Atypical CD increases the need for T4. The effect was reversed by GFD or by increasing T4 dose. Malabsorption of T4 may provide the opportunity to detect CD that was overlooked until the patients were put under T4 therapy.

Many reports indicate a hypercoagulative state in diabetes mellitus as result of endothelial damage. Experimental evidence suggests that a metabolic derangement triggers a cascade of biochemical events that lead to vascular dysfunction. The net effect is to convert the endothelium from thromboresistant to thrombogenic surface. In literature, a strong association between type 1 diabetes mellitus (DM1) and celiac disease (CD) has been reported. We do not have information about the hemostatic system in these associated conditions. Our study aims at evaluating whether the presence of CD in a group of DM1 patients is associated with a different expression of some hemostatic factors and with a different manifestation and/or progression of microvascular complications of DM1 in comparison with patients with only diabetes. Ninety-four adult DM1 patients were enrolled in the study and subsequently screened for CD. Anti-endomysial antibodies (EMA) were positive in 13 of 94 DM1 patients (13.8%). CD diagnosis was confirmed by histology and organ culture. The mean age and duration of DM1 of patients also affected by CD were similar to those of only diabetic patients, but the metabolic control and the hemocoagulative parameters were significantly different between the two groups: DM1 patients also affected by CD presented significantly lower concentrations of glycosylated hemoglobin (HbA1c) (P < 0.05), cholesterol (P < 0.001), triglycerides (P < 0.001), factor VII antigen (FVII:ag) (P < 0.005), factor VII coagulant activity (FVII:c) (P < 0.05), and prothrombin degradation fragments (F1+2) (P < 0.001), as well as higher values of activated C protein (APC) (<0.001). No retinal abnormalities and no signs of renal damage were observed in DM1 patients also affected by CD. Our results suggest a potential protective role of CD in the prothrombotic state of DM1.

In the observational study cited above, we evaluated whether the presence of undiagnosed CD in a group of adult DM1 patients is associated with a different expression of some hemostatic factors, as well as with a different manifestation and/or progression of microvascular complications in comparison with patients suffering from DM1 only. The Ventura group has carefully examined and commented on this study, but we are only partially in agreement with their observations. First, the including criterion HbA1c B 7.5% or 58 mmol/mol was chosen to ensure the selection of DM1 patients with a satisfactory long-standing metabolic control. This is to prevent that, during the disease progression, an inadequate metabolic control may have affected adversely on the study parameters. The evaluation of hemostatic factors and microvascular complications in DM1 patients also suffering from CD and presenting an unsatisfactory metabolic control could become the object of a future study.Second, we have chosen to assess the metabolic control by means of HbA1c in order to obtain long-standing information reflecting the chronic state that may culminate in microvascular complications. On the other hand, the metabolic control of adult patients with a long-standing DM1 is generally better than that found in diabetic children, to whom the Ventura group refers. This is because children have a shorter disease duration and they are more exposed to factors that can alter their metabolic control. In relation to the other parameters able to evaluate the metabolic control, the diabetologists have obviously considered the presence of frequent hypoglycemic events, the extreme glycemia variability, and the increment in daily insulin needs as an implicit exclusion criterion.Third, in most of the patients evaluated in our study, the presence of other autoimmune diseases has been investigated by means of a wide autoantibody serum panel (data not shown), and the results are not relevant. Finally, since our study was performed on a group of adult DM1 patients, we have obviously not considered anthropometric parameters because the patients enrolled in our study were all already adult, eventually affected by CD, and presenting negative malabsorption clinical picture. It would however be interesting to assess, in the future, the role of CD on hemostatic factors and microvascular complications also in diabetic children.In conclusion, we observed a better metabolic control and a thromboresistant condition in adult patients with both DM1 and undiagnosed CD, even if our opinion is that gluten-free diet is mandatory in all patients suffering from CD.Rome. 22 July 2011.

Introduction Treatment of acromegaly resistant to first generation somatostatin analogues (first gen-SSA) is often difficult. We aimed to investigate the role of partial response and resistance to first gen-SSA in the choice of second line treatments and their outcomes. Patients and methods A retrospective and multicenter study was conducted on 100 SSA-resistant acromegaly patients and treated with Pasireotide Lar (Pasi-Lar), Peg-V in monotherapy (m-Peg-V) or in combination with first gen-SSA (c-Peg-V). Results Thirty-three patients (33%) were treated with m-Peg-V, 36 (36%) with c-Peg-V and 31 with Pasi-Lar (31%). According to logistic regression, m-Peg-V was chosen in older patients (p = 0.01) and with not-invasive adenomas (p = 0.009), c-Peg-V therapy in younger patients (p = 0.001), with invasive adenomas (p = 0.02), Pasi-Lar was in invasive adenomas (p = 0.01) and in patients partially responsive to first-gen SSA (p = 0.01). At the last follow-up, 68 patients (68%) reached the acromegaly control: 22 with m-Peg-V (32.4%), 23 with c-Peg-V (33.8%) and 23 with Pasi-Lar (33.8%). Patients non-responsive to c-Peg-V had higher IGF-I levels (median 3.2 x ULN, IQR: 1.6, p < 0.001) and required higher Peg-V dosage (median 30 mg/daily IQR: 10, p = 0.002) as compared to responsive patients (median IGF-I x ULN: 2.1 IQR: 1.4; median Peg-V dosage 20 mg/daily IQR: 10). All patients responsive to Pasi-Lar were partially responsive to first gen-SSAs (p = 0.02). Conclusion Our data showed that c-Peg-V and Pasi-Lar are chosen for the treatment of invasive tumors. The partial response to first gen-SSA seems to be the main determinant for the choice of Pasi-Lar and positively predicts the treatment outcome.

