What are the symptoms and treatment options for hyperparathyroidism, particularly in postmenopausal women or individuals with a history of kidney disease?

Symptoms of Hyperparathyroidism

Hyperparathyroidism today presents predominantly as an asymptomatic or mildly symptomatic condition discovered incidentally through routine biochemical screening, particularly in postmenopausal women, with severe manifestations like kidney stones and bone disease now occurring in less than 5% of cases. 1, 2

Clinical Presentation by Disease Severity

Asymptomatic Disease (Most Common)

• Up to 80% of patients with primary hyperparathyroidism in Western countries are asymptomatic or have only mild, nonspecific symptoms discovered through incidental hypercalcemia on routine laboratory testing 1, 3
• The shift from symptomatic to asymptomatic presentation occurred with widespread adoption of automated serum calcium measurement in the 1970s-1980s 2

Mild to Moderate Symptoms

• Nonspecific constitutional symptoms include weakness, fatigue, and mental depression, which are the most common complaints in contemporary practice 2
• Neurocognitive disorders and psychological disturbances can occur with chronic hyperparathyroidism 1
• Muscle weakness affects neuromuscular function 1
• Arterial hypertension may be present as a cardiovascular manifestation 2

Skeletal Manifestations

• Bone pain and osteopenia are present in many patients, though severe hyperparathyroid bone disease now occurs in less than 5% of cases 1, 2
• Progressive skeletal and articular pain occurs particularly when PTH exceeds 500-800 pg/mL 1
• Bone pain, pathological fractures, and skeletal deformities develop when PTH levels persistently exceed 10 times the upper normal limit, representing severe hyperparathyroid bone disease 1
• Bone demineralization and osteoporosis increase fracture risk 1

Renal Manifestations

• Nephrolithiasis (kidney stones) and nephrocalcinosis occur in less than 5% of contemporary cases, compared to 57% historically 1, 2
• Persistent hypercalcemia driven by elevated PTH causes progressive renal damage 1
• Nephrocalcinosis develops from calcium deposition in renal parenchyma, creating a vicious cycle that worsens kidney function 1

Severe Manifestations (Rare in Modern Practice)

• Intractable pruritus is a debilitating symptom in secondary hyperparathyroidism, often requiring surgical intervention when PTH levels exceed 500 pg/mL 1
• Hypercalcemic crisis requires urgent parathyroidectomy 4
• Calciphylaxis with elevated PTH levels necessitates urgent surgical intervention 4

Special Populations

Postmenopausal Women

• Primary hyperparathyroidism has the highest incidence in postmenopausal women, making this the most commonly affected demographic 5
• The combination of hyperparathyroidism and postmenopausal bone loss creates additive risk for osteoporosis 1

Patients with Chronic Kidney Disease

• Biochemical evidence of hyperparathyroidism persists in many patients after kidney transplantation, with PTH levels declining by 50% within 14 days but remaining elevated long-term 6
• Hypercalcemia occurs in 1-5% of transplant recipients due to persistent hyperparathyroidism, potentially requiring parathyroidectomy 6
• Persistent hyperparathyroidism after transplant increases risk for hypercalcemia, hypophosphatemia, worsening bone disease, and possibly acute tubular necrosis 6
• Elevated alkaline phosphatase reflects increased osteoblastic activity attempting to compensate for PTH-driven bone resorption 1
• Generalized bone pain contributes to functional impairment and disability, affecting mental status and quality of life 1

Gastrointestinal and Cardiovascular Symptoms

• Gastrointestinal symptoms can occur as part of the classical manifestation spectrum 3
• Cardiovascular abnormalities and reduced quality of life may develop in symptomatic disease 7
• Progressive calcification of vessels occurs with persistent hypercalcemia and hyperphosphatemia, contributing to increased cardiovascular morbidity and mortality in CKD patients 1

Critical Clinical Pearls

The dramatic evolution in clinical presentation means that clinicians must maintain high suspicion for hyperparathyroidism even in patients with vague, nonspecific symptoms rather than waiting for classic severe manifestations that rarely occur in modern practice 2. The diagnosis is typically made biochemically with elevated or high-normal intact PTH in the setting of elevated total or ionized calcium 1.