Asymptomatic primary hyperparathyroidism: new issues and new questions--bridging the past with the future

The earliest clinical descriptions of PHPT pointed to an inexorably progressive disorder. Now, in many asymptomatic individuals who do not meet any surgical guidelines. PHPT in general, does not seem to be progressive. Most asymptomatic patients seem to remain asymptomatic over many years of observation. In those with major clinical manifestations, nephrolithiasis is by far the most common. In these patients, surgery is clearly indicated. Bone densitometry is an indispensable component of the evaluation as well as in monitoring because there is evidence of bone involvement in most patients. This contrasts with the skeletal X-ray, which is invariably negative. Nevertheless, patients with PHPT can show a bone mass measurement either at the cortical or cancellous skeleton that is more than 2 SDs below age- and sex-matched control subjects. Bone density, serum calcium concentration, and/or urinary calcium excretion per se can show evidence for progression in as many as 25% of patients with asymptomatic PHPT. There are newer pharmacologic approaches to PHPT that are the subject of intense investigation. The bisphosphonates and the calcimimetics show particular promise in this regard. Unanswered are such questions as whether the lower bone density in the milder patients will increase substantially as in those who undergo successful parathyroidectomy and whether fracture risk would therefore be reduced. Can medical therapy reduce serum calcium. parathyroid hormone levels, and other biochemical indices of PHPT? Can medical therapy improve bone density without the need for surgery. The issues outlined in this presentation and further amplified in other presentations given in this workshop lead to a series of questions that, in turn, may lead to modified guidelines for the management of these patients. The questions are as follows. (1) Should there be any changes in diagnostic criteria for PHPT? (2) Should the guidelines for surgery in PHPT be changed in light of new data over the past decade? What should those guidelines be? (3) At present, is there sufficient evidence of clinical benefit with specific medical therapies to recommend their use? In which patients? (4) Can some patients be followed without surgery? If so, how should they be monitored? (5) When surgery is the preferred option, what are the relative merits of minimally invasive procedures compared with more conventional surgery? (6) What is the role of localization techniques in identifying abnormal parathyroid tissue preoperatively and intraoperatively? Are they sufficiently helpful and cost effective to warrant their use in all patients who undergo parathyroid surgery? If not, in what patients should they be recommended? (7) What items should be placed on the research agenda for PHPT over the next decade?