urology         Carmen Iordachescu1, Marcela Covic 2
“Iuliu Hatieganu” University of Medicine and               1 “C.I.Parhon“ Naþional Institute of Endocrinology,
Pharmacy Cluj-Napoca, Romania                              Bucharest, 2 ”Ana Aslan” National Institute of Geriatry and
                                                           Gerontology, Bucharest
Aging is associated with gradual reduction of
testicular endocrine activity (andropause), decreased      Objective. An on-going epidemiological populational study
DHEA/DHEA-S secretion without changes of                   examined hormone balance during aging in women, and -
cortisol/ACTH production (adrenopause) and                 whether there was a difference in endogenous serum hormone
decreased liver and tissue IGF-1 due to diminished
                                                           levels between a postmenopausal women group with
GH        secretion      (somatopause).       GH/IGF-1
hyposecretion is involved in age-related osteoporosis      moderately cognitive impairment and a healthy age-matched
and changes in body composition and metabolism.            women group. Subjects and methods. 163 women aged 25 to 80
Low DHEA concentrations in the elderly have been           years were classified into three groups: (1 ) 124 subjects aged
correlated with increased mortality in men,                55-80 years with moderately cognitive impairment
osteoporosis, atherogenic and diabetogenic effects.        (MMSE<28); (2) 87 age-matched subjects without cognitive
Recent data suggest that late-onset hypogonadism           impairment (MMSE ³ 28); (3-control) 96 healthy subjects under
(LOH) is associated with a proinflammatory state,          44 years. Total morning levels of serum 17-OHP, DHEA,
increasing cardiovascular risk. We enrolled 355 men        DHEAS, androstendion, estradiol, estrone, progesterone,
with erectile dysfunction (ED) as a primary symptom        testosterone, free testosterone, DHT, SHBG, inhibin A and
in a study aiming to evaluate their hormonal status. Of    inhibin B, LH, FSH, Prl, TSH, GH, IGF1, insulin, cortisol and
the 355 men, 59 had low or subnormal total
                                                           thyroid hormones were measured. Results. There was a marked
testosterone (TTe) levels as follows: 27 men with TTe
< 2 ng/ml (group A, mean age 69.5 years) and 32 men        decline of sex steroid metabolism associated with an increase of
with TTe between 2 and 3 ng/ml (group B, mean age          gonadotropins in postmenopausal women. All androgens and
65.1 years). An age-matched group (mean age 66.2           estrogens were significantly decreased (p< 0.001) with no
years) of 21 men with ED and TTe > 3 ng/ml (group          significant change in SHBG levels; gonadotropins (LH, FSH)
C) was considered as the control group. Serum              were significantly increased (p<0.001) Also, metabolic balance
interleukin-6, as a proinflammatory marker, was            was significantly altered. The endocrine changes were
determined by ELISA in all groups. Serum estradiol         associated with a cognitive decline (p=0.01); serum cortisol
levels were significantly different between groups         levels and thyroid hormones showed a minimal overall change
(p=0.01, ANOVA), with the highest levels in group C,       in basal levels with aging. In postmenopausal women with
and were positively related to TTe. Likewise, free         moderately cognitive impairment there was a decrease of serum
testosterone was positively associated with both TTe
                                                           thyroxine level (p=0.006) but no significant differences in
and estradiol, but the association was not statistically
significant. Serum interleukin-6 was significantly         estrogens and androgens levels as compared to the age-matched
higher (p=0.02, ANOVA) in men from groups A                group; however, there was a higher rate in their decline.
(14.2±7.4 pg/ml) and B (12.4±7.0 pg/ml) in comparison      Conclusions. Endocrine deficiencies in postmenopausal
to men from the control group (10.9±5.4 pg/ml),            women include a decrease in the peripheral levels of estrogens
suggesting that LOH may represent a proinflammatory        and androgens with an increase in LH, FSH associated with a
state and that, hypothetically, testosterone replacement   cognitive decline. The moderately cognitive impairment didn’t
treatment may reduce cardiovascular risk associated to     significantly affect mean both sex steroid and gonadotropin
this state. However, the lack of hormonal cut-offs to      levels. Finally, our results emphasize the complexities of
start anti-aging endocrine replacement therapy makes       hormone action, particularly related to estrogens and androgens
hormonal anti-aging therapy controversial, raising the     associated with a cognitive decline during the menopausal and
need for large, prospective studies that may lead to
                                                           postmenopausal years.
clinical guidelines of diagnosis and therapy.
                                                           Acknowledgements. This study was supported by the
                                                           Romanian Academy of Medical Sciences – Ministry of
                                                           Education and Research, CEEX no.100/2006.

                                        PLENARY LECTURES

Testosterone in aged people - sexuality, cognition     Characteristics of aging people – a geriatric point
                                                           of view on Romanian non-endocrine drugs
Voichita Mogos                                         G. Prada
“Gr. Popa”UMF, Iasi, Romania                           “Carol Davila” University of Medicine and Pharmacy,
          Informative abstract not available
                                                       During the last decades a global demographic aging
         Early maturation: phylogeny lessons           phenomenon has developed. Elderly live longer and
                                                       they represent the fastest growing segment of
Mircea Popa                                            population. This trend is more obvious in developing
“C.I Parhon” National Institute of Endocrinology       countries, including Romania. If old people (those 65
Bucharest, Romania                                     years and over) represented 10% of population in
                                                       1990, in 2008 they are more than 15% of the
          Informative abstract not available           Romanian population. In Romanian in 2002 there
                                                       were more than 45,000 people with ages of 90 years
  Is there a neuroendocrinology of osteoporosis?       and over and 310 centenarians. Almost 60% live in
                                                       rural areas and almost 67% are women. The pyramid
Catalina Poiana                                        of ages in Romania is shrinking at the bottom (younger
“Carol Davila” University of Medicine and Pharmacy,    ages) and enlarges at the top (elderly). It is estimated
“C.I. Parhon” Institute of Endocrinology, Bucharest,   that until 2050 the pyramid of ages will be reversed as
Romania                                                compared to the situation in 1990. During 100 years
                                                       (1950-2050) the dependency ratio will change
          Informative abstract not available           dramatically: it will increase very fast especially after
                                                       the year 2000 and this increment will be due to elderly
                                                       people while the contribution of younger generations
                                                       to this ratio will decrease (both as a percentage and in
                                                       actual values). Diseases have specific manifestations
                                                       in old people, and elderly themselves have several
                                                       characteristics. Presentation of diseases in the elderly
                                                       is atypical, silent, late and with fewer symptoms and
                                                       signs. There are four major syndromes that can be the
                                                       clinical presentation of most of the diseases in old
                                                       people: instability, immobility, incontinence and
                                                       intellectual impairment. Elderly have several
                                                       concomitant diseases (6-7 as compared to 3-4 in
                                                       adults). Elderly patients have reduced mobility,
                                                       cognitive impairment and depression. All these
                                                       aspects create specific problems when prescribing and
                                                       using various medicines for elderly.

