Multiple endocrine neoplasia syndrome refers to a clinical syndrome in which two (or more) endocrine adenomas or hyperplasia occur simultaneously in the same patient, which is a autosomal dominant disease. There is a familial incidence, and no significant difference in the prevalence of men and women. In the past, this disease was called multiple endocrine adenoma (MEA), but some of the lesions were confirmed by clinical and pathological examination to be malignant or hyperplastic, such as medullary thyroid carcinoma, islet cell carcinoma and parathyroid hyperplasia. Therefore, the disease is now called multiple endocrine neoplasia syndrome. Clinically, according to the affected glands, it is divided into 3 types: MEN-1 type, MEN-2 type A, and MEN-2 type B. In addition, there are still MEN-1 and MEN-2 overlapping types. The MEN-1 was first reported by Wermer in 1954, so it is also known as Wermer syndrome, which mainly involves the parathyroid gland, the intestine-pancreas and the anterior pituitary. MEN-2 type A, also known as SIpple syndrome, is mainly characterized by medullary thyroid carcinoma, pheochromocytoma and parathyroid adenoma. In addition to the MEN-2 type A, the MEN-2 type B also has mucosal neuromas (lingual, lip, eyelid, gastrointestinal tract) and class of Marfan syndrome.
Etiology and Pathogenesis
The onset of multiple endocrine neoplasia (MEN) syndrome type 1 is associated with gene mutation located on the long arm of chromosome 11 (11q13). This gene contains 10 exons and is a tumor suppressor gene, encoding a menin protein consisting of 610 amino acids. The occurrence of MEN-1 requires mutation of both alleles at this site, and the patient acquires a mutant allele by inheritance, while the cells at the tumor site lose another allele by somatic mutation. Tumor suppressor genes play an important role in regulating cell growth, differentiation, and death. Mutations in both alleles cause cell growth to be out of control, and lead to tumor genesis. According to the above characteristics, MEN-1 is autosomal dominant in hereditary way, but it is recessive in the mechanism of tumor formation, and both alleles need to be mutated.
Case Study
The etiology of multiple endocrine neoplasia is complicated, and the involvement of multiple glands can be simultaneously or sequentially. Some patients often have other glandular lesions after several years of lesions in the first gland, which makes the diagnosis difficult and easily missed diagnosis or misdiagnosis. For patients with an endocrine adenoma, the possibility of MEN should be considered and the medical history should be detailed. In particular, attention should be paid to the relevant endocrine gland hormones and imaging examinations for common glands to avoid missed diagnosis of affected organ lesions.so as to be more thoroughly treated. So far, surgical removal of the tumor remains the first choice for the treatment of MEN. Therefore, the sooner the MEN is detected, the easier it is to treat. The detection of MEN in advance is also the focus of our research. Because 68Galium-DOTATATE PET/CT is used to detect neuroendocrine tumors (NETs) most accurately. In the study to be introduced next, we will introduce 68Galium-DOTATATE PET/CT to screen and check MEN1.
Design:
We prospectively compared the accuracy of 68Galium-DOTATATE PET/CT, 111In-pentetreotide single-photon emission CT (SPECT/CT), and anatomic imaging with CT scan in addition to clinical and biochemical screening in patients with MEN1.
Participants:
A total of 26 patients with a known diagnosis of MEN1 were enrolled with a mean age of 42 years old. Of these 26 patients, 14 had previous history of histologically proven NET (7 nonfunctioning pancreatic NETs [PNETs]; 3 insulinoma; 3 gastrinoma; 1 thymic carcinoid).
Length of Enrollment Period:
Four weeks
Statistical analyses
Statistical analyses were performed using GraphPad Prism 5 software (GraphPad software). Data were analyzed using Pearson and Spearman correlation tests. Two-tailed p < 0.05 was considered statistically significant. Data were presented as mean ± standard deviation (SD) or median (range).
Results:
The study of cohort demographics, clinical characteristics, and biochemical profiles are summarized in table1. 68Galium-DOTATATE PET/CT detected 107 lesions; 111In-pentetreotide single-photon emission CT (SPECT/CT) detected 33 lesions; and CT scan detected 48 lesions. Lesions detected on 68Galium-DOTATATE PET/CT had high standard uptake value (SUV)max (median SUV max=72.8[range 19 to 191]). In 7 of the 26 patients (27%), 68Galium-DOTATATE PET/CT was positive, with a negative 111In-pentetreotide SPECT/CT, and in 10 patients (38.5%), additional metastases were detected (range 0.3 cm to 1.5 cm). in 8 of the 26 patients (31%), there was a change in management recommendations as a result of the findings on 68Galium-DOTATATE PET/CT that were not seen on 111In-pentetreotide SPECT/CT and CT scan.
Table 1. Clinical and biochemical profile of MEN1 study cohort
The study of cohort demographics, clinical characteristics, and biochemical profiles are summarized in Table 1. The median chromogranin A level was 284 ng/mL (range 23 to 18,710 ng/mL; normal < 93 ng/mL), the median fasting gastrin level was 194 pg/mL (range 10 to 17,290 pg/mL; normal <100 pg/mL), and the median pancreatic polypeptide was 225 pg/mL (range 61 to 2,500 pg/mL; normal < 291 pg/mL).
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References:
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2. van Asselt Sophie J, Brouwers Adrienne H, van Dullemen Hendrik M, et al. (2015) ‘EUS is superior for detection of pancreatic lesions compared with standard imaging in patients with multiple endocrine neoplasia type 1’, Gastrointest. Endosc, 81(1):159-167.e2.
3. Sadowski Samira M, Millo Corina, Cottle-Delisle Candice, et al. (2015) ‘Results of (68) Gallium-DOTATATE PET/CT Scanning in Patients with Multiple Endocrine Neoplasia Type 1’, J. Am. Coll. Surg., 221(2):509-17.
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