Endocrinology

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Endocrinology
Pediatric Board Review
Graeme Frank, MD
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Calcium
3

• 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 dataGlucose 88
  mg/dLSodium 141 mEq/LCalcium 5.1
  mg/dLPhosphorus 9.1 mg/dLMagnesium 2.1 mg/dL
• The most likely diagnosis is
• Pseudohypoparathyroidism
• Hypoparathyroidism
• Vitamin D deficiency
• Albrights hereditary osteodystrophy

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Actions of PTH

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• 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 dataGlucose 88
  mg/dLSodium 141 mEq/LCalcium 5.1
  mg/dLPhosphorus 9.1 mg/dLMagnesium 2.1 mg/dL
• The most likely diagnosis is
• Pseudohypoparathyroidism
• Hypoparathyroidism
• Vitamin D deficiency
• Albrights hereditary osteodystrophy

6

• 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 dataGlucose 88
  mg/dLSodium 141 mEq/LCalcium 5.1
  mg/dLPhosphorus 9.1 mg/dLMagnesium 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

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Biochemical changes in rickets
Ca PO4 Bone Urine
Stage 1
Stage 2
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Initial
Ca PO4 Alk Phos
9.7 3.1 2514
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Which is consistent with vitamin D deficiency
rickets?
CALCIUM PHOS ALK PHOS

1. Normal Normal Low
2. Low Low Low
3. Low Increased Increased
4. Low Normal Normal
5. Normal Low Increased

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Choose correct answer

1. Vitamin D deficiency rickets
2. Renal osteodystrophy (renal rickets)
3. Both
4. Neither

B
1. Increased phosphate level 2. Increased PTH
level 3. Increased creatinine level
C
B
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THYROID
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• 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 lt 20
• T4 10.1 ?g/dl 9-19
• This child
• Has congenital hypothyroidism and should be
  referred to a congenital hypothyroidism treatment
  center
• Will likely develop mental retardation if
  untreated
• Likely does not have any thyroid abnormality
• Has an altered hypothalamic set-point for T4
• Should be started on thyroxine replacement
  immediately
•  

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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 gt200 ?IU/ml lt 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)
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Congenital hypothyroidism

• Thyroid dysgenesis/agenesis
• Prevalence 1 in 4,000 Whites 1 in 2,000 Blacks
  1 in 32,000
• 21 female to male ratio
• Clinical features includehypotonia, enlarged
  posterior fontanelle, umbilical hernia, indirect
  hyperbilirubinemia
• Laboratory findings Very high TSH and low T4
• Therapy Thyroxine keep TSH in normal range

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6 month female with congenital hypothyroidism
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• 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 showedT4 2.1 µg/dL
  (4.5-12.5) TSH 2.3 µIU/mL (0.3-5.0)
• The most likely diagnosis is
• Hypothyroidism due to dysgenesis of the thyroid
  gland
• Central hypothyroidism
• TBG deficiency
• Hypothyroidism from excess iodine exposure
• Normal thyroid function (as the TSH is normal)

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Central hypothyroidism - rare
vs.
TBG deficiency12800
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Thyroxine (T4)

• Major product secreted by the thyroid
• Circulates bound to thyroid binding proteins -
  thyroid binding globulin (TBG)
• Only a tiny fraction (lt 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

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TBG deficiency
Central hypothyroidism
Free T4 Low Normal TBG level Normal
Low T3RU Low High
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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
•  

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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
• INH
• Ortho Tri-Cylen
• Retinoid acid
• Ciprofloxacin
• Doxycycline

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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
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• 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

• Infectious
• Inflammatory
• Autoimmune
• Toxic (drug)
• Neoplastic

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Normal thyroid
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DC

• 16 year 7 month
• Growth failure x 1 1/2 years

• LabsTSH 1008 µIU/ ml (0.3-5.0)T4
  lt1.0 µg/dl (4-12)Antithyro Ab. 232
  U/ml (0-1)A-perox Ab. 592 IU/ml (lt0.3)Prolact
  in 29 ng/ml (2-18)
• Cholesterol 406 mg/dl (100-170)

