Continuous subcutaneous insulin infusion is associated with a better glycemic control than multiple daily insulin injections without difference in diabetic ketoacidosis and hypoglycemia admissions among Emiratis with Type 1 diabetes.

AIMS: To characterizes Emiratis patients with Type 1 diabetes (T1D) and compares outcomes between continuous subcutaneous insulin infusion (CSII) versus multiple daily insulin injections (MDI) users. The WHO-Five Well-Being Index (WHO-5) score was used to screen for depression. METHODS: In this cross-sectional study; sociodemographic, clinical characteristics and insulin replacement regimens were collected on patients with T1D between 2015-2018. RESULTS: 134 patients with mean age of 20.9±7.5 years were included. Females constitute 56.7% and 50.7% had diabetes duration of >10 years. Diabetic ketoacidosis (DKA) at presentation was reported in 46.3%. Average glycemic control over preceding 12months was satisfactory (less than 7.5%), suboptimal (7.5-9%), and poor (more than 9%) in 26.6%, 42.7% & 30.6% of the patients, respectively. Higher proportion of patients using CSII achieved satisfactory or suboptimal glycemic control compared to patients with MDI (P = 0.003). The latest median /IQR HbA1c was significantly lower (P = 0.041) in patients using CSII (8.2 /1.93%) compared to MDI (8.5/2.45%). There was no significant difference between two groups in DKA, severe hypoglycemia or total WHO-5 score. CONCLUSIONS: CSII usage was associated with better glycemic control than MDI, although no difference in DKA and severe hypoglycemia. The overall glycemic control among Emiratis subjects with T1D is unsatisfactory and needs more rigorous patient counseling and education.

Characteristics and Challenges of Primary Adrenal Insufficiency in Africa: A Review of the Literature.

Backgrounds: Africa comprises 54 countries with varying degrees of economic development. As with other healthcare systems, rare diseases such as adrenal insufficiency are neglected and poorly documented. Objectives: We wished to explore primary adrenal insufficiency (PAI) in Africa, its prevalence, aetiology, genetics, presentation, diagnosis, and treatment and to determine the unmet needs in clinical care, education, and research. Materials and Methods: A narrative nonsystematic review of the literature was undertaken. We searched two online databases (PubMed and Google scholar) using the search terms "Addison's disease/PAI, primary adrenal insufficiency coupled with "Africa," "country names," and "genetic disorders." A total of 184 PAI records were reviewed. The exclusion of abstracts, conference proceedings, single case reports, and duplicate studies covering the same subject matter yielded 124 articles, of which 97 informed the final manuscript. Results: A wide range of aetiology of PAI was encountered, but their true prevalence is unknown. Aetiology varied with region and age of presentation as reflected by predominantly TB, HIV, and infective causes occurring in sub-Saharan Africa and more congenital forms described in North Africa associated with consanguinity. In Africa, the diagnostic criteria for PAI do not universally accord with conventional criteria, and there is a heavy reliance on clinical suspicion and biochemistry, including random cortisol of <400 nmol/L, rather than the tetracosactide test where stimulated cortisol <500-550 nmol/L confirms the diagnosis. Conclusions: A high index of suspicion is warranted to diagnose PAI in resource-limited settings, especially where tetracosactide tests are not universally available.

Relationship between lipid profile, inflammatory and endothelial dysfunction biomarkers, and type 1 diabetes mellitus: a case-control study.

OBJECTIVE: Inflammation is a major factor in endothelial dysfunction (ED) which is the earliest predictor of cardiovascular disease and premature mortality in type 1 diabetes mellitus (T1DM) patients. This study aimed to describe the possible relationship between plasma lipids and inflammatory and ED biomarkers in young Emirati patients with and without T1DM. METHODS: This case-control study included 158 patients with T1DM and 157 healthy controls from the local population of the United Arab Emirates (UAE). Anthropometric data, clinical variables, lipid profiles, liver enzymes, HbA1c, inflammatory, and ED biomarkers were measured for all participants using sophisticated techniques and assays. RESULTS: The mean ages ± SD of patients with T1DM and healthy controls was 19.3 ± 6.4 years (59.5% females) and 9.2 ± 6.8 years (61.5% females), respectively. The mean duration of T1DM was 9.3 ± 5.7 years, with HbA1c of 8.9 ± 2.1%. BMI, WC, SBP, and DBP significantly differed between the two groups. The mean lipid profiles (HDL, TG, TC, ApoA, and ApoB), liver enzymes (GGT, ALT), inflammatory (IL-6, adiponectin, TNF-α, hs-CRP), and ED biomarker levels (ICAM-1, VCAM-1, selectin, and ET-1) were also significantly different between patients and controls. Based on Spearman's rank and logistic regression analysis, there was a significant association between elevated lipid profile, liver enzymes, inflammatory markers, and ED markers in T1DM patients compared to controls. Among the biomarkers studied, ApoA, ApoB, and TC were significantly increased in T1DM patients compared to controls. CONCLUSION: This study revealed a strong association between an elevated lipid profile and inflammatory and ED markers with T1DM, which could lead to cardiovascular events in the UAE population.

