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									Pediatric Board Review

   Endocrinology


     Graeme Frank, MD
Calcium
    An otherwise healthy 6-week infant presents with a
    generalized seizure. She is exclusively breast fed. The
    child is somewhat sleepy with a non focal examination.
    Lab data:
    Glucose         88 mg/dL
    Sodium          141 mEq/L
    Calcium         5.1 mg/dL
    Phosphorus      9.1 mg/dL
    Magnesium       2.1 mg/dL


The most likely diagnosis is:
a) Pseudohypoparathyroidism
b) Hypoparathyroidism
c) Vitamin D deficiency
d) Albright’s hereditary osteodystrophy
 Actions of PTH                             Ca   PO4
                                1.



                                2.
     3.          25 OH Vit D
1 hydroxylase
                                     Gut
                 1,25 (OH)2 Vit D



                               NET EFFECT
    An otherwise healthy 6-week infant presents with a
    generalized seizure. She is exclusively breast fed. The
    child is somewhat sleepy with a non focal examination.
    Lab data:
    Glucose         88 mg/dL
    Sodium          141 mEq/L
    Calcium         5.1 mg/dL
    Phosphorus      9.1 mg/dL
    Magnesium       2.1 mg/dL


The most likely diagnosis is:
a) Pseudohypoparathyroidism
b) Hypoparathyroidism
c) Vitamin D deficiency
d) Albright’s hereditary osteodystrophy
An otherwise healthy 6-week infant presents with a
generalized seizure. She is exclusively breast fed. The
child is somewhat sleepy with a non focal
examination.
Lab data:
Glucose         88 mg/dL
Sodium          141 mEq/L
Calcium         5.1 mg/dL
Phosphorus      9.1 mg/dL
Magnesium       2.1 mg/dL

What is an important diagnostic consideration
(i.e. what else is the child at risk for)

DiGeorge syndrome – thymic aplasia, congenital heart
disease, immune deficiency
    Biochemical changes in rickets


          Ca   PO4    Bone         Urine

Stage 1              Minimal
                N    changes
                                Aminoaciduria
Stage 2   N           Rickets   Phosphaturia
            Initial   2 ½ weeks   4 months




Ca:             9.7      9.8        10.5
PO4:            3.1      3.5         6.5
Alk Phos:      2514     2185        518
   Which is consistent with
   vitamin D deficiency rickets?
 CALCIUM      PHOS           ALK PHOS

A. Normal      Normal         Low

B. Low         Low            Low

C. Low         Increased      Increased

D. Low         Normal         Normal

E. Normal      Low            Increased
      Choose correct answer
A. Vitamin D deficiency rickets
B. Renal osteodystrophy (renal rickets)
C. Both
D. Neither

      1. Increased phosphate level    B

      2. Increased PTH level          C

      3. Increased creatinine level   B
THYROID
   A 15 day infant has an abnormal newborn thyroid
   screen result:
   The baby was born on 5/27/07. His newborn screening
   tests, performed on 5/29/07 revealed:
                         Normal range
TSH         37 IU/ml         < 20
T4          10.1 g/dl        9-19

This child:
a) Has congenital hypothyroidism and should be referred
   to a congenital hypothyroidism treatment center
b) Will likely develop mental retardation if untreated
c) Likely does not have any thyroid abnormality
d) Has an altered hypothalamic set-point for T4
e) Should be started on thyroxine replacement
   immediately
   You are contacted by your state Neonatal Thyroid
Screening Program. Baby X was born on 1/4/01.
His newborn screening tests, performed on 1/6/01
revealed:

                 Initial filter paper
                                    Normal range
                 TSH    >200 IU/ml      < 20
                 T4      2.1 g/dl       9-19


   Venipuncture: (1/25/01)
                             Normal range
   TSH   488 IU/ml          (0.3-5.5)
   T4    1.2 g/dl           (4.5-12.5)
        Congenital hypothyroidism

