Endocrinology

What is osteoporosis?

A skeletal condition in which loss of bone mineral density (BMD) leads to decreased bone strength and increased risk of fractures.

What is lost in osteoporosis?

Both trabecular and cortical bone mass, leading to bone weakness.

What is osteopenia?

A condition of decreased bone strength that is less severe than osteoporosis.

What are the two main types of primary osteoporosis?

Postmenopausal osteoporosis and senile osteoporosis.

What causes postmenopausal osteoporosis?

Decreased estrogen levels after menopause leading to increased bone resorption.

What is the mechanism of bone loss in postmenopausal osteoporosis?

↓Estrogen → ↑Bone resorption → ↑[Ca2+] → ↓PTH → ↓Calcitriol (vitamin D) → ↓Bone formation.

What causes senile osteoporosis?

Gradual loss of bone mass with age due to ↓Estrogen, ↓GFR, and ↓Vitamin D → ↓[Ca2+] → ↑PTH → ↑Bone resorption.

What are the main causes of secondary osteoporosis?

Drugs, endocrine/metabolic disorders, malignancy, lifestyle factors, and malabsorption.

Which drugs can cause osteoporosis?

Long-term corticosteroids, anticonvulsants, anticoagulants, and PPIs.

What endocrine/metabolic conditions can cause osteoporosis?

Hypercortisolism, hypogonadism, hyperthyroidism, and hyperparathyroidism.

Which lifestyle factors increase osteoporosis risk?

Excessive alcohol use, cigarette smoking, immobilization, and low physical activity.

How does malabsorption cause osteoporosis?

Poor absorption or dietary deficiency of calcium and vitamin D reduces bone mineralization.

What is the most common clinical presentation of osteoporosis?

Often asymptomatic until the first fragility fracture after minor trauma.

What are common fracture sites in osteoporosis?

Vertebral bodies, hip, and distal radius (wrist).

What spinal deformities can occur in osteoporosis?

Vertebral compression causing height loss, thoracic kyphosis, and compensatory lumbar lordosis.

What symptoms may occur due to vertebral fractures?

Acute back pain, abdominal pain, and a shortened spine.

What is the gold standard test for diagnosing osteoporosis?

Dual-energy X-ray absorptiometry (DEXA) scan.

What does a DEXA scan measure?

Bone mineral density (BMD) at the lumbar spine and hip/femoral neck.

What are the two main scores reported in a DEXA scan?

T-score and Z-score.

What does a T-score compare?

A person's BMD to that of a healthy young adult.

What does a Z-score compare?

A person's BMD to others of the same age and sex.

What is considered a normal T-score?

≥ -1 standard deviation (SD).

What T-score range indicates osteopenia?

Between -1 and -2.5 SD.

What T-score indicates osteoporosis?

≤ -2.5 SD.

What is the main goal of osteoporosis treatment?

Optimize bone health and prevent fractures.

What nutritional supplements are important in osteoporosis management?

Calcium and vitamin D.

How do bisphosphonates help in osteoporosis?

They inhibit osteoclasts, reducing bone resorption.

What are examples of bisphosphonates?

Alendronate and zoledronate.

What are examples of non-bisphosphonate drugs for osteoporosis?

Denosumab, raloxifene, and calcitonin.

When are non-bisphosphonate therapies used?

When patients cannot take bisphosphonates or if bisphosphonate therapy is ineffective.

What does a higher T-score indicate?

Stronger bones and higher bone mineral density.

What does a T-score closer to +1 mean?

Normal bone density and low risk of fracture.

What does a lower (more negative) T-score mean?

Lower bone mineral density and increased fracture risk.

What T-score range is considered normal?

Between +1 and -1 SD.

At what T-score does osteoporosis begin?

≤ -2.5 SD.

Initial diagnostic step in evaluating a thyroid nodule

Measure serum TSH level.

Next step if TSH is suppressed in thyroid nodule evaluation

"Perform thyroid scintigraphy to check for a hyperfunctioning (""hot"") nodule."

