Is isoenergetic high-intensity interval exercise superior to moderate-intensity continuous exercise for cardiometabolic risk factors in individuals with type 2 diabetes mellitus? A single-blinded randomized controlled study.

The aim of this study was to compare the effect of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) with equal energy expenditure on glycaemic and cardiometabolic risk factors in people with Type 2 Diabetes Mellitus (T2DM) when compared to the control. Sixty-three people with T2DM were randomly assigned to HIIT, MICT, or non-exercising controls. Individuals were trained with HIIT at 90 and 30% of their VO2peak (1:2 min ratio) starting from 8 up to 16 intervals and MICT at 50% of VO2peak, on a cycle ergometer, 3 times/week for 12 weeks under supervision. The primary outcome measure was the change in HbA1c. Aerobic capacity, cardiovascular responses, anthropometric measures, body composition, glycaemic, and cardiometabolic risk factors were measured at the beginning and the end of the 12-week training period. There was no significant difference between HIIT and MICT or when compared to the control for HbA1c, glucose, insulin resistance, blood lipids, cardiovascular responses, anthropometric measures, body composition, and abdominal and visceral fat (padj > 0.05). HIIT and MICT increased VO2peak significantly compared to controls (p < 0.05) but not to each other (p > 0.05). Both HIIT and MICT improved VO2peak and HbA1c after 12 weeks of training compared to their baseline, furthermore, only MICT caused additional improvements in cardiovascular responses, anthropometric measures, and abdominal fat compared to baseline (p < 0.05). As a conclusion, isoenergetic HIIT or MICT did not improve HbA1c. The two protocols were equally efficient for improvement in aerobic capacity but had little effect on other cardiometabolic factors.Trial registration: ClinicalTrials.gov identifier: NCT03682445.HighlightsHIIT and MICT with equal energy expenditure were equally efficient for aerobic capacity compared to controls.Isoenergetic HIIT or MICT were not superior for improving HbA1c.Isoenergetic HIIT and MICT were not superior to each other for anthropometric measures, body composition, and cardiometabolic risk factors.

Effects of Treatment Adherence on Quality of Life in Hypoparathyroid Patients.

OBJECTIVES: This study aimed to evaluate the current situation of hypoparathyroid patients and to investigate the relationship between treatment adherence and quality of life. STUDY DESIGN: Prospective, multicentre study. METHODS: Adult patients presenting with the diagnosis of hypoparathyroidism to 20 different endocrinology clinics were included. They were receiving conventional therapies for hypoparathyroidism, using calcium, active vitamin D, and magnesium. We collected data on demographic features, disease- and treatment-related information, and results of routine laboratory tests, treatment adherence, and presence of complications. Beck Depression Inventory, Beck Anxiety Inventory, and Short Form-36 quality of life assessments were administered. RESULTS: Among the 300 patients studied, 60.7% were adherent to their treatment, and 34.1% had complications. Anxiety and depression scores were significantly higher in non-adherent versus treatment-adherent patients (p<0.001 and p=0.001, respectively). Most of the domains of quality-of-life scores were also significantly lower in non-adherent patients. Both anxiety and depression scores showed significant, negative correlations with serum calcium and magnesium concentrations (r=-0.336, p<0.001 and r=-0.258, p<0.001, respectively). CONCLUSIONS: Nearly 40% of the patients were non-adherent to conventional treatment for hypoparathyroidism, and such patients had higher anxiety and depression scores and poorer quality of life scores. Conventional treatment might not be sufficient to meet the needs of patients with hypoparathyroidism. In addition to seeking new therapeutic options, factors influencing quality of life should also be investigated and strategies to improve treatment adherence should be developed.

The acromegaly registry of ten different centers in Turkey.

