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Detailed Treatment Regimens - Endocrinology & Internal Medicine

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DR. MANOJ KUMAR

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1. PANHYPOPITUITARISM

Sequence of Replacement (CRITICAL ORDER)

Always replace glucocorticoids FIRST, then thyroid hormone. Giving thyroid hormone alone can precipitate an adrenal crisis by accelerating cortisol metabolism.

A. Glucocorticoid Replacement (Adrenal axis)

• Hydrocortisone 15-20 mg/day in divided doses
  • 10 mg on waking + 5 mg at noon + 5 mg at 4-5 PM (mimics diurnal rhythm)
• Alternative: Prednisolone 3-5 mg/day once in the morning
• Sick day rules: Double/triple the dose during illness, fever, surgery, or trauma ("stress dosing")
• Adrenal crisis: IV Hydrocortisone 100 mg bolus, then 50-100 mg every 6-8 hours

B. Thyroid Hormone Replacement (after glucocorticoid is established)

• Levothyroxine (T4) 1.6 mcg/kg/day orally (start low, titrate up)
• Monitor free T4 (NOT TSH - TSH is meaningless in secondary hypothyroidism)
• Target free T4 in the upper half of the normal reference range

C. Sex Hormone Replacement

• Males: Testosterone replacement
  • IM: Testosterone enanthate/cypionate 200-250 mg every 2-4 weeks
  • Transdermal gel 1-2% (50-100 mg/day)
  • Monitor libido, energy, hemoglobin, bone density
• Females: Estrogen-progesterone replacement (if premenopausal)
  • Estradiol + cyclic progesterone
  • For fertility: Gonadotropin therapy (FSH + LH/hCG injections)

D. Growth Hormone Replacement

• Somatropin (recombinant GH) SC injection
  • Adults: Start 0.2-0.3 mg/day, titrate to IGF-1 levels
  • Children: 0.025-0.05 mg/kg/day SC
• Monitor IGF-1 levels to guide dosing
• Contraindicated in active malignancy

E. ADH Replacement (if Central DI present)

• Desmopressin (DDAVP): 0.1-0.2 mg orally BID-TID, or 10-20 mcg intranasally BD

F. Monitoring

• Regular assessment of energy, body weight, libido, bone density (DEXA scan), lipids, glucose

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2. ACROMEGALY

A. Surgery (First-Line)

• Transsphenoidal surgery (TSS) - preferred for most adenomas
• Cure rates: ~80-90% for microadenomas, ~40-60% for macroadenomas
• Pre-operatively: Consider SST analogue for 3-6 months to shrink tumor and improve surgical conditions (controversial)

B. Medical Therapy (Post-surgical failure or awaiting surgery)

• Octreotide LAR: 10-30 mg IM every 4 weeks (start 20 mg)
• Lanreotide Autogel: 60-120 mg deep SC every 4 weeks
• Pasireotide LAR: 40-60 mg IM every 4 weeks (binds SST1,2,3,5; especially useful in refractory acromegaly)
• Normalize GH/IGF-1 in ~50-60% of patients
• Side effects: Diarrhea, nausea, gallstones (~25%), bradycardia, hyperglycemia (especially pasireotide)

• Pegvisomant: 40 mg SC loading dose, then 10-30 mg/day SC
• Titrate based on IGF-1 levels (measured every 4-6 weeks initially)
• Normalizes IGF-1 in >90% of patients
• Monitor liver function tests; does NOT shrink tumor (GH levels rise)

• Cabergoline: 0.5-3.5 mg/week orally
• Less effective (~30% response) but oral and inexpensive

C. Radiotherapy (Third-line, adjuvant)

• Stereotactic radiosurgery (Gamma Knife): For residual adenoma after surgery
• Fractionated external beam radiotherapy: For large tumors near optic chiasm
• Takes years to achieve full GH/IGF-1 normalization; risk of hypopituitarism

D. Monitoring

• IGF-1 every 3-6 months; pituitary MRI annually; screen for complications (cardiomegaly, diabetes, colon polyps, sleep apnea)

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DR. DAYANAND

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3. THYROID DISORDERS

A. HYPOTHYROIDISM

• Treat if TSH >10 mIU/L, or if symptomatic, or pregnant
• Levothyroxine 25-50 mcg/day; titrate up by 25 mcg every 6-8 weeks

• Levothyroxine (T4) 1.6 mcg/kg/day - full replacement dose
• Elderly or cardiac patients: Start with 12.5-25 mcg/day, increase slowly
• Monitor TSH every 6-8 weeks until stable, then annually
• Take on empty stomach 30-60 minutes before food; avoid calcium, iron within 4 hours
• Target TSH: 0.5-2.5 mIU/L (lower in pregnancy: 0.1-2.5 mIU/L)

• IV T4 (levothyroxine) 300-500 mcg loading dose, then 50-100 mcg/day IV
• Consider IV T3 (liothyronine) 5-20 mcg every 8 hours (faster acting)
• IV Hydrocortisone 100 mg every 8 hours (concurrent, as adrenal axis may be compromised)
• Passive rewarming, supportive ICU care

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B. HYPERTHYROIDISM (Graves' Disease / Toxic Nodule)

• Propranolol 20-40 mg every 6-8 hours (or Atenolol 25-100 mg/day) - controls palpitations, tremor, anxiety
• Calcium channel blockers if beta-blockers contraindicated (e.g., asthma)

• Methimazole (MMI) - preferred (once-daily dosing)
  • Initial: 10-40 mg/day; maintenance: 5-10 mg/day
  • Euthyroid state in 3-8 weeks
• Propylthiouracil (PTU) - preferred in 1st trimester pregnancy and thyroid storm
  • Initial: 100-200 mg every 8 hours; maintenance: 50-100 mg TID
  • Also blocks T4→T3 conversion

• Radioactive Iodine (RAI) - I-131: 10-15 mCi orally (most common in adults); contraindicated in pregnancy; achieves euthyroidism in 6-18 months
• Surgery (thyroidectomy): For large goiter, ophthalmopathy, pregnancy preference, coexisting malignancy

• Propylthiouracil (PTU) 600-1000 mg loading dose, then 200-250 mg every 4-6 hours
• Iodide (SSKI 5 drops TID or Lugol's 8-10 drops TID) - given 1 hour AFTER PTU to block hormone release
• Propranolol IV/oral for rate and sympathetic control
• Hydrocortisone 100 mg IV every 8 hours (blocks T4→T3 conversion, prevents relative adrenal insufficiency)
• Supportive care: cooling, fluids, treat precipitant

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4. MULTIPLE ENDOCRINE NEOPLASIA (MEN) SYNDROMES

MEN 1 (Wermer's Syndrome) - "3 P's": Parathyroid, Pituitary, Pancreas

• Subtotal parathyroidectomy (removal of 3.5 glands) - definitive treatment
• Minimally invasive parathyroidectomy NOT recommended (all glands affected)
• Medical option (if surgery contraindicated): Cinacalcet (calcimimetic) 30-90 mg BD

• Prolactinomas: Cabergoline 0.5-2 mg/week or Bromocriptine 2.5-15 mg/day
• GH-secreting: Transsphenoidal surgery → SST analogues
• Non-functioning: Surgery if causing mass effect

