Summary: Endocrinology

Table of Contents
1. Pheochromocytoma
2. Thyroid
3. Sick Euthyroid Syndrome (SES)
4. Thyrotoxicosis
5. Thyroid Storm
6. Grave's Ophthalmopathy
7. Hypothyroidism
8. Thyroiditis
9. Insulinoma
10. Multiple Endocrine Neoplasia (MEN)
11. Parathyroid Gland & Bone Metabolism
12. Magnesium Metabolism
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Pheochromocytoma

• Tumour notes: Associated with MEN 2A (Sipple syndrome) (more epinephrine than norepinephrine; ~10% malignant). Extraadrenal pheochromocytomas ~15% (common at organ of Zuckerkandl). Familial cases 10-15%; ~10% bilateral.
• Diagnosis: MRI (abdomen preferred for medullary lesions); MIBG scintigraphy if MRI inconclusive; PET useful for extra-adrenal lesions.
• Symptoms: Headaches, sweating attacks, palpitations/tachycardia, episodic or sustained hypertension, anxiety/panic, pallor, paradoxical drug responses, polyuria/polydipsia, orthostatic hypotension, dilated cardiomyopathy, erythrocytosis, hyperglycaemia.
• Screening & investigation: 24-hour urinary fractionated metanephrines (sensitive); plasma fractionated metanephrines (investigation of choice; more specific than catecholamines); imaging as above for localisation and metastasis.
• Treatment: Definitive is surgical resection (contraindicated in malignant disease). Preoperative oral phenoxybenzamine (non-selective α-blocker); intraoperative IV phentolamine; intra/postoperative IV nitroprusside and IV labetalol as needed for crises.

Thyroid

• T3 Resin Uptake Test: Assesses labelled T3 binding to resin to infer thyroid binding globulin (TBG). Increased binding seen in TBG deficiency; decreased binding in hypothyroidism.
• Isotope scan: Identifies causes of hyperthyroidism, retrosternal goitre, ectopic thyroid, and metastases. ~20% of cold nodules are malignant; hot nodules rarely malignant.
• Causes of low radioactive iodine uptake (thyrotoxicosis with low RAIU): thyrotoxicosis factitia, Hashimoto's thyrotoxicosis, struma ovarii, excess iodine, metastatic follicular carcinoma, amiodarone, De Quervain's thyroiditis.
• Causes of increased radioactive iodine uptake: hyperthyroidism, iodine deficiency, pregnancy, recovery phase of subacute/silent/postpartum thyroiditis, rebound after stopping antithyroid drugs, lithium therapy, Hashimoto's.
• Endemic cretinism: Maternal iodine deficiency causes newborn hypothyroidism. Blood profile: ↓T3, ↓T4, ↓free T3/T4, ↑TSH. Clinical features: large, lethargic infant; hypothermia, coarse skin, prolonged jaundice, delayed myelination and motor milestones, risk of mental retardation.
• Diagnosis/screening for endemic cretinism: heel-prick screening after 72 hours of birth; thyroid function tests as above. Treatment: levothyroxine replacement ~1.6 µg/kg/day (≈100-150 µg if no residual thyroid function).

Sick Euthyroid Syndrome (SES)

• Systemic illness alters TFTs. Typical pattern: low T3 syndrome (↓total and unbound T3), normal T4 and TSH. Severity of illness correlates with T3 fall.
• Pathophysiology: reduced peripheral conversion of T4→T3, ↑reverse T3 (rT3) mainly from decreased clearance; T4 may convert to inactive T3 sulfate.
• Severe illness can produce low T4 syndrome (↓T4 and T3), and the most advanced state shows ↓TSH, ↓T4, ↓T3.

Thyrotoxicosis

• Primary (Graves' disease): Autoimmune, female-predominant, caused by long-acting thyroid-stimulating antibodies (LATS). Lab: ↑T4/T3, ↓TSH.
• Secondary thyrotoxicosis: Pituitary cause (e.g., adenoma), usually older patients; labs show ↑T4/T3 and ↑TSH.
• Common clinical features:
  • Goitre: diffuse enlargement ± bruit.
  • Gastrointestinal: weight loss with normal/increased appetite; diarrhea; alimentary glycosuria.
  • Cardiorespiratory: palpitations, sinus tachycardia, atrial fibrillation, increased pulse pressure, soft systolic murmur, angina, cardiomyopathy, possible reversible diastolic dysfunction and low-output failure.
  • Neuromuscular: nervousness, irritability, tremor, hyperreflexia, muscle weakness, hypokalemic periodic paralysis, proximal myopathy; chorea rare.
  • Dermatological: finger clubbing (acropachy), pretibial myxedema.
  • Reproductive: amenorrhea/oligomenorrhea, infertility, spontaneous abortion, decreased libido.
  • Ocular: wide staring (Kocher), upper lid retraction (Dalrymple), lid lag (Von Graefe), decreased blinking (Stellwag).
• Investigations for Graves: thyroid function tests showing ↑total and free T4/T3; thyroid scan uses I-123.
• Treatment: patients <45 years="" -="">antithyroid drugs (propylthiouracil, methimazole) which inhibit coupling; risk of agranulocytosis; surgical subtotal thyroidectomy (6-8 g) if drug complication. Propylthiouracil is safe in pregnancy and breastfeeding. Patients >45 years - radioiodine (I-131) ablation.

