Clinical Learning Notes: Endocrine Disorders

1. DIABETES MELLITUS (DM)

Definition & Epidemiology

• DM is a coronary artery disease (CAD) risk equivalent - nearly 80% of people with diabetes will die of cardiovascular disease.

Classification

Pathophysiology of Type 2 DM

1. Insulin resistance in muscle, liver, and adipose tissue - the liver continues to produce glucose despite hyperglycemia (failed suppression of hepatic gluconeogenesis).
2. Compensatory hyperinsulinemia maintains normoglycemia initially.
3. Beta cell exhaustion - progressive loss of beta cell mass leads to frank hyperglycemia.
4. Atherogenic lipid triad - insulin resistance reduces lipoprotein lipase activity, causing elevated triglycerides, small dense LDL particles, and low HDL. This accelerates atherogenesis through diffuse endothelial dysfunction and accumulation of advanced glycation end products (AGEs) in the vasculature.

Diagnostic Criteria (ADA Standards)

• Fasting plasma glucose ≥ 126 mg/dL (on two occasions)
• 2-hour glucose ≥ 200 mg/dL during 75 g OGTT
• HbA1c ≥ 6.5%
• Random glucose ≥ 200 mg/dL with classic symptoms (polyuria, polydipsia, unexplained weight loss)

Clinical Features

• Classic symptoms: Polyuria, polydipsia, polyphagia, weight loss (Type 1), fatigue, blurred vision
• Type 2 often asymptomatic at diagnosis - found on routine screening
• DKA (Type 1): Nausea, vomiting, abdominal pain, Kussmaul respirations, fruity breath, dehydration
• HHS (Hyperosmolar Hyperglycemic State) (Type 2): Extreme hyperglycemia (>600 mg/dL), profound dehydration, altered consciousness, no significant ketosis

Complications

• Nephropathy: Microalbuminuria (30-300 mg/day) → proteinuria → declining GFR → ESRD. Screen annually with urine albumin-to-creatinine ratio. ACE inhibitors or ARBs are first-line treatment (reduce intraglomerular pressure). Nephropathy independently increases CVD risk.
• Retinopathy: Leading cause of adult-onset blindness. Background (non-proliferative) → pre-proliferative → proliferative (neovascularization, vitreous hemorrhage, traction retinal detachment). Screen with dilated fundoscopy.
• Neuropathy: Distal symmetric polyneuropathy (stocking-glove) is most common. Also autonomic neuropathy (gastroparesis, erectile dysfunction, orthostatic hypotension, silent MI), mononeuropathies (CN III palsy).

• Accelerated atherosclerosis affecting coronary, cerebral, and peripheral vasculature. DM magnifies risk of MI, stroke, sudden death, CHF.
• Peripheral artery disease + neuropathy = diabetic foot (ulceration, infection, Charcot arthropathy, amputation)

Management Targets

• HbA1c: < 7% (individualized - less strict for elderly, high hypoglycemia risk, limited life expectancy)
• BP: < 130/80 mmHg
• LDL: < 70 mg/dL (high cardiovascular risk)
• Lifestyle: Medical nutrition therapy, weight loss, physical activity

Pharmacological Management

• Basal-bolus regimen: Long-acting insulin (glargine, detemir) + rapid-acting (lispro, aspart) with meals.

1. Metformin (first-line, unless contraindicated) - decreases hepatic glucose production, improves insulin sensitivity; inexpensive, weight neutral, may cause GI upset; contraindicated in eGFR < 30.
2. Add agents based on patient profile:
   • SGLT-2 inhibitors (empagliflozin, dapagliflozin) - urinary glucose excretion; cardiovascular and renal benefits; risk of DKA, UTI, genital infections.
   • GLP-1 receptor agonists (liraglutide, semaglutide) - weight loss, cardiovascular benefit; injectable (except oral semaglutide); nausea common.
   • DPP-4 inhibitors (sitagliptin) - weight neutral, low hypoglycemia risk.
   • Sulfonylureas (glipizide, glibenclamide) - insulin secretagogues; hypoglycemia and weight gain risks.
   • Thiazolidinediones (pioglitazone) - improve insulin sensitivity; edema, weight gain, heart failure risk.
3. Insulin when targets not achieved, or at diagnosis with severe hyperglycemia.