• Gastrinoma (Zollinger-Ellison syndrome): High-dose PPIs (omeprazole 40-80 mg/day); surgery for localized disease
• Insulinoma: Surgical resection; Diazoxide 100-600 mg/day to suppress insulin
• Non-functioning/large tumors: Surgery to prevent metastasis
• Metastatic disease: Everolimus (mTOR inhibitor) or Sunitinib (TKI); SST analogues for symptom control; Streptozocin-based chemotherapy

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MEN 2A (Sipple's Syndrome) - Medullary thyroid cancer (MTC), Pheochromocytoma, Parathyroid

• Total thyroidectomy with central neck dissection - early, even prophylactic in RET mutation carriers
• Timing based on RET codon mutation risk category
• Adjuvant: Vandetanib or Cabozantinib (RET kinase inhibitors) for metastatic/unresectable MTC

• Alpha-blockade first: Phenoxybenzamine 10-40 mg/day for 10-14 days (irreversible); or Doxazosin/Terazosin
• Then beta-blockade: Propranolol 10-40 mg TID AFTER adequate alpha-blockade
• Volume expansion with liberal salt/fluid intake
• Surgical adrenalectomy (laparoscopic preferred)

• Milder than MEN 1; often single gland - focused parathyroidectomy acceptable

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MEN 2B - MTC + Pheo + Mucosal neuromas (no parathyroid disease)

• Same treatment principles as MEN 2A for MTC and pheo
• Prophylactic thyroidectomy in infancy (most aggressive RET mutations)

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DR. RAGHUNATHAN

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5. ELECTROLYTE DISORDERS

A. HYPONATREMIA (Na+ <135 mEq/L)

• 3% Hypertonic saline IV: 100-150 mL over 10-20 min; may repeat x2 if needed
• Target: raise Na+ by 4-6 mEq/L in first hour
• CRITICAL: Never correct Na+ by >8-10 mEq/L per 24 hours (risk of osmotic demyelination syndrome)

• Fluid restriction to <1000 mL/day (first line)
• Demeclocycline 300-600 mg BD (for chronic SIADH)
• Vaptans (ADH receptor antagonists): Tolvaptan 15-60 mg/day orally; Conivaptan IV

• Isotonic saline (0.9% NaCl) to restore volume; body will then excrete excess free water

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B. HYPERNATREMIA (Na+ >145 mEq/L)

• Calculate free water deficit: 0.45 x lean body weight (kg) x [(Na/140) - 1]
• Replace slowly over 48-72 hours (correct no faster than 0.5 mEq/L/hour)
• Use 5% Dextrose water (D5W) or 0.45% NaCl
• Central DI: Desmopressin (DDAVP) SC/IV/intranasal

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C. HYPOKALEMIA (K+ <3.5 mEq/L)

• Mild (3.0-3.5): Oral KCl 40-60 mEq/day in divided doses
• Moderate-severe (<3.0): IV KCl at max 10-20 mEq/hour (peripheral) or 40 mEq/hour (central, with monitoring)
• Co-replace magnesium (refractory hypokalemia is often due to Mg deficiency)

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D. HYPERKALEMIA (K+ >5.5 mEq/L)

• ECG changes present (peaked T waves, sine wave, VF):
  • IV Calcium gluconate 10 mL 10% solution over 2-3 min (stabilize myocardium)
  • IV Insulin 10 units + Dextrose 50% 50 mL (drives K into cells within 20 min)
  • IV Sodium bicarbonate if acidotic
  • Salbutamol nebulizer 10-20 mg (rapid K shifting)
• Remove K from body:
  • Furosemide 40-80 mg IV (renal excretion)
  • Kayexalate (sodium polystyrene sulfonate) 15-60 g orally (GI exchange)
  • Patiromer or Sodium zirconium cyclosilicate (newer binders)
  • Hemodialysis for renal failure patients or severe refractory cases

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E. HYPOMAGNESEMIA

• IV Magnesium sulfate: 1-2 g over 15-60 min for severe cases; 0.5 mEq/kg/day maintenance
• Oral: Magnesium oxide or citrate 300-400 mg/day

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F. HYPOPHOSPHATEMIA

• Severe (<1.0 mg/dL): IV phosphate 0.08-0.64 mmol/kg at max 7 mmol/hour
• Mild-moderate (1.0-2.4 mg/dL): Oral sodium or potassium phosphate salts
• Continue 5-7 days (large extravascular stores slow correction)

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6. HEART-RELATED ILLNESSES

• Lifestyle first: Low-sodium diet, weight loss, aerobic exercise
• 1st line drugs: ACE inhibitors (enalapril, ramipril) / ARBs (losartan, telmisartan), thiazide diuretics, calcium channel blockers (amlodipine)
• Diabetic patients: ACE-I or ARB preferred; add CCB or thiazide as needed
• CKD: ACE-I/ARB + loop diuretics
• Target: <130/80 mmHg (most guidelines)

• ACE-I or ARB (or ARNi - Sacubitril/Valsartan preferred if tolerated)
• Beta-blocker: Carvedilol, metoprolol succinate, or bisoprolol
• Aldosterone antagonist (MRA): Spironolactone 25-50 mg/day or eplerenone
• SGLT2 inhibitor: Dapagliflozin or empagliflozin (proven mortality benefit)
• Loop diuretic: Furosemide for fluid overload/symptoms

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DR. ANANTHAKUMAR

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7. DIABETIC KETOACIDOSIS (DKA) AND HYPEROSMOLAR HYPERGLYCEMIC STATE (HHS)

DKA Diagnostic Criteria

• Glucose >250 mg/dL (may be euglycemic DKA on SGLT2i)
• pH <7.3, bicarbonate <18 mEq/L
• Positive ketones (serum/urine)

DKA Treatment Protocol (ADA guidelines)

• 0.9% NaCl: 1-2 L in first hour
• Then 0.45% NaCl at 250-500 mL/hour (based on hydration status)
• When glucose reaches 200-250 mg/dL: Switch to Dextrose 5% in 0.45% NaCl

• Do NOT start insulin until K+ >3.5 mEq/L (risk of fatal hypokalemia)
• Regular insulin IV infusion: 0.1 units/kg/hour (or 0.1 units/kg bolus, then 0.1 units/kg/hour)
• Target glucose fall of 50-75 mg/dL/hour
• When glucose 200-250 mg/dL: Reduce to 0.02-0.05 units/kg/hour; switch to D5W fluids
• Transition to SC insulin when: pH >7.3, bicarbonate >18, anion gap closed, patient eating

• K+ <3.5: Give KCl 20-40 mEq/hour and HOLD insulin until K+ >3.5
• K+ 3.5-5.5: Give KCl 20-30 mEq/L in IV fluids to keep K+ 4.0-5.0
• K+ >5.5: Hold potassium, monitor every 2 hours

• Give 100 mEq NaHCO3 in 400 mL sterile water + 20 mEq KCl over 2 hours if pH <6.9

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HHS Treatment

• Similar to DKA but more profound dehydration, minimal ketosis, very high glucose (>600 mg/dL), osmolality >320 mOsm/kg
• Fluids: Larger volumes - 0.9% NaCl initially (1-2 L/hour x 1-2 hours)
• Then 0.45% NaCl; correct over 24-48 hours (not faster - risk of cerebral edema)
• Insulin: Lower rates than DKA (0.05 units/kg/hour); delay until glucose no longer falling with fluids alone
• Anticoagulation: Consider heparin (high thrombosis risk)
• Identify and treat precipitant (infection, dehydration, medications)

