Clinical characteristics and treatment outcomes in acromegaly, a retrospective single-center case series from Thailand

Introduction: acromegaly, an overproduction of growth hormone (GH), is associated with high rate of morbidity and mortality particularly in case of delayed in diagnosis and treatment. A wide variation of clinical presentations, treatment outcomes and morbidities have been reported. Methods: a retrospective study was conducted to review clinical characteristics and treatment outcomes of patients with acromegaly treated in King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 2006 and 2018. Results: eighty-four patients (31 males and 53 females) were reviewed, mean age at diagnosis was 45.7 ± 12.6 years (±SD), mean time of disease onset was 7.6 ± 6.4 years and mean follow-up period was 7.8 ± 5.3 years. The most common presenting symptoms were maxillofacial change (96.8%) and acral enlargement (94.7%). Hypertension (39.3%), diabetes mellitus (28.6%) and dyslipidemia (23.8%) were prevalent co-existing conditions. Four patients were identified having cancer at presentation; however, no additional malignancy was reported during the follow up. Most patients harbored macroadenomas, only 10 were found to have microadenomas. The outcomes of treatment were controlled disease in 70% of microadenoma and 64.9% of macroadenoma. Permanent loss of pituitary function was found in about 21.3% and there was one case reported of mortality. The logistic regression analysis for controlled disease outcome showed the IGF-I index after surgery was associated with controlled disease outcome with statistically significant result (P-value=0.006).==Replace this with the results section of the abstract== Conclusion: our study offers descriptive clinical data of case series of acromegalic patients, which had favorable outcomes comparable with previous reports. In addition, IGF-I index after surgery is a predictive parameter for outcome of treatment

Association of osteoporosis and sarcopenia with fracture risk in transfusion-dependent thalassemia

Abstract Patients with transfusion-dependent thalassemia (TDT) have an increased risk of osteoporosis and fractures. They also have several potential factors associated with sarcopenia. There has been currently no study on sarcopenia and its association with falls and fractures in TDT. This study aims to determine the prevalence of and factors associated with osteoporosis, fragility fractures, and sarcopenia in adults with TDT. A cross-sectional study was conducted at the hematologic clinic at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Clinical data and laboratory testing were collected. Bone mineral density and morphometric vertebral fracture were assessed. Sarcopenia was defined using the 2014 and 2019 Asian Working Group for Sarcopenia (AWGS) criteria. We included 112 TDT patients aged 35.1 ± 12.5 years. The prevalence of osteoporosis was 38.4%. Fragility fractures were found in 20.5% of patients. Lower BMI (OR 0.29; 95% CI 0.12–0.72, P = 0.007) and hypogonadal state (OR 3.72; 95% CI 1.09–12.74, P = 0.036) were independently associated with osteoporosis. According to the 2014 AWGS criteria, the prevalence of overall sarcopenia and severe sarcopenia was 44.6% and 13.4%, respectively. Severe sarcopenia was strongly associated with fragility fractures (OR 4.59, 95% CI 1.21–17.46, P = 0.025). In conclusion, osteoporosis, fragility fractures, and sarcopenia were prevalent in adults with TDT. Severe sarcopenia was associated with fragility fractures. Early osteoporosis and sarcopenia screening and prevention may reduce fracture risk and its complications in these patients

Bone mineral density changes among people living with HIV who have started with TDF-containing regimen: A five-year prospective study.

There are limited data regarding long-term BMD changes over time among treatment-naïve people living with HIV (PLHIV) after initiating combined antiretroviral therapy (cART) in Asia. We aimed to study bone mineral density (BMD) changes among treatment-naïve PLHIV started treatment with tenofovir disoproxil fumarate (TDF)- or non-TDF-containing regimen and HIV-uninfected controls in an Asian setting. The study was a five-year prospective study. BMD at lumbar spine (LS) (L1 to L4), total hip (TH), and femoral neck (FN) were measured by dual energy X-ray absorptiometry (DEXA) scans at baseline, months 12, 24 and 60. Multivariate logistic regression models were used to explore factors associated with mean BMD ≥5% reduction after 5 years of cART. A total of 106 PLHIV (75 and 31 started TDF- and non-TDF-containing regimen, respectively) and 66 HIV-uninfected individuals were enrolled. The mean percent changes of BMD were significantly different longitudinally between TDF and non-TDF users (p<0.001 for LS, p = 0.006 for TH and p = 0.02 for FN). HIV-positive status and on TDF-containing regimen was independently associated with BMD loss ≥5% at month 60 (adjusted odds ratio [aOR] 7.0, 95% confidence interval [95%CI] 2.3-21.0, P = 0.001 for LS; aOR 4.9, 95%CI 1.7-14.3, P = 0.003 for TH and aOR 4.3, 95%CI 1.6-11.2, P = 0.003 for FN) compared to HIV-uninfected individuals. In a multivariate model for PLHIV only, TDF use (vs. non-TDF, P = 0.005) and pre-treatment CD4+ count <350 cells/mm3 (vs. ≥350 cells/mm3, P = 0.02) were independently associated with ≥5% BMD loss in TH at month 60. Treatment-naïve PLHIV initiating treatment with TDF-containing regimen have higher BMD loss in a Thai cohort. TDF use and low pre-treatment CD4 count were independently associated with BMD loss at month 60 at TH. Earlier treatment initiation and interventions to prevent bone loss could improve skeletal health among PLHIV. Clinicaltrials.gov: NCT01634607

Gain of function of Malate Dehydrogenase 2 (MDH2) and familial hyperglycemia

Objective: We set out to identify the genetic cause of hyperglycemia in multigenerational families with an apparent autosomal dominant form of adult-onset diabetes not due to mutations in known monogenic diabetes genes. Methods: Existing Whole Exome Sequencing (WES) data were used to identify exonic variants segregating with diabetes in 60 families from the US and Italy. Functional studies were carried out in vitro (transfected MIN6-K8 cells) and in vivo (Caenorhabditis elegans) to assess the diabetogenic potential of two variants in the Malate Dehydrogenase 2 (MDH2) gene linked with hyperglycemia in two of the families. Results: A very rare mutation (p.Arg52Cys) in MDH2 strongly segregated with hyperglycemia in one family from the US. An infrequent MDH2 missense variant (p.Val160Met) also showed disease co-segregation in a family from Italy, although with reduced penetrance. In silico, both Arg52Cys and Val160Met were shown to affect MDH2 protein structure and function. In transfected HepG2 cells, both variants significantly increased MDH2 enzymatic activity, thereby decreasing the NAD+/NADH ratio - a change known to affect insulin signaling and secretion. Stable expression of human wild type MDH2 in MIN6-K8 cell lines enhanced glucose- and GLP-1-stimulated insulin secretion. This effect was blunted by the Cys52 or Met160 substitutions. Nematodes carrying equivalent changes at the orthologous positions of the mdh-2 gene showed impaired glucose-stimulated insulin secretion. Conclusions: Our findings suggest a central role of MDH2 in human glucose homeostasis and indicate that gain of function variants in this gene may be involved in the etiology of familial forms of diabetes