NEET PG Exam > NEET PG Notes > Medicine > CheatSheet: Endocrinology
CheatSheet: Endocrinology
1. Thyroid Disorders
1.1 Hypothyroidism
| Etiology | Details |
|---|---|
| Primary (95%) | Hashimoto's thyroiditis (autoimmune, anti-TPO, anti-thyroglobulin), iodine deficiency, post-ablative, drugs (lithium, amiodarone) |
| Secondary | Pituitary failure (low TSH, low T4) |
| Tertiary | Hypothalamic failure (low TRH) |
| Clinical Features | Manifestations |
|---|---|
| General | Fatigue, cold intolerance, weight gain, constipation, bradycardia |
| Skin/Hair | Dry skin, hair loss, coarse hair, periorbital puffiness, non-pitting edema (myxedema) |
| Neurological | Delayed relaxation of reflexes (slow relaxing ankle jerk), carpal tunnel syndrome, cerebellar ataxia |
| Cardiac | Bradycardia, pericardial effusion, decreased cardiac output |
| Lab Findings | Anemia (normocytic), hyperlipidemia, hyponatremia, elevated CPK |
1.1.1 Myxedema Coma
- Severe hypothyroidism with altered sensorium, hypothermia (<35°c), hypoventilation,="" bradycardia,="">
- Precipitants: infection, cold exposure, sedatives, surgery
- Treatment: IV T4 (300-500 µg loading), IV T3 (5-20 µg), hydrocortisone 100 mg IV q8h, supportive care
1.2 Hyperthyroidism
| Etiology | Key Features |
|---|---|
| Graves' Disease (70-80%) | Diffuse goiter, exophthalmos, pretibial myxedema, TSH receptor antibodies (TRAb), diffuse uptake on scan |
| Toxic Multinodular Goiter | Older patients, irregular goiter, patchy uptake on scan, no eye signs |
| Toxic Adenoma | Single hot nodule on scan, suppressed TSH |
| Thyroiditis | Painful (de Quervain's) or painless, low uptake on scan, transient hyperthyroidism |
| Clinical Features | Manifestations |
|---|---|
| General | Weight loss, heat intolerance, increased appetite, sweating, anxiety, tremor |
| Cardiac | Tachycardia, atrial fibrillation (10-15%), high output failure, systolic hypertension |
| Neuromuscular | Fine tremor, proximal myopathy, hyperreflexia, periodic paralysis (Asian males) |
| Eye Signs (Graves') | Lid lag, lid retraction, exophthalmos, ophthalmoplegia, diplopia |
1.2.1 Thyroid Storm
- Fever (>38.5°C), tachycardia (>140 bpm), altered mental status, GI symptoms, cardiovascular instability
- Treatment: Propylthiouracil 600-1000 mg loading (blocks T4 to T3 conversion), iodine (1 hour after PTU), propranolol 60-80 mg q4h, hydrocortisone 100 mg IV q8h, cooling, supportive care
1.3 Thyroid Nodules and Cancer
| Nodule Evaluation | Approach |
|---|---|
| Initial Test | TSH measurement; if low, perform thyroid scan (hot nodule = rarely malignant) |
| USG Features (Suspicious) | Hypoechoic, microcalcifications, irregular margins, taller than wide, increased vascularity |
| FNAC Indication | Nodule >1 cm with suspicious features or >1.5 cm with normal TSH |
| Thyroid Cancer Type | Characteristics |
|---|---|
| Papillary (80%) | Orphan Annie nuclei, psammoma bodies, lymphatic spread, best prognosis, associated with radiation exposure |
| Follicular (10-15%) | Hematogenous spread (lung, bone), requires histology (capsular/vascular invasion), second best prognosis |
| Medullary (5%) | From parafollicular C cells, secretes calcitonin, amyloid stroma, MEN 2A/2B association, measure calcitonin and CEA |
| Anaplastic (2%) | Elderly, rapidly growing, very poor prognosis (months), often inoperable |
2. Diabetes Mellitus
2.1 Classification and Diagnosis
| Type | Characteristics |
|---|---|
| Type 1 (5-10%) | Autoimmune destruction of β-cells, anti-GAD, anti-IA2, anti-insulin antibodies, absolute insulin deficiency, ketosis-prone |
| Type 2 (90%) | Insulin resistance + relative insulin deficiency, associated with obesity, metabolic syndrome |
| MODY | Monogenic, autosomal dominant, onset <25 years,="" non-obese,="" family="" history="" in="" multiple=""> |
| Gestational | Diagnosed during pregnancy, screen at 24-28 weeks with 75g OGTT |
| Diagnostic Criteria | Values |
|---|---|
| Fasting Plasma Glucose | ≥126 mg/dL (≥7.0 mmol/L) on two occasions |
| HbA1c | ≥6.5% (≥48 mmol/mol) |
| 2-hour OGTT (75g glucose) | ≥200 mg/dL (≥11.1 mmol/L) |
| Random Plasma Glucose | ≥200 mg/dL with symptoms |
| Category | Fasting (mg/dL) |
|---|---|
| Normal | <> |
| Prediabetes (IFG) | 100-125 |
| Diabetes | ≥126 |
2.2 Acute Complications
2.2.1 Diabetic Ketoacidosis
| Parameter | Findings |
|---|---|
| Features | Hyperglycemia (>250 mg/dL), high anion gap metabolic acidosis (pH <7.3), ketonemia/ketonuria,=""> |
