Endocrine Care


    Adriana Toma1, B. Diaconu1, Monica Gheorghiu2,4, Nicoleta Sava1, Laura
   Nedelcu1, Raluca Trifanescu4, Mariana Sava2, D. Barbos3, M. Coculescu2,4,*

          Endocrinology Department, Arges County Hospital, Pitesti, Romania
            2 “C.I. Parhon” Institute of Endocrinology, Bucharest, Romania
                    3 Institute of Nuclear Research, Pitesti, Romania
      4 “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

      The subCarpathian areas of Arges county are now characterized by a moderate
endemia of iodine deficiency disorders (IDD) due to salt iodization. However, we found
some cases of endemic cretinism (EC), that is the major expression of anomalies in the
physical and intellectual development caused by a severe iodine deficiency. There are
presented 5 patients, 4 men and 1 woman, with neurological endemic cretinism (NEC) (n=2)
and mixed forms of the disease (n=3), coming from 2 old endemic areas (medium urinary
iodine excretion in the studied patients 20.8 g/day), diagnosed and treated in outpatients
clinics or in hospitals. Four patients are members of the same family. The age of the patients
is between 36 and 84 years old, the average age being 69. The intellectual capacity was
assessed by using the Wechsler and Raven tests, the average intelligence quotient (IQ) value
was of 20.8 points ± 1.47. The thyroid volumes (TV) were estimated by palpatory method
and by ultrasonography and were between 8.7-200 ml. TSH values in studied patients
ranged between 3.8-26 IU/ml and free T4 ranged between 0.272-1.22 ng/dl. Aggregation
of more cases of endemic cretinism in the same family suggests the occurrence of some
genetic factors.
      In conclusion, the old age (over 70 years old) of 4 cretins shows they are remnants of
the old IDD endemia. However, there is also an isolated case of middle age (36 years old)
suggesting an inadequate iodine intake, despite a law regarding salt iodization which has
been operating since 1962. More attention to the universal salt iodization and to
consumption of iodized salt in the rural areas is necessary.
      Key words: neurological endemic cretinism, IDD, subCarpathian area.

*Correspondence to: Mihail Coculescu, Institute of Endocrinology, 36 Bd. Aviatorilor, 011863,
Bucharest, Romania, e-mail:

                                      Acta Endocrinologica (Buc), vol. I, no. 3, p. 311-324, 2005

                                  Adriana Toma et al.


      Brain damage and irreversible mental retardation are the most important
disorders induced by iodine deficiency. An essential link between iodine deficiency,
thyroid function and brain development has emerged from a combination of
clinical, epidemiologic and experimental studies. The clinical picture varies from
the most extreme form of mental retardation called endemic cretinism, encountered
mainly in severe iodine deficient areas, to more subtle neuropsychointellectual
deficits in children and adults from mild to moderate iodine deficient regions: lower
IQ (by 5-10 points), psychomotor or mental development (1-9), higher incidence of
attention deficit and hyperactivity disorder (10).
      The term endemic cretinism describes clusters of people with goiter and
cretinism in defined geographic areas with severe iodine deficiency. The endemic
cretinism is characterized by severe brain damage - intelligence quotient (IQ) under
30 points, deaf mutism and a neurologic syndrome, with a spastic state of hands and
feet (11). In severely iodine deficient areas, a “minor” form of cretinism, with
hearing impairment, short stature and an IQ < 70 points, has been described (12).
      Since these changes could be prevented by iodine supplementation in mothers
before or during the first two trimesters of pregnancy (13), iodine deficiency is now
regarded by the WHO as the most common preventable cause of mental retardation,
with at least 30 million people suffering from this preventable condition (14).
      Iodized salt is considered as the most appropriate measure for iodine
supplementation. We describe 5 patients with cretinism from a rural subCarpathian
area with severe endemia of IDD in the 50’s (15) and where a moderate to severe
iodine deficiency persisted despite a law concerning salt iodization which has been
operating since 1962.

