Guzin Fidan Yaylali

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.

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-γ) 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-γ 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-γ agonist administration would be required to determine its usefulness in the treatment in this group of patients.

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.

Relationship of apelin, procalcitonin, and fetuin-A concentrations with carotid intima-media thickness in acromegaly

Background Acromegaly is characterized by excess growth hormone and insulin-like growth factor-1 concentrations. There is conflicting evidence as to whether acromegaly is associated with an increased risk of atherosclerosis. Apelin is an adipose tissue-derived peptide that may be associated with hyperinsulinemia. Fetuin-A is a hepatocyte produced plasma glycoprotein that has an important role as a calcification inhibitor. The aim of this study was to examine apelin, fetuin-A, and procalcitonin concentrations and to assess their relationship with carotid intima medial thickness (cIMT) in subjects with acromegaly. Methods Apelin, fetuin-A, and procalcitonin serum concentrations were measured in 37 (20 inactive and 17 active) subjects with acromegaly and 30 control subjects, along with carotid intima medial thickness. Results The concentrations of apelin, fetuin-A, and procalcitonin were increased in subjects with acromegaly. There were significant correlations between apelin, fetuin-A, and procalcitonin in subjects with acromegaly. Carotid intima medial thickness values were similar between control subjects and subjects with acromegaly. Conclusions Carotid intima medial thickness was not increased in subjects with acromegaly. It is possible that the increased apelin and fetuin-A concentrations observed play a protective role against the development of atherosclerosis in subjects with acromegaly.

GH/IGF‐1 axis in patients with subclinical hypothyroidism

Introduction Changes in thyroid status have a major effect on the GH/IGF-1 axis. Subclinical hypothyroidism occurs in 4%–10% of the general population, and is especially prevalent in elderly women. The natural history of subclinical hypothyroidism is variable; thyroid function normalizes spontaneously in some subjects, whereas it progresses to overt hypothyroidism in others. Potential risks of subclinical hypothyroidism include progression to overt hypothyroidism, dyslipidaemia, cardiovascular complications, and neurological and neuropsychiatric effects. To the best of our knowledge, there are no data about the possible influences of subclinical hypothyroidism on the GH/IGF-1 axis. Our aim was to evaluate serum concentrations of GH, IGF-1 and IGFBP-3 in patients with subclinical hypothyroidism before and after normalization of thyroid function.

Adiponectin and Cardiac Hypertrophy in Acromegaly.

BACKGROUND Adiponectin is an adipocytes-derived hormone which has been shown to possess insulin-sensitizing, antiatherogenic, and anti-inflammatory properties. In acromegaly, the data on adiponectin is contradictory. The relationship between adiponectin levels and cardiac parameters has not been studied. OBJECTIVES The aim of this study was to find out how adiponectin levels were affected in acromegalic patients and the relationship between adiponectin levels and cardiac parameters. MATERIAL AND METHODS We included 30 subjects (15 male, 15 female), diagnosed with acromegaly and 30 healthy (10 male, 20 female) subjects. Serum glucose, insulin, GH, IGF-1 and adiponectin levels were obtained and the insulin resistance of the subjects was calculated. Echocardiographic studies of the subjects were performed. RESULTS We determined that adiponectin levels were significantly higher in the acromegalic group than the control group. In the acromegalic group, there was no statistically significant relation between serum adiponectin and growth hormone (GH), or insulin-like growth factor-1 (IGF-1) levels (p = 0.3, p = 0.1). We demonstrated that cardiac function and structure are affected by acromegaly. IVST, PWT, LVMI, E/A ratio, DT, ET, IVRT, VPR, and LVESV values were increased and the results were statistically significant. In the acromegalic group, adiponectin levels were positively related with left ventricle mass index (LVMI) but this correlation was found to be statistically weak (p = 0.03). In our study, there was a positive correlation between VAI and LVM. We also could not find any correlation between VAI and adiponectin levels. CONCLUSIONS Although insulin resistance and high insulin levels occur in active acromegaly patients, adiponectin levels were higher in our study as a consequence of GH lowering therapies. Our study showed that adiponectin levels may be an indicator of the cardiac involvement acromegaly. However, the usage of serum adiponectin levels in acromegalic patients as an indicator of cardiac involvement should be supported with other, wide, multi-centered studies.

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.

Serum leptin levels and GHR-d3/fl gene polymorphism in acromegalic patients with thyroid nodules

BACKGROUND Acromegaly is a rare and serious syndrome that is commonly associated with pituitary neoplasms. Thyroid multinodular disease is a common finding in acromegaly. Leptin is a polypeptide hormone, and studies have shown that it can increase cell proliferation and inhibit apoptosis. OBJECTIVES The aim of the study was to determine the relationship of serum leptin levels with certain blood parameters and determine if growth hormone receptor (GHR)-d3/fl gene polymorphism is associated with thyroid nodules in acromegalic patients. MATERIAL AND METHODS A total of 24 acromegalic patients with or without thyroid nodules were included in the study. Gene polymorphisms and blood parameters were examined. RESULTS A marked increase was observed in serum leptin concentration in acromegalic patients with thyroid nodules compared to patients without them (p < 0.05). GH levels were lower in patients without nodules than in patients with nodules (p < 0.05). Blood glucose levels were higher in patients with nodules compared to those without them (p < 0.05), and the presence of thyroid nodules was associated with decreased blood low-density lipoprotein (LDL) levels compared to patients without nodules (p < 0.05). A significant relationship was observed between growth hormone receptor (GHR)-d3/fl gene polymorphism and leptin levels in acromegalic patients with thyroid nodules (p < 0.001). CONCLUSIONS These data from acromegalic patients indicate that thyroid nodules are associated with increased serum leptin, GH and blood glucose levels and with decreased LDL levels. GHR-d3/fl gene polymorphism status was strongly related to higher leptin levels.

Significance of IMP3, nucleophosmin, and Ki-67 expression in papillary thyroid carcinoma.

The purpose of our study was to investigate the diagnostic value of expression