 Thyroid dysgenesis/agenesis
 Prevalence 1 in 4,000 [Whites 1 in 2,000; Blacks
  1 in 32,000]
 2:1 female to male ratio
 Clinical features include:
  hypotonia, enlarged posterior fontanelle,
  umbilical hernia, indirect hyperbilirubinemia
 Laboratory findings: Very high TSH and low T4
 Therapy: Thyroxine – keep TSH in normal range
6 month female with         ..following 4 months
congenital hypothyroidism   therapy
     A baby who was born with gastroschisis has an
     abnormal newborn thyroid screen at 3 days which
     revealed a low T4 and normal TSH.

     Repeat venipuncture showed:
     T4            2.1 μg/dL   (4.5-12.5)
     TSH           2.3 μIU/mL (0.3-5.0)

     The most likely diagnosis is:
a)   Hypothyroidism due to dysgenesis of the thyroid gland
b)   Central hypothyroidism
c)   TBG deficiency
d)   Hypothyroidism from excess iodine exposure
e)   Normal thyroid function (as the TSH is normal)
Central hypothyroidism - rare

             vs.

      TBG deficiency
         1:2800
                Thyroxine (T4)
 Major product secreted by the thyroid
 Circulates bound to thyroid binding proteins
  - thyroid binding globulin (TBG)
 Only a tiny fraction (< 0.1%) is free and diffuses
  into tissues
 When we measure T4, we measure the T4 that is
  bound to protein
 The level of T4 is therefore largely dependent on
  the amount of TBG
 Changes in T4 may reflect TBG variation rather
  than underlying pathology
               Central          TBG
            hypothyroidism   deficiency


Free T4       Low              Normal

TBG level     Normal           Low

T3RU          Low              High
17 year old female who complains of easy fatigability.
Her mother developed Graves’ disease at the same
age.

Thyroid function:                Normal range
TSH: 3.7 IU/ml                  0.3-5.5
T4:   13.4 g/dl                 4.5-12
17 year old female who complains of easy fatigability.
Her mother developed Graves’ disease at the same
age.

Thyroid function:                 Normal range
TSH: 3.7 IU/ml                   0.3-5.5
T4:   13.4 g/dl                  4.5-12

Which of the following medication could explain the thyroid
  function abnormality

a)   INH
b)   Ortho Tri-Cylen
c)   Retinoid acid
d)   Ciprofloxacin
e)   Doxycycline
Conditions that cause alterations in TBG

Increased TBG         Decreased TBG
Infancy               Familial deficiency
Estrogen              Androgenic steroid treatment
 - OC Pill            Glucocorticoids (large dose)
 - pregnancy          Nephrotic syndrome
Familial excess       Acromegaly
Hepatitis
Tamoxifen treatment
     A 12-yr female has diffuse enlargement of the
     thyroid. She is asymptomatic. Her disorder is
     most likely associated with which of the following
     pathological processes

a)   Infectious
b)   Inflammatory
c)   Autoimmune
d)   Toxic (drug)
e)   Neoplastic
  Normal thyroid




Hashimoto thyroiditis
                                 DC
     16 year 7 month
     Growth failure x 1 1/2 years

Labs:

TSH:            1008 µIU/ ml   (0.3-5.0)
T4:             <1.0 µg/dl     (4-12)

Antithyro Ab.   232 U/ml       (0-1)
A-perox Ab.     592 IU/ml      (<0.3)

Prolactin:       29   ng/ml    (2-18)
Cholesterol:     406 mg/dl     (100-170)
                DC




Start of thyroxine
               Hashimoto thyroiditis
Background:
 Autoimmune destruction of the thyroid
 Family history in 30-40%
 Lymphocytic infiltration
Clinical:
 Growth failure, constipation, goiter, dry skin, weight
 gain, slow recoil of DTR
Laboratory:
 High TSH
 Anti-thyroglobulin and anti-peroxidase antibodies

Therapy:
 Thyroxine
15 year old female with a history of easy fatigability.
Found to have an elevated pulse rate at recent MD visit