Clinical characteristics and outcomes of care in patients hospitalized with diabetic ketoacidosis.

AIMS: To assess the clinical characteristics and outcomes of patients hospitalized with DKA. METHODS: We examined the hospital database for patients admitted with DKA to all government hospitals in Qatar over 6 years. RESULTS: We evaluated a total of 1330 patients [(37.3 % with type 1 diabetes (T1DM) and 62.7 % with type 2 diabetes (T2DM)] with 1613 episodes of DKA. Patients with T2DM were older than those with T1DM [48.0 (38.0-60.0), 26.0 (21.0-31.0) years] while there was no difference in DKA severity and laboratory values on admission or time to resolution of DKA. Admission to the intensive care unit was higher (38.9 % vs. 26.6 %; P < 0.001) with a longer hospital stay [5 (2.0-9.0) vs. 2 (2.0-4.0) days, P < 0.001] and markedly higher mortality (7.4 % vs. 1 %; P < 0.001) in patients with T2DM compared to T1DM. On multivariable logistic regression analysis, significant predictors of mortality were older age (odds ratio, 1.11; 95 % CI, 1.07-1.15; P = 0.0001), and admission to the intensive care unit (odds ratio, 3.61; 95 % CI, 1.69-7.72;P = 0.001). CONCLUSION: In this national cohort of patients hospitalized with DKA, those with T2DM had a 7-fold increase in inpatient mortality associated with older age and admission to the intensive care unit.

Proportion and predictors of Hypogonadism Recovery in Men with Macroprolactinomas treated with dopamine agonists.

INTRODUCTION: Hypogonadism is the most common form of hypopituitarism in men with macroprolactinoma. However, evidence on factors related to hypogonadism recovery is limited. OBJECTIVES: We estimated the proportion of hypogonadism in men with macroprolactinoma exclusively treated with dopamine agonists, and we assessed the factors predicting hypogonadism recovery. PATIENTS AND METHODS: This was a multicenter retrospective study of men with macroprolactinoma identified using ICD 9 and 10 codes and treated between 2009 and 2019 in five centers in the United Arab Emirates and Saudi Arabia. We evaluated hypogonadism, defined as low total testosterone (TT) level with normal or low gonadotropins on presentation and during the last clinic visit. RESULTS: A total of 79 patients (median age 32 years) were included in the study. The most common symptoms at presentation were headache (73.7%), erectile dysfunction (55.4%), and low libido (54.3%). The median tumor size was 2.9 cm (1.0-9.7) at diagnosis. Sixty-three patients (79.7%) had hypogonadism at baseline. Growth hormone deficiency (GHD) and hypothyroidism were present in 34.4% and 32.9% of patients, respectively. The median serum prolactin (PRL) level was 20,175 (min-max 2254 - 500,000) mIU/l with a median serum TT of 4.5 (min-max 0.4-28.2) nmol/l. Most patients were treated with cabergoline (n = 77, 97.5%) with a median of 6 (min-max 0.6-22) years. At follow-up, 65% of patients recovered their pituitary-testicular axis. Patients with recovered hypogonadism had smaller median tumor size (2.4 [1-5.4] vs. 4.3 [1.6-9.7], p = 0.003), lower PRL level (18, 277 [2254 - 274, 250] vs. 63,703 [ 3,365-500,000], p = 0.008 ), higher TT level (4.6 [0.6-9.2] vs. 2.3 [0.5-7.3], p = 0.008), lower PRL normalization time on medical therapy (8 months (0.7-72) vs. 24 (3-120), p = 0.009) as well as lower frequency of GHD (17.1% vs. 60%, p = 0.006) and secondary hypothyroidism (17.9% vs. 57.1%, p = 0.003) compared with those with persistent hypogonadism respectively. Age at diagnosis, presenting symptoms and duration of medical therapy did not predict hypogonadism recovery. CONCLUSIONS: About two-thirds of men with macroprolactinoma recover from hypogonadism, mostly with 24 months of therapy. Smaller adenoma size, lower prolactin level, earlier prolactin normalization, and higher testosterone patients were related to testosterone normalization.

