Review – Kaplan Pediatrics: Endocrine Disorders

PITUITARY DISORDERS

Hypopituitarism

•                Deficiency of growth hormone ± other hormones; also delay in pubertal develop- ment is common; results in postnatal growth impairment corrected by growth hormone

• Isolated growth-hormone deficiency or multiple pituitary deficiencies
  • Congenital—autosomal dominant, recessive, or X-linked recessive
  • Acquired—any lesion that damages the hypothalamus, pituitary stalk, or anterior pituitary (most common is craniopharyngioma)
• Clinical presentation
  • Congenital hypopituitarism:

°      Normal size and weight at birth; then severe growth failure in first year

• Infants—present with neonatal emergencies, g., apnea, hypoglycemic seizures, hypothyroidism, hypoadrenalism in first weeks or boys with microphallus and small testes ± cryptorchidism
• Also have a variety of dysmorphic features; appearance

• Acquired hypopituitarism:
  • Findings appear gradually and progress:

} Growth failure

} Pubertal failure, amenorrhea

} Symptoms of both decreased thyroid and adrenal function.

} Possible DI

• If there is an expanding tumor:

} Headache, vomiting

} Visual changes, decreased school performance

} Papilledema, cranial nerve palsies

• Laboratory evaluation

−   Screen for low serum insulin-like growth factor (IGF)-1 and IGF-binding protein-3 (IGF-BP3)

• Definitive test—growth-hormone stimulation test

−    Examine other pituitary function:

• Thyroid-stimulating hormone (TSH), T4
• Adrenocorticotropic hormone (ACTH), cortisol, dehydroepiandrosterone (DHEA) sulfate, gonadotropins, and gonadal steroids

 

 

 

 

 

Note

If there is a normal response to hypothalamic-releasing hormones, the pathology

is located within the hypothalamus.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Note

If the history suggests anything other than familial tall stature or obesity, or if there are positive physical findings, then the patient needs laboratory evaluation.

• Other studies
  • X-ray most helpful with destructive lesions (enlargement of sella, erosions)
  • Calcification

−   Bone age—skeletal maturation markedly delayed (BA 75% of CA)

− MRI is indicated in all patients with hypopituitarism. (superior to CT scan)

• Differential diagnoses (the major ones)

− Systemic conditions (Weight is often proportionally much less than height.)

• Constitutional delay (delayed BA, delayed adolescent growth spurt, and pubertal development)
• Familial short stature (BA = CA, short parents)

−   Primary hypothyroidism

• Emotional deprivation (psychosocial dwarfism)
• Treatment
  • Classic growth-hormone deficiency—recombinant growth hormone
  • Need periodic thyroid evaluation—develop reversible hypothyroidism

•        Indications—growth hormone currently approved in United States for

• Documented growth-hormone deficiency
• Turner syndrome
• End-stage renal disease before transplant
• Prader-Willi syndrome
• Intrauterine growth retardation (IUGR) without catch-up growth by 2 years of age

– Idiopathic pathologic short stature

 

Hyperpituitarism

• Primary—rare; most are hormone-secreting adenomas
• Majority are deficiencies of target organs and because of negative feedback, there are increases in hypothalamus and pituitary hormones
• Laboratory evaluation
  • Screen—IGF-1 and IGF-BP3 for growth hormone excess; confirm with a glucose suppression test

−    Need MRI of pituitary

• Chromosomes especially in tall males (decreased upper- to lower-body segment ratio suggests XXY; mental retardation suggests fragile X)

−    Thyroid tests

• Management
  • Treatment only if prediction of adult height (based on BA) >3 SD above the mean or if there is evidence of severe psychosocial impairment
  • Trial of sex steroids (accelerates puberty and epiphyseal fusion)

 

Precocious Puberty

• Definition
  • Girls—sexual development <8 years old
  • Boys—sexual development <9 years old

 

 

• Most common etiologies
  • Sporadic and familial in girls
  • Hamartomas in boys
• Clinical presentation—advanced height, weight, and bone age; early epiphyseal closure and early/fast advancement of Tanner stages
• Evaluation
  • Screen—significant increase in leuteinizing hormone
  • Definitive—GnRH stimulation test; give intravenous GnRH analog for a brisk, leuteinizing hormone response
  • If positive, then order MRI
• Treatment—stop sexual advancement and maintain open epiphyses (stops BA advancement) with leuprolide