Next step if TSH is normal or elevated in thyroid nodule evaluation

Perform neck ultrasound (US).

Ultrasound features suspicious for malignancy

Hypoechogenicity, microcalcifications, solid consistency, irregular margins, lack of halo sign, hypervascularization.

Probability of malignancy in a nodule with microcalcifications

Approximately 70%.

Definitive diagnostic test for thyroid nodules

Fine-needle aspiration biopsy (FNAB).

FNAB classification system used

Bethesda classification system.

Bethesda categories with associated malignancy risk

Insufficient 1-4%, Benign 0-3%, AUS/FLUS 5-15%, Follicular neoplasia 15-30%, Suspicious for malignancy 60-75%, Malignant 97-99%.

When should genetic or molecular testing be considered?

In indeterminate cytology (AUS/FLUS or follicular neoplasm) to improve diagnostic accuracy.

Common molecular tests for thyroid nodules

Afirma Veracyte, ThyroSeq v2/v3, ThyroCan (NGS-based).

Sensitivity and specificity of ThyroCan test

Sensitivity 79%, specificity 86%, PPV 89%, NPV 75%.

Most common genetic mutations in papillary thyroid carcinoma (PTC)

BRAF, RET/PTC, RAS.

Clinical relevance of BRAF mutation

Associated with extrathyroidal growth, lymph node involvement, radioiodine resistance, and recurrence risk.

Common mutations in follicular thyroid carcinoma (FTC)

RAS, PAX8/PPAR-gamma, RET/PTC.

Imaging methods used for staging and follow-up

Neck ultrasound, scintiscan, bone scan, chest X-ray, CT.

Tumor marker used for follow-up after thyroid cancer treatment

Serum thyroglobulin (TG) and anti-thyroglobulin antibodies (aTG).

Tumor marker for medullary thyroid carcinoma

Serum calcitonin.

Main treatment options for differentiated thyroid cancer

Surgery, radioiodine therapy, and L-thyroxine suppression therapy.

Indication for surgery in thyroid nodules

Malignant cytology, indeterminate with molecular positivity, or compressive symptoms.

Role of radioiodine therapy in thyroid cancer

To ablate remnant thyroid tissue and treat metastatic disease in differentiated cancers.

Purpose of L-thyroxine suppression therapy

To suppress TSH and reduce stimulation of residual or recurrent thyroid cancer.

Follow-up methods after thyroid cancer therapy

Thyroglobulin and aTG measurement, neck ultrasound, scintigraphy, rhTSH stimulation test, chest X-ray, bone scan if indicated.

When should secondary hypertension be suspected?

Hypertension in patients

Most common endocrine causes of secondary hypertension?

Primary hyperaldosteronism, pheochromocytoma, Cushing's syndrome, acromegaly, thyrotoxicosis, hypothyroidism, hyperparathyroidism.

Definition of primary hyperaldosteronism (Conn's syndrome)

Primary adrenal overproduction of aldosterone → suppressed renin, hypertension, ± hypokalemia (in 50%).

Main causes of primary hyperaldosteronism

35-50% aldosterone-producing adenoma; 50-65% bilateral adrenal hyperplasia;

Screening test for primary hyperaldosteronism

Plasma aldosterone-to-renin activity ratio (ARR).

Positive ARR screening criteria

ARR > 30 and plasma aldosterone concentration > 15 ng/dL (416 pmol/L); renin suppressed (

Preconditions for reliable ARR test

Morning fasting sample, resting 20-30 min, normokalemia essential, adjust or stop interfering drugs.

Drugs that make ARR invalid (6-week stop)

Spironolactone, eplerenone, amiloride.

Drugs causing false-positive ARR (10-14 days stop)

Beta-blockers, alpha-methyldopa, clonidine, NSAIDs.

Drugs causing false-negative ARR (10-14 days stop)

ACE inhibitors, ARBs, diuretics, dihydropyridine calcium-channel blockers, estrogens.