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8. DIABETES MELLITUS AND CHRONIC COMPLICATIONS

Type 2 DM - Stepwise Management

• Medical nutrition therapy, weight loss (5-10% reduces A1C by 1-2%)
• 150 min/week moderate-intensity aerobic exercise

• Metformin 500 mg BD → titrate to 1000 mg BD (reduces hepatic glucose production)
  • Contraindicated: eGFR <30, IV contrast within 48 hours, liver disease, alcohol excess
  • Start low, titrate slowly to minimize GI side effects

• Add basal insulin (Insulin glargine or detemir) 10 units at bedtime if A1C uncontrolled
• Titrate by 2 units every 3 days to fasting glucose target 80-130 mg/dL
• Add prandial insulin (aspart/lispro) if still uncontrolled - TID with meals
• Full basal-bolus regimen for Type 1 DM

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Chronic Complications Management

• ACE-I or ARB (first-line to reduce proteinuria and slow progression)
• SGLT2 inhibitor (canagliflozin, dapagliflozin) - proven renoprotective
• Control hypertension <130/80 mmHg; restrict protein 0.8 g/kg/day if CKD
• Finerenone (non-steroidal MRA) for proteinuric CKD in T2DM

• Glycemic control is cornerstone
• Pain: Duloxetine 60-120 mg/day (first-line), Pregabalin 75-300 mg BD, Amitriptyline 10-75 mg at night
• Topical: Capsaicin cream, Lidocaine patches

• Strict glycemic and BP control
• Anti-VEGF agents (ranibizumab, bevacizumab) for proliferative disease/macular edema
• Laser photocoagulation for proliferative retinopathy
• Annual ophthalmology screening

• Regular foot inspection; pressure offloading
• Infected ulcers: Broad-spectrum antibiotics (piperacillin-tazobactam or amoxiclav)
• Debridement, wound care
• Severe ischemia: Revascularization; amputation if non-viable

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DR. DAYANAND (Next Week)

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9. CUSHING'S SYNDROME

A. Cushing's Disease (Pituitary ACTH-secreting adenoma)

• Transsphenoidal surgery (TSS) - first-line (remission in 70-85% microadenomas)
• If surgical failure or recurrence:
  • Repeat TSS, or
  • Stereotactic radiotherapy (Gamma Knife) - takes 12-18 months for effect
  • Bilateral adrenalectomy (if persistent hypercortisolism despite above)

• Ketoconazole 200-400 mg TID (inhibits adrenal steroidogenesis) - liver toxicity concern
• Metyrapone 500-1000 mg QID (blocks 11-beta hydroxylase)
• Osilodrostat 1-30 mg BD (newer, potent 11-beta hydroxylase inhibitor)
• Mifepristone 300-1200 mg/day (glucocorticoid receptor antagonist) - for CS with DM
• Cabergoline 0.5-7 mg/week (dopamine agonist for ACTH-secreting adenomas)
• Pasireotide 0.3-0.9 mg SC BD (SST analogue; FDA-approved for Cushing's disease) - causes hyperglycemia

B. Adrenal Cushing's (adrenal adenoma/carcinoma)

• Adrenalectomy (laparoscopic for adenoma)
• Post-op: Hydrocortisone replacement for months until contralateral gland recovers
• Adrenocortical carcinoma: Mitotane (adrenolytic) ± chemotherapy (EDP - Etoposide, Doxorubicin, Cisplatin)

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10. ADDISON'S DISEASE (Primary Adrenal Insufficiency)

Chronic Replacement

• Hydrocortisone 15-20 mg/day in split doses (10 mg morning + 5 mg noon + 5 mg early afternoon)
• Alternative: Prednisolone 3-5 mg/day once in the morning
• Sick day rules: Double/triple dose during illness, fever, surgery; patient should carry emergency hydrocortisone injection kit (100 mg IM)

• Fludrocortisone 50-200 mcg once daily (essential in primary AI; NOT needed in secondary)
• Monitor BP, electrolytes, renin levels (target renin upper limit of normal)

• DHEA 25-50 mg/day orally in women with fatigue/low libido despite other replacement

Acute Adrenal Crisis (Emergency)

• IV Hydrocortisone 100 mg bolus immediately (DO NOT WAIT for confirmatory tests)
• IV 0.9% NaCl 1-2 L rapidly (volume resuscitation; supplement with 5% dextrose)
• IV Hydrocortisone 50-100 mg every 6-8 hours for 24-48 hours
• Identify and treat precipitant (infection, surgery, trauma, medication missed)
• Once stable: Step down to oral hydrocortisone; add fludrocortisone once oral intake resumes

• Medical alert bracelet; educate about sick-day rules; emergency injection training

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11. OBESITY

A. Lifestyle Intervention (First-line for all)

• Caloric deficit of 500-750 kcal/day (target 0.5-1 kg/week weight loss)
• Low-carbohydrate, Mediterranean, or low-fat dietary patterns
• 150-300 min/week moderate-intensity aerobic exercise + resistance training
• Behavioral therapy (CBT-based weight management programs)

B. Pharmacotherapy (BMI ≥30, or ≥27 with comorbidities)

C. Bariatric Surgery (BMI ≥40, or ≥35 with comorbidities, failed medical therapy)

• Roux-en-Y Gastric Bypass (RYGB): Most effective; 25-35% EWL; resolves T2DM in 80%
• Sleeve Gastrectomy: Simpler; 20-30% EWL; now most common globally
• Adjustable Gastric Band: Less effective; falling out of favor
• Pre-op: Psychological evaluation, nutritional counseling, optimize comorbidities
• Post-op: Lifelong vitamin/mineral supplementation (B12, iron, folate, calcium, vitamin D)

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DR. RAGHUNATHAN (Next Week)

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12. METABOLIC ACIDOSIS / ALKALOSIS

A. METABOLIC ACIDOSIS

• Methanol, Uremia, DKA, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, Salicylates
• Treat the underlying cause
• Lactic acidosis (Type A): Restore perfusion/oxygenation; treat sepsis; sodium bicarbonate only if pH <7.1
• DKA: (see above - insulin, fluids, electrolytes)
• Methanol/Ethylene glycol: IV Fomepizole (alcohol dehydrogenase inhibitor) 15 mg/kg loading; hemodialysis; folate/thiamine
• Salicylate toxicity: Urinary alkalinization (IV NaHCO3); dialysis for severe cases

• GI bicarbonate loss (diarrhea): Treat cause; oral NaHCO3 1-2 g TID
• Renal tubular acidosis (RTA): Type 1 (distal RTA) - oral NaHCO3 or Shohl's solution (sodium citrate)
• Type 2 (proximal RTA): Potassium citrate or bicarbonate

• Reserve for pH <7.1-7.15, severe hyperkalemia with acidosis, bicarbonate-losing causes
• Formula: Bicarbonate deficit = 0.5 x weight (kg) x (target HCO3 - measured HCO3)
• Give half the deficit over 4-8 hours; reassess

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B. METABOLIC ALKALOSIS

• Replace volume: Isotonic saline (0.9% NaCl)
• Replace KCl (hypokalemia perpetuates alkalosis)
• Stop diuretics if possible
• Severe cases: Consider dilute HCl infusion or Acetazolamide 250-500 mg IV

• Usually due to hyperaldosteronism, Cushing's, Bartter/Gitelman syndromes
• Spironolactone (for hyperaldosteronism)
• Treat the underlying cause