 

Incomplete Precocious Puberty

• Premature thelarche
  • Usually isolated, transient (from birth due to maternal estrogens)
  • May be first sign of true precocious puberty
• Premature adrenarche—early adrenal androgen production (variation of normal)— axillary, inguinal, and genital It is familial.
• Premature menarche—very rare (other causes of bleeding much more common)

 

 

THYROID DISORDERS

 

Hypothyroidism

A 2-month-old patient appears to be having inadequate weight gain. His mother states he is constipated. On examination, he has decreased muscle tone, a large fontanel, a large tongue, and an umbilical hernia.

• Congenital hypothyroidism—most are primary (i.e., from thyroid gland)
  • Sporadic or familial; with or without a goiter
    • Most common is thyroid dysgenesis (hypoplasia, aplasia, ectopia); no goiter
    • Defect in thyroid hormone synthesis—goitrous; autosomal recessive

°      Transplacental passage of maternal thyrotropin (transient)

• Exposure to maternal antithyroid drugs
• Radioiodine exposure/fetal exposure to excessive iodine (topical iodine antiseptics) (now rare in S.)
• Iodine deficiency or endemic goiter
• Central hypopituitarism

• Clinical presentation is known as “cretinism.”

°      Prolonged jaundice

• Large tongue
• Umbilical hernia
• Edema

 

 

 

 

 

 

 

 

 

 

 

Note

Autoimmune Polyglandular Disease

Type I

• Hypoparathyroidism
• Addison disease
• Mucocutaneous candidiasis
• Small number with autoimmune thyroiditis

Type II (Schmidt syndrome)

• Addison disease, plus:
• Insulin-dependent DM
• With or without thyroiditis

 

Note

Thyroid cancer in children is uncommon, but you should know about medullary carcinoma (parafollicular cells), seen in 2 of the multiple endocrine neoplasias (MEN):

• MEN IIA: hyperplasia or cancer of thyroid plus adrenal medullary hyperplasia or

pheochromocytoma plus

parathyroid hyperplasia

• MEN IIB (mucosal neuroma syndrome): multiple neuromas plus medullary thyroid cancer plus pheochromocytoma

°      Mental retardation; developmental delay

• Anterior and posterior fontanels wide
• Mouth open
• Hypotonia

• Other findings—weight and length normal at birth, feeding difficulties, apnea, sluggish, decreased appetite, increased sleep, constipation, decreased temperature, skin cold and mottled, peripheral anemia; apathetic appearance
• Laboratory evaluation:

°      Low serum T4 or free T4; increased TSH

• Treatment—sodium thyroxine
• Acquired hypothyroidism
  • Hashimoto; thryroiditis is most common cause; may be part of autoimmune poly- glandular syndrome
  • Typically presents in adolescence

− Other causes—iatrogenic (medications, irradiation, surgery, radioiodine); systemic disease (cystinosis, histiocytic infiltration)

• Clinical presentation
  • Many more girls than boys

−                  First sign usually deceleration of growth

• Then myxedema, constipation, cold intolerance, decreased energy, increased sleep, delayed osseous maturation, delayed puberty, headache, visual problems
• Diffusely increased, firm, nontender thyroid; but may be atrophic so can be non- goitrous
• Laboratory and treatment—same as congenital

 

Hyperthyroidism

A 12-year-old girl has a 6-month history of hyperactivity and declining school performance. Appetite is increased; but she shows no weight gain. Physical examination reveals a slight tremor of the fingers, mild exophthalmos, and a neck mass.

