International Journal of Endocrinology and Metabolism
Volume:16 Issue: 3, Jul 2018

Context: Celiac disease (CD) is a common phenomenon in children with Type 1 diabetes (T1D). In the present review, we have discussed the pathogenesis, diagnostic biomarkers, risk factors, and prognosis of CD in the context of pediatric T1D.
Evidence Acquisition: Literature published in Web of Science, PubMed, Scopus, Google Scholar, and Cochrane Library were scrutinized up to the end of 2017. The keywords of celiac disease, Type 1 diabetes, children, and pediatric were used in different combinations.
Immune cytotoxic reactions along with dampen immune regulatory functions contribute to CD in the context of pediatric T1D. Many children with simultaneous CD and T1D do not represent with the clinical signs of the enteropathy rendering a diagnostic challenge. The most common screening tests in these children are routine serological tests of CD, anti - endomysial, anti - transglutaminase, and anti - deamidated gliadin peptide antibodies. Typing for human leukocyte antigens of DQ - 2 and DQ - 8 may assist in the diagnosis of silent CD in children with T1D. The most significant shared non - HLA genetic loci of CD and T1D comprise CTLA - 4, TAGAP, IL - 18RAP, PTPN2, RGS1, SH2B3, CCR5. Interactions between these loci can be important in susceptibility to CD in T1D. Some new biomarkers have been suggested for diagnosis of CD including ischemia-modified albumin (IMA), soluble syndecan-1 (SSDC-1), regenerating gene Iα (REG-Iα), Neurotensin, and Zonulin, which can be useful for diagnosis and screening of CD in childhood T1D.
Overall, active seropositive CD seems to be of clinical importance in T1D with significant impacts on the quality of life and predisposition to diabetes associated complications. It is important to detect CD in the context of T1D to prevent potential risks contributing to morbidities and mortalities associated with either CD or T1D.

For addressing the burden of non-communicable diseases and policymaking, the world health organization uses World Bank income group to classify countries. This calcification method might not be optimal. This study aimed to investigate the role of World Bank income group, health expenditure, and cardiometabolic risk factors of countries in explaining the gap between their cardiometabolic mortality.
In total, 190 countries were categorized into four income groups according to the World Bank definition. The energy consumption, health expenditure, and data of sex-specified age-standardized prevalence of obesity, hypercholesterolemia, hypertension, diabetes, smoking, and physical inactivity in 2008 and cardiometabolic mortality in 2012 were used. Multivariable-adjusted mixed-effect linear regression models were applied to relate country-level predictors to their mortality outcomes.
While the lowest cardiometabolic mortality was recorded in high-income countries in both genders, the highest rates were recorded in the low-income category for women and in low and middle-income for men. Countries had lower cardiometabolic mortality for women compared to men; however, such a difference was not shown in low-income countries. World Bank income group of countries, per se, explained one-third of the variation in their mortality outcomes while adding health expenditure, energy consumption, and cardiometabolic risk factors increased the explanatory power of the model considerably. Moreover, the more the health expenditure, the weaker the association of prevalence of hypertension with cardiometabolic mortality.
Adding countries’ health expenditure and/or the prevalence of risk factors to their World Bank income group may contribute to the better explanation of the gap between them in cardiometabolic mortality.

Short stature in children represents a heterogeneous group with different etiologies. Primary Insulin like growth factor 1 (IGF - 1) deficiency in short stature can present with normal or elevated growth hormone (GH) production. Currently there is no model that can reliably predict response to recombinant (r)GH therapy and/or rIGF - 1 therapy in children with non - GH deficient short stature.
Hypothesis: Baseline Insulin like growth factor binding protein 3 (IGFBP - 3) along with ∆ IGF - 1 in the first 3 months of GH therapy level can be a marker of growth response to the rGH and/or rIGF - 1 therapy in children with non - growth hormone deficiency short stature.
To study the relationship between baseline IGFBP - 3 and IGF - 1 levels and the response to rGH and rIGF - 1 therapy in children with short stature, normal GH secretion and low IGF - 1 SDS.
43 children, age 9.07 ± 2.75 years with height -2.72 ± 0.7 SD and baseline IGF - 1 of -2.76 ± 0.58 SD, who passed the growth hormone releasing hormone (GHRH) stimulation test were included in a retrospective chart review. They were treated with rGH therapy with a mean dose of 0.46 ± 0.1 mg/kg/week. Growth velocity (GV), IGF - 1 and IGFBP - 3 levels were done at 3 and 6 months of therapy. Subjects with poor response to rGH after 6 months of therapy were switched to rIGF - 1 therapy at 0.24 mg/kg/day for the next 6 months. Subjects were divided according to their growth rate into responders to rGH (N = 23); non - responders to rGH, responders to rIGF - 1 (N = 14) and non - responders to rGH and rIGF-1 (N = 6).
There was no correlation between GV and peak GH level at GHRH test. Growth velocity positively correlated with ΔIGF - 1 SD among subjects treated with rGH therapy. Height SD positively correlated with IGFBP - 3 SD. Baseline IGFBP - 3 also inversely correlated with GH peak during GHRH test.
In subjects with short stature and low IGF - 1 level, baseline IGFBP - 3 levels can predict the growth response to rGH and/or rIGF - 1 therapy.