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DC
Start of thyroxine
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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
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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 lt 0.1
?IU/ml 0.3-5.5 T4 14.8 ?g/dl 4.5-12 T3 580
ng/dl 90-190
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Restlessness, poor attention span
Eye changes
Goiter
Tachycardia, wide pulse pressure
Increased GFR - polyuria

Diarrhea
Menstrual abnormalities
Myopathy
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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
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Sexual differentiation
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• 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
• Testosterone
• 17-hydroxyprogesterone
• Serum sodium and potassium
• DHEAS
• DHEAS/androstenedione ratio

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Cholesterol
Desmolase
17-OH
Pregnenolone
17 (OH) pregnenolone
DHEA
3-?-HSD
3-?-HSD
3-?-HSD
17-OH
17 (OH) progesterone
Androstenedione
Progesterone
21-OH
21-OH
DOCA
Compound S
TESTOSTERONE
11-OH
11-OH
Corticosterone
CORTISOL
ALDOSTERONE
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• If she has salt wasting congenital adrenal
  hyperplasia, which abnormalities are likely to
  develop. True or False for each
• Increased serum potassium
• Decreased serum sodium
• Decreased bicarbonate
• Decreased plasma cortisol
• Increased plasma renin activity

T
T
T
T
T
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• A 1-year male infant has non palpable testes.
  Of the following, the most appropriate next step
  would be

• Schedule a re-examination in 18 months
• Refer the patient for an exploratory laparotomy
• Begin therapy with LHRH
• Measure the plasma testosterone after stimulation
  with HCG
• Begin therapy with testosterone enanthate, 50 mg
  IM monthly for 3 months.

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

• Fluid resuscitation20 ml/kg Normal saline
• Glucocorticoid2 mg/kg Solucortef IV
• Monitor EKG

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Modes of presentation

• Classical
• Simple virilizing
• Virilizing with salt loss
• Non classical / Late onset

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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

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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?
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Complete androgen insensitivity
XY Genotype
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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
• Blood pressure in all 4 extremities
• Careful fundoscopic examination
• Rectal examination
• Measurement of blood pressure with postural
  change
• Cubitus valgus and shield shaped chest

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Early Puberty
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• The earliest sign of puberty in a male is

• Enlargement of the penis
• Enlargement of the testes
• Growth acceleration
• Pubic hair growth
• Axillary hair growth

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• 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
• Ingestion of her mothers OCPs
• Precocious puberty
• Premature adrenarche
• Premature thelarche
• McCune Albright Syndrome

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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

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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 chartNormal growth without growth
acceleration

• Most likely diagnosis
• Precocious puberty
• Benign premature adrenarche
• Non-classical congenital adrenal hyperplasia
• Adrenal tumor
• Pinealoma

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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)

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Choose correct answer

1. Premature theralche
2. Premature adrenarche
3. Both
4. Neither

D
1. Growth acceleration 2. Normal adolescent
sexual development 3. Onset of gonadal function
usually in 2-3 years
C
B
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• You suspect a 16 year female has Turner syndrome.
  The most definitive diagnostic test is

• Buccal smear
• Chromosome analysis
• Measuring her FSH and LH
• Determining her bone age
• Determining her testosterone level

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

• Possible sources of androgens
• Liver
• Adrenal
• Ovary
• Pituitary
• Pineal

F
T
T
F
F
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• 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
• Central precocious puberty
• Congenital adrenal hyperplasia
• McCune Albright syndrome
• Benign premature adrenarche
• Adrenal tumor

F
T
F
F
T
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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
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Why

• Reactivation of hypothalamic pituitary gonadal
  axis

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Gonadatropin dependent (central) precocious
puberty

• Clock turns on early
• Idiopathic
• gt 95 girls 50 boys
• Hypothalamic hamartoma (Gelastic seizures)
• NF (optic glioma)
• Head trauma
• Neurosurgery
• Anoxic injury
• Hydrocephalus

