Background
Multiple Endocrine Neoplasia type 1 (MEN 1) is an autosomal dominant neoplastic disorder resulting from inactivating mutations of the MEN1 gene. There is significant variability in phenotypic presentation, however the majority of patients with MEN 1 will ultimately develop primary hyperparathyroidism.
Aim
To determine the age-related progression and natural history of untreated primary hyperparathyroidism in MEN 1 patients.
Methods
A retrospective cohort study of 144 MEN 1 patients with a confirmed MEN 1 genotype undergoing biochemical screening for parathyroid function prior to parathyroidectomy. Data for serum calcium, parathyroid hormone (PTH), phosphate, magnesium and alkaline phosphatase (ALP) were analysed in 5-year age categories spanning birth to 50 years of age. The peak serum calcium in conjunction with the paired serum PTH concentration and the serum phosphate, magnesium and ALP concentrations were determined for each patient within each age category.
Results
Serum calcium was elevated in 81% of cases by 20-25 years. The mean serum calcium in this cohort reached a peak in the fourth decade of life. The corresponding serum PTH progressively increased over time, with the calcium:PTH homeostatic ratio showing a declining trend with advancing age, suggestive of progressively increasing parathyroid hormone resistance. Serum phosphate and ALP exhibited a decline from childhood levels to the normal adult range during the second decade of life in the majority of patients, though ALP showed a late rise from 40-44.9 years. Serum magnesium remained within normal limits in all age groups, and was stable over time.
Conclusions
The prevalence of MEN 1-related primary hyperparathyroidism increases during adolescence and early adulthood, with maximal serum calcium levels achieved by the fourth decade of life in the majority of patients. Advancing age was associated with evidence of increasing PTH resistance.