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 to aid clinicians in their decision making. However, evidence supporting its use is non-existent.
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, other potentially useful parameters were calculated.
Results: The TCT was considered inconclusive in three cases (12%). PHPT was diagnosed in thirteen (52%), and SHPT in nine (36%) patients. Baseline serum albumin-adjusted calcium (AACa) and serum total calcium (TCa) were similar between patients with PHPT and SHPT-IH. During the TCT, albumin-adjusted calcium (AACa) rose 0,11mmol/l (±0,10) in patients with PHPT and 0,0071mmol/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 serum total calcium (TCa), which rose 0,14mmol/l (±0,12) in patients with PHPT compared to 0,012mmol/l (±0,15) in patients with SHPT-IH (one-sided P=0,024). The TCT has a calculated sensitivity of 81,8%, a specificity of 77,8% and a likelihood ratio of 3,68. We observed no differences in serum parathormone (PTH) levels and urinary calcium excretion (UCE) between patients with PHPT and SHPT-IH (101,7ng/l (±26,9) vs. 105,7ng/l (±53,8) and 10,9mmol/24 hours (±3,0) vs. 9,4mmol/24 hours (±3,2) respectively). 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. Mean serum potassium levels declined from 4,6mmol/l (±0,4) to 3,8mmol/l (±0,4) during the TCT (P<0,001). No severe hypokalemia (<3,0mmol/l) was observed. Creatinine values did not change significantly 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. Notwithstanding mild hypokalemia occurs frequently, we observed no severe side effects. 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.