OBJECTIVES: To describe biochemical and clinical features, and therapeutic outcomes of acromegaly patients in Turkey. METHODS: Retrospective multicenter epidemiological study of 547 patients followed in 10 centers of the Turkish Acromegaly registry. RESULTS: A total of 547 acromegaly patients (55% female) with a median age of 41 was included in this study. Majority of patients had a macroadenoma (78%). Transsphenoidal surgery was performed as primary treatment in 92% of the patients (n = 503). Surgical remission rate was 39% (197/503) in all operated patients. Overall disease control was achieved in 70% of patients. Remission group were significantly older than non-remission group (p = .002). Patients with microadenomas had significantly higher remission rates than patients with macroadenomas (p < .001). Patients with microadenomas were significantly older at the time of diagnosis when compared to patients with macroadenomas (p < .001). Preoperative growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were significantly lower in the remission group (p < .001). Initial IGF-1 and GH levels were significantly higher in macroadenomas compared to microadenomas (p < .001). Medical treatment was administered as a second-line treatment (97%) in almost all patients without remission. Radiotherapy was preferred in 21% of the patients mostly as a third line treatment. CONCLUSIONS: This is one of the largest real life studies evaluating the epidemiological characteristics and treatment outcomes of patients with acromegaly who were followed in different centers in Turkey. Transsphenoidal surgery in the treatment of acromegaly still remains the most valid method. Medical treatment options may improve long-term disease outcomes in patients who cannot be controlled with surgical treatment (up to 70%).

Clinical spectra of neuromuscular manifestations in patients with lipodystrophy: A multicenter study.

Lipodystrophy is a heterogeneous group of disorders characterized by loss of adipose tissue. Here, we report on clinical spectra of neuromuscular manifestations of Turkish patients with lipodystrophy. Seventy-four patients with lipodystrophy and 20 healthy controls were included. Peripheral sensorimotor neuropathy was a common finding (67.4%) in lipodystrophic patients with diabetes. Neuropathic foot ulcers were observed in 4 patients. Drop foot developed in 1 patient with congenital generalized lipodystrophy type 1. Muscle symptoms and hypertrophy were consistent findings in congenital generalized lipodystrophy (21/21) and familial partial lipodystrophy (25/34); on the other hand, overt myopathy with elevated creatine kinase activity was a distinctive characteristic of congenital generalized lipodystrophy type 4. Muscle biopsies revealed myopathic changes at different levels. Accumulation of triglycerides was observed which contributes to insulin resistance. All patients with congenital generalized lipodystrophy suffered from tight Achilles tendons at various levels. Scoliosis was observed in congenital generalized lipodystrophy type 4 (2/2) and familial partial lipodystrophy type 2 (2/17). Atlantoaxial instability was unique to congenital generalized lipodystrophy type 4 (2/2). Bone cysts were detected in congenital generalized lipodystrophy type 1 (7/10) and congenital generalized lipodystrophy type 2 (2/8). Our study suggests that lipodystrophies are associated with a wide spectrum of neuromuscular abnormalities.

Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy.

OBJECTIVE: Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat. METHODS: This multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison. RESULTS: Pathogenic variants of the LMNA gene were determined in nine families. Of those, typical exon 8 codon 482 pathogenic variants were identified in four families. Analysis of the LMNA gene also revealed exon 1 codon 47, exon 5 codon 306, exon 6 codon 349, exon 9 codon 528, and exon 11 codon 582 pathogenic variants. Analysis of the PPARG gene revealed exon 3 p.Y151C pathogenic variant in two families and exon 7 p.H477L pathogenic variant in one family. A non-pathogenic exon 5 p.R215Q variant of the LMNB2 gene was detected in another family. Five other families harbored no mutation in any of the genes sequenced. MRI studies showed slightly different fat distribution patterns among subjects with different point mutations, though it was strikingly different in subjects with LMNA p.R349W pathogenic variant. Subjects with pathogenic variants of the PPARG gene were associated with less prominent fat loss and relatively higher levels of leptin compared to those with pathogenic variants in the LMNA gene. Various metabolic abnormalities associated with insulin resistance were detected in all subjects. End-organ complications were observed. CONCLUSION: We have identified various pathogenic variants scattered throughout the LMNA and PPARG genes in Turkish patients with FPLD. Phenotypic heterogeneity is remarkable in patients with LMNA pathogenic variants related to the site of missense mutations. FPLD, caused by pathogenic variants either in LMNA or PPARG is associated with metabolic abnormalities associated with insulin resistance that lead to increased morbidity.