                                                                 Updates in treatment of obesity
                                                       I. Gh. Totoianu
                                                       “Lucian Blaga” University, Faculty of Medicine,
                                                       Sibiu, Romania
                                                                Informative abstract not available

                                                 PLENARY LECTURES

The bone-brain relationship. Is fat tissue the key?                       Vitamin D insufficiency: fact of fiction

Dumitru D. Brãniºteanu, Corina Gãlesanu                             D. Grigorie, Alina Sucaliuc, Mirela Ivan, Elena
UMF “Gr. Popa”, Iasi
Leptin is a small polypeptide hormone secreted primarily by         “Carol Davila” University of Medicine and
the adipocytes. It controls body weight, gonadal and adrenal        Pharmacy, “C.I. Parhon” Institute of Endocrinology,
function following its binding to a specific receptor located       Bucharest, Romania
in the hypothalamus. Puberty onset appears when a critical
fat tissue mass is reached by children. Obese children start        Vitamin D is essential for both calcium and bone
their puberty earlier than lean children, and leptin secretion      metabolism. Currently, the vitamin D status of an
might play a role in this difference. Gonadal failure induces
                                                                    individual is assessed by measuring the serum
bone loss while obesity prevents it. This raises the possibility
that bone mass, body weight, and gonadal function are               concentrations of 25 hydroxy-vitamin D (25OHD).
regulated by common pathways. Since it is known that obese          Classically, vitamin D deficiency, when prolonged
patients generally have higher bone mineral density (BMD),          and severe, can lead to osteomalacia, a condition
it was supposed that various substances synthesized in the          characterized by insufficient mineralization of the
adipose tissue, such as leptin, might have direct effects upon      osteoid, and almost always associated with secondary
bone turnover. However, as is the case in type II diabetes
patients who show insulin resistance, it appears that obese
                                                                    hyperparathyroidism. Vitamin D insufficiency (VDI)
individuals are resistant to the biologic effects of leptin. This   is a recent disorder receiving intense attention in the
resistance may be due to a partial failure to transport leptin      medical literature, and which definition and clinical
to the central nervous system in obesity. Hypothalamic              relevance are considered controversial by many
leptin-dependent antiosteogenic networks differ from the            experts. Twenty years ago, VDI was defined as a mild
anorexigenic pathways, appearing to be neuronal. Indeed,
                                                                    form of vitamin D deficiency leading to secondary
leptin deficiency results in low sympathetic tone, and genetic
or pharmacological ablation of adrenergic signaling leads to        hyperparathyroidism and consequent loss of bone
a leptin-resistant high bone mass. Beta-adrenergic receptors        mass. A precise definition of VDI requires a standard
on osteoblasts regulate their proliferation, and a beta-            definition of optimal vitamin D status, which is
adrenergic agonist decreases bone mass in leptin-deficient          actually not the case. A recent consensus panel, argued
and wild-type mice while a beta-adrenergic antagonist               for optimal vitamin D serum concentrations clustered
increases bone mass in wild-type and ovariectomized mice,
none of these manipulations affecting body weight. These
                                                                    between 28-32 ng/ml, based on several crirteria : the
studies demonstrate a leptin - dependent sympathetic                level associated with maximal suppression of serum
neuronal regulation of bone formation. Cocaine                      PTH concentrations, with the greatest calcium
amphetamine regulated transcript (CART), a neuropeptide             absorbtion, the highest bone mineral density, reduced
whose expression is controlled by leptin and nearly                 rates of falling, and reduced fracture rates. Based on
abolished in ob/ob mice, inhibits bone resorption by
                                                                    this definition, VDI is quite prevalent both in normal
modulating Rankl expression. Thus leptin controls bone
resorption through, at least, two distinct and antagonistic         population, osteoporosis patients and community-
pathways. This novel adipose tissue-brain-bone regulatory           dwelling elderly. In a recent analysis, based on more
loop describes a mechanism able to overcome the                     than a thousand romanian patients with
deleterious effects of gonadal failure and hypercortisolism         postmenopausal osteoporosis, we found a high
on bone mass, modifying our understanding of bone                   prevalence of both vitamin D deficiency ( 22%) and
remodeling and of osteoporosis. How are these novel
regulatory pathways and the classical autocrine/paracrine
                                                                    insufficiency (60%). This high prevalence makes VDI
regulation contributing to bone remodeling? Conceivably,            a common health problem worldwide. It remains,
leptin and other secreted molecules could regulate bone             however, to be prospectively shown that correction of
mass by affecting the synthesis or the function of local            VDI would produce skeletal benefits.
factors present in the bone microenvironment. Alternatively,
these two pathways may act independently of each other.
The distinction between these two possibilities allowed the
identification of the leptin osteoblastic cell downstream

                                             PLENARY LECTURES

             Plenary Lectures:                                                 Plenary Lectures:
  Hormones and motivation during adolescence                                 Neuroendocrine tumors

