BIOCHEMICAL DYNAMICS OF UNTREATED PRIMARY HYPERPARATHYROIDISM: AN OBSERVATIONAL STUDY.

OBJECTIVE: The natural biochemical history of untreated primary hyperparathyroidism (PHPT) is poorly understood. The purpose of this study was to determine the extent of biochemical fluctuations in patients with PHPT.

DESIGN: Retrospective cohort study from January 1, 1995 to December 31, 2014.

METHODS: Serum calcium and parathyroid hormone (PTH) levels in patients with classic (Ca > 10.5 mg/dL, PTH > 65 pg/mL) and non-classic (Ca > 10.5 mg/dL, PTH 40-65 pg/mL) PHPT were followed longitudinally at one, two, and five years. Biochemical profiles in follow-up were ranked in descending biochemical severity as classic PHPT, non-classic PHPT, normal calcium with elevated PTH (Ca < 10.5 mg/dL, PTH > 65 pg/mL), possible PHPT (Ca > 10.5 mg/dL, PTH 21-40 pg/mL), or absent PHPT (Ca > 10.5 mg/dL, PTH < 21 pg/mL or Ca <10.5 mg/dL, PTH < 65 pg/mL).

RESULTS: Of 10,598 patients, 1,570 were treated with parathyroidectomy (n=1433) or medications (n=137), and 4,367 were censored due to study closure, disenrollment, or death. In the remaining 4,661 untreated patients with five years of follow-up, 235 (5.0%) progressed to a state of increased biochemical severity, whereas 972 (20.8%) remained the same, and 3,454 (74.1%) regressed to milder biochemical states. In 2,522 untreated patients with classic PHPT, patients most frequently transitioned to the normal calcium with elevated PTH group (n=1,257, 49.8%). In 2,139 untreated patients with non-classic PHPT, patients most frequently transitioned to the absent PHPT group (n=1,354, 63.3%).

CONCLUSIONS: PHPT is a biochemically dynamic disease with significant numbers of patients exhibiting both increases and decreases in biochemical severity.