β-Thalassemias are a group of hereditary blood disorders characterized by abnormalities in the synthesis of the β hemoglobin (Hb) chains. This disease causes excessive storage of iron in all organs and endocrine glands. Treatment of β-thalassemia major (β-TM) consists of regular blood transfusions, iron chelation and management of secondary complications of iron overload. Endocrine abnormalities are frequently observed. In the last 25 years, the clinical picture of the disease has changed progressively thanks to improvement of treatments. Today, the majority of thalassemic patients reach adult age. The better prognosis and the longer lifespan of affected patients could be responsible for the susceptibility to other concomitant diseases which can manifest during their life. In this context, the possibility and recent literature reports about some cases of malignancy in thalassemic patients open new scenarios for oncoming years. We describe first reports of endocrine malignancies in thalassemic patients.

OBJECTIVE To prove equivalence of individual, clinically titrated basal insulin doses of glargine 300 units ⋅ mL−1 (Gla-300) and degludec 100 units ⋅ mL−1 (Deg-100) under steady state conditions in a single-blind, randomized, crossover study, on the glucose pharmacodynamics (PD) in people with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Subjects with T1D (N = 22, 11 men, age 44.3 ± 12.4 years, disease duration 25.5 ± 11.7 years, A1C 7.07 ± 0.63% [53.7 ± 6.9 mmol ⋅ mL−1], BMI 22.5 ± 2.7 kg · m−2), naïve to Gla-300 and Deg-100, underwent 24-h euglycemic clamps with individual clinical doses of Gla-300 (0.34 ± 0.08 units ⋅ kg−1) and Deg-100 (0.26 ± 0.06 units ⋅ kg−1), dosing at 2000 h, after 3 months of optimal titration of basal (and bolus) insulin. RESULTS At the end of 3 months, Gla-300 and Deg-100 reduced slightly and, similarly, A1C versus baseline. Clamp average plasma glucose (0–24 h) was euglycemic with both insulins. The area under curve of glucose infused (AUC-GIR[0–24 h]) was equivalent for the two insulins (ratio 1.04, 90% CI 0.91–1.18). Suppression of endogenous glucose production, free fatty acids, glycerol, and β-hydroxybutyrate was 9%, 14%, 14%, and 18% greater, respectively, with Gla-300 compared with Deg-100 during the first 12 h, while glucagon suppression was no different. Relative within-day PD variability was 23% lower with Gla-300 versus Deg-100 (ratio 0.77, 90% CI 0.63–0.92). CONCLUSIONS In T1D, individualized, clinically titrated doses of Gla-300 and Deg-100 at steady state result in similar glycemic control and PD equivalence during euglycemic clamps. Clinical doses of Gla-300 compared with Deg-100 are higher and associated with quite similar even 24-h distribution of PD and antilipolytic effects.

This study confirms the necessity to screen the status of GH/IGF-I axis in this group of patients, even in adult age. The presence of GH deficiency does not seem to be correlated with the efficacy parameters of transfusional and chelation therapy. Other mechanisms, additional to iron overload, could therefore play a role in the pathogenesis of this clinical condition. The presence of GH deficit seems to be very important on clinical aspects, like bone disease, that are crucial for quality of life in these patients.

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Clinical trials have demonstrated that azilsartan is superior to other angiotensin-receptor blockers in lowering blood pressure. However, the clinical blood pressure trials of azilsartan published to date have been mainly conducted in patients without serious comorbidities and it is not clear if azilsartan has advantages over other angiotensin-receptor blockers in the treatment of these types of hypertensive patients. In addition, it remains to be determined whether the specific pharmacologic and pharmacokinetic characteristics of azilsartan will have a clinically significant impact on long-term cardiovascular outcomes.