   Adolescence and its vulnerability from the                   Role of somatostatine agonists after surgery and
 perspective of neuro-psycho-biological theories               radiosurgery in GH-secreting pituitary adenomas
(Attachment, Resilience, Mentalization and Brain
                 Reward System)                                V. Ciubotaru*, Irina Ogrezeanu*, R. Perin*,
                                                               C. Badiu**, M. Coculescu**, Al.Constantinovici
Iuliana Dobrescu1,2, Florina Rad1,2, Gianina                   *3rd Neurosurgical Department, “Prof. Dr. Bagdasar-
Niculae2, Simona Buzilã2, Lucian Ilie2                         Arseni” Emergency Hospital, Bucharest, Romania **
1 ”CarolDavila”University of Medicine and Pharmacy, 2          “C. I. Parhon” Institute of Endocrinology, Bucharest,
Dept. of Child and Adolescent Psychiatry, „Prof. Dr.           Romania
Alex. Obregia” Hospital , Bucharest                            Surgery is the treatment of choice in GH-secreting
                                                               pituitary adenomas. Tumor invasion in the cavernous
Adolescence, a period of major physics, psychic and            sinuses is often followed by failure to achieve
neurobiological changes, is a time when the child is           complete microsurgical removal. In these cases
extremely vulnerable for the beginning of psychic              stereotactic radiosurgery by gamma-knife (GK) is an
disorders. In this period there are a lot of neurobiological   attractive therapeutic option in order to obtain the
changes, changes in cognitive parameter, myelinization is      arrest of cell proliferation and hormone
finishing, cortical - sub cortical neuronal circuits are in    hypersecretion. Most recent analysis of long-term
full process of development, frontal region are grown-up,      results regarding tumor shrinkage and hormonal
affectivity has quick changes and the steroids change the      effects of gamma knife radiosurgery suggested that
response to social stimulus.                                   consistant efficacy (significant reduction or
In this paper we will present four concepts (neuro-            normalization of hormone secretion) was obtained
psycho-biological constructs) which explain the fail in        after more than 36 months. Cure of acromegaly means
adolescence, in the meaning of the beginning of                biochemical remission, therefore we propose to
psychiatric      disorders:     attachment,      resilience,   analyse the opportunity of medical treatment
mentalization and brain reward system (BRS).                   (somatostatine agonists) as adjuvant therapy to
These concepts can explain the beginning in adolescence        surgery and radiosurgery. The study presents our
of the most frequent psychiatric disorders: depression,        experience in 51 cases of operated and irradiated
conduct disorders, addiction, psychotic disorders and          (Gamma Knife surgery) GH-secreting pituitary
personality disorder. A child with a safe attachment, a        adenomas, in the time interval 2001-2008: non-
resilient child, with a good mentalization and an efficient    invasive microadenomas (4 cases), invasive
BRS is a child who deals with adolescence’s challenges.        microadenomas           (9    cases),     non-invasive
He will have all the abilities that he needs for adaptation,   macroadenomas (1 case), invasive macroadenomas
he will be successful in life’s “problems”, he will know       (37 cases), from a total of 150 cases Gh-secreting
to plan, to organize and solve problems, he will know to       pituitary adenomas operated in our department in the
work in team and to show a “positive mentality”. So he         same time interval. Transsphenoidal approach was
will be a successful adult.                                    used in all the cases, followed by radiosurgery after 1-
                                                               63 months (median 13.3 months) using a Leksell
           Anxiety - premenstrual syndrome.                    Gamma Knife Model C. Volumes of tumoral rests
                Therapeutical options.                         were 1-3 cmc (median 1.3 cmc) in 26 cases; 3.1-6 cmc
                                                               (median 4.6 cmc) in 18 cases and 6.1-15 cmc (median
C. Galesanu                                                    9.6 cmc) in 9 cases. Dose plan aimed at delivering 15-
“Gr. Popa” University of Medicine, Iasi, Romania               25 Gy at 45-60% isodose. Therapeutical strategies of
                    Abstract not available                     introducing Somatuline as adjuvant medical therapy in
   492                                                         individual cases are explained.
                                             POSTER SESSIONS

     Neurobiological implications in cognitive                  Diazoxide therapy as an alternative in a case of
       impairment for depressed patients                          insulinoma with surgical contraindication

Emanuela Stoica Spahiu, D.Marinescu, Elena Albu             Ionela Baciu1, S. Radian1,2, Aurelia Bold 1, Marinela
Neuropsychiatry Clinical Hospital - Craiova                 Serban3, M. Coculescu1,2
                                                            1 “C.I. Parhon” Institute of Endocrinology, 2 Department
The discoveries from the past decades have shown that       of Endocrinology, “C Davila” University of Medicine, 3
depression is mostly associated with cognitive              Department of Cardiology, “C Davila “University. of
impairment, which is correlated with neurobiological        Medicine, Bucharest
changes in depression.                                      Management of insulinoma can be challenging,
Therefore, there have been detected structural and          especially in older patients, with concurrent disease.
functional brain changes, such as: reduction in the         Aim. To present a model-case of difficulty to manage
metabolic activity of the prefrontal cortex, as well as     an insulinoma patient. Case report. We present the
neural atrophy in the prefrontal cortex, and limbic         case of a 67 years old female, an obese
structures such as the hippocampus and amygdala. The        (BMI=35.05kg/m 2) heavy smoker with significant
hippocampal atrophy in depressive disorder could be         coronary heart disease: tri-coronary lesions and PTCA
explained by the toxic effects of glucocorticoids           with drug-eluting stent on LAD, myocardial infarction
hypersecretion due to the hypothalamic-pituitary-           sequelae, hypertension and repeated minor strokes.
adrenal axis alteration that typically occurs in            She was admitted to our unit for loss of consciousness
depression.                                                 episodes, without other signs or symptoms suggestive
Recent studies reported that the chronic administration     of hypoglycemia, despite a glycemia of 22mg/dl.
of cortisol leads to cognitive deficits in normal male      A 2-hours glycemia-insulinemia profile after
volunteers. This deficit appears to be mediated in part     overnight fast showed hypoglycemia (30 to 46mg/dL)
via the frontal lobe, suggesting that this brain area may   with hyper-insulinemia. HbA1c was 4.3%. The patient
be also sensitive to the neurodegenerative effects of       presented stage III chronic renal failure. Abdominal
cortisol.                                                   CT revealed a small tumor in the pancreatic head,
The structural changes to the cerebral levels were          7mm in diameter and bilateral nodular adrenal
highlighted using the help of neuroimagistic                hypertrophy. Chest CT demonstrated an ill-defined
investigations made to a set of depressed patients,         mass in the left superior pulmonary field, possibly a
compared with a control set of patients. At the same        primary lung tumor or a malignant insulinoma.
time, these patients are used to evaluate the degree of     Bronchoscopy could not be performed so CT
cognitive impairment using a set of clinical                monitoring was recommended. Patient management.
intelligence tests.                                         Surgical ablation of the insulinoma could not be
For the patients with depression that were compared         performed due to high cardiovascular risk, therefore
with the control patients, the preliminary results          oral diazoxide was initiated at a 3mg/kg/day dose,
showed for the first category an atrophy to the frontal     divided in three doses. Glycemia levels were
lobe level involved in cognitive processes. These           normalized and stable under therapy. Creatinine levels
results are very important in order to understand the       increased slightly and remained constant afterwards.
mechanisms involved in cognitive impairment for the         Screening for endocrine hypertension detected basal
depressed patients and to find new methods to treat         plasma catecholamines 2.5 times higher than normal,
depression.                                                 suggestive of pheochromocytoma or hypoglycemia-
                                                            induced hypercatecholaminemia. Conclusion. Our
                                                            patient showed a good and prompt response to
                                                            diazoxide therapy. Diazoxide confirms to be an
                                                            efficient alternative to surgery in inoperable
                                                 POSTER SESSIONS

 Pachydermoperiostosis mimicking acromegaly in                       Pituitary apoplexy mimicking tuberculous
     a patient with pituitary microadenoma                                   meningitis - 2 cases reports

