General Medicine
Final Professional MBBS — General Medicine. Long Questions (10 marks) and Short Notes (5 marks) across 15 systems, exam-formatted with clinical pearls, drug doses and mnemonics.
15chapters304questions48High-Yield
WHO DIAGNOSTIC CRITERIA FOR DM
Test Diabetes Impaired (Pre-diabetes) Normal FPG (fasting plasma glucose) ≥ 7.0 mmol/L (126 mg/dL) 6.1–6.9 mmol/L (IFG ) < 6.1 mmol/L 2-hr PG (75g OGTT) ≥ 11.1 mmol/L (200 mg/dL) 7.8–11.0 mmol/L (IGT ) < 7.8 mmol/L Random PG + symptoms ≥ 11.1 mmol/L + polyuria/polydipsia/weight loss N/A N/A HbA1c ≥ 48 mmol/mol (≥ 6.5%) 39–47 mmol/mol (5.7–6.4%) < 39 mmol/mol (< 5.7%) 💡CLINICAL PEARL: One abnormal test on a SYMPTOMATIC patient = diagnosis confirmed. ASYMPTOMATIC patients require 2 abnormal tests on 2 separate occasions.PATHOGENESIS OF TYPE 2 DM
- Insulin resistance — reduced response to insulin in muscle, liver, adipose tissue; driven by obesity (especially central/visceral), inflammation, free fatty acids
- Beta-cell dysfunction — progressive decline in pancreatic beta-cell insulin secretion; initially compensatory hypersecretion → then failure as beta-cells exhaust
- Incretin defect — impaired GLP-1 and GIP response → reduced post-meal insulin, increased glucagon
MANAGEMENT — STEPWISE APPROACH
- Lifestyle modification (cornerstone at all stages) — weight loss (5–10% body weight → significant Hb A1c reduction); Mediterranean/low-carb diet; exercise 150 min/week aerobic; stop smoking
▶ STEP 1 — Metformin (first-line) 500 mg OD/BD → up to 1000 mg BD:
MOA: ↓ hepatic glucose output (inhibits gluconeogenesis); ↑ peripheral insulin sensitivity
Benefits: HbA1c ↓1–1.5%; weight neutral; CV protective (UKPDS ); NO hypoglycaemia as monotherapy
Contraindicated: eGFR < 30 mL/min; hepatic failure; acute illness (lactic acidosis risk ); IV contrast (hold 48 hrs)
Side effects: GI (nausea/diarrhoea — take with food ); B12 deficiency (long-term ); metallic tasteAdd 2nd agent based on patient profile:
Drug Class Example HbA1c ↓ Weight CV/Renal Benefit Key S/E SGLT2i Empagliflozin
Dapagliflozin
Canagliflozin0.5–1% ↓ Weight CVD + CKD benefit (HFrEF + proteinuric CKD ) UTI/genital thrush; DKA (euglycaemic DKA ); limb amputation (cana) GLP-1 RA Semaglutide
Liraglutide
Dulaglutide1–1.5% ↓↓ Weight (best) CVD + weight ; GLP-1 first for obesity+DM Nausea/vomiting; pancreatitis risk; ↑ HR; avoid in thyroid Ca Hx DPP-4i Sitagliptin
Vildagliptin0.5–0.8% Weight neutral CV neutral Well tolerated; arthralgia; pancreatitis (rare) Pioglitazone (TZD) Pioglitazone 30 mg 0.5–1% ↑ Weight ↓ CV events (PROactive) Fluid retention; HF risk; osteoporosis; bladder Ca risk Sulphonylurea Glimepiride
Glibenclamide1–1.5% ↑ Weight No CV benefit Hypoglycaemia (main risk); avoid elderly/renal failure Insulin Basal (glargine/detemir); premixed Variable ↑ Weight Essential in T1DM + GDM Hypoglycaemia ; weight gain; injection site lipohypertrophy MONITORING
- HbA1c target: General: < 7% (53 mmol/mol); Elderly/comorbid: < 8%; Young/no complications: < 6.5%
- HbA1c reflects average blood glucose over preceding 8–12 weeks ; measured 3-monthly initially, then 6-monthly
- Annual screening for complications: Urine ACR (nephropathy); serum creatinine; fundoscopy (retinopathy); foot examination; lipids; BP
COMPLICATIONS OF DM
Complication Pathogenesis Features Management Diabetic Nephropathy Glomerular hyperfiltration → microalbuminuria → macroalbuminuria → CKD Earliest sign: microalbuminuria (ACR 3–30 mg/mmol); progresses to macroalbuminuria → CKD → ESRD ACEi/ARB (slow progression); SGLT2i (finerenone); BP < 130/80; protein restriction Diabetic Retinopathy Non-enzymatic glycation of retinal vessels + VEGF Background: microaneurysms, dot-blot haemorrhages; Pre-proliferative: cotton-wool spots; Proliferative: new vessels → vitreous haemorrhage; CSME (clinically significant macular oedema) = most common cause of visual loss Annual fundoscopy; laser photocoagulation; anti-VEGF (ranibizumab ) Diabetic Neuropathy Polyol pathway + sorbitol accumulation + oxidative stress Peripheral: glove-stocking sensory loss; burning pain (neuropathic); ↓ ankle jerks; Charcot foot; Autonomic: gastroparesis, ED, postural hypotension, sweating abnormalities Glucose control; Duloxetine or pregabalin/gabapentin for pain; Amitriptyline; TCA; foot care Macrovascular Accelerated atherosclerosis; foam cell formation IHD (#1 cause of death in T2DM ); Stroke; Peripheral arterial disease; Diabetic foot (PAD + neuropathy + infection) Statin; antiplatelet (aspirin); BP control; SGLT2i; GLP-1 RA (CV benefit) DEFINITION
Addison's disease (Primary Adrenal Insufficiency) = inadequate production of cortisol and aldosterone due to bilateral adrenal cortex destruction , causing BOTH glucocorticoid AND mineralocorticoid deficiency (distinguishes from secondary/tertiary where only cortisol low).
