Endocrine Gland Disorders & Disorders of Growth and Puberty

Forfar & Arneil 7th Edition · Growth hormone deficiency · Hypothyroidism · Hyperthyroidism · Diabetes insipidus · Adrenal insufficiency · Congenital adrenal hyperplasia · Precocious puberty · Delayed puberty · Short stature · Turner syndrome
📌 Key principles: Growth velocity is more informative than single measurement. Short stature workup includes bone age, IGF-1, thyroid function. Delayed puberty: constitutional delay vs hypogonadism. Precocious puberty: central vs peripheral. Congenital adrenal hyperplasia presents with salt-wasting crisis or ambiguous genitalia.

📖 Core concepts: growth, puberty & endocrine disorders

📏 Growth assessment
Measure height, weight, head circumference. Plot on centile charts. Height velocity (cm/year) is key. Bone age (Greulich & Pyle) predicts remaining growth. Delayed bone age = constitutional delay or endocrinopathy.
🩺 Short stature differential
Familial short stature, constitutional delay (CDGP), GH deficiency, hypothyroidism, Turner syndrome, skeletal dysplasias, chronic disease. IGF-1 and GH stimulation tests for GHD.
⏳ Puberty – normal timing
Girls: breast development (Tanner B2) 8-13y, menarche ~2y later. Boys: testicular volume >4ml (Tanner G2) 9-14y. Adrenarche (pubic hair) can occur independently.
⚡ Precocious puberty
Secondary sexual characteristics <8y (girls) or <9y (boys). Central (GnRH-dependent) vs peripheral (gonadotropin-independent). GnRH agonist test differentiates. MRI brain for CNS lesions.
🦋 Thyroid disorders
Congenital hypothyroidism: newborn screening, delayed treatment causes intellectual disability. Acquired hypothyroidism: Hashimoto, autoimmune. Hyperthyroidism: Graves disease (neonatal transient or childhood).
🥔 Adrenal disorders
CAH: 21-hydroxylase deficiency (95%) – salt-wasting (vomiting, collapse, hyponatremia, hyperkalemia) or simple virilizing. Adrenal insufficiency: cortisol ± mineralocorticoid replacement.
📊 Key investigations: Bone age X-ray (left wrist), IGF-1, IGFBP-3, GH stimulation tests (clonidine, glucagon, arginine), TSH, fT4, cortisol, ACTH, 17-OHP, karyotype (Turner), pelvic ultrasound (ovaries), GnRH agonist test.

🔍 Clinical approach to growth and pubertal disorders

1
Accurate anthropometry & plotting – Height, weight, head circumference on appropriate centile charts. Calculate height velocity (cm/yr) over 6-12 months.
2
Bone age assessment – Left wrist X-ray (Greulich & Pyle). Bone age < chronological age: constitutional delay, GH deficiency, hypothyroidism. Bone age advanced: precocious puberty, obesity, hyperthyroidism.
3
Evaluate short stature – Rule out chronic disease (celiac, IBD, renal, cardiac). Screen thyroid (TSH, fT4), IGF-1, karyotype (girls for Turner). GH provocation tests if height <-2.5 SDS or low IGF-1.
4
Delayed puberty workup – Tanner staging, testicular volume (orchidometer), bone age. Constitutional delay vs hypogonadotropic hypogonadism (low LH/FSH) vs hypergonadotropic (Turner, Klinefelter).
5
Precocious puberty – Confirm secondary sexual characteristics. GnRH agonist test: stimulated LH >5 IU/L → central precocious puberty. MRI brain if central. Peripheral: rule out adrenal tumor, McCune-Albright, hCG-secreting tumor.
6
Thyroid assessment – TSH, fT4. Autoantibodies (TPO, Tg) for Hashimoto. TRAb for neonatal Graves. Ultrasound if nodule.
7
Adrenal crisis recognition – Vomiting, hypotension, hyponatremia, hyperkalemia in infant. Emergency: hydrocortisone, IV fluids, fludrocortisone.
📌 Clinical pearl: Height velocity <4 cm/year between 4 years and puberty is pathological regardless of height centile. Always investigate.