Raluca Trifanescu1,2, Ligia Radulescu2, Anda                     Monica Gheorghiu1,2, Mara Mangalagiu2,              D.
Dumitrascu 2, Maria Iacob 2, Denisa Predeteanu1,3, M.            Niculescu1,2, Anda Dumitraºcu2, M. Coculescu1,2
Coculescu 1,2                                                    1“Carol Davila” University, 2 “C. I. Parhon” Institute
1“Carol    Davila” University of Medicine and                    of Endocrinology, Bucharest, Romania
Pharmacy, 2“C.I. Parhon” Institute of Endocrinology,
3”Sf. Maria” Rheumatology Clinics Bucharest.                     Pituitary apoplexy is a well-known clinical syndrome
Aim. To present the pitfalls in the differential diagnosis of    resulting from hemorrhagic infarction associated with
extremities’ enlargement. Patient and methods. V.A.,             a pituitary adenoma. However, the actual presenting
male, 32 years old; GH: radioimmunoassay; PRL, FSH,              conditions may vary and can mimic aseptic
LH: fluoroimmunoassay with Europium; bone imaging:               meningitis. We present here the evolution of two cases
radiographs, pituitary imaging: computed tomography
                                                                 of pituitary apoplexy in a GH-secreting
scan. Case report. Previous medical history of the
                                                                 macroadenoma and a non-functioning pituitary
patient consists in arthritis in small joints at the age of 15
years; at the age of 20, patient presented acromegaloid          macroadenoma respectively mimicking tuberculous
enlargement of feet and hands, without other acromegalic         meningitis. Both patients, a 37 years old female with
features, dental changes, or visual field loss. Clinical         acromegalic features and a 72 years old male,
examination revealed coarsening of facial features, oily         presented with symptoms and sign of meningeal
facial skin with acne, enlargement of fingers and of the         irritation (headache, photophobia, fever) and
toes, clubbing of fingers and toes, paronychial                  oculomotor nerves palsy (palpebral ptosis, diplopia).
thickening. Minimum GH during oral glucose tolerance             The lumbar puncture revealed an aseptic meningitis
test (OGTT) was 0.1 ng/mL, IGF-I was low-normal                  with lymphocytic leukocytosis (63/mmc with 70%
(61.07 ng/mL), excluding acromegaly. Normal                      lymphocytes and 180/mmc with 60% lymphocytes
glycaemias during OGTT and normal HbA1c excluded                 respectively), low CSF glucose levels, 38 mg/dL and
severe resistance to insulin. Serum calcium (9.37 mg/dL),
                                                                 63 mg/dL respectively, and high CSF protein levels,
serum phosphorus (2.5 mg/dL), alkaline phosphatase
                                                                 242 mg/dL and 136 mg/dL respectively, interpreted as
(61.9 IU/L) and PTH (77.15 pg/mL) were normal. The
patient had normal pituitary, thyroid and gonadic axes.
                                                                 a tuberculous meningitis. Antituberculous therapy was
Long bones’ radiographs revealed swelling of                     initiated. The CT scan revealed a 1.8 (tr)/2.1 (v) cm
periarticular tissue, subperiostal new bone formation both       iodophil, heterogeneous hypophyseal tumoral mass
in forearm (with deformation of radios and cubitus) and          suggestive for intratumoral necrosis and a 2.1 (tr)/2.3
in calf bones. Radiographs of hands and feet revealed            (v) cm hypophyseal tumoral mass suggestive for
subluxation of distal phalanges, deformed, thick                 intratumoral hemorrhage. Transsphenoidal surgery
metacarpian and metatarsian bones, narrowing of                  was performed for the non-functioning pituitary
interphalangeal                spaces,             suggesting    macroadenoma. The patients recovered normal ocular
pachydermoperiostosis. CT scan showed a 0.87/0.58                movements. Hypopituitarism persisted in both cases.
pituitary microadenoma. The patient is HLA B 08-44,              Pituitary apoplexy cannot be excluded clinically in a
antiCCP antibodies were negative; colonoscopy showed
                                                                 patient who has headaches and meningism, especially
mucosal erosions and biopsy revealed chronic
                                                                 when neuroophthalmological and endocrine
inflammatory infiltrate, suggestive for an inflammatory
bowel disease, known as a possible association with
                                                                 symptoms are present. Neuroimaging is mandatory.
pachydermoperiostosis. Sulfasalasine and non steroidal
anti inflammatory drugs were started. Conclusion.
pachydermoperiostosis should be considered in patients
with acromegaloid features and normal somatotroph axis,
even in the presence of a pituitary microadenoma.

                                           POSTER SESSIONS

  The study of electrical and vascular cerebral                 Turner Syndrome – Difficulties in height
  activity to a group of chronic alcoholic people                achievement in peripubertal patients

Simona Gusti 1, Adriana Nicolaescu2, Alice Gusti3,        Catalina Poiana1,2, Mara Carsote1, Corina Chirita 2,
Constanta Iliescu4, Carmen Vacaru 4                       D.Hortopan 2, Corina Neamtu 2, Cristina Ene2
1Department   of Physiology, Faculty of Medicine,         1“Carol  Davila” University of Medicine and
University of Medicine and Pharmacy, 2Clinical            Pharmacy, 2“C.I.Parhon” Institute of Endocrinology,
Hospital of Neurology, 3Department of Physiology,         Bucharest, Romania
Faculty of Physical Education and Sport, University of    Turner Syndrome (TS) is a gonadal dysgenesis caused by
Craiova,4Department of Internal Medicine, Rosiorii de     complete or partial loss of a X chromosome. It is an important
                                                          cause of short stature and primary amenorrhea in girls. Short
Vede Hospital
                                                          stature is present in all 45X0 patients, and is caused by the
                                                          lack of a pseudo-autosomal gene, SHOX, located on the short
The authors studied electrical and vascular cerebral      arm of chromosome X. In the peripubertal patients, the major
activity using noninvasive methods: EEG and Doppler       challenges are the treatment of height and the induction of
(D) vascular exploration. We examined clinically and      sexual development, knowing that excess estrogens close the
                                                          growth cartilages. We report a case of TS diagnosed at the age
paraclinically a lot of 45 male patients with chronic
                                                          of 14 years, to whom both growth hormone and estrogen
alcoholism, 25-55 years old. The selected patients        therapy were necessary. On admission, she presented primary
were hospitalized for the first time and they had no      amenorrhea and short stature. The clinical examination
clinical or biological symptoms of liver or nervous       revealed short stature (height – 135 cm), with a squarely
system disorders.                                         shaped chest, high palate, short fourth metatarsal, and
We recorded EEG with a Bioscript 2000. We                 micrognathia. Her Tanner stages were: P1, B2. The hormonal
                                                          profile was: high levels of gonadotrops (FSH – 18 mUI/mL,
determined the systolic and diastolic blood pressure
                                                          LH – 36 mUI/mL), low estradiol (E2 – 20 pg/mL), normal
and the cardiac rate, in clino and orthostatism. We       levels of prolactine, basal growth hormone and insulin like
used a color echo-Doppler Aloka and Angio Power           growth factor 1 (Prl – 15 ng/mL, GH – 0.27 ng/mL, IGF 1 –
with a probe of 4,5 MHz and a color Siemens Sonoline      170 ng/mL). She had normal thyroid function (TSH – 3.52
versa Plus Doppler and Angio Power with a probe of        ìUI/mL, fT4 – 17.89 pM/L) and no sign of thyroid antibodies.
                                                          The renal and cardiac ultrasound scans were normal, and the
7.5 MHz for registration of common carotidian curves.
                                                          pelvic ultrasound revealed only a small right ovary, without
We calculated and statistically processed the D. curves   any uterus or left ovary. The CT of the pelvis showed a similar
parameters to the studied lot and compared them with      aspect. The X-ray of the hand showed open growth cartilages.
a control lot of 40 healthy people who did not consume    The kariotype was 45X0. Based on these, the patient was
alcohol.                                                  diagnosed with TS. Oral estrogen therapy (oral estradiol: 1 mg
We noticed an increase of resistance index with 17%       per day) was started in order to induce sexual development,
                                                          associated with a small dose of levothyroxin (25 µg/day).
explained by the presence of generalized and cerebral
                                                          The menarche did not appear. During the first year of the
hypertonicity (systolic pressure was 110 mmHg and         therapy, she had a growth speed of 0.58 cm per month (height
diastolic pressure discretely increased - 80 mmHg).       gain of 7 cm in one year). Her Tanner stages were P2, B3. The
On the EEG we remarked theta waves with an                pelvic ultrasound showed an uterus and small ovaries. The X-
incidence of 12%(insignificant correlation r= 0.24,       Ray of the left hand showed open growth cartilages. The
                                                          estrogen therapy was stopped and the patient was started on
with systolic speed) to the 5% of studied lot. On
                                                          growth hormone therapy (1.5 mg per day, s.c.). After 6
Computer Tomography (CT) we remarked a cortical           months, her growth speed was 0.34 cm per month (height gain
unilateral atrophy to the 85% of studied lot.             2 cm in 6 months). One year later estrogen therapy was added
                                                          (oral estradiol 1 mg per day). The growth after the initiation of
                                                          growth hormone therapy was relatively disappointing,
                                                          probably because it was initiated at older age. The estrogen
                                                          therapy in low dose was used in order to induce sexual
                                                          development and to increase the peak bone mass. The timing
                                                          of each kind of therapy is still a challenging issue.