| Precipitants | Infection (40%), insulin omission, MI, pancreatitis, new-onset T1DM |
| Lab Findings | K+ variable (total body depleted but initial may be high), Na+ low (pseudohyponatremia), elevated BUN/Cr, leukocytosis |
| Treatment | IV fluids (NS 1L/hr initially), regular insulin 0.1 U/kg/hr IV, K+ replacement (when <5.3 meq/l="" and="" urine="" output="" present),="" identify=""> |
| Add Dextrose When | Blood glucose <200 mg/dl="" (continue="" insulin="" until="" anion="" gap=""> |
2.2.2 Hyperosmolar Hyperglycemic State
- Severe hyperglycemia (>600 mg/dL), hyperosmolality (>320 mOsm/kg), minimal/no ketosis, pH >7.3, altered sensorium
- Type 2 DM, elderly, precipitants: infection, dehydration, medications (steroids, diuretics)
- Treatment: aggressive IV hydration (NS initially, then 0.45% NS), insulin (lower doses than DKA), K+ replacement
- Higher mortality than DKA (10-20%)
2.2.3 Hypoglycemia
| Severity | Features and Management |
|---|---|
| Mild-Moderate | Autonomic symptoms (sweating, tremor, palpitations, hunger), blood glucose <70 mg/dl,="" treat="" with="" 15g="" oral=""> |
| Severe | Neuroglycopenic symptoms (confusion, seizure, coma), requires assistance, give 25g IV dextrose or 1mg IM glucagon |
| Whipple's Triad | Symptoms of hypoglycemia + low glucose + relief with glucose administration |
2.3 Chronic Complications
2.3.1 Diabetic Nephropathy
- Leading cause of ESRD; stages: hyperfiltration → microalbuminuria (30-300 mg/day) → overt proteinuria (>300 mg/day) → declining GFR → ESRD
- Kimmelstiel-Wilson nodules (nodular glomerulosclerosis) on biopsy
- Screen annually with urine albumin-creatinine ratio; treat with ACE-I/ARB (first-line, renoprotective)
- Target BP <130 0="" mmhg,="" glycemic="" control="" (hba1c=""><>
2.3.2 Diabetic Retinopathy
| Stage | Findings |
|---|---|
| Non-Proliferative (Mild) | Microaneurysms only |
| Non-Proliferative (Moderate) | Microaneurysms + hemorrhages, hard exudates, cotton-wool spots |
| Non-Proliferative (Severe) | 4-2-1 rule: hemorrhages in 4 quadrants, venous beading in 2 quadrants, IRMA in 1 quadrant |
| Proliferative | Neovascularization (disc or elsewhere), vitreous hemorrhage, retinal detachment; requires pan-retinal photocoagulation |
| Maculopathy | Macular edema, exudates involving macula; leading cause of vision loss; treat with anti-VEGF or laser |
2.3.3 Diabetic Neuropathy
| Type | Features |
|---|---|
| Distal Symmetric Polyneuropathy | Glove-and-stocking distribution, loss of vibration sense first, then pain/temperature, then proprioception; gabapentin, pregabalin, duloxetine for pain |
| Autonomic Neuropathy | Gastroparesis, postural hypotension, resting tachycardia, erectile dysfunction, neurogenic bladder, loss of hypoglycemia awareness |
| Mononeuropathy | Cranial (CN III palsy - pupil spared, CN VI, VII), median nerve (carpal tunnel), peroneal nerve (foot drop) |
| Radiculopathy | Truncal radiculopathy, diabetic amyotrophy (proximal motor neuropathy of lower limbs) |
2.4 Management
| Drug Class | Key Points |
|---|---|
| Metformin | First-line for T2DM, decreases hepatic glucose production, weight neutral, risk of lactic acidosis (contraindicated if eGFR <30), stop="" before=""> |
| Sulfonylureas | Stimulate insulin secretion, risk of hypoglycemia and weight gain, glimepiride preferred (less hypoglycemia) |
| DPP-4 Inhibitors (-gliptins) | Increase incretin levels, weight neutral, no hypoglycemia, well tolerated |
| GLP-1 Agonists | Injectable (except oral semaglutide), weight loss, low hypoglycemia risk, nausea common, cardiovascular benefits (liraglutide, semaglutide), pancreatitis risk |
| SGLT-2 Inhibitors (-gliflozins) | Increase urinary glucose excretion, weight loss, BP reduction, cardiovascular and renal benefits, risk of UTI, genital infections, euglycemic DKA |
| Thiazolidinediones | Increase insulin sensitivity, weight gain, fluid retention (contraindicated in heart failure), osteoporosis risk, bladder cancer (pioglitazone) |
| Insulin | Basal (glargine, detemir, degludec), prandial (lispro, aspart, glulisine), premixed; all T1DM need insulin, T2DM when inadequate control |
3. Adrenal Disorders
3.1 Cushing Syndrome
| Etiology | Details |
|---|---|
| ACTH-Dependent (80%) | Cushing disease (pituitary adenoma, 70%), ectopic ACTH (SCLC, carcinoid, 10%) |
| ACTH-Independent (20%) | Adrenal adenoma, adrenal carcinoma, exogenous steroids (most common overall cause) |