                        PATIENTS AND METHODS

     Patients. Five patients (four men and one woman, mean age 69 years old,
range 36-84 years old) with endemic cretinism, from two subCarpathian villages,
Arges county, with severe long standing iodine deficiency endemia were presented.
They were assessed either as outpatients or inpatients in the year 2000. The
neurological form of endemic cretinism was diagnosed in 2 patients (E.M, female,
73 years old, C.I.M., male, 74 years old) and the mixed form of endemic cretinism
in the other 3 patients (C.M., male, 78 years old, Gh.M., male, 84 years old, I.P.,
male, 36 years old). Four patients were from the same family.
     Methods. Clinical, anthropometrical, neurological and psychological
evaluation was performed in all patients. Combined Raven and Wechsler scales
were used for assessment of intellectual abilities. Samples of drinking water from
the 2 subCarpathian villages were analyzed for iodine content by molecular
spectrophotometry. The content of soil in heavy metals was analyzed by the fast and

                 Neurological cretinism in iodine deficient subCarpathian area

thermal neutrons activating method. The urinary iodine value was determined by
the Sandell-Kolthoff reaction. Iodine was measured in samples of iodized salt
collected in one village (Albesti) in the laboratory of Arges County Hospital.
      The thyroid volume was estimated by inspection and palpation and measured
by ultrasonography, using a Siemens Sonoline with a 7.5 MHz linear array
transducer. The TSH and free T4, total T4 and total T3 in the 5 patients were
measured with the ELISA method. In one inpatient cerebral computed tomography,
electroencephalogram and audiogram were performed.


       All the five studied patients were born and live in 2 subCarpathian villages
(Tigveni and Albesti) in Arges county, with severe longstanding iodine deficiency.
Samples of drinking water collected in 1999 from these 2 villages showed an extreme
low iodine content (0.09 g/l in Tigveni and 0.14 g/l in Albesti, respectively).
Samples of soil from these 2 areas, analyzed by the method of fast thermal neutrons
activation showed a higher than expected content in heavy metals (chromium: 96.3
ppm, normal values < 30 ppm) and bromide: 16.7 ppm, normal values < 14.8 ppm.
       All patients, but one were born before 1962, the year of implementation of the
first law concerning salt iodization with 15-25 mg kalium iodate (KIO3) or 10 mg
iodine /kg salt.
       Table 1 shows that despite the implementation of this law, medium urinary
iodine excretion in the studied patients was extremely low (20.8 g/l), although in
that area in 1999 there was only a moderate iodine deficiency (median urinary
iodine: 47.5 g/l). The characterization of regional IDD was recently published by
us (16). Thyroid function tests showed overt hypothyroidism in 3 patients (cases 1,
3, 5), subclinical hypothyroidism in one patient (case 4) and normal thyroid
function in one patient (case 2) (Table 1).
            Table 1. Urinary iodine excretion and thyroid tests in 5 patients with
                                     endemic cretinism

                     Patient                Urinary iodine       TSH          FT4
                                                ( g/l)         ( IU/ml)      (ng/dl)
         Case 1 (C. M., male, 78 yrs)            20              21.01        0.49
         Case 2 (E. M., female, 73 yrs)          22.0             3.8         0.69
         Case 3 (Gh. M., male, 84 yrs)           20.5              26         0.79
         Case 4 (C. I. M., male, 74 yrs)          21              6.88        1.22
         Case 5 (I. P., male, 36 yrs)            20.5             20.4        0.272

     Four patients (3 men and 1 woman, mean age 77.2 years, range 73-84 years)
belong to the same family. In this family there were 7 affected patients; three of
them died before our study (Fig. 1). The 4 studied patients with endemic cretinism

                                   Adriana Toma et al.

were 2 pairs of brothers and they were cousins (their fathers were brothers). Clinical
features of these 4 related patients were: disharmonic nanism (mean height: 135 cm,
range: 128-145 cm), severe mental retardation (mean IQ: 19.8 ± 1.47 points, range:
18-22), deaf-mutism, asthenia and neurological syndrome.

                      Figure 1. Genealogical tree in one affected family.

      Case 1 (C. M, male, 78 years old) lives in Tigveni, a subCarpathian village
with old moderate–severe endemia (median urinary iodine 50.65 g/l, prevalence of
goiter in 6-12 years old schoolchildren 57.85%). He showed a mixed form of
endemic cretinism, with severe neurological impairment and clinical and
biochemical hypothyroidism. The anthropometric measurements showed severe
growth retardation: Height (H)= 135 cm, Weight (W)= 38 kg, BMI= 21 kg/m2.
There was a severe mental retardation (IQ= 19 ± 5 points); there is no school
education (he was analphabet).
      The clinical examination showed at inspection extrapyramidal syndrome with
specific posture, proximal rigidity of both lower and upper extremities and the
trunk: anterior flexed trunk, flexed forearms and knees with severe gait and
coordination troubles. Apart from this, the patient also had a thalamic syndrome,
with the presence of the ancestral suckling reflex. Other features were: goiter, deaf
mutism, microcephalia with cretinoid facies, micrognatia, convergent strabismus in
left eye and hypertelorism (Fig. 2).
      There was not a previous medical history of birth injury or meningitis that can
be also encountered for cerebral palsy.
      From the biochemical point of view, this patient showed hypothyroidism with
TSH= 21.01 IU/ml and FT4= 0.49 ng/dl and a severe iodine deficiency (urinary
iodine excretion= 20 g/l), as shown in Table 1. Thyroid volume measured by
ultrasonography indicated a 21 ml thyroid volume with hypo and hyperechoic areas,
small cysts and micro calcifications (Table 2).

