Efficacy and Cardiovascular Safety of Meglitinides.

Meglitinides are a group of oral hypoglycemic medications currently approved for the treatment of type 2 diabetes mellitus (T2DM). Two meglitinide molecules, Repaglinide and Nateglinide, are presently in use. Repaglinide is preferred because of its superior glycemic efficacy. They have modest efficacy with a mean decrement of glycosylated haemoglobin (HbA1c) ranging between -0.2 to -1.50% with individual therapy. Additional HbA1c reduction can occur with combination therapy with other oral hypoglycemics. This class of drugs is effective in controlling postprandial hyperglycemia with minimal risk of hypoglycemia. It is also useful in patients with variable meal timings, especially in the elderly, and in patients with renal failure. There are a dearth of long-term studies on meglitinides to assess cardiovascular outcomes or mortality in T2DM, although the Nateglinide and Valsartan in Impaired Glucose ToleranceOutcomes Research (NAVIGATOR) study showed no difference between Nateglinide and placebo with regard to the core composite cardiovascular outcomes. Based on a PubMed literature search using key words: 'meglitinides', 'repaglinide', 'nateglinide', 'HbA1c', 'glycated haemoglobin', 'cardiovascular safety', 'cardiovascular events', 'cardiovascular outcome trials', 'type 2 diabetes mellitus' and heart failure, and combining the search terms using Boolean operators 'AND', 'OR' and 'NOT' as needed we compiled current evidence for use of these oral hypoglycemic agents in clinical use. This article is an attempt to review the efficacy and cardiovascular (CV) safety of Meglitinides to help clinicians to use this class of oral hypoglycaemic agents prudently.

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.

Prevalence and characteristics of sellar masses in the city of Al Ain, United Arab Emirates: 2010 to 2016.

BACKGROUND: The prevalence of sellar masses (SMs) is reported in Europe and North America but only limited data are available from the Middle East and North Africa (MENA) region. OBJECTIVES: Assess the prevalence and characteristics of SMs in Al Ain city, United Arab Emirates. DESIGN: Retrospective, descriptive multicenter study. SETTING: Three endocrine centers in Al Ain. PATIENTS AND METHODS: All patients diagnosed with SMs in the city of Al Ain, Emirate of Abu Dhabi, between 2011 and 2016 were evaluated. Cases were identified using ICD 9 and 10 codes and demographic and clinical data were collected. The prevalence rate was calculated for patients alive and residing in Al Ain city until 31 December 2016. MAIN OUTCOME MEASURES: Clinical presentations and prevalence rate. SAMPLE SIZE: 272. RESULTS: The mean (SD) age on presentation was 40.8 (14.3) years (range: 6-114 years, median: 40.0). The 170 (61.8%) females and 128 (46.5%) were native citizens of the United Arab Emirates. Two hundred and forty five (90%) patients had pituitary adenomas (PAs) while 27 (10%) had non-pituitary sellar lesions. The four most common SMs were prolactinoma (n=139, 51.1%), nonfunctioning adenoma (NFA) (n= 69, 25.4%), somatotroph adenoma (n=32, 11.8%) and craniopharyngioma (n=15, 5.5%). Patients with prolactinoma, corticotroph adenoma, and Rathke's cleft cyst had small sellar masses (<1 centimeter) while the majority of patients with other SMs had macroadenomas. Hypogonadism and growth hormone deficiency was present in 41.8% and 20.5% of the patients, respectively. Of 268 patients with available data, 82 patients underwent surgery while 25 patients received radiotherapy. At the end of 2016, 197 patients were residing in Al Ain city. The overall prevalence of SMs was 25.7/100 000 with PAs constituting most of these masses (n=177) for a prevalence of 23.1/100 000. CONCLUSIONS: This is the first study of SMs in the United Arab Emirates and the MENA region. Prolactinoma and NFA were the two most common SMs. Further studies are needed to explore the reasons for the lower prevalence of SMs in our region compared with other countries. LIMITATIONS: Retrospective design, relatively small sample size. CONFLICT OF INTEREST: None.

Etiology and clinical profile of patients with Cushing's syndrome: A single center experience.

BACKGROUND: There is little published literature on the profile of patients with Cushing's syndrome (CS) from India. The aim of this study was to compile data of CS patients treated at this hospital. MATERIALS AND METHODS: Patients referred to the endocrine services of this hospital for diagnosis/treatment of CS from January 1985 to July 2012 were the subjects for this study. All patients had detailed medical history, physical examination and biochemical and hormonal assays (which changed with availability of tests and changing views). Assays for plasma adrenocorticotropic hormone (ACTH) (late 90s), salivary cortisol estimation, IJV sampling for ACTH and corticotrophin releasing hormone stimulation tests were added on later. Imaging included computed tomography (CT), magnetic resonance imaging (since the late 80's) and (68)Ga DOTA-TOC/FDG PET-CT (2008). RESULTS: Three hundred sixty-four patients (250 females, 114 males, age 6 months to 65 years, mean 28 years + 12 years) were diagnosed to have CS during this period. Two hundred and ninety-three patients (80.5%) were ACTH dependent (CD 215, ectopic ACTH syndrome 22, occult ACTH source 56) while 71 (19.5%) were ACTH independent (adrenal carcinoma 36, adenoma 30, primary pigmented nodular adrenal disease 4, AIMAH 1). Pituitary macro adenoma was seen in 14% of the CD cases. The most common presenting complaints were hypertension and diabetes mellitus. A total of 63% patients complained of weight gain while 15% had lost weight. Myopathy, infections, skeletal fractures and psychiatric problems were the other common observations in our patients. CONCLUSION: The clinical spectrum was broad. CD was the most common cause for CS.