| Clinical Features | Manifestations |
|---|---|
| General | Central obesity, moon facies, buffalo hump, supraclavicular fat pad, weight gain |
| Skin | Purple striae (>1 cm), easy bruising, thin skin, acne, hirsutism, hyperpigmentation (ACTH excess) |
| Metabolic | Glucose intolerance/diabetes, hypertension, hypokalemia (ectopic ACTH), osteoporosis |
| Muscular | Proximal myopathy |
| Psychiatric | Depression, psychosis, emotional lability |
3.1.1 Diagnostic Approach
| Step | Test and Interpretation |
|---|---|
| Screening (any one) | 24-hour urinary free cortisol (>3x ULN), late-night salivary cortisol (elevated), 1mg overnight dexamethasone suppression test (cortisol >1.8 µg/dL = positive) |
| Confirm Hypercortisolism | Repeat abnormal test or perform second test |
| Determine Etiology | Plasma ACTH: suppressed (<5 pg/ml)="adrenal" cause;="" normal/elevated=""> |
| If ACTH-Dependent | High-dose dexamethasone (8 mg): suppression >50% = pituitary, no suppression = ectopic; CRH test: rise in ACTH/cortisol = pituitary; bilateral inferior petrosal sinus sampling (BIPSS) if needed |
| Imaging | Pituitary MRI for Cushing disease, CT chest/abdomen for ectopic, CT adrenal for adrenal cause |
3.2 Primary Adrenal Insufficiency (Addison's Disease)
| Etiology | Causes |
|---|---|
| Autoimmune (80%) | Isolated or part of APS-1 (with hypoparathyroidism, mucocutaneous candidiasis) or APS-2 (with thyroid disease, T1DM) |
| Infectious | Tuberculosis (most common worldwide), fungal, CMV (HIV patients) |
| Infiltrative | Metastases (lung, breast), lymphoma, amyloidosis, hemochromatosis |
| Hemorrhage | Waterhouse-Friderichsen syndrome (meningococcemia), anticoagulation |
| Clinical Features | Details |
|---|---|
| General | Fatigue, weakness, weight loss, anorexia, nausea, vomiting, abdominal pain |
| Skin | Hyperpigmentation (palmar creases, buccal mucosa, pressure points) due to high ACTH |
| Cardiovascular | Postural hypotension, hypotension |
| Lab Findings | Hyponatremia, hyperkalemia, hypoglycemia, mild acidosis, eosinophilia, lymphocytosis |
3.2.1 Diagnosis
- Morning cortisol <3 µg/dl="diagnostic;">15 µg/dL = excludes; 3-15 µg/dL = perform ACTH stimulation test
- ACTH stimulation test: give 250 µg cosyntropin IV, measure cortisol at 0, 30, 60 min; cortisol <18 µg/dl="" at="" 30="" or="" 60="" min="adrenal">
- High ACTH (>100 pg/mL) with low cortisol confirms primary adrenal insufficiency
- 21-hydroxylase antibodies positive in autoimmune cases
3.2.2 Adrenal Crisis
- Acute adrenal insufficiency: severe hypotension/shock, abdominal pain, fever, altered mental status, hypoglycemia, hyponatremia, hyperkalemia
- Precipitants: infection, trauma, surgery, abrupt steroid withdrawal
- Treatment: IV hydrocortisone 100 mg bolus then 50 mg q6h (or 200 mg/24h continuous infusion), IV NS aggressive resuscitation, treat precipitant, do NOT wait for test results
3.3 Hyperaldosteronism
| Type | Features |
|---|---|
| Primary (Conn Syndrome) | Adrenal adenoma (60%), bilateral adrenal hyperplasia (40%), hypertension, hypokalemia, metabolic alkalosis, low renin, high aldosterone |
| Secondary | High renin and high aldosterone; causes: renal artery stenosis, renin-secreting tumor, heart failure, cirrhosis, diuretics |
3.3.1 Diagnosis
- Screen with aldosterone-renin ratio (ARR): ARR >20 with aldosterone >15 ng/dL suggests primary hyperaldosteronism
- Confirm with saline suppression test or oral sodium loading (aldosterone remains elevated)
- Distinguish adenoma vs hyperplasia: CT adrenal, adrenal vein sampling (if surgery considered)
- Treatment: surgery for adenoma, spironolactone for bilateral hyperplasia
3.4 Pheochromocytoma
- Tumor of adrenal medulla (90%) or extra-adrenal chromaffin tissue (10%), secretes catecholamines
- Rule of 10s: 10% bilateral, 10% extra-adrenal, 10% malignant, 10% familial (MEN 2A/2B, VHL, NF1, SDH mutations)
- Classic triad: headache, sweating, palpitations; hypertension (paroxysmal or sustained), hyperglycemia
- Diagnosis: 24-hour urine metanephrines and catecholamines (>2x ULN), or plasma free metanephrines
- Imaging: CT/MRI adrenal, MIBG scan for extra-adrenal tumors
- Treatment: surgery after α-blockade (phenoxybenzamine 10-14 days) then β-blockade; never β-blocker alone (unopposed α-stimulation)
4. Pituitary Disorders
4.1 Acromegaly
- Growth hormone excess in adults, almost always from pituitary adenoma (>95%)