HLA-DRB1 and -DQB1 Alleles, Haplotypes and Genotypes in Emirati Patients with Type 1 Diabetes Underscores the Benefits of Evaluating Understudied Populations.

Background: HLA class II (DR and DQ) alleles and antigens have historically shown strong genetic predisposition to type 1 diabetes (T1D). This study evaluated the association of DRB1 and DQB1 alleles, genotypes, and haplotypes with T1D in United Arab Emirates. Materials and Methods: Study subjects comprised 149 patients with T1D, and 147 normoglycemic control subjects. Cases and controls were Emiratis and were HLA-DRB1 and -DQB1 genotyped using sequence-based typing. Statistical analysis was performed using Bridging Immunogenomic Data-Analysis Workflow Gaps R package. Results: In total, 15 DRB1 and 9 DQB1 alleles were identified in the study subjects, of which the association of DRB1*03:01, DRB1*04:02, DRB1*11:01, DRB1*16:02, and DQB1*02:01, DQB1*03:02, DQB1*03:01, and DQB1*06:01 with altered risk of T1D persisted after correcting for multiple comparisons. Two-locus haplotype analysis identified DRB1*03:01∼DQB1*02:01 [0.44 vs. 0.18, OR (95% CI) = 3.44 (2.33-5.1), Pc = 3.48 × 10-10]; DRB1*04:02∼DQB1*03:02 [0.077 vs. 0.014, OR = 6.06 (2.03-24.37), Pc = 2.3 × 10-3] and DRB1*04:05∼DQB1*03:02 [0.060 vs. 0.010, OR = 6.24 (1.79-33.34), Pc = 0.011] as positively associated, and DRB1*16:02∼DQB1*05:02 [0.024 vs. 0.075, OR = 0.3 (0.11-0.74), Pc = 0.041] as negatively associated with T1D, after applying Bonferroni correction. Furthermore, the highest T1D risk was observed for DR3/DR4 [0.104 vs. 0.006, OR = 25.03 (8.23-97.2), Pc = 2.6 × 10-10], followed by DR3/DR3 [0.094 vs. 0.010, OR = 8.72 (3.17-25.32), Pc = 3.18 × 10-8] diplotypes. Conclusion: While DRB1 and DQB1 alleles and haplotypes associated with T1D in Emiratis showed similarities to Caucasian and non-Caucasian populations, several alleles and haplotypes associated with T1D in European, African, and Asian populations, were not observed. This underscores the contribution of ethnic diversity and possible diverse associations between DRB1 and DQB1 and T1D across different populations.

Characteristics and Management of Papillary Thyroid Microcarcinoma in the United Arab Emirates: Experience from a Large Tertiary Hospital.

Background: Recent guidelines in the management of papillary thyroid microcarcinoma (PTMC) recommend limiting surgery. However, trends in the characteristics and management of PTMC from the Middle East and North Africa region is lacking. Objectives: To determine the clinical features, management strategy, and outcomes of PTMC in a large tertiary care center in the United Arab Emirates (UAE). Patients and Methods: This retrospective study included all patients diagnosed with PTMC (i.e., size ≤10 mm) at Tawam Hospital, Al Ain, UAE, between 2008 and 2019. Tumor histopathology, management strategy, and outcomes were the primary analyzed variables. Results: A total of 213 patients with PTMC met the inclusion criteria, of which 83.6% were women and 58.7% were Emiratis. The majority had the classical tumor subtype (76.1%) and tumor of size 5-10 mm (71.4%). Multifocal disease was present in 41.1% and lymph node metastasis (LNM) in 16.6% of the patients. According to the 2015 American Thyroid Association categorization, the majority (93.9%) had a low-risk disease, and all except one patient had Stage 1 disease. Total thyroidectomy was performed in 91.1% of the patients, and 47.9% received radioiodine (RAI) therapy. None of the patients were under active surveillance strategy. RAI treatment was used more often in patients with non-incidental tumors, larger tumor size, multifocal disease, positive LNM, tumors in the intermediate/high ATA category, and those who underwent total thyroidectomy or neck dissection (for all, P < 0.05). After a median follow-up of 32.4 months, about 73% had an excellent response to dynamic risk stratification assessment, and only one patient had disease recurrence. Conclusions: The majority of the patients had low-risk PTMC, yet most patients underwent total thyroidectomy, and almost 50% were treated with RAI ablation. Further studies are needed to determine if these trends are also present regionally and to explore reasons for not adopting a less aggressive approach in this indolent tumor.

