Background: Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence ofAIPmutamong sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments.Methods: We included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at <30 years of age.Results: Overall, 19/163 (11.7%) patients had germlineAIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms.AIPmutwere identified in 8/39 (20.5%) pediatric patients. TenAIPmutwere identified in 11/83 (13.3%) sporadic somatotropinoma patients, in 7/61 (11.5%) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients withAIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21AIPmut-screened carriers; both had asymptomatic microadenomas.Conclusion: GermlineAIPmutoccur in 11.7% of patients <30 years with sporadic pituitary macroadenomas and in 20.5% of pediatric patients.AIPmutmutation testing in this population should be considered in order to optimize clinical genetic investigation and management.

Background: In contrast to cabergoline, evidence-based information about a possible profibrotic effect of bromocriptine in prolactinoma patients is extremely limited.Objective: To assess the prevalence of valvular lesions among patients on long-term bromocriptine or cabergoline therapy.Design: Case–control study.Methods: A transthoracic echocardiographic evaluation was performed in 334 subjects divided into four groups: 103 cabergoline treated, 55 bromocriptine treated, 74 naïve patients, and 102 controls.Results: Clinically relevant valve regurgitations were equally prevalent in all investigated groups whereas subclinical valve fibrosis was significantly more frequent in both bromocriptine- and cabergoline-treated patients (40 vs 43.6 vs 21.6 vs 23.5%; P=0.004). The odds ratio (OR) for developing valvular fibrosis was 2.27 (95% CI 1.17–4.41; P=0.016) for cabergoline and 2.66 (95% CI 1.22–5.78; P=0.014) for bromocriptine groups compared with subjects not exposed to dopamine agonists (DAs). A significantly higher pulmonary arterial pressure corresponding to the longer treatment duration was observed among patients taking bromocriptine compared with cabergoline-treated subjects.Conclusions: Long-term treatment with cabergoline and bromocriptine seems not to be associated with an increased risk of clinically significant valve disease but possible subclinical lesions should be expected. An echocardiographic examination is recommended at the beginning and periodically during therapy with DAs acting as full or partial agonists of 5-hydroxytrytamine 2B receptors (cabergoline and bromocriptine). Bromocriptine seems not to be a safe alternative for patients receiving cabergoline treatment who have preexisting or diagnosed abnormalities suggesting valvular, interstitial myocardial, or pulmonary fibrosis. Further studies are needed to investigate the possible impact of DA treatment on pulmonary arterial pressure.

Endogenous/exogenous Cushing's syndrome is characterized by a cluster of systemic manifestations of hypercortisolism, which cause increased cardiovascular risk. Its biological basis is glucocorticoid excess, acting on various pathogenic processes inducing cardiovascular damage. Hypertension is a common feature in Cushing's syndrome and may persist after normalizing hormone excess and discontinuing steroid therapy. In endogenous Cushing's syndrome, the earlier the diagnosis the sooner management can be employed to offset the deleterious effects of excess cortisol. Such management includes combined treatments directed against the underlying cause and tailored antihypertensive drugs aimed at controlling the consequences of glucocorticoid excess. Experts on endocrine hypertension and members of the Working Group on Endocrine Hypertension of the European Society of Hypertension (ESH) prepared this Consensus document, which summarizes the current knowledge in epidemiology, genetics, diagnosis, and treatment of hypertension in Cushing's syndrome.

Objective: To evaluate whether age-related differences exist in clinical characteristics, diagnostic approach, and management strategies in patients with Cushing's syndrome (CS) included in the European Registry on Cushing's Syndrome (ERCUSYN).Design: Cohort study.Methods: We analyzed 1791 patients with CS, of whom 1234 (69%) had pituitary-dependent CS (PIT-CS), 450 (25%) adrenal-dependent CS (ADR-CS), and 107 (6%) had an ectopic source (ECT-CS). According to the WHO criteria, 1616 patients (90.2%) were classified as younger (<65 years old) and 175 (9.8%) as older (≥65 years old).Results: Older patients were more frequently males and had a lower Body Mass Index (BMI) and waist circumference when compared with the younger. Older patients also had a lower prevalence of skin alterations, depression, hair loss, hirsutism, and reduced libido, but a higher prevalence of muscle weakness, diabetes, hypertension, cardiovascular disease, venous thromboembolism, and bone fractures than younger patients, regardless of sex (P < .01 for all comparisons). Measurement of urinary free cortisol supported the diagnosis of CS less frequently in older patients when compared with the younger (P < .05). An extrasellar macroadenoma (macrocorticotropinoma with extrasellar extension) was more common in older PIT-CS patients than in the younger (P < .01). Older PIT-CS patients more frequently received cortisol-lowering medications and radiotherapy as a first-line treatment, whereas surgery was the preferred approach in the younger (P < .01 for all comparisons). When transsphenoidal surgery was performed, the remission rate was lower in the elderly when compared with their younger counterpart (P < .05).Conclusions: Older CS patients lack several typical symptoms of hypercortisolism, present with more comorbidities regardless of sex, and are more often conservatively treated.