1. Hyperthyroidism – Graves' disease in children, neonatal thyrotoxicosis, clinical features, TFTs, imaging, management (ATDs, radioiodine, surgery), thyroid storm.
2. Precocious Puberty – Central vs peripheral, causes, Tanner staging, bone age, GnRH stimulation test, imaging (MRI brain, pelvic USG), management (GnRH analogues).
3. Obesity – Definition (BMI charts), etiology (exogenous vs endogenous), assessment, complications (metabolic syndrome, NAFLD, PCOS, sleep apnea), management (lifestyle, pharmacotherapy, bariatric surgery in select cases).
4. Congenital Adrenal Hyperplasia (CAH) – Enzyme defects (21-hydroxylase most common), classic salt-wasting/simple virilizing/non-classic forms, clinical presentation in males vs females, diagnosis (17-OHP, ACTH stimulation), management (glucocorticoid/mineralocorticoid replacement, surgery), salt-wasting crisis management.
5. Diabetes (Type 1 DM in children) – Pathophysiology, clinical presentation, diagnostic criteria, insulin regimens, DKA management, monitoring, complications, newer technologies (CGM, pumps).

1. Hyperthyroidism – Graves' disease in children, neonatal thyrotoxicosis, clinical features, TFTs, imaging, management (ATDs, radioiodine, surgery), thyroid storm.
2. Precocious Puberty – Central vs peripheral, causes, Tanner staging, bone age, GnRH stimulation test, imaging (MRI brain, pelvic USG), management (GnRH analogues).
3. Obesity – Definition (BMI charts), etiology (exogenous vs endogenous), assessment, complications (metabolic syndrome, NAFLD, PCOS, sleep apnea), management (lifestyle, pharmacotherapy, bariatric surgery in select cases).
4. Congenital Adrenal Hyperplasia (CAH) – Enzyme defects (21-hydroxylase most common), classic salt-wasting/simple virilizing/non-classic forms, clinical presentation in males vs females, diagnosis (17-OHP, ACTH stimulation), management (glucocorticoid/mineralocorticoid replacement, surgery), salt-wasting crisis management.
5. Diabetes (Type 1 DM in children) – Pathophysiology, clinical presentation, diagnostic criteria, insulin regimens, DKA management, monitoring, complications, newer technologies (CGM, pumps).

1. Precocious Puberty (15 marks)

• Central (true/GnRH-dependent) precocious puberty (CPP): premature activation of the hypothalamic-pituitary-gonadal axis. Causes: idiopathic (most common in girls, ~80-90%), CNS lesions (hypothalamic hamartoma, tumors, hydrocephalus, post-radiation/infection/trauma), neurofibromatosis-1.
• Peripheral (pseudo) precocious puberty (PPP)/GnRH-independent: gonadotropin-independent sex steroid production - CAH, McCune-Albright syndrome, ovarian/testicular/adrenal tumors, hCG-secreting tumors, exogenous hormone exposure, familial male-limited precocious puberty.
• Incomplete/variant forms: premature thelarche, premature adrenarche, premature menarche - benign, non-progressive.

• Bone age (left wrist X-ray, Greulich-Pyle) - advanced in true PP.
• Basal LH, FSH, estradiol/testosterone.
• GnRH (or GnRH-analogue) stimulation test - gold standard to differentiate central vs peripheral; pubertal LH rise confirms CPP.
• Pelvic USG in girls (ovarian/uterine size, multicystic ovaries).
• Testicular USG in boys with asymmetric enlargement.
• MRI brain/hypothalamic-pituitary region - mandatory in all boys with CPP and girls <6 years with CPP (higher CNS lesion risk).
• 17-OH progesterone, DHEAS, ACTH stimulation test if CAH suspected.
• Thyroid function (primary hypothyroidism can cause peripheral precocity - Van Wyk-Grumbach syndrome).