Resistin and leptin levels in acromegaly: lack of correlation with echocardiographic findings.

PURPOSE: To find out how resistin and leptin levels were affected in patients with acromegaly and whether there is a relation between resistin levels and cardiac parameters. We also aimed to investigate whether resistin and leptin may be a link between insulin resistance and cardiac functions as well as these affected cardiac functions in the patients with acromegaly. METHODS: We included 30 subjects (15 men and 15 women) who had a diagnosis of acromegaly and 30 healthy (10 men and 20 women) subjects. Serum glucose, insulin, growth hormone, insulinlike growth factor 1 (IGF-1), resistin, and leptin levels were obtained, and insulin resistance of subjects were calculated. Echocardiographic studies of the subjects were performed. RESULTS: Resistin levels of the patients with acromegaly were found lower than controls. This difference was statistically significant (P = 0.001). Leptin levels were lower in the patients with acromegaly than in the controls, but this difference was not statistically significant. Resistin and leptin levels were not correlated with growth hormone, IGF-1, and with insulin-like growth factor binding protein 3 levels. Homeostasis model assessment of insulin resistance was positively correlated with resistin levels. (P = 0.03; r = 0.531) but not correlated with leptin levels. There was a positive correlation between body mass index and leptin levels in the patients with acromegaly (P = 0.007; r = 0.482). Interventricular septum thickness, posterior wall thickness, left ventricle mass index, peak early mitral inflow velocity-peak late mitral inflow velocity ratio, deceleration time, ejection time, isovolumetric relaxation time, velocity propagation, and left ventricular end-systolic volume values were significantly greater in the patients with acromegaly. Leptin levels in the acromegalic patients were not correlated with any of them. CONCLUSIONS: We found biventricular hypertrophy and impairment of diastolic and systolic function in the patients with acromegaly. We conclude that changes in resistin and leptin levels are unlikely to account for the insulin resistance of acromegaly. They do not also seem to be contributing factors of cardiovascular changes in patients with acromegaly.

Evaluation of body fat distribution in PCOS and its association with carotid atherosclerosis and insulin resistance.

OBJECTIVE: The aim of this study was to compare body fat distribution in PCOS with healthy controls and to investigate the factors associated with carotid artery intima media thickness (IMT) and insulin resistance. SUBJECTS AND METHODS: A case control study was conducted in 46 women with PCOS and 43 age matched controls. Anthropometrical measurements, hormonal levels, lipid and glucose profile were evaluated. Body fat thickness in four regions and carotid IMT were measured. Body fat distribution was compared between groups. Correlation of these parameters with carotid artery IMT and insulin resistance was investigated. RESULT(S): Visceral and subcutaneous fat thickness and the mean carotid artery IMT were significantly higher in PCOS subjects (p < 0.01). In correlation analysis, age, body mass index (BMI) and waist hip ratio (WHR) showed correlation with carotid artery IMT (r = 0,55, p < 0,001; r = 0.41, p < 0.008 and r = 0.34 p = 0.03, respectively), whereas visceral fat thickness presented a correlation with HOMA-IR index as a sign of insulin resistance. CONCLUSION(S): Fat accumulation is more prominent in visceral and subcutaneous regions in PCOS. Increased BMI and abdominal type of obesity are closely related to the increased carotid artery IMT and insulin resistance. Weight control and regional weight loss are important part of the treatment for the future health of women with PCOS.

Growth hormone/insulin-like growth factor axis in patients with subclinical thyroid dysfunction.

