Hyperparathyroidism for USMLE Step 3

Hyperparathyroidism for the USMLE Step 3 Exam

Parathyroid hormone (PTH) regulates calcium and phosphate metabolism. It increases serum calcium by promoting bone resorption, enhancing renal reabsorption of calcium, and stimulating 1,25-dihydroxyvitamin D production to increase intestinal calcium absorption. PTH also promotes renal phosphate excretion.
Primary Hyperparathyroidism: Autonomous overproduction of PTH, most commonly caused by a parathyroid adenoma (85%), leads to hypercalcemia.
Secondary Hyperparathyroidism: Results from chronic hypocalcemia, often due to chronic kidney disease (CKD) or vitamin D deficiency, stimulating increased PTH secretion.
Tertiary Hyperparathyroidism: Develops after prolonged secondary hyperparathyroidism, typically in CKD patients, leading to autonomous PTH secretion despite normal or elevated calcium levels.

Primary Hyperparathyroidism:
Parathyroid Adenoma: Most common cause, responsible for over 80% of cases.
Parathyroid Hyperplasia: Causes 10-15% of cases and can occur in familial syndromes (e.g., MEN1, MEN2A).
Parathyroid Carcinoma: Rare cause but presents with severe hypercalcemia.
Secondary Hyperparathyroidism:
Chronic Kidney Disease: Decreased renal activation of vitamin D and phosphate retention result in hypocalcemia, leading to compensatory PTH secretion.
Vitamin D Deficiency: Reduces calcium absorption, leading to increased PTH secretion.

Primary Hyperparathyroidism:
Asymptomatic: Many patients are asymptomatic and diagnosed during routine labs.
Symptomatic Hypercalcemia:
Bone pain and fractures: Due to increased bone resorption (osteoporosis).
Nephrolithiasis: Kidney stones caused by hypercalciuria.
Gastrointestinal symptoms: Nausea, constipation, and abdominal pain.
Neuropsychiatric symptoms: Fatigue, depression, confusion.
Secondary Hyperparathyroidism:
Bone pain and muscle weakness due to chronic hypocalcemia and elevated PTH. Often seen in patients with CKD or vitamin D deficiency.

Serum Calcium: Elevated in primary hyperparathyroidism; low or normal in secondary hyperparathyroidism.
Serum PTH: Elevated in both primary and secondary hyperparathyroidism.
Serum Phosphate: Low in primary hyperparathyroidism, but elevated in CKD-related secondary hyperparathyroidism.
Vitamin D Levels: Assessed to rule out vitamin D deficiency.
Imaging:
Sestamibi Scan: Localizes parathyroid adenomas in preparation for surgery.
Neck Ultrasound: Helps identify parathyroid gland enlargement.

Primary Hyperparathyroidism:
Parathyroidectomy: Definitive treatment for symptomatic patients or those with complications like osteoporosis or nephrolithiasis. It is also recommended in asymptomatic patients with significant hypercalcemia (>1 mg/dL above normal), decreased bone density (T-score ≤ -2.5), or impaired renal function (eGFR <60 mL/min).
Medical Management:
Hydration: To prevent kidney stones.
Cinacalcet: A calcimimetic used in patients who are not surgical candidates; it decreases PTH secretion.
Bisphosphonates: Used to treat osteoporosis by reducing bone resorption.
Secondary Hyperparathyroidism:
Vitamin D Supplementation: Corrects vitamin D deficiency.
Phosphate Binders: Used in CKD to lower serum phosphate levels.
Calcitriol: Active vitamin D used to suppress PTH in CKD.
Cinacalcet: Lowers PTH in patients with CKD who are not candidates for surgery.

Osteoporosis and Fractures: Prolonged hyperparathyroidism increases the risk of bone loss and fractures.
Nephrolithiasis: Kidney stones due to hypercalciuria.
Hypercalcemic Crisis: Severe hypercalcemia (>14 mg/dL) leading to dehydration, confusion, and arrhythmias, requiring aggressive treatment with IV fluids, bisphosphonates, and calcitonin.
Renal Impairment: Chronic hypercalcemia can cause nephrocalcinosis and CKD.

Key Points

Primary Hyperparathyroidism is most commonly caused by a parathyroid adenoma, leading to hypercalcemia. Symptoms include bone pain, nephrolithiasis, and neuropsychiatric disturbances. Parathyroidectomy is the definitive treatment for symptomatic or high-risk patients.
Secondary Hyperparathyroidism results from chronic hypocalcemia, commonly seen in CKD or vitamin D deficiency. Treatment focuses on correcting the underlying cause with vitamin D supplements, phosphate binders, or calcimimetics.
Complications of hyperparathyroidism include osteoporosis, nephrolithiasis, and hypercalcemic crisis, which may require aggressive medical intervention.