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BACKGROUND/AIMS: The natural course of Graves' orbitopathy (GO) has been poorly documented. The aim of this review is to provide current knowledge regarding the natural course of mild GO, trying to address the issue of whether and to what extent it constitutes a chronic remitting or transient disease. METHODS: We systematically searched PubMed for English language publications until August 2016 under the following terms: "Graves' orbitopathy" OR "Graves' ophthalmopathy" OR "thyroid eye disease" AND "natural course" OR "natural history". RESULTS: Few studies have investigated the course of mild orbital disease in patients with GO. Large controlled trials are lacking and data can be extracted mainly from small retrospective and some prospective studies, after excluding patients who had received radioiodine for thyrotoxicosis or surgical treatment for GO. In general, more than half of GO patients may show spontaneous improvement in their clinical features, whereas no safe conclusions can be drawn with regard to complete resolution, with percentages ranging from 6 to 58 %. CONCLUSIONS: The question whether mild GO is a remitting, albeit chronic disease, or even a transient event in the course of Graves' disease, remains currently unanswered.

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OBJECTIVE: Analysis of patients with acromegaly followed-up at a single centre, focusing on baseline characteristics, morbidity and efficacy of treatment. DESIGN AND METHODS: Retrospective review of electronic medical records of acromegalics from 1987 to 2009. RESULTS: One hundred and fifteen patients (45 men), aged 47 ± 14 years, with a mean follow-up of 8.8 ± 0.8 years were studied. Twenty-five per cent had micro- and 75% macroadenomas. Forty-three per cent presented with visual field defects, 49% had hypertension, 25% diabetes mellitus and 35% dyslipidaemia. At follow-up, 50% had myocardial hypertrophy, 55% colon polypodiasis, 74% nodular thyroid disease and 18% adrenal masses. Surgery was performed in 79% (8% twice), followed by conventional radiotherapy in 27%. Fifty-two per cent of the patients achieved remission. Disease control was reported in 65% of microadenomas and 41% of macroadenomas. Remission rates with surgery alone were 41%. Improvement of remission rates was achieved with subsequent treatment with somatostatin analogues (SSA) (53%), or conventional radiotherapy (63%). Nevertheless, pituitary reserve was compromised with the latter. SSA significantly improved outcomes in microadenomas, even as a monotherapy (remission in 89%), in contrast to macroadenomas (0%), although these agents were associated with impaired glucose metabolism and cholelithiasis in half of the patients. CONCLUSIONS: Acromegaly is associated with an increased morbidity. About half of the treated patients achieved remission (2/3 of microadenomas). The best outcomes were reported for the combination of surgery with radiotherapy, in spite of a higher risk of hypopituitarism. SSA led to remission in a significant percentage of microadenomas, but was associated with increased rates of cholelithiasis and impaired glucose homeostasis.

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AIM: Pituitary incidentalomas (PIs) are diagnosed in about 10% of the patients undergoing radiological investigation for non-pituitary disorders. The aim of this study was to describe the morphological and hormonal characteristics of PIs in a cohort of patients, followed up in a single centre from 1982-2009. METHODS: Retrospective analysis of electronic medical records of patients with PIs was carried out. All patients underwent basal and dynamic evaluation of the hypothalamus-pituitary axis. Mass size was assessed at yearly intervals. RESULTS: Sixty-one patients (38 men/23 women, aged 53±2 years) were studied. The mean follow-up time was 48±8 months, and mean size of PIs was 20±2 mm. Twelve PIs (20%) were microadenomas, 48 (78%) were macroadenomas and one (2%) was a Rathke's cyst. The most common reasons that led to their discovery were headaches, dizziness, syncope, stroke and head injury. Forty-seven of the 61 PIs (77%) were non-functioning, 11 (18%) prolactinomas, and two (3%) GH-secreting adenomas. Hypopituitarism was present in 12% at diagnosis. Forty-eight per cent of the patients were submitted to surgery with conventional radiotherapy in 8%. Relapse in size was observed in 48% of the surgically treated patients. Of the PIs followed conservatively, 78% remained stable, 11% showed decrease and 11% increase in size during follow up. Hypopituitarism rose to 57% postoperatively. CONCLUSIONS: Majority of PIs are non-functioning adenomas that remain stable in size. Relapse in size and hypopituitarism postoperatively are common. PIs, for which conservative management was initially considered appropriate, did not progress in size.

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INTRODUCTION: To describe the clinical imaging and hormonal characteristics and the natural course of patients with clinically non-functioning pituitary adenomas (NFPAs) presenting at our department from 1984 to 2009. MATERIALS AND METHODS: Retrospective review of electronic medical records of patients with NFPAs. The patients underwent basal and dynamic evaluation of the hypothalamic-pituitary axis. Size and functional alterations were estimated at yearly intervals. RESULTS: 114 patients (55 men and 59 women, aged 47±2) were studied. The mean follow-up time was 55±6 months (range 0-240). 45% of the adenomas were incidentally discovered and 75% were macroadenomas (73% with extrasellar extension). At diagnosis, 53% had headache and 76% of those with macroadenomas had visual field defects. Disruption of ≥1 pituitary axes was identified in 31% of patients at diagnosis. Surgery was performed in 59% and radiotherapy in 9% of the cases. 88% of surgically treated patients reported improvement in headache and 59% in visual fields. However, the prevalence of permanent diabetes insipidus increased from 2% at diagnosis to 15% postoperatively. The prevalence of ≥1 pituitary deficiencies and panhypopituitarism increased significantly postoperatively. 58% of the adenomas relapsed in size. 29% of the patients were managed conservatively and tumor size remained stable in 83% of them. CONCLUSIONS: The majority of NFPAs not selected for surgery at diagnosis remained stable in size. Pituitary dysfunction and visual defects at diagnosis were common. Surgical debulking led to clinical improvement, but relapse occurred in 2/3 of the cases.

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Type 2 diabetes mellitus is a well-established risk factor for cardiovascular disease (CVD). New therapeutic approaches have been developed recently based on the incretin phenomenon, such as the degradation-resistant incretin mimetic exenatide and the glucagon-like peptide-1 (GLP-1) analogue liraglutide, as well as the dipeptidyl dipeptidase (DPP)-4 inhibitors, such as sitagliptin, vildagliptin, saxagliptin, which increase the circulating bioactive GLP-1. GLP-1 exerts its glucose-regulatory action via stimulation of insulin secretion and glucagon suppression by a glucose-dependent way, as well as by weight loss via inhibition of gastric emptying and reduction of appetite and food intake. These actions are mediated through GLP-1 receptors (GLP-1Rs), although GLP-1R-independent pathways have been reported. Except for the pancreatic islets, GLP-1Rs are also present in several other tissues including central and peripheral nervous systems, gastrointestinal tract, heart and vasculature, suggesting a pleiotropic activity of GLP-1. Indeed, accumulating data from both animal and human studies suggest a beneficial effect of GLP-1 and its metabolites on myocardium, endothelium and vasculature, as well as potential anti-inflammatory and antiatherogenic actions. Growing lines of evidence have also confirmed these actions for exenatide and to a lesser extent for liraglutide and DPP-4 inhibitors compared with placebo or standard diabetes therapies. This suggests a potential cardioprotective effect beyond glucose control and weight loss. Whether these agents actually decrease CVD outcomes remains to be confirmed by large randomized placebo-controlled trials. This review discusses the role of GLP-1 on the cardiovascular system and addresses the impact of GLP-1-based therapies on CVD outcomes.

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