• Treat underlying cause (surgery for tumor, treat hypothyroidism, glucocorticoids for CAH).
• CPP: GnRH agonist (leuprolide/triptorelin depot) suppresses pituitary-gonadal axis, halts pubertal progression, preserves height potential and psychosocial well-being. Continue till appropriate pubertal age (~11 in girls), then stop.
• Peripheral causes: treat cause; GnRH agonists ineffective as axis not activated (except in McCune-Albright with superimposed central component).
• Psychological counseling for child and family.
• Recent evidence: A 2025 systematic review/meta-analysis (PMID: 40760548) on pharmacotherapy for CPP confirms GnRH analogues remain the mainstay, with combination GnRHa + growth hormone showing added height benefit in select cases with compromised predicted height - useful updated point to mention.

2. Congenital Adrenal Hyperplasia (15 marks)

• 21-hydroxylase deficiency (CYP21A2) - >90-95% of cases. Three forms:
  • Salt-wasting (classic, severe) - both cortisol and aldosterone deficient.
  • Simple virilizing (classic) - cortisol deficient, aldosterone adequate.
  • Non-classic (late-onset) - mild, presents later (premature pubarche, hirsutism, infertility).
• 11β-hydroxylase deficiency - virilization + hypertension (excess deoxycorticosterone).
• 17α-hydroxylase deficiency - decreased androgens/cortisol, hypertension, sexual infantilism.
• 3β-HSD deficiency - salt wasting, ambiguous genitalia in both sexes.

• Female (46XX) with classic 21-OH deficiency: ambiguous genitalia at birth (clitoromegaly, labial fusion, urogenital sinus) - Prader staging.
• Male: normal genitalia at birth, may present later with salt-wasting crisis (vomiting, dehydration, hyponatremia, hyperkalemia, shock) around 1-3 weeks of life, or with precocious pseudopuberty/penile enlargement later in simple virilizing form.
• Salt-wasting crisis: poor feeding, vomiting, failure to thrive, dehydration, hypotension, hyponatremia, hyperkalemia, metabolic acidosis, hypoglycemia - adrenal crisis, life-threatening.
• Hyperpigmentation (from elevated ACTH/MSH).
• Advanced bone age, tall as child but short final adult height if untreated.

• Elevated 17-hydroxyprogesterone (17-OHP) - screening and diagnostic (markedly elevated in classic 21-OH deficiency; neonatal screening programs use this).
• ACTH stimulation test for equivocal/non-classic cases.
• Serum electrolytes (hyponatremia, hyperkalemia in salt wasters), low aldosterone, elevated plasma renin.
• Karyotype in ambiguous genitalia.
• Genetic mutation analysis (CYP21A2).
• Pelvic USG/genitogram to assess internal genital anatomy.

• Acute salt-wasting crisis: IV normal saline, dextrose for hypoglycemia, IV hydrocortisone (stress dose), correct hyperkalemia.
• Chronic glucocorticoid replacement: hydrocortisone (preferred in growing children to minimize growth suppression), divided doses; dexamethasone/prednisolone avoided in children due to growth suppression except in special situations.
• Mineralocorticoid replacement: fludrocortisone + extra salt supplementation in infancy for salt wasters.
• Stress dosing (illness, surgery) - "triple the dose" rule, emergency hydrocortisone injection kit for parents.
• Monitor growth, bone age, virilization, 17-OHP, androgens, renin/electrolytes for dose titration (avoid over/under-treatment).
• Surgical correction (feminizing genitoplasty/clitoral reduction) - timing individualized, often delayed with informed consent debates.
• Genetic counseling; prenatal dexamethasone therapy in subsequent pregnancies is controversial/investigational.
• Lifelong follow-up, medical alert bracelet.