- Features: frontal bossing, prognathism, macroglossia, large hands/feet, coarse facial features, wide tooth spacing, deep voice, carpal tunnel syndrome
- Complications: hypertension, diabetes, cardiomyopathy, sleep apnea, colon polyps (increased colorectal cancer risk), arthropathy
- Diagnosis: elevated IGF-1, oral glucose tolerance test (GH fails to suppress to <1 ng/ml="" after="" 75g="" glucose),="" mri="">
- Treatment: transsphenoidal surgery (first-line), somatostatin analogs (octreotide, lanreotide), GH receptor antagonist (pegvisomant), dopamine agonists (cabergoline) if co-secreting prolactin
4.2 Prolactinoma
| Parameter | Details |
|---|---|
| Most Common Type | Most common functional pituitary adenoma; microadenoma (<1 cm)="" in="" women,="" macroadenoma="" (="">1 cm) in men |
| Clinical Features | Women: galactorrhea, amenorrhea, infertility; Men: decreased libido, erectile dysfunction, hypogonadism, mass effect (headache, visual field defects) |
| Diagnosis | Elevated prolactin; level >200 ng/mL virtually diagnostic of prolactinoma; MRI pituitary |
| Causes of Hyperprolactinemia | Prolactinoma, pregnancy/lactation, drugs (antipsychotics, metoclopramide, methyldopa), hypothyroidism, renal failure, PCOS, stalk effect (mass compressing stalk, prolactin <100> |
| Treatment | Dopamine agonists: cabergoline (first-line, better tolerated) or bromocriptine; surgery if drug-resistant or intolerant |
4.3 Hypopituitarism
| Etiology | Causes |
|---|---|
| Mass Lesions | Pituitary adenoma (most common), craniopharyngioma, meningioma, metastases |
| Inflammatory/Infiltrative | Lymphocytic hypophysitis, sarcoidosis, hemochromatosis, histiocytosis X |
| Vascular | Sheehan syndrome (postpartum pituitary necrosis), pituitary apoplexy |
| Traumatic/Iatrogenic | Head trauma, surgery, radiation |
4.3.1 Order of Hormone Loss
- Most vulnerable first: GH → FSH/LH → ACTH → TSH → Prolactin (least vulnerable)
- Clinical manifestations depend on which hormones are deficient
4.3.2 Pituitary Apoplexy
- Hemorrhage/infarction of pituitary adenoma; acute severe headache, visual field defects, ophthalmoplegia, altered mental status, acute hypopituitarism
- Medical emergency; give IV hydrocortisone immediately, urgent neurosurgical evaluation
4.4 Diabetes Insipidus
| Type | Characteristics |
|---|---|
| Central DI | ADH deficiency; causes: idiopathic, head trauma, surgery, tumors (craniopharyngioma), infiltrative (sarcoidosis, histiocytosis); responds to desmopressin |
| Nephrogenic DI | Renal resistance to ADH; causes: lithium, hypercalcemia, hypokalemia, chronic kidney disease, genetic; does NOT respond to desmopressin |
| Primary Polydipsia | Excessive water intake; low-normal sodium, appropriately dilute urine |
4.4.1 Diagnosis
| Test | Findings |
|---|---|
| Initial Labs | Hypernatremia, high serum osmolality (>295 mOsm/kg), low urine osmolality (<300 mosm/kg),="" high="" urine="" output="" (="">3 L/day) |
| Water Deprivation Test | Withhold fluids, monitor weight/osmolality; DI: urine osmolality remains <300 despite="" rising="" serum=""> |
| Desmopressin Test | After water deprivation, give desmopressin; central DI: urine osmolality increases >50%; nephrogenic DI: minimal response; primary polydipsia: urine concentrates during water deprivation |
5. Calcium and Bone Disorders
5.1 Hypercalcemia
| Etiology | Key Features |
|---|---|
| Primary Hyperparathyroidism | Most common outpatient cause; high Ca2+, high/inappropriate PTH, low phosphate, high urine calcium, high alkaline phosphatase; parathyroid adenoma (80%); treat with parathyroidectomy |
| Malignancy | Most common inpatient cause; humoral hypercalcemia (PTHrP from SQCLC, renal, bladder) or osteolytic metastases; low/suppressed PTH, high calcium |
| Other Causes | Vitamin D intoxication, granulomatous disease (sarcoidosis, TB - elevated 1,25-OH vitamin D), thiazide diuretics, milk-alkali syndrome, immobilization |
| Clinical Features | Details |
|---|---|
| Mnemonic | "Stones, Bones, Abdominal Groans, Psychiatric Moans" |
| Renal | Nephrolithiasis, nephrocalcinosis, polyuria, nephrogenic DI |
| Skeletal | Osteoporosis, osteitis fibrosa cystica, brown tumors, subperiosteal resorption |
| GI | Constipation, nausea, vomiting, peptic ulcers, pancreatitis |
| Neuropsychiatric | Confusion, depression, psychosis, weakness, hyporeflexia |
| Cardiac | Shortened QT interval, arrhythmias |
5.1.1 Treatment of Severe Hypercalcemia
