Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course.

Acne is a disorder of the pilosebaceous unit, common among adolescents, which may be extended to adulthood. The aim of this study was to assess the prevalence of hormonal disorders in women with acne resistance to conventional therapy. We included 72 women aged between 15 and 36 years (divided in two age groups) who presented to our clinic between May and October 2014, suffering from moderate and severe forms of papulopustular and nodulocystic acne. The subjects were non-responsive to classic dermatological treatment or had clinical manifestation of hyperandrogenism. Based on age, we divided the women into two groups, group I with 40 patients aged 15–22years and group II with 32 patients aged 23–36 years. Using ELISA, a hormonal profile was performed for each patient in days 1–3 of the menstrual cycle including, total testosterone, dehydroepiandrosterone sulfate (DHEA-S), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, and plasma cortisol. For statistical analysis we used Stata 13 software. We compared the hormonal profile of the two groups and identified significant differences for: testosterone levels (mean value, 0.64±0.35 vs. 0.97±0.50 ng/ml; p<0.0001), DHEA-S levels (mean value, 0.85±0.27 vs. 1.05±0.33 mg/24 h; p=0.001), prolactin levels (mean value, 281.85±91.113 vs. 353.969±102.841 mIU/ml; p=0.002) and LH levels (14.8±6.7 vs. 20.1±8.2 mIU/ml; p=0.002) were higher in group II. No statistically significant differences were found for estradiol (p=0.588) and cortisol (p=0.182) levels. In conclusion, refractory acne can be the first sign of systemic illness including polycystic ovary syndrome. Thus, for a correct therapeutic approach it is necessary to interpret the clinical and biochemical elements in correlation with the medical history.

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Guidelines recommend adults with pituitary disease in whom GH therapy is contemplated, to be tested for GH deficiency (AGHD); however, clinical practice is not uniform. Aims (1) To record current practice of AGHD management throughout Europe and benchmark it against guidelines; (2) To evaluate educational status of healthcare professionals about AGHD. Design Online survey in endocrine centres throughout Europe. Patients and methods Endocrinologists voluntarily completed an electronic questionnaire regarding AGHD patients diagnosed or treated in 2017–2018. Results Twenty-eight centres from 17 European countries participated, including 2139 AGHD patients, 28% of childhood-onset GHD. Aetiology was most frequently non-functioning pituitary adenoma (26%), craniopharyngioma (13%) and genetic/congenital midline malformations (13%). Diagnosis of GHD was confirmed by a stimulation test in 52% (GHRH+arginine: 45%; insulin-tolerance: 42%, glucagon: 6%; GHRH alone and clonidine tests: 7%); in the remaining, ≥3 pituitary deficiencies and low serum IGF-I were diagnostic. Initial GH dose was lower in older patients, but only women <26 years were prescribed a higher dose than men; dose titration was based on normal serum IGF-I, tolerance and side-effects. In one country, AGHD treatment was not approved. Full public reimbursement was not available in four countries and only in childhood-onset GHD in another. AGHD awareness was low among non-endocrine professionals and healthcare administrators. Postgraduate AGHD curriculum training deserves being improved. Conclusion Despite guideline recommendations, GH replacement in AGHD is still not available or reimbursed in all European countries. Knowledge among professionals and health administrators needs improvement to optimise the care of adults with GHD.

Purpose The efficacy of levoketoconazole for endogenous Cushing’s syndrome was demonstrated in a phase 3, open-label study (SONICS). This study (LOGICS) evaluated drug-specificity of cortisol normalization. Methods LOGICS was a phase 3, placebo-controlled, randomized-withdrawal study with open-label titration-maintenance (14–19 weeks) followed by double-blind, randomized-withdrawal (~ 8 weeks), and restoration (~ 8 weeks) phases. Results 79 patients received levoketoconazole during titration-maintenance; 39 patients on a stable dose (~ 4 weeks or more) proceeded to randomization. These and 5 SONICS completers who did not require dose titration were randomized to levoketoconazole (n = 22) or placebo (n = 22). All patients with loss of response (the primary endpoint) met the prespecified criterion of mean urinary free cortisol (mUFC) > 1.5 × upper limit of normal. During randomized-withdrawal, 21 patients withdrawn to placebo (95.5%) lost mUFC response compared with 9 patients continuing levoketoconazole (40.9%); treatment difference: − 54.5% (95% CI − 75.7, − 27.4; P = 0.0002). At the end of randomized-withdrawal, mUFC normalization was observed among 11 (50.0%) patients receiving levoketoconazole and 1 (4.5%) receiving placebo; treatment difference: 45.5% (95% CI 19.2, 67.9; P = 0.0015). Restoration of levoketoconazole reversed loss of cortisol control in most patients who had received placebo. Adverse events were reported in 89% of patients during treatment with levoketoconazole (dose-titration, randomized-withdrawal, and restoration phases combined), most commonly nausea (29%) and hypokalemia (26%). Prespecified adverse events of special interest with levoketoconazole were liver-related (10.7%), QT interval prolongation (10.7%), and adrenal insufficiency (9.5%). Conclusions Levoketoconazole reversibly normalized urinary cortisol in patients with Cushing’s syndrome. No new risks of levoketoconazole treatment were identified.