    Thyroid function:      Normal range
    TSH < 0.1 IU/ml       0.3-5.5
    T4   14.8 g/dl        4.5-12
    T3   580 ng/dl         90-190
                Restlessness,
Eye changes
                poor attention span

                Goiter
                Tachycardia, wide pulse
                pressure

Increased GFR
- polyuria
                Diarrhea
Menstrual
abnormalities

Myopathy
   Therapy for Graves disease:

Antithyroid medication (Methimazole or Propylthiouracil [PTU])
       Pros : 25% remission rate every 2 years
       Cons: Drug induced side effects
              - skin rashes, agranulocytosis, lupus-like reaction
Radioactive iodine (131I)
      Pros : Easy. Essentially free of side effects
      Cons: Long term hypothyroidism

Surgery

 Blockers if markedly hyperthyroid
Sexual differentiation
     Ambiguous genitalia is found in a newborn.
     The baby is noted to be hyperpigmented.
     Ultrasound demonstrates the presence of a
     uterus. The most useful test to aid in the
     diagnosis of this medical condition is:

a)   Testosterone
b)   17-hydroxyprogesterone
c)   Serum sodium and potassium
d)   DHEAS
e)   DHEAS/androstenedione ratio
Cholesterol
     Desmolase
                 17-OH
Pregnenolone             17 (OH) pregnenolone   DHEA
      3--HSD                    3--HSD            3--HSD

                 17-OH
Progesterone             17 (OH) progesterone   Androstenedione
      21-OH                      21-OH


  DOCA                      Compound S
      11-OH                                     TESTOSTERONE
                                 11-OH

Corticosterone              CORTISOL


ALDOSTERONE
     If she has salt wasting congenital adrenal
     hyperplasia, which abnormalities are likely to
     develop. True or False for each


a)   Increased serum potassium            T
                                          T
b)   Decreased serum sodium
c)   Decreased bicarbonate                T
d)   Decreased plasma cortisol            T
e)   Increased plasma renin activity      T
     A 1-year male infant has non palpable testes.
     Of the following, the most appropriate next step
     would be


a) Schedule a re-examination in 18 months
b) Refer the patient for an exploratory laparotomy
c) Begin therapy with LHRH
d) Measure the plasma testosterone after
   stimulation with HCG
e) Begin therapy with testosterone enanthate, 50
   mg IM monthly for 3 months.
History
9 day old male infant
1 day history of decrease feeding, vomiting and lethargy.


Examination
Ill appearing infant with poor respiratory effort
Vital signs: T 99 F HR 100/min BP 61/40 RR 24/min
Resp:          Subcostal retractions but clear to auscultation
Cardiac:       Regular rate and rhythm. Normal S1 and S2
Abdomen: Soft, non distended. Non tender. No HSM
Neuro:         Lethargic. No focal deficit
Genitalia:     Normal male. Bilateral descended testes
  Laboratory data:


    WBC 16.7                Na           121
                            K            9.3
    Hb  16.4
                            Cl           83
    Hct 49
                            CO2          6.7
    Plt 537 K
                            Glucose      163
                            BUN/Creat    33/0.2
CSF:
Chemistry: Protein 74   Glucose    82
Microscopy: WBC 6       RBC        100
          Emergency therapy

Fluid resuscitation:
20 ml/kg Normal saline

Glucocorticoid
2 mg/kg Solucortef IV

Monitor EKG
Modes of presentation


   Classical
   Simple virilizing
   Virilizing with salt loss

   “Non classical” / Late onset
 Therapy and evaluation of therapy

Glucocorticoid (Hydrocortisone)
Monitor growth, 17-OHP, urinary pregnanetriol

Fluorocortisol (Florinef 0.1 – 0.45 mg/day)
Blood pressure, plasma renin activity (PRA)

Supplemental salt
Until introduction of infant food
History
15 year female presents with primary amenorrhea
Breast development began at 10 years