ETIOLOGY
- Autoimmune adrenalitis — #1 cause in developed countries (80%); anti-21-hydroxylase antibodies; associated with other autoimmune endocrine diseases: Schmidt syndrome (Addison's + Autoimmune thyroid disease); APS type 1 and 2
- TB adrenalitis (#1 cause in India and developing world ) — bilateral adrenal involvement; calcified adrenals on CT (characteristic ); often associated with active TB elsewhere
- Bilateral adrenal haemorrhage (Waterhouse-Friderichsen syndrome — meningococcaemia; anticoagulation; DIC)
- Metastatic cancer (lung, breast, melanoma — bilateral adrenal mets); HIV (CMV, MAC adrenalitis); fungal (histoplasmosis)
- Drugs: Rifampicin/phenytoin (↑ cortisol metabolism); ketoconazole/etomidate (block cortisol synthesis )
CLINICAL FEATURES
- Glucocorticoid deficiency: Fatigue (#1 symptom; profound); weight loss; nausea/vomiting/anorexia; hypoglycaemia (especially fasting); HYPOTENSION; myalgia
- Mineralocorticoid deficiency: Postural hypotension (most specific symptom); salt craving; dizziness; syncope; dehydration; hyponatraemia + hyperkalaemia (aldosterone deficiency → ↑ Na loss + K⁺ retention); metabolic acidosis
- ↑ ACTH (feedback): Hyperpigmentation — pathognomonic of PRIMARY adrenal insufficiency; bronze/tan pigmentation; buccal mucosa, palmar creases, scars, pressure areas, sun-exposed skin, nipples, genitalia; caused by ACTH/MSH stimulation of melanocytes
- Other: Loss of body hair (↓ adrenal androgens) in women; amenorrhoea; depression; joint pains
INVESTIGATIONS
- 8 AM cortisol — < 83 nmol/L (3 μg/dL) = strongly suggests adrenal insufficiency; > 497 nmol/L = normal; GREY ZONE 83–497 nmol/L → Synacthen test
- Short Synacthen Test (SST) (250 μg ACTH IV/IM) — Gold standard; peak cortisol < 550 nmol/L (20 μg/dL) at 30 or 60 min = ABNORMAL (adrenal insufficiency); peak > 550 = normal
- Plasma ACTH — HIGH in primary (↑ feedback drive); low in secondary/tertiary (pituitary/hypothalamic)
- Anti-21-hydroxylase antibodies (autoimmune); CT adrenals (bilateral calcification = TB; haemorrhage; enlarged = malignancy)
- Biochemistry: Hyponatraemia + Hyperkalaemia (Na:K ratio < 30:1 ); hypoglycaemia; eosinophilia; lymphocytosis
TREATMENT
▶ Hydrocortisone 15–25 mg/day in divided doses (10 mg morning + 5 mg afternoon — mimic diurnal cortisol rhythm ); FIRST-LINE replacement
▶ Fludrocortisone 50–150 μg OD (morning) — mineralocorticoid replacement; for primary adrenal insufficiency only (NOT secondary — aldosterone production preserved )
- Sick day rules ('double/triple dosing'): During illness/surgery/stress → double oral hydrocortisone dose (or triple for major illness); for vomiting/surgery → parenteral hydrocortisone 100 mg IM/IV immediately + 6-hourly; all patients must carry steroid card + emergency injection kit
ADDISONIAN CRISIS
Addisonian crisis = acute life-threatening adrenal insufficiency; precipitated by: infection, surgery, trauma, vomiting (unable to take oral steroids), or withdrawal of steroids.
- Features: Severe hypotension; abdominal pain; vomiting; fever; hypoglycaemia; confusion → coma
▶ Emergency treatment:
1. IV hydrocortisone 100 mg STAT then 50–100 mg q6–8h
2. IV 0.9% NaCl 1 L rapidly (1 hr) then guided by BP/UO
3. Treat hypoglycaemia: 10% dextrose infusion
4. Identify + treat precipitant (blood/urine cultures; antibiotics)
5. Fludrocortisone NOT needed acutely (hydrocortisone > 50 mg has mineralocorticoid activity )- Causes: Graves' disease (70–80%; autoimmune — TSH-R Ab); Toxic multinodular goitre (Plummer's disease); Toxic adenoma; Subacute thyroiditis (de Quervain's ); Thyroiditis; Excess iodine (Jod-Basedow ); Amiodarone (iodine-rich )
- Clinical features: Heat intolerance; palpitations; sweating; weight loss despite good appetite; diarrhoea; tremor; anxiety/nervousness; AF (15%); proximal myopathy; lid lag (von Graefe's sign) + lid retraction (sympathetic overstimulation — ALL causes); pretibial myxoedema + exophthalmos + thyroid acropachy (Graves' only = Graves' triad)
- Investigations: ↓ TSH (most sensitive test ) + ↑ Free T4/T3; TRAb (TSH receptor antibodies — diagnostic of Graves'); anti-TPO; thyroid USS; radio-iodine uptake scan (↑ diffuse = Graves'; ↑ focal = toxic adenoma; ↓ = thyroiditis )
▶ Carbimazole (CBZ) 20–40 mg OD (or propylthiouracil 300–450 mg/day for pregnancy 1st trimester ) — block thyroid peroxidase → ↓ T3/T4 synthesis; SE: agranulocytosis (0.5%; sore throat → STOP immediately; check WBC)
▶ Propranolol 40 mg TDS — immediate symptom relief (tremor, palpitations, HR); blocks T4→T3 conversion (high dose); use while awaiting antithyroid drug effect
▶ Radioiodine (¹³¹I) — definitive treatment; destroys thyroid; avoid in pregnancy + active ophthalmopathy; leads to hypothyroidism (then thyroxine replacement)
- Surgery (total thyroidectomy) — large goitre; contraindication to RAI/antithyroid drugs; cosmetic; malignancy concern
- Complications: atrial fibrillation and other arrhythmias, heart failure, osteoporosis, thyroid storm, and (in Graves) thyroid eye disease; thyrotoxic periodic paralysis in susceptible patients.
- Special situations & monitoring: in pregnancy use propylthiouracil in the first trimester then carbimazole; monitor free T4 and TSH to titrate antithyroid drugs; warn about agranulocytosis (sore throat/fever - check FBC) and avoid radioiodine in pregnancy and active eye disease.
Thyroid storm (Thyrotoxic crisis) = life-threatening exacerbation of thyrotoxicosis; mortality 10–25%. Precipitants: Surgery (thyroid or other), infection, trauma, iodine load, radioiodine, stress, childbirth.
- Clinical features: High fever > 40°C; Burch-Wartofsky score (temperature + CNS effects + GI-hepatic dysfunction + HR + CHF + precipitant); CNS: agitation → delirium → coma; GI: vomiting + diarrhoea + jaundice; Cardiovascular: HR > 140; AF; haemodynamic instability
◆ Thyroid Storm — BBBBSI Treatment ▸ B = Block synthesis: PTU 600–800 mg STAT then 200 mg q4h (PTU preferred over CBZ — also blocks T4→T3 conversion ) ▸ B = Block release: Lugol's iodine (5 drops TDS, given 1 hr AFTER PTU to avoid organification ) ▸ B = Block peripheral effects: Propranolol 60–80 mg q4–6h (or IV Esmolol in haemodynamically unstable) ▸ B = Block T4→T3 conversion: PTU + Propranolol + Hydrocortisone 100 mg q8h ▸ S = Supportive: IV fluids; paracetamol (NOT aspirin — ↑ free T4 ); cooling; treat precipitant ▸ I = ICU admission - Precipitants: infection or sepsis, surgery, trauma, iodinated contrast or amiodarone, radioiodine therapy, abrupt withdrawal of antithyroid drugs, DKA, and childbirth.
- Supportive care & monitoring: ICU care - cooling and paracetamol for hyperthermia (avoid aspirin, which displaces T4), IV fluids and glucose, treat heart failure/arrhythmia, and treat the precipitant; the Burch-Wartofsky score guides the diagnosis.
- Burch-Wartofsky criteria: scoring system for diagnosis - temperature, CNS effects (agitation, delirium, psychosis, coma), heart rate, heart failure, GI/hepatic dysfunction, and precipitating cause; score >= 45 = thyroid storm, 25-44 = impending storm; guides ICU admission.