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Treatment

• Why
• Psychosocial
• Height
• What
• GnRH agonist

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Gonadotropin independent precocious puberty
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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 PMSH
nil of note Mother had menarche at 12 yrFather
had normal timing of his puberty Medications
none
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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
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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 GenitaliaPubic hair - Tanner 2Scrotal
thinningTestes 5 ml bilaterally (pubertal gt3
ml) Rest unremarkable
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7 year male with signs of puberty
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Precocious puberty in the male
Gonadotropins
Prepubertal Pubertal Gonadotropin
independent Central precocious precocious
puberty puberty
LH
G
Leydig cell
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Final diagnosis Gonadotropin independent
precocious puberty secondary to an ßHCG
secreting hepatoblastoma
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• 5 year old with breast development
• and growth acceleration - Estradiol 62 pg/ml
  (lt10)
• FSH lt0.1 mIU/mL
• LH lt0.1 mIU/mL

Gonadotropin independent precocious puberty

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• McCune Albright syndrome
• Café au lait macules
• Gonadotropin independentprecocious puberty
• Polyostotic fibrous dysplasia

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Growth disorders anddelayed puberty
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Delayed puberty
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• 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 bone age of 12 ½ years
• Growth hormone deficiency
• Adult height in the normal range
• Acceleration of growth and sexual maturation over
  the next 2 years.
• History of normal length and weight at birth

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• A 15 yr male has delayed puberty. He also has
  headaches, diplopia and increased urination. His
  height is lt 3rd percentille
• Which of the following is the most likely
  diagnosis?

• Diabetes mellitus
• Pinealoma
• Cerebellar tumor
• Craniopharyngioma
• Pituitary adenoma

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• 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

• Treatment with an anti-estrogen (e.g. Tamoxifen)
• Treatment with an aromatase inhibitor
• Treatment with a dopamine agonist (bromocryptine)
• Surgery
• Reassurance

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Diabetes
75

• 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

1. insulin drip 0.1 units/kg/hour
2. ½ Normal Saline with 40 meq K at 2x maintenance
3. Bicarbonate 1 meq/kg slowly over 1 hour
4. 20 ml/kg normal saline bolus IV

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• 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

1. Type 2 diabetes
2. Impaired glucose tolerance but normal fasting
   glucose
3. Normal glucose tolerance
4. Both impaired fasting glucose and impaired
   glucose tolerance

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Definition of diabetes
lt 100
lt 140
Normal
Fasting
2 hr post load
78

• 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

1. Type 2 diabetes
2. Dyslipidemia
3. Hypertension
4. Slipped capital femoral epiphysis
5. Hashimoto thyroiditis

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• A 13 year male has new onset type 1 diabetes
  mellitus. Therapy for this child may include
  all of the following EXCEPT

1. Glargine (Lantus) and Lipro insulin (Humalog)
2. Detemir (Levemir) and Aspart insulin (Novolog)
3. Metformin
4. Analog insulin administered via an insulin pump

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Miscellaneous
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Hypoglycemia

• Decreased substrate
• Poor intake
• Defective glycogenolysis or gluconeogenesis
• Increase utilization
• Sepsis
• Hyperinsulinism
• Absent counter regulatory hormones
• GH
• Cortisol

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Choose correct answer

1. Hypoglycemia from hyperinsulinemia
2. Hypoglycemia from metabolic fuel depletion
3. Both
4. Neither

1. Usually preceded by ketosis 2. Brisk respones
to glucagon 3. Usually responds to oral glucose
B
A
B
83

• Side effects of corticosteroids include all of
  the following except

• hypertension
• hypoglycemia
• decrease bone mineralization
• myopathy
• cataracts

84

• What is the most likely diagnosis in this newborn
  infant?
• Mother has SLE
• Anasarca from cardiac failure
• Systemic allergic reaction
• Congenital nephrotic syndrome
• Turner syndrome

85
5 year old male with short stature

1. Turner syndrome
2. VATER syndrome
3. Albrights hereditary osteodystrophy
4. Noonan syndrome
5. Goldenhar syndrome

86

• A moderately obese adolescent female has
  irregular periods, hirsutism and acne
• Of the following, which is the most likely
  diagnosis?

• Cushing syndrome
• Polycystic ovarian syndrome
• Virilizing adrenal tumor
• Non-classical CAH
• Hyperprolactinemia

87
Choose correct answer

1. Diabetes mellitus
2. Diabetes insipidus
3. Both
4. Neither

2 Na BUN/2.8 Gluc/18
C
1. Osmolality of serum gt 300 Osm/L 2. Osmolality
of urine gt 500 mOsm/L 3. Hypernatremia
A
B