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Objective: This study evaluated short- and long-term efficacy and safety of the second-generation somatostatin receptor ligand pasireotide alone or in combination with dopamine agonist cabergoline in patients with Cushing’s disease (CD). Study design: This is an open-label, multicenter, non-comparative, Phase II study comprising 35-week core phase and an optional extension phase. All patients started with pasireotide, and cabergoline was added if cortisol remained elevated. Eligible patients had active CD, with or without prior surgery, were pasireotide naïve at screening or had discontinued pasireotide for reasons other than safety. Primary endpoint was proportion of patients with a mean urinary free cortisol (mUFC) level not exceeding the upper limit of normal (ULN) at week 35 with missing data imputed using last available post-baseline assessments. Results: Of 68 patients enrolled, 26 (38.2%) received pasireotide monotherapy and 42 (61.8%) received pasireotide plus cabergoline during the core phase. Thirty-four patients (50.0%; 95% CI 37.6–62.4) achieved the primary endpoint, of whom 17 (50.0%) received pasireotide monotherapy and 17 (50.0%) received combination therapy. Proportion of patients with mUFC control remained stable during the extension phase up to week 99. Treatment with either mono or combination therapy provided sustained improvements in clinical symptoms of hypercortisolism up to week 99. Hyperglycemia and nausea (51.5% each), diarrhea (44.1%) and cholelithiasis (33.8%) were the most frequent adverse events. Conclusion: Addition of cabergoline in patients with persistently elevated mUFC on maximum tolerated doses of pasireotide is an effective and well-tolerated long-term strategy for enhancing control of hypercortisolism in some CD patients. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT01915303, identifier NCT01915303.

Objective: Paget disease of bone (PDB) is a metabolic bone disease that has been rarely reported in the Eastern countries. This study aimed to evaluate the clinical and demographic characteristics of patients with PDB followed up at endocrinology clinics in Turkey. Methods: an invitation was sent to tertiary endocrinology clinics to complete a survey on the demographic, clinical, radiological, and laboratory parameters, as well as treatment modalities of patients with PDB. This study enrolled clinically and radiologically proven 185 patients with PDB from 18 endocrinology centers based in 10 cities of Turkey. Results: this cohort of PDB had female preponderance (women/men: 105/80) with a mean age, during diagnosis, of 57±10 years. Most of the patients (59.6%) were symptomatic at diagnosis. Bone pain and headache were the predominant clinical symptoms. Polyostotic disease was observed in 67.5% (n=125) of patients. Frequently affected bones were skull (41.6%), pelvis (53.5%), spine (41%), and femur (25.4%). Moreover, 17 patients with skull involvement had hearing loss. Mean serum alkaline phosphatase (ALP) level (552±652 IU/L; range: 280-5762 IU/L) was over the normal reference cutoff with normal serum calcium levels. Intravenous bisphosphonates (zoledronic acid, 5 mg; pamidronate, 60-90 mg) were the most used drugs (75%) for the treatment of PDB. Most of the patients (87.1%) treated with intravenous bisphosphonates responded well, with a decrease in serum ALP level (117±114 IU/L) in the 12th month of therapy. Furthermore, 16 patients relapsed after the second year of therapy; 3 patients did not respond to the initial intravenous bisphosphonate treatment. Conclusion: the patients with PDB followed up by endocrinology clinics of Turkey exhibited polyostotic disease with classical clinical, radiological, and biochemical features and women's predominance with good response to intravenous bisphosphonate therapy., NA

Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec, which provides long-lasting basal insulin coverage, and insulin aspart, which targets postprandial glycaemia. This review provides expert opinion on the practical clinical use of IDegAsp, including: dose timings relative to meals, when and how to intensify treatment from once-daily (OD) to twice-daily (BID) dose adjustments, and use in special populations (including hospitalized patients). IDegAsp could be considered as one among the choices for initiating insulin treatment, preferential to starting on basal insulin alone, particularly for people with severe hyperglycaemia and/or when postprandial hyperglycaemia is a major concern. The recommended starting dose of IDegAsp is 10 units with the most carbohydrate-rich meal(s), followed by individualized dose adjustments. Insulin doses should be titrated once weekly in two-unit steps, guided by individualized fasting plasma glucose targets and based on patient goals, preferences and hypoglycaemia risk. Options for intensification from IDegAsp OD are discussed, which should be guided by HbA1c, prandial glucose levels, meal patterns and patient preferences. Recommendations for switching to IDegAsp from basal insulin, premixed insulins OD/BID, and basal-plus/basal-bolus regimens are discussed. IDegAsp can be co-administered with other antihyperglycaemic drugs; however, sulphonylureas frequently need to be discontinued or the dose reduced, and the IDegAsp dose may need to be decreased when sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists are added. Considerations around the initiation or continuation of IDegAsp in hospitalized individuals are discussed, as well as in those undergoing medical procedures.