📋 Stepwise management of endocrine disorders in children

1
Growth hormone deficiency – Confirmed by two GH stimulation tests (peak GH <7-10 mcg/L). MRI brain (pituitary/hypothalamus). Treatment: recombinant GH (25-50 mcg/kg/day). Monitor height velocity, IGF-1, bone age annually.
2
Congenital hypothyroidism (CHT) – Newborn screening (elevated TSH). Start levothyroxine (10-15 mcg/kg/day) immediately. Goal: TSH 0.5-5 mIU/L, fT4 in upper half. Monitor growth, development.
3
Graves disease (hyperthyroidism) – Carbimazole (0.5-1 mg/kg/day) or propylthiouracil. Propranolol for symptoms. Definitive: radioiodine or thyroidectomy. Neonatal Graves: maternal TRAb; transient, treat with carbimazole.
4
Congenital adrenal hyperplasia (21-hydroxylase deficiency) – Salt-wasting crisis: hydrocortisone IV, 0.9% saline, fludrocortisone. Maintenance: hydrocortisone (10-15 mg/m²/day) + fludrocortisone (0.05-0.2 mg/day). Monitor 17-OHP, electrolytes, renin, growth.
5
Central precocious puberty (CPP) – GnRH agonist (leuprolide acetate monthly IM). Halts progression, preserves adult height. Monitor bone age, growth velocity, pubertal regression.
6
Delayed puberty – constitutional delay – Reassure, monitor. Consider low-dose testosterone (boys 50-100 mg IM monthly x 4-6 months) or estrogen (girls 0.3-0.6 mcg/kg/day) if psychosocial distress. Treat underlying hypogonadism.
⚠️ Emergency endocrine presentations: Salt-wasting CAH (hyponatremia, hyperkalemia, shock), adrenal crisis (hypotension, hypoglycemia), diabetic ketoacidosis (hyperglycemia, acidosis, dehydration), thyrotoxic storm (fever, tachycardia, agitation).

🧠 Reflex prompts: growth & endocrine disorders

📏 A 6-year-old boy height <3rd centile, growth velocity 3.5 cm/year, bone age 4 years. Next step?
Short stature with delayed bone age. Screen for GH deficiency (IGF-1, GH stimulation tests), hypothyroidism (TSH, fT4), celiac, chronic disease.
👧 A 7-year-old girl with breast development (Tanner B2), pubic hair. Bone age 10 years. Diagnosis?
Central precocious puberty (GnRH-dependent). GnRH agonist test confirms. MRI brain to exclude hypothalamic hamartoma or tumour.
🧒 A 14-year-old boy with no testicular enlargement, height <3rd centile, bone age 11 years. Most likely?
Constitutional delay of growth and puberty (CDGP). Positive family history. Reassure; consider low-dose testosterone if distressed.
🦋 A neonate with prolonged jaundice, hypotonia, large fontanelle, hoarse cry. Diagnosis?
Congenital hypothyroidism. Confirm with TSH, fT4. Start levothyroxine immediately. Screen results from heel prick.
🩺 A 2-week-old with vomiting, poor feeding, hyponatremia, hyperkalemia, hypotension. Diagnosis?
Salt-wasting congenital adrenal hyperplasia (21-hydroxylase deficiency). Emergency: hydrocortisone, fludrocortisone, IV fluids, sodium chloride.
🚺 A 12-year-old girl with primary amenorrhea, short stature, webbed neck, cubitus valgus. Diagnosis?
Turner syndrome (45,XO). Karyotype confirms. Growth hormone therapy, estrogen replacement at puberty.
📈 A 5-year-old with rapid growth, advanced bone age, but normal pubertal examination. Consider?
Growth hormone excess (pituitary adenoma) or hyperthyroidism. Check IGF-1, GH suppression test, TSH, fT4.
🧬 A boy with tall stature, long limbs, small testes, gynecomastia, learning difficulties. Karyotype?
Klinefelter syndrome (47,XXY). Testosterone replacement after puberty if hypogonadism.
🩺 A 10-year-old with weight loss, heat intolerance, tachycardia, goiter. Diagnosis?
Graves disease (autoimmune hyperthyroidism). Check TSH (low), fT4 (high), TRAb. Carbimazole/propranolol.
⚡ A 3-year-old with isolated pubic hair (no breast/testes, no growth acceleration). Most likely?
Premature adrenarche (benign). Bone age normal or slightly advanced. No treatment. Differentiate from true precocious puberty.