Evaluation of the relation between subclinical systolic dysfunction defined by four-dimensional speckle-tracking echocardiography and growth differentiation factor-15 levels in patients with acromegaly.

PURPOSE: In patients with acromegaly, the long-term presence of elevated GH and IGF-1 levels is associated with an unfavorable cardiovascular risk profile. We aimed to assess the relationship of four-dimensional speckle tracking echocardiographic (4DSTE) measurements with growth differentiation factor-15 (GDF-15) levels and the Framingham Cardiovascular Risk Score (FRS) in patients with acromegaly. METHODS: A single-center, cross-sectional study was conducted. The study included 40 acromegaly and 32 age- and gender-matched controls. Anthropometric, biochemical, and echocardiographic assessments were performed. GDF-15 levels were measured using ELISA. RESULTS: In the controlled acromegaly group, global longitudinal (GLS), circumferential (GCS), area (GAS), and radial (GRS) strain measurements identified by 4DSTE were lower than those of the controls (p < 0.05). Moreover, strain parameters were lower in active acromegaly patients than in controls, but the difference was not statistically significant. The GLS was negatively correlated with age, the estimated disease duration, and FRS. Serum GDF-15 levels showed no significant difference between the acromegaly and control groups. In patients with acromegaly, serum GDF-15 levels were positively correlated with age, waist-to-hip ratio, systolic and diastolic blood pressure, FRS, fasting plasma glucose, and HbA1c, but not with strain parameters. The multiple regression analysis revealed that FRS was an independent factor associated with serum GDF-15 levels in patients with acromegaly and the overall cohort (p < 0.001). CONCLUSION: Our study demonstrates that while LVEF was within normal limits, global strain parameters (GLS, GCS, GAS, and GRS) measured by using a novel imaging technique, 4DSTE, were lower in patients with acromegaly, suggesting the presence of subclinical systolic dysfunction in patients with acromegaly. GDF-15 can be a potential predictor of cardiovascular risk in patients with acromegaly.

Effect of post-transplant diabetes mellitus on cardiovascular events and mortality: a single-center retrospective cohort study.

PURPOSE: This study aims to investigate the impact of post-transplant diabetes mellitus (PTDM) on cardiovascular events, graft survival, and mortality and to determine the risk factors involved in developing PTDM. METHODS: A total of 703 patients who underwent kidney transplantation were included in the study. The total sample was subdivided into three groups: (i) patients with PTDM; (ii) patients who had diabetes before the transplantation (DM); and (iii) patients without diabetes (NoDM). The data on graft failure, cardiovascular events, all-cause mortality, and the potential risk factors that play a role in developing PTDM were recorded and analyzed. RESULTS: The patients were followed for a median of 80 (6-300) months after transplantation. Out of all patients, 41 (5.8%) had DM before transplantation, and 101 (14.4%) developed PTDM. Recipient BMI, post-transplant fasting plasma glucose, and hepatitis C seropositivity were independent risk factors for PTDM development. The incidence of cardiovascular events was 6.1% in the NoDM group, 14.9% in the PTDM group, and 29.3% in the DM group (p < 0.001). In PTDM patients, hepatitis C seropositivity and the recipient's age at transplant were independent predictors of a cardiovascular event. There were no significant differences between the groups regarding the risk of graft loss. PTDM had no significant effect on all-cause mortality. However, the survival rates of DM patients were significantly reduced compared to those with NoDM or PTDM. CONCLUSIONS: PTDM had no impact on patient survival. Hepatitis C seropositivity and recipient age at transplant predicted cardiovascular events in PTDM patients.

Factors that predict development of chronic kidney disease in patients with rheumatoid arthritis receiving biologic DMARDs and mortality rates.