Management of Diabetes Insipidus following Surgery for Pituitary and Suprasellar Tumours.

Central diabetes insipidus (CDI) is a common complication after pituitary surgery. However, it is most frequently transient. It is defined by the excretion of an abnormally large volume of dilute urine with increasing serum osmolality. The reported incidence of CDI after pituitary surgery ranges from 0-90%. Large tumour size, gross total resection and intraoperative cerebrospinal fluid leak usually pose an increased risk of CDI as observed with craniopharyngioma and Rathke's cleft cysts. CDI can be associated with high morbidity and mortality if not promptly recognised and treated on time. It is also essential to rule out other causes of postoperative polyuria to avoid unnecessary pharmacotherapy and iatrogenic hyponatremia. Once the diagnosis of CDI is established, close monitoring is required to evaluate the response to treatment and to determine whether the CDI is transient or permanent. This review outlines the evaluation and management of patients with CDI following pituitary and suprasellar tumour surgery to help recognise the diagnosis, consider the differential diagnosis, initiate therapeutic interventions and guide monitoring and long-term management.

Knowledge gaps and perceptions of future research directions on management of diabetes during Ramadan fasting: An online survey of physicians.

OBJECTIVES: Current knowledge and research on diabetes and Ramadan form the basis for evidence-based clinical practice. In this context, we aimed to explore physicians' perceptions of current knowledge gaps about research fasting (RF), barriers to, and foreseeable directions for advancement of the field. METHODS: We conducted an online survey of a convenience sample of 260 physicians from 27 countries. The survey questionnaire addressed three main domains: perceived current knowledge gaps and unmet needs in research about RF and diabetes, barriers to the conduct of research, and future directions for furthering the evidence in this field. RESULTS: Majority of respondents (65.7%) were senior physicians in adult endocrinology/diabetes (45.9%) working at tertiary centers (65.2%). The majority (67.3%) reported seeing an average of 20+ patients with diabetes weekly and felt "very or fairly confident" in managing diabetes during RF (67.7%). The knowledge gaps identified were the management of high-risk patients with diabetes (54.1%), such as renal impairment (59.8%), and pregnancy (61.5%). The main barriers to research were lack of adequate funding to academic centers (75.7%) and lack of interest of institutions in the subject (64.6%). Future efforts should be directed at the conduct of large epidemiological studies (49.5%) or double-blinded, placebo-controlled clinical trials (48.6%) to address the former gaps. Research findings should be widely disseminated via hands-on workshops (recommended by 70.3% of respondents) or international conferences (61.2%). CONCLUSIONS: There is a wide agreement regarding the knowledge gaps in the management of diabetes during RF. Future efforts should focus on addressing these critical deficiencies.

Changing how we risk-categorise in Ramadan: Does the IDF-DAR scoring system achieve the requirements for people with diabetes internationally?

The IDF-DAR guidance was most recently updated this year. The most notable change is the moving to a scoring system from a tabulated risk categorization to determine and classify the risk of harm from fasting derived from an online survey. This change may be appealing and is welcomed. However, such a system and the methodology underpinning it is not without limitations. This commentary highlights some of these limitations and the associated limited safe options available to individuals with diabetes desiring to fast during Ramadan. Overlooked clinical considerations that deserve formal recognition include the role of technology (aspects relating to glucose monitoring and/or insulin delivery) and previous experience of safe Ramadan fasting. Further, duration of fast (which can almost double in temperate regions from winter to summer) needs greater emphasis. We also advocate separate scoring systems for people with type 1 diabetes and complex type 2 diabetes. The guidance acknowledges fasting is an individual's decision, however the general message needs to be more person-centred and currently only presents a binary approach to fasting - all or nothing choices. We propose and discuss addition options including, trial fasting of voluntary fasts, starting the fast and terminating due to health and/or safety, intermittent fasting and winter fasting.

