Multiple Pituitary Adenomas: A Systematic Review

Abstract

PubMed, Scopus, and Web of Science Core Collection databases were systematically searched for studies reporting synchronous double or multiple pituitary adenomas (MPA), a rare clinical condition, with a vague pathogenesis. Multiple adenomas of the pituitary gland are referred to as morphologically and/or immunocytochemically distinct tumors that are frequently small-sized and hormonally non-functional, to account for the low detection rate. There is no general agreement on how to classify MPA, various criteria, such as tumor contiguity, immunoreactivity, and clonality analysis are being used. Among the component tumors, prolactin (PRL)-immunopositive adenomas are highly prevalent, albeit mute in the majority of cases. The most frequent clinical presentation of MPA is Cushing’s syndrome, given the fact that in more than 50% of reported cases at least one lesion stains for adrenocorticotrophic hormone (ACTH). Plurihormonal hyperactivity may be diagnosed in a patient with MPA when more than one tumor is clinically active (e.g., ACTH and PRL) or in cases with at least one composite tumor (e.g., GH and PRL), to complicate the clinical scenario. Specific challenges associated with MPA include high surgical failure rates, enforcing second-look surgery in certain cases, and difficult preoperative neuroradiological imaging evaluation, with an overall sensitivity of only 25% for magnetic resonance imaging to detect distinct multiple tumors. Alternatively, minor pituitary imaging abnormalities may raise suspicion, as these are not uncommon. Postoperative immunohistochemistry is mandatory and in conjunction to electron microscopy scanning and testing for transcription factors (i.e., Pit-1, T-pit, and SF-1) accurately define and classify the distinct cytodifferentiation of MPA.

Kisspeptin and RFRP-3 differentially regulate food intake and metabolic neuropeptides in the female desert jerboa

“…We also report that this robust orexigenic effect is associated with an increase in the mRNA level of the orexigenic Npy together with a concomitant decrease in the mRNA level of the anorexigenic Pomc . Our finding of an orexigenic role of RFRP-3 in the jerboa is in agreement with previous results obtained in rats, mice, sheep and non-human primates21222324, but our data are the first to demonstrate that this metabolic effect might involve an increase in Npy and decrease in Pomc gene regulation. This finding is supported by earlier reports of the presence of the RFRP receptor and RFRP fiber terminals in the ARC of rodents84249 with some studies showing that RFRP terminals are in close apposition to NPY3050 and POMC30 neurons.…”

“…RFRP-3 increases food intake in rodents, sheep and non-human primates21222324 while Kp displays an anorexigenic effect in overnight fasted mice25. In line with these feeding behaviors, other studies indicate that both peptides may regulate POMC or NPY arcuate neurons.…”

“…The Rfrp gene encodes different RFRPs among which RFRP-3 regulates reproduction in various mammalian species (for review see refs 2,48). Here, we reveal that RFRP-3 exerts a potent orexigenic effect in the female jerboa as central injection of the peptide induced a marked increase in food intake as early as 1 h and up to 24 h post-injection, with no difference between spring and autumn.…”

Effectiveness of Bilateral Inferior Petrosal Sinuses Sampling in Tumor Lateralization: Intraoperative Findings and Postoperative Results

“…12 Nevertheless, a significant number of patients had a clearly lateralized sampling and were found to have a contralateral macroscopic lesion 20 or as described previously in several case reports, patients may have several lesions. 21,22 However, in patients with a high burden of disease in whom no lesion was found and had been on one or more pharmacological treatment trials, BIPSS and a very thorough microsurgical dissection were shown to have a 71% cure rate at 12 months. Although one would like this figure to be higher, having a two-thirds cure rate in a very challenging disease where several other alternatives that have failed must be taken into account and considered appropriately.…”

Multiple Pituitary Adenomas with Functional Follicle-Stimulating Hormone Secretion Leading to Ovarian Hyperstimulation Syndrome

“…Prior analysis of incidentally found multiple pituitary adenomas has demonstrated that FSH and null cell tumors were common (12). However, there have been no reported cases of multiple pituitary adenomas with a functional FSH component in the literature.…”