Monitoring

• HbA1c every 3 months until stable, then every 6 months
• Annual: fundoscopy, urine microalbumin, foot exam, lipid panel, renal function
• Self-monitoring of blood glucose (SMBG) - essential for insulin users

2. CUSHING SYNDROME

Definition

Causes & Classification

• Iatrogenic glucocorticoid administration - the most common cause worldwide.

• Cushing disease (pituitary ACTH-secreting adenoma): ~70% of endogenous cases. Most are microadenomas (<1 cm). Two-thirds of patients are female. ACTH drives bilateral adrenal hyperplasia.
• Ectopic ACTH syndrome: ~10% of cases. ACTH produced by non-pituitary malignancies (small cell lung cancer, bronchial carcinoid, pancreatic islet cell tumors, pheochromocytoma). Adrenal glands are markedly hyperplastic due to high ACTH levels.
• Ectopic CRH syndrome: Extremely rare (<1%).

• Adrenal adenoma or carcinoma (unilateral)
• Primary pigmented nodular adrenocortical disease (PPNAD) - bilateral; associated with Carney complex
• ACTH-independent macronodular adrenal hyperplasia (AIMAH)

Pathophysiology

Clinical Features

• Proximal muscle weakness/myopathy (difficulty rising from chair)
• Easy bruising (ecchymoses)
• Wide (>1 cm), violaceous (purple) striae on abdomen, thighs, breasts
• Plethoric moon face
• Dorsocervical fat pad (buffalo hump) and supraclavicular fat deposition
• Hypertension (from mineralocorticoid effect of cortisol)
• Osteoporosis/fractures (vertebral collapse)

• Central obesity, truncal fat deposition, weight gain
• Thin extremities (muscle wasting)
• Hyperglycemia/diabetes
• Hypokalemia (especially in ectopic ACTH)
• Hirsutism, acne, oily skin, oligomenorrhea/amenorrhea (from androgen excess)
• Depression, emotional lability, cognitive impairment
• Poor wound healing, recurrent infections
• Edema

Diagnosis

• 24-hour urinary free cortisol (UFC) - elevated (>2-3x upper limit of normal is strongly suggestive; multiple collections recommended)
• Late-night salivary cortisol - elevated (normally low at midnight; sensitive for loss of diurnal variation)
• Low-dose dexamethasone suppression test (DST): 1 mg dexamethasone at 11 PM; measure cortisol at 8 AM. Normal = suppression to <1.8 mcg/dL. Failure to suppress suggests Cushing syndrome.

• Measure plasma ACTH:
  • Low/undetectable ACTH → ACTH-independent → CT adrenal imaging
  • Normal/elevated ACTH → ACTH-dependent → investigate pituitary vs. ectopic source

• Pituitary MRI - but note: 50% of Cushing disease patients have no visible pituitary lesion; 10% of the general population have incidental pituitary abnormalities.
• High-dose DST (8 mg overnight): Cortisol suppresses in Cushing disease (pituitary adenoma retains some feedback sensitivity), but NOT in ectopic ACTH syndrome.
• CRH stimulation test: ACTH and cortisol rise in Cushing disease, minimal response in ectopic.
• Inferior petrosal sinus sampling (IPSS) - gold standard to distinguish pituitary from ectopic ACTH. Bilateral sampling after CRH stimulation; central:peripheral ACTH ratio >2 (basal) or >3 (post-CRH) indicates Cushing disease.