                                            POSTER SESSIONS

 A newborn with ambigous genitalia - case report              P450 oxidoreductase deficiency - an exquisite
                                                                form of congenital adrenal hyperplasia
Corina Lichiardopol, E Coletã, F Mixich, M Gheonea,
A Georgescu, O Neacºu, A Vîlcu                             Corina Lichiardopol, C Busuioc, S Bondari, N Florea,
                                                           M Bãcãnoiu, F Mixich
UMF Craiova, Romania
                                                           UMF Craiova, Romania
Genital anomalies occur in 1:4500 births and despite
the progress made over understanding the genetic           Recently a novel variant of congenital adrenal
basis of human sexual development a specific               hyperplasia caused by P450 oxidoreductase deficiency
molecular diagnosis can be established in only 20% of      was described, which associates skeletal
the cases. In 46,XX individuals genital ambiguity          malformations and genital ambiguity in both sexes but
appears in cases with ovotesticular and testicular         with unprogressive virilization in females.
disorders of sex development and in hyperandrogenic        A 46,XX patient with ambiguous genitalia (Prader
states of fetal, fetoplacental and maternal origin.        IV), nonpalpable gonads, microcephaly, retrognathia,
A newborn with ambiguous genitalia (Stage IV               pear-shaped nose, hypertelorism, short stature,
Prader) was delivered at term by cesarean section with     underwent genitoplasty was reassured as female at the
weight and length under the 25th percentile (2810g and     age of 10 years. At the age of 12.5 years she presented
47cm). Karyotype was 46,XX and hormonologic                with absent pubertal signs, short stature (-5.43SD),
assessment revealed: high ACTH 90 pg/mL, high              underweight (-2.7SD), delayed bone age, prepubertal
progesterone 60ng/mL, very high 17OHP above                internal genitalia and pituitary hypoplasia.
20ng/mL, high testosterone 0.66 ng/mL and normal           Hormonologic assessment: cortisol 14 µg/dL
gonadotropin levels – LH 0.6 mUI/mL and FSH 0.46           (stimulated 37.5 µg/dL), 17OHP 0.48 ng/mL
mUI/mL. Clinical and hormonologic data were                (stimulated 0.65 ng/mL), DHEAS 63.76 µg/dL
consistent with 21 hydroxylase deficiency – classical      (stimulated 67.11 µg/dL), progesterone 0.05 ng/mL
variant – which is responsible for the majority of cases   (stimulated 0.581 ng/mL), ACTH 16.4 pg/mL,
with ambiguous genitalia in 46,XX individuals.             testosterone 0.02 ng/mL, estradiol 24.55 pg/mL, FSH
                                                           3.5 mUI/mL (stimulated 8.6 mUI/mL), LH 2.6
                                                           mUI/mL (stimulated 5.2 mUI/mL), GH= 0.11 ng/mL
                                                           (stimulated 0.78 ng/ml).
                                                           POR mutations (7q11.2) affect 21 hydroxylase, 17
                                                           hydroxylase and aromatase activities and prove the
                                                           existence of an alternative foetal pathway in human
                                                           androgen synthesis which explains female virilization
                                                           despite the low levels of androgens.

                                            POSTER SESSIONS

  CYP21A1P deletions and nonclassic congenital                  Precocious puberty in a kindred with 11α
            adrenal hyperplasia                                          hidroxylase deficiency

Corina Lichiardopol*, A Zimmermann**, E Schulze**          Corina Lichiardopol, C Busuioc, M Popescu, N
                                                           Florea, M Bãcãnoiu, F Mixich
*UMF Craiova **University of Heidelberg, Germany
                                                           UMF Craiova, Romania
The nonclassical form of 21 hydroxylase deficiency
occurs with an incidence of 1:100 to 1:500 and is          11α hydroxylase deficiency is responsible of 5-8%
characterized by postnatal androgen excess in both         congenital adrenal hyperplasia cases. Its classic
sexes. CYP21A2 mutations are not identified in 20%         variant results in virilization of the external genitalia in
cases suggesting the involvement of regulatory             females and postnatal virilization with precociuos
regions. Recently, mutations in the CYP21A2                pseudopuberty, accelerated somatic growth and
promoter were described in 11.7% of such cases.            advanced bone age leading to final short stature in
CYP21A2 gene and 400bp upstream were sequenced             both sexes. Accumulation of mineralcorticoid
from peripheral leukocytes genomic DNA in 8 female         precursors generates hypertension.
patients with nonclassical 21 hydroxylase deficiency       A 46,XX patient was born with ambiguous genitalia
and their first degree relatives (40 alleles). Mutations   (Stage IV Prader), karyotype was performed and the sex
were found in one patient – P453S on the paternal          of rearing was established female. After one year
allele and a double mutation (P30L + I2 splice) on the     adrenarche started. She was referred at the age of 10.5
maternal allele. In five patients CYP21A1P deletions       years. Hormonologic evaluation showed high levels of
were found – heterozygous in 4 cases and                   ACTH 144 pg/mL, progesterone 21.54 ng/mL,
homozygous in one case – all maternally inherited.         testosterone 0.313ng/mL, high normal 17OHP
The nonclassical phenotype in patients with CYP21A1P       0.68ng/mL and low normal cortisol 9.1 µg/dL. Three of
deletions can be explained by misalignment of the RCCX     her siblings (two boys and one girl) were healthy and
module with unequal crossingover generating DNA loss       another two (two boys) were affected. An older brother,
from regulatory regions that results in reduction of       12 years-old presented with adult type genitalia,
CYP21A2 transcriptional activity.                          hypertension and short stature and another newborn
                                                           brother presented with penile hypertrophy,
                                                           hyperpigmented scrotum. Though 11α hydroxylase
                                                           deficiency is an autosomal recessive disorder 50% of this
                                                           kindred was affected.