Diagnosis and management of X-linked hypophosphatemia in children and adolescent in the Gulf Cooperation Council countries.

INTRODUCTION: X-linked hypophosphatemia (XLH) is a rare inherited cause of hypophosphatemic rickets and osteomalacia. It is caused by mutations in the phosphate-regulating endopeptidase homolog, X-linked (PHEX). This results in increased plasma fibroblast growth factor-23 (FGF23), which leads to loss of renal sodium-phosphate co-transporter expression leading to chronic renal phosphate excretion. It also leads to low serum 1,25-dihydroxyvitamin D (1,25(OH)2D), resulting in impaired intestinal phosphate absorption. Chronic hypophosphatemia in XLH leads to impaired endochondral mineralization of the growth plates of long bones with bony deformities. XLH in children and adolescents also causes impaired growth, myopathy, bone pain, and dental abscesses. XLH is the most frequent inherited cause of phosphopenic rickets/osteomalacia. Hypophosphatemia is also found in calcipenic rickets/osteomalacia as a result of secondary hyperparathyroidism. Thus, chronic hypophosphatemia is a common etiologic factor in all types of rickets. RESULTS: There is considerable overlap between symptoms and signs of phosphopenic and calcipenic rickets/osteomalacia. Wrong diagnosis leads to inappropriate treatment of rickets/osteomalacia. Nutritional rickets and osteomalacia are common in the Gulf Cooperation Council countries which include Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Bahrain, and Oman. Due to high levels of consanguinity in the region, genetic causes of phosphopenic and calcipenic rickets/osteomalacia are also common. CONCLUSION: This guideline was developed to provide an approach to the diagnosis of XLH, especially where there is no family history of the disease, and that other related conditions are not mistaken for XLH. We also guide the medical management of XLH with conventional treatment and with burosumab, a recombinant human IgG1 monoclonal antibody to FGF23.

Management of diabetic ketoacidosis in special populations.

Diabetic ketoacidosis (DKA) is an acute complication of diabetes mellitus that can be associated with increased morbidity and mortality, particularly if it is diagnosed late and not treated appropriately. The management of DKA includes careful clinical evaluation, correction of metabolic abnormalities with intravenous fluids, insulin and electrolyte replacement with frequent monitoring of the patients' clinical and laboratory findings and also identification and treatment of the precipitating condition. There are special populations where features, management and outcome may differ from the usual patient with diabetes. Data on management of DKA in such special populations such as chronic kidney disease and pregnancy are sparse and recommendations are based mainly on small case series and expert opinion. Clinicians need to recognize and manage euglycaemic DKA in patients prescribed sodium-glucose cotransporter inhibitors. DKA is particularly a major health concern due to high rates of hospital admissions and mortality in resource-limited settings due to financial constraints, limiting the adequate provision of insulin and access to health care systems, and dysfunctional health systems. We review the challenges of diagnosis and management of DKA in these specific groups and provide recommendations on optimal patient care.

Association of variants in PTPN22, CTLA-4, IL2-RA, and INS genes with type 1 diabetes in Emiratis.

Type 1 diabetes (T1D) is a chronic autoimmune disease with a complex interrelation of genetic and environmental factors. Genetic studies have reported HLA and non-HLA loci as significant contributors to T1D. However, the genetic basis of T1D among Emiratis is unexplored. This study aims to determine the contribution of four genes PTPN22, CTLA-4, IL2-RA, and INS to T1D risk among Emiratis. The association between variants in PTPN22 (rs2476601, rs1310182), CTLA-4 (rs11571316, rs231775, rs3087243, rs1427676, and rs231727), IL2-RA (rs7090530), and INS (rs7111341) with T1D was tested in 310 Emiratis (139 T1D patients and 171 controls). A significant association was found at rs1310182, and rs2476601 both in PTPN22, rs3087243, and rs231775 both in CTLA-4, and rs12251307 in IL2-RA. Moreover, a haplotype constituted from GG and AG genotypes at rs231727 and rs231775, respectively, in CTLA-4 was significantly associated with an increased T1D risk. The cumulative effects of risk alleles for all significantly associated SNPs showed 11.8 higher relative risk for T1D for those who carry 5-6 compared to 0-1 risk alleles. This study illustrated that PTPN22, CTLA-4, and IL2-RA gene variants could confer risk alleles for T1D among the Emirati population.