Treatment

• Cushing disease: Transsphenoidal pituitary adenomectomy (first-line). Radiation if surgery fails. Bilateral adrenalectomy (last resort - risks Nelson syndrome: ACTH-secreting tumor enlargement with hyperpigmentation).
• Adrenal adenoma: Unilateral adrenalectomy (laparoscopic).
• Ectopic ACTH: Treat underlying tumor; if not resectable, steroidogenesis inhibitors (ketoconazole, metyrapone, mitotane).
• Medical adjuncts: Ketoconazole, metyrapone (inhibit cortisol synthesis) used preoperatively or when surgery is not possible.
• Post-treatment: Adrenal insufficiency is expected after cure - glucocorticoid replacement required until contralateral adrenal recovers (may take 6-12 months).

Complications

3. ACROMEGALY

Definition

Etiology

• Pituitary GH-secreting adenoma - responsible for 98% of cases. Most are macroadenomas at diagnosis.
• Rare: Ectopic GHRH-secreting tumors (lung, pancreatic carcinoid) stimulate pituitary GH hypersecretion.
• May occur as part of: MEN type 1, Carney complex, McCune-Albright syndrome.

Clinical Features

• Facial coarsening: Prognathism (jaw protrusion), frontal bossing (enlarged supraorbital ridges), enlarged nose, thick lips, macroglossia
• Acral enlargement: Large hands and feet (patients notice rings/shoes no longer fit) - fingers enlarge until they "resemble drumsticks"
• Cutis verticis gyrata (furrowed scalp skin) in ~30%
• Skin thickening, oily feel, hypertrichosis, hyperpigmentation, hyperhidrosis (persistent even after treatment)
• Skin tags (acrochordon) - frequently present

• Cardiovascular: Cardiomegaly (specific acromegalic cardiomyopathy), LVH, hypertension, arrhythmias - leading cause of death
• Metabolic: Insulin resistance, impaired glucose tolerance, frank diabetes (~25-30%)
• Respiratory: Sleep apnea (central and obstructive) - from macroglossia and pharyngeal soft tissue hypertrophy
• Musculoskeletal: Arthralgia/arthropathy (cartilage and synovial hypertrophy), carpal tunnel syndrome, back pain
• Neurological: Headaches (direct tumor effect), visual field defects (bitemporal hemianopia from optic chiasm compression by macroadenoma)
• Visceral enlargement: Thyroid, liver, spleen, kidneys enlarge. Colonic polyps (increased colorectal cancer risk).
• Galactorrhea if adenoma co-secretes prolactin

Diagnosis

1. Serum IGF-1 (screening test) - elevated for age and sex; best single screening test; reflects integrated GH secretion.
2. GH suppression test (OGTT): 75 g glucose load; normal GH suppresses to <1 ng/mL. In acromegaly, GH fails to suppress (paradoxical rise may occur). Gold standard for diagnosis.
3. MRI pituitary - identifies tumor, assess mass effect.
4. Baseline GH (not useful alone due to pulsatile secretion).

Treatment

• Cure rate: ~80% for microadenomas, ~50% for macroadenomas.
• Remission defined as: IGF-1 normal for age, GH < 1 ng/mL on OGTT.

• Somatostatin analogues (SSAs) - octreotide LAR, lanreotide autogel (monthly/biweekly IM depot injections). Potently suppress GH. Fatigue, paresthesias, and headaches improve rapidly. Soft tissue swelling and facial coarsening improve as GH declines. After 18-24 months of therapy, ~50% normalize GH/IGF-1. Hyperhidrosis persists in most. Side effects: gallstones, GI upset.
• Dopamine agonists (cabergoline, bromocriptine) - suppress GH secretion. Adjuvant use in some cases. Less effective than SSAs but oral administration.
• GH receptor antagonist - pegvisomant (blocks peripheral GH receptor; normalizes IGF-1 in >95% but does not shrink tumor; expensive).