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13. CALCIUM DISORDERS

A. HYPOCALCEMIA (Ca2+ <8.5 mg/dL)

• IV Calcium gluconate 1-2 g (10-20 mL of 10% solution) over 10-20 minutes
• Continuous infusion: 0.5-1.5 mg/kg/hour elemental calcium
• Monitor ECG

• Oral calcium carbonate 1-3 g elemental calcium/day (most absorbed with meals)
• Calcitriol (1,25-OH Vit D) 0.25-2 mcg/day (especially in hypoparathyroidism)
• Treat underlying cause: hypoparathyroidism (calcitriol + calcium), vitamin D deficiency (cholecalciferol 50,000 IU weekly)

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B. HYPERCALCEMIA (Ca2+ >10.5 mg/dL)

• IV Saline hydration: 0.9% NaCl 200-300 mL/hour (enhance urinary Ca excretion)
• Furosemide only after adequate volume repletion (calciuretic)
• IV Bisphosphonates: Zoledronic acid 4 mg IV over 15 min (onset 2-4 days; lasts weeks); or pamidronate 60-90 mg IV
• Calcitonin 4 units/kg SC/IM every 12 hours (rapid but tachyphylaxis in 48 hours - useful as bridge)
• Denosumab 60-120 mg SC (for bisphosphonate-refractory hypercalcemia)
• Dialysis: For severe cases with renal failure
• Malignancy-associated: Treat the malignancy; Cinacalcet for parathyroid carcinoma
• Sarcoidosis/granulomatous: Prednisone 20-40 mg/day (reduces 1,25-OH Vit D production)

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14. OSTEOPOROSIS

A. Non-Pharmacological

• Calcium intake: 1000-1200 mg/day (dietary + supplements if needed)
• Vitamin D: 600-800 IU/day (up to 2000 IU if deficient)
• Weight-bearing exercise: 30 min/day, balance training
• Fall prevention: Remove home hazards; hip protectors if high fall risk
• Avoid smoking and excessive alcohol

B. Pharmacological (T-score <-2.5, or <-1.0 with fracture)

• Alendronate 70 mg orally once weekly (take with water, remain upright 30 min)
• Risedronate 35 mg weekly or 150 mg monthly
• Zoledronic acid 5 mg IV once yearly (preferred for adherence/GI intolerance)
• Duration: 3-5 years, then reassess (drug holiday for low-risk patients)
• Monitor: Dental health (risk of osteonecrosis of jaw); atypical femur fractures with long-term use

• Denosumab 60 mg SC every 6 months (RANK-L inhibitor; antiresorptive)
  • Do not stop abruptly (rebound vertebral fractures); transition to bisphosphonate on stopping
• Teriparatide (PTH 1-34) 20 mcg SC daily (anabolic; max 2 years)
  • For severe osteoporosis, multiple fractures, bisphosphonate failure
• Abaloparatide (PTHrP analogue) 80 mcg SC daily (anabolic; max 2 years)
• Romosozumab 210 mg SC monthly x 12 months (dual action: anabolic + antiresorptive)
  • Use with caution in high CV risk (slight increased stroke/MI risk)

• Estrogen ± progesterone - effective for bone but not first-line for osteoporosis alone (breast cancer, CV risk)

• Bisphosphonates (alendronate, zoledronic acid) - approved
• If testosterone deficient: testosterone replacement also improves bone density

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PHARMACOLOGICAL & SURGICAL MANAGEMENT - FINAL YEAR MBBS

Complete Endocrinology & Internal Medicine Regimens

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DR. MANOJ KUMAR

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1. PANHYPOPITUITARISM

Overview

GOLDEN RULE of Replacement Sequence

Always replace GLUCOCORTICOIDS first, then THYROID hormone. Thyroid hormone accelerates cortisol metabolism - giving T4 alone can precipitate fatal adrenal crisis.

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PHARMACOLOGICAL MANAGEMENT

A. Glucocorticoid Replacement (Adrenal Axis)

• Sick day rules: Double/triple dose during fever, illness, minor surgery; 100 mg IM hydrocortisone for major surgery/vomiting
• Patients must carry emergency steroid card and hydrocortisone injection kit

B. Thyroid Hormone Replacement

• Levothyroxine (T4): 1.6 mcg/kg/day orally
• Elderly/cardiac: Start 12.5-25 mcg/day, increase by 25 mcg every 4-6 weeks
• Monitor free T4 (NOT TSH - TSH is unreliable in central hypothyroidism)
• Target: Free T4 in upper half of normal range
• Take on empty stomach; separate from calcium/iron by 4 hours

C. Sex Hormone Replacement

• Testosterone enanthate/cypionate: 200-250 mg IM every 2-4 weeks
• Testosterone gel 1% topical: 50-100 mg/day
• Monitor hematocrit, PSA, bone density

• Estradiol + cyclic progesterone (oral or transdermal)
• For fertility: Exogenous gonadotropins (FSH + hCG injections) - refer to fertility specialist

D. Growth Hormone Replacement

• Somatropin (rhGH): SC injection daily
  • Adults: Start 0.2-0.3 mg/day; titrate to normalize IGF-1
  • Children: 0.025-0.05 mg/kg/day
• Monitor IGF-1 every 6 months; contraindicated in active malignancy
• Benefits: Improved body composition, bone density, lipid profile, quality of life

E. ADH Replacement (if Central Diabetes Insipidus)

• Desmopressin (DDAVP):
  • Oral: 0.1-0.2 mg BD-TID
  • Intranasal: 10-20 mcg BD
  • SC/IV: 2-4 mcg BD
• Titrate to control polyuria/polydipsia without causing hyponatremia

ACUTE ADRENAL CRISIS (Emergency Management)

1. IV Hydrocortisone 100 mg bolus immediately
2. IV 0.9% NaCl 1-2 L rapidly + 5% dextrose (for hypoglycemia)
3. IV Hydrocortisone 50-100 mg every 6-8 hours continuously
4. Treat precipitant (infection, trauma, medication missed)
5. Taper to maintenance once stable

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SURGICAL MANAGEMENT

• Surgery is directed at the underlying cause (e.g., pituitary adenoma, craniopharyngioma)
• Transsphenoidal surgery (TSS): For pituitary macroadenoma causing compression
• Craniotomy: For suprasellar tumors (craniopharyngioma, meningioma)
• Post-operative: All patients require hormone replacement assessment
• Radiation therapy (if surgery fails or incomplete resection): Fractionated radiotherapy or Gamma Knife stereotactic radiosurgery
• Note: Surgery and radiation themselves can cause or worsen panhypopituitarism - lifelong follow-up mandatory

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2. ACROMEGALY

Overview

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SURGICAL MANAGEMENT (First-Line)

Transsphenoidal Surgery (TSS)

• Endoscopic endonasal transsphenoidal surgery - standard of care
• Cure rates:
  • Microadenoma (<10 mm): 80-90%
  • Macroadenoma (>10 mm): 40-60%
• Pre-operative SST analogue: Used in some centers to shrink tumor, improve surgical field, reduce anesthesia risk (macroglossia, difficult airway)
• Post-operative: Reassess GH/IGF-1 at 12 weeks; if not cured - add medical/radiation therapy

Stereotactic Radiosurgery (Gamma Knife / CyberKnife)