                  Neurological cretinism in iodine deficient subCarpathian area

      Figure 2. Case 1 (Patient C. M., male, 78 years old), mixed form of endemic cretinism.

     Case 2 (E.M, female, 73 years old) was the younger sister of the patient
presented above. She showed the neurological form of the endemic cretinism –
extrapyramidal syndrome with proximal spasticity, ataxia, and divergent strabismus
in both eyes. The anthropometric measurements showed: H= 132 cm, W= 33 kg,
BMI= 18.96 kg/m2. There was a severe mental retardation (IQ= 22 ± 5 points); she
was also analphabet.
     From the biochemical point of view, this patient had low–normal thyroid
function (TSH = 3.8 IU/ml, FT4 = 0.69 ng/dl) and a severe iodine deficiency (urinary
iodine = 22 g/l), as shown in Table 1. Thyroid volume measured by ultrasonography
showed a 16.33 ml thyroid volume with inhomogeneous hypo and hyperechoic areas
and one cm diameter nodule in the left thyroid lobe (as shown in Table 2).
                Table 2. Echographic pattern in 5 patients with endemic cretinism
 Patient     Thyroid            Echogeneity              Solid/cystic nodules       Calcifications
           volume (ml)
Case 1         21          hypo/hyperechoic areas            Small cysts                Micro
Case 2        16.33           Inhomogeneous,             Solid 1cm diameter               -
                           hypo/hyperechoic areas       nodule in the left lobe
Case 3         8.7         hypo/hyperechoic areas                 -                       -
Case 4        23.5       Inhomogeneous predominant             -                          -
                             hypoechoic pattern
Case 5        >200            Inhomogeneous        Multiple solid and cystic           Macro

      Cases 3 and 4 (Gh. M, male, 84 years old and C. I. M., male, 74 years old)
were brothers and cousins with the previously 2 reported cases and they were living
in the same subCarpathian village.

                                  Adriana Toma et al.

      Patient Gh. M. had a mixed form of endemic cretinism with both neurological
syndrome and hypothyroidism: TSH= 26 IU/ml, FT4= 0.79 ng/dl (Table 1). The
anthropometric measurements showed: H= 128 cm, W= 38 kg, BMI= 23.31 kg/m2.
He had epilepsy with grand mal crisis from his early childhood and a large
inguinoscrotal hernia. There was a severe mental retardation (IQ= 19 ± 5 points);
he was also analphabet. Severe iodine deficiency was proved by a low urinary
iodine excretion (20.5 g/l). Ultrasonography in patient Gh. M. revealed thyroid
atrophy with a 8.7 ml thyroid volume.
      Patient C. I. M. also showed a neurological form of endemic cretinism associated
only with subclinical hypothyroidism (TSH= 6.88 IU/ml, FT4= 1.22 ng/dl). The
anthropometric measurements showed: H= 145 cm, W= 46 kg, BMI= 21.9 kg/m2).
There was a severe mental retardation (IQ= 21 ± 5 points); he was also analphabet.
Severe iodine deficiency was proved by a low urinary iodine excretion (21 g/l).
Ultrasonography in patient C.I.M. had a 23.5 ml thyroid volume, with
inhomogeneous hypoechoic pattern (Table 2). This patient also presented with large
inguinoscrotal hernia.
      Case 5 (I. P., male, 36 years old) was resident in Albesti, another
subCarpathian village with severe iodine deficiency endemia (median urinary
iodine 49.9 g/l, prevalence of goiter in 6-12 years old schoolchildren 58.37%).
Goiter was present in his family for generations. He was born in 1969, seven years
after the implementation of the law concerning salt iodization with 15-25 mg/kg
KIO3, showing the inefficacy of this law in some rural areas with old goiter
endemia. The urinary iodine excretion was very low both in the patient (20.5 g/l)
and his mother (20 g/l), who also shows a mild degree of mental retardation (IQ =
70), revealing the persistence of severe iodine deficiency endemia despite the salt
iodization law implementation. The mother and two brothers of the patient were
euthyroid (TSH = 1.78 IU/ml, FT4 = 0.85 ng/dl – patient’s mother and TSH = 1.91
  IU/ml and 1.85 IU/ml respectively patient’s brothers) when patient I. P. was 36
years old. In 1993, the iodine content of iodized salt in householding was only 7.3
mg/kg salt, much lower than the limits stipulated by law (target values by legislation
are 34 ± 8.5 mg KIO3/kg salt).
      The previous medical history of this patient included diagnosis of chronic
infantile encephalopathy at the age of 2 years because of severe psychomotor
retardation. Since the age of 8, he showed a slow growing goiter. Now, he is
presenting with a grade II multinodular goiter with compressive phenomena on
esophagus, trachea and recurrential nerves, as shown by radiological images and
      This patient shows a normal height (H= 164 cm, W= 86 kg, BMI= 32 kg/m2)
despite the presence of overt clinical hypothyroidism: puffy face and limbs, sinus
bradycardia (heart rate= 56 beats/minute) associated with Hoffman syndrome (pseudo-
hypertrophy of cervical and upper limb muscles) and the neurological syndrome
(proximal spasticity with markedly exaggerated deep tendon reflexes, bilateral
Babinski signs, ataxia) (Fig. 3). Bilateral perception hypoacusia of medium severity

