Management of Elevated Calcium and Albumin with Normal GGT and PTH
When calcium and albumin are both elevated with normal GGT and normal PTH, this pattern suggests primary hyperparathyroidism with inappropriately "normal" PTH (which is actually abnormal in the setting of hypercalcemia), rather than a hepatobiliary or bone disorder. 1, 2
Diagnostic Interpretation
The key to understanding this presentation lies in recognizing that PTH should be suppressed in the presence of hypercalcemia. A "normal" PTH in this context is pathologically inappropriate and diagnostic of primary hyperparathyroidism. 3, 1
Normal GGT rules out hepatobiliary disease as the source of elevated alkaline phosphatase (if ALP is also elevated), since GGT rises in parallel with ALP in liver pathology but remains normal in bone-derived ALP elevation. 3, 4
Elevated albumin may indicate dehydration (common in hypercalcemia due to polyuria) or may be causing falsely elevated total calcium measurements. 3, 5
Immediate Diagnostic Steps
First, calculate corrected calcium using the formula: Corrected Ca (mg/dL) = serum calcium + 0.8 × (4.0 - serum albumin g/dL). 6, 5
If corrected calcium remains elevated with normal or elevated PTH, this confirms primary hyperparathyroidism. 1, 2
Measure 25-OH vitamin D levels to exclude vitamin D deficiency as a cause of secondary hyperparathyroidism, targeting levels >20 ng/mL (50 nmol/L). 3, 1, 5
Assess renal function with serum creatinine and eGFR, as eGFR <60 mL/min/1.73 m² represents an additional surgical indication. 5
Obtain 24-hour urine calcium to evaluate for hypercalciuria (>400 mg/24h), which increases risk of nephrolithiasis and represents a surgical indication. 1, 5
Management Algorithm
For Confirmed Primary Hyperparathyroidism:
Parathyroidectomy is the only definitive cure and should be pursued in patients meeting surgical criteria. 1, 2
Surgical indications include: 1, 5
- Corrected serum calcium >1 mg/dL above upper limit of normal
- Marked hypercalciuria (>400 mg/24h)
- eGFR <60 mL/min/1.73 m²
- Presence of nephrolithiasis or nephrocalcinosis
- Age <50 years
- Bone density T-score <-2.5 at any site
Pre-operative Evaluation:
Obtain localization imaging with ultrasound and/or dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT to identify parathyroid adenoma location. 3, 1, 5
Immediate Supportive Management:
Initiate aggressive hydration to achieve urine output of at least 2.5 liters daily, which helps lower calcium levels and prevent nephrolithiasis. 1, 5, 6
Vigorous saline hydration is essential, aiming for urine output of approximately 2 L/day. 6
Avoid thiazide diuretics, as they reduce urinary calcium excretion and worsen hypercalcemia in primary hyperparathyroidism. 5
Loop diuretics should only be used after adequate hydration is achieved, not before correction of hypovolemia. 6
For Severe Hypercalcemia (corrected calcium >13.5 mg/dL):
Consider intravenous pamidronate 90 mg as a single dose over 2-24 hours if symptomatic or awaiting surgery. 6
- Note that pamidronate's safety and efficacy in hyperparathyroidism-related hypercalcemia has not been formally established by FDA, though it is effective for malignancy-associated hypercalcemia. 6
Post-Surgical Monitoring
Monitor ionized calcium every 4-6 hours for the first 48-72 hours after parathyroidectomy, then twice daily until stable. 1, 2, 5
Initiate calcium gluconate infusion if calcium levels fall below normal. 1, 2
Provide oral calcium carbonate and calcitriol when oral intake is possible. 1, 2
Watch for "hungry bone syndrome," where calcium rapidly shifts into bone, causing severe hypocalcemia that may manifest weeks after surgery with symptoms like mouth sores and diffuse skin burning/itching. 1
Critical Pitfalls to Avoid
Do not dismiss "normal" PTH as reassuring in the setting of hypercalcemia—this represents inappropriate PTH secretion and confirms primary hyperparathyroidism. 3, 1, 2
Do not delay surgical referral in patients with marked hypercalciuria and primary hyperparathyroidism, as this leads to progressive renal damage and recurrent nephrolithiasis. 5
Do not supplement with calcium or vitamin D if serum calcium is elevated or high-normal, as this worsens hypercalcemia. 5
Do not use bisphosphonates routinely in patients with eGFR <30 mL/min/1.73 m² without strong clinical rationale. 3