3. Hyperthyroidism (15 marks)

• Graves' disease (autoimmune, TSH-receptor stimulating antibodies - TRAb/TSI) - most common, peak in adolescent girls.
• Neonatal thyrotoxicosis - transplacental passage of maternal TSI in infants of mothers with Graves' disease (transient, resolves as maternal antibody clears, weeks to months).
• Hashitoxicosis (transient hyperthyroid phase of Hashimoto thyroiditis).
• Toxic adenoma/multinodular goiter (rare in children).
• McCune-Albright syndrome, TSH-secreting pituitary adenoma (rare).
• Exogenous thyroid hormone ingestion (factitious).

• Goiter (diffuse, smooth, bruit may be present in Graves').
• Tachycardia, palpitations, widened pulse pressure, systolic hypertension.
• Weight loss despite increased appetite.
• Heat intolerance, sweating, tremors, irritability, emotional lability, deteriorating school performance/attention issues.
• Exophthalmos, lid retraction/lag (ophthalmopathy less florid than in adults but occurs).
• Accelerated growth velocity but advanced bone age with eventual compromised final height if uncontrolled.
• Menstrual irregularities in adolescent girls.
• Neonatal thyrotoxicosis: irritability, tachycardia, poor weight gain, exophthalmos, goiter, occasionally craniosynostosis; can be life-threatening (arrhythmia, heart failure).

• Serum TSH (suppressed), free T4/T3 elevated.
• TRAb/TSI positive in Graves' disease.
• Anti-TPO, anti-thyroglobulin antibodies (autoimmune association).
• Thyroid USG/radioiodine uptake scan if nodularity or diagnostic doubt.
• ECG for arrhythmia if severe.

• Antithyroid drugs (ATDs) - methimazole is drug of choice in children (propylthiouracil avoided as first line due to hepatotoxicity risk, reserved for thyroid storm/first trimester pregnancy only); typically 1-2 year course, remission rates ~30-50% in children (lower than adults), relapse common.
• Beta-blockers (propranolol) for symptomatic control of adrenergic symptoms (tachycardia, tremor) while awaiting ATD effect.
• Definitive therapy if relapse/non-compliance/adverse drug reaction: radioactive iodine (I-131) ablation (avoid in very young children due to theoretical malignancy risk with growing thyroid, and avoid if active ophthalmopathy) or total/near-total thyroidectomy by an experienced pediatric surgeon.
• Neonatal thyrotoxicosis: methimazole, propranolol, supportive care; usually self-limiting as maternal antibody clears; monitor closely for cardiac decompensation.
• Thyroid storm (rare, life-threatening): high-dose PTU/methimazole, iodine solution (Lugol's), propranolol, corticosteroids, supportive ICU care.
• Regular monitoring of TFTs, growth, bone age, watch for ATD side effects (agranulocytosis, hepatotoxicity, rash - warn parents to stop drug and seek care if fever/sore throat/jaundice).

4. Obesity (15 marks)

• Exogenous (simple/primary) obesity - >95% of cases - due to positive energy imbalance from dietary excess, sedentary lifestyle, screen time, genetic predisposition, family/environmental factors. Children are typically tall for age with normal/advanced bone age.
• Endogenous (secondary) obesity - <5% - due to identifiable pathology:
  • Endocrine: hypothyroidism, Cushing syndrome, growth hormone deficiency, pseudohypoparathyroidism.
  • Genetic syndromes: Prader-Willi syndrome, Bardet-Biedl syndrome, Down syndrome.
  • Hypothalamic obesity (post-tumor/surgery/trauma affecting satiety centers).
  • Drug-induced: corticosteroids, antipsychotics, valproate.
  • Monogenic obesity: leptin/leptin-receptor deficiency, MC4R mutations. Suspect secondary causes when child is short/growth-retarded rather than tall, or has dysmorphism/developmental delay.

• Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus.
• Dyslipidemia, hypertension, atherosclerosis risk.
• Non-alcoholic fatty liver disease (NAFLD).
• Obstructive sleep apnea.
• Orthopedic: slipped capital femoral epiphysis (SCFE), genu valgum, Blount disease.
• PCOS in adolescent girls.
• Psychosocial: low self-esteem, depression, bullying/social stigma.
• Pseudotumor cerebri (idiopathic intracranial hypertension).

