What is the relationship between elevated Parathyroid Hormone (PTH) levels and hypercalcemia, and how should a patient with primary hyperparathyroidism and elevated calcium levels be managed?

Primary Hyperparathyroidism Diagnosis and Immediate Management

Your patient has primary hyperparathyroidism (PHPT) with calcium 11.2 mg/dL (>1 mg/dL above normal upper limit of 10.3 mg/dL) and PTH 90 pg/mL (elevated or inappropriately normal), and this patient requires surgical evaluation for parathyroidectomy. 1, 2

Understanding the Biochemical Relationship

The combination of elevated calcium (11.2 mg/dL) with a PTH of 90 pg/mL represents autonomous parathyroid hormone secretion characteristic of PHPT. 1, 3, 4

• In normal physiology, elevated calcium should suppress PTH to very low levels (<20 pg/mL). 5
• In PHPT, the parathyroid glands autonomously secrete PTH despite hypercalcemia, resulting in elevated or "inappropriately normal" PTH levels (typically >65 pg/mL when calcium is elevated). 1, 2, 6
• This patient's PTH of 90 pg/mL is frankly elevated in the context of hypercalcemia, confirming autonomous parathyroid function. 1, 3

Immediate Diagnostic Workup Required

Before proceeding to surgery, complete the following essential tests:

Mandatory Laboratory Tests

• 25-hydroxyvitamin D level - Vitamin D deficiency can complicate PTH interpretation and must be excluded before confirming PHPT diagnosis. 1, 2
• Serum creatinine and eGFR - Essential for assessing kidney function and surgical candidacy. 1, 2
• Serum phosphate - Typically low or low-normal in PHPT. 1, 2
• 24-hour urine calcium - To exclude familial hypocalciuric hypercalcemia (FHH) if urine calcium-to-creatinine clearance ratio is <0.01. 3, 4
• Ionized calcium - For definitive assessment if albumin is abnormal. 2

Critical Pitfall to Avoid

Do not proceed with parathyroid imaging until biochemical diagnosis is confirmed. 2 Imaging is for surgical localization only, not diagnosis. 1, 3

Surgical Indications - This Patient Qualifies

Your patient meets absolute criteria for parathyroidectomy based on calcium >1 mg/dL above the upper limit of normal (11.2 mg/dL vs. normal upper limit 10.3 mg/dL). 1, 2

Additional surgical indications to assess include:

• Age ≥50 years 1
• Osteoporosis on DEXA scan 1, 2
• eGFR <60 mL/min/1.73 m² 1, 2
• History of kidney stones or nephrocalcinosis 1, 2
• 24-hour urine calcium >400 mg/day (increased risk for kidney stones and bone complications) 1

Pre-Operative Localization Imaging

Once biochemical diagnosis is confirmed and surgery is planned:

• First-line: Neck ultrasound - Recommended as initial localization study. 1, 2
• Second-line: Dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT - Provides high sensitivity for adenoma localization. 1, 7
• Combination of ultrasound + sestamibi offers highest sensitivity for localization. 1
• Consider 4D-CT or MRI if initial imaging is negative or for reoperative cases. 1, 2

Medical Management If Surgery Contraindicated or Delayed

If parathyroidectomy cannot be performed immediately or patient refuses surgery:

Cinacalcet (Calcimimetic Agent)

Cinacalcet is FDA-approved for hypercalcemia in primary hyperparathyroidism when parathyroidectomy is indicated but patient is unable to undergo surgery. 8

• Starting dose: 30 mg twice daily 8
• Titrate every 2 weeks to maximum 90 mg four times daily 8
• Goal: Serum calcium ≤10 mg/dL 8
• Efficacy: 75.8% of patients achieved calcium ≤10.3 mg/dL in controlled trials 8
• Mean calcium reduction: 2.3 mg/dL from baseline 8

Immediate Lifestyle Modifications

• Maintain normal calcium intake (1000-1200 mg/day) - Avoid both high and low calcium diets. 2
• Total elemental calcium intake should not exceed 2000 mg/day. 2
• Discontinue all vitamin D supplements until hypercalcemia resolves. 2, 5
• Discontinue thiazide diuretics if currently prescribed. 2
• Ensure adequate hydration to prevent worsening hypercalcemia. 2

Monitoring During Medical Management

• Serum calcium and ionized calcium every 1-2 weeks until stable. 5
• PTH levels every 3 months. 9
• Serum creatinine to monitor kidney function. 2

Differential Diagnosis Considerations

Secondary hyperparathyroidism is excluded because it presents with normal or LOW calcium, not hypercalcemia. 1, 2

Tertiary hyperparathyroidism occurs in end-stage renal disease with hypercalcemia and elevated PTH, but requires history of chronic dialysis. 1

Familial hypocalciuric hypercalcemia (FHH) must be excluded if 24-hour urine calcium-to-creatinine clearance ratio is <0.01 in the absence of thiazide use or severe vitamin D deficiency. 3, 4

Referral Pathway

Refer to endocrinology and an experienced parathyroid surgeon for surgical evaluation. 2 Surgery is the definitive treatment and offers cure in >95% of cases with solitary adenoma. 10, 7