Ramadan fasting and diabetes 2019: The year in review.

INTRODUCTION: The literature on health aspects of Ramadan fasting is widely spread in many journals making it not readily available to those interested in the subject. MATERIALS AND METHODS: A narrative, non-systematic review of the international literature from two major online databases (viz. Scopus, PubMed) in one year (2019). The search term "Ramadan fasting AND Diabetes" was used, and relevant literature was narrated in a concise thematic account. RESULTS: Research design included qualitative, quantitative, and mixed methods. Articles included controlled trials, critical appraisals, literature narrations, and systematic reviews, and meta-analyses. The publications spanned a vast array of topics related to Ramadan fasting, including assessments of current safety and efficacy profiles of newer diabetes therapies, modes of insulin delivery, and utilization of advanced technology for the treatment and monitoring of blood glucose during Ramadan fasting. Increased interest was particularly evident in capturing the experience element manifested by perceptions, attitudes, and practices of both patients and healthcare professionals during Ramadan. The current literature consolidates previous data on the safety of fasting practices amongst the well-controlled. On the other hand, it emphasizes the need for more aggressive interventions for high-risk patients, promoting the usage of newer anti-diabetic agents and advanced glucose monitoring technology for safer fasting practices. CONCLUSIONS: The volume of global literature production related to Ramadan fasting and Diabetes remains modest. Observational studies of small size prevail. Greater improvements in both quality and quantity of research on Ramadan are needed.

Tiered healthcare in South Africa exposes deficiencies in management and more patients with infectious etiology of primary adrenal insufficiency.

OBJECTIVE: We wished to determine the prevalence, etiology, presentation, and available management strategies for primary adrenal insufficiency (PAI) in South Africa (SA), hypothesizing a prevalence greater than the described 3.1 per million. There is great inequity in healthcare allocation, as two parallel healthcare systems exist, potentially modifying PAI patients' clinical profiles, private being better resourced than public healthcare. METHODS: An online survey of physicians' experience relating to PAI. RESULTS: The physicians were managing 811 patients, equal to a prevalence of 14.2 per million. Likely causes of PAI in public/ academic vs private settings included: AIDS-related [304 (44.8%) vs 5 (3.8%); p<0.001], tuberculosis [288 (42.5%) vs 8 (6.0%); p<0.001], autoimmune disease [50 (7.4%) vs 88 (66.2%); p<0.001], malignancy [27 (4.0%) vs 7 (5.3%); p = 0.500], genetic including adrenoleukodystrophy (ALD) [5 (0.7%) vs 16 (12.0%); p<0.001], respectively. Overall, more patients presented with nausea [101 (74.3%) and vomiting 89 (65.9%), than diarrhoea 76 (58.9%); p = 0.008 and 126 (15.5%) in adrenal crisis. Features suggestive of a crisis were hypoglycaemia [40 (78.4%) vs 42 (48.8%); p = 0.001], shock [36 (67.9%) vs 31(36.9%); p<0.001], and loss of consciousness [25 (52.1%) vs 27 (32.9%); p = 0.031]. Greater unavailability of antibody testing in the public vs. the private sector [32 (66.7%) vs 30 (32.1%); p = 0.001], [serum-ACTH 25 (52.1%) vs 16 (19.5%); p<0.001] and glucocorticoids were [26 (54.2%) vs 33 (40.2%); p = 0.015]. Many patients, 389(66.7%) were not using identification, indicating that they need steroids in an emergency. CONCLUSION: A survey of South African physicians suggests a higher prevalence than previously reported. Patients presented with typical symptoms, and 15.5% presented in adrenal crisis. Significant disparities in the availability of physicians' expertise, diagnostic resources, and management options were noted in the public versus private settings. Greater awareness among health practitioners to timeously diagnose PAI is required to prevent a life-threatening outcome.

Clinical Presentation, Treatment, and Outcome of Acromegaly in the United Arab Emirates.