                                                POSTER SESSIONS

      Fahr’s disease and thyroid involvement                    Pyramidal lobe well-differentiated thyroid carcinoma
                 - two cases report                             mimicking ectopic thyroid carcinoma - a case report

Mara Carsote1, Corina Chirita2, D. Hortopan2, Anda              Aurelia Bold 1, S. Radian 1,2, Ionela Baciu 1,
Dumitrascu 2, A. Goldstein2, D. Ioachim2, Catalina              B. Stanescu 1,2, D. Ioachim 1, Dana Terzea 1,
Poiana1,2                                                       M. Coculescu 1,2
1.“Carol Davila” University of Medicine and                     1 “C.I. Parhon” Institute of Endocrinology 2 Department
Pharmacy, 2.“C.I.Parhon” Institute of Endocrinology,            of Endocrinology, “C Davila” University of Medicine,
Bucharest, Romania                                              Bucharest
Bilateral calcifications of the basal ganglia also known as
Fahr’s disease is a rare idiopathic degenerative malady.        Differential diagnosis of thyroid carcinomas
Some authors consider it as an autoimmune disease, but
                                                                developing in unusual cervical locations can prove
others appreciate as more important the genetic features
(the cases may be familial, autosomal recessive or even         difficult.
rarer dominant, or sporadic). The main abnormality is the       Aim. To present a case of thyroid carcinoma with pre-
calcium deposits and cell loss in certain brain areas that      hyoidian location. Case report. We present the case of
induce progressive cognitive impairment up to dementia,         a 74 years old female, previously diagnosed with toxic
loss of the acquired skills, spastic paralysis, atherosis.
                                                                goiter (2003) and treated with antithyroid drugs for
Aim. We report two incidentally discovered
asymptomatic cases in female patients. Both women               four years. On admission (Nov 2007) she presented for
associate thyroid pathology as Grave’s disease and              progressive weight loss, tachycardia and a cervical
hypothyroidism due to endemic goiter. Case report. The          mass. Clinical examination revealed an enlarged
first case is T.E., a 56 year old female patient with           inhomogeneous thyroid and a distinct hard, painless,
exophtalmopathy since age of 53 and diagnosis of                midline pre-hyoidian mass with soft tissue adherence
Grave’s disease since age of 55 when she was started on
                                                                and a permeation skin lesion. Thyroid tests showed
thyamazol for the last year. While accusing continuous
non hypertensive headache, a computed tomography                suppressed TSH and high total T4. Cervical
(CT) was performed and cerebral calcifications in the           ultrasonography revealed an enlarged micronodular,
basal ganglia were revealed. At the moment, no                  hypo-echoic thyroid, bilateral cervical lymph nodes
neurological findings are found. The second case is M.G.,       and a solid ill-defined pre-laryngeal tumor, 3.7cm in
a 55 year old female patient. She came to our attention for
                                                                diameter, with microcalcifications. Compression of
evaluation of a goiter. Anterior cervical ultrasound
showed a hypoechogenic nodule of 1.05 by 0.5cm on the           the larynx and trachea was evident on X-ray
left thyroid lobe. The hormonal profile showed                  examination. The fine-needle aspiration biopsy was
hypothyroidism. The fine needle aspiration biopsy               suggestive for papillary carcinoma with poorly
revealed adenomatous nodule with very well                      differentiated areas.
differentiated follicular epithelium. She also accused          Management. Surgical excision was performed,
continuous headache. On X-ray, mild enlargement of the
                                                                during which gross examination revealed a pyramidal
sella turcica was seen. CT scan was performed. Empty
sella and microcalcifications of the epyphisar region of        lobe tumor with skin invasion that was completely
0.84 by 0.69 cm together with bilateral basal nuclei were       excised along with the thyroid. The histopathological
presented. The patient was also asymptomatic                    diagnosis of the tumor was follicular-variant papillary
neurologically.                                                 carcinoma, with muscular and skin invasion. External
Discussion. The two cases have some similarities: both
                                                                beam irradiation was commenced because of local
patients have normal parameters of the phosphor-calcium
metabolism and no evident hypercalcemia was seen.               invasion, to be followed by radioiodine therapy.
Both cases refer to women in the sixth decade. The              Conclusion. This case is peculiar with respect to the
neurological findings were not present, except for the          unusual location within the thyroid where carcinoma
headache that might have many causes. Because the               developed and its association with hyperthyroidism.
cause of Fahr’s disease is still unclear, the spectrum of the   The true origin of this tumor could only be assessed at
possible associations including autoimmune or non
                                                                surgery. Skin and muscle infiltration by a well-
autoimmune thyroid pathology is still open.
                                                                differentiated thyroid carcinoma is also a rare finding.
                                           POSTER SESSIONS