Examination
Height: 5 ft 7 in Weight 130 lb
Tanner 5 breast development
Scant pubic hair




          What is your diagnosis?
  Complete androgen insensitivity

XY Genotype


Testosterone    Androgen
                Receptor




                Estrogen
    Estradiol   Receptor
History
15 year female presents with primary amenorrhea
Breast development began at 10 years
Examination
Height: 5 ft 7 in Weight 130 lb
Tanner 5 breast development
Scant pubic hair

     Which of the following clinical features is the most likely
     to give you the correct diagnosis
a)   Blood pressure in all 4 extremities
b)   Careful fundoscopic examination
c)   Rectal examination
d)   Measurement of blood pressure with postural change
e)   Cubitus valgus and shield shaped chest
Early Puberty
     The earliest sign of puberty in a male is:




a)   Enlargement of the penis
b)   Enlargement of the testes
c)   Growth acceleration
d)   Pubic hair growth
e)   Axillary hair growth
  2 year old girl with breast development
  – No growth acceleration
  – No bone age advancement
  – No detectable estradiol, LH or FSH

The most likely diagnosis is:
a) Ingestion of her mother’s OCPs
b) Precocious puberty
c) Premature adrenarche
d) Premature thelarche
e) McCune Albright Syndrome
    Benign Premature Thelarche

Isolated breast development
 – 80% before age 2
 – Rarely after age 4
Not associated with other signs of puberty
(growth acceleration, advancement of bone age)
Children go on to normal timing of puberty and
normal fertility
Benign process
Routine follow-up
5 year female with 6 months of pubic hair growth.
Very fine axillary hair as well as adult odor to sweat.
No breast development

No exposure to
androgens

Growth chart:
Normal growth without
growth acceleration

    Most likely diagnosis:
    1. Precocious puberty
    2. Benign premature adrenarche
    3. Non-classical congenital adrenal hyperplasia
    4. Adrenal tumor
    5. Pinealoma
   Benign Premature Adrenarche
Production of adrenal androgens before true
pubertal development begins
Presents as isolated pubic hair in mid childhood
 – No growth acceleration
 – No testicular enlargement in boys
If normal growth rate, routine follow-up
If accelerated growth and/or bone age
advancement, screen for
 – CAH
 – Virilizing tumor (adrenal/gonadal)
        Choose correct answer
A. Premature theralche
B. Premature adrenarche
C. Both
D. Neither


1. Growth acceleration                              D

2. Normal adolescent sexual development             C

3. Onset of gonadal function usually in 2-3 years   B
You suspect a 16 year female has Turner
syndrome. The most definitive diagnostic test is




a)   Buccal smear
b)   Chromosome analysis
c)   Measuring her FSH and LH
d)   Determining her bone age
e)   Determining her testosterone level
5 year old girl with pubic hair and rapid growth.
She has no breast development

      Possible sources of androgens:

      1.Liver           F

      2.Adrenal         T

      3.Ovary           T

      4.Pituitary       F

      5.Pineal          F
 5 year old girl with pubic hair and rapid growth.
 She has no breast development

Which of the following should be considered
Answer T or F for each:

a) Central precocious puberty            F

b) Congenital adrenal hyperplasia        T

c) McCune Albright syndrome              F

d) Benign premature adrenarche           F

e) Adrenal tumor                         T
 When does puberty occur?
Classic teaching
– 8 -13 in girls   (menarche ~ 2 years
                    after onset of puberty)
– 9 -14 in boys


Case:
Breast development:    6 years
Mother had menarche:   9.5 years
                     Why

Reactivation of
hypothalamic –
pituitary –gonadal
axis
    Gonadatropin dependent
  (central) precocious puberty
Clock turns on early
Idiopathic
  > 95 % girls
   ~ 50 % boys
– Hypothalamic hamartoma (Gelastic seizures)
– NF (optic glioma)
– Head trauma
– Neurosurgery
– Anoxic injury
– Hydrocephalus
            Treatment
Why
– Psychosocial
– Height
What
– GnRH agonist
Gonadotropin independent
   precocious puberty
7 year male presents with 6 month history of pubic
and axillary hair growth as well as adult body odor.
Mother thinks he is growing faster than his peers
No exposure to androgens