• For residual/recurrent adenoma not amenable to repeat surgery
• Normalizes IGF-1 in 40-60% over 5-10 years
• Risk: Hypopituitarism (30-50%), rare visual deterioration

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PHARMACOLOGICAL MANAGEMENT

A. Somatostatin Analogues (SST) - First-Line Medical Therapy

• Normalizes IGF-1 in 50-70% of patients; can reduce tumor size
• Pasireotide binds SST 1,2,3,5 - more effective in some refractory cases; causes significant hyperglycemia
• Side effects (all SST): Diarrhea, nausea, gallstones (~25%), bradycardia, glucose intolerance

B. GH Receptor Antagonist - Second-Line (Post-surgical failure)

• Pegvisomant: 40 mg SC loading dose, then 10-30 mg SC daily
• Mechanism: Blocks GH receptor dimerization → no JAK-STAT signaling → no IGF-1 production
• Normalizes IGF-1 in >90% of patients
• Monitor: Liver enzymes (monthly x 6 months, then 6-monthly); tumor size by MRI (GH levels rise - NOT a marker of failure)
• Can combine with SST analogues for additive effect

C. Dopamine Agonists - Third-Line (mild disease / mixed GH+PRL adenoma)

• Cabergoline: 0.5-3.5 mg/week orally (cheap, oral)
• Normalizes IGF-1 in only ~30%; useful in mild disease or as add-on

D. Combination Therapy

• SST analogue + Pegvisomant: For partial responders
• SST analogue + Cabergoline: Modest additive benefit

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DR. DAYANAND

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3. THYROID DISORDERS

A. HYPOTHYROIDISM

Pharmacological Management

• Levothyroxine (T4) - Drug of choice
  • Full replacement: 1.6 mcg/kg/day orally
  • Young healthy adults: Start at full dose
  • Elderly or ischemic heart disease: Start 12.5-25 mcg/day, increase by 12.5-25 mcg every 4-6 weeks
• Monitor TSH every 6-8 weeks until stable (target TSH 0.5-2.5 mIU/L)
• Special populations:
  • Pregnancy: Target TSH 0.1-2.5 mIU/L; increase dose by ~30% as soon as pregnancy confirmed
  • Central hypothyroidism: Monitor free T4 (not TSH)

• Liothyronine (T3) added when T4 monotherapy leaves persistent symptoms
• Not routine; used selectively

Myxedema Coma (Emergency)

1. IV Levothyroxine 300-500 mcg loading, then 50-100 mcg/day IV
2. Consider IV Liothyronine (T3) 5-20 mcg every 8-12 hours (faster T3 onset)
3. IV Hydrocortisone 100 mg every 8 hours (concurrent - always cover adrenal axis)
4. Passive rewarming; treat precipitant; IV fluids; mechanical ventilation if needed
5. ICU-level care

Surgical Management

• Thyroidectomy rarely needed for hypothyroidism itself
• Post-thyroidectomy hypothyroidism: Lifelong levothyroxine

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B. HYPERTHYROIDISM (Graves' Disease / Toxic Multinodular Goiter / Solitary Toxic Adenoma)

Pharmacological Management

• Propranolol 20-80 mg every 6-8 hours OR Atenolol 25-100 mg/day
• Controls tachycardia, tremor, anxiety, heat intolerance within 24-48 hours
• If beta-blockers contraindicated: Diltiazem 60-90 mg TID

• Euthyroid in 3-8 weeks; treat for 12-18 months (Graves')
• Monitor: CBC (agranulocytosis <0.5% - stop if neutrophils <1000/mm3), LFTs
• Relapse rate after stopping ATD: ~50% in Graves' - then offer definitive therapy

• Pre-operative preparation: Reduces vascularity; 5-10 drops TID for 10-14 days before surgery
• Thyroid storm: Given 1 hour AFTER PTU loading (prevents new hormone synthesis)

Thyroid Storm (Thyrotoxic Crisis) - Emergency

Surgical Management of Hyperthyroidism

• Total thyroidectomy preferred (lower recurrence than subtotal)
• Indications: Large goiter with compressive symptoms, failed/contraindicated RAI/ATD, thyroid cancer coexisting, severe ophthalmopathy (RAI may worsen it), pregnant patient uncontrolled on ATD
• Pre-operative preparation MANDATORY:
  • ATD to achieve euthyroid state
  • Beta-blockers
  • Lugol's iodine for 10-14 days (reduces intraoperative bleeding)
• Complications of thyroidectomy: Hypoparathyroidism (transient/permanent), RLN injury (hoarseness), thyroid storm (if unprepared)
• Post-thyroidectomy: Lifelong levothyroxine (calcium/vitamin D if hypoparathyroidism occurs)

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4. MULTIPLE ENDOCRINE NEOPLASIA (MEN) SYNDROMES

MEN 1 - "Wermer's Syndrome" (3 Ps)

Parathyroid Disease Treatment

• Subtotal parathyroidectomy (remove 3.5 glands) + bilateral cervical thymectomy - standard
• Minimally invasive NOT recommended (all glands typically affected)
• Cryopreserve remnant parathyroid tissue
• Risk of permanent hypoparathyroidism: ~5-10%

• Cinacalcet (Sensipar) 30-90 mg BD (calcimimetic - acts on calcium-sensing receptor, lowers PTH)

Pancreatic NET Treatment

• Medical (lifelong): High-dose PPI (omeprazole 40-80 mg BD, or IV pantoprazole 80 mg/day)
• Surgical: Resect localized gastrinoma if identified; difficult in MEN 1 (multiple/small tumors)
• Metastatic: Everolimus 10 mg/day or Sunitinib 37.5 mg/day; SST analogues (octreotide LAR)

• Surgical: Enucleation/resection (preferred; usually benign in MEN 1)
• Medical (pre-op or unresectable): Diazoxide 100-300 mg BD-TID (opens ATP-K channel, inhibits insulin secretion); Octreotide LAR; Everolimus
• Malignant: Streptozocin + doxorubicin chemotherapy

Pituitary Tumors (MEN 1)

• Prolactinoma: Cabergoline 0.5-2 mg/week (first-line) or bromocriptine
• GH-secreting: Transsphenoidal surgery → SST analogues if residual
• Large/compressive: Surgery regardless of type

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MEN 2A - "Sipple's Syndrome"

Treatment Order: Pheochromocytoma FIRST, then thyroid, then parathyroid

• Alpha-blockade FIRST (10-14 days minimum):
  • Phenoxybenzamine (irreversible) 10-40 mg/day, titrate
  • Or Doxazosin 2-16 mg/day (selective alpha-1, reversible)
• Beta-blockade AFTER adequate alpha-blockade:
  • Propranolol 20-40 mg TID (never before alpha - hypertensive crisis risk)
• Liberal salt and fluid intake for volume expansion
• Surgical: Laparoscopic adrenalectomy (bilateral if bilateral pheo; consider cortical-sparing)

• Total thyroidectomy + central lymph node dissection - curative intent
• Prophylactic thyroidectomy in RET mutation carriers:
  • Highest risk (codon 918): < 6 months of age
  • High risk (codon 634): By age 5 years
  • Moderate risk (others): By age 5-10 years
• Metastatic/unresectable MTC:
  • Vandetanib 300 mg/day (RET + VEGFR inhibitor) - FDA approved
  • Cabozantinib 140 mg/day (RET + MET + VEGFR inhibitor) - FDA approved
  • Selpercatinib (highly selective RET inhibitor) - newer, well-tolerated