Thyroid Storm

• Intraoperative release of large T4 amounts (toxic nodular goitre) converts to T3 and triggers a hyperadrenergic crisis (thyroid storm) that can cause high-output heart failure.
• Management:
  • IV hydrocortisone.
  • Propylthiouracil via nasogastric tube or rectally (drug of choice).
  • External cooling.
  • Sodium bicarbonate as needed.
  • Give Lugol's iodine or potassium iodide.
• Prevention: Lugol's iodine for 10 days preoperatively to reduce gland size and iodine trapping (Wolff-Chaikoff effect).
• Conditions causing elevated T4: thyrotoxicosis factitia; gestational trophoblastic neoplasia (hCG-mediated TSH effect).

Grave's Ophthalmopathy

• Signs: stare from Müller's muscle retraction → reduced blink and corneal dryness; external ophthalmoplegia → diplopia (inferior rectus commonly affected); proptosis (uni-/bilateral/asymmetrical); retrobulbar neuritis may cause blindness.
• Treatment: pulse methylprednisolone.

Hypothyroidism

• Causes of secondary hypothyroidism: Sheehan syndrome, pituitary apoplexy, empty sella, thyroiditis, endemic goitre, food goitrogens (cabbage, cassava, turnip).
• Complications: myxedema heart (pericardial effusion, atherosclerosis), myxedema madness (psychosis), myxedema coma with hypothermia (<35°c) treated="" with="" iv="" liothyronine="">

Thyroiditis

• Noted as a cause of thyroid dysfunction and of low RAIU in specific types (e.g., De Quervain's).

Insulinoma

• Definition: pancreatic tumour from β-cells causing endogenous hyperinsulinism and hypoglycaemia.
• Diagnosis: based on Whipple's triad (hypoglycaemic symptoms, documented low glucose during symptoms, symptom relief with glucose) and confirmed by the 72-hour prolonged fasting test measuring glucose, insulin, C-peptide, proinsulin, beta-hydroxybutyrate and sulfonylurea screen.
• Typical biochemical thresholds after fast: low plasma glucose (~45 mg/dL), elevated insulin and C-peptide (200 pmol/L), elevated proinsulin, low beta-hydroxybutyrate (~2.7 mmol/L), negative sulfonylurea screen.
• Preoperative localisation: endoscopic ultrasound.
• Treatment: medical control with octreotide; surgical options include enucleation or distal pancreatectomy (potentially curative).
• Causes of hypoglycaemia listed: fasting, drugs (insulin, sulfonylureas, ethanol, quinine, pentamidine, salicylates, sulfonamides), critical illness, hepatic/renal/cardiac failure, sepsis, hormone deficiencies (cortisol, GH, glucagon, epinephrine), non-β-cell tumours, autoimmune hyperinsulinism, insulinoma.

Multiple Endocrine Neoplasia (MEN)

• Gastroenteropancreatic neuroendocrine tumours (GEP-NETs): ~50% are non-secretory; among functional GEP-NETs, insulinoma is most common. Functional GEP-NETs associate with MEN1, von Hippel-Lindau, NF-1, and tuberous sclerosis complex.

Parathyroid Gland & Bone Metabolism

• Serum alkaline phosphatase (ALP): usually normal in multiple myeloma (low osteoblast activity despite bone lesions). ALP is increased in Paget's disease, bone metastases, rickets/osteomalacia; low in hypophosphatasia.
• Hypercalcaemia causes: lithium, thiazides, phenytoin; cancers (breast, lung, kidney, multiple myeloma, lymphoma); vitamin D/A intoxication; hyperparathyroidism, hyperthyroidism, pheochromocytoma; immobilisation; milk-alkali syndrome; familial hypercalciuric hypercalcaemia. Most common cause of asymptomatic hypercalcaemia: primary hyperparathyroidism.
• Management of acute hypercalcaemia: hydration (saline), forced diuresis with loop diuretics (furosemide drip), bisphosphonates (drug of choice: etidronate, pamidronate, zoledronate), glucocorticoids for specific causes, inhaled calcitonin, dialysis if severe renal failure.
• Types of hypoparathyroidism: primary (gland failure), idiopathic/autoimmune (most common), infantile (DiGeorge, thymic aplasia), postoperative, post radio-iodine, hypomagnesemia. Pseudohypoparathyroidism: renal resistance to PTH with hypocalcaemia and elevated PTH; associated phenotypic abnormalities. Pseudopseudohypoparathyroidism: phenotypic features without hypocalcaemia; defect beyond PTH receptor (Gs-alpha gene).

Magnesium Metabolism

• Normal serum magnesium: 1.5-2.3 mg%. Magnesium important for PTH secretion and function; serum magnesium and calcium are usually related but vary in conditions like chronic renal failure (hypocalcaemia with hypermagnesemia) and Gitelman syndrome (hypomagnesemia with hypocalcaemia).
• Causes of hypermagnesemia: acute/chronic renal failure, Addison disease, magnesium-containing drugs, hemolysis.
• Causes of hypomagnesemia: poor intake (alcoholics, TPN), GI losses (chronic diarrhea), renal losses (diuretics, Gitelman), acute pancreatitis, certain drugs (foscarnet).
• Note: QT prolongation can occur with both magnesium excess and deficit.