Double adenomas in the pituitary gland are a rare occurrence.
The ability to cure a functioning pituitary neuroendocrine tumor with surgery is dependent on the ability to identify and completely remove the correct adenoma. The relative frequency of each subtype of hormone-secreting adenomas confirmed with magnetic resonance image (MRI), surgery and immunohistochemistry is not defined.
Following PRISMA guidelines, Ogando-Rivas et al. performed a systematic review of PubMed Central, Google Scholar, Scopus Database, Cochrane database and Science Research, using the key-words: “double pituitary neuroendocrine tumors”, “multiple pituitary neuroendocrine tumors” and only papers where multiple or truly separate double pituitary neuroendocrine tumors were identified pre-surgically by MRI and/or confirmed by pathology/immunohistochemistry staining were included.
They reviewed papers from 1975 to 2016 and found 17 cases with two pituitary neuroendocrine tumors and 1 with three pituitary neuroendocrine tumors. The ages ranged from 22 to 67 years old, and there were twelve females and five males. Immunohistochemical staining showed that the most common double pituitary neuroendocrine tumors were growth hormone (GH)- followed by adrenocorticotropic (ACTH)-secreting.
Double pituitary neuroendocrine tumors are rare but most commonly found with GH secreting pituitary neuroendocrine tumor- or ACTH producing pituitary neuroendocrine tumor. It is critical to remove all identified possible adenomas to achieve biochemical cure and clinicians should have heightened sensitivity in patients with acromegaly or Cushing's Disease. 1).
Sano et al. report 6 cases of double pituitary neuroendocrine tumors, which consisted of two histologically and/or immunohistochemically different areas among approximately 450 surgical specimens. Five out of 6 patients were men and the age was ranged between 18 and 61 years old. All these 6 patients presented acromegaly or acrogigantism and hyperprolactinemia was noted in 3 patients. In 2 patients (cases 1 and 2) the two adenomas belonged to different adenoma groups (GH-PRL-TSH group and FSH/LH group), while in the remaining 4 patients (cases 3-6) the two adenomas belonged to the same group (GH-PRL-TSH group). Thus, in all patients at least one of the two adenomas was GH-producing adenoma. Reasons for a high incidence of GH-producing adenomas in surgically resected double pituitary neuroendocrine tumors may include the presence of a variety of histologic subtypes among GH-producing adenomas and the advantage of cytokeratin immunostaining to distinguish these subtypes. In regard to pathogenesis of double pituitary neuroendocrine tumors, adenomas in cases 1 and 2 may be of multicentric occurrence, while those in cases 3-6 may occur through different clonal proliferation within originally one adenoma, resulting in diverse phenotypic expressions. Since there were patients with familial MEN 1 (case 2) and familial pituitary neuroendocrine tumor unrelated MEN 1 (case 3), genetic background should be also considered. Double pituitary neuroendocrine tumors in surgically resected material may not be so infrequent. Further molecular analysis will provide new insights into understanding the pathogenesis of pituitary neuroendocrine tumors and their mechanisms of multidirectional phenotypic diffrentiation 2).
a 51-year-old female with symptoms of both hypercortisolism and acromegaly during the past 2 years. Endocrine evaluation confirmed active acromegaly and revealed adrenocorticotropin hormone-dependent hypercortisolemia. Preoperative magnetic resonance imaging of the pituitary demonstrated separated double microadenomas with different intensity. Immunohistochemical analysis of each separate adenoma confirmed an exact diagnosis. The diagnosis of acromegaly and adrenocorticotropin hormone-dependent Cushing's disease was confirmed.
This is the third reported case in the literature of synchronous clinical manifestation of acromegaly and Cushing's disease. Extensive surgical exploration of the sella must be performed to avoid surgical failures from residual tumor. Immunohistochemical analysis is required to confirm an exact diagnosis for each of the double pituitary neuroendocrine tumors 3)
Miyagi et al. present a quite unique case of double pituitary neuroendocrine tumors associated with persistent trigeminal artery (PTA) treated by endoscopic surgery. To the best of our knowledge, this is the first report in the literature. A 64-year-old woman was referred to our hospital for suspicion of acromegaly. Preoperative magnetic resonance imaging revealed two separate intrasellar masses with intrasellar vascular structure. Right cerebral angiography showed medial-type PTA. The patient underwent endoscopic transsphenoidal surgery and both tumors were resected completely. Postoperative immunohistopathologic examination revealed two histologic types of adenoma: the first tumor was positive for growth hormone (GH), while the second was considered nonfunctioning. Postoperatively, the patient's serum levels of GH and insulin-like growth factor-1 returned to normal. We observed an extremely rare case of double pituitary neuroendocrine tumors associated with PTA. Preoperative neuroimaging and modern endoscopic surgery are valuable to confirm diagnosis of double pituitary neuroendocrine tumors and identify anatomical localization of PTA 4).