                   Neurological cretinism in iodine deficient subCarpathian area

was noticed on audiogram. The patient is mute. His very low IQ (20 points on
Wechsler/Raven scale) proves severe mental retardation.

Figure 3. Case 5 (patient I. P., male, 36 years old) - mixed form
                     of endemic cretinism.

      Thyroid functions tests revealed overt hypothyroidism (TSH= 20.4 IU/ml,
FT4= 0.272 ng/dl, TT4= 4.56 g/dl, TT3= 1.21 ng/ml), with high thyroglobulin
levels (> 1000 ng/ml), and slightly elevated anti-TPO antibodies titres
(45.94 UI/ml) due to a large goiter. Thyroid volume estimated by ultrasonography
was 200 ml, with multiple hypo and hyperechoic macronodules, cysts larger than
2 cm and frequent macro calcifications (Table 2).
      Electroencephalography shows predominant θ rhythm and ∆ waves discharges
diffusely spread. Cerebral computed tomographic aspect was normal. The patient was
treated with levothyroxine 100 g/day, with a significant decrease in goiter’s size,
improvement of compressive signs and normalization of thyroid status (Table 3).

      Table 3. Thyroid tests in case 5 before and after levothyroxine treatment (100   g/day)

                        Before treatment        After 1 year of          After 2 years of
                             (2000)            treatment (2001)         treatment (2002)
       TSH ( IU/ml)            20.4                  9.32                       2.4
        FT4 (ng/dl)           0.272                  0.60                      1.09
        TT4 ( g/dl)            4.56
        TT3 (ng/ml)            1.21

     Consequently, asthenia disappeared and the effort tolerance increased. All the
patients with hypothyroidism received levothyroxine replacement treatment. In the
patient without goiter (case 3) iodized oil was also administered (200 mg iodine/cp).

                                      Adriana Toma et al.

    The neurological pattern in our series of five patients with neurological and
mixed form of endemic cretinism is summarized in Table 4.
              Table 4. Neurological impairment in 5 patients with endemic cretinism

                       Type of neurological impairment                          No. of cases
                      Severe mental retardation (IQ: 20-25)                          5
                      Deafness (different grades of severity)                        5
                       Mutism (different grades of severity)                         5
      Pyramidal syndrome – spasticity, hyperreflexia, presence of Babinski sign      4
                            Extrapyramidal syndrome                                  3
                              Thalamic syndrome                                      1
                                      Ataxia                                         3
                         Gait and walking disturbances                               1
                                   Strabismus                                        3
                                     Epilepsy                                        1


