Primary Hyperparathyroidism

Excerpt

Primary hyperparathyroidism (PHPT) is an endocrine disorder defined by autonomous overproduction of parathyroid hormone (PTH), resulting in hypercalcemia and disrupted calcium homeostasis. The most common etiology is a single benign adenoma, while multigland hyperplasia, multiple adenomas, and parathyroid carcinoma are less frequent. Variants, eg, normocalcemic and normohormonal PHPT, represent milder biochemical manifestations of the same disease process. PHPT is the leading cause of hypercalcemia in the outpatient setting, predominantly affecting postmenopausal women. The incidence of PHPT is rising due to increased routine biochemical screening. The underlying pathophysiology involves a shift in the calcium-sensing receptor (CaSR) set point, causing persistent PTH secretion despite elevated serum calcium. This leads to increased bone resorption, renal calcium reabsorption, and intestinal calcium absorption.

Histopathologically, parathyroid adenomas are well-circumscribed lesions composed primarily of chief cells with reduced stromal fat. Hyperplasia is characterized by diffuse enlargement of all 4 glands, whereas carcinoma is identified by capsular or vascular invasion. The clinical presentation has shifted from classic symptomatic disease, such as nephrolithiasis, bone pain, and fractures, to predominantly asymptomatic hypercalcemia detected incidentally. Diagnostic evaluation relies exclusively on biochemical testing, focusing on confirming elevated or inappropriately elevated PTH in the presence of hypercalcemia after secondary causes have been excluded. Imaging studies for localization are reserved solely for surgical planning.

Parathyroidectomy remains the only curative treatment, with cure rates exceeding 95%. Medical management and observation are suitable for selected patients who are asymptomatic or considered poor surgical candidates. Prognosis is excellent with timely surgical intervention, as both bone density and renal function typically improve, and recurrence is rare. Patients managed conservatively often remain stable for years with appropriate monitoring. Untreated PHPT can result in complications, eg, osteoporosis, nephrolithiasis, neuropsychiatric symptoms, and cardiovascular changes. Surgical complications, including transient hypocalcemia, hungry bone syndrome, or recurrent laryngeal nerve injury, are uncommon and generally manageable by experienced clinicians.