OBJECTIVE: Our aim was to evaluate serum concentrations of GH, IGF-I, and insulin-like growth factor-binding protein-3 (IGFBP-3) in patients with subclinical thyroid dysfunction before and after normalization of thyroid function. DESIGN AND METHODS: The study included 51 patients (mean age 42.2+/-1.8 years) with subclinical hypothyroidism and 30 patients (mean age 44.3+/-2.4 years) with subclinical hyperthyroidism. A group of 37 euthyroid healthy subjects were studied as controls. Serum concentrations of TSH, FT4, FT3, GH, insulin, IGF-I, and IGFBP-3 were measured in all patients before starting therapy and after normalization of thyroid function. The dosage of levothyroxine (LT4) and antithyroid drugs was adjusted in attempt to keep the serum-free thyroxine (FT4) and thyrotropin (TSH) concentrations within the normal range. MAIN OUTCOME: Baseline growth hormone levels were similar with hypothyroid group and hyperthyroid group in relation to euthyroid control subjects. Fasting serum IGF-I levels were significantly lower in the subclinical hypothyroid group compared with the control group. On the other hand, IGF-I levels of subclinical hyperthyroid patients and control group were similar. After normalization of thyroid function tests, IGF-I concentrations were increased in subclinical hypothyroid subjects, but unchanged in subclinical hyperthyroid subjects. Patients with subclinical hyperthyroidism showed slightly lower mean serum IGFBP-3 concentrations than those found in control group, but the difference was not statistically significant. Serum GH and IGFBP-3 levels were unaltered by treatment. CONCLUSIONS: In this study, it was shown that GH-IGF axis was not affected in patients with subclinical hyperthyroidism, while it was affected in patients with subclinical hypothyroidism. That is, investigation of the axis in subclinical hyperthyroidism would not bring any extra advantages, but LT4 replacement therapy could prevent abnormalities related to GH-IGF axis in patients with subclinical hypothyroidism.

Phaeochromocytoma combined with subclinical Cushing's syndrome and pituitary microadenoma.

OBJECTIVES: Phaeochromocytoma (PHEO) occasionally associates with pathological lesions of the adrenal cortex. The coexistence of PHEO and pre-clinical Cushing's syndrome (PCS) of the same adrenal gland has rarely been reported. We report a case of PHEO and PCS originating from the same adrenal gland and discuss the peculiar diagnostic aspects of this entity. CLINICAL PRESENTATION: A 64 yr old man was hospitalized to evaluate the right adrenal mass which was discovered incidentally by ultrasonography. He had a history of type 2 diabetes mellitus and hyperlipidemia. Blood pressure measurements were all normal during his hospital stay. Laboratory examination showed: urinary catecholamines were markedly increased. HbA1C of 14.3 %, midnight cortisol of 11(microg/dL), cortisol was not suppressed after the overnight 1 mg oral dexamethasone suppression test (DST): 3.42(microg/dL), 24 hr free cortisol in the urine : 213 microg/day (10-100), cortisol levels were suppressed more than 50% with 8 mg of dexamethasone. CT scan of the adrenal glands showed a 6 cm well encapsulated right adrenal mass together with a clearly normal left adrenal gland. MRI investigation of the sella turcica revealed a pituitary microadenoma on the right side of the adenohypophysis He was treated with alpha and subsequent beta blockers after the diagnosis of PHEO and PCS was made. Right adrenalectomy was performed. The pathology showed typical PHEO with adrenocortical hyperplasia. VMA, metanefrin and free cortisol levels were normalized one month after surgery. CONCLUSION: The present report is a rare case of PHEO combined with PCS in the same adrenal gland.

The use of lithium carbonate in the preparation for definitive therapy in hyperthyroid patients.