• Almost all cases are Graves disease
• Peak at age 11–15 years; more girls than boys
• Most with family history of some form of autoimmune thyroid disease
• Findings
  • Infiltration of thyroid and retro-orbital tissue with lymphocytes and plasma cells → exopthalmos

−   Lymphadenopathy and splenomegaly

− Thymic hyperplasia

• In whites, association with HLA-B8 and DR3 is also seen with other DR3-related dis- orders (Addison disease, diabetes mellitus, myasthenia gravis, celiac disease).
• Clinical
  • Most signs and symptoms appear gradually

−   Earliest usually emotional lability and motor hyperactivity

 

 

− Decreased school performance, tremor, increased appetite with weight loss, skin flushed with increased sweating, muscle weakness, tachycardia, palpitations, arrhythmias, hypertension

− Goiter, exophthalmos

− Thyroid storm—acute onset of hyperthermia, severe tachycardia, restlessness →

rapid progression to delirium, coma, and death

• Laboratory evaluation

− Increased T4, T3, free T4

• Decreased TSH
• Measurable TRS-AB (and may have thyroid peroxidase antibodies)
• Treatment

−   Propylthiouracil (PTU) or methimazole

• Beta blockers for acute symptoms (thyroid storm)
• If medical treatment not adequate, radioablation or surgery; then treat as hypothy- roid (daily thyroxine replacement)

 

 

PARATHYROID DISORDERS

 

Hypoparathyroidism

• Parathyroid hormone (PTH) deficiency
• Etiologies
  • Aplasia/hypoplasia—most with DiGeorge or velocardiofacial syndrome
  • X-linked recessive—defect in embryogenesis
  • Autosomal dominant—mutation in calcium-sensing receptor
  • Postsurgical (thyroid)
  • Autoimmune—polyglandular disease
  • Idiopathic (cannot find other cause)
• Clinical presentation
  • Early—muscle pain/cramps, numbness, tingling

−   Laryngeal and carpopedal spasm

• Seizures (hypocalcemic seizures in newborn; think DiGeorge)

• Laboratory evaluation
  • Decreased serum calcium (5–7 mg/dL)
  • Increased serum phosphorus (7–12 mg/dL)
  • Normal or low alkaline phosphatase
  • Low 1,25 [OH]2D3 (calcitriol)
  • Normal magnesium
  • Low parathyroid hormone (immunometric assay)
  • EKG: prolongation of QT
• Treatment
  • Emergency for neonatal tetany → intravenous 10% calcium gluconate and then 1,25[OH]2D3 (calcitriol); this normalizes the calcium

 

 

• Chronic treatment with calcitriol or vitamin D2 (less expensive) plus adequate cal- cium intake (daily elemental calcium)
• Decrease foods high in phosphorus (milk, eggs, cheese)

 

Vitamin D Deficiency

• Most common cause of rickets
• Poor intake, inadequate cutaneous synthesis
• Low serum phosphate, normal to low serum calcium lead to increased PTH and increased alkaline phosphatase
• Increased 25-hydroxy vitamin D
• Fractures, rachitic rosary, craniotabe bone deformities
• Treatment: initial vitamin D replacement and calcium, then adequate dietary calcium and phosphate

 

 

ADRENAL DISORDERS

TheFetus.net.

 

Figure 16-1. Ambiguous Genitalia Seen in Congenital Adrenal Hyperplasia

 

 

Congenital Adrenal Hyperplasia (CAH)

A 1-month-old infant is seen with vomiting and severe dehydration. Physical examination reveals ambiguous genitalia; laboratory tests show hyponatremia.

•        21-Hydroxylase deficiency (most common)

• Autosomal-recessive enzyme deficiency
• Decreased production of cortisol → increased ACTH → adrenal hyperplasia
• Salt losing (not in all cases; some may have normal mineralocorticoid synthesis)

 

 

 

• Precursor steroids (17-OH progesterone) accumulate
• Shunting to androgen synthesis → masculinizes external genitalia in females
• Findings (with salt losing):

• Progressive weight loss (through 2 weeks of age), anorexia, vomiting, dehydration
• Weakness, hypotension
• Hypoglycemia, hyponatremia, hyperkalemia

°      Affected females—masculinized external genitalia (internal organs normal)

• Males normal at birth; postnatal virilization
• Laboratory evaluation

−   Increased 17-OH progesterone

• Low serum sodium and glucose, high potassium, acidosis
• Low cortisol, increased androstenedione and testosterone
• Increased plasma renin and decreased aldosterone
• Definitive test—measure 17-OH progesterone before and after an intravenous bolus of ACTH

• Treatment

−   Hydrocortisone

• Fludrocortisone if salt losing

−   Increased doses of both hydrocortisone and fludrocortisone in times of stress

• Corrective surgery for females

 

Cushing Syndrome

• Exogenesis—most common reason is prolonged exogenous glucocorticoid adminis-
• Endogenous