• Milder disease; often single gland adenoma
• Focused parathyroidectomy acceptable (unlike MEN 1)

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MEN 2B

• MTC + Pheochromocytoma + Marfanoid habitus + Mucosal neuromas (lips, tongue) + Intestinal ganglioneuromas
• NO parathyroid disease
• Most aggressive MTC: Prophylactic thyroidectomy in infancy (ideally within first 6 months)
• Same pheo management as MEN 2A

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DR. RAGHUNATHAN

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5. ELECTROLYTE DISORDERS

A. HYPONATREMIA (Na+ <135 mEq/L)

Classify first: Hypovolemic / Euvolemic (SIADH) / Hypervolemic

• 3% Hypertonic Saline: 100-150 mL IV bolus over 10-20 minutes; repeat twice if seizures persist
• Target: Raise Na+ by 4-6 mEq/L in first hour to stop seizures
• NEVER correct >8-10 mEq/L in 24 hours (osmotic demyelination syndrome)

1. Fluid restriction <800-1000 mL/day (cornerstone)
2. Salt tablets 1-3 g/day (increase solute load)
3. Demeclocycline 300-600 mg BD (induces nephrogenic DI - chronic SIADH)
4. Vaptans (V2 receptor antagonists):
   • Tolvaptan 15-60 mg/day orally (aquaretic - excretes free water)
   • Conivaptan 20 mg IV loading, then 20-40 mg/day infusion (hospital use)
   • Risk: Overcorrection - monitor Na+ every 6 hours initially
5. Treat underlying cause (malignancy, CNS disease, drugs)

• Isotonic saline (0.9% NaCl) to restore volume (autocrection will follow)
• Treat underlying cause (fludrocortisone for Addison's)

• Fluid restriction + treat underlying disease
• Vaptans may help (cirrhosis: tolvaptan); loop diuretics for cardiac/renal

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B. HYPERNATREMIA (Na+ >145 mEq/L)

Deficit (L) = 0.45 × weight(kg) × [(Na/140) - 1]

• Correct no faster than 0.5 mEq/L/hour (max 10-12 mEq/L/day)
• Use D5W (hypotonic) or 0.45% NaCl for replacement
• Central DI: DDAVP 1-4 mcg SC/IV BD + low-solute diet
• Nephrogenic DI: Treat cause + low-sodium diet + hydrochlorothiazide 25 mg/day + amiloride or indomethacin

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C. HYPOKALEMIA (K+ <3.5 mEq/L)

• Replace Magnesium first - hypomagnesemia perpetuates K+ wasting (target Mg >0.8 mmol/L)
• Monitor ECG: Prominent U waves, T-wave flattening
• Causes: Diarrhea/vomiting, diuretics, hyperaldosteronism, alkalosis

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D. HYPERKALEMIA (K+ >5.5 mEq/L)

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E. HYPOMAGNESEMIA (Mg2+ <0.7 mmol/L)

• IV Magnesium sulfate 4-8 g in 100 mL NS over 1-2 hours; then 2 g/hour infusion
• Monitor reflexes, respiratory rate (loss of patellar reflex = toxicity warning)

• Oral magnesium oxide or citrate 300-400 mg/day

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F. HYPOPHOSPHATEMIA (<2.5 mg/dL)

• Severe (<1.0 mg/dL): IV phosphate 0.08-0.64 mmol/kg at max 7 mmol/hour
• Moderate (1.0-1.9 mg/dL): Oral sodium or potassium phosphate salts
• Treat for 5-7 days (large extravascular phosphate stores)
• Refeeding syndrome: Monitor phosphate closely when feeding malnourished patients

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6. HEART-RELATED ILLNESSES

HYPERTENSION

• Target BP: <130/80 mmHg (most guidelines)
• Add 2nd agent if uncontrolled at 4 weeks; 3+ agents = resistant HTN → investigate for secondary causes

• IV Labetalol 20-80 mg every 10 min (or infusion 0.5-2 mg/min)
• IV Nicardipine 5-15 mg/hour (preferred in neurological emergencies)
• IV Sodium nitroprusside infusion (intensive care; max 10 mcg/kg/min)
• Target: Reduce MAP by no more than 25% in first hour, then 160/100 over 2-6 hours

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HEART FAILURE WITH REDUCED EF (HFrEF EF <40%)

• Loop diuretic (Furosemide): 20-160 mg/day for congestion/symptom control
• Ivabradine: 5-7.5 mg BD if HR >70 in sinus rhythm on maximally tolerated beta-blocker
• Digoxin: 0.125-0.25 mg/day - reduces hospitalizations in AF + HF
• Hydralazine + Isosorbide dinitrate: For ACE-I/ARB intolerant patients (especially in Black patients)
• Vericiguat or Omecamtiv mecarbil: Newer agents for advanced HF

• ICD (Implantable Cardioverter Defibrillator): EF <35% on optimal medical therapy, NYHA Class II-III → prevents sudden cardiac death
• CRT (Cardiac Resynchronization Therapy): EF <35% + LBBB + QRS >130 ms + NYHA Class II-IV
• LVAD (Left Ventricular Assist Device): Bridge to transplant or destination therapy in advanced HF
• Heart transplantation: End-stage HF, no contraindications

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ACUTE CORONARY SYNDROME (ACS)

• Primary PCI (within 90 min of first medical contact): Gold standard
• Thrombolysis (if PCI not available within 120 min): Streptokinase, Alteplase, Tenecteplase
• Anti-platelets: Aspirin 300 mg loading + Ticagrelor 180 mg OR Prasugrel 60 mg (DAPT)
• Anticoagulation: Heparin UFH or LMWH; Bivalirudin during PCI
• Beta-blocker (oral, within 24 hours if hemodynamically stable)
• ACE-I, High-intensity statin (atorvastatin 40-80 mg)

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DR. ANANTHAKUMAR

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7. DIABETIC KETOACIDOSIS (DKA) AND HYPEROSMOLAR HYPERGLYCEMIC STATE (HHS)

DKA MANAGEMENT

Diagnostic Criteria

Step-by-Step DKA Protocol

• 0.9% NaCl: 1-2 L in first hour
• Next 2-6 hours: 0.9% or 0.45% NaCl at 500-1000 mL/hour (based on dehydration)
• When glucose reaches 200-250 mg/dL: Change to Dextrose 5% in 0.45% NaCl

If K+ <3.5 mEq/L: Give 20-40 mEq KCl/hour, HOLD insulin

• Regular insulin: 0.1 units/kg/hour IV infusion (or 0.1 units/kg bolus then 0.1 units/kg/hour)
• Alternative (mild DKA): 0.3 units/kg SC as bolus, then 0.1 units/kg SC every hour
• Target glucose fall: 50-75 mg/dL/hour
• When glucose 200-250 mg/dL: Reduce to 0.02-0.05 units/kg/hour

• Glucose <200 mg/dL
• Bicarbonate >15 mEq/L
• pH >7.3
• Anion gap closed (<12)
• Patient eating and drinking

• Only if pH <6.9: 100 mEq NaHCO3 + 40 mEq KCl in 400 mL sterile water over 2 hours
• Risks: Paradoxical CNS acidosis, hypokalemia, delayed ketone clearance