The coexistence of intracranial aneurysm (IA) is generally thought to be highest in patients with pituitary adenomas (PAs). Different mechanisms may play a role in aneurysm formation, but whether the PA contributes to aneurysm formation is still unclear. In the literature, there are numerous reported cases of this association; however, the analyses of the characteristics of PAs, aneurysms, and treatment management are rare and limited to a restricted number of case reports. We report a rare case of an embedded aneurysm in a macroprolactinoma treated with therapeutic management tailored to the clinical, neurological, and radiological characteristics of the patient. To select the best treatment, we reviewed the literature and reported the only cases in which the radiological characteristics of aneurysms, PAs, therapeutic management, and patient outcome are described. We aimed to understand what are the variables that determine the best therapeutic management with the best possible outcome. The presence of a large pseudoaneurysm of the internal carotid artery completely embedded in a giant macroprolactinoma is rare and needs a tailored treatment strategy. The importance of the preoperative knowledge of asymptomatic IA coexisting with PA can avoid accidental rupture of the aneurysm during surgical resection and may lead to planning the best treatment. A high degree of suspicion for an associated aneurysm is needed, and if magnetic resonance imaging shows some atypical features, digital subtraction angiography must be performed prior to contemplating any intervention to avoid iatrogenic aneurysmal rupture. Our multimodal approach with the first-line therapy of low-dose cabergoline to obtain prolactin normalization with minimum risks of aneurysms rupture and subsequent endovascular treatment with flow diverter has not been described elsewhere to our knowledge. In the cases, we suggest adopting a tailored low-dose cabergoline therapy scheme to avoid rupture during cytoreduction and initiate a close neuroradiological follow-up program.

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Background Acromegaly is a rare disease due to chronic growth hormone (GH) excess and the consequent increase in insulin-like growth factor-1 (IGF-1) levels. Both GH and IGF-1 play a role in intermediate metabolism affecting glucose homeostasis. The association between hyperinsulinemia/impaired glucose tolerance and an increased risk of cancer has been clarified. Insulin has a mitogenic effect through its interaction with the IGF-1 receptor (IGF-1R) that also binds IGF-1. On the other hand, metformin, an anti-hyperglycemic drug that decreases serum levels of insulin and IGF-1, could have a protective role in the treatment of endocrine tumors. Methods A retrospective, observational, multicenter study in 197 acromegalic patients, receiving/not receiving metformin, was performed to assess whether the prevalence of neoplasms might be correlated with insulin resistance and could eventually be modified by metformin treatment. Results In general, the occurrence of secondary neoplasia among our patients was significantly (pV = 0.035) associated with a positive family history of malignancy and with disease duration; a trend towards significance was observed in patients aged > 50 years. Acromegalic subjects who had undergone surgery showed a lower probability of developing a malignant tumor, whereas a higher prevalence of malignancies was observed in obese patients. No significant statistical difference was found when comparing metformin-treated or -untreated subjects for the presence of a second tumor. More interestingly, a trend towards statistical significance (pV = 0.065) was demonstrated in the metformin-treated group for the onset of a benign neoplasm. Conclusion Metformin could act directly on tumor cell metabolism and may have an adjuvant role in benign lesion progression.

Purpose: To evaluate the prevalence and clinical performance of obstructive sleep apnoea syndrome (OSAS) in acromegalic patients, focusing on the possible correlation between alterations of pulmonary microcirculation and patient's clinical and hormonal parameters. Methods: We enrolled 22 acromegalic patients with apnea hypopnea index (AHI) ≥ 5 if symptomatic, or ≥15 in the absence of sleep related symptoms. Patients underwent the following evaluations: GH and IGF-1 serum levels, arterial blood gas test, spirometry, carbon monoxide diffusing capacity (DLCO), home-based cardiorespiratory sleep and pulmonary function test. Results: The prevalence of OSAS was 66.6%. Patients with a severe form of OSAS appeared to be affected from acromegaly for more years than those with a lower severity of disease and those with acromegaly duration > 10 years had significantly higher levels of glycated hemoglobin. We observed a positive correlation between GH level at diagnosis and DLCO value, showing that acromegalic patients have an increase in static and dynamic respiratory volumes and alveolar-capillary exchange surface compared to the general population. We also observed a positive correlation between baseline serum IGF-1 level and DLCO/VA and between years of disease and DLCO/VA, showing the association of increased lung volume and increase of the exchange surface. Conclusions: The results of this study add new information on lung volume and alveolar gas exchange in acromegaly. Our findings highlight the role of SSA as therapy with positive impact on complication and comorbidities of acromegaly.