Recommended antihypertensives during ARR screening

Doxazosin, prazosin, verapamil, hydralazine.

Confirmatory tests for primary hyperaldosteronism

IV or oral sodium loading, fludrocortisone suppression, captopril test.

Idea behind Na loading, fludrocortisone suppression, captopril test.

Na loading: aldosterone should decrease in levels in response to a high amount of Na/ volume increase Fludrocortisone supression: aldosterone should be suppressed Captopril test: ACEi which should decrease Aldosterone levels

Next diagnostic step after biochemical confirmation

Localization imaging: adrenal CT (first line), possibly MRI.

Gold standard for subtype differentiation

Adrenal vein sampling (aldosterone/cortisol ratio bilaterally).

Interpretation of adrenal vein sampling

≥3-4× higher aldosterone/cortisol ratio on one side → adenoma; little/no difference → bilateral hyperplasia.

Treatment of unilateral adenoma

Adrenalectomy (surgical removal).

Postoperative effect after adrenalectomy

Temporary hypoaldosteronism, possible hyperkalemia.

Treatment of bilateral adrenal hyperplasia

Medical: mineralocorticoid receptor antagonists (spironolactone, eplerenone ± amiloride).

Side effects of spironolactone

Gynecomastia, dysmenorrhea, impotence, breast tenderness (antiandrogen/progestogenic effects).

Definition of pheochromocytoma

Catecholamine-producing neuroendocrine tumor of adrenal medulla or extra-adrenal paraganglia.

Most common catecholamines produced

Norepinephrine (all), epinephrine (only adrenal), dopamine (some).

Hereditary syndromes linked to pheochromocytoma

MEN 2A/2B (RET), VHL, NF1, SDH mutations, TMEM127, MAX.

Classic triad of pheochromocytoma

Palpitations, Headache, Excessive sweating.

Other signs of pheochromocytoma

Paroxysmal or sustained hypertension, pallor, anxiety/panic, weight loss, orthostatic hypotension.

Biochemical confirmation test

Plasma or 24-hour urine (nor)metanephrines.

Positive biochemical criteria

>3× upper limit of normal (ULN) for metanephrines.

Additional tumor marker

Chromogranin A (correlates with tumor size).

Imaging after biochemical confirmation

Adrenal CT/MRI; full-body scan for extra-adrenal or multifocal forms.

Functional imaging options

123I-MIBG scintigraphy (95-100% sensitivity), 18F-fluorodopa or 18F-fluorodopamine PET/CT.

Contraindicated diagnostic procedure in pheochromocytoma

Biopsy (risk of catecholamine crisis).

Preoperative management

MUST PRETREAT WITH ALPHA BLOCKER (phenoxybenzamine, doxazosin, prazosin, urapidil) for ≥2 weeks before beta-blocker.

Surgical treatment

Adrenalectomy after adequate alpha-blockade; ligate adrenal vein first; avoid tumor manipulation.

Postoperative issues

Transient hypotension; possible persistent hypertension.

Malignant pheochromocytoma frequency and risk genes

5-26% of cases; SDHB mutations increase malignancy risk.

Metastasis sites in malignant pheochromocytoma

Liver, bone, lung, skull.

Long-term follow-up

Lifelong follow-up with genetic testing and surveillance for associated tumors.

What are the three principal hormones regulating calcium homeostasis?

Parathyroid hormone (PTH), Vitamin D, and Calcitonin.

Which organs are the main targets of calcium-regulating hormones?

Kidney, intestine, and bone.

What is the normal total serum calcium level?

2.2-2.6 mmol/L (8.5-10.5 mg/dL).

What is the normal ionized calcium (iCa) level?

1.0-1.3 mmol/L.

How does pH affect calcium binding?

A fall in pH by 0.1 increases ionized calcium by ~0.1 mmol/L.

What is the best test to measure calcium status in acute settings?

Direct measurement of ionized calcium.