• Replace only if <1.0 mg/dL or cardiac dysfunction: IV potassium phosphate

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HHS MANAGEMENT

• More profound dehydration (fluid deficit 8-12 L); minimal ketosis; elderly type 2 DM
• High risk of thromboembolism

• Correct over 24-48 hours (not faster - risk of cerebral edema)
• Target serum osmolality decrease of 3-8 mOsm/hour

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8. DIABETES MELLITUS AND CHRONIC COMPLICATIONS

TYPE 1 DM

Insulin Regimens

• Basal insulin (once or twice daily):
  • Insulin Glargine (U100 or U300) once daily at bedtime
  • Insulin Detemir once-twice daily
  • Insulin Degludec once daily (ultra-long; lowest hypoglycemia risk)
• Bolus (prandial) insulin (with each meal):
  • Rapid-acting: Insulin Aspart (NovoRapid), Lispro (Humalog), Glulisine (Apidra)
  • Give 5-15 min before meals; dose = carbohydrate counting + correction factor
• Insulin pump (CSII): Continuous SC insulin infusion - best glycemic control

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TYPE 2 DM - Pharmacological Management

• Metformin 500-2000 mg/day (in divided doses with meals)
  • Mechanism: Reduces hepatic glucose output, improves insulin sensitivity
  • Contraindications: eGFR <30, IV contrast (hold 48 h), liver failure, severe heart failure, alcohol excess

• Start: Basal insulin glargine/detemir 10 units at bedtime
• Titrate: Add 2 units every 3 days until fasting glucose 80-130 mg/dL
• If still uncontrolled: Add prandial insulin before largest meal (basal-bolus escalation)

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CHRONIC COMPLICATIONS

Diabetic Nephropathy

• Glycemic control (A1C <7%)
• BP control <130/80 (target <120/80 in proteinuric CKD)
• ACE-I or ARB: Reduce intraglomerular pressure, slow progression (first-line)
• SGLT2 inhibitor: (canagliflozin, dapagliflozin) proven to reduce renal progression - add regardless of glycemic control
• Finerenone (non-steroidal MRA): Reduces CKD progression + CV events in T2DM + CKD - add to RAAS blockade
• Restrict protein 0.8 g/kg/day; avoid NSAIDs/nephrotoxins
• Dialysis (HD/PD) or renal transplantation when ESRD

Diabetic Neuropathy

• Glycemic control is cornerstone (slows progression)
• Painful peripheral neuropathy:
  1. Duloxetine 60-120 mg/day (first-line, FDA-approved)
  2. Pregabalin 75-300 mg BD (first-line, FDA-approved)
  3. Amitriptyline 10-75 mg at bedtime (low-cost; watch cardiac QTc)
  4. Gabapentin 300-1200 mg TID
  5. Topical Capsaicin 0.075% cream or Lidocaine patch
  6. Tramadol or Tapentadol (opioid - last resort)

Diabetic Retinopathy

• Annual dilated fundus examination
• Glycemic + BP control (most important prevention)
• NPDR - PDR: Panretinal laser photocoagulation (PRP)
• Diabetic macular edema (DME): Intravitreal anti-VEGF (ranibizumab, aflibercept, bevacizumab) - first-line; laser for persistent cases
• Vitrectomy for vitreous hemorrhage/tractional retinal detachment

Diabetic Foot

• Glycemic control; regular foot inspection
• Offloading: Total contact cast, diabetic footwear
• Infected ulcer: Wound swab → Antibiotics (amoxiclav for mild; piperacillin-tazobactam/meropenem for severe/osteomyelitis)
• Debridement; negative pressure wound therapy
• Ischemic foot: Peripheral revascularization (angioplasty or bypass surgery)
• Osteomyelitis: 6 weeks antibiotics ± surgical debridement/bone resection
• Non-viable limb: Amputation (try to preserve as much length as possible)

Macrovascular Disease

• Aspirin 75-100 mg/day (secondary prevention)
• High-intensity statin (atorvastatin 40-80 mg)
• ACE-I + beta-blocker post-MI
• Aggressive risk factor control

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DR. DAYANAND (Next Week)

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9. CUSHING'S SYNDROME

Overview

SURGICAL MANAGEMENT

Cushing's Disease (Pituitary)

• Transsphenoidal surgery (TSS) - First-line
  • Remission: 70-90% microadenomas; 50-60% macroadenomas
  • Criteria for remission: Morning cortisol <50 nmol/L post-op
• If TSS fails or recurs:
  • Repeat TSS (if residual adenoma identified)
  • Stereotactic radiosurgery (Gamma Knife) - takes 12-18 months; effective in 50-60%
  • Bilateral adrenalectomy: Definitive for refractory Cushing's; lifelong steroid replacement required; risk of Nelson's syndrome (ACTH-secreting tumor enlargement - needs pituitary irradiation prophylaxis)

Adrenal Cushing's

• Adrenal adenoma: Laparoscopic adrenalectomy (standard)
• Post-operative: Hydrocortisone replacement for 6-24 months while contralateral adrenal recovers
• Adrenocortical carcinoma:
  • Open adrenalectomy (complete resection)
  • Adjuvant: Mitotane 2-6 g/day (adrenolytic) - monitor levels (target 14-20 mg/L)
  • Chemotherapy for metastatic disease: EDP regimen (Etoposide 100 mg/m² + Doxorubicin 20 mg/m² + Cisplatin 40 mg/m², days 1,2,3,4) + Mitotane

Ectopic ACTH

• Surgical resection of the primary tumor (lung carcinoid, SCLC, thymic carcinoid)
• If not resectable: Medical control of hypercortisolism ± bilateral adrenalectomy

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PHARMACOLOGICAL MANAGEMENT

• Mifepristone (Korlym) 300-1200 mg/day: Glucocorticoid receptor antagonist; approved for CS with T2DM/glucose intolerance; cortisol levels rise (not useful as monitoring marker)

• Pasireotide LAR 10-40 mg SC monthly (SST analogue; approved for Cushing's disease) - causes hyperglycemia in 70%
• Cabergoline 0.5-7 mg/week (dopamine agonist; modest response ~30-40%)
• Osilodrostat preferred over older agents for medical management

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10. ADDISON'S DISEASE (Primary Adrenal Insufficiency)

PHARMACOLOGICAL MANAGEMENT

Chronic Replacement

• Overtreatment signs: Cushing features, weight gain, hyperglycemia
• Undertreatment signs: Fatigue, nausea, weight loss, hyperpigmentation worsening

• Fludrocortisone 50-200 mcg once daily
• Monitor: BP (supine/standing), electrolytes (Na+/K+), plasma renin (target upper normal)
• Increase dose in hot weather/heavy exercise (increased sweat Na+ loss)

• DHEA 25-50 mg/day orally (for women with fatigue, low libido, poor well-being despite other replacement)

• Minor illness/fever: Double hydrocortisone dose
• Vomiting/unable to take oral: Hydrocortisone 100 mg IM injection (patient self-injects from emergency kit); attend hospital
• Surgery/procedure: Hydrocortisone 50-100 mg IV at induction; infusion post-op; taper over 1-3 days

Adrenal Crisis - Emergency Management

1. Hydrocortisone 100 mg IV bolus immediately (do not wait for lab results - it can be life-threatening)
2. IV 0.9% NaCl 1 L over 30-60 min (volume resuscitation); continue 1-2 L/hour as needed; add dextrose if hypoglycemic
3. Hydrocortisone 50-100 mg IV every 6 hours for 24-48 hours (sufficient mineralocorticoid activity at this dose - no separate fludrocortisone needed acutely)
4. Identify and treat precipitant (most common: infection - sepsis screen + broad-spectrum antibiotics)
5. Once clinical improvement: Step down to oral hydrocortisone; reintroduce fludrocortisone when oral intake resumes

