Endocrine Abstracts

Background: Treatment of primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism due to idiopathic hypercalciuria (SHPT-IH) is markedly different. Nevertheless, differentiating one from another remains a challenge and robust diagnostic tools are lacking. The thiazide challenge test (TCT) has been proposed as a means to aid clinicians in their decision making. However, evidence supporting its use is scarce.

Materials and Methods: We performed a retrospective analysis of 25 patients who underwent a TCT at the Ghent University Hospital (Belgium). We assessed serum and urinary samples before and after testing, clinical and imaging outcomes as well as therapy and long-term follow-up to evaluate the efficacy of the TCT. Based on literature and the calcium load test, other potentially useful parameters were calculated.

Results: Baseline serum albumin-adjusted calcium (AACa) and serum total calcium (TCa) were not significantly different between patients with PHPT and SHPT-IH (2.54 (±0.072) vs 2.55 mmol/l (±0.13) and 2.63 (±0.069) vs 2.64 mmol/l (±0.15) respectively). During the TCT, AACa rose 0.11 mmol/l (±0.10) in patients with PHPT and 0.0071 mmol/l (±0.10) in patients with SHPT-IH. The change in AACa is significantly different between both groups (one-sided P=0.025). A similar result was found for TCa, which rose 0.14 mmol/l (±0.12) in patients with PHPT compared to 0.012 mmol/l (±0.15) in patients with SHPT-IH (one-sided P=0.024). The TCT can detect PHPT based on an increment in AACa of at least 0.10 mmol/l or in TCa of at least 0.13 mmol/l with a calculated sensitivity of 81.8% and a specificity of 77.8%. Serum parathormone (PTH) levels and urinary calcium excretion (UCE) did not differ between patients with PHPT and SHPT-IH (101.7 ng/l (±26.9) vs 105.7 ng/l (±53.8) and 10.9 mmol/24 hours (±3.0) vs 9.4 mmol/24 hours (±3.2) respectively). PTH levels, UCE, the calcium-phosphorous ratio (Ca/P), the PTH-inhibition rate (PTH-IR) and the parathyroid function index (PF-index) did not differ significantly between patients with PHPT and SHPT-IH during the TCT.

Conclusion: The TCT can aid in discriminating patients with PHPT from those with SHPT-IH based on the rise in serum calcium. It can be easily used in all patients with nephrolithiasis or hypercalciuria, an elevated PTH, and a normal to slightly elevated serum calcium. Even though mild hypokalemia occurs frequently, and caution is warranted, no severe side effects were observed. Other variables such as serum PTH, UCE, Ca/P, PTH-IR and PF-index did not differentiate between both groups. Larger prospective trials are necessary to reassess the relevance of different biochemical parameters and the diagnostic potential of the TCT.