Symptoms of Hyperparathyroidism
Hyperparathyroidism presents with a spectrum of symptoms ranging from asymptomatic biochemical abnormalities to severe manifestations affecting multiple organ systems, with the most common symptoms being bone pain, kidney stones, cognitive dysfunction, and gastrointestinal complaints. 1
Primary Hyperparathyroidism Symptoms
Classic Symptoms ("Bones, Stones, Abdominal Groans, and Psychic Moans")
Skeletal manifestations:
- Bone pain and tenderness
- Pathological fractures
- Osteoporosis and bone demineralization
- Osteitis fibrosa cystica (in advanced cases)
Renal manifestations:
- Nephrolithiasis (kidney stones)
- Nephrocalcinosis
- Polyuria
- Reduced renal function
Gastrointestinal symptoms:
- Constipation (66% of symptomatic patients) 2
- Nausea and vomiting
- Abdominal pain
- Anorexia
Neuropsychiatric symptoms:
- Cognitive impairment (44% of symptomatic patients) 2
- Depression and anxiety
- Fatigue and weakness
- Memory problems
- Changes in sensorium
Severity-Based Symptoms
Mild to Moderate Hypercalcemia (10.5-12 mg/dL):
- Polyuria and polydipsia
- Muscle weakness (especially proximal)
- Fatigue
- Mild cognitive changes
Severe Hypercalcemia (>12 mg/dL):
- Severe dehydration
- Confusion and altered mental status
- Stupor progressing to coma (with levels >14 mg/dL)
- Cardiac arrhythmias
- Hypertension 2
Secondary Hyperparathyroidism Symptoms
Secondary hyperparathyroidism (commonly seen in chronic kidney disease) presents with:
- Renal osteodystrophy
- Bone pain and fractures
- Extraskeletal calcifications
- Pruritus (severe and intractable) 1
- Progressive skeletal and articular pain 1
- Calciphylaxis (in severe cases)
Tertiary Hyperparathyroidism Symptoms
Tertiary hyperparathyroidism (autonomous parathyroid function after longstanding secondary hyperparathyroidism) presents with:
- Persistent hypercalcemia
- Symptoms similar to primary hyperparathyroidism
- Metastatic calcifications
- Bone disease 3
Risk Factors for Symptomatic Presentation
Patients are more likely to present with hypercalcemic symptoms if they have:
- Older age (median 71 years vs 64 years in asymptomatic patients) 2
- Higher serum calcium levels (>12.3 mg/dL) 2
- Reduced kidney function (eGFR <45 ml/min) 2
- Multiple comorbidities and polypharmacy 2
- Higher PTH levels
Laboratory Findings
- Elevated serum calcium (or inappropriately normal in normocalcemic variant)
- Elevated or inappropriately normal PTH levels
- Low serum phosphorus
- Elevated alkaline phosphatase (indicating increased bone turnover)
- Elevated 24-hour urinary calcium excretion
- Low or normal 25-hydroxyvitamin D levels
Important Clinical Considerations
Modern presentation pattern: In countries with routine biochemical screening (US, Canada, Europe), PHPT predominantly presents as an asymptomatic disorder, while in countries without routine screening, symptomatic presentation is more common 1
Diagnostic pitfalls:
- Always exclude vitamin D deficiency, which can mask hypercalcemia
- Consider familial hypocalciuric hypercalcemia as a differential diagnosis
- Differentiate from malignancy-associated hypercalcemia (which typically has suppressed PTH) 1
Monitoring recommendations:
- Serum calcium, phosphorus, and PTH levels should be checked every 3-6 months depending on CKD stage 4
- More frequent monitoring for those with severe disease or on treatment
Emergency presentation: Severe hypercalcemia (>13.5-14 mg/dL) requires immediate treatment due to risk of cardiac, neurological, gastrointestinal, and renal injury 3
By recognizing these symptoms early, clinicians can initiate appropriate treatment, which may include surgical intervention for primary hyperparathyroidism or medical management for secondary forms, ultimately improving morbidity, mortality, and quality of life outcomes.