- Sequence of drug therapy: give PTU first (blocks synthesis AND conversion of T4 to T3); wait 1 hour then give iodine (to block hormone release - the Wolff-Chaikoff effect; iodine given before PTU could increase hormone synthesis transiently); add dexamethasone (reduces peripheral T4 to T3 conversion and treats relative adrenal insufficiency).
- Complications: high-output cardiac failure, arrhythmia, hyperthermia, dehydration, and a 10-25% mortality if untreated.
HYPOTHYROIDISM
- Causes: Hashimoto's (autoimmune) (#1 cause worldwide; anti-TPO + anti-thyroglobulin Ab; goitre); Post-radioiodine/thyroidectomy; Iodine deficiency (#1 cause worldwide — developing world ); Drugs (amiodarone, lithium, carbimazole); Sheehan's syndrome; Pituitary failure (secondary)
- Clinical features: Cold intolerance; weight gain (despite poor appetite); constipation; bradycardia; slowing of mental function (dementia-like); depression; lethargy; dry skin; coarse hair; hoarse voice (myxoedema of vocal cords); non-pitting oedema (myxoedema — glycosaminoglycan deposition); periorbital puffiness; delayed relaxation of ankle jerks (hung-up reflexes — pathognomonic ); anaemia; hypercholesterolaemia ; hyponatraemia
- Investigations: ↑ TSH (most sensitive ) + ↓ Free T4; anti-TPO antibodies (Hashimoto's); lipid profile (↑ cholesterol)
▶ Levothyroxine (T4) — 25–50 μg OD initially; ↑ by 25 μg every 4–6 weeks; target TSH 0.5–2.5 mIU/L; take fasting 30–60 min before breakfast; caution in elderly/IHD (start low )
MYXOEDEMA COMA
- Definition: Life-threatening decompensated hypothyroidism; mortality 20–40%; precipitants: infection, cold exposure, drugs (sedatives, opioids), surgery
- Features: Hypothermia (core temp < 35°C — cardinal feature); coma; bradycardia; hyponatraemia (SIADH); hypercapnia (hypoventilation); bradycardia; ileus; hypoglycaemia
▶ Treatment: IV T4 (levothyroxine 200–500 μg loading → 50–100 μg OD) OR IV T3 (preferred for faster action: 10–20 μg loading); IV hydrocortisone 50–100 mg q6h (co-existing adrenal insufficiency common; give steroids BEFORE thyroid hormone ); IV fluids + rewarming; treat precipitant; ICU
- Clinical features of hypothyroidism: fatigue, weight gain, cold intolerance, constipation, dry skin and hair, hair loss, bradycardia, peri-orbital puffiness, non-pitting oedema (myxoedema), delayed ankle jerk relaxation, hoarse voice, carpal tunnel syndrome, menorrhagia, and hypercholesterolaemia.
- Investigations: TSH is the best screening test (elevated in primary hypothyroidism); free T4 (low); anti-TPO antibodies (Hashimoto thyroiditis); lipid profile (hypercholesterolaemia); anaemia (normocytic or macrocytic - pernicious anaemia association); ECG (bradycardia, low-voltage, pericardial effusion).
- Levothyroxine treatment: start low and go slow in elderly patients and in those with cardiac disease (risk of precipitating angina/arrhythmia); usual maintenance 1.6 mcg/kg/day; check TSH 6 weeks after any dose change; target TSH 0.5-2.5 mU/L (lower in the young, higher in the elderly).
GRAVES' DISEASE
Graves' disease = most common cause of hyperthyroidism in iodine-sufficient areas; autoimmune — TSH receptor stimulating antibodies (TRAb/TSHR-Ab/LATS) mimic TSH → uncontrolled T3/T4 synthesis → thyrotoxicosis. F:M = 7:1; HLA-DR3 association.
- Specific features (not seen in other thyrotoxicosis):
- Ophthalmopathy — proptosis/exophthalmos; periorbital oedema; chemosis; restriction of EOM (inferior rectus first → vertical diplopia); optic nerve compression (↓ acuity) — may be absent in euthyroid state (euthyroid Graves'); managed with glucocorticoids (IV methylprednisolone ) + orbital radiation ± decompression; teprotumumab (anti-IGF-1R)
- Pretibial myxoedema (dermopathy) — raised indurated violaceous plaques/nodules on anterior shins; glycosaminoglycan deposition; 5% of Graves'
- Thyroid acropachy — rare; periosteal reaction in fingers/toes resembling clubbing; triad with pretibial myxoedema + exophthalmos
HASHIMOTO'S THYROIDITIS
Hashimoto's (Autoimmune thyroiditis) = #1 cause of hypothyroidism worldwide; lymphocytic infiltration of thyroid; goitre (firm, rubbery, non-tender); may initially cause transient thyrotoxicosis (Hashitoxicosis ); progresses to hypothyroidism; anti-TPO (anti-microsomal Ab — 95% positive ) + anti-thyroglobulin Ab; associated with T1DM, coeliac, Addison's, vitiligo; ↑ risk of thyroid lymphoma (rare).
- Treatment: Levothyroxine when TSH ↑; serial monitoring; no intervention in euthyroid Hashimoto's
- Graves - investigations & treatment: suppressed TSH with raised free T4/T3, positive TSH-receptor antibodies, and a diffuse uptake on a radioiodine scan; treat with antithyroid drugs (carbimazole), radioiodine, or thyroidectomy, plus a beta-blocker for symptoms; manage eye disease with selenium, steroids or orbital decompression.
- Hashimoto - features & associations: goitre or an atrophic gland with features of hypothyroidism (fatigue, weight gain, cold intolerance, constipation, dry skin); positive anti-TPO antibodies; associated with other autoimmune disease and a small risk of thyroid lymphoma.
DKA = absolute/relative insulin deficiency + ↑ counter-regulatory hormones → hyperglycaemia + ketosis + metabolic acidosis . Predominant in T1DM ; rare in T2DM (unless severe illness). Precipitants: Infection (#1), insulin omission, new T1DM, MI, stress.
DKA Diagnostic Criteria DKA HHS Blood glucose ≥ 11 mmol/L (200 mg/dL) > 30 mmol/L (540 mg/dL) (extremely high) pH < 7.3 > 7.3 (no significant acidosis) Bicarbonate < 15 mmol/L > 15 mmol/L Ketones Moderate-large (urine ++ or blood > 3 mmol/L) Absent/trace Osmolality Mildly raised > 320 mOsm/kg (hyperosmolar) Typical patient T1DM ; younger; known DM T2DM ; elderly; may not have known DM - Clinical features: Nausea/vomiting; abdominal pain (may mimic acute abdomen); polydipsia/polyuria; dehydration; Kussmaul breathing (deep, sighing — compensatory for metabolic acidosis); fruity/acetone breath (ketones); altered consciousness; hypotension
▶ IV Fluid resuscitation: 0.9% NaCl 1 L in 1 hr, then guided by clinical assessment (typically 0.9% NaCl 4–6 L in 24 hrs); switch to 0.45% NaCl if Na⁺ rising; add 5% dextrose when BG < 14 mmol/L (but continue insulin)
▶ IV Insulin: Fixed-rate IV insulin infusion (FRIII) 0.1 units/kg/hr; do NOT give insulin bolus routinely; adjust by protocol
▶ Potassium replacement: K⁺ shifts with insulin; monitor K⁺ hourly; replace if < 5.5 mmol/L (20–40 mmol/hr IV ); NEVER give insulin if K⁺ < 3.5 mmol/L until repleted
- Resolution criteria: pH > 7.3 + HCO₃ > 15 + blood ketones < 0.6 mmol/L (or urine ketones < ++) → transition to SC insulin
- Bicarbonate NOT routinely given (only if pH < 6.9 with haemodynamic instability)
- Precipitants: infection (most common - 30-40%, especially UTI and pneumonia), new-onset T1DM, insulin omission/pump failure, drugs (steroids, antipsychotics, SGLT2 inhibitors - euglycaemic DKA), myocardial infarction, and surgery.