PM&SH – nil of note
Mother had menarche at 12 yr
Father had normal timing of his puberty
Medications – none
Height 50th percentile (last height at 25th)
Weight 40th percentile
No café au lait macules
No goiter
Heart and lungs: normal
Abdomen: Firm hepatomegaly with irregular border

    Prepubertal          Asymmetric        Pubertal




   Adrenal source   Enlarged testicle   Precocious puberty
Height 50th percentile (last height at 25th)
Weight 40th percentile
No café au lait macules
No goiter
Heart and lungs: normal
Abdomen: Firm hepatomegaly with irregular border
Genitalia:
  Pubic hair - Tanner 2
  Scrotal thinning
  Testes 5 ml bilaterally (pubertal >3 ml)
Rest unremarkable
         7 year male with signs of puberty

                     Gonadotropins


                                          Pubertal
LABS:
Testosterone 48 ng/dl (<10)               Central precocious
                                          puberty
FSH         <0.1 mIU/mL
                                     LH
LH          <0.1 mIU/mL

                                                        G
TSH         1.0 μIU/mL                    Leydig cell
T4          8.9 μg/dL
             Precocious puberty in the male

                             Gonadotropins


               Prepubertal                        Pubertal

       Gonadotropin independent                   Central precocious
       precocious puberty                         puberty
HCG                                         LH


             *            G                                     G
                      *                           Leydig cell
                  McCune Albright
Familial male       syndrome             1. Gonadotropin independent PP
Precocious puberty                       2. Polyostotic Fibrous Dysplasia
(testotoxicosis)                         3. Café au lait macules
Final diagnosis: Gonadotropin independent precocious
puberty secondary to an βHCG secreting hepatoblastoma
5 year old with breast development
and growth acceleration

- Estradiol 62 pg/ml (<10)
- FSH      <0.1 mIU/mL
- LH      <0.1 mIU/mL



  Gonadotropin independent
  precocious puberty
McCune Albright syndrome:
1. Café au lait macules
2. Gonadotropin independent
   precocious puberty
3. Polyostotic fibrous dysplasia
Growth disorders and
  delayed puberty
                      Delayed puberty


                       Hypogonadism

Hypergonadotropic                    Hypogonadotropic
Hypogonadism (↑FSH, LH)              Hypogonadism (FSH, LH)

                                 Constitutional   Central
 Primary gonadal failure
 - Chromosomal
                                 delay            Hypogonadism
                                                  - Isolate gonad. def.
 - iatrogenic (cancer therapy)
                                                  - MPHD
 - autoimmune oophoritis
                                                  - Kallmann (anosmia)
 - galactosemia
                                                  - Functional
 - test. biosynthetic defect
     A 15 yr boy has short stature and delayed
     puberty. He is now in early puberty (Tanner 2).
     His parents are of average stature. His height
     and weight are just below 3rd percentile.

All of the following are likely except:

a) A bone age of 12 ½ years
b) Growth hormone deficiency
c) Adult height in the normal range
d) Acceleration of growth and sexual maturation
   over the next 2 years.
e) History of normal length and weight at birth
A 15 yr male has delayed puberty. He also has
headaches, diplopia and increased urination.
His height is < 3rd percentille

Which of the following is the most likely
diagnosis?