OBJECTIVES: We aimed to determine the choice of biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/ts-DMARDs), factors associated with the development of chronic kidney disease (CKD), and mortality in RA patients with CKD receiving b/ts-DMARDs. METHODS: Two thousand one hundred forty-one RA (79.4% female) patients were included in the analysis from the HUR-BIO prospective registry. Patients were divided into the CKD group and the non-CKD group. Age and gender-matched patients were selected from the non-CKD group, and then three main groups were determined. CKD was staged according to the glomerular filtration rate criteria. The clinical characteristics of the patients, disease activities, treatment choices, drug retention rate, and mortality rates were compared between the groups. RESULTS: CKD was detected in 90/2141 (4.2%) RA patients on b/ts-DMARDs. Forty patients (2.3%) developed CKD during follow-up after the initiation of b/ts-DMARDs. In the CKD group, anti-TNF agents were chosen as the first-line b/ts-DMARDs therapy in 64.4% of patients, with etanercept leading in 31 (34.4%) patients. In multivariate analysis, age at the start of treatment, DAS-28-ESR at last visit, amyloidosis, hypertension, and history of smoking were the factors associated with the development of CKD in RA patients receiving b/ts-DMARDs. The mortality rate in RA-CKD patients until the onset of the pandemic was 15.41 per 1000 patient years, whereas it was 85.9 per 1000 patient years after the pandemic. CONCLUSION: Comorbidities and control of disease activity are critical in the development of CKD in RA patients receiving b/ts-DMARDs. While there was no significant difference in mortality rate between CKD and non-CKD patients, the overall mortality rate increased after the COVID-19 pandemic duration in both groups.

Follow, consider, and catch: second primary tumors in acromegaly patients.

BACKGROUND AND AIM: The risk of second primary tumors is increased in general cancer population, however, there is no data on acromegalic cancer patients in this regard. The aim of this study is to determine the prevalence of patients with two primary tumors among acromegalic cancer patients and to evaluate if patients with two primaries have distinct clinical characteristics or risk factors compared to those with one. METHODS: This is a single-center retrospective cohort study. The study included 63 patients with at least one malignant tumor out of a total number of 394 acromegaly patients. Patients with multiple primary neoplasms were evaluated in detail. RESULTS: This study revealed a 16% cancer prevalence in acromegaly patients, with 14% (9/63) having two primary neoplasms. Papillary thyroid carcinoma was the most prevalent tumor in the entire cancer cohort (41%, 26/63), and in the group of patients with two primaries (44%, 4/9). Patients with two primary tumors were older than those with one when diagnosed with acromegaly (48.3 ± 16.6 vs. 43.3 ± 10.7 years), which might be attributed to a longer diagnostic delay (median of 4.5 vs. 2 years). The period between the onset of acromegaly symptoms and diagnosis was not associated with earlier cancer diagnosis. No relationship between circulating GH or IGF-I levels and the number of neoplasms was found. CONCLUSION: The development of second primary tumors in acromegalic patients with cancer diagnosis is not rare. Acromegalic cancer patients should be closely monitored for new symptoms or signs that could be associated with second primary tumors.

Giant growth hormone-secreting pituitary adenomas from the endocrinologist's perspective.

OBJECTIVES: Since giant (≥40 mm) GH-secreting pituitary adenomas are rarely encountered, data on their characteristics and treatment outcomes are limited. We aimed to investigate the characteristics of giant GH-secreting pituitary adenomas and to compare their clinical, biochemical, imaging and histopathological features with non-giant macroadenomas. MATERIALS AND METHODS: We have evaluated 15 (six female/nine male) and 57 (29 female/28 male) patients with acromegaly in giant and <40 mm adenoma groups, respectively. Patients with <40 mm adenoma were further divided into subgroups with adenoma size 20-29 mm and 30-39 mm. RESULTS: In giant adenoma group, median (IQR) preoperative maximal diameter of adenoma was 40 mm (5 mm), median preoperative GH level was 40 (153.4) ng/mL and median baseline IGF-1 level was 2.19 (1.88) × ULN for age and sex. The number of surgeries was significantly higher in giant adenoma group (median 2, IQR 2) in which 66.7% of patients underwent repeated surgeries (p = 0.014). Residual tumor was detected after last operation in all patients with giant adenoma. Total number of treatment modalities administered postoperatively increased as adenoma size increased (p = 0.043). After a median follow-up duration of 10 years (IQR 10), hormonal remission was achieved in six patients (40%) of giant adenoma group, while the rate of hormonal remission in non-giant adenoma group was 37%. Although preoperative GH and IGF-1 levels and Ki-67 index tended to be higher with increasing adenoma size, there was no statistically significant difference between groups in terms of these variables, as well as age, sex and invasion status. CONCLUSION: Hormonal remission rates of acromegaly patients with ≥20 mm pituitary macroadenoma were comparable. However, giant GH-secreting pituitary adenomas require an aggressive multimodal treatment approach.