- Cerebral oedema: most dangerous complication, especially in children; risk factors include very high glucose, sodium correction too rapid, hypotonic fluids, excessive insulin; presents with headache, altered consciousness, and bradycardia; treat with IV mannitol 0.5-1 g/kg or hypertonic saline; prevent by avoiding hypotonic fluids.
- SGLT2 inhibitor-associated DKA: euglycaemic DKA (glucose may be near-normal); can occur after stopping insulin or with physiological stress; SGLT2 inhibitors increase glucagon:insulin ratio and promote ketogenesis; stop the SGLT2 inhibitor at least 3-4 days before elective surgery.
Hypoglycaemia = blood glucose < 3.9 mmol/L (70 mg/dL) (Whipple's triad: symptoms + low BG + relief with glucose correction).
Symptoms Mechanism Autonomic/Adrenergic (early): Sweating; tremor; palpitations; hunger; anxiety — occur first ↑ Catecholamines + glucagon (counter-regulatory response) Neuroglycopenic (later): Confusion; altered consciousness; seizures; coma; focal neurology Direct CNS glucose deprivation Hypoglycaemic unawareness — autonomic symptoms absent (recurrent hypo → blunted response); diabetics on insulin for years — very dangerous Impaired counter-regulation - Causes: Insulin overdose (#1 in diabetics); sulphonylureas (long-acting — risk in elderly/renal failure); insulinoma (fasting hypoglycaemia; Whipple's triad; ↑ proinsulin; 72-hr fast test; CT/EUS); alcohol (blocks gluconeogenesis); Addison's; Pituitary failure; Reactive (post-prandial)
▶ Mild-moderate (conscious): 15–20 g fast-acting oral glucose (glucose tablets; juice; dextrose solution); recheck in 15 min; repeat if < 4 mmol/L; then eat complex carbohydrate
▶ Severe (unconscious/unable to swallow): IV 50% dextrose 50 mL (= 25 g glucose) OR IM/SC Glucagon 1 mg (raises BG by stimulating glycogenolysis; avoid if liver disease/alcohol); admit + 10% dextrose infusion
ALWAYS give Thiamine BEFORE glucose in alcoholics/malnourished — IV thiamine 100 mg; prevents Wernicke's encephalopathy precipitated by glucose load. - Investigations: during a spontaneous episode take paired glucose, insulin, C-peptide and sulfonylurea screen - high insulin with high C-peptide suggests insulinoma or sulfonylurea, high insulin with low C-peptide suggests exogenous insulin; a 72-hour fast confirms insulinoma.
- Prevention in diabetics: review insulin/sulfonylurea dosing, regular meals and carbohydrate, structured education, glucose monitoring, and awareness of hypoglycaemia unawareness; relax HbA1c targets in those with recurrent severe hypos.
HHS
- HHS = severe hyperglycaemia (> 30 mmol/L) + hyperosmolality (> 320 mOsm/kg) + marked dehydration WITHOUT significant ketosis; typically T2DM , elderly, precipitated by infection/MI/CVA/drugs
- Clinical: Profound dehydration; confusion → coma; NO Kussmaul breathing (no acidosis); osmotic symptoms; hyperosmolar state → thrombotic complications (DVT/PE/stroke from haemoconcentration)
▶ Management: 0.9% NaCl cautiously (correct fluid deficit over 48 hrs ); low-dose insulin infusion 0.05 units/kg/hr; LMWH anticoagulation (high DVT risk); monitor Na (can rise dangerously as glucose falls → use 0.45% NaCl if Na rising)
DIABETIC FOOT
- Diabetic foot = combination of peripheral neuropathy + peripheral arterial disease + reduced immunity → foot ulceration → infection → gangrene → amputation
- Neuropathic ulcer: Painless (neuropathy); pressure points (sole, over metatarsal heads); punched-out; well-perfused (warm, pulses present); Charcot arthropathy (painless joint destruction from neuropathy)
- Ischaemic/Neuroischaemic ulcer: Painful; edges of foot; absent pulses; cold; pale/cyanotic; ABI < 0.9
- Wagner grade: 0 = intact skin; 1 = superficial ulcer; 2 = deep to tendon/capsule; 3 = osteomyelitis/abscess; 4 = forefoot gangrene; 5 = widespread gangrene → amputation
- Management: Debridement; wound care; off-loading (total contact cast ); antibiotics (empirical: broad-spectrum + MRSA cover if severe); vascular intervention (angioplasty/bypass for ischaemic); amputation if tissue not viable; glycaemic control; foot care education
- HHS - precipitants & complications: precipitated by infection, myocardial infarction, stroke, new diabetes or poor compliance, and high-dose steroids; complications include venous thromboembolism (give prophylaxis), arterial thrombosis, seizures and a high mortality.
- Diabetic foot - assessment & prevention: assess sensation (10 g monofilament), pulses and skin; prevention - annual foot screening, good footwear, podiatry, glycaemic and vascular risk control; refer urgently if spreading infection, ischaemia or suspected osteomyelitis.
CUSHING'S SYNDROME
Feature Details Causes: Iatrogenic (exogenous steroids) (#1 overall) → ↓ ACTH; Pituitary Cushing's (Cushing's disease — ACTH-secreting pituitary adenoma → ↑ bilateral adrenal hyperplasia; #1 endogenous cause ); Ectopic ACTH (SCLC — most common ectopic); Adrenal tumour (adenoma/carcinoma ) Clinical features: Central obesity (buffalo hump + moon face ); Proximal myopathy ; Purple striae (wide, > 1 cm — specific for Cushing's); Easy bruising ; Thin skin; Hypertension; DM; Osteoporosis; Hirsutism (females); Amenorrhoea; Hypokalaemia (especially ectopic ); Acne; Psychological disturbance Investigations: 1st line SCREENING: 24h urine free cortisol OR Late-night salivary cortisol (most sensitive) OR Overnight 1 mg Dexamethasone Suppression Test (DST) (cortisol > 50 nmol/L after 1 mg = Cushing's)
CONFIRMATION: 48h 2 mg LDDST
LOCALISATION: Plasma ACTH (high = ACTH-dependent; low = adrenal); CRH test; IPSS (inferior petrosal sinus sampling — to distinguish pituitary vs ectopic ACTH); MRI pituitary; CT chest (ectopic)CONN'S SYNDROME (Primary Hyperaldosteronism)
Conn's syndrome = excess aldosterone from adrenal (adenoma 40%; bilateral hyperplasia 60% ) → HTN + hypokalaemia + metabolic alkalosis (Na retained, K⁺ excreted, H⁺ excreted). Most common endocrine cause of hypertension. Suspect in: resistant HTN + spontaneous hypokalaemia + adrenal incidentaloma.