 a)   Diabetes mellitus
 b)   Pinealoma
 c)   Cerebellar tumor
 d)   Craniopharyngioma
 e)   Pituitary adenoma
   A 14 yr male has tender gynecomastia (3 cm in
   diameter bilaterally). He is in early to mid
   puberty. In most cases the best management for
   this gynecomastia is:


a) Treatment with an anti-estrogen (e.g. Tamoxifen)
b) Treatment with an aromatase inhibitor
c) Treatment with a dopamine agonist
   (bromocryptine)
d) Surgery
e) Reassurance
Diabetes
A 12 year female patient presents with a 4 week history
of polyuria, polydipsia, and marked weight loss.
She is noted to have deep, sighing respiration.
Glucose is 498 mg/dL, pH is 7.06. Her electrolytes
show Na 132, K 4.8, Cl 95 CO2 6 BUN 20 Creat 0.9.
The MOST important initial management is:


a) insulin drip 0.1 units/kg/hour

b) ½ Normal Saline with 40 meq K at 2x maintenance

c) Bicarbonate 1 meq/kg slowly over 1 hour

d) 20 ml/kg normal saline bolus IV
       An obese 16 year male is found to have glycosuria at
       routine urinalysis done as part of regular health care
       maintenance. You order a glucose tolerance test.
       GTT

       Time                     Glucose (mg/dL)
       -0-                      109
       -120-                    188
       Which of the following statements are correct?

     This patient has:

a)    Type 2 diabetes
b)    Impaired glucose tolerance but normal fasting glucose
c)    Normal glucose tolerance
d)    Both impaired fasting glucose and impaired glucose tolerance
  Definition of diabetes


                 Diabetes
≥ 126                           ≥ 200
        < 126                           < 200

                Pre-diabetes
        ≥ 100                           ≥ 140
< 100                           < 140

                 Normal

 Fasting                       2 hr post load
 An obese 14 year male is found to have glycosuria.

 Fasting GTT is ordered and the results are as follows:

 Time                        Glucose (mg/dL)
 -0-                         109
 -120-                       188
 This patient is at risk for the development of all the
 following EXCEPT


a)   Type 2 diabetes
b)   Dyslipidemia
c)   Hypertension
d)   Slipped capital femoral epiphysis
e)   Hashimoto thyroiditis
A 13 year male has new onset type 1 diabetes
mellitus. Therapy for this child may include all
of the following EXCEPT:


a) Glargine (Lantus) and Lipro insulin (Humalog)

b) Detemir (Levemir) and Aspart insulin (Novolog)

c) Metformin

d) Analog insulin administered via an insulin pump
Miscellaneous
             Hypoglycemia
Decreased substrate
– Poor intake
– Defective glycogenolysis or gluconeogenesis
Increase utilization
– Sepsis
– Hyperinsulinism
Absent counter regulatory hormones
– GH
– Cortisol
      Choose correct answer
A. Hypoglycemia from hyperinsulinemia
B. Hypoglycemia from metabolic fuel depletion
C. Both
D. Neither


  1. Usually preceded by ketosis        B

  2. Brisk respones to glucagon         A

  3. Usually responds to oral glucose   B
     Side effects of corticosteroids include all of the
     following except



a)   hypertension
b)   hypoglycemia
c)   decrease bone mineralization
d)   myopathy
e)   cataracts
What is the most likely diagnosis in this newborn infant?

1.   Mother has SLE
2.   Anasarca from cardiac failure
3.   Systemic allergic reaction
4.   Congenital nephrotic syndrome
5.   Turner syndrome
                    5 year old male with short stature




1.   Turner syndrome
2.   VATER syndrome
3.   Albright’s hereditary osteodystrophy
4.   Noonan syndrome
5.   Goldenhar syndrome
A moderately obese adolescent female has
irregular periods, hirsutism and acne

Of the following, which is the most likely
 diagnosis?
a) Cushing syndrome
b) Polycystic ovarian syndrome
c) Virilizing adrenal tumor
d) Non-classical CAH
e) Hyperprolactinemia
       Choose correct answer
A. Diabetes mellitus
B. Diabetes insipidus
C. Both
D. Neither             2 Na + BUN/2.8 + Gluc/18

1. Osmolality of serum > 300 Osm/L     C

2. Osmolality of urine > 500 mOsm/L    A

3. Hypernatremia                       B

								
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