Prognosis

4. HYPERPARATHYROIDISM

Definition & Overview

Types

• Autonomous, non-suppressible excess PTH production.
• Common endocrine disorder; prevalence increased dramatically in the latter 20th century due to routine calcium measurement.
• Causes (frequency):
  • Solitary parathyroid adenoma: 85-95%
  • Primary hyperplasia (diffuse or nodular, multi-glandular): 5-10%
  • Parathyroid carcinoma: ~1%

• Cyclin D1 gene rearrangements - inversion on chromosome 11 drives abnormal cyclin D1 expression → parathyroid cell proliferation (found in 10-20% of adenomas)
• MEN1 mutations - tumor suppressor gene on chromosome 11; biallelic inactivation in 30-35% of sporadic parathyroid tumors

• Reactive, compensatory PTH hypersecretion in response to chronic hypocalcemia.
• Most common cause: Chronic kidney disease (CKD) - reduced 1,25(OH)2D3 production, hyperphosphatemia, hypocalcemia → all stimulate PTH.
• Also seen in: Vitamin D deficiency, malabsorption syndromes, rickets.
• Biochemistry: High PTH, low-normal calcium, high phosphate (in CKD).

• Autonomous PTH hypersecretion after prolonged secondary hyperparathyroidism (usually in long-term dialysis patients).
• The glands become autonomous - PTH no longer suppresses despite restored calcium levels.

Clinical Features of Primary Hyperparathyroidism

• Bones: Osteitis fibrosa cystica (severe/late): bone pain, pathological fractures, subperiosteal bone resorption (radial side of middle phalanges on X-ray), "salt and pepper" skull, brown tumors (giant cell lesions), osteosclerosis. Osteoporosis in earlier/milder disease.
• Stones: Nephrolithiasis (calcium oxalate/phosphate stones) and nephrocalcinosis. Most common presentation today.
• Groans: Nausea, vomiting, constipation, anorexia, pancreatitis, peptic ulcer disease (hypercalcemia increases gastrin).
• Psychic moans: Confusion, depression, lethargy, cognitive impairment, psychosis (in severe hypercalcemia).
• Other: Muscle weakness, polyuria/polydipsia (nephrogenic DI from hypercalcemia), hypertension, band keratopathy (calcium in Bowman layer of cornea).

Biochemistry

• Primary: High PTH, high calcium, low phosphate, high urine calcium and phosphate, elevated alkaline phosphatase (if bone disease), elevated 1,25(OH)2D3
• Secondary (CKD): High PTH, low-normal calcium, high phosphate
• Tertiary: High PTH, high calcium (now autonomous)
• Malignancy-associated hypercalcemia: Low PTH, high calcium, high PTHrP (PTH-related protein)

Radiology (X-ray findings)

• Subperiosteal - radial sides of middle phalanges (pathognomonic)
• Subchondral - sacroiliac joints, acromioclavicular joints, distal clavicle, symphysis pubis
• Subligamentous - calcaneum (Achilles tendon insertion)
• Trabecular - "salt and pepper" skull (diploic space)
• Intracortical - cortical striations Additional: Brown tumors, chondrocalcinosis, rugger-jersey spine (osteosclerosis alternating with resorption in secondary HPT), soft tissue calcification

Treatment

• Indications in asymptomatic disease: Serum calcium >1 mg/dL above upper normal limit, eGFR <60, T-score < -2.5, age <50, 24-hr urine calcium >400 mg.
• Sestamibi scan + ultrasound for preoperative localization.
• Cure rate of surgery >95%.
• Post-op: Hungry bone syndrome (rapid bone uptake causing hypocalcemia) - monitor closely.

• Cinacalcet (calcimimetic - sensitizes CaSR to calcium, reduces PTH) - lowers calcium but does not improve bone density.
• Bisphosphonates - protect bone density.
• Adequate hydration.

• Phosphate binders, active vitamin D analogues (calcitriol, paricalcitol), cinacalcet. Dialysis optimization.
• Parathyroidectomy if refractory (>800 pg/mL PTH despite medical therapy).

5. OVERVIEW OF THYROTOXICOSIS

Definition & Key Distinction

• Hyperthyroidism = overproduction of thyroid hormone by the thyroid gland.
• Thyrotoxicosis = excess thyroid hormone in circulation from any cause.

