Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome (MEN1): a case-control study in a series of 77 patients versus 2509 non-MEN1 patients.

Patients affected by the multiple endocrine neoplasia type I syndrome (MEN1) display a high incidence of pituitary adenomas, though it is still unknown whether these pituitary tumors have specific pathologic features that would distinguish them from sporadic pituitary adenomas. Pituitary tissue specimens of 77 MEN1 patients from the GTE (Groupe d'étude des Tumeurs Endocrines) register were compared with unselected 2509 non-MEN1 sporadic pituitary tumors and also to a control subgroup of 296 cases, where 1 MEN1 tumor was matched with 4 sporadic tumors of the same hormonal immunoprofile. Sex, age, size, and invasiveness of tumors, and menin gene mutations were documented. Histologic analysis took into account 33 items, including immunocytochemical data, the proliferative marker Ki-67, and an examination of the juxtatumoral pituitary. MEN1 tumors were significantly larger and more often invasive by histology. MEN1 patients with large pituitary tumors (grade IV) were younger than non-MEN1 patients. MEN1 tumors had no other characteristic histologic features and no predominance of any one hormone producing subtype. However, plurihormonal adenomas versus monohormonal and nonimmunoreactive adenomas were more frequent in MEN1 tumors (39%) than in the control non-MEN1 group (P = 0.001). Especially, the growth hormone and prolactin plurihormonality with unusual association with follicle-stimulating hormone, luteinizing hormone, or adrenocorticotropic hormone was more frequent in MEN1 tumors. In addition, multiple adenomas were significantly more frequent (4% vs. 0.1%; P < 0.0001), especially prolactin-adrenocorticotropic hormone. Somatotroph hyperplasia, with or without a microadenoma was found in only 3 MEN1 patients, with growth hormone-releasing hormone hypersecretion by a pancreatic tumor in 2 of them. All types of mutation were observed, including frameshifts, nonsenses, missenses, and 1 case of germline MEN1 encompassing large deletion, strongly suggesting the absence of any phenotype-genotype correlation.

Accuracy of bilateral inferior petrosal or cavernous sinuses sampling in predicting the lateralization of Cushing's disease pituitary microadenoma: influence of catheter position and anatomy of venous drainage.

Bilateral inferior petrosal sinus sampling (BIPSS) is the most reliable procedure for distinguishing Cushing's disease from ectopic ACTH secretion. However, it is less reliable at predicting the lateralization of the pituitary corticotroph microadenoma. We sought to determine whether this could be improved by taking into account the pattern of venous drainage and the precise location of the catheters. We retrospectively studied data from 86 patients who underwent BIPSS. Cushing's disease was predicted in 74 patients, of whom 69 underwent transsphenoidal surgery. Surgical cure was obtained in 65 patients, with identification of a corticotroph microadenoma in 58 cases. In 49 patients the location of the microadenoma predicted by the intersinus ACTH gradient could be compared with the pathologist's data. BIPSS accurately predicted the lateralization of the microadenoma in only 57% of these patients. Prediction was improved to 71% when both venograms and catheters were symmetric (35 patients). In this subgroup accuracy was 86% in patients with both catheters in the inferior petrosal sinuses compared with 50% in patients with both catheters in the cavernous sinuses (CS). Two transient sixth nerve palsies occurred during CS catheterization. Our data suggest that BIPSS results are much improved when venous drainage is symmetric. Catheterization of CS did not improve the results and was less safe.