- Diagnosis: Plasma aldosterone:renin ratio (ARR) (ARR > 30 = Conn's); confirm with fludrocortisone suppression test; CT adrenals; adrenal vein sampling (AVS) (gold standard to differentiate unilateral vs bilateral )
- Treatment: Unilateral adenoma → laparoscopic adrenalectomy (curative); bilateral hyperplasia → spironolactone (aldosterone antagonist; may require lifelong)
PRIMARY HYPERPARATHYROIDISM
- Cause: Solitary parathyroid adenoma (85%); hyperplasia (15%); carcinoma (rare)
- Clinical — 'Bones, Stones, Groans, Psychic Moans':
- Bones: Osteitis fibrosa cystica; subperiosteal resorption (radial aspect middle phalanx ); Brown tumours; 'salt-and-pepper' skull; Looser zones in rickets (osteomalacia)
- Stones: Renal calcium oxalate stones; nephrocalcinosis; polyuria (hypercalciuria)
- Groans: Nausea; vomiting; constipation; peptic ulcer disease; pancreatitis
- Psychic moans: Depression; confusion; drowsiness; coma (hypercalcaemic crisis)
- Investigations: ↑ Ca²⁺ + ↓ PO₄³⁻ + ↑ PTH; ↑ ALP; ↑ urine Ca²⁺; ↑ 24h urine calcium; USS parathyroids; ⁹⁹Tc-sestamibi scan (localise adenoma ); DXA bone density
- Treatment: Surgery (parathyroidectomy) for symptomatic; Cinacalcet 30–90 mg BD (calcimimetic — ↓ PTH secretion; for non-surgical candidates)
HYPOPARATHYROIDISM
- Causes: Post-thyroidectomy/parathyroidectomy (#1 cause ); autoimmune; idiopathic; hypomagnesaemia
- Clinical: Tetany (Trousseau's + Chvostek's ); perioral tingling; carpopedal spasm; seizures; cataracts; ↑ QTc on ECG (hypocalcaemia prolongs QT ); papilloedema
- Investigations: ↓ Ca²⁺ + ↑ PO₄³⁻ + ↓ PTH; ↓ 25-OH vitamin D
▶ Acute: IV calcium gluconate 10% 10–20 mL over 10 min (+ cardiac monitoring); then infusion
▶ Maintenance: Calcium carbonate 1–2 g elemental Ca OD + Alfacalcidol (1α-OH vitamin D₃) 0.25–2 μg OD (bypasses absent PTH-mediated 1α-hydroxylation ); Recombinant PTH (palopegteriparatide) for refractory
- Secondary & tertiary hyperparathyroidism: secondary - raised PTH with low/normal calcium driven by chronic kidney disease or vitamin D deficiency (treat the cause, phosphate binders, vitamin D analogues); tertiary - autonomous PTH secretion with hypercalcaemia after long-standing secondary disease (may need parathyroidectomy).
- Pseudohypoparathyroidism: target-organ resistance to PTH - low calcium, high phosphate, but raised PTH; Albright hereditary osteodystrophy features (short stature, short 4th/5th metacarpals).
Feature Osteomalacia Osteoporosis Definition ↓ Mineralisation of osteoid (unmineralised bone matrix) ↓ Bone mass with normal mineralisation Cause Vitamin D deficiency (most common — dietary/sunlight/malabsorption/renal); Ca deficiency; phosphate deficiency (X-linked hypophosphataemic rickets ); anticonvulsants Post-menopausal (↓ oestrogen ); age-related (senile); secondary: steroid use (most common 2° cause ); hyperthyroidism; hypogonadism; CKD; alcohol; immobility Biochemistry ↓ Ca²⁺; ↓ PO₄; ↑ ALP; ↓ 25-OH Vit D; ↑ PTH (2° hyperparathyroidism ) Normal Ca, PO4, ALP, Vit D — biochemistry NORMAL Radiology Looser zones (pseudofractures) (transverse bands of rarefaction in cortex — cortical ribbon; milkman's syndrome ); Triradiate pelvis; deformities T-score ≤ −2.5 on DEXA (osteoporosis); −1 to −2.5 = osteopenia; vertebral compression fractures; Colles' fracture; NOF fracture Treatment Vitamin D: Cholecalciferol (D₃) 800–1000 IU/day maintenance; STAT dose 300,000 IU IM/oral for deficiency; + Calcium supplementation Bisphosphonates: Alendronate 70 mg weekly (oral); Zoledronic acid 5 mg IV annually; SE: oesophagitis (oral); ONJ; atypical femur fracture; Denosumab 60 mg SC 6-monthly; Teriparatide; Ca + Vit D supplementation for all - Osteoporosis - risk and assessment: risk factors - age, postmenopausal oestrogen loss, steroids, smoking, alcohol, low BMI, immobility and family history; usually silent until fragility fracture (hip, vertebra, wrist); diagnosed by DEXA (T-score <= -2.5); FRAX estimates fracture risk.
- Osteoporosis - management: calcium and vitamin D, weight-bearing exercise, lifestyle change, and bisphosphonates (alendronate) first-line; denosumab or teriparatide for high risk; bloods are typically normal (calcium, phosphate, ALP).
- Osteomalacia: defective mineralisation, usually from vitamin D deficiency; bone pain, proximal myopathy and Looser zones (pseudofractures); low calcium and phosphate with raised ALP and low 25-OH vitamin D; treat with vitamin D and calcium.
Metabolic syndrome = cluster of metabolic risk factors conferring increased CV and DM risk. Multiple diagnostic criteria exist; most used: IDF (International Diabetes Federation) 2006 and NCEP-ATP III .
Component IDF Criteria (3 of 5 required; central obesity essential) Central obesity (essential for IDF) Waist circumference: ≥ 90 cm (M) / 80 cm (F) in South Asians/Indians (lower cut-offs than Caucasians ) Triglycerides ≥ 1.7 mmol/L (150 mg/dL) OR on fibrate/nicotinic acid HDL cholesterol < 1.03 mmol/L (40 mg/dL) in M; < 1.29 mmol/L (50 mg/dL) in F OR on treatment Blood pressure SBP ≥ 130 mmHg OR DBP ≥ 85 mmHg OR on antihypertensive Fasting glucose ≥ 5.6 mmol/L (100 mg/dL) OR T2DM - Pathogenesis: Insulin resistance (central) → ↑ free fatty acids → impaired glucose metabolism → hyperinsulinaemia → endothelial dysfunction → atherosclerosis; Visceral adipose tissue releases pro-inflammatory cytokines (TNF-α, IL-6, ↓ adiponectin)
- Clinical importance: 2× CV risk; 5× T2DM risk; associated with NAFLD, PCOS, sleep apnoea
- Treatment: Weight loss (↓ waist circumference); exercise; Mediterranean diet; treat individual components (HTN, DM, dyslipidaemia); GLP-1 RA/SGLT2i improve multiple components
- Associated conditions: non-alcoholic fatty liver disease, polycystic ovary syndrome, obstructive sleep apnoea, hyperuricaemia/gout, and a prothrombotic, pro-inflammatory state.