- IV NS hydration (first step, 200-300 mL/hr), furosemide after adequate hydration
- Bisphosphonates (zoledronic acid, pamidronate): onset 2-4 days, duration weeks
- Calcitonin: rapid onset (hours) but tachyphylaxis develops
- Denosumab for refractory cases
- Dialysis for severe refractory hypercalcemia with renal failure
5.2 Hypocalcemia
| Etiology | Details |
|---|---|
| Hypoparathyroidism | Post-surgical (thyroid/parathyroid surgery, most common), autoimmune, DiGeorge syndrome, hypomagnesemia; low Ca2+, high phosphate, low/inappropriately normal PTH |
| Vitamin D Deficiency | Nutritional, malabsorption, chronic kidney disease (decreased 1α-hydroxylase), liver disease; low Ca2+, low/normal phosphate, high PTH, low 25-OH vitamin D |
| Pseudohypoparathyroidism | PTH resistance (Albright hereditary osteodystrophy); low Ca2+, high phosphate, high PTH; short stature, brachydactyly, subcutaneous ossification |
| Other Causes | Acute pancreatitis, tumor lysis syndrome, massive blood transfusion (citrate), rhabdomyolysis |
| Clinical Features | Manifestations |
|---|---|
| Neuromuscular | Paresthesias (perioral, fingers, toes), tetany, carpopedal spasm, muscle cramps, seizures |
| Signs | Chvostek sign (facial twitch on tapping facial nerve), Trousseau sign (carpopedal spasm with BP cuff inflation), hyperreflexia |
| Cardiac | Prolonged QT interval, arrhythmias, heart failure |
| Chronic Changes | Cataracts, basal ganglia calcification, dental hypoplasia |
5.2.1 Treatment
- Severe/symptomatic: IV calcium gluconate 10% 10-20 mL over 10 minutes, then continuous infusion
- Chronic: oral calcium carbonate, vitamin D (calcitriol for hypoparathyroidism), correct hypomagnesemia if present
5.3 Osteoporosis
| Diagnosis | DEXA Scan T-Score |
|---|---|
| Normal | T-score ≥ -1.0 |
| Osteopenia | T-score -1.0 to -2.5 |
| Osteoporosis | T-score ≤ -2.5 |
| Severe Osteoporosis | T-score ≤ -2.5 with fragility fracture |
| Risk Factors | Details |
|---|---|
| Primary | Age, female sex, menopause, family history, low BMI, Caucasian/Asian |
| Secondary | Glucocorticoids (most common), hyperthyroidism, hyperparathyroidism, hypogonadism, malabsorption, chronic kidney disease, multiple myeloma |
| Lifestyle | Smoking, alcohol, sedentary lifestyle, low calcium/vitamin D intake |
5.3.1 Treatment
- Lifestyle: weight-bearing exercise, calcium 1200 mg/day, vitamin D 800-1000 IU/day, smoking cessation, limit alcohol
- Bisphosphonates (alendronate, risedronate, zoledronic acid): first-line, reduce fracture risk; side effects: esophagitis, osteonecrosis of jaw, atypical femur fractures
- Denosumab: RANKL inhibitor, SC injection q6 months, rebound vertebral fractures if stopped abruptly
- Teriparatide: PTH analog, anabolic, use for severe osteoporosis, max 2 years
- Raloxifene: selective estrogen receptor modulator, prevents vertebral fractures, reduces breast cancer risk
5.4 Paget Disease of Bone
- Increased bone remodeling (high turnover): excessive osteoclastic resorption followed by abnormal osteoblastic formation
- Features: bone pain, deformity (skull enlargement, bowing of long bones), fractures, deafness (CN VIII compression), high-output heart failure (if extensive)
- Lab: markedly elevated alkaline phosphatase (10-25x normal), normal calcium and phosphate
- X-ray: thickened cortex, mixed lytic-sclerotic lesions, V-shaped osteolytic front in long bones
- Complications: pathologic fractures, osteosarcoma (<1%, suspect="" if="" sudden="" pain="" increase),="">
- Treatment: bisphosphonates (zoledronic acid preferred), indicated for symptomatic disease or complications
6. Lipid Disorders
6.1 Dyslipidemia Classification
| Type | Lipid Pattern |
|---|---|
| Type I (Familial Chylomicronemia) | Very high triglycerides (>1000 mg/dL), lipoprotein lipase deficiency, eruptive xanthomas, pancreatitis, lipemic serum |
| Type IIa (Familial Hypercholesterolemia) | High LDL, normal triglycerides, LDL receptor defect, tendon xanthomas, corneal arcus, premature CAD |
| Type IIb (Combined Hyperlipidemia) | High LDL and high triglycerides |
| Type III (Dysbetalipoproteinemia) | High VLDL remnants, palmar xanthomas (pathognomonic), premature atherosclerosis, apoE2/E2 genotype |
| Type IV (Familial Hypertriglyceridemia) | High VLDL, high triglycerides, normal/low LDL |
| Type V | High chylomicrons and VLDL, very high triglycerides, pancreatitis risk |
6.2 Secondary Causes of Dyslipidemia
- High LDL: hypothyroidism, nephrotic syndrome, cholestatic liver disease, anorexia nervosa