       A causal relationship between iodine deficiency and mental retardation has
been proved since the 50’s, when it was shown that, in the affected regions,
cretinism is frequent and is prevented by iodization of pregnant women before or
early during gestation (15, 17). Globally, in a meta-analysis of 19 studies on
neuromotor and cognitive functions in conditions of moderate to severe iodine
deficiency, Bleichrodt and Born (7) concluded that iodine deficiency resulted in a
loss of 13.5 IQ points at the level of the global population. A recent meta-analysis
of studies conducted in China on over 12,000 children showed that children living in
iodine sufficient communities have higher intelligence levels by 12.45, 12.3, 4.8 IQ
points as compared with those living in severely iodine deficient areas with no
iodine supplementation, with inadequate iodine supplementation, or children who
had received iodine during their mothers’ pregnancy and after birth. Furthermore,
there was an increase of 17.25 IQ points on Binet or 12 IQ points on Raven Scale
for children born more than 3.5 years after iodine supplementation program was
introduced (18).
       Our patients are all born in an area historically known as severely iodine-
deficient, in which, after salt iodization implementation in 1962, still persisted a
moderate iodine deficiency with a very high incidence of goiter in schoolchildren.
Despite improvement of the urinary iodine and decrease in goiter prevalence in this
region after the reinforcement of iodine supplementation in 2004 (16), there is a
persistence of moderate – with pockets of severe – iodine deficiency, a fact described
also by other authors (19). In these areas occasional cases of endemic cretinism are
still recorded (5 of 650,502 inhabitants = 7.8 cases/106). Four out of our five patients
are aged hallmarks of the previous severe iodine deficiency.

                Neurological cretinism in iodine deficient subCarpathian area

      They have the classical clinical features of neurological cretinism, with severe
mental retardation and, in 3 out of 5 patients, also with signs of hypothyroidism
(mixed forms).
      The currently accepted mechanism for the effect of iodine deficiency on fetal
brain development is the hypothyroidism induced both in the fetus and the mother (20).
This will affect the development of certain fetal brain structures that are influenced by
the T3 early generated in the brain from the circulating T4 by the spatially- and
temporally-specific type II monoamine-deiodase (21).
      The brain structures that are severely affected in neurological cretinism develop
before midgestation. A placental transfer of maternal T4 to the fetus (22, 23) accounts
for the detectable fetal serum T4 levels (1% of the maternal levels), associated with
a biologically relevant fT4 level (1/3 of the maternal level) in the first trimester of
gestation, before the onset of secretion of T4 by the fetal thyroid (20 - 24 weeks of
gestation) (24). This transfer, albeit small, is enough to prevent irreversible
neurological damage at birth in neonates with congenital hypothyroidism. Despite
having a non-functional thyroid, their cord blood T4 levels at birth were 25-50% of
the values recorded in normal newborns (25), probably of maternal origin. Moreover,
the brain damage in untreated children with sporadic congenital hypothyroidism is
less severe than in patients with endemic cretinism (26). The severe mental and
neurological picture described in our patients argues for an endemic neurological
cretinism, due to maternal hypothyroxinemia in early pregnancy.
      The demonstration of a pattern of ontogeny of fetal cerebral cortex deiodinases
and thyroid hormone receptors, beginning by 7-8 weeks’ gestation, is circumstantial
evidence that thyroid hormone plays an important role in fetal neurodevelopment
(27, 28). T3, acting through the nuclear receptors, controls the expression of several
genes involved in myelination, cell differentiation, migration, and signaling (20, 27).
      In animals treated with an iodine-deficient diet, there is a reduction of the fetal
and maternal plasma T4 levels and neurological impairment, which can be at least
partially reversed by iodization of the mother early during pregnancy. Combined
maternal thyroidectomy (carried out 6 wk before pregnancy) and fetal thyroidectomy
induced on the fetal brain similar effects with those observed in iodine deficiency,
but much more severe, associated with a greater reduction in maternal and fetal
thyroid hormone levels than in iodine deficiency (29).
      Biological effects of thyroid hormone have not been identified yet in early
human fetal brain, but maternal hypothyroidism early in pregnancy results in the
inappropriate expression of specific genes in the fetal rat brain (30) and in
irreversible alterations of the migration of cells in the cortex and hippocampus (31).
The latter are also observed in the progeny from iodine-deficient rat dams (32) that
are hypothyroxinemic but not hypothyroid. A very short period of goitrogen-induced
mild hypothyroxinemia early in pregnancy is also sufficient to induce both abnormal
migration and permanent neurological damage (i.e. increased audiogenic seizure
susceptibility) (33). Alterations of migration have also been observed in human
fetuses from an iodine-deficient area (34). In humans, the frequency of maternal

                                   Adriana Toma et al.