Several different classes of medications have been shown to be efficacious at preventing fractures in patients with osteoporosis. No study has compared real world efficacy at preventing fractures between all currently approved medications.
To directly compare the efficacy of all currently available osteoporosis medications by using a large population claims database.
The Truven Health Analytics MarketScan® database from 2008 - 2012 was used to identify all patients who started a new osteoporosis medication. Patients who experienced a fracture after at least 12 months of treatment were identified and risk factors for fracture for all patients were recorded. Logistic regression was used to account for and quantify the contribution of risk factors, and to make direct comparisons between different osteoporosis medications.
A total of 51649 patients were included in the cohort, with an average age of 56 years. The overall incidence rate of fracture was 1.55 per 100 person - years of treatment. Orally administered medications had the lowest fracture rates, led by raloxifene and alendronate (1.24 and 1.54 respectively), while parenterally administered medications including teriparatide and zolerdonic acid had the highest rates (3.90 and 1.98 respectively). No statistically significant differences found between oral or parenterally administered bisphosphonate medications.
While patients taking orally administered drugs including bisphosphonates had less frequent incident fracture no statistically significant differences were found between most drugs in head - to - head comparisons, even considering the route of administration of bisphosphonates. These findings support previous evidence that minimal differences in efficacy exist between different osteoporosis medications. This is the first study using a large database to compare all currently available osteoporosis treatments and will hopefully be augmented by further study to provide more evidence to make clinical decisions on osteoporosis medication use.

Pre-hypertension is proposed as an independent risk factor for the incidence of cardiovascular diseases.
This study aimed to explore the main factors associated with pre-hypertension via testing a hypothesized model in Tehranian adults.
The study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS) between 2009 - 2011 on 4640 adults without hypertension, aged ≥ 20 years.
The mean age of participants was 38.61 ± 12.14 years and 56.6% of them were female. More than one third of the studied participants had pre-hypertension (35.4%) with significantly higher prevalence in males compared to females (46.5% vs. 26.9%; χ2 = 190.7, P Level of TG and WC in both genders are direct modifiable associated factors of pre-hypertension. These findings could be considered in designing future health promotion programs aimed at preventing high blood pressure and its consequences among Tehranian adults.

Although growth hormone (GH) has essential roles in the growth of animals, it has no growth-promoting effect during infancy period. The molecular mechanism underlying lack of growth-promoting effect of GH during infancy period remains unclear. Important signaling pathways are mediated by GH, including Janus kinase 2 (JAK2), extracellular signal-regulated kinase 1/2 (ERK1/2), signal transducers, and activators of transcription 5, 3, and 1 (STATs 5, 3 and 1).
This study explored the underlying molecular mechanisms driving to the lack of growth-promoting effect of GH in the early stage of life by in vivo assessment of intracellular signal response (STAT5/ 3/ 1, JAK2 and ERK1/ 2) to GH at different physiological stages.
In this study, five age groups of rats (1-, 4-day-old, and 1-, 2-, 3-week-old) were selected. The rats were anesthetized using pentobarbital (100 mg/kg) and then received the rat GH (2mg/kg) via inferior vena cava injection. The control rats were injected with normal saline during the same period. The intracellular signal response to GH was assessed by Western blot analysis.
JAK2 and STAT5 were expressed in 1-day and 4-day-old newborn rats and their expression levels were comparable with the levels of the 1-, 2-, and 3-week-old rats; however, JAK2/STAT5 phosphorylation was not observed in 1-day-old and 4-day-old newborn rats after stimulation with GH in the liver. Similar to JAK2 and STAT5, we did not detect STAT3/1 activation during infancy stages although basic STAT3 and STAT1 were also expressed in hepatocytes from newborn rats. In addition we detected ERK1/2 activation in 4-day-old, 1-, 2-, and 3-week-old rats but not in 1-day-old rats.
JAK2, STAT5, STAT3, STAT1, and ERK1/2 were not simultaneously activated by GH in newborn rats; this finding may be one of the underlying mechanism of GH insensitivity in newborn rats.