- High triglycerides: diabetes mellitus, obesity, alcohol, oral estrogen, thiazides, beta-blockers, renal failure
- Low HDL: smoking, obesity, sedentary lifestyle, beta-blockers, anabolic steroids
6.3 Management
| Drug Class | Mechanism and Effects |
|---|---|
| Statins | HMG-CoA reductase inhibitor, decrease LDL 30-50%, first-line for LDL lowering; side effects: myopathy, elevated transaminases, increased diabetes risk; avoid in pregnancy |
| Ezetimibe | Inhibits intestinal cholesterol absorption, decrease LDL 15-20%, used with statin or alone if statin-intolerant |
| PCSK9 Inhibitors | Injectable (evolocumab, alirocumab), decrease LDL 50-60%, for FH or ASCVD with inadequate response to statins |
| Fibrates | PPAR-α agonist, decrease triglycerides 30-50%, increase HDL; first-line for high triglycerides; risk of myopathy with statins |
| Niacin | Decrease triglycerides, increase HDL, decrease LDL; side effects: flushing (reduced with aspirin), hyperglycemia, hyperuricemia, hepatotoxicity |
| Omega-3 Fatty Acids | Decrease triglycerides, used for severe hypertriglyceridemia (>500 mg/dL) |
6.3.1 Treatment Targets
- Very high risk (established ASCVD): LDL <70 mg/dl="" (or=""><55 mg/dl="" for="" very="" high="">
- High risk (diabetes, CKD, FH): LDL <100>
- Triglycerides >500 mg/dL: urgent treatment to prevent pancreatitis (fibrates, omega-3)
7. Male Reproductive Endocrinology
7.1 Hypogonadism
| Type | Features |
|---|---|
| Primary (Hypergonadotropic) | Testicular failure; low testosterone, high LH/FSH; causes: Klinefelter syndrome (47,XXY, small firm testes, gynecomastia, azoospermia), mumps orchitis, trauma, chemotherapy, radiation |
| Secondary (Hypogonadotropic) | Hypothalamic/pituitary dysfunction; low testosterone, low/normal LH/FSH; causes: Kallmann syndrome (GnRH deficiency + anosmia), hyperprolactinemia, pituitary tumors, chronic illness, obesity, medications (opioids, steroids) |
7.1.1 Clinical Features
- Prepubertal onset: eunuchoid proportions, small testes, absent secondary sexual characteristics, delayed puberty
- Postpubertal onset: decreased libido, erectile dysfunction, decreased muscle mass, decreased bone density, fatigue, hot flashes, gynecomastia
7.1.2 Treatment
- Testosterone replacement: IM (testosterone enanthate/cypionate q2-3 weeks), transdermal gel, patch; monitor hematocrit (contraindicated if Hct >54%), PSA
- If fertility desired: hCG + FSH for secondary hypogonadism
- Contraindications: prostate cancer, breast cancer, uncontrolled heart failure, untreated sleep apnea
7.2 Gynecomastia
| Etiology | Examples |
|---|---|
| Physiologic | Neonatal, pubertal, aging |
| Drugs | Spironolactone, ketoconazole, cimetidine, antiandrogens (finasteride), estrogens, digoxin, marijuana, alcohol |
| Hypogonadism | Klinefelter syndrome, testicular failure |
| Increased Estrogen | Liver cirrhosis, hyperthyroidism, adrenal tumors, hCG-secreting tumors (testicular, lung) |
| Other | Chronic kidney disease, malnutrition/refeeding |
7.2.1 Evaluation
- Assess for tenderness, duration, drug history, exclude pseudogynecomastia (adipose tissue)
- Labs: testosterone, LDH, FSH, estradiol, hCG, liver function, renal function, TSH
- Mammography if unilateral, hard, fixed, or bloody nipple discharge (exclude breast cancer)
- Treatment: stop offending drug, treat underlying cause; tamoxifen or raloxifene for symptomatic; surgery if cosmetically concerning or persistent
8. Female Reproductive Endocrinology
8.1 Polycystic Ovary Syndrome
8.1.1 Diagnostic Criteria (Rotterdam - 2 of 3)
- Oligo-ovulation or anovulation
- Clinical or biochemical hyperandrogenism (hirsutism, acne, elevated testosterone)
- Polycystic ovaries on ultrasound (≥12 follicles 2-9 mm or ovarian volume >10 mL)
- Exclude other causes: congenital adrenal hyperplasia, Cushing syndrome, androgen-secreting tumors, hyperprolactinemia
8.1.2 Clinical Features
- Reproductive: oligomenorrhea/amenorrhea, infertility, recurrent pregnancy loss
- Hyperandrogenism: hirsutism, acne, male pattern baldness, acanthosis nigricans
- Metabolic: insulin resistance, obesity (central), type 2 diabetes, dyslipidemia, metabolic syndrome
- Increased risk: endometrial hyperplasia/cancer (unopposed estrogen), cardiovascular disease
8.1.3 Treatment
| Goal | Treatment |
|---|---|
| Menstrual Regulation | Combined oral contraceptives (first-line, also treat hirsutism), cyclic progestins |
