Hyperparathyroidism for USMLE Step 2

Hyperparathyroidism for the USMLE Step 2 Exam

Parathyroid hormone (PTH) plays a key role in regulating serum calcium by increasing bone resorption, enhancing renal calcium reabsorption, and stimulating vitamin D activation to promote gastrointestinal calcium absorption. PTH also promotes renal phosphate excretion.
Primary Hyperparathyroidism: Occurs when one or more of the parathyroid glands autonomously secrete excessive PTH, leading to hypercalcemia. Most cases are due to a parathyroid adenoma (85%), with fewer cases caused by parathyroid hyperplasia (10-15%) or, rarely, parathyroid carcinoma.
Secondary Hyperparathyroidism: Develops as a compensatory response to chronic hypocalcemia, commonly seen in chronic kidney disease (CKD) or vitamin D deficiency.
Tertiary Hyperparathyroidism: Occurs when prolonged secondary hyperparathyroidism leads to autonomous PTH secretion, often in patients with end-stage renal disease.

Primary Hyperparathyroidism:
Parathyroid Adenoma: The most common cause.
Parathyroid Hyperplasia: Often associated with familial syndromes like MEN1 or MEN2A.
Parathyroid Carcinoma: Rare, but presents with severe hypercalcemia.
Secondary Hyperparathyroidism:
Chronic Kidney Disease (CKD): Impaired renal function leads to reduced vitamin D activation, hypocalcemia, and compensatory PTH secretion.
Vitamin D Deficiency: Causes hypocalcemia, prompting increased PTH secretion.

Primary Hyperparathyroidism:
Often asymptomatic, diagnosed during routine screening for hypercalcemia.
Symptomatic Hypercalcemia:
Bone pain and fractures: Due to increased bone resorption (osteoporosis, osteitis fibrosa cystica).
Nephrolithiasis: Kidney stones due to hypercalciuria.
Gastrointestinal symptoms: Nausea, constipation, and abdominal pain.
Neuropsychiatric symptoms: Fatigue, depression, and cognitive impairment.
Secondary Hyperparathyroidism:
Bone pain and muscle weakness due to chronic hypocalcemia and high PTH levels.
Underlying conditions like CKD or vitamin D deficiency are common.

Serum Calcium: Elevated in primary hyperparathyroidism, but low or normal in secondary.
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: Checked to rule out deficiency, especially in secondary hyperparathyroidism.
Imaging:
Sestamibi Scan: Localizes parathyroid adenomas for surgical planning.
Neck Ultrasound: Can help identify enlarged parathyroid glands.

Primary Hyperparathyroidism:
Parathyroidectomy: The definitive treatment, especially indicated in symptomatic patients or those with complications (osteoporosis, nephrolithiasis, or significant hypercalcemia). It is also recommended for asymptomatic patients with calcium >1 mg/dL above the upper normal limit, osteoporosis, reduced kidney function, or age <50.
Medical Management:
Hydration: To prevent kidney stones.
Cinacalcet: A calcimimetic that reduces PTH secretion, used in patients who are not surgical candidates.
Bisphosphonates: Used to treat osteoporosis by reducing bone resorption.
Secondary Hyperparathyroidism:
Treat the underlying cause: Vitamin D supplementation and managing CKD.
Phosphate Binders: Lower serum phosphate in CKD.
Active Vitamin D Analogues (Calcitriol): Suppress PTH secretion in CKD.
Cinacalcet: Useful in reducing PTH levels in CKD patients who cannot undergo surgery.

Osteoporosis and Fractures: Due to excessive bone resorption.
Nephrolithiasis: Kidney stones from chronic hypercalcemia and hypercalciuria.
Hypercalcemia Crisis: Severe hypercalcemia leading to dehydration, confusion, and cardiac arrhythmias. Requires aggressive treatment with IV fluids, bisphosphonates, and calcitonin.
Renal Impairment: Hypercalcemia can cause nephrocalcinosis and renal insufficiency.

Key Points

Primary Hyperparathyroidism is most often caused by a parathyroid adenoma and leads to hypercalcemia. Common clinical features include bone pain, kidney stones, and gastrointestinal or neuropsychiatric symptoms.
Secondary Hyperparathyroidism arises due to chronic hypocalcemia, commonly seen in CKD or vitamin D deficiency. Treatment focuses on correcting the underlying cause with phosphate binders and vitamin D supplementation.
Parathyroidectomy is the definitive treatment for symptomatic primary hyperparathyroidism, while cinacalcet and bisphosphonates are used in patients who are not surgical candidates.
Complications include osteoporosis, nephrolithiasis, and, in severe cases, hypercalcemic crisis.