Gonadotropin releasing hormone (GnRH) antagonists may cause chemical castration in males by suppressing the pituitary-gonadal axis, hence reducing testosterone level. There are limited data on the effects of degarelix, a newer series of potent and long acting GnRH antagonist on bone.
The current study aimed at determining the effects of degarelix on bone turnover, bone densitometry, and bone mechanical strength in male rats.
Eighteen male Sprague-Dawley rats were randomly divided into sham (SHAM), orchidectomized (ORX), and degarelix-induced (DGX) groups. Chemical castration was performed by subcutaneous degarelix injection (2 mg/kg) at the scapular region. The rats were scanned for baseline bone mineral area (BMA), bone mineral content (BMC), and bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA). Following six weeks of experimental period, BMA, BMC, and BMD were measured again with DXA and blood was collected for testosterone and bone biomarkers (osteocalcin and C-terminal of type I collagen crosslink (CTX-1)) measurements. The rats were euthanized and femora were dissected for bone biomechanical strength analysis.
Bilateral orchidectomy and degarelix administration significantly lowered serum testosterone level, decreased whole body BMC, femoral BMA, femoral BMC, and femoral BMD (P In conclusion, degarelix administration had comparable effects on bone as bilateral orchidectomy. Administration of degarelix provides an alternative method of inducing testosterone deficient-osteopenia in male rats without need for removing the testes.

Currently, various clinical and laboratory diagnostic methods are used to detect overt hypothyroidism during pregnancy. The Billewicz scoring index, as a clinical scale for detection of hypothyroidism, has been applied in general populations; however, its application during pregnancy remains a controversial subject of ongoing research.
The purpose of this study was to evaluate the diagnostic value of Billewicz scoring index for overt hypothyroidism in a general population of Iranian pregnant women.
This study was conducted on 1843 pregnant women. A comprehensive questionnaire, including Billewicz scoring items, was completed, and relevant clinical examinations were performed. The participants underwent serum measurements of thyroxine (T4), thyroid hormone uptake, thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb). Using the receiver operating characteristic (ROC) curve analysis, the optimal sensitivity and specificity were determined as values with maximum yields on the Youden and Rsquo’s Index (sensitivity specificity-1).
The prevalence of overt hypothyroidism and subclinical hypothyroidism was 3.3% and 28.6%, respectively. Overall, 3.6%, 18.9%, and 50% of euthyroid, subclinical hypothyroid, and overt hypothyroid women were TPOAb-positive, respectively. The mean Billewicz scores of euthyroid, overt hypothyroid, and subclinical hypothyroid women were -41.16 (11.16), -17.11 (13.63), and -40.1 (11.2), respectively. Based on the Billewicz scale, at least one sign of hypothyroidism was reported in 38.84% (n, 491) of euthyroid women. Scores ≤ -26.5 (sensitivity, 100%; specificity, 90.82%) were considered as the optimal scores for predicting overt hypothyroidism (Ldquo, Norisk, and Rsquo).
The Billewicz clinical scoring system, as a reliable and inexpensive clinical tool, used along with laboratory measurements, can help screen overt hypothyroidism during pregnancy, primarily in low-resource settings.

Ketoconazole has long been the first-line medical therapy for controlling hypercortisolism secondary to either pituitary or adrenal pathology. However, it is largely unavailable in most countries. As a result, we have turned to fluconazole as a viable alternative in view of its favourable safety profile.
A 50-year-old lady developed recurrent Cushing’s disease after being in remission following transsphenoidal surgery (TSS) for a left pituitary microadenoma 16 years ago. The repeat MRI showed a right pituitary microadenoma (1.7 mm × 1.3 mm) for which she underwent a second TSS. However, she continued to have persistent hypercortisolism despite repeated MRIs showing absence of tumour recurrence. She refused bilateral adrenalectomy and external radiotherapy. Ketoconazole was commenced at 200 mg twice daily for disease control but this was hindered by intolerable side effects including pruritus and skin exfoliation. In the meantime, she suffered a right hypertensive basal ganglia hemorrhage. Treatment was subsequently switched to cabergoline and the dose titrated to 0.5 mg daily. Fluconazole 400 mg daily was later added to control the persistent disease. Her clinical and biochemical parameters improved markedly three months after the addition of fluconazole. No adverse event was reported. Her disease has remained stable for the last 15 months up until the time of the recent clinic review.
This case demonstrates the long-term efficacy of fluconazole in tandem with cabergoline for the control of recurrent Cushing’s disease.

Schaaf-Yang syndrome (SYS) is caused by truncating point mutations of the paternal allele of MAGEL2, an imprinted gene located in the critical region of Prader-Willi syndrome (PWS). These patients present a phenotype with neurodevelopmental delay, hypotonia, joint contractures, and a particularly high prevalence of autism (up to 75% in affected individuals). The loss of function of MAGEL2 is suggested to contribute to endocrine hypothalamic dysfunction in individuals with PWS.
The current study presented the case of a patient with SYS and a novel de novo truncating mutation of MAGEL2 and phenotypic characteristics typical of this Prader-Willi-like syndrome and also including partial hypopituitarism, hypothyroidism, growth hormone deficiency, and hyperprolactinemia.
The clinical and molecular similarities between SYS and PWS suggested the need for a thorough endocrinological follow-up to improve the prognosis and long-term quality of life for patients with SYS.