28.2 Pediatric Endocrine & Metabolic Disorders: Short Stature and Growth Hormone, Gigantism, Diabetes Insipidus, Congenital Hypothyroidism, Graves Disease & Goiter, Type 1 Diabetes and DKA, Congenital Adrenal Hyperplasia, Cushing Syndrome, Pheochromocytoma and Adrenal Crisis

Why this area matters

The TOS endocrine competencies are to:

• identify the burden of these disorders;
• reach a diagnosis and differential diagnosis;
• prioritize tests and recognize emergencies (DKA, adrenal crisis, thyroid storm);
• manage them and educate the family.

Expanded newborn screening detects congenital hypothyroidism and congenital adrenal hyperplasia before symptoms, so intellectual disability and salt-wasting deaths can be prevented. Type 1 diabetes often presents late in DKA.

Short stature, gigantism and diabetes insipidus

• Measuring growth: plot height on WHO growth charts and compare it with mid-parental height. A growth velocity that is crossing percentiles downward is more worrying than height alone.
• Normal variants:
  • familial short stature: short parents, normal growth velocity, bone age equal to chronological age, normal puberty;
  • constitutional delay of growth and puberty: often a family history of "late bloomers", delayed bone age, late puberty, normal adult height.
• Pathologic causes:
  • growth hormone deficiency: slow growth, chubby immature face, micropenis or neonatal hypoglycemia in congenital cases; low IGF-1 with failed GH stimulation tests; treated with recombinant GH;
  • hypothyroidism;
  • Turner syndrome (karyotype every short girl without explanation);
  • chronic disease (renal, celiac, cardiac, malnutrition);
  • glucocorticoid excess;
  • skeletal dysplasias such as achondroplasia (FGFR3; disproportionate short limbs, large head, normal intelligence), the commonest cause of disproportionate dwarfism;
  • psychosocial deprivation.
• Gigantism: GH excess before epiphyseal closure, usually a pituitary adenoma (sometimes McCune-Albright syndrome). It causes very tall stature and is diagnosed by raised IGF-1 and failure of GH suppression with glucose.
• Diabetes insipidus:
  • Central DI: lack of ADH from craniopharyngioma, trauma, surgery, histiocytosis or idiopathic causes.
  • Nephrogenic DI: renal resistance, from X-linked V2 receptor mutations, lithium or hypercalcemia.
  • Both cause polyuria with dilute urine and hypernatremia, and infants risk dehydration.
  • A water deprivation test followed by desmopressin separates them: urine concentrates after desmopressin in central DI.
  • Treat central DI with desmopressin. Treat nephrogenic DI with thiazides, a low-solute diet and adequate water.

Thyroid disorders

• Congenital hypothyroidism:
  • the most common preventable cause of intellectual disability; usually thyroid dysgenesis;
  • most babies look normal at birth, which is why newborn screening is essential;
  • later signs are prolonged jaundice, constipation, large anterior fontanel, umbilical hernia, macroglossia, hoarse cry, hypotonia and lethargy;
  • confirm with high TSH and low free T4, then start levothyroxine 10 to 15 mcg/kg/day as soon as possible, ideally within the first 2 weeks, with frequent monitoring.
• Graves disease in children: mostly adolescent girls, with goiter, weight loss, tremor, tachycardia, behavior and school problems, and eye signs. Treated with methimazole, then radioiodine or surgery if needed. Propylthiouracil is avoided in children because of liver failure.
• Neonatal thyrotoxicosis follows transplacental TSH-receptor antibodies from a mother with Graves disease.
• Goiter:
  • iodine deficiency is the main preventable cause, prevented by iodized salt (the ASIN Law, RA 8172);
  • chronic lymphocytic (Hashimoto) thyroiditis is common in adolescents, with euthyroidism or hypothyroidism.
  • Severe iodine deficiency in pregnancy causes cretinism.

Type 1 diabetes mellitus and DKA

• Type 1 diabetes:
  • autoimmune destruction of beta cells, peaking at 5 to 7 years and at puberty;
  • polyuria, polydipsia, weight loss, new bedwetting, fatigue and candidiasis;
  • DKA is the first presentation in many.
  • Treatment is lifelong insulin (basal-bolus or pump), glucose monitoring, carbohydrate counting, exercise and education, with screening for thyroid and celiac disease.
• Diabetic ketoacidosis:
  • definition: glucose above 200 mg/dL, venous pH below 7.3 or bicarbonate below 18 mmol/L, and ketonemia or ketonuria;
  • fluids: restore circulation with 10 to 20 mL/kg of isotonic saline, then replace the deficit over 24 to 48 hours;
  • insulin: an infusion of 0.05 to 0.1 units/kg/hour started after the first hour of fluids, without a bolus;
  • potassium: add it once urine output is confirmed, because total body potassium is depleted even when serum K is normal or high;
  • add dextrose when glucose falls to about 250 to 300 mg/dL;
  • bicarbonate is avoided except in life-threatening hyperkalemia.
• Cerebral edema is the main cause of DKA death in children. It presents with headache, bradycardia, hypertension, falling consciousness and recurrent vomiting, and is treated with mannitol or hypertonic saline and reduced fluids.
• Type 2 diabetes is increasing in obese adolescents, with acanthosis nigricans and insulin resistance.

Adrenal disorders

• Congenital adrenal hyperplasia (21-hydroxylase deficiency):
  • autosomal recessive;
  • cortisol and aldosterone fall while adrenal androgens rise;
  • girls have ambiguous genitalia at birth with a 46,XX karyotype and a normal uterus;
  • boys look normal but present at 1 to 3 weeks with a salt-wasting crisis: vomiting, dehydration, hyponatremia, hyperkalemia, hypoglycemia and shock;
  • simple virilizing forms cause early puberty and tall childhood stature with advanced bone age;
  • diagnosis: raised 17-hydroxyprogesterone, also detected on ENBS;
  • treatment: hydrocortisone plus fludrocortisone and salt, stress dosing and genital surgery when appropriate.
• Cushing syndrome: in children it is usually exogenous steroids. Endogenous causes are adrenal tumors in young children and pituitary adenoma in older children. The hallmark is weight gain with falling growth velocity, unlike simple obesity, where height is normal or tall.
• Pheochromocytoma: a catecholamine-secreting tumor causing sustained or paroxysmal hypertension, headache, sweating and palpitations. It is linked to MEN 2, von Hippel-Lindau and NF1. Diagnose with plasma or urine metanephrines. Give alpha-blockade before beta-blockade and surgery.
• Neuroblastoma arises from the adrenal medulla and is covered under oncology.
• Adrenal insufficiency and adrenal crisis:
  • causes are CAH, autoimmune Addison disease, adrenal hemorrhage (meningococcemia), and abrupt withdrawal of long-term steroids;
  • crisis brings vomiting, abdominal pain, hypotension, hypoglycemia, hyponatremia and hyperkalemia;
  • treat with IV hydrocortisone at once (about 50 to 100 mg/m²), saline and dextrose;
  • children on steroid replacement need stress doses during illness, injury or surgery, and families carry an emergency injection.