hypothyroxinemia during the first trimester of pregnancy exceeds 50% in severe 110
iodine deficient areas (35), and goes up to 30% in areas with moderate deficiency
(36). Both endemic cretinism and the affected neurodevelopment of the noncretin
population were related to the low circulating T4 of the pregnant women, but not to
T3 or TSH (37). The poorest outcome of pregnancy (assessed by fetal and infant
mortality, birth of cretins and poor psychomotor development of noncretins) was
recorded in women with T4 values below 2.5 g/dl, comprising 20% of women
(38). These women were not hypothyroid, because a compensatory increase in
serum T3 level occurs in the context of iodine deficiency, usually maintaining an
almost normal serum TSH and an euthyroid clinical appearance, as is the case of the
mother of one of our patients (I. P.).
      The neonatal screening for congenital hypothyroidism showed that the
severity of iodine deficiency is correlated with a higher incidence of transient
neonatal hypothyroidism (0.036% in Arges county in 2004), which has been
correlated with an impaired psychoneurological development of children (39-41).
      The protective role of maternal thyroid hormones during pregnancy is further
delineated by the finding that maternal hypothyroidism unassociated with any fetal
thyroid abnormality has been correlated with an impairment in psychomotor
development in the offspring (i.e. a mean 4 points IQ deficit in 7 – 9 year old
children) (42-45).
      When there is a combined maternal-fetal hypothyroidism, as in the materno-
fetal POU1F1 (formerly called Pit 1) deficiency (46) or a TSH receptor blocking
antibody-induced congenital hypothyroidism (47), significant developmental delay
despite early and adequate postnatal therapy has also been reported. The importance
of the maternal thyroid hormones (and perhaps also of the elemental iodine per se)
during early gestation is also reflected by the finding that endemic cretinism can be
prevented only if mother iodization is undertaken before pregnancy or until the
second trimester.
      There has been no support for the role of elemental iodine deficiency from the
animal models. However, an additional direct effect of iodine itself cannot be excluded
from the existing data (48). No obvious effect of excess iodine was found on mental
development of schoolchildren (49).
      Apart from selenium, which influences the type I deiodinase (a selenoprotein)
(50), it is tempting to suggest that many other geochemical elements may be
involved in the iodine-deficiency endemia. The influence of the elevated
concentration of heavy metals found by us in these villages from the subCarpathian
area is far from been clarified.
      It has long been suspected that a genetic factor could contribute to the familial
aggregation of metal retardation in iodine-deficient area. On the basis of studies of 70
families with endemic cretinism from Highland Ecuador, Held et al. (51) suggested
that an autosomal recessive predisposition is the major etiologic factor. The high
frequency of cretinism in our studied family did not suggest a recessive transmission
pattern. The apolipoprotein E gene encodes a lipoprotein that possesses a thyroid

                   Neurological cretinism in iodine deficient subCarpathian area

hormone-binding domain, and the APOE genotype might affect the efficacy with
which thyroid hormones influence neuronal cell growth during the first and second
trimesters of fetal development. Wang et al. found that APOE4 genotypes were
significantly enriched in fetal iodine deficiency disorder Chinese probands (52).
      Recently, Guo TW et al. (53) showed that the allelic variation of the type II
deiodinase may affect the amount of available T3, which may increase the risk for
mental retardation in an iodine-deficient environment. This might be also the case
in 4 of our patients who belong to the same family. Mutations in the X-linked gene
of the thyroid hormone monocarboxylate transporter 8 (MCT8) have been
associated to a neurologic deficit similar to the endemic cretinism, described in
male patients with an elevated serum T3 (54). Unfortunately, serum T3 levels have
not been assessed in other members of the same family, where there was also an
affected female. It is also striking that the major neurological abnormalities
described in these patients did not affect their life span.
      Treatment with thyroxine in our series of patients with hypothyroidism
normalized the serum thyroid hormone levels, but did not improve the mental
and/or neurological status. The irreversibility of iodine deficiency-induced brain
damage reinforces the necessity of prophylactic iodization in iodine-deficient areas.


     The old age (over 70 years old) of four cretins shows they are remnants of the
old IDD endemia. However, there is also an isolated case of middle age (36 years
old) suggesting an inadequate iodine intake, despite a law regarding salt iodization
which has been operating since 1962. More attention to the universal salt iodization
and to consumption of iodized salt in the rural areas is necessary. The familial
aggregation of neurologic cretinism in a small and isolated population exposed to
iodine deficiency may be due to a yet unrevealed genetic factor, perhaps related to
a high degree of consanguinity.


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