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11. OBESITY

PHARMACOLOGICAL MANAGEMENT (BMI ≥30, or ≥27 with comorbidities, after lifestyle failure)

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SURGICAL MANAGEMENT (Bariatric Surgery)

• BMI ≥40, OR
• BMI ≥35 with obesity-related comorbidities (T2DM, HTN, OSA, joint disease), OR
• BMI 30-35 with poorly controlled T2DM (emerging evidence)

• Multidisciplinary assessment: Bariatric surgeon, dietitian, psychologist, physician
• Endoscopy, cardiac evaluation, sleep study (if OSA)
• Nutritional optimization; stop smoking ≥6 weeks before

• Multivitamin daily
• Calcium citrate 1200-1500 mg/day + Vitamin D 3000 IU/day
• Vitamin B12 (parenteral/sublingual preferred - RYGB impairs oral B12 absorption)
• Iron 45-60 mg elemental iron/day (especially women of childbearing age)
• Folate supplementation

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DR. RAGHUNATHAN (Next Week)

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12. METABOLIC ACIDOSIS / ALKALOSIS

METABOLIC ACIDOSIS

Step 1: Anion Gap = Na - (Cl + HCO3); Normal = 8-12 mEq/L

High Anion Gap Metabolic Acidosis (HAGMA) - Mnemonic: MUDPILES

Normal Anion Gap (Hyperchloremic) Acidosis

• Mnemonic: HARDUPS (Hyperalimentation, Addison's disease, RTA, Diarrhea, Ureteroenterostomy, Pancreatic fistula, Saline infusion)

• Indication: pH <7.1 OR severe hyperkalemia with acidosis OR bicarbonate-losing states
• Dose: Bicarbonate deficit (mEq) = 0.5 × weight (kg) × (target HCO3 - measured HCO3)
• Give half the calculated deficit over 4-8 hours; reassess; do not fully correct acutely

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METABOLIC ALKALOSIS

Causes: Vomiting, NG suction, diuretics, hyperaldosteronism, milk-alkali syndrome, antacids

• Severe/symptomatic alkalosis (pH >7.6): Consider Acetazolamide 250-500 mg IV (carbonic anhydrase inhibitor - promotes HCO3 excretion)
• Hydrogen chloride infusion: Rarely, for refractory cases in ICU
• Bartter's syndrome: Indomethacin + KCl + spironolactone
• Gitelman's syndrome: KCl + Mg2+ supplementation + amiloride

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13. CALCIUM DISORDERS

A. HYPOCALCEMIA (Total Ca <8.5 mg/dL; Ionized Ca <1.1 mmol/L)

• IV Calcium gluconate 10-20 mL of 10% solution (contains 93 mg elemental Ca) IV over 10-20 min
• Repeat if symptoms recur; then continuous infusion: 0.5-1.5 mg/kg/hour elemental calcium
• Monitor ECG; check and replace Mg2+ (hypomagnesemia perpetuates hypocalcemia)

• Oral Calcium carbonate 500-1500 mg elemental calcium BD-TID (with meals for absorption)
• Calcitriol (1,25-OH Vitamin D3) 0.25-2 mcg/day (essential when PTH deficient - cannot activate vitamin D)
• Vitamin D deficiency: Cholecalciferol (D3) 50,000 IU/week x 8-12 weeks, then maintenance 2000 IU/day
• Recombinant PTH 1-34 (Teriparatide) or PTH 1-84 (Natpara): For chronic hypoparathyroidism not controlled with conventional therapy

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B. HYPERCALCEMIA (Total Ca >10.5 mg/dL)

• Primary Hyperparathyroidism: Parathyroidectomy (definitive) - indicated for symptomatic disease, Ca >1 mg/dL above ULN, age <50, osteoporosis, nephrolithiasis, eGFR <60
• Minimally invasive parathyroidectomy (MIP): When single adenoma identified on sestamibi scan or ultrasound
• Bilateral neck exploration: If preoperative localization fails or multigland disease suspected

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14. OSTEOPOROSIS

Definition: T-score ≤ -2.5 (DXA). Treat all fragility fractures regardless of T-score.

Non-Pharmacological (ALL patients)

• Calcium: 1000-1200 mg/day total (dietary + supplement if needed; calcium carbonate with meals / calcium citrate any time)
• Vitamin D: 800-2000 IU/day (target 25-OH vitamin D >50 nmol/L)
• Weight-bearing and resistance exercise
• Fall prevention: Home hazard assessment, balance training, vision correction, review medications (benzodiazepines, antihypertensives)
• Smoking cessation, reduce alcohol (<2 units/day)

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PHARMACOLOGICAL MANAGEMENT

A. ANTIRESORPTIVE AGENTS

• Take oral bisphosphonates with large glass of water, remain upright for 30 min after, 30 min before food/medications
• Reduce vertebral fractures by ~40-70%; hip fractures by ~30-50%
• Duration: 3-5 years → reassess with FRAX score; drug holiday for low-risk (continue in high-risk)
• Monitor: Dental examination before starting (risk of osteonecrosis of jaw, <1%); atypical femoral fractures with >5 years use

• 60 mg SC every 6 months
• Mechanism: Inhibits RANKL → prevents osteoclast differentiation → reduces bone resorption
• Effective for vertebral, hip, and non-vertebral fractures
• Preferred: Renal impairment (CKD - no dose adjustment needed), patients who cannot tolerate oral bisphosphonates
• CRITICAL: Do NOT stop abruptly → rebound vertebral fractures; must transition to bisphosphonate on discontinuation
• Monitor: Calcium levels (hypocalcemia risk, especially in CKD); osteonecrosis of jaw

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B. ANABOLIC AGENTS (For severe osteoporosis, multiple fractures, bisphosphonate failure)

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C. OTHER ANTIRESORPTIVES

• Raloxifene (SERMs): 60 mg/day orally; reduces vertebral fractures; increases VTE risk; no hip fracture reduction; also reduces breast cancer risk - use in younger postmenopausal women
• Hormone Replacement Therapy (HRT): Effective for bone but NOT first-line for osteoporosis alone (breast cancer, CV, VTE risk)
• Calcitonin nasal spray: 200 IU/day; weakest agent; mainly analgesic use in acute vertebral fracture

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SURGICAL MANAGEMENT

• Vertebroplasty / Kyphoplasty: Percutaneous cement injection for painful vertebral compression fractures (acute, refractory to conservative management)
  • Kyphoplasty (balloon first) can restore vertebral height
• Hip fracture surgery: Internal fixation (hemiarthroplasty or total hip replacement) - within 24-48 hours
• Fragility fracture surgery: Appropriate orthopedic fixation with concurrent initiation of osteoporosis medical therapy

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Sources: Goodman & Gilman's Pharmacological Basis of Therapeutics, 14e | Harrison's Principles of Internal Medicine, 22e (2025) | Goldman-Cecil Medicine | Lippincott Illustrated Reviews: Pharmacology | Washington Manual of Medical Therapeutics | Current Surgical Therapy, 14e | Andrews' Diseases of the Skin