Hyperparathyroidism for USMLE Step 1

Hyperparathyroidism for the USMLE Step 1 Exam

Parathyroid hormone (PTH): Regulates calcium homeostasis by increasing bone resorption, promoting renal calcium reabsorption, and enhancing vitamin D-mediated intestinal calcium absorption. PTH also promotes renal phosphate excretion.
Primary Hyperparathyroidism: Results from autonomous overproduction of PTH, usually due to a parathyroid adenoma (85%) or, less commonly, hyperplasia or carcinoma. This leads to hypercalcemia.
Secondary Hyperparathyroidism: Occurs due to compensatory PTH secretion in response to chronic hypocalcemia, usually from chronic kidney disease (CKD) or vitamin D deficiency.
Tertiary Hyperparathyroidism: Develops after prolonged secondary hyperparathyroidism, often seen in patients with end-stage renal disease, when the parathyroid glands become hyperplastic and autonomous.

Primary Hyperparathyroidism:
Parathyroid Adenoma: The most common cause of primary hyperparathyroidism.
Parathyroid Hyperplasia: Less common, often associated with familial conditions like MEN1 or MEN2A.
Parathyroid Carcinoma: Rare, but causes severe hypercalcemia.
Secondary Hyperparathyroidism:
Chronic Kidney Disease (CKD): The most common cause due to reduced renal activation of vitamin D, leading to hypocalcemia.
Vitamin D Deficiency: Reduces calcium absorption, triggering PTH release.

Primary Hyperparathyroidism:
Asymptomatic Hypercalcemia: Often diagnosed incidentally through routine labs.
Symptomatic Hypercalcemia:
"Bones": Osteoporosis, bone pain, and fractures from increased bone resorption.
"Stones": Nephrolithiasis (kidney stones) from hypercalciuria.
"Abdominal Groans": Constipation, nausea, and peptic ulcers.
"Psychic Moans": Fatigue, depression, and cognitive dysfunction.
Secondary Hyperparathyroidism:
Related to underlying conditions like CKD, causing hypocalcemia and bone pain.

Serum Calcium: Elevated in primary hyperparathyroidism; low or normal in secondary.
Serum PTH: Elevated in both primary and secondary hyperparathyroidism.
Serum Phosphate: Low in primary hyperparathyroidism, elevated in CKD-related secondary hyperparathyroidism.
Vitamin D Levels: Assessed to rule out vitamin D deficiency.
24-hour Urine Calcium: Elevated in primary hyperparathyroidism, helping to distinguish it from familial hypocalciuric hypercalcemia (FHH), which presents with low urinary calcium.
Bone Mineral Density (DEXA Scan): Evaluates for osteoporosis, particularly at cortical bone sites.
Imaging:
Sestamibi Scan: Used to localize parathyroid adenomas.
Neck Ultrasound: Helps identify enlarged parathyroid glands.

Primary Hyperparathyroidism:
Parathyroidectomy: Definitive treatment, especially in symptomatic patients or those with complications such as nephrolithiasis, osteoporosis, or severe hypercalcemia. It is also recommended in asymptomatic patients with significant hypercalcemia, reduced renal function, or osteoporosis.
Medical Management:
Hydration and Loop Diuretics: Increase urinary calcium excretion and prevent kidney stones.
Bisphosphonates: Reduce bone resorption in osteoporosis.
Cinacalcet: A calcimimetic that reduces PTH secretion in patients who are not surgical candidates.
Secondary Hyperparathyroidism:
Vitamin D Supplementation: Corrects deficiency.
Phosphate Binders: Used in CKD to lower serum phosphate levels.
Calcitriol: Active vitamin D analogs that suppress PTH in CKD patients.
Cinacalcet: Used to reduce PTH in patients with CKD who do not respond to other treatments.

Osteoporosis and Fractures: Result from prolonged bone resorption.
Nephrolithiasis: Kidney stones from increased calcium excretion.
Hypercalcemia Crisis: Severe hypercalcemia leading to confusion, dehydration, and cardiac arrhythmias, requiring urgent treatment with IV fluids, bisphosphonates, and calcitonin.
Renal Impairment: Prolonged hypercalcemia can cause nephrocalcinosis and renal failure.

Key Points

Primary Hyperparathyroidism is most commonly caused by a parathyroid adenoma, leading to hypercalcemia. Clinical features include bone pain, kidney stones, gastrointestinal symptoms, and cognitive dysfunction. Diagnosis is confirmed by elevated calcium and PTH levels.
Secondary Hyperparathyroidism results from chronic hypocalcemia due to conditions like CKD or vitamin D deficiency. Treatment focuses on correcting the underlying cause with vitamin D supplements or phosphate binders.
Parathyroidectomy is the definitive treatment for symptomatic primary hyperparathyroidism, while medical management includes hydration, bisphosphonates, and calcimimetics.
Complications include osteoporosis, nephrolithiasis, and in severe cases, a hypercalcemic crisis.