Management and Long-Term Follow-Up of Hyperparathyroidism in Multiple Endocrine Neoplasia Type 1: Single Center Experience

Abstract

Background: Primary hyperparathyroidism (PHPT) in the most common and earliest manifestation of multiple endocrine neoplasia type-1 (MEN1). Epidemiological data have been reported in MEN1 patients but data on long-term follow-up focusing on PHPT are scarce. Methods: In this retrospective cohort study, we included patients diagnosed with MEN1-related PHPT that were under regular follow-up in our institution. Results: Data on 68 patients (39 males), with a mean age at MEN1-diagnosis of 39 ± 13.06 years, were analyzed. Pancreatic neuroendocrine tumors were encountered in 82% (71% nonsecreting) followed by pituitary adenomas in 66% (49% nonsecreting). Mean age at PHPT diagnosis was 35.2 ± 4.0 years. Parathyroidectomy was performed in 57 patients (82.3%), of whom 56% achieved long-term remission, while 12.2% and 31.5% had persistent and recurrent disease, respectively (median follow-up of 4 years; range 1–21 years). Cinacalcet restored serum calcium levels in 33.8%, both as first and as a second line treatment. Permanent hypoparathyroidism occurred in 19.2%. MEN1 pathogenic variants were identified in 77.2% of the tested individuals, but no genotype-phenotype associations were reported. Conclusions: MEN1-related PHPT involves a multiglandular disease and its management remains a therapeutic challenge, as recurrent disease can develop even after 20 years of follow-up. Prolonged follow-up of these patients at referral centers is critical for their optimal management.

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance

“…The studies' overview (n = 7) showed cohorts that primarily included patients with MEN1-related insulinomas (n = 2) or MEN1-associated primary hyperparathyroidism (n = 2) or analyses of genetic testing in MEN1 (n = 3), a wide spectrum of objectives being registered across these data. They were all retrospective studies enrolling between 17 and 517 individuals per study, for a total of 877 MEN1 subjects [109][110][111][112][113][114][115] (Table 5). PHP with single-gland involvement: 47% (N1) versus 0% (N2)…”

“…MEN1-associated parathyroid NETs (N = 585), as the most common and usually the first clinical element in MEN1, were meticulously addressed from the surgical perspective and post-parathyroidectomy outcome since this step of management is essential for an overall better prognosis. For instance, Yavropoulou et al [ 112 ] showed in 68 patients with MEN1-related primary hyperparathyroidism that the average age at syndrome recognition was 39 ± 13.06 years and at parathyroid condition confirmation, 35.2 ± 4 years. The surgical outcome for those 82% of subjects who underwent parathyroidectomy included the following: long-term remission (56%), recurrent hyperparathyroidism (31.5%), persistent hyperparathyroidism (12.2%), and permanent hypoparathyroidism (19.2%) for a 4-year median follow-up.…”

“…A total of 82% of them were associated with pancreatic NETs (71% of these tumors being hormonally non-functioning), and 66% of the individuals were identified with a pituitary NET (almost half being non-functioning). Among the persons who had a MEN1 genetic analysis, 77% harbored pathogenic variants without genotype/phenotype correlation [ 112 ].…”

“…Clinical studies introducing MEN1-related pancreatic NETs associated with specific data regarding the presence of primary hyperparathyroidism (within our timeframe and methods of research)[109][110][111][112][113][114][115].…”