Serum growth differentiation factor-15 levels are associated with the severity of diabetic foot ulcer.

AIMS: To assess serum growth differentiation factor-15 (GDF-15) levels in patients with diabetic foot ulcer and to reveal whether any association exists between GDF-15 and the severity of diabetic foot ulcer. DESIGN: A cross-sectional study including three age- and sex-matched cohorts comprising 17 patients (7 F, mean age: 52 ± 7 years) with diabetic foot ulcer (DMf), 17 patients with type 2 diabetes (6 F, mean age: 51 ± 6 years) with no foot complication (DM), and 20 healthy controls (8 F, mean age: 50 ± 8 years) (C) was conducted. RESULTS: DMf had higher GDF-15 levels, followed by DM and C (GDF-15, median ± IQR (pg/mL), DMf: 1039 (884-1566), DM: 649 (375-1148), and C: 296 (212-534), p < 0.001). The severity of diabetic foot disease was positively associated with serum GDF-15 (GDF-15, median ± IQR (pg/mL), Wagner grade 1: 893 (698-1039), Wagner grade 3: 1705 (1348-2197), and Wagner grade 4: 3075 (1974-4176), p for trend = 0.006). In multivariate regression model, only Wagner grade (ß = 0.55, 95% CI (87-753), p = 0.02) was found to be an independent factor affecting serum GDF-15 concentration. CONCLUSIONS: Serum GDF-15 levels are high in patients with diabetic foot ulcer. The level is higher in more advanced lesions. GDF-15 measurement can have clinical utility in the management of diabetic foot ulcers.

Reduced irisin levels in patients with acromegaly.

OBJECTIVES: Several metabolic disturbances are seen in acromegaly however, data regarding the contribution of irisin to these disturbances is currently insufficient. In a cohort of patients with acromegaly, we measured serum irisin levels in active and controlled cases and determined independent factors that effect serum irisin including fibronectin type III domain-containing protein 5 (FNDC5) genotyping. METHODS: A cross-sectional case-control study including 46 patients with acromegaly (28 F/18 M, age: 50.3 ± 12.1 year, BMI: 30.7 ± 5.1 kg/m2) and 81 age-, gender-, body mass index- and body composition-matched healthy controls was conducted. 15 acromegalic patients (33%) had active disease. Irisin levels were measured by enzyme-linked immunosorbent assay. Three different regions (rs3480, rs1746661, and rs16835198) of FNDC5 were subjected to polymorphism analyses. RESULTS: Both groups were overweight and had similar body composition. Irisin levels were lower in patients with acromegaly than controls (median [IQR]: 44.8 [41.7-46.7] ng/mL vs. 51.7 [45.5-60.1] ng/mL, p≤0.001, respectively). Active and controlled patients had similar irisin levels. Irisin was not correlated with growth hormone (GH), insulin-like growth factor 1 (IGF-1), and IGF-1 index. In multiple linear regression model, somatostatin receptor ligand use (ß=-20.30, 95% CI [-34]-[-6], p=0.006) was determined as the only independent factor that affect serum irisin. CONCLUSIONS: Serum irisin levels are low in patients with acromegaly who are on somatostatin receptor ligand therapy. Single nucleotide polymorphisms (SNPs) of FNDC5 have no independent effects on circulating irisin levels under somatostatin ligand action. Endocrine muscle functions also seem to be regulated by somatostatin action, which requires further studies.