OBJECTIVES: We sought to ascertain the clinical characteristics and control rate of acromegaly in the UAE. METHODS: We conducted a multicenter retrospective analysis of all patients presenting with acromegaly to six endocrine centers in the UAE between November 2010 and December 2018. Demographic, clinical, biochemical, and radiologic data were collected. Patients were considered controlled if normal insulin-like growth factor-1 (IGF-1) level and growth hormone < 1 mcg/L were achieved at their last visit. RESULTS: A total of 75 patients were included in the study (60.0% males, 33.3% native UAE nationals). The mean age at diagnosis was 37.2 (range: 12-69) years. Common clinical features at diagnosis were headache (82.4%), coarse facial features (82.4%), acral enlargement (79.7%), and sweating (31.3%). Diabetes mellitus/prediabetes and hypertension were present in 45.2% and 35.5% of patients, respectively. About 82.2% had pituitary macroadenoma on pituitary magnetic resonance imaging. At presentation, 27.0% and 3.2% of the patients had secondary hypogonadism and diabetes insipidus, respectively. Overall, 76.7% of the patients underwent surgery, 20.8% received radiotherapy, and 50.7% received medical therapy. At their last clinic visit, only 43.7% of all patients achieved disease control. CONCLUSIONS: Our study shows a high prevalence of pituitary macroadenoma in our acromegalic population, suggesting a delayed diagnosis. Also, a significant proportion of patients remained uncontrolled. Efforts to increase physician's awareness of acromegaly and to improve disease control are underway.

Evolving physicians' perceptions and practices regarding use of SGLT2 inhibitors for type 2 diabetes during Ramadan fasting.

OBJECTIVES: We followed up the evolving perceptions and practices regarding use of SGLT-2 inhibitors in Ramadan. METHODS: We compared results of the three survey in 2015, 2017, 2019. RESULTS: Senior doctors represented 43.5-66.4% and endocrinologists accounted for 38.1-60.2%. There was a steady reduction in the proportions of respondents who did not know SGLT2-Is at all, who have just heard about the class and those who are quite familiar with the class but have not yet used any. Whereas the proportions of those using the SGLT2-Is class occasionally only was stable. However those who use the SGLT2-Is regularly increased from 11.0% to 45.6% and 62.6%. The respondents' who SGLT2-Is are safe and may be used in all fasting diabetic patients increased from 15.5%, 14.7% to 23.1%. Whereas the view that SGLT2-Is should not be used decreased progressively. Majority of respondents in the three surveys suggested that specific advice is given if they allow the use of SGLT2-Is during Ramadan. More respondents advise taking the medication with the first evening meal than before the last pre-dawn meal and advised to attend to their hydration status. One third of respondents would resume SGLT2-Is immediately after the end of Ramadan; 15% after 1-2 weeks, or prefer to wait till the next medical or educator's clinic visit and others would re-evaluate patients' management plan. CONCLUSIONS: The medical professions' knowledge and perceptions regarding the use of SGLT2-Is during Ramadan fasting have evolved over the last few years due to increasing research and experience.

Management of adrenal insufficiency during Ramadan fasting: a survey of physicians.

INTRODUCTION: Appropriate dose adjustments of glucocorticoids replacement therapy for adrenal insufficiency (AI) is vital. OBJECTIVE: We sought to scope physicians' perceptions, and practices regarding Ramadan fasting (RF) impact on the management of AI. METHODS: A web-based survey of a convenience sample of endocrinologists. RESULTS: Nearly two-thirds of 145 respondents (64.1%) were adult endocrinologists and almost half (49%) saw more than 10 hypoadrenal patients per year. Most respondents (78.6%) prescribed hydrocortisone, while the minority prescribed other preparations. The glucocorticoid doses were reportedly divided twice daily by 70.8% and thrice daily by 22.2% of respondents. Respondents recognized RF as having potential consequences in adrenal insufficiency patients included causing hypoglycaemia, undue tiredness, and fatigue, hypotension, feeling dizzy, and light-headedness. Symptoms of under-replacement were thought to happen in the late afternoon by 59.3% of respondents. Almost half (45.5%) of respondents thought that RF has some probable or definite impact on glucocorticoid therapy that certainly warrants specific concern and possible action. Three quarters (76.4%) of respondents confirmed providing specific management recommendations during RF. The most frequently reported recommendation was taking in the usual morning dose of hydrocortisone just before pre-dawn meal (Suhor) (57.8%). A third switch patients from hydrocortisone to prednisolone/prednisone. Half reported providing patients with specific recommendations regarding breaking their fast and/or seeking help if hypoadrenal symptoms occur. CONCLUSIONS: There is a remarkable variation in the physicians' perceptions and practices regarding the management of AI during Ramadan. This warrants professional effort to increase the awareness and dissemination of evidence-based guidelines.

