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Background Cushing's disease is the most prevalent cause of endogenous Cushing's syndrome. This study aimed to scope the current clinical practice pattern in managing Cushing's disease by endocrinologists in the Middle Eastern and North African (MENA) region. Methods A questionnaire dealing with diagnosis, treatment, and follow-up of patients with Cushing's disease was adopted and sent electronically to a convenience sample of endocrinologists from the MENA region. Results Out of 125 responses received, 88 were eligible for inclusion in the analysis. Most respondents selected the overnight dexamethasone suppression test (ONDST) and 24-hour urinary-free cortisol (UFC) as the best screening tests, 58 (66.7%) and 50 (57.5%) respectively, followed by midnight serum cortisol and midnight salivary cortisol. Measurement of serum adrenocorticotropic hormone (ACTH; 86.2%) and classic high-dose dexamethasone suppression test (40.2%) were selected for localization of the primary lesion. The primary choice of treatment was transsphenoidal pituitary surgery (98.8%). For the recurrence of Cushing's disease, medical therapy was the preferred modality followed by repeated pituitary surgery or bilateral adrenalectomy. In case of treatment failure following the first pituitary surgery and ketoconazole treatment, 36.9% selected pasireotide, while 32.1% chose bilateral adrenalectomy. Conclusion ONDST and UFC are the two most common tests used to screen an index case with features of hypercortisolism. Pituitary surgery is the primary choice of treatment in Cushing's disease. However, medical treatment by ketoconazole is preferred for recurrent cases. Bilateral adrenalectomy is followed by pasireotide may be chosen in case of treatment failure after pituitary surgery and ketoconazole.

Asia is projected to account for the largest proportion of the rising burden of osteoporotic fractures worldwide. Data from the Middle East is scarce. We performed a systematic review on the epidemiology of vertebral and hip osteoporotic fractures in 22 Arab League countries, using Scopus, PubMed, and Embase. We identified 67 relevant publications, 28 on hip and 39 on vertebral fractures. The mean age of patients was 70-74 years, female to male ratio 1.2:2.1. Age-standardized incidence rates, to the UN 2010 population, were 236 to 290/100,000 for women from Kuwait and Lebanon, lower in Morocco. Risk factors for hip fractures included lower BMD or BMI, taller stature, anxiolytics, and sleeping pills. Most patients were not tested nor treated. Mortality derived from retrospective studies ranged between 10 and 20% at 1 year, and between 25 and 30% at 2-3 years. Among 39 studies on vertebral fractures, 18 described prevalence of morphometric fractures. Excluding grade 1 fractures, 13.3-20.2% of women, mean age 58-74 years, had prevalent vertebral fractures, as did 10-14% of men, mean age 62-74 years. Risk factors included age, gender, smoking, multiparity, years since menopause, low BMD, bone markers, high sclerostin, low IgF1, hypovitaminosis D, abdominal aortic calcification score, and VDR polymorphisms. Vertebral fracture incidence in women from Saudi Arabia, mean age 61, was 6.2% at 5 years, including grade 1 fractures. Prospective population-based fracture registries, prevalence studies, predictive models, fracture outcomes, and fracture liaison services from Arab countries are still lacking today. They are the pillars to closing the care gap of this morbid disease.

In adults, growth hormone deficiency (GHD) has been associated with low bone mineral density (BMD), an effect counteracted by growth hormone (GH) replacement. Whether GH is beneficial in adults with age-related bone loss and without hypopituitarism is unclear. We conducted a systematic literature search using Medline, Embase and the Cochrane Register of Controlled Trials. We extracted and analyzed data according to the bone outcome included [bone mineral content (BMC), BMD, and bone biomarker, fracture risk]. We performed a meta-analysis when possible. We included eight studies. Seven randomized 272 post-menopausal women, 61–69 years, to GH or control, for 6–24 months, and the eighth was an extension trial. Except for one study, all women received concurrent osteoporosis therapies. There was no significant effect of GH, as compared to control, on BMD at the lumbar spine (Weighted mean difference WMD = −0.01 [−0.04, 0.02]), total hip (WMD = 0 [−0.05, 0.06]) or femoral neck (WMD = 0 [−0.03, 0.04]). Similarly, no effect was seen on BMC. GH significantly increased the bone formation marker procollagen type-I carboxy-terminal propeptide (PICP) (WMD = 14.03 [2.68, 25.38]). GH resulted in a trend for increase in osteocalcin and in bone resorption markers. Patients who received GH had a significant decrease in fracture risk as compared to control (RR = 0.63 [0.46, 0.87]). Reported adverse events were not major, mostly related to fluid retention. GH may not improve bone density in women with age-related bone loss but may decrease fracture risk. Larger studies of longer duration are needed to further explore these findings in both genders, and to investigate the effect of GH on bone quality.

Dopamine agonists (DAs) represent a cornerstone in the management of patients with hyperprolactinemia and have an important role in the treatment of neurologic disorders, including Parkinson’s disease and restless legs syndrome. A growing body of evidence has identified impulse control disorders (ICDs) as possible adverse effects of DA therapy. A variety of ICDs may occur in patients treated with DA, including compulsive shopping, pathologic gambling, stealing, hypersexuality and punding (repetitive performance of tasks, such as collecting, sorting, disassembling and assembling objects). These behaviors can have devastating effects on patients’ life and family. In the present review article, we summarize available data on ICDs in patients with hyperprolactinemia as well as other disorders. Possible risk factors for the emergence of ICDs in patients treated with DA are discussed and the putative pathophysiologic mechanisms underlying the development of ICDs in this setting are reviewed. In addition, strategies for the early identification and management of ICDs in patients on DA are discussed. In conclusion, a wide variety of ICDs can occur in patients treated with DA, including those with hyperprolactinemia. The development of ICDs can have serious implications for patients’ well-being and family. Endocrinologists and other physicians involved in the care of patients on DA therapy must be aware of this potential adverse effect, counsel patients regarding pertinent symptoms and regularly evaluate treated patients for the development of ICDs. Early detection of ICDs and discontinuation of DA therapy can mitigate the potential harms associated with ICDs in these patients.