- Pathophysiology in detail: central adiposity causes excess free fatty acid flux to the liver (hepatic insulin resistance, dyslipidaemia, NAFLD); skeletal muscle insulin resistance impairs glucose uptake; compensatory hyperinsulinaemia drives RAAS activation and sympathetic nervous system activity, raising blood pressure.
- Cardiovascular risk calculation: use Framingham, SCORE2, or India-specific risk equations; metabolic syndrome doubles the 10-year cardiovascular risk and increases the risk of type 2 diabetes fivefold; the cluster of risk factors is more dangerous than the sum of individual components.
- Management targets: intensive lifestyle change is central; then treat each component to target - BP < 130/80, statin for dyslipidaemia, glucose control (metformin/SGLT2/GLP-1), and weight loss; consider aspirin only where cardiovascular risk warrants.
- Definition: BMI > 30 kg/m²; Obese class I: 30–34.9; Class II: 35–39.9; Class III (morbid): ≥ 40; South Asian cut-offs : overweight ≥ 23 kg/m², obese ≥ 27.5 kg/m²
- Complications: T2DM; HTN; dyslipidaemia; OSAHS (obstructive sleep apnoea); CVD; NAFLD/NASH; cancers (endometrium, colon, breast, kidney ); OA; GORD; depression; infertility/PCOS
- Pickwickian syndrome (Obesity hypoventilation syndrome) = obesity (BMI > 30) + daytime hypercapnia (PaCO₂ > 45 mmHg) + hypoxaemia + polycythaemia ± right heart failure; CPAP + weight loss
▶ GLP-1 agonists (anti-obesity): Semaglutide (Wegovy) 2.4 mg SC weekly — 15% weight loss; Liraglutide (Saxenda) 3 mg SC daily (12% weight loss); approved for BMI ≥ 30 OR ≥ 27 + comorbidity
▶ Orlistat (Xenical) 120 mg TDS with meals — pancreatic lipase inhibitor; blocks 30% dietary fat absorption; SE: steatorrhoea; fat-soluble vitamin malabsorption
▶ Bariatric surgery: Roux-en-Y gastric bypass (gold standard; most weight loss 30–35%; reverses T2DM 80% ); sleeve gastrectomy (restrictive; 25% weight loss); for BMI ≥ 40 OR ≥ 35 + comorbidity
- Assessment & secondary causes: measure BMI and waist circumference (use South Asian cut-offs); screen for complications and secondary causes - hypothyroidism, Cushing syndrome, hypothalamic disease and drug-induced weight gain (steroids, antipsychotics, insulin).
- Management ladder: lifestyle (diet, physical activity, behavioural support) first; add pharmacotherapy (GLP-1 agonist, orlistat) for BMI >= 30 (or >= 27 with comorbidity); bariatric surgery for BMI >= 40 (or >= 35 with comorbidity) when other measures fail.
- Obesity paradox: in some chronic disease populations (elderly, heart failure, CKD) higher BMI is paradoxically associated with better survival; however this does not negate the overall harms of obesity across the general population.
- Newer pharmacotherapy: tirzepatide (dual GIP/GLP-1 agonist) produces > 20% weight loss and is now approved for obesity; semaglutide 2.4 mg/week (SELECT trial) also reduces cardiovascular events independent of glycaemia; combination therapy with lifestyle intervention achieves the greatest weight loss.
SIADH
- SIADH (Syndrome of Inappropriate ADH) = excess ADH → water retention → dilutional hyponatraemia + concentrated urine (UOsm > POsm paradoxically) + urinary Na > 40 mEq/L (despite hyponatraemia) WITHOUT oedema (euvolaemia )
- Causes: SCLC (#1 ectopic ADH); CNS disease (meningitis, SAH, encephalitis, stroke); drugs (SSRIs, carbamazepine, cyclophosphamide, chlorpropamide); pulmonary (TB, pneumonia); pain; nausea; post-surgery
- Treatment: Fluid restriction (800–1000 mL/day ) — first-line; treat cause; Tolvaptan (V2 receptor antagonist — vaptans; aquaretic — excretes free water ± Na; correct Na < 12 mmol/L in 24h to avoid osmotic demyelination )
PROLACTINOMA
- Most common pituitary tumour (40%); causes hyperprolactinaemia; microadenoma (< 10 mm) or macroadenoma (> 10 mm — visual field defects from chiasm compression )
- Clinical: Women: galactorrhoea + amenorrhoea + infertility; Men: ↓ libido + impotence + gynaecomastia (present later — often macroadenoma)
▶ Dopamine agonists (first-line): Cabergoline 0.5–2 mg twice weekly (preferred — more effective, fewer SE) OR Bromocriptine 2.5 mg TDS; causes tumour shrinkage; SE: nausea, postural hypotension, cardiac valve disease (high-dose cabergoline ); surgery (transsphenoidal) if dopamine agonist fails
ACROMEGALY
- GH-secreting pituitary adenoma → excess IGF-1 → acral overgrowth + systemic effects. Before epiphyseal fusion → gigantism; after → acromegaly
- Features: Enlarged hands + feet (ring size ↑, shoe size ↑); prognathism (jaw protrusion); macroglossia; frontal bossing; wide spacing of teeth; carpal tunnel syndrome (thenar wasting); hyperhidrosis; HTN; DM; sleep apnoea; colonic polyps (↑ cancer risk )
- Diagnosis: ↑ IGF-1 (screening test); failure to suppress GH during OGTT (75 g glucose) — GH should suppress to < 1 μg/L; GH > 1 μg/L confirms acromegaly; MRI pituitary
- Treatment: Transsphenoidal surgery (curative in 85% of microadenomas); Octreotide LAR 20–30 mg monthly (somatostatin analogue — ↓ GH); Pegvisomant (GH receptor antagonist ); radiotherapy if surgery fails
Complication Earliest Sign Monitoring Treatment Nephropathy Microalbuminuria
(ACR 3–30 mg/mmol)Annual urine ACR + eGFR ACEi/ARB; SGLT2i; glycaemic control; BP < 130/80 Retinopathy Microaneurysms Annual dilated fundoscopy Photocoagulation (laser); anti-VEGF; glycaemic control Neuropathy Loss of vibration sense (great toe); ↓ ankle jerk Annual foot exam + monofilament Duloxetine /pregabalin/gabapentin; TCAs; glucose control Macrovascular (IHD = #1 death ) — BP + lipids + HbA1c Statin; SGLT2i/GLP-1 RA (CV benefit ); antiplatelet - Microvascular - retinopathy: non-proliferative (microaneurysms, dot/blot haemorrhages, hard exudates) progressing to proliferative (neovascularisation, vitreous haemorrhage, retinal detachment); maculopathy threatens central vision; annual screening with laser or anti-VEGF treatment.
- Microvascular - nephropathy & neuropathy: nephropathy starts as microalbuminuria, then proteinuria and falling eGFR (treat with ACE inhibitor/ARB and SGLT2 inhibitor); neuropathy - distal sensory glove-and-stocking loss, autonomic neuropathy (gastroparesis, postural drop, erectile dysfunction) and mononeuropathies.