Oxysterol species generated by auto-oxidation in subclinical hypothyroidism.

BACKGROUND: Auto-oxidized oxysterols are implicated in the pathogenesis of various chronic diseases. Their concentrations are indicators of oxidative stress in vivo and associated with atherosclerosis. Subclinical hypothyroidism is related with cardiac diseases and oxidative stress, but the exact mechanisms underlying these associations are not clear yet. OBJECTIVE: To investigate the auto-oxidized oxysterols, 7-ketocholesterol (7-KC) and cholestane-3ß,5α,6ß-triol (chol-triol), in patients with subclinical hypothyroidism, as well as to evaluate the impact of restoring euthyroidism on oxysterol concentrations. METHODS: In this prospective observational study, 64 patients with newly diagnosed autoimmune thyroiditis (41 with subclinical hypothyroidism and 23 euthyroidism), and 45 healthy controls were enrolled. Age, gender, and body mass index were matched among patient groups and healthy controls. Anthropometric measurements were obtained and fasting plasma 7-ketocholesterol and cholestane-3ß,5α,6ß-triol concentrations were measured by using liquid chromatography coupled with tandem mass spectrometry. Levothyroxine was then administered to all patients with subclinical-hypothyroidism. After three months, measurements of the oxysterols and serum cholesterols from the patients who have become euthyroid were repeated. RESULTS: Concentrations of 7-ketocholesterol and cholestane-3ß,5α,6ß-triol were significantly higher in patients with subclinical-hypothyroidism when compared to both euthyroid patients and healthy controls (p < 0.001 for both oxysterols). After restoration of euthyroidism, concentrations of 7-ketocholesterol and cholestane-3ß,5α,6ß-triol decreased significantly and reached similar concentrations observed in healthy controls (p < 0.001 for both oxysterols). CONCLUSIONS: Auto-oxidized oxysterol species are higher in patients with mild thyroid dysfunction, and supported the rationale for treating subclinical-hypothyroidism.

Cancer incidence in familial Mediterranean fever patients: a retrospective analysis from central Anatolia.

Although chronic inflammation has been associated with increased cancer risk in various disease including hepatitis or inflammatory bowel disease, a lower incidence of cancer has been reported recently in familial Mediterranean fever (FMF) which is an auto-inflammatory disease with persistent inflammation. We have assessed cancer incidence among FMF patients with or without amyloidosis to investigate this hypothesis. We performed a retrospective review of FMF patients, diagnosed and treated in Hacettepe University hospitals between 2001 and 2018. We identified patients from the hospital medical records using the ICD-10 code for FMF. We collected data on demographic and clinical features, drug history, the presence of amyloidosis and subsequent diagnosis of cancer. The expected cancer incidence was estimated using age- and gender-specific standardized incidence rates (SIRs) in comparison with the general Turkish population according to Turkish National Cancer Registry data at 2014. Total of 3899 FMF patients (120 patients had also amyloidosis) were included. Median age was 22 and 56% were females. Thirty-eight patients were diagnosed with cancer during 100,283 person-years of follow-up. The most common cancer was breast cancer in females (7/28 patients) and leukemia (2/10 patients) in males. The overall cancer incidence among patients with FMF was significantly lower in both males {SIR 0.42 [95% confidence interval; (CI) 0.21-0.75], p = 0.019} and females [SIR 065 (95% CI 0.44-0.93), p = 0.002]. The overall cancer incidence among patients with FMF and amyloidosis was [SIR 1.21 (95% CI 0.49-2.52), p = 0.73] without gender difference. Cancer incidence was significantly lower in FMF patients compared with the general Turkish population. We found no increased cancer incidence in FMF patients having amyloidosis. Possible underlying mechanisms need to be explained.