| Hyperandrogenism | OCPs, spironolactone (antiandrogen), finasteride, eflornithine cream (facial hirsutism) |
| Insulin Resistance | Metformin (also helps with weight loss and ovulation induction), lifestyle modification |
| Infertility | Clomiphene citrate (first-line ovulation induction), letrozole, metformin, gonadotropins, IVF |
8.2 Amenorrhea
8.2.1 Primary Amenorrhea
- No menses by age 15 with normal secondary sexual characteristics, or by age 13 with no secondary sexual characteristics
- Causes: Turner syndrome (45,X0 - short stature, streak gonads, high FSH), Mullerian agenesis (normal breast development, absent uterus/upper vagina, normal testosterone/estrogen), androgen insensitivity (46,XY, female phenotype, testes, blind vaginal pouch), constitutional delay
8.2.2 Secondary Amenorrhea
| Etiology | Features |
|---|---|
| Pregnancy | Most common cause, check hCG first |
| Hypothalamic | Functional hypothalamic amenorrhea (stress, weight loss, excessive exercise), Kallmann syndrome; low LH, low FSH, low estrogen |
| Pituitary | Hyperprolactinemia, Sheehan syndrome, pituitary tumors; low LH, low FSH |
| Ovarian | Premature ovarian insufficiency (<40 years),="" pcos;="" high="" fsh="" (poi),="" variable=""> |
| Uterine | Asherman syndrome (intrauterine adhesions post-D&C, endometritis); normal hormones |
| Other | Thyroid disorders, Cushing syndrome |
8.2.3 Workup
- Exclude pregnancy (β-hCG), measure TSH, prolactin, FSH, estradiol
- Progestin withdrawal test: give medroxyprogesterone 10 mg x 10 days; bleeding indicates anovulation with adequate estrogen (e.g., PCOS); no bleeding suggests estrogen deficiency or anatomic defect
- Estrogen-progestin challenge if no bleeding: bleeding indicates anatomic defect; no bleeding indicates end-organ (uterine) problem
8.3 Menopause
- Permanent cessation of menses for 12 consecutive months; average age 51 years
- Symptoms: vasomotor (hot flashes, night sweats), urogenital atrophy (vaginal dryness, dyspareunia, urinary urgency), mood changes, sleep disturbance
- Lab: elevated FSH (>30-40 IU/L), low estradiol; diagnosis is clinical (labs not needed)
- Long-term effects: osteoporosis, cardiovascular disease risk increases
- Treatment: hormone replacement therapy (estrogen ± progestin if uterus intact) for moderate-to-severe vasomotor symptoms, shortest duration at lowest dose; contraindicated in breast cancer, VTE, stroke, CAD; non-hormonal options: SSRIs, gabapentin, clonidine
9. Multiple Endocrine Neoplasia Syndromes
| Syndrome | Components |
|---|---|
| MEN 1 | Parathyroid adenoma (hyperparathyroidism, 95%), pancreatic islet cell tumors (gastrinoma most common - Zollinger-Ellison syndrome, insulinoma), pituitary adenoma (prolactinoma most common); mnemonic: 3 Ps (Parathyroid, Pancreas, Pituitary); mutation: MEN1 gene (menin) |
| MEN 2A | Medullary thyroid carcinoma (95-100%), pheochromocytoma (50%), parathyroid hyperplasia (20-30%); mutation: RET proto-oncogene; prophylactic thyroidectomy recommended in childhood |
| MEN 2B | Medullary thyroid carcinoma (100%, aggressive), pheochromocytoma (50%), mucosal neuromas (lips, tongue), ganglioneuromatosis, Marfanoid habitus; mutation: RET proto-oncogene; prophylactic thyroidectomy in infancy |
9.1 Screening and Management
- MEN 1: screen for hyperparathyroidism (calcium, PTH annually), pancreatic tumors (gastrin, insulin, chromogranin A, imaging), pituitary tumors (prolactin, IGF-1, MRI)
- MEN 2: genetic testing (RET mutation), screen for pheochromocytoma before any surgery (plasma metanephrines), measure calcitonin; prophylactic thyroidectomy based on genotype and age
- Always exclude pheochromocytoma first in MEN 2 before operating on other tumors (risk of hypertensive crisis)
10. Metabolic Syndrome and Obesity
10.1 Metabolic Syndrome Criteria (3 of 5)
| Component | Criteria |
|---|---|
| Waist Circumference | >102 cm (40 inches) in men, >88 cm (35 inches) in women |
| Triglycerides | ≥150 mg/dL or on treatment |
| HDL Cholesterol | <40 mg/dl="" in="" men,=""><50 mg/dl="" in="" women,="" or="" on=""> |
| Blood Pressure | ≥130/85 mmHg or on antihypertensive treatment |
| Fasting Glucose | ≥100 mg/dL or on treatment for diabetes |
10.2 Obesity Management
| BMI Category | Classification |
|---|---|
| <> | Underweight |
| 18.5-24.9 | Normal weight |
| 25-29.9 | Overweight |
| 30-34.9 | Obesity Class I |
| 35-39.9 | Obesity Class II |
| ≥40 | Obesity Class III (Severe) |
