Association between Intracellular Calcium Signaling and Tumor Recurrence in Human Non-Functioning Pituitary Adenomas.

Clinically non-functioning pituitary adenomas (CNFPAs) are the second most frequent sellar tumor among studies on community-dwelling adults. They are characterized by the absence of hormonal hypersecretion syndrome, and patients present with compressive symptoms, such as a headache and visual field defects. Immunohistochemically, most CNFPAs are of gonadotrope differentiation, with only a few of them being truly null cell adenomas. Although these tumors express receptors for one or more hypothalamic releasing hormones, to what extent this has an impact on the biological and clinical behavior of these neoplasms remains to be defined. In this research, we evaluated the basal and hypothalamic secretagogue-stimulated intracellular calcium mobilization in 13 CNFPAs, trying to correlate this response to the phenotypic features of the patients. Our results indicate that the recurrence of a CNFPA correlates positively with cellular responsiveness, as measured by spontaneous intracellular calcium activity and the ability to respond to multiple hypothalamic secretagogues. We conclude that this finding may be a useful tool for predicting the clinicopathologic behavior of CNFPAs, by testing the variation of cellular responsiveness to hypothalamic secretagogues.

Is systematic Gadolinium injection relevant during MRI follow-up for non-functioning pituitary macroadenomas?

OBJECTIVE: To compare the performance of coronal contrast-enhanced T1-weighted (ceT1-w) and T2-weighted (T2-w) sequences for diagnosing progression during the MRI follow-up of Non-Functioning Pituitary MacroAdenomas (NFPMAs). PATIENTS AND METHODS: 106 patients, who had at least two MRIs for the follow-up of NFPMA, were enrolled retrospectively. The largest adenoma diameter was measured on coronal ceT1-w sequences and separately on T2-w sequences for all follow-up MRIs. Interobserver variability was also assessed by 2 independent neuroradiologists in a sample series of 100 examinations. Progression was defined by an increase ≥ 2 mm in diameter between 2 MRIs. Progression thresholds of 3 and 4 mm were also tested. The results of ceT1-w and T2-w sequences were analysed for concordance. RESULTS: 93.1% concordance was achieved between ceT1-w and T2-w coronal sequences in 580 follow-up MRIs. In the case of progression detected on at least one sequence, 64.4% concordance was documented for a 2-mm threshold, 87.7% for 3-mm and 97.1% for 4-mm. Discordance was mainly observed on the first postoperative MRI and in case of NFPMAs with multiple recurrences. Kappa was better for diagnosing progression on T2-w than on ceT1-w sequences (0.67 vs. 0.54). It should be noted that 100% agreement was observed between the 2 sequences in the 82 follow-up MRIs of patients with complete surgical resection. CONCLUSION: 93.1% concordance was achieved for coronal ceT1-w and T2-w sequences during the MRI follow-up of NFPMAs, thus challenging systematic injection of gadolinium. If MRI without gadolinium injection is a first-line option, our results suggest that ceT1-w sequences should be reserved for the first postoperative MRI and for the follow-up of aggressive and recurrent NFPMAs.

A Non-Secreting Pituitary Adenoma That Changed to a Prolactinoma.

Pituitary adenomas (PAs) are the third most common brain tumors in adults right after meningiomas and gliomas. Taking into account their hormonal activity in vivo, they can be divided in functioning PAs, which secrete hormones, and nonfunctioning pituitary adenomas (NFPAs), which are not associated with increased hormone secretion. We present the case of a man diagnosed with pituitary apoplexy. A transsphenoidal surgery was performed with subtotal removal of the mass. Pituitary hormones were measured before and after the procedure on several occasions, showing always normal PRL values, so he was diagnosed with a clinically NFPA. Two years later, the patient noticed a visual deficit. A new magnetic resonance imaging study was performed, showing adenomatous recurrence, and the patient underwent a new surgery. After this, hormonal evaluation revealed high levels of PRL on several occasions. After treatment with cabergoline was started, PRL levels normalized, the visual deficit improved, and there was a slight adenoma reduction. This case report represents an exception to the paradigm that in the presence of a macroadenoma and normal PRL levels (avoiding the "hook effect"), a prolactinoma can be discarded. Moreover, it stresses the importance of comprehensive, regular, and lifelong surveillance of patients with NFPAs and the close monitoring of serum PRL.

Post-surgical management of non-functioning pituitary adenoma.

Post-surgical surveillance of non-functioning pituitary adenoma (NFPA) is based on magnetic resonance imaging (MRI) at 3 or 6 months then 1 year. When there is no adenomatous residue, annual surveillance is recommended for 5 years and then at 7, 10 and 15 years. In case of residue or doubtful MRI, prolonged annual surveillance monitors any progression. Reintervention is indicated if complete residue resection is feasible, or for symptomatic optic pathway compression, to create a safety margin between the tumor and the optic pathways ahead of complementary radiation therapy (RT), or in case of post-RT progression. In case of residue, unless the tumor displays elevated growth potential, it is usually recommended to postpone RT until progression is manifest, as efficacy is comparable whether treatment is immediate or postponed. The efficacy of the various RT techniques in terms of tumor volume control is likewise comparable. RT-induced hypopituitarism is frequent, whatever the technique. The choice thus depends basically on residue characteristics: size, delineation, and proximity to neighboring radiation-sensitive structures. Reduced rates of vascular complications and secondary brain tumor can be hoped for with one-dose or hypofractionated stereotactic RT, but there has been insufficient follow-up to provide evidence. Somatostatin analogs and dopaminergic agonists have yet to demonstrate sufficient efficacy. Temozolomide is an option in aggressive NFPA resistant to surgery and RT.

Management of clinically non-functioning pituitary adenoma.

Clinically NFPA is currently the preferred term for designing all the pituitary adenomas which are not hormonally active (in other words, not associated with clinical syndromes such as amenorrhea-galactorrhea in the context of prolactinomas, acromegaly, Cushing's disease or hyperthyroidism secondary to TSH-secreting adenomas). They account for 15-30% of pituitary adenomas. Diagnosis is usually made either in the context of mass effect due to a macroadenoma or, increasingly, fortuitously during imaging performed for some unrelated purpose; the latter case is known as pituitary incidentaloma. Surgery is indisputably indicated in case of tumoral syndrome, but other aspects of NFPA (hormonal work-up, follow-up, and especially postoperative follow-up, management of remnant or recurrence, the special case of incidentaloma, or apoplexy) remain controversial. The French Endocrinology Society (SFE) therefore set up an expert working group of endocrinologists, neurosurgeons, ophthalmologists, neuroradiologists, pathologists and biologists to draw up guidelines, at the 2012 SFE Congress in Toulouse, France. The present article presents the guidelines suggested by this group of French-speaking experts.