  Graves’ disease in a patient with mediastinal B          Coexisting primary hyperparathyroidism and
  cell NON-HODGKIN’S lymphoma producing                                   nodular goiter
                                                         H.Ursu1,2, Simona Verzea 1, Monica Chirita 1,
                                                         D. Ioachim1, D. Hortopan 1, Anda Dumitrascu 1, Ligia
Nicoleta Baculescu 1, Camelia Dobrea 4,                  Muntianu3, B. Stanescu 1, A.Golstein 1
Ioan Cordos1,3, Mihail Coculescu 1,2
1“Carol Davila” University of Medicine and               1 “C.I.Parhon” Institute of Endocrinology, 2 “Carol
Pharmacy, 2 “C.I.Parhon” Institute of Endocrinology,     Davila” University of Medicine and Pharmacy,
3“Marius Nasta” Institute of Pneumology, 4“V Babes”      Departament of Endocrinology, 3 “Carol Davila”
National Institute, Bucharest, Romania                   University of Medicine and Pharmacy, Faculty of
                                                         Dental Medicine, Bucharest, Romania
An increased risk of non-Hodgkin’s lymphoma was
found for a personal history of autoimmune               Prevalence of nodular goiters is increased in the
conditions: rheumatoid arthritis, systemic lupus         patients with primary hyperparathyroidism, ranging
erythematosus, celiac disease, autoimmune hemolytic      from 25-52%.
anemia, Crohn’s disease, psoriasis, sarcoidosis and      Coexisting of thyroid macronodules with parathyroid
thyroiditis. The associations may not be general but     adenomas increases the difficulty in preoperative
rather mediated through specific non-Hodgkin’s           localizing parathyroid lesions, as it happened in one of
lymphoma subtypes. These non-Hodgkin’s lymphoma          our three cases. Mean age of our three female patients
subtypes develop during postantigen exposure stages of   was 52.6 (age range: 39-72 years) and one of them had
lymphocyte differentiation, consistent with a role of    asymptomatic primary hyperparathyroidism.
antigenic      drive      in     autoimmunity-related    A nodular goiter with euthyroidism was found in two out
lymphomagenesis.                                         of the three cases reported and the parathyroid lesion (2.9
We present the case of a 30 years old male, with         cm) mimicked clinically a thyroid nodule in the third
simultaneous diagnosis of Graves’ disease and a huge     patient (thyroid gland having a normal volume in the last
anterior mediastinal mass whitch was actually the        mentioned patient ). Coexisting of non-medullary
mediastinal involvement of a diffuse large B-cell        carinoma is found in 3-6 % of patients operated for
lymphoma stage III, and discuss the possible             primary hyperparathyroidism. None of the two patients
relationship between the two diseases. The patient had   that required concomitant parathyroid-
also hypercalcemia, remitted after two courses of        ectomy and thyroidectomy had associated thyroid
chemotherapy, and we discuss the role of parathyroid     carcinoma.
hormone related peptide PTHrP in paraneoplastic          Transient            postoperative           symptomatic
syndrome and its predominant local role in this case.    hypoparathyroidism occurred in one of our patients.

                                           POSTER SESSIONS

       Secondary osteoporosis treated with                   Osteogenesis imperfecta – a seldom cause of
     biphosphonates in cases of the Clinic of                        fractures in young people
 Endocrinology Târgu-Mureº, between 2004-2008
  Kun I., Krisztina Stoica, Zsuzsanna Szántó, Anisie      Ligia Radulescu1 ,        Raluca     Trifanescu 1,2 ,   M.
          Nãsãlean, J.Balázs, Camelia Gliga               Coculescu1,2
Târgu-Mureº University of Medicine and                    1“C.I. Parhon” Institute of Endocrinology, 2“Carol
Pharmacy,Clinic of Endocrinology                          Davila”     University     of    Medicine     and
                                                          Pharmacy,Bucharest, Romania
Secondary osteoporosis can be determined by
endocrine diseases (hypogonadism, thyreotoxicosis         Osteogenesis imperfecta is an inherited connective
and endogenous or exogenous hypercorticism,               tissue disorder, also called “brittle bone disease”.
hyperparathyroidism, hyposecretion of STH and of          Case report. E.S., male, 30 years old. Family history
growth factors, hyperprolactinemia), by malignant         revealed multiple fractures and dwarfism in father,
diseases as well as by other favouring factors
                                                          uncle, sister and grandfather. Personal medical history
(sedentarism, caucasian race, low BMD, etc.).
Aim. Analysis of etiology of secondary osteoporosis       consisted in multiple fractures )4 days after birth –
treated with biphosphonates in cases of the Clinic of     thigh bone fracture, 12 years – right radius fracture, 16
Endocrinology Târgu-Mureº between 2004 and 2008.          years – tibial fracture, 20 years - left radius fracture, 30
Material and methods. We processed the data of 73         years – posttraumatic vertebral fracture C5-C6 with
patients (69 women and 4 men) admitted in the clinic      incomplete medullar compression syndrome. Clinical
for secondary osteoporosis and treated with               examination showed disharmonic dwarfism (H= 148
biphosphonates. The diagnosis of osteoporosis was         cm, G= 51 kg), warm, smooth skin, but without blue
established in most cases (62) by DEXA and in 11          sclerae; dentinogenesis imperfecta, osseous
patients by bone radiographies. The diagnosis of the      deformation with bending of left forearm, bending of
diseases was made by specific investigations. Results.    thighs, calves, right foot were present. No hearing
The average age of patients was 69 years and              impairment was noticed; there were no signs of
menopause at 46 years. In 41 cases osteoporosis was
                                                          pituitary deficiencies. Radiographs showed curved left
determined by endocrine diseases: 30 patients suffered
from premature ovarian failure, 3 patients were           thigh bone with thick diaphyseal compact, curved
diagnosed with hypogonadism of other etiology, 8          radius and cubitus, especially on left side. Lumbar
patients     with     thyreotoxicosis.      Exogenous     DXA exam showed osteopenia: T-score= -1.4 SD, Z-
hypercorticism (following the therapy with                score= -1 SD, BMD= 1.026 g/cm2. Hip DXA exam
glucocorticoids for a long time) led to osteoporosis in   was normal: T-score= 1.5 SD, Z-score= 1.9 SD,
20 cases, of whitch 8 also had thyreotoxicosis.           BMD= 1.24 g/cm2. Serum calcium (9.79 mg/dL),
Malignant diseases were present in 4 cases, 2 of them     serum phosphorus (3.43 mg/dL) and alkaline
associated with an endocrine disease. The 4 endocrine     phosphatase (128 IU/L) were normal. Mild vitamin D
patients also present other osteoporosis risk factors     deficiency (25 OH vitamin D= 13.15 pg/ml) with
and one case had 3 causes of secondary osteoporosis       increased bone turnover markers (β crosslaps= 1.06
(thyreotoxicosis, hypercortisolism and other risk         ng/mL, osteocalcin= 35.89 ng/mL) were noticed.
factors). 50.7% (37 patients) of all cases studied
                                                          Normal somatotroph axis was confirmed by a normal
presented with osteoporotic fractures. Conclusions:
Premature ovarian failure (under the age of 40 years)     increase of GH levels during insulin tolerance test, up
was the most frequent cause of secondary osteoporosis     to 72.2 ng/mL and normal IGF-I levels (108 ng/mL),
treated with biphosphonates, followed by exogenous        excluding pituitary dwarfism.
hypercorticism (induced by long therapy with              Conclusion. osteogenesis imperfecta, a seldom cause
glucocorticoides), and then by thyreotoxicosis            of fractures, should be considered in young patients
(determined by suppresive doses of thyroid hormones,      with positive personal and family history of bone
used in the therapy of differentiated forms of thyroid    fragility.
                                             POSTER SESSIONS

    Tocotrienols improve the antioxidant status in             Hemorrhagic galactorrhea in an acromegalic
     streptozotocin-induced diabetic rat tissues                        patient – Case report