OBJECTIVE: The aim of this study was to elucidate the effectiveness of lithium carbonate prior to thyroidectomy or radioiodide therapy in patients with thyrotoxicosis. SUBJECTS AND METHODS: Lithium carbonate was used as preoperative preparation or radioiodide therapy in 5 patients with Graves' disease and in 1 patient with toxic multinodular goiter because of side effects of thionamide in 5 patients and ineffectiveness of antithyroid medication in the remaining patient. RESULTS: All 6 patients had a benign course following treatment without thyroid storm. No adverse effects or complications of lithium carbonate were observed. CONCLUSION: This report shows that lithium carbonate can be safely used preoperatively or prior to radioiodide therapy in circumstances where antithyroid medications are contraindicated and are ineffective in obtaining an euthyroid status.

Effect of methimazole on warfarin anticoagulation in a case of Graves' disease.

The article describes a case of Graves' disease treated with methimazole and examines the influence of methimazole-induced alterations of thyroid hormone concentrations during warfarin therapy. A 22-year-old woman presented at our endocrinology outpatient clinic with palpitations, sweating, fatigue, tremors, and diarrhea. She had a pain in her right leg and had difficulty walking. Her thyroid profile was consistent with hyperthyroidism. The patient was treated with warfarin 5 mg once a day for deep vein thrombosis for 2 days. Since a therapeutic range of International Normalized Ratio levels could not be achieved, methimazole was stopped due to drug-drug interaction. Lithium was started instead. A euthyroid state was obtained in 2 weeks together with a therapeutic International Normalized Ratio level. Interactions between warfarin and drugs that alter thyroid hormone concentrations have been reported; however, the extent and significance of the interaction between methimazole and warfarin have been inadequately described. Concomitant therapy with warfarin and antithyroid drugs should be managed by frequent monitoring of both thyroid function and the International Normalized Ratio. Lithium is employed only to provide temporary control of thyrotoxicosis in patients who cannot take thionamide and iodide. The administration of lithium alone or in combination with other drugs is shown to be an effective method of controlling hyperthyroidism when conventional antithyroid drugs show adverse effects or become insufficient. When warfarins are used together with antithyroid medications, adequate anticoagulation may not be obtained due to drug-drug interactions. Lithium can be an alternative drug for antithyroid medication in patients on warfarin therapy.

The PPAR-gamma activator rosiglitazone fails to lower plasma growth hormone and insulin-like growth factor-1 levels in patients with acromegaly.

BACKGROUND/AIM: Despite combined therapy consisting of surgery, external X-ray, and medical therapy, a significant number of acromegaly patients continue to have uncontrolled growth hormone (GH) secretion and active disease. These patients, particularly those with large or invasive tumors, require additional therapy to decrease their GH levels. Our aim was to investigate whether patients with documented GH-secreting pituitary adenomas leading to acromegaly would respond with attenuation of GH and insulin-like growth factor-1 (IGF-1) levels after treatment with a peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist. METHODS: We conducted prospective analyses in the Endocrinology Clinic of the Pamukkale University. Acromegaly patients who had active disease participated in two admissions: before and after 6 weeks of daily treatment with 8 mg of oral rosiglitazone. Four male and 3 female patients have completed the study. Basal and nadir GH levels during an oral glucose tolerance test were determined, and the IGF-1 and IGF-binding protein-3 levels were also measured both before and 6 weeks after the rosiglitazone treatment. RESULTS: Treatment with rosigitazone did not reduce basal and nadir GH levels during the oral glucose tolerance test and the IGF-1 levels in the patient population as a whole (p > 0.05). CONCLUSIONS: The PPAR-gamma activator rosiglitazone, used at maximum approved dosage, did not reduce plasma GH and IGF-1 levels in patients with acromegaly. Further studies with higher doses and longer duration of PPAR-gamma agonist administration would be required to determine its usefulness in the treatment in this group of patients.

Successful treatment of visceral leishmaniasis with fluconazole and allopurinol in a patient with renal failure.

Standard treatments for visceral leishmaniasis (antimonials, amphotericin B and pentamidine) pose several problems. Failure of antimonials or severe toxicity is particularly troublesome in patients with renal insufficiency. We report a case of visceral leishmaniasis and renal insufficiency successfully treated with fluconazole and allopurinol for 4 months.