Causes (by frequency)

1. Graves disease - autoimmune; TSH receptor antibodies (TSH-RAb) stimulate thyroid → 60-90% of spontaneous thyrotoxicosis cases. Associated with ophthalmopathy and pretibial myxedema (dermopathy).
2. Toxic multinodular goiter (TMNG) - autonomous functioning nodules
3. Toxic adenoma (autonomous functioning adenoma)
4. Thyroiditis (subacute, silent/painless, postpartum) - transient release of preformed hormone. Onset is acute. Self-limiting. Not true hyperthyroidism.
5. Exogenous/factitious thyrotoxicosis - ingestion of exogenous thyroid hormone
6. Rare: TSH-secreting pituitary adenoma, struma ovarii, hyperemesis gravidarum (hCG stimulation), amiodarone-induced.

Epidemiology

• More common in females and in persons of northern European descent; rare in Black individuals.
• Acute onset of thyrotoxicosis almost always suggests thyroiditis.
• Insidious onset over months = Graves disease.
• Thyrotoxic patient with non-palpable thyroid: suspect painless thyroiditis, Graves, or exogenous thyroxine.
• Thyrotoxic patient with goiter or ophthalmopathy = Graves disease until proven otherwise.

Clinical Features

• Palpitations, tachycardia, atrial fibrillation
• Heat intolerance, sweating, warm/moist skin
• Weight loss despite increased appetite (hyperphagia)
• Anxiety, irritability, emotional lability, tremor (fine postural)
• Diarrhea, increased stool frequency
• Oligomenorrhea/amenorrhea in women
• Muscle weakness, proximal myopathy
• Lid lag, lid retraction (sympathetic overstimulation - NOT specific to Graves)
• Goiter

• Apathy, lethargy, pseudodementia, depression, weight loss
• Absence of tachycardia, hyperphagia, goiter
• Dominated by cardiovascular symptoms: atrial fibrillation, dyspnea on exertion, exercise intolerance
• Easily confused with primary depression or dementia - always check TSH in depression/dementia workup

• Decreased peripheral resistance, increased cardiac output, increased blood volume, fluid retention
• Wide pulse pressure, resting tachycardia
• Atrial fibrillation (uncommon in young; 5-15% in elderly with thyrotoxicosis)
• Signs/symptoms of CHF (common in both young and old) - dependent edema from secondary aldosteronism
• Mild hypercalcemia (<12 mg/dL) from increased bone turnover - responds to beta-blockers
• Ischemic CHF can occur in patients with pre-existing CAD but resolves with antithyroid treatment

• Ophthalmopathy (Graves orbitopathy): Exophthalmos (proptosis), periorbital edema, chemosis, diplopia, optic nerve compression. TSH receptor antibody-mediated. Can worsen after radioiodine. Treated with steroids, orbital decompression.
• Pretibial myxedema (dermopathy): Non-pitting, indurated plaques over the shins
• Thyroid acropachy: Clubbing, soft tissue swelling, periosteal new bone formation - rare

Diagnosis

• TSH (sTSH) - suppressed (<0.1 mIU/L) in primary thyrotoxicosis. First-line test.
• Free T4 (FT4) and Free T3 - elevated in most cases
• TSH receptor antibodies (TSH-RAb) - elevated in Graves disease
• Radioactive iodine uptake (RAIU) and scan:
  • Diffuse high uptake: Graves disease
  • Patchy/nodular uptake: Toxic MNG or toxic adenoma
  • Low/absent uptake: Thyroiditis (destructive), exogenous thyrotoxicosis
• Thyroid peroxidase antibodies (TPO Ab): Elevated in Graves and Hashimoto

Treatment - Three Objectives:

1. Ameliorate acute symptoms
2. Suppress synthesis and secretion of thyroid hormones
3. Treat the primary cause

• Symptomatic relief (palpitations, tremor, anxiety) while awaiting definitive therapy.
• Propranolol also inhibits peripheral T4→T3 conversion.
• Do NOT wait for test results - treat hypermetabolic symptoms immediately.

