This article aims to discuss the diagnostic approach to increased serum parathyroid hormone (PTH) levels in normocalcemic, normophosphatemic patients. This biological disorder is commonly detected in routine practice, especially given that the established PTH reference values used by clinical laboratories refer to subjects with adequate vitamin D levels and a normal renal function. The first diagnostic step consists in ruling out a cause of secondary hyperparathyroidism (SHPT). Among these, the most frequent include vitamin D deficiency, very low calcium intake, impaired renal function, malabsorption, drugs interfering with calcium/bone metabolism (e.g., lithium salts and antiresorptive therapies for osteoporosis), and renal leak hypercalciuria. If no cause of SHPT is found, the diagnosis of normocalcemic primary hyperparathyroidism (PHPT) should be considered. A calcium load test is a very useful tool for diagnosing this condition, which is characterized by a serum PTH being not sufficiently decreased while calcemia rises frankly above the upper normal limit. In normocalcemic patients with hypercalciuria and high serum PTH levels, a thiazide challenge test may help differentiate SHPT due to a renal calcium leak from normocalcemic PHPT. In addition to these diagnostic considerations, the article also discusses the advantages and difficulties of measuring and interpreting ionized calcemia and 24-hour calciuria.
Parathyroid hormone, vitamin D, primary hyperparathyroidism, secondary hyperparathyroidism, hypercalciuriamellitus, cardiovascular diseases