Highlights d Molecular classes of PitNETs are identified by integrated pangenomic analyses d PitNETs molecular classification mainly reflects pituitary lineage, driven by PIT1 d Gonadotroph signatures are found in some corticotroph and somatotroph PitNETs d USP8-mutated corticotroph PitNETs correspond to a group with limited aggressiveness

X-linked acro-gigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and a microduplication in chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in 2 families was dominant with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2–3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight SDS score of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF-1 and prolactin, usually due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high somatostatin receptor subtype-2 expression in tumor tissue. Postoperative adjuvant pegvisomant achieved control of IGF-1 all 5 cases in which it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management.

Temozolomide treatment may be an effective option for some aggressive pituitary tumors or carcinomas. Response to a trial of three cycles of treatment seems sufficient to identify responders and more reliable than patient MGMT status.

This large prospective cohort study confirms the very low prevalence of germline AIP mutations in patients with apparently sporadic pituitary adenomas. We propose to limit AIP testing to patients diagnosed before age 40 yr with apparently sporadic large pituitary adenomas, especially GH- or PRL-secreting adenomas.

Context: Adequate postoperative management of nonfunctioning pituitary macroadenomas (NFMAs) remains a challenge for the clinician. Objective: To identify predictive factors of NFMA relapse after initial surgery. Patients and methods: This retrospective study included 142 patients operated for an NFMA in two academic centers (CHU Bicêtre in France and UCL St Luc in Belgium). The rate of tumor relapse, defined as recurrence after total surgical resection or regrowth of a surgical remnant, as well as predictive factors was analyzed. Results: During a mean follow-up of 6.9 years, 10 out of 42 patients (24%) who had complete macroscopic resection of their tumor had recurrence, and 47 out of 100 patients (47%) with a surgical remnant experienced regrowth. The overall relapse rates were 25, 43, and 61% at 5, 10, and 15 years respectively. Invasion of the cavernous sinus, absence of immediate radiotherapy after the first neurosurgery, and immunohistochemical features of the tumor (mainly positive immunostaining for several hormones or for hormones other than gonadotropins) were independent risk factors for tumor relapse. Incomplete excision was only associated with relapse when invasion was withdrawn from the analysis, suggesting that these two factors are closely linked. Conclusion: NFMAs frequently recur/regrow after initial surgery, particularly when tumor is invasive, precluding complete removal. Immunohistochemical features such as positive immunostaining for several hormones or for hormones other than gonadotropins could help to predict undesirable outcomes.

Responses of GH-secreting adenomas to multimodal management of acromegaly vary widely between patients. Understanding the behavioral patterns of GH-secreting adenomas by identifying factors predictive of their evolution is a research priority. The aim of this study was to clarify the relationship between the T2-weighted adenoma signal on diagnostic magnetic resonance imaging (MRI) in acromegaly and clinical and biological features at diagnosis. An international, multicenter, retrospective analysis was performed using a large population of 297 acromegalic patients recently diagnosed with available diagnostic MRI evaluations. The study was conducted at ten endocrine tertiary referral centers. Clinical and biochemical characteristics, and MRI signal findings were evaluated. T2-hypointense adenomas represented 52.9% of the series, were smaller than their T2-hyperintense and isointense counterparts (P!0.0001), were associated with higher IGF1 levels (PZ0.0001), invaded the cavernous sinus less frequently (PZ0.0002), and rarely caused optic chiasm compression (P!0.0001). Acromegalic men tended to be younger at diagnosis than women (PZ0.067) and presented higher IGF1 values (PZ0.01). Although in total, adenomas had a predominantly inferior extension in 45.8% of cases, in men this was more frequent (P!0.0001), whereas in women optic chiasm compression of macroadenomas occurred more often (PZ0.0067). Most adenomas (45.1%) measured between 11 and 20 mm in maximal diameter and bigger adenomas were diagnosed at younger ages (PZ0.0001). The T2-weighted signal differentiates GH-secreting adenomas into subgroups with

Objectives Only few retrospective studies have reported an efficacy rate of temozolomide (TMZ) in pituitary tumors (PT), all around 50%. However, the long-term survival of treated patients is rarely evaluated. We therefore aimed to describe the use of TMZ on PT in clinical practice and evaluate the long-term survival. Design Multicenter retrospective study by members of the French Society of Endocrinology. Methods Forty-three patients (14 women) treated with TMZ between 2006 and 2016 were included. Most tumors were corticotroph (n = 23) or lactotroph (n = 13), and 14 were carcinomas. Clinical/pathological characteristics of PT, as well as data from treatment evaluation and from the last follow-up were recorded. A partial response was considered as a decrease in the maximal tumor diameter by more than 30% and/or in the hormonal rate by more than 50% at the end of treatment. Results The median treatment duration was 6.5 cycles (range 2–24), using a standard regimen for most and combined radiotherapy for six. Twenty-two patients (51.2%) were considered as responders. Silent tumor at diagnosis was associated with a poor response. The median follow-up after the end of treatment was 16 months (0–72). Overall survival was significantly higher among responders (P = 0.002); however, ten patients relapsed 5 months (0–57) after the end of TMZ treatment, five in whom TMZ was reinitiated without success. Discussion Patients in our series showed a 51.2% response rate to TMZ, with an improved survival among responders despite frequent relapses. Our study highlights the high variability and lack of standardization of treatment protocols.

Intracranial dural arteriovenous shunts can be safely managed by transarterial embolization, which can be considered in most instances as an effective first-intention treatment. Acrylic glue still allows a cheap, fast, and effective treatment with high rates of cures that compare favorably to those obtained with new embolic materials.