A 52-year-old woman presents with recurrent kidney stones and bone pain. Serum calcium is 11.2 mg/dL (normal 8.5–10.5), phosphate is 2.8 mg/dL (normal 2.5–4.5), and PTH is markedly elevated at 185 pg/mL (normal 15–65). What is the most common cause of primary hyperparathyroidism in this patient?

Explanation

## Most Common Cause of Primary Hyperparathyroidism **Key Point:** Solitary parathyroid adenoma accounts for approximately 80–85% of all cases of primary hyperparathyroidism. ### Epidemiology of Primary Hyperparathyroidism | Cause | Frequency | Clinical Features | |-------|-----------|------------------| | Solitary adenoma | 80–85% | Single enlarged gland; normal other glands | | Parathyroid hyperplasia | 10–15% | All four glands enlarged; often familial or syndromic | | Parathyroid carcinoma | 1–2% | Rare; very high PTH and calcium; palpable neck mass | | Tertiary hyperparathyroidism | <1% | Post-transplant; autonomous PTH secretion | ### Clinical Context in This Case **High-Yield:** The patient presents with classic features of primary hyperparathyroidism: - Hypercalcemia (11.2 mg/dL) - Hypophosphatemia (2.8 mg/dL) - Markedly elevated PTH (185 pg/mL) - Nephrolithiasis (kidney stones) - Bone disease (osteitis fibrosa cystica) These findings are consistent with a solitary adenoma, which is the most common pathological entity underlying primary hyperparathyroidism in the general population. **Clinical Pearl:** Parathyroid carcinoma is rare (1–2% of cases) and typically presents with more severe hypercalcemia (>14 mg/dL), very high PTH levels (>500 pg/mL), and a palpable neck mass. Hyperplasia is associated with familial syndromes (MEN 1, MEN 2A) or occurs in younger patients with multiglandular involvement. ### Pathophysiology A solitary adenoma arises from clonal proliferation of a single parathyroid cell population, leading to autonomous PTH secretion independent of serum calcium feedback. This results in: 1. Increased renal tubular reabsorption of calcium (via PTH-mediated effects on the distal convoluted tubule) 2. Increased 1,25-dihydroxyvitamin D production (via PTH stimulation of 1α-hydroxylase in the proximal tubule) 3. Increased osteoclastic bone resorption 4. Net result: hypercalcemia and hypophosphatemia **Mnemonic:** CHOP for features of primary hyperparathyroidism — **C**alcium elevated, **H**yperparathyroidism, **O**steitis fibrosa cystica, **P**hosphatemia low.