The aim of this article is to discuss the diagnostic approach of an increased serum PTH concentration in a normocalcemic, normophosphatemic patient. Detection of this
biological presentation is frequent in routine practice all the more that PTH reference values established in
vitamin D replete subjects with a normal renal function are used by the clinical laboratories. The first step in this diagnostic approach will be to rule out a cause of
secondary hyperparathyroidism (SHPT). Among these, the most frequent are
vitamin D deficiency, very low
calcium intake, impaired renal function, malabsorptions, drugs interfering with
calcium/bone metabolism, such as
lithium salts and antiresorptive
osteoporosis therapies,
hypercalciuria due to a renal
calcium leak. If no cause of SHPT are evidenced, the diagnosis of normocalcemic
primary hyperparathyroidism (PHPT) should be considered. A
calcium load test is a very useful tool for this diagnosis if it shows that serum PTH is not sufficiently decreased when calcemia rises frankly above the upper normal limit. In a normocalcemic patient with
hypercalciuria and a high serum PTH concentration, a
thiazide challenge test may help to differentiate SHPT due to a renal
calcium leak from normocalcemic PHPT. Beyond the discussion of this diagnostic flowchart, we also discuss some points about the merits and the difficulties of measuring and interpreting ionized calcemia and 24-h calciuria.