Paediatric and Young Adult Manifestations and Outcomes of Multiple Endocrine Neoplasia Type 1

Madhuni Herath; Venkat Parameswaran; Michael Thompson; Michelle Williams; John Burgess

Disclosures

Clin Endocrinol. 2019;91(5):633-638. 

In This Article

Results

We identified 180 patients (103 female, 57.2%) with MEN 1 born between 1843 and 2018 with a median birth year 1961.

Retrospective Group (DOB < 1965), n = 96

The comparative survival data for 96 MEN 1 (57.3% female)–positive and 120 of their MEN 1 (48.3% female)–negative offspring of MEN 1–positive patient siblings born between 1843 and 1964 were analysed.

Survival Analysis. There was no significant difference in the number of MEN 1–positive to MEN 1–negative offspring who reached early adulthood (2.26 ± 1.94 vs 2.88 ± 2.24, P = .18) when compared on a per parent basis. Of the 216 offspring who lived until at least 22 years of age, 96 were MEN 1–positive and 120 were MEN 1–negative compared to a theoretical frequency of 108 each (P = .24).

Phenotypic Presentation. Seven of 96 patients were diagnosed with an MEN 1–related phenotype prior to age 22 years: primary hyperparathyroidism (n = 3), insulinoma (n = 2) and prolactinoma (n = 2). Symptomatic presentations prior to age 22 years occurred in six (6.3%) patients and related to functional parathyroid, pituitary and pancreatic diseases. The three patients with PHPT were diagnosed at 12, 20 and 21 years of age, and one with symptomatic renal calculi at age 12 years for which PHPT was managed successfully with parathyroidectomy. Two patients were diagnosed with symptomatic insulinoma (aged 19 and 20 years) and successfully treated by resection of a benign pancreatic insulinoma. Two patients presented with amenorrhoea and were found to have hyperprolactinaemia, one macroadenoma and one microadenoma at age 21 and 16 years, respectively. Both were successfully treated with bromocriptine. One additional patient died from intracranial haemorrhage possibly related to pituitary apoplexy aged 9 years. No cases of gastrinoma or adrenal disease were identified.

Prospective Group (DOB ≥ 1965) n = 84

Between 1965 and 2018, there were 84 identified patients with MEN 1 (57.1% female, median birth year 1983). No childhood mortality was identified in this group over the period 1965–2018. Informative screening data on parathyroid, pituitary and enteropancreatic pathology were available for 70 (83.3%) patients of whom 62.1% were female. There were 46 individuals (54.8%) diagnosed with phenotypic disease prior to 22 years of age: PHPT (n = 42), pNEN (n = 13) and pituitary (n = 13) (Table 1). Thirteen (15.5%) of these patients were symptomatic prior to age 22 years. The youngest age for diagnosed phenotypic disease was eight years for PHPT, 13 years for pNEN and 12 years for pituitary disease. One case of symptomatic atypical bronchopulmonary carcinoid–related mass effect was diagnosed at age 20 years and successfully managed with lobectomy. No cases of gastrinoma or adrenal disease were identified. There were 51 patients with screening data for all three of pituitary, pancreatic and parathyroid assessment, of which 17.6% of patients were diagnosed with all three manifestations.

Parathyroid Disease. Screening identified PHPT in 42 (50%) patients (64.3% female). In 28 (33.3%) patients, PHPT was either the initial manifestation or identified synchronously with other MEN 1 manifestation in six patients (mean age at diagnosis was 17.2 ± 3.3 years, range: 8–21 years). The maximum recorded serum ionized calcium was 1.58 mmol/L in a 13-year-old female patient. No patients exhibited renal dysfunction due to hypercalcaemia. Sixteen patients underwent parathyroidectomy: one underwent total parathyroidectomy, 11 underwent resection of 3.5 parathyroid glands with concurrent parathyroid autotransplantation, and four others underwent resection of <3.5 parathyroid glands. Six patients (37.5%) undergoing parathyroidectomy achieved initial normocalcaemia (although recurrent PHPT occurred in two cases within four years). Six (37.5%) experienced postoperative hypoparathyroidism persisting for <12 months.

Pituitary Disease. Biochemical pituitary screening was undertaken in 56 individuals and identified 11 (19.6%) with pathology: nine with hyperprolactinaemia and two with Cushing's disease. Structural pituitary imaging was performed in 38 patients, with disease identified in thirteen (34.2%). Four were diagnosed with macroadenoma, six with microadenomas and three with nonfunctioning pituitary microadenomas. Dopamine agonists were effective in six of the eight patients with prolactinoma, and transsphenoidal surgery was required in one patient with macroprolactinoma as well as the patients with microadenoma associated with Cushing's disease. The three patients with nonfunctioning pituitary adenomas did not require intervention.

Enteropancreatic Neuroendocrine Tumours. Pancreatic NENs were identified in 12 of the 45 patients (26.7%) undergoing abdominal imaging. Seven patients had pancreatic lesions <1 cm in diameter, three of which were symptomatic insulinoma that were successfully treated surgically (two patients were diagnosed at 14 years of age, while the third was diagnosed at 18 years of age). Three patients had benign pNENs between 1.1 and 2 cm in diameter that were non-secretory and managed surgically, and two patients had pancreatic lesions >2 cm diameter, one of which was resected and found to have perineural invasion. No cases of gastrinoma were diagnosed.

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