Marius-Ionut Ungureanu1, Irina Chis 2, Ramona               Corina Chirita1, Mara Carsote 2, D.Hortopan1,
Simedrea 2, Adriana Muresan2, Patricia Suteu1 ,             Cristina Ene1, A. Goldstein1, D.Ioachim 1, Catalina
Adriana Marton 1, Nicoleta Decea 2                          Poiana1,2
1 Student, Faculty of Medicine, 2 Department of             1.“C.I.Parhon” Institute of Endocrinology, 2.“Carol
Physiology, “Iuliu Hatieganu” University of Medicine        Davila” University of Medicine and Pharmacy,
and Pharmacy Cluj-Napoca, Romania                           Bucharest, Romania

Tocotrienols are natural compounds, having a                Acromegaly is caused by excess of the growth hormone (GH),
structure which resembles vitamin E. Tocotrienols are       usually from an adenoma of the pituitary gland. It is associated
                                                            with enlargement of organs and increased risk for benign
believed to have antioxidant properties. Most of the
                                                            tumors (goiter, uterine leiomyomas and premalignant colonic
studies performed with these compounds focused on           polyps). Aim. We present the case of a female patient with
their effects on lipid metabolism. In order to find out     acromegaly in remission after transsphenoidal resection of the
more about the properties of these compounds, we aim        somatothropinoma, with persistent bilateral hemorrhagic
at revealing their implications in experimental             galactorrhea due to bilateral intraductal papilloma. Case
                                                            report. A 45 years old female patient was admitted in our
diabetes mellitus.
                                                            hospital 2 years ago for enlargement of the hands and feet,
Materials and methods. Our study included 30 white          coarsening of the voice and diffuse joint pain. 4 months prior
male Wistar rats, with a body weight ranging between        to admission she had suffered total hysterectomy with
200 g and 250 g. Diabetes mellitus was induced by a         bilateral anexectomy for uterine leiomyomas. The clinical
single dose of Streptozotocin, 50 mg/kg, dissolved in       examination also revealed bilateral expressible hemorrhagic
citrate buffer(0.1 M, pH=4.5) The rats were divided         galactorrhea. The nadir of the GH during an oral glucose
                                                            tolerance test (OGTT) was 3.29 ng/mL. Insulin-like Growth
into 3 groups of 10 animals each: -group I- animals in
                                                            Factor 1 (IGF1) was 150 ng/mL (normal range: 101-267).
which vegetable oil was administered, by gavage;-           She associated hypercholesterolemia. The computed
group II-animals in which palm-tree oil was                 tomography (CT) scan of the pituitary gland showed a
administered, by gavage, 100 mg/kg (0.6 ml/rat),            microadenoma of 0.83 by 0.46 cm. The cytological
dissolved in vegetable oil;-group III-animals in which      examination of the mammary secretion showed ductal
                                                            ectasia without atypical cells. Based on these, the diagnosis
vitamin E was administered, by gavage, 100 mg/kg
                                                            of acromegaly was sustained. 5 months later,
(0.6 ml/rat), dissolved in vegetable oil. We assessed       transsphenoidal resection of the tumor was performed. The
the levels of lipid peroxides, carbonylated proteins and    histopathological exam confirmed the diagnosis. After the
hydrogen donors from the tissue homogenates.                surgery, the hormonal parameters showed remission, with no
Results. Except for the first group, the other groups of    pituitary insufficiency (the nadir GH during OGTT - 0.9
animals showed an increased level of hydrogen donors        ng/mL, IGF 1 – 80 ng/mL, prolactine – 12.09 ng/mL, plasmatic
                                                            cortisol – 11.31 µg/dL, TSH – 4.3 µUI/mL, T3 – 176 ng/mL and
and decreased levels of lipid peroxides and
                                                            T4 – 7.9 µg/dL). The pituitary CT showed secondary empty
carbonylated proteins after receiving the treatment         sella. The lipid profile was within normal range. But the
with tocotrienols and vitamin E.                            galactorrhea persisted. The mammary ultrasound showed
Conclusion. As a previous study showed, diabetes            only dilatated ducts. The mammography revealed ductal
mellitus associates an increased level of the oxidative     dilatations. Ductography showed bilateral ductal papillomas.
                                                            The patient was referred for sectorial bilateral mamectomy
stress, but we showed that the treatment with
                                                            which she delayed for one year. Particularities: 1.The level
tocotrienols and vitamin E can, at least in part, restore   of IGF1 was in normal range from the beginning even the
the pro-oxidan - antioxidant balance in the diabetic        acromegaly was active, and IGF1 decreased under the
status.                                                     normal range after treatment. 2. In acromegalic patients
                                                            galactorrhea may have other causes than hyperprolactinemia
                                                            and thus other causes should not be ignored. 3. Hemorrhagic
                                                            aspect of the nipple discharge is usually suggestive of a local
                                                            mammary pathology.
                                            POSTER SESSIONS

Natural history of sporadic goiter: a case of giant
               thyroid carcinoma

 Cristina Stancu 2, S. Radian 1,2, B. Stanescu 1,2, D.
       Ioachim 1, Terzea D 1, M. Coculescu 1,2

 1 Institute of Endocrinology C.I. Parhon, Bucharest
 2 Department of Endocrinology, C Davila Univ. of
                 Medicine, Bucharest

Background. Longstanding goiter can delay the
diagnosis and treatment of thyroid cancer.
Aim. To present a case of giant thyroid carcinoma
developed within a remnant thyroid lobe, long after
Case report. The patient, a 77 years old female, from
a non-iodine-deficient area, with a history of right
hemi-thyroidectomy for goiter, 36 yrs. before
presentation, was hospitalized for a giant left-sided
cervical mass. This developed slowly after operation
and had grown rapidly within the last 5 months. On
examination, a firm, non-tender left cervical mass
(15/12cm in diameter) with suprajacent skin changes,
emaciation, palor and tachycardia were present.
Laboratory evaluation showed supressed TSH with
normal freeT4, anemia (hemoglobin=8.4 g/dL) and
elevated ESR. CT examination demonstrated a
heterogeneous mass extending to the mediastinum,
with calcifications and necrosis. Tumor diameters
were 17/12/14 cm. Trachea was displaced, with
diameters of 2.26/1.38 cm. FNAB was not diagnostic
for carcinoma. Management. After correction of
anemia, total thyroidectomy was performed.
Thyroxine substitution was begun and the anemia
recovered spontaneously. The hystopathological
diagnosis was follicular poorly differentiated, highly
invasive and angio-invasive carcinoma, stage PT4B
PNX ST4B G3 R1 V1. External beam radiotherapy
was planned, but could not be performed because of a
local ulcerated recurrence of the tumor, six weeks after
thyroidectomy. The patient decided against further
surgery and was lost to follow-up.
Conclusion. Thyroid carcinoma should be suspected
in patients with progressive enlargement of
preexisting goiter. In our patient, recurrence of the
goiter on the remnant lobe after hemi-thyroidectomy
led to a delay in diagnosis.


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