- Macrovascular: accelerated atherosclerosis causing ischaemic heart disease, stroke and peripheral arterial disease - the leading cause of death; manage with statin, blood-pressure control, antiplatelet where indicated and smoking cessation.
- Prevention: individualised tight glycaemic control plus BP and lipid management, and annual screening of eyes, kidneys and feet.
- Neuropathy screening and treatment: annual 10 g monofilament and vibration testing; painful diabetic neuropathy treated with duloxetine 60 mg OD (first-line), pregabalin 75-300 mg BD, or amitriptyline 10-75 mg nocte; topical capsaicin or lidocaine patches as adjuncts.
- Retinopathy treatment: non-proliferative retinopathy managed by optimising glucose, BP, and lipids; macular oedema treated with anti-VEGF injections (ranibizumab/bevacizumab) or laser; proliferative retinopathy treated with pan-retinal photocoagulation (PRP) laser; vitrectomy for vitreous haemorrhage or retinal detachment.
Feature DKA HHS Hypoglycaemic Coma BG (mmol/L) 11–33 > 30 (very high) < 3 (very low) pH < 7.3 > 7.3 Normal Ketones Positive Absent Negative Osmolality Mildly ↑ > 320 (markedly ↑) Normal/↓ Onset Hours Days Minutes Skin Dry; warm Very dry; wrinkled Diaphoretic (sweating — key!) Breathing Kussmaul Normal (no acidosis) Normal Treatment IV fluid + Insulin + K⁺ IV fluid (slow) + Low-dose insulin Glucose (IV/oral/glucagon) - DKA management: IV 0.9% saline, a fixed-rate insulin infusion (0.1 units/kg/h), potassium replacement once the level is known, and monitoring of ketones, glucose and pH; treat the precipitant and switch to subcutaneous insulin once ketones clear and the patient is eating.
- HHS management: cautious IV fluids to correct the large deficit over about 48 h, low-dose insulin only after fluids (or once glucose stops falling with fluids alone), potassium replacement, and VTE prophylaxis because of the high thrombosis risk.
- Hypoglycaemia management: oral fast-acting carbohydrate if conscious, IV dextrose or IM glucagon if unconscious, then recheck glucose and give longer-acting carbohydrate; review the cause (insulin/sulfonylurea, missed meal, alcohol).
- Key distinctions: DKA - ketones and acidosis, often type 1 and younger; HHS - very high glucose and hyperosmolality without significant acidosis, older type 2; hypoglycaemic coma - very low glucose with rapid recovery on glucose.
- Diagnostic approach: check blood glucose immediately in any patient with altered consciousness; if < 3.9 mmol/L, treat as hypoglycaemia; if > 11 mmol/L with ketones, consider DKA; if > 30 mmol/L without significant ketones and altered consciousness, consider HHS; calculate osmolality and anion gap.
- Monitoring in DKA: hourly blood glucose and ketones; 2-hourly electrolytes (especially potassium, which changes rapidly with insulin therapy); fluid balance chart; repeat VBG at 2, 4, 6, 8 hours; escalate if ketones not falling by 0.5 mmol/L/h or glucose not falling by 3 mmol/L/h.
Sheehan's syndrome = postpartum pituitary necrosis due to haemorrhage and hypovolemic shock during/after delivery → ischaemic infarction of the anterior pituitary (enlarged during pregnancy — hyperplastic lactotrophs → more vulnerable ).
- Clinical features: Failure to lactate postpartum (first sign — ↓ prolactin ); failure to resume menstruation; pubic/axillary hair loss (↓ FSH/LH + ACTH stimulating adrenal androgens ); hypothyroid symptoms (↓ TSH); adrenal insufficiency (most dangerous — hypotension, hypoglycaemia, hyponatraemia)
- Investigations: MRI pituitary (empty sella ); hormone profile: ↓ FSH/LH, ↓ TSH, ↓ ACTH, ↓ GH, ↓ prolactin
- Treatment: Replace all deficient hormones: Hydrocortisone FIRST (most urgent — adrenal crisis); then Levothyroxine; then oestrogen-progesterone (HRT); GH if deficient
- Pathophysiology & risk: the pituitary enlarges in pregnancy; severe postpartum haemorrhage causes hypotension and infarction of the gland, leading to partial or complete hypopituitarism; risk rises with major obstetric haemorrhage.
- Presentation - acute vs chronic: acutely there may be failure to lactate and postpartum collapse from adrenal insufficiency; chronically, amenorrhoea, fatigue, cold intolerance and features of secondary hypothyroidism and hypoadrenalism develop over months to years.
- Replacement detail: replace hydrocortisone FIRST (before levothyroxine, to avoid precipitating adrenal crisis), then thyroxine and oestrogen/progesterone; growth hormone in selected cases.
- Severity: ranges from mild (partial pituitary insufficiency, preserved periods) to severe (complete panhypopituitarism with failure to lactate, no menstruation, and clinical hypothyroidism and hypoadrenalism); severity depends on the extent of pituitary necrosis.
- Long-term follow-up: lifelong hormone replacement; annual review for adequacy of replacement; stress dosing for illness/surgery; women should not attempt pregnancy without specialist endocrine review and gonadotropin stimulation if desired.
- Triggers: Infection (most common ); surgery; vomiting (cannot take oral steroids); GI haemorrhage; sudden steroid withdrawal; bilateral adrenal haemorrhage (Waterhouse-Friderichsen )
- Features: Severe hypotension → shock; acute abdominal pain (may mimic surgical abdomen ); fever; vomiting; profound weakness; confusion → coma; hypoglycaemia ; hyponatraemia + hyperkalaemia
▶ Emergency treatment:
IV hydrocortisone 100 mg STAT → 50–100 mg q6–8h × 24 hrs → taper to oral
IV 0.9% NaCl 1 L rapidly (fluid resuscitation)
50% dextrose 50 mL IV if hypoglycaemic
Identify + treat precipitant (cultures + antibiotics)
Monitor electrolytes + glucose hourly✍️EXAM TIP: Fludrocortisone NOT needed acutely — high-dose hydrocortisone (> 50 mg) has sufficient mineralocorticoid activity. Restart fludrocortisone when hydrocortisone dose < 50 mg/day.- Pathophysiology: acute deficiency of cortisol (and aldosterone in primary disease) causing vasodilatory shock, hyponatraemia, hyperkalaemia and hypoglycaemia; commonly unmasked by stress in a patient with known or undiagnosed adrenal insufficiency.
- Investigations: take blood for cortisol and ACTH before steroids but do NOT delay treatment; expect low sodium, high potassium, low glucose and eosinophilia; a short Synacthen test confirms the diagnosis later.
- Prevention (sick-day rules): patients should double their oral steroid dose during illness, carry a steroid card and emergency hydrocortisone, and switch to parenteral steroids if vomiting.
- Primary vs secondary adrenal insufficiency: primary (Addison disease) - low cortisol, HIGH ACTH, hyponatraemia, hyperkalaemia, hyperpigmentation, low aldosterone; secondary (pituitary ACTH deficiency) - low cortisol, LOW ACTH, no hyperpigmentation, no hyperkalaemia (aldosterone preserved), often due to exogenous steroid withdrawal.
