ADRENAL NEOPLASMS — Adenoma vs Carcinoma

This document outlines key distinctions between adrenal adenoma and carcinoma, details various Multiple Endocrine Neoplasia syndromes, and differentiates parathyroid cell types. It further explains the various types of Renal Tubular Acidosis, emphasizing their unique characteristics, and provides a comprehensive overview of the pathogenesis, morphology, and clinical progression of Diabetic Nephropathy. The content highlights critical diagnostic features and clinical implications across these endocrine and renal disorders. Key Points Cytology alone cannot diagnose adrenal carcinoma; only vascular invasion, capsular invasion, or metastasis confirms malignancy. MEN1 mutation is found in 30–35% of sporadic parathyroid adenomas. RET mutation in MEN2 requires screening of family members and prophylactic thyroidectomy in carriers. Phaeochromocytoma patients should always be screened for MEN2. Chief cells predominate and are the functional cells of the parathyroid gland. Oxyphil cells increase with age and typically appear after puberty. Stromal fat in the parathyroid gland increases up to age 25, then plateaus at approximately 30% of the gland. Adenomas are mostly composed of chief cells , while oxyphil adenomas are rare. Water-clear cell hyperplasia involves glycogen-rich clear cells and is seen in some hyperplasia cases. Type 4 Renal Tubular Acidosis is the only RTA with hyperkalaemia , while all other types present with hypokalaemia. Type 4 Renal Tubular Acidosis is the most common RTA in clinical practice, often associated with diabetic nephropathy . Microalbuminuria is the earliest detectable sign of diabetic nephropathy . ACEi/ARBs slow the progression of diabetic nephropathy by reducing intraglomerular pressure through efferent arteriole dilation. Both afferent and efferent arteriolar hyalinosis are unique to diabetic nephropathy , distinguishing it from hypertensive nephropathy which typically affects only the afferent arteriole. Detailed Notes ADRENAL NEOPLASMS — Adenoma vs Carcinoma Feature Adenoma Carcinoma --- --- --- Size Small, <50g Large, often 100g Gross Yellow, well-circumscribed, smooth Grey-white, irregular, necrotic Histology Uniform clear cells, thin capsule, no invasion Pleomorphic cells, mitoses, necrosis, vascular invasion Capsule Intact Breached — invasion is diagnostic Metastasis No Yes — only reliable criterion of malignancy alongside invasion CDC73/parafibromin Intact Mutated in ~70% ACTH Suppressed (autonomous cortisol) Suppressed Prognosis Excellent after adrenalectomy Poor — local recurrence in 1/3, distant metastasis in 1/3 MEN SYNDROMES (Multiple Endocrine Neoplasia) Feature MEN1 MEN2A MEN2B --- --- --- --- Gene MEN1 (chromosome 11q13, tumour suppressor) RET proto-oncogene RET proto-oncogene Parathyroid Hyperplasia/adenoma ✅ Hyperplasia ✅ No Pancreas Islet cell tumours ( gastrinoma, insulinoma ) ✅ No No Pituitary Adenoma ( prolactinoma most common) ✅ No No Adrenal No Phaeochromocytoma ✅ Phaeochromocytoma ✅ Thyroid No Medullary thyroid carcinoma ✅ Medullary thyroid carcinoma ✅ Other — — Marfanoid habitus , mucosal neuromas Mnemonic: MEN1 = 3 Ps — Parathyroid + Pancreas + Pituitary MEN2A = 2 Ps — Parathyroid + Phaeochromocytoma + medullary thyroid MEN2B = Phaeochromocytoma + medullary thyroid + marfanoid/neuromas (no parathyroid) PARATHYROID CELL TYPES Cell Type Size Cytoplasm Function Granules --- --- --- --- --- Chief cells 12–20 μm, predominant Light to dark pink, polygonal PTH synthesis and secretion PTH secretory granules present Oxyphil cells Larger than chief cells Deeply eosinophilic, packed with mitochondria Unknown (transitional/inactive) Sparse/absent secretory granules RENAL TUBULAR ACIDOSIS (RTA) Definition: Defect in renal acid-base handling, leading to normal anion gap metabolic acidosis despite normal or near-normal GFR. Feature Type 1 (Distal) Type 2 (Proximal) Type 4 --- --- --- --- Defect Impaired H⁺ excretion in collecting duct Impaired HCO₃⁻ reabsorption in proximal tubule Hypoaldosteronism → impaired H⁺ and K⁺ excretion Urine pH Always 5.5 (cannot acidify) <5.5 (can acidify when plasma HCO₃⁻ low) 5.5 Serum K⁺ ↓ Hypokalaemia ↓ Hypokalaemia ↑ Hyperkalaemia Serum HCO₃⁻ Very low Moderately low Mildly low Causes Sjögren's, SLE, amphotericin B, medullary sponge kidney Fanconi syndrome, multiple myeloma, Wilson's disease Diabetic nephropathy , ACEi/ARBs , Addison's disease Complications Nephrocalcinosis , nephrolithiasis , osteomalacia Rickets/osteomalacia Arrhythmias from hyperkalaemia Treatment Oral bicarbonate (small doses) Large oral bicarbonate + treat cause Fludrocortisone , dietary K⁺ restriction DIABETIC NEPHROPATHY — Pathogenesis & Morphology Pathogenesis (stepwise): The pathogenesis of diabetic nephropathy is a stepwise process initiated by chronic hyperglycaemia . This leads to the glycation of proteins, forming advanced glycation end products (AGEs) , which contribute to mesangial expansion . Hyperglycaemia also increases intraglomerular pressure due to aff