Summary This document provides comprehensive notes on endocrine and renal pathology, covering a range of diseases affecting the adrenal glands, pancreas, parath
Summary This document provides comprehensive notes on endocrine and renal pathology, covering a range of diseases affecting the adrenal glands, pancreas, parathyroid glands, and kidneys. It details the definitions, causes, clinical presentations, diagnostic methods, morphological features, and treatment strategies for conditions such as adrenal insufficiency, Cushing's syndrome, hyperaldosteronism, phaeochromocytoma, and various types of diabetes mellitus. Additionally, it delves into parathyroid disorders, porphyrias, renal function evaluation, acute and chronic kidney injury, and renal calculi. The document also includes information on lung tumours, their paraneoplastic syndromes, and lung transplantation, highlighting key features and management approaches for each. Key Points - Adrenal Insufficiency (Addison's Disease): Inadequate cortisol and potentially aldosterone production, with primary causes including autoimmune disease and TB, and secondary causes often linked to prolonged steroid use. Diagnosis involves an ACTH stimulation test, and treatment requires hormone replacement. - Cushing's Syndrome: Chronic excess cortisol, categorized by exogenous steroid use (most common) or endogenous causes like pituitary adenomas (Cushing's disease) or ectopic ACTH production. Clinical features include central obesity and hypertension. - Hyperaldosteronism (Conn's Syndrome): Excess aldosterone leading to hypertension and hypokalaemia, often caused by adrenal adenomas or hyperplasia. The aldosterone:renin ratio is a key diagnostic marker. - Phaeochromocytoma: A catecholamine-secreting tumour of the adrenal medulla, characterized by the "5 Ps" (palpitations, perspiration, pallor, pain, pressure). Diagnosis relies on elevated urinary catecholamines and metanephrines, with alpha-blockade preceding surgical removal. - Diabetes Mellitus: Types 1 (autoimmune beta-cell destruction) and 2 (insulin resistance and beta-cell exhaustion) have distinct mechanisms, onset, and clinical features. Diagnosis is based on glucose levels and HbA1c, with management focused on glycemic control and preventing complications. - Parathyroid Disorders: PTH regulates calcium and phosphate. Primary hyperparathyroidism involves autonomous PTH secretion, often from an adenoma, leading to hypercalcaemia. Secondary hyperparathyroidism results from chronic hypocalcaemia, commonly due to renal failure. - Porphyrias: Enzyme defects in haem biosynthesis leading to toxic accumulation. Acute porphyrias cause neurological symptoms, while cutaneous porphyrias manifest with photosensitivity. - Renal Function Evaluation: GFR is the primary marker of kidney function, assessed via eGFR. Urine studies, including casts and crystals, aid in diagnosing specific renal pathologies. - Acute Kidney Injury (AKI): A rapid decline in kidney function, classified as prerenal, intrinsic renal damage (ATN, AIN, GN), or postrenal obstruction. - Chronic Kidney Disease (CKD): Persistent kidney damage or reduced GFR for over three months, most commonly caused by diabetic and hypertensive nephropathy. Complications include anaemia, secondary hyperparathyroidism, and cardiovascular disease. - Renal Calculi: Kidney stones formed from calcium oxalate, uric acid, struvite, or cystine, presenting with severe colic and haematuria. Treatment varies based on stone type and size. - Lung Tumours: Adenocarcinoma, squamous cell carcinoma, and small cell carcinoma are the main types, strongly associated with smoking. Paraneoplastic syndromes and local effects are common. - Lung Transplantation: A treatment for end-stage lung disease, with early complications including infections and later complications like acute rejection and chronic bronchiolitis obliterans. Detailed Notes 1. ADRENAL INSUFFICIENCY (ADDISON'S DISEASE) Definition: Inadequate cortisol ± aldosterone production. Primary causes: Autoimmune ( 1 in developed world), TB ( 1 in developing world), Waterhouse-Friderichsen syndrome, metastases, fungal infections. Secondary causes: Prolonged steroid use ( 1 overall), pituitary tumours, Sheehan's syndrome. Feature Primary Secondary --- --- --- ACTH ↑ High ↓ Low Aldosterone ↓ Low Normal Hyperpigmentation Yes No Hyperkalaemia Yes No Cause Adrenal destroyed Pituitary/hypothalamus fails Clinical: Fatigue, weight loss, postural hypotension, salt craving, nausea, hypoglycaemia, hyperpigmentation (primary only). Diagnosis: Short ACTH stimulation test (gold standard), ↑ACTH (primary), ↓ACTH (secondary), hyponatraemia, hyperkalaemia, anti-21-hydroxylase antibodies. Morphology: - Autoimmune → small atrophic glands, lymphocytic infiltration, cortical fibrosis - TB → enlarged, caseating granulomas, Langhans giant cells - Waterhouse-Friderichsen → bilateral haemorrhagic necrosis, DIC Treatment: Hydrocortisone + fludrocortisone (primary only). Stress dose during illness/surgery. Patient education — emergency injection, MedicAlert bracelet. CASE 8.1 17-year-old woman. Tiredness, dizziness, pigmentation of buccal mucosa, palmar creases and old scar. BP drops from 120/80 → 90/50 on standing. Na⁺ 128, K⁺ 5.4, glucose 2.5. Cortisol 150 → 160 nmol/L post-ACTH (no rise). ACTH 500 ng/L. Anti-adrenal antibodies positive. Q: What is the diagnosis and explain the findings. A: Primary autoimmune adrenal insufficiency (Addison's disease). - Hyperpigmentation → ↑ACTH stimulates melanocytes (POMC precursor shared with MSH) - Postural hypotension → aldosterone deficiency → Na⁺ loss → volume depletion - Hyponatraemia + hyperkalaemia → aldosterone deficiency - Hypoglycaemia → cortisol deficiency → impaired gluconeogenesis - Failed ACTH stimulation test → adrenal cortex destroyed, cannot respond - ACTH 500 ng/L (10× normal) → no feedback suppression from cortisol - Positive anti-adrenal antibodies → confirms autoimmune cause 2. CUSHING'S SYNDROME Definition: Chronic excess cortisol — exogenous or endogenous. Cause ACTH Adrenal Appearance --- --- --- Exogenous steroids ( 1) ↓ Suppressed Bilateral atrophy Cushing's Disease (pituitary adenoma) ↑↑ High Bilateral hyperplasia Ectopic ACTH (small cell lung, carcinoid) ↑↑↑ Very high Bilateral hyperplasia Adrenal adenoma ↓ Suppressed Unilateral nodule Adrenal carcinoma ↓ Suppressed Large necrotic mass Clinical: Central obesity, moon face, buffalo hump, wide purple striae, proximal muscle weakness, hypertension, hyperglycaemia, osteoporosis, hirsutism, amenorrhoea, easy bruising, depression. Ectopic ACTH: Rapid onset, severe hypokalaemic alkalosis, hyperpigmentation — no classic cushingoid features (tumour grows too fast). Diagnosis: - Confirm hypercortisolism: 24h urinary free cortisol, 1mg dexamethasone suppression test (cortisol not suppressed = abnormal) - Find cause: plasma ACTH (↑ = ACTH-dependent; ↓ = adrenal) - Localise: pituitary MRI, CT adrenals, high-dose (8mg) dexamethasone suppression test Morphology: - Pituitary adenoma → small basophilic corticotroph adenoma, ACTH immunostain positive - Adrenal adenoma → yellow, well-circumscribed, uniform clear cells, thin capsule - Adrenal carcinoma → large, irregular, necrotic, pleomorphic cells, vascular invasion Treatment: Transsphenoidal surgery (pituitary), adrenalectomy (adrenal), treat primary tumour (ectopic). Medical: ketoconazole, metyrapone, mifepristone. 3. HYPERALDOSTERONISM (CONN'S SYNDROME) Definition: Excess aldosterone → hypertension + hypokalaemia. Feature Primary (Conn's) Secondary --- --- --- Cause Adrenal adenoma/hyperplasia Renal artery stenosis, CCF, cirrhosis Renin ↓ Suppressed ↑ Elevated Aldosterone ↑↑ ↑ Aldosterone:Renin ratio 30 (diagnostic) Normal/low Clinical: Resistant hypertension, hypokalaemia (weakness, cramps, polyuria), metabolic alkalosis. No oedema. Diagnosis: Aldosterone:Renin ratio 30, CT adrenals, adrenal venous sampling (gold standard for lateralisation). Treatment: Unilateral adenoma → laparoscopic adrenalectomy. Bilateral hyperplasia → spironolactone. CASE 8.4 27-year-old woman. BP 158/106 on routine check. K⁺ 3.3 mmol/L. Aldos