- Steroid equivalences: hydrocortisone 20 mg = prednisolone 5 mg = dexamethasone 0.75 mg; hydrocortisone is the preferred replacement as it has the most physiological profile; dexamethasone is used for the Synacthen test (does not interfere with cortisol assay).
- Vitamin D: Synthesised in skin (UV → cholecalciferol D3) → hepatic 25-hydroxylation → renal 1α-hydroxylation (PTH-stimulated) → 1,25-(OH)₂D₃ (calcitriol) (active form); promotes intestinal Ca + PO₄ absorption; bone mineralisation; immunomodulation
- Vitamin D deficiency causes: ↓ sunlight exposure (indoor workers, veiled women ); dietary deficiency; malabsorption (coeliac, Crohn's ); CKD (↓ 1α-hydroxylation ); anticonvulsants (↑ metabolism); liver disease
- Rickets (children): Bowing of legs; rachitic rosary (costochondral beading ); craniotabes; Harrison's sulcus; delayed dentition
- Osteomalacia (adults): Bone pain + tenderness; proximal myopathy; Looser zones; ↓ Ca, ↓ PO₄, ↑ ALP, ↓ 25-OH Vit D
- Hypervitaminosis D: Hypercalcaemia (most dangerous complication); renal stones; soft tissue calcification; nausea; avoid excessive supplementation
- Obesity hypoventilation syndrome (OHS/Pickwickian syndrome): BMI > 30 + PaCO₂ > 45 mmHg (hypercapnia) + hypoxaemia + exclusion of other causes of hypoventilation; treat with CPAP/BiPAP + weight loss; high mortality if untreated
- Vitamin D - role & sources: skin synthesis from sunlight plus dietary sources (oily fish, fortified foods); activated by hepatic 25-hydroxylation then renal 1-alpha-hydroxylation; it raises calcium and phosphate absorption and supports bone mineralisation.
- OHS - management: weight loss is central; non-invasive ventilation (CPAP/BiPAP) for sleep-disordered breathing and daytime hypercapnia; treat coexisting obstructive sleep apnoea and cor pulmonale; supplemental oxygen as needed.
- OHS diagnostic criteria: BMI > 30 kg/m2, daytime hypercapnia (PaCO2 > 45 mmHg or 6 kPa) on ABG, and no other explanation for hypoventilation (e.g. COPD, neuromuscular disease, severe kyphoscoliosis); 90% of patients have co-existing obstructive sleep apnoea.
- Consequences of untreated OHS: cor pulmonale (right heart failure from chronic hypoxia-driven pulmonary hypertension), polycythaemia (secondary erythrocytosis from hypoxia), recurrent hospitalisations with hypercapnic respiratory failure, and excess mortality compared with obese patients without hypoventilation.
Diabetes Insipidus (DI) = inability to concentrate urine → polyuria (> 3 L/day) + polydipsia with dilute urine (UOsm < POsm ). Two types: Central (↓ ADH production) and Nephrogenic (ADH resistance).
Feature Central DI Nephrogenic DI Cause Head injury; pituitary surgery; tumour (craniopharyngioma ); granuloma (sarcoid, histiocytosis X ); idiopathic Drugs: Lithium (#1 drug cause ); Demeclocycline; Amphotericin
Electrolytes: hypercalcaemia; hypokalaemia; congenital V2R mutation (X-linked ); CKDADH level ↓ (absent/low) ↑ (high — ADH present but tubules resistant) Response to DDAVP test YES (UOsm rises > 50% ) NO (tubules resist) Water deprivation test UOsm remains low; rises with DDAVP (central) UOsm remains low; does NOT rise with DDAVP ▶ Central DI: Desmopressin (DDAVP) — intranasal (10–40 μg OD-BD) or oral (0.1–0.4 mg OD-BD); synthetic ADH analogue
▶ Nephrogenic DI: Remove cause (stop lithium); Thiazide diuretic (paradoxical effect ) — induces mild volume depletion → ↑ proximal tubule reabsorption → less water delivered to collecting duct → less polyuria; NSAID (indomethacin) + low-salt/low-protein diet
- Clinical features & complications: large volumes of dilute urine with intense thirst and nocturia; if access to water is limited, hypernatraemic dehydration with confusion can develop.
- Water deprivation test: stop fluids; measure urine and plasma osmolality hourly; in a normal person, urine osmolality rises above 750 mOsm/kg; in DI, urine remains dilute (< 300 mOsm/kg); giving DDAVP then: urine concentrates in central DI (> 50% rise) but not in nephrogenic DI (< 10% rise).
- Hypernatraemia in DI: if the patient cannot access water (e.g. unconscious, infant), severe hypernatraemia develops rapidly; correct slowly with hypotonic fluids (no faster than 0.5 mEq/L/h) to avoid cerebral oedema; treat the DI with DDAVP simultaneously.
- Investigations: confirm true polyuria, then a water-deprivation test - urine fails to concentrate; giving desmopressin then concentrates the urine in central DI but not in nephrogenic DI; check serum sodium, glucose, calcium and potassium and image the pituitary in central DI.
Galactosaemia = inherited disorder of galactose metabolism ; autosomal recessive ; most common type: Classical galactosaemia — GALT (galactose-1-phosphate uridylyltransferase) deficiency → galactose-1-phosphate accumulates → toxic to liver, brain, kidneys.
- Clinical features: Neonatal presentation after breast/cow's milk feeding (lactose → glucose + galactose ); neonatal jaundice + hepatomegaly + hepatic dysfunction ; E. coli neonatal sepsis (classic association ); cataract (sorbitol deposition in lens); intellectual disability; hyperchloraemic metabolic acidosis; reducing substances in urine (Clinitest +ve; glucose oxidase NEGATIVE )
- Galactosuria = galactose in urine; detected by: urine reducing substances (Clinitest/Benedict's ) — positive for all reducing sugars including galactose; but glucose oxidase dipstick NEGATIVE (specific for glucose)
- Treatment: Eliminate all galactose from diet (no lactose) — soy-based formula; galactose-restricted diet lifelong; screen neonates (newborn screening )
- Enzyme defect: classical galactosaemia is an autosomal recessive deficiency of galactose-1-phosphate uridyltransferase (GALT); toxic galactose-1-phosphate and galactitol accumulate after milk feeds.
- Diagnosis & screening: urine reducing substances positive but urine glucose oxidase (dipstick) negative; confirmed by red-cell GALT enzyme assay; included in newborn screening in many countries.
- Complications: untreated disease causes liver failure, E. coli sepsis, cataracts and intellectual disability; even on diet, long-term speech delay, learning difficulty and ovarian failure can occur.
- Newborn screening: detected on Guthrie card by measuring total galactose or GALT enzyme activity; early diagnosis and dietary restriction prevent the acute neonatal crisis (liver failure, sepsis); routine screening in most developed countries and now some Indian states.
- Duarte galactosaemia: a common variant with 50% residual GALT activity; milder phenotype; most patients do not require strict dietary restriction but need regular monitoring; does not cause acute neonatal illness but may have subtle developmental effects.