• Methimazole (MMI): First-choice in most situations. Once-daily dosing. Inhibits thyroid peroxidase (TPO), blocking organification of iodine.
• Propylthiouracil (PTU): Preferred in first trimester pregnancy, thyroid storm (also blocks T4→T3 conversion). Riskier hepatotoxicity profile.
• Side effects: Agranulocytosis (0.3% - check WBC if fever/sore throat), rash, hepatotoxicity.

• Destroys thyroid tissue. Definitive treatment for Graves and TMNG.
• Most patients become hypothyroid (anticipated outcome with full-dose RAI).
• Contraindicated in pregnancy, active Graves orbitopathy (may worsen), when fast resolution needed.

• Total/near-total thyroidectomy for large goiters, compressive symptoms, malignancy concern, failed medical therapy, pregnancy, patient preference.
• Risks: Permanent hypothyroidism (expected), hypoparathyroidism, recurrent laryngeal nerve palsy.

• Life-threatening exacerbation. Precipitated by surgery, infection, trauma, RAI in unprepared patients.
• Features: Hyperpyrexia (>40°C), severe tachycardia, AF, CNS dysfunction (agitation, psychosis, coma), GI symptoms.
• Treatment: PTU + Lugol's iodine (SSKI - given 1 hour after PTU) + high-dose beta-blockers + steroids (hydrocortisone - block T4→T3 + treat relative adrenal insufficiency) + supportive care.

6. HYPOTHYROIDISM

Definition

Classification

• TSH deficiency from pituitary failure
• Rare; suggested by low/absent TSH with low FT4 without symptoms of hyperthyroidism
• Evaluate for panhypopituitarism

• Post-thyroidectomy, post-radioiodine therapy
• Head and neck radiation
• Thyroiditis (postpartum, sporadic, subacute) - transient hypothyroid phase
• Drugs: amiodarone, lithium, interferon-alpha, tyrosine kinase inhibitors
• Infiltrative disorders: amyloidosis, sarcoidosis, hemochromatosis

Hashimoto Thyroiditis (CAT)

• Most common cause of hypothyroidism in the US
• Autoimmune: Anti-TPO antibodies (primary driver) + anti-thyroglobulin (anti-Tg) antibodies attack thyroidal stroma → progressive fibrosis → reduced T4 production
• Demographics: F:M ratio 10-14:1; typically diagnosed in the fifth decade; progressive
• Diagnosis: Elevated TSH + low-normal to low FT4 + positive TPO antibodies
• Associated with other autoimmune diseases: T1DM, rheumatoid arthritis, pernicious anemia, vitiligo, Addison disease (polyglandular autoimmune syndrome)
• Slightly increased risk of thyroid lymphoma (very rare)

Clinical Features

• Metabolic/general: Fatigue, weight gain (from fluid retention/decreased metabolism), cold intolerance, constipation
• Cardiovascular: Bradycardia, diastolic hypertension, pericardial effusion, cardiomegaly, elevated cholesterol/triglycerides → accelerated atherosclerosis
• Neurological/psychiatric: Depression, cognitive slowing (hypothyroid dementia), carpal tunnel syndrome, delayed relaxation phase of deep tendon reflexes (hung reflexes), paresthesias
• Musculoskeletal: Myalgia, weakness, elevated CK (myopathy)
• Skin/hair/nails: Dry, coarse, cool, pale skin; coarse brittle hair; hair loss (diffuse alopecia); loss of outer third of eyebrows; pitting edema → myxedema (non-pitting edema due to glycosaminoglycan deposition - especially around eyes)
• Reproductive: Menorrhagia (women), erectile dysfunction (men), infertility
• Voice: Hoarse, deep voice (myxedematous changes in larynx)
• Goiter: May or may not be present; in Hashimoto, firm, rubbery goiter with irregular surface