Thyrotropin (TSH)-secreting pituitary adenomas are uncommon pituitary neoplasms. They have been increasingly recognized with the advent of ultrasensitive TSH assays and advanced pituitary imaging. Clinically, patients may often present with signs and symptoms of hyperthyroidism. Some patients may present with tumor-related local mass effect, anterior hypopituitarism or syndromes related to co-secretion of other pituitary hormones. Their diagnosis and differential diagnosis from other causes of hyperthyroidism and ‘inappropriate TSH secretion’ often presents a clinical challenge. While trans-sphenoidal pituitary adenomectomy remains the therapeutic modality of choice, medical treatment with somatostatin receptor agonists or dopamine agonists is often needed as adjunctive therapy or perhaps as a potential alternative to surgery. Radiation therapy to the sella may be advised as a third-line therapy.

GH deficiency is associated with decreased bone mineral density (BMD) and increased fracture risk. Because the effects of recombinant human GH (rhGH) therapy on BMD and bone mineral content have not been systematically investigated, we conducted a meta-analysis of pertinent studies.A thorough search of the literature (MEDLINE, EMBASE, and the Cochrane Register) was performed. Relevant studies were divided and analyzed according to their design (randomized/controlled or prospective/retrospective) and duration of rhGH therapy (≤12 months and12 months).Administration of rhGH led to a significant increase in lumbar spine (LS) and femoral neck (FN) BMD in randomized/controlled studies of more than 1 year [weighted mean difference (95% confidence interval)] of 0.038 g/cm(2) (0.011-0.065) and 0.021 g/cm(2) (0.006-0.037) at the LS and FN, respectively, and a nonsignificant drop at the same sites in studies of shorter duration. In prospective studies, a significant increase in the LS and FN BMD was obtained. On meta-regression, a negative association was observed between the change in LS and FN BMD and subjects' age and a positive association between the BMD change and treatment duration. In a subgroup analysis, the increase in LS and FN BMD was significant in men [0.048 g/cm(2) (0.033-0.064) and 0.051 g/cm(2) (0.003-0.098), respectively] but not in women.This meta-analysis suggests a beneficial effect of rhGH replacement on BMD in adults with GH deficiency. This effect is affected by gender, age, and treatment duration. Larger studies are needed to evaluate the effect of rhGH on fracture risk.

The use of dopamine agonists (DAs) has been associated with increased impulsivity and impulse control disorders in several diseases, including Parkinson's disease. Such an effect of DAs on impulsivity has not been clearly characterized in hyperprolactinemic patients, where DAs are the mainstay of therapy. We studied the effects of DAs on impulsivity in hyperprolactinemic patients treated at a tertiary pituitary center, using validated psychometric tests. Cross-sectional study. Impulsivity was evaluated in 30 subjects, 10 hyperprolactinemic patients on DAs compared to two control groups; one comprising untreated hyperprolactinemic patients (n = 10) and a second group consisting of normoprolactinemic controls with pituitary lesions (n = 10). Measures of impulsivity included both self-report questionnaires as well as laboratory-based tasks. Hyperprolactinemic patients on DAs had a higher score (mean ± SD) in one self-report measure of impulsivity, the attention subscale of the Barratt Impulsiveness Scale (16.2 ± 2.7), as compared to the hyperprolactinemic control group (12.3 ± 2.5) and the normoprolactinemic group (14.7 ± 4.4) (p = 0.04). No statistically significant difference was found between groups with regards to the other impulsivity scales. In the DA-treated group, a correlation was observed between increased impulsivity (as assessed in the Experiential Discounting Task) and higher weekly cabergoline dose (r(2) = 0.49, p = 0.04). The use of DAs in hyperprolactinemic patients is associated with an increase in one aspect of impulsivity. This effect should be further characterized in larger, longitudinal studies.

Laboratories are increasingly shifting to new automated 25-hydroxyvitamin D (25-OHD) assays, with subsequent variability in results.We describe the experience at our center with such a shift and illustrate its clinical implications.25-OHD levels were measured in 494 patients using Immunodiagnostic Systems RIA (IDS-RIA) and DiaSorin Liaison assays. Sources of variability between the assays were investigated in a subset of 83 samples, retested in the reference laboratory in the United States, and by reviewing the performance reports issued by the International Vitamin D External Quality Assessment Scheme, DEQAS. 25-OHD cut-points for target levels were used to compare the two assays.25-OHD concentrations were significantly lower when measured with Liaison as compared to IDS-RIA: mean bias was -5 ng/ml, range was -38.1 to 18.7 ng/ml, P0.001; the absolute bias was independent of 25-OHD value. Interassay variability was also detected in values obtained in the reference laboratory and in DEQAS reports. Using 20 ng/ml as the target 25-OHD level, 52% of patients required treatment when tested by Liaison, as opposed to 36% by IDS-RIA (P0.001). Using 30 ng/ml as the desirable level, the proportions were 79 and 64%, respectively (P0.001). The two assays agreed in only 41-68% of subjects, proportions that depended on criteria used to define agreement.A change in 25-OHD assays has a significant impact on results, patient classification, and treatment recommendations. Such variability cannot be ignored when deriving and applying vitamin D guidelines. It also renders universal assay standardization a pressing call.