• Lifestyle modification is first line: dietary counseling (balanced calorie-appropriate diet, reduce sugary drinks/junk food), increased physical activity (≥60 min/day), reduced screen time (<2 hr/day), behavior modification therapy, family-based intervention (whole family involvement improves success).
• Treat underlying secondary cause if identified.
• Pharmacotherapy: considered in adolescents with severe obesity/comorbidities who fail lifestyle measures - metformin (especially with insulin resistance/PCOS), GLP-1 receptor agonists (liraglutide, semaglutide - now approved down to age 12 in several countries) increasingly used per recent guidelines.
• Bariatric surgery: considered in select adolescents with severe obesity (BMI ≥35-40 with serious comorbidities) who have failed other measures, per multidisciplinary evaluation.
• Prevention emphasis: promote breastfeeding, healthy school meal programs, community-level physical activity promotion.
• Recent guideline note: a 2025 CMAJ clinical practice guideline (PMID: 40228835) and a recommendations-mapping systematic review (PMID: 38914759) both reinforce combined lifestyle + selective pharmacotherapy/bariatric surgery approach with shared decision-making, aligning with (and updating) the traditional stepwise approach taught in textbooks.

5. Diabetes Mellitus in Children (15 marks)

• Classic triad: polyuria, polydipsia, polyphagia with weight loss.
• Nocturnal enuresis (new onset) in a previously toilet-trained child - important clue.
• Fatigue, blurred vision.
• Diabetic ketoacidosis (DKA) as presenting feature in a significant proportion (especially young children) - vomiting, abdominal pain, Kussmaul breathing, acetone breath, dehydration, altered sensorium, coma if severe.

• Fasting plasma glucose ≥126 mg/dL, or
• Random/casual plasma glucose ≥200 mg/dL with classic symptoms, or
• 2-hour OGTT glucose ≥200 mg/dL, or
• HbA1c ≥6.5% (used cautiously in children, less reliable in acute new-onset).
• Confirm with autoantibodies to distinguish Type 1 vs Type 2/other forms; C-peptide level (low/undetectable in Type 1).

• Acute DKA management: careful fluid resuscitation (avoid rapid correction - risk of cerebral edema), IV regular insulin infusion (0.05-0.1 U/kg/hr), gradual correction of glucose and electrolytes (watch potassium closely, add potassium once urine output confirmed and levels known), bicarbonate rarely needed, hourly monitoring, treat precipitating infection.
• Long-term insulin therapy:
  • Basal-bolus regimen: long-acting basal insulin (glargine/detemir) + rapid-acting bolus insulin (lispro/aspart) with meals - most physiological.
  • Conventional twice-daily premixed regimens still used where resources limited.
  • Insulin pump (CSII) and continuous glucose monitoring (CGM)/hybrid closed-loop "artificial pancreas" systems increasingly used, per current ISPAD/ADA and 2025 BSPED-type recommendations, improving glycemic control and reducing hypoglycemia.
• Monitoring: self-monitoring of blood glucose (SMBG) or CGM, HbA1c every 3 months (target individualized, generally <7-7.5%), growth monitoring, screening for associated autoimmune conditions (thyroid, celiac disease) and microvascular complications (retinopathy, nephropathy, neuropathy) after puberty/duration >5 years.
• Diet and exercise: carbohydrate counting, consistent meal timing, insulin dose adjustment around physical activity (per 2024 EASD/ISPAD position statement on exercise and automated insulin delivery, PMID: 39657609).
• Sick day rules: never omit insulin, increase monitoring frequency, check ketones, adjust doses, seek care early to prevent DKA.
• Psychosocial support: diabetes education for child/family, transition planning to adult care, screening for diabetes distress/depression, school diabetes management plans.
• Hypoglycemia management: recognition, glucose/glucagon administration, prevention through dose/activity adjustment.