10.2.1 Pharmacotherapy
- Orlistat: lipase inhibitor, GI side effects (steatorrhea), malabsorption of fat-soluble vitamins
- Phentermine-topiramate: appetite suppressant, contraindicated in pregnancy (teratogenic)
- Liraglutide (3.0 mg): GLP-1 agonist, weight loss 5-10%, nausea common, cardiovascular benefits
- Semaglutide (2.4 mg): GLP-1 agonist, weight loss up to 15%, weekly injection
- Naltrexone-bupropion: opioid antagonist + antidepressant combination
10.2.2 Bariatric Surgery
- Indications: BMI ≥40 or BMI ≥35 with comorbidities (diabetes, hypertension, sleep apnea)
- Roux-en-Y gastric bypass: most effective for weight loss and diabetes remission, risk of dumping syndrome, marginal ulcers, vitamin B12/iron/calcium deficiency
- Sleeve gastrectomy: removes fundus, reduces ghrelin, less malabsorption than bypass
- Adjustable gastric banding: least invasive, lower weight loss, risk of band slippage/erosion
11. Miscellaneous Endocrine Disorders
11.1 Syndrome of Inappropriate ADH Secretion
| Parameter | Details |
|---|---|
| Features | Euvolemic hyponatremia, low serum osmolality (<275 mosm/kg),="" inappropriately="" concentrated="" urine="" (="">100 mOsm/kg), urine sodium >40 mEq/L |
| Causes | Malignancy (SCLC most common, ectopic ADH), CNS disorders (meningitis, head trauma, stroke), pulmonary disease (pneumonia, TB), drugs (SSRIs, carbamazepine, vincristine, cyclophosphamide) |
| Treatment | Fluid restriction (<800 ml/day)="" first-line,="" treat="" underlying="" cause,="" salt="" tablets,="" demeclocycline="" (induces="" nephrogenic="" di),="" vaptans="" (tolvaptan="" -="" v2="" receptor="" antagonist)="" for="" severe/refractory=""> |
| Caution | Correct sodium slowly (<8-10 meq/l="" per="" 24="" hours)="" to="" avoid="" osmotic="" demyelination=""> |
11.2 Carcinoid Syndrome
- From carcinoid tumors (neuroendocrine), secrete serotonin, bradykinin, histamine
- Features: episodic flushing, secretory diarrhea, bronchospasm, right-sided valvular heart disease (tricuspid regurgitation, pulmonary stenosis)
- Carcinoid crisis: severe flushing, bronchospasm, hypotension; triggered by anesthesia, surgery, tumor manipulation
- Diagnosis: 24-hour urine 5-HIAA (serotonin metabolite), elevated chromogranin A; CT/MRI for tumor localization, octreotide scan (somatostatin receptor scintigraphy)
- Treatment: octreotide (controls symptoms, prevent crisis during surgery), surgical resection if localized, liver-directed therapy for metastases
11.3 VIPoma (Verner-Morrison Syndrome)
- Pancreatic islet cell tumor secreting vasoactive intestinal peptide (VIP)
- WDHA syndrome: Watery Diarrhea (massive, >3 L/day), Hypokalemia, Achlorhydria (or hypochlorhydria)
- Flushing, hypotension, hyperglycemia, hypercalcemia
- Diagnosis: elevated serum VIP, CT/MRI pancreas
- Treatment: octreotide (controls diarrhea), surgical resection
11.4 Glucagonoma
- Pancreatic α-cell tumor secreting glucagon
- Features: necrolytic migratory erythema (pathognomonic - erythematous rash with central clearing, affects perioral, groin, extremities), diabetes, weight loss, glossitis, stomatitis, anemia, DVT
- Diagnosis: elevated glucagon (>500 pg/mL), CT/MRI pancreas
- Treatment: octreotide, surgical resection, zinc supplementation for rash
11.5 Insulinoma
- Pancreatic β-cell tumor, most common functional pancreatic tumor, 90% benign
- Whipple's triad: symptoms of hypoglycemia (confusion, palpitations, sweating), documented low glucose (<55 mg/dl),="" relief="" with="">
- Symptoms worse with fasting or exercise
- Diagnosis: supervised 72-hour fast (glucose <55 mg/dl="" with="" elevated="" insulin="" and="" c-peptide,="" low="" β-hydroxybutyrate);="" insulin/glucose="" ratio="">0.3; CT/MRI pancreas, endoscopic ultrasound
- Treatment: surgical resection (curative), diazoxide (inhibits insulin release) if inoperable
11.6 Zollinger-Ellison Syndrome
- Gastrinoma (pancreatic or duodenal) secreting excessive gastrin
- Features: multiple/refractory peptic ulcers, ulcers in unusual locations (jejunum), severe GERD, secretory diarrhea, steatorrhea
- 60% malignant, 25% associated with MEN 1
- Diagnosis: fasting gastrin >1000 pg/mL (with gastric pH <2) virtually="" diagnostic;="" secretin="" stimulation="" test="" (paradoxical="" rise="" in="" gastrin);="" ct/mri,="" somatostatin="" receptor="">
- Treatment: high-dose PPIs, octreotide, surgical resection if localized
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