Should a patient with normocalcemic primary hyperparathyroidism, elevated parathyroid hormone, borderline high serum calcium, severe hypercalciuria, normal 25‑hydroxyvitamin D, a confirmed parathyroid adenoma, and refractory neuropsychiatric symptoms undergo urgent parathyroidectomy?

Parathyroidectomy for Normocalcemic Primary Hyperparathyroidism with Severe Hypercalciuria and Neuropsychiatric Symptoms

This patient should proceed urgently to parathyroidectomy based on confirmed normocalcemic primary hyperparathyroidism (NPHPT) with severe hypercalciuria (>400 mg/24hr) and profoundly debilitating neuropsychiatric symptoms that represent target-organ manifestations of parathyroid disease. 1

Diagnostic Confirmation

Your patient meets the strict diagnostic criteria for NPHPT:

• Persistently elevated PTH (126 pg/mL) with consistently normal albumin-corrected serum calcium (10.1 mg/dL is within normal range of 8.6-10.3 mg/dL) after exclusion of all secondary causes 1
• Vitamin D status is adequate (normal 25-OH vitamin D), ruling out the most common cause of secondary hyperparathyroidism 1
• Normal albumin eliminates pseudo-hypercalcemia 1
• Confirmed parathyroid adenoma on imaging provides anatomic confirmation 2

The biochemical profile is definitive: NPHPT is not a benign entity and carries a risk profile comparable to hypercalcemic primary hyperparathyroidism despite normal serum calcium. 1

Surgical Indications Met

This patient fulfills multiple established surgical criteria for parathyroidectomy:

Severe Hypercalciuria

• 24-hour urine calcium of 446 mg exceeds the surgical threshold of >300 mg/24hr, which is a recognized indication for parathyroidectomy 3
• Severe hypercalciuria places the patient at high risk for nephrocalcinosis and progressive renal calcifications 2

Symptomatic Disease with Target-Organ Manifestations

• Neurocognitive symptoms (refractory depression, emotional lability, cognitive impairment, "brain fog," memory loss) represent recognized target-organ involvement in primary hyperparathyroidism 2
• The profound functional impairment (occupational dysfunction, inability to perform basic tasks without written cues, loss of childhood memories) constitutes symptomatic disease warranting surgical intervention 2
• Patient preference for definitive treatment is recognized as a valid indication for surgical referral in NPHPT 1

Clinical Manifestations Are Equivalent Between NPHPT and Hypercalcemic PHPT

• Research demonstrates that normocalcemic patients present with comparable frequencies of nephrolithiasis (36%), fragility fractures (12%), and osteoporosis (25%) as hypercalcemic patients 4
• No significant difference exists in clinical manifestations, complications, or bone mineral density between NPHPT and hypercalcemic PHPT 5, 4
• Normocalcemic subjects should be managed identically to hypercalcemic subjects with PHPT 4

Addressing the "Observational Approach" Recommendation

The previously suggested observational approach is inappropriate for this patient:

• Treatment of PHPT is surgical excision of abnormally functioning parathyroid tissue and is typically indicated even when asymptomatic, given potential negative effects of long-term hypercalcemia 2
• Your patient is profoundly symptomatic with documented target-organ involvement (neuropsychiatric manifestations and severe hypercalciuria), making observation contraindicated 2
• The presence of a confirmed adenoma with markedly elevated PTH (126 pg/mL) indicates significant biological activity requiring removal 2

Surgical Planning and Expected Outcomes

Preoperative Localization

• The confirmed adenoma on imaging allows for minimally invasive parathyroidectomy (MIP), which offers shorter operating times, faster recovery, and decreased perioperative costs 2, 3
• MIP requires confident preoperative localization of a single parathyroid adenoma and intraoperative PTH monitoring to confirm removal of the hyperfunctioning gland 2

Expected Biochemical and Clinical Outcomes

• In normocalcemic PHPT, improvements in bone mineral density (+5.6%) occur when PTH normalizes postoperatively 6
• Resolution of neuropsychiatric symptoms is expected with removal of the metabolic driver (elevated PTH) 2
• Persistently elevated PTH after surgery occurs in approximately 46.5% of NPHPT cases, but this does not negate the benefit of surgery for symptomatic patients 6

Critical Postoperative Monitoring

• Measure ionized calcium every 4-6 hours for the first 48-72 hours after surgery to detect "hungry bone syndrome" 1, 3
• If ionized calcium drops below 0.9 mmol/L (≈3.6 mg/dL), initiate IV calcium gluconate infusion at 1-2 mg elemental calcium per kg per hour 1
• Begin oral calcium carbonate 1-2 g three times daily plus calcitriol up to 2 µg/day once oral intake is tolerated 1

Common Pitfalls to Avoid

Do Not Delay Surgery for Calcium Supplementation Trial

• A recent study showed that calcium supplementation can normalize PTH in 55% of normocalcemic patients with insufficient calcium intake, but your patient has normal vitamin D and the clinical context (confirmed adenoma, severe hypercalciuria, profound symptoms) makes secondary hyperparathyroidism extremely unlikely 7
• The severe hypercalciuria (446 mg/24hr) is inconsistent with calcium deficiency, which typically presents with low urinary calcium 7

Do Not Attribute Symptoms Solely to Psychiatric Disease

• The temporal relationship between biochemical abnormalities and treatment-resistant neuropsychiatric symptoms, combined with failure of psychiatric management, strongly suggests parathyroid disease as the primary driver 2
• Neurocognitive disorders are recognized target-organ manifestations of PHPT in countries without routine biochemical screening 2

Ensure Referral to High-Volume Parathyroid Surgeon

• All patients meeting surgical criteria should be referred to an experienced, high-volume parathyroid surgeon, as outcomes are significantly better with specialized expertise 3
• Parathyroid reoperations have lower cure rates and higher complication rates, making first-time surgical success critical 2

Urgency Justification

The combination of severe hypercalciuria (risk of irreversible renal calcifications), progressive cognitive decline (loss of childhood memories, inability to function occupationally), and confirmed anatomic disease (adenoma) justifies urgent rather than routine referral. 2, 1 The patient's quality of life is profoundly impaired, and delay risks permanent cognitive sequelae and renal damage.