Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women with hypercalcemia and parathyroid hormone (PTH) levels that are either frankly elevated or inappropriately normal. It is caused by excessive synthesis and secretion of PTH by one or more of the four parathyroid glands [1], [2].

When PHPT was first described almost a century ago, in the 1930's, the disease was associated with severe hypercalcemia and serious skeletal and renal complications. The indelible association of PHPT with signs (kidney stones and fractures) and symptoms (due to hypercalcemia) persisted until the 1970's when biochemical screening tests became routinely employed, first in the United States and then elsewhere. The clinical phenotype of PHPT changed from overt bone and renal involvement to asymptomatic hypercalcemia. These patients were discovered essentially in the context of biochemical screening and not for any signs or symptoms that would have prompted the health care provider to measure the serum calcium. Four more decades passed when yet another phenotype of PHPT emerged, namely a normocalcemic variant in which albumin-corrected and ionized serum calcium concentrations were persistently normal but the PTH level was persistently elevated. Of course, all known secondary causes for a high PTH have to be ruled out [3]. Not the subject of this discussion, but it is noteworthy that patients have recently been recognized with PHPT but only by pathological examination of parathyroid tissue. The calcium and PTH levels are normal [4], [5].

These different clinical phenotypes of PHPT have raised many issues with regard to parathyroid surgery, the definitive management of the disease. In the hands of expert parathyroid surgeons, parathyroidectomy (PTX) offers very high cure rates [6], but in patients who are completely asymptomatic, a surgical option is not necessarily the obvious one. The normocalcemic variant of PHPT presents yet another challenge in the decision to recommend parathyroid surgery or not. To this end, the Fourth International Workshop on Asymptomatic PHPT [7], recently revisited by others [8], [9], *[10], offers reasonable evidence-based guidance as to who is best advised to have parathyroid surgery.

In this article, we review these different profiles of PHPT with particular emphasis on recent publications.