Contemporary Management of Clinically Non-functioning Pituitary Adenomas: A Clinical Review.

Non-functioning pituitary adenomas (NFPAs) are benign pituitary tumours that constitute about one-third of all pituitary adenomas. They typically present with symptoms of mass effects resulting in hypopituitarism, visual symptoms, or headache. Most NFPAs are macroadenomas (>1 cm in diameter) at diagnosis that can occasionally grow quite large and invade the cavernous sinus causing acute nerve compression and some patients may develop acute haemorrhage due to pituitary apoplexy. The progression from benign to malignant pituitary tumours is not fully understood; however, genetic and epigenetic abnormalities may be involved. Non-functioning pituitary carcinoma is extremely rare accounting for only 0.1% to 0.5 % of all pituitary tumours and presents with cerebrospinal, meningeal, or distant metastasis along with the absence of features of hormonal hypersecretion. Pituitary surgery through trans-sphenoidal approach has been the treatment of choice for symptomatic NFPAs; however, total resection of large macroadenomas is not always possible. Recurrence of tumours is frequent and occurs in 51.5% during 10 years of follow-up and negatively affects the overall prognosis. Adjuvant radiotherapy can decrease and prevent tumour growth but at the cost of significant side effects. The presence of somatostatin receptor types 2 and 3 (SSTR3 and SSTR2) and D2-specific dopaminergic receptors (D2R) within NFPAs has opened a new perspective of medical treatment for such tumours. The effect of dopamine agonist from pooled results on patients with NFPAs has emerged as a very promising treatment modality as it has resulted in reduction of tumour size in 30% of patients and stabilization of the disease in about 58%. Despite the lack of long-term studies on the mortality, the available limited evidence indicates that patients with NFPA have higher standardized mortality ratios (SMR) than the general population, with women particularly having higher SMR than men. Older age at diagnosis and higher doses of glucocorticoid replacement therapy are the only known predictors for increased mortality.

Significant barriers to diagnosis and management of adrenal insufficiency in Africa.

BACKGROUND: The burden and management of primary adrenal insufficiency (PAI) in Africa have not been well documented. We aimed to identify specific disease characteristics, patient demographics, and patterns of clinical management in established PAI in Africa. METHODS: An online survey of physicians' experience relating to PAI. RESULTS: There were 1334 responses received, 589 were complete, and 332 respondents reported managing patients with hypoadrenalism. The described responses were related to a calculated pool of 5787 patients with hypoadrenalism (2746 females, 3041 males), of whom 2302 had PAI. The likely causes of PAI in Sub-Saharan Africa (SSA) vs the Middle East and North Africa (MENA) regions included autoimmune disease (20% vs 60.3%; P < 0.001), tuberculosis (34% vs 4.1%; P < 0.001), AIDS (29.8% vs 1%; P < 0.001), malignancy, and genetic conditions. Sixteen percent of AD patients (376/2302) presented in an adrenal crisis. Medical emergency identification was not used by 1233 (83.6%) SSA vs 330 (40.4%) MENA patients (P < 0.001), respectively. Relative non-availability of diagnostic tests across both regions included adrenal antibodies 63% vs 69.6% (P = 0.328), s-cortisol 49.4 % vs 26.7% (P = 0.004), s-ACTH 55.7% vs 53.3% (P = 0.217), and adrenal CT scans 52.4% vs 31.8% (P = 0.017) in the SSA and MENA region, respectively. Across the entire cohort, the overall hydrocortisone use and extrapolated proportion of synacthen use were 59.4% and 50.7%, respectively. CONCLUSIONS: Through the perception and practice of healthcare professionals, we identified significant challenges in the diagnosis and management of PAI which may herald high mortality. Differences between regions may reflect the allocation of healthcare resources.