• Slow pulse, delayed tendon reflexes, periorbital puffiness, macroglossia, dry skin

Diagnosis

• TSH (primary): Elevated in primary hypothyroidism (most sensitive test)
• Free T4: Low in overt hypothyroidism
• Subclinical hypothyroidism: TSH elevated (typically 4-10 mIU/L), FT4 normal - patient may be asymptomatic
• TPO antibodies: Confirms autoimmune etiology (Hashimoto)
• Anti-Tg antibodies: Less specific

Special Situations

• Myxedema coma: Life-threatening decompensation. Precipitated by cold exposure, infection, sedatives, surgery. Features: Hypothermia, bradycardia, hypotension, hyponatremia, hypoglycemia, CO2 retention, altered consciousness → coma. Treatment: IV T4 (or T3) + hydrocortisone (until adrenal co-insufficiency excluded) + supportive care (warming, fluids, ventilatory support).

Treatment

• Average replacement dose: 1.6 mcg/kg/day orally
• Taken fasting, 30-60 minutes before breakfast (calcium, iron, antacids reduce absorption)
• Starting dose considerations:
  • Young healthy adult: Start at full replacement dose
  • Age >50 or coronary artery disease: Start low (25-50 mcg/day), titrate slowly every 4-6 weeks (rapid correction can precipitate angina/MI)
  • Elderly: Even lower starting doses
• Monitor TSH every 4-6 weeks after dose change; annual TSH once stable
• Target TSH: 1.0-2.5 mIU/L (or upper half of normal range in pregnancy: 0.1-2.5 mIU/L)

• Some patients with normal TSH on T4 monotherapy continue to report hypothyroid symptoms.
• T4 resistance is controversial; combination T4+T3 (liothyronine) can be tried.
• Keep TSH >1.0 mIU/L to avoid iatrogenic hyperthyroidism.

• Treat if: TSH >10 mIU/L (most guidelines), pregnancy or planning pregnancy, symptomatic, positive TPO antibodies (high conversion risk), goiter, age <60.
• TSH 4-10 mIU/L: Individualize based on symptoms, antibody status, cardiovascular risk.

• Low-dose T4 on a temporary basis if symptomatic; usually recovers in 3-6 months.

Quick Reference Summary Table

1. Diabetes Mellitus - Classification (T1/T2/MODY/GDM), pathophysiology of T2DM (insulin resistance, beta cell failure, atherogenic lipid triad), ADA diagnostic criteria, micro- and macrovascular complications, management targets, and the full pharmacological ladder from metformin through SGLT-2 inhibitors and GLP-1 agonists to insulin.
2. Cushing Syndrome - Complete HPA axis physiology, full cause classification (exogenous, ACTH-dependent, ACTH-independent), the discriminatory clinical features (violaceous striae, proximal myopathy, easy bruising), the three-step diagnostic algorithm (UFC → ACTH level → IPSS), and treatment by etiology.
3. Acromegaly - GH/IGF-1 axis, classic acral and facial changes, systemic complications (cardiomyopathy, sleep apnea, colonic polyps), diagnostic tests (OGTT-GH suppression + IGF-1), and the treatment hierarchy (surgery → SSAs → pegvisomant → radiotherapy).
4. Hyperparathyroidism - All three types (primary/secondary/tertiary) with distinct biochemistry, pathogenesis of adenomas (cyclin D1, MEN1), the "bones, stones, groans, moans" clinical picture, characteristic X-ray findings, and surgical vs. medical management.
5. Thyrotoxicosis - Critical distinction from hyperthyroidism, causes by frequency, classic vs. apathetic (elderly) presentations, Graves-specific features, diagnostic workup including RAIU scan, and the three treatment modalities (thionamides, RAI, surgery) plus thyroid storm management.
6. Hypothyroidism - Hashimoto thyroiditis as the dominant cause, clinical features by system, myxedema coma, levothyroxine dosing principles (age-adjusted), and the T4/T3 combination therapy debate.