The effects of inhaled corticosteroids on growth in children.

Inhaled corticosteroids (ICS) are recommended as the first-line therapy for children with persistent asthma. These agents are particularly effective in reducing underlying airway inflammation, improving lung function, decreasing airway hyper-reactivity, and reducing intensity of symptoms in asthmatics. Chronic diseases, such as asthma, have growth-suppressing effects independent of the treatment, which inevitably complicates growth studies. One year studies showed a small, dose-dependent effect of most ICS on childhood growth, with some differences across various ICS molecules, and across individual children. Some ICS at the doses studied did not affect childhood growth when rigorous study designs were used. Most studies did not conform completely with the FDA guidance. The data on effects of childhood ICS use on final adult height are conflicting, but one recent well-designed study showed such an effect, clearly warranting additional studies. In spite of these measurable effects of ICS on childhood growth, it is important to understand that the safety profile of all ICS preparations, with focal anti-inflammatory effects on the lung, is significantly better than oral glucocorticoids.

Cushing's disease: results of treatment and factors affecting outcome.

OBJECTIVE: To analyze the therapeutic results of intervention and the factors affecting the outcome of patients with Cushing's disease (CD) cared for at the All Indian Institute of Medical Science (AIIMS), New Delhi. DESIGN: Patients with Cushing's disease treated at a teritiary care centre from January 2000 to December 2009 were prospectively studied. RESULTS: Ninety-seven patients received treatment for CD during this period. Mean duration of follow-up was 3.4 ± 2.2 (mean ± SD) years. Eighty-one patients (83.5%) underwent transsphenoidal surgery (TSS) as the primary treatment modality. Fifty-four patients (66.7%) went into remission after initial TSS; ten (18.5%) of them relapsed after a mean follow-up period of 2.9 ± 2.1 (mean ± SD) years. Histopathologic examination of resected tissue showed corticotroph adenoma in 48 of the 54 (88.9%) who went into remission and 17 of the 27 (63.0%) who did not go into remission after the initial TSS. Sixteen patients with severe hypercortisolism underwent bilateral adrenalectomy (BA) as a life-saving measure which was followed by pituitary surgery 6 to 12 months later. Five patients including one with a large macroadenoma required three or more procedures to achieve eucortisolism. CONCLUSION: Fifty-four out of 81 (66.7%) of our patients with CD had remission following initial TSS, ten of whom relapsed later on. Sixteen patients unerwent BA as a life-saving procedure. Factors affecting outcome were, age, gender, low dose dexamethasone suppression test cortisol value and histologic confirmation of corticotroph adenoma.

Gender identity of children and young adults with 5alpha-reductase deficiency.

Male pseudohermaphroditism (46,XY DSD) due to 5alpha-reductase deficiency has been recognized for the last few decades. There is scant literature on this entity in India. We compiled data on five patients with this disorder. Four of our five patients were reared as females. Our assessment of these children reveals that they had male gender identity from childhood. Three of the four reared as females chose to change gender role at adolescence, while the fourth is still prepubertal. We conclude that all these patients had male gender identity from early childhood. The parents took note of this only after the appearance of male secondary sexual characteristics at puberty, thereby giving an impression of change in gender identity and gender role.

Partial duplication of the hypophysis in adult patients: report of 2 cases.

Complete duplication of the pituitary gland is an extremely rare condition which is associated with a wide range of anomalies. An incomplete duplication affecting only the anterior pituitary gland or the pituitary stalk has not been described so far. We report 2 such cases of partial duplication of the hypophysis and briefly review the literature.

Medullary thyroid carcinoma: a 20-year experience from a centre in South India.

BACKGROUND: Management of medullary thyroid carcinoma (MTC) remains controversial despite many advances over the past five decades. We attempt to review the presentation, management and prognosis of MTC at our institution over the last two decades. METHODS: We conducted a retrospective review of the records of 40 patients with MTC over a period of 20 years. RESULTS: Ten patients had hereditary MTC and 30 had sporadic MTC. The mean age of presentation was 41 years. Sixty-five per cent of the patients had a definite thyroid swelling and 43% had lymphadenopathy at the time of presentation. Total thyroidectomy with a central neck dissection was carried out in 82.5% of patients. Adjuvant therapy was given in 75% of patients because of extensive/residual disease. Postoperative hypercalcitoninaemia was seen 73% of patients. (131)I metaiodobenzylguanidine scanning was carried out in 16 patients with persistent hypercalcitoninaemia; the uptake was positive in 10 and negative in 6, indicating a positivity of 62%. CONCLUSION: Medullary thyroid carcinoma accounts for 2.5% of thyroid carcinomas. There is a small male preponderance. In our series (131)I metaiodobenzylguanidine scan had a better positivity than what has been reported in the published work. Persistent postoperative hypercalcitoninaemia was associated with a poorer prognosis that did not reach statistical significant.