What complications occur if primary hyperparathyroidism is left untreated?

Risks of Untreated Primary Hyperparathyroidism

Untreated primary hyperparathyroidism carries substantial risks including kidney stones, progressive bone disease, cardiovascular complications, neurocognitive impairment, and potentially life-threatening hypercalcemic crisis, with mortality rates that exceed the risks of surgical intervention. 1, 2, 3

Life-Threatening Complications

Hypercalcemic crisis represents the most severe acute complication, characterized by severe symptomatic hypercalcemia requiring urgent parathyroidectomy. 2 This condition can be fatal if not promptly recognized and treated. 3

In a landmark observational study of 47 patients with untreated primary hyperparathyroidism followed for minimum 5 years, 34% experienced major complications and four deaths were directly attributed to hyperparathyroidism-related complications—a mortality rate that significantly exceeded surgical risks. 3

Renal Complications

• Kidney stones develop in a significant proportion of untreated patients and represent a clear indication for parathyroidectomy. 2
• Progressive decline in renal function occurs in untreated disease, with five patients in one series experiencing decreased kidney function over the observation period. 3
• Nephrocalcinosis (calcium deposition in kidney tissue) can develop, leading to irreversible kidney damage. 2
• Acute kidney injury may result from severe hypercalcemia, requiring urgent surgical intervention. 2

Skeletal Complications

• Osteoporosis develops as excessive parathyroid hormone mobilizes calcium from bone, increasing fracture risk. 4, 2
• Osteitis fibrosa cystica (severe bone disease with cystic lesions) can occur in longstanding untreated cases. 2
• Pathologic fractures result from progressive bone mineral density loss. 4
• Lower bone mineral density with risk for osteopenia progresses over time without treatment. 5

Cardiovascular Complications

• Cardiac arrhythmias can result from hypercalcemia, including ventricular conduction defects (one case in the observational series). 3
• QT interval prolongation on electrocardiogram predisposes to dangerous arrhythmias. 5
• Cardiomyopathy rarely develops in severe, prolonged untreated hypercalcemia. 5
• Calciphylaxis (vascular calcification) represents a severe complication requiring urgent parathyroidectomy when PTH is elevated. 2

Gastrointestinal Complications

• Peptic ulcer disease occurred in eight of 47 patients (17%) in the untreated cohort, representing the most common complication observed. 3
• Chronic hypercalcemia increases gastric acid secretion, predisposing to ulcer formation. 3

Neurocognitive and Quality of Life Impact

• Neurocognitive disorders including cognitive impairment, mood disturbances, and fatigue are common presenting features that worsen without treatment. 2, 6
• Muscle weakness develops from the effects of elevated parathyroid hormone on neuromuscular function. 2
• Fatigue and irritability are frequently reported symptoms that significantly impact quality of life. 5, 6
• Abnormal involuntary movements can occur with hypocalcemia or hypercalcemia. 5

Critical Unpredictability of Disease Course

A crucial finding from long-term observational data is that no measured parameter—including initial calcium level, PTH level, or other biochemical markers—accurately predicted which patients would develop complications. 3 While serum calcium levels did not progressively worsen over time in most patients, this stability provided false reassurance, as one-third still developed serious complications. 3

This unpredictability makes conservative management particularly hazardous, as clinicians cannot reliably identify which asymptomatic patients will remain stable versus those who will develop life-threatening complications. 3

Comparative Risk Assessment

The 34% complication rate and mortality observed with conservative management substantially exceeds the morbidity and mortality rates from parathyroidectomy performed by experienced surgeons, where permanent complications (recurrent laryngeal nerve injury and hypoparathyroidism) occur in approximately 2-3% of cases. 5, 3 This risk-benefit analysis strongly favors surgical intervention for most patients. 1, 3

Common Clinical Pitfalls

• Assuming asymptomatic disease is benign: Many "asymptomatic" patients have subtle neurocognitive symptoms that only become apparent after successful treatment. 6
• Relying on stable calcium levels for reassurance: Disease progression and complications occur independent of calcium level trends. 3
• Delaying surgery in younger patients: Age <50 years is itself an indication for parathyroidectomy due to cumulative lifetime risk. 2
• Overlooking cardiovascular monitoring: Regular ECG monitoring for QT prolongation is essential in untreated patients. 5