Adrenal Involvement in Multiple Endocrine Neoplasia Type 1

Abstract

Adrenal lesions belong to the spectrum of multiple endocrine neoplasia type 1 (MEN-1) syndrome. However, the prevalence of adrenal involvement, the characteristics, and the clinical management of adrenal lesions have not yet been clearly defined. A total of 66 patients with confirmed MEN1 germline mutations and 1 additional patient with typical manifestations in three organ systems were monitored in a regular screening program that included evaluation of the adrenals (median follow-up 96 months; range 12 to 300 months). Age at the diagnosis of MEN-1 and of adrenal tumors and the clinical characteristics, genotype, treatment, and follow-up of adrenal disease were analyzed. Adrenal lesions were identified in 18 of 67 (26.8%) MEN-1 patients and were diagnosed 5 years later than MEN-1. The median tumor diameter at diagnosis was 3.0 cm (range 1.2-15.0 cm), with most tumors being 3 cm or smaller. Eight patients had bilateral tumors. Ten patients had nonfunctional benign tumors, three had benign adrenal Cushing syndrome, and one patient had a pheochromocytoma. Four patients developed adrenocortical carcinomas (ACCs), three of which were functional. Nine adrenalectomies and one subtotal adrenalectomy were performed in six patients. Three patients with ACC died owing to the tumor. Patients with mutations in exons 2 and 10 developed adrenal tumors significantly more often than patients with other mutations (p <0.01). Adrenal tumors are a common feature of MEN-1 but occur later in the course of the disease. The lesions are often small and nonfunctional and can therefore be managed by close surveillance; others have significant malignant potential and should be considered for surgery when they are 3 cm or larger.

The appearance of the adrenal glands on computed tomography in multiple endocrine neoplasia type 1

“…Where hyperplasia is suspected, measurements have not been performed, nor have the size of the glands been compared with normal values, making the changes arbitrary (3,4). Interestingly, those benign adrenal lesions that have been studied do not show inactivation of the remaining non-mutated menin gene, suggesting that they do not fit a classical two-hit theory of neoplasia (4).…”

“…We have documented the presence, number and size of any adrenal nodules and compared these findings with those described in the normal population (7). The majority of adrenal lesions in MEN1 have previously been reported to be non-functioning (3,8,9). We reviewed the patients' serum cortisol secretory dynamics and sought potential correlations with adrenal morphology.…”

15 YEARS OF PARAGANGLIOMA: The association of pituitary adenomas and phaeochromocytomas or paragangliomas

“…Although described, the association of phaeos with MEN1 is rare, being present in !1% of large series (Skogseid et al 1992, Burgess et al 1996, Trump et al 1996, Langer et al 2002, Gatta-Cherifi et al 2012. The prevalence of phaeos is significantly higher, up to 7%, in the Men1 heterozygous knockout mouse model (Crabtree et al 2001).…”

“…Only four cases of co-existing phaeo/PGL and PA have been reported in patients with MEN1 mutations (Table 1; Dackiw et al 1999, Langer et al 2002, Jeong et al 2014 Dénes et al 2015); three had a phaeo, one had an abdominal PGL. Loss of heterozygosity at the MEN1 locus combined with absent menin staining in the phaeo sample was demonstrated in one of these cases ( Fig.…”

A new double substitution mutation in the MEN1 gene: a limited penetrance and a specific phenotype

“…Most of the MEN1-associated adrenal adenomas are reported to be non-secreting and stable during follow-up. 20 …”