Le neoplasie associate a feocromocitoma/paraganglioma in quadri SDHx positivi o negativi: adenomi ipofisari, tumori stromali gastro-intestinali e tumori renali

SommarioI feocromocitomi e paragangliomi (PPGL) sono geneticamente determinati in almeno il 30% dei casi. Le mutazioni identificate più recentemente, in particolare quelle dei geni SDHx, possono favorire, seppur raramente, anche l'insorgenza di tumori stromali gastro-intestinali, carcinomi renali e adenomi ipofisari. Pertanto, in caso di diagnosi di una delle suddette neoplasie, il clinico dovrebbe valutare l'anamnesi personale e familiare alla ricerca di eventuali PPGL, così come in pazienti con PPGL associato a mutazione di SDHx, TMEM127 e MAX si dovrebbe indagare la presenza di neoplasie potenzialmente correlate

USEFULNESS OF AN AD HOC QUESTIONNAIRE (ACRO-CQ) FOR THE SYSTEMATIC ASSESSMENT OF ACROMEGALY COMORBIDITIES AT DIAGNOSIS AND THEIR MANAGEMENT AT FOLLOW-UP

Purpose: To determine the validity of a self-administered questionnaire (Acro-CQ) developed to systematically assess the presence, type and time of onset of acromegaly comorbidities. Methods: This is a cross-sectional study; 105 acromegaly patients and 147 controls with other types of pituitary adenoma, referred to a specialized Italian Center, autonomously compiled Acro-CQ in an outpatient clinical setting. To test its reliability in a different setting, Acro-CQ was administered via mail to 78 patients with acromegaly and 100 with other pituitary adenomas, referred to a specialized US Center. Data obtained from questionnaires in both settings were compared with medical records (gold standard). Results: Demographics of patients and controls from both countries were similar. In both settings, >95 % of the questionnaires were completely filled; only one item was missed in the others. Concordance with medical record was excellent (k > 0.85) for most of the items, independently from the way of administration, patient age, gender and nationality, pituitary adenoma type and disease activity. Conclusions: Acro-CQ is an inexpensive, highly accepted from patients and reliable tool recommended to expedite systematic collection of relevant clinical data in acromegaly at diagnosis, to be replicated at follow-ups. This tool may guide a targeted, cost-effective management of complications. Moreover, it could be applied to retrieve data for survey studies in both acromegaly and other pituitary adenomas, as information is easily and rapidly accessible for statistical analysis

Antagonists of Growth Hormone-Releasing Hormone Inhibit the Growth of Pituitary Adenoma Cells by Hampering Oncogenic Pathways and Promoting Apoptotic Signaling

Pituitary adenomas (PAs) are intracranial tumors, often associated with excessive hormonal secretion and severe comorbidities. Some patients are resistant to medical therapies; therefore, novel treatment options are needed. Antagonists of growth hormone-releasing hormone (GHRH) exert potent anticancer effects, and early GHRH antagonists were found to inhibit GHRH-induced secretion of pituitary GH in vitro and in vivo. However, the antitumor role of GHRH antagonists in PAs is largely unknown. Here, we show that the GHRH antagonists of MIAMI class, MIA-602 and MIA-690, inhibited cell viability and growth and promoted apoptosis in GH/prolactin-secreting GH3 PA cells transfected with human GHRH receptor (GH3-GHRHR), and in adrenocorticotropic hormone ACTH-secreting AtT20 PA cells. GHRH antagonists also reduced the expression of proteins involved in tumorigenesis and cancer progression, upregulated proapoptotic molecules, and lowered GHRH receptor levels. The combination of MIA-690 with temozolomide synergistically blunted the viability of GH3-GHRHR and AtT20 cells. Moreover, MIA-690 reduced both basal and GHRH-induced secretion of GH and intracellular cAMP levels. Finally, GHRH antagonists inhibited cell viability in human primary GH- and ACTH-PA cell cultures. Overall, our results suggest that GHRH antagonists, either alone or in combination with pharmacological treatments, may be considered for further development as therapy for PAs

Copeptin adaptive response to SGLT2 inhibitors in patients with type 2 diabetes mellitus: The GliRACo study

IntroductionIn type 2 diabetes mellitus (T2DM), the antidiuretic system participates in the adaptation to osmotic diuresis further increasing urinary osmolality by reducing the electrolyte-free water clearance. Sodium glucose co-transporter type 2 inhibitors (SGLT2i) emphasize this mechanism, promoting persistent glycosuria and natriuresis, but also induce a greater reduction of interstitial fluids than traditional diuretics. The preservation of osmotic homeostasis is the main task of the antidiuretic system and, in turn, intracellular dehydration the main drive to vasopressin (AVP) secretion. Copeptin is a stable fragment of the AVP precursor co-secreted with AVP in an equimolar amount.AimTo investigate the copeptin adaptive response to SGLT2i, as well as the induced changes in body fluid distribution in T2DM patients.MethodsThe GliRACo study was a prospective, multicenter, observational research. Twenty-six consecutive adult patients with T2DM were recruited and randomly assigned to empagliflozin or dapagliflozin treatment. Copeptin, plasma renin activity, aldosterone and natriuretic peptides were evaluated at baseline (T0) and then 30 (T30) and 90 days (T90) after SGLT2i starting. Bioelectrical impedance vector analysis (BIVA) and ambulatory blood pressure monitoring were performed at T0 and T90.ResultsAmong endocrine biomarkers, only copeptin increased at T30, showing subsequent stability (7.5 pmol/L at T0, 9.8 pmol/L at T30, 9.5 pmol/L at T90; p = 0.001). BIVA recorded an overall tendency to dehydration at T90 with a stable proportion between extra- and intracellular fluid volumes. Twelve patients (46.1%) had a BIVA overhydration pattern at baseline and 7 of them (58.3%) resolved this condition at T90. Total body water content, extra and intracellular fluid changes were significantly affected by the underlying overhydration condition (p < 0.001), while copeptin did not.ConclusionIn patients with T2DM, SGLT2i promote the release of AVP, thus compensating for persistent osmotic diuresis. This mainly occurs because of a proportional dehydration process between intra and extracellular fluid (i.e., intracellular dehydration rather than extracellular dehydration). The extent of fluid reduction, but not the copeptin response, is affected by the patient’s baseline volume conditions.Clinical trial registrationClinicaltrials.gov, identifier NCT03917758

Markers of Aggressiveness in Pituitary Tumors: Update and Perspectives

Pituitary neuroendocrine tumors (PitNETs) are relatively common intracranial neoplasms, potentially originating from various pituitary cell types [...

Court dwarfs: An overview of European paintings from fifteenth to eighteenth century

Since antique times, dwarfs have been commonly employed at court, mostly as servants, entertainers, or personal attendants upon noble women and noblemen. Their presence at European Renaissance courts was very common, as demonstrated by their presence alongside to their masters or mistress in several artworks of that period. Aim of our paper is to derive clinical information regarding the type of dwarfism affecting people living and acting at European courts from an overview of paintings dating fifteenth to the eighteenth century. \uc2\ua9 2012 Springer Science+Business Media, LLC