− In infants—adrenocortical tumor (malignant)

− Excess ACTH from pituitary adenoma results in Cushing disease (age >7 years)

• Clinical findings

−   Moon facies

• Truncal obesity
• Impaired growth

− Striae

−    Delayed puberty and amenorrhea

• Hyperglycemia
• Hypertension common
• Masculinization

−   Osteoporosis with pathologic fractures

• Laboratory evaluation

−   Dexamethasone-suppression test (single best test)

• Determine cause—CT scan (gets most adrenal tumors) and MRI (may not see if microadenoma)

• Treatment—remove tumor; if no response, remove adrenals; other tumor-specific protocols

Note

The other 3 main defects in CAH:

• 3-beta-hydroxysteroid deficiency: salt-wasting, male and female pseudohermaphrodites, precocious pubarche; increased 17-OH pregnenolone and DHEA
• 11-beta-hydroxylase deficiency: female pseudohermaphroditism, postnatal virilization, hypertension; increased compound S, DOC, serum androgens, and hypokalemia
• 17-alpha hydroxyl/17,20 lyase deficiency: male pseudohermaphroditism, sexual infantilism, hypertension; increased DOC, 18-OH DOC, 18-OH corticosterone, and
  • alpha-hydroxylated steroids; hypokalemia

 

 

DIABETES MELLITUS

 

Type 1

An 8-year-old boy is seen in the emergency department with vomiting and abdominal pain of 2 days’ duration. His mother states he has been drinking a lot of fluids for the past month, and reports weight loss during that time. Physical examination reveals a low-grade fever, and a moderately dehydrated boy who appears acutely ill. He is somnolent but asks for water. Respirations are rapid and deep. Laboratory tests reveal a metabolic acidosis and hyperglycemia.

 

• Etiology—T-cell−mediated autoimmune destruction of islet cell cytoplasm, insulin autoantibodies (IAA)
• Pathophysiology—low insulin catabolic state
  • Hyperglycemia → osmotic diuresis; when renal threshold for glucose reabsorption is reached (180 mg/dL) → glycosuria
  • Loss of fluid, electrolytes, calories, and dehydration
  • Accelerated lipolysis and impaired lipid synthesis → increased free fatty acids → ketone bodies → metabolic acidosis and Kussmaul respiration → decreased consciousness
• Clinical presentation

−   Polyuria

• Polydipsia
• Polyphagia
• Weight loss
• Most initially present with diabetic ketoacidosis

• Diagnostic criteria
  • Impaired glucose tolerance test
    • Fasting blood sugar 110–126 mg/dL or 2-hour glucose during OGTT<200 mg/ dL but ≥125 mg/dL
  • Diabetes
    • Symptoms + random glucose ≥200 mg/dL or
    • Fasting blood sugar ≥126 mg/dL or
    • 2 hour OGTT glucose ≥200 mg/dL

−   Diabetic ketoacidosis—hyperglycemia, ketonuria, increased anion gap, de- creased HCO3 (or total CO2), decreased pH, increased serum osmolality

• Treatment
  • Insulin administration, dosed primarily with meals
  • Testing before meals and at night
  • Diet modification
  • Close patient follow up

 

 

 

• Diabetic ketoacidosis:

°      Insulin must be started at beginning of treatment.

• Rehydration also lowers
• Monitor blood sugar, electrolytes; avoid rapid changes
• Sodium falsely low

• Exercise
  • All forms of exercise or competitive sports should be
  • Regular exercise improves glucose
  • May need additional CHO exchange

 

Type 2

•        Most common cause of insulin resistance is childhood obesity.

• Symptoms more insidious
  • Usually excessive weight gain
  • Fatigue
  • Incidental glycosuria (polydipsia and polyuria uncommon)
• Features of the metabolic syndrome
• Hyperglycemia (insulin)
• Hyperinsulinism secondary to insulin resistance
• Hyperlipidemia
• Hypertension
• Acanthosis nigricans
• Nutritional education is the most important initial approach—weight loss and increased physical activity
• Most develop type II DM at younger adult age—will need oral hypoglycemic
• Differentiate from Maturity Onset Diabetes of Youth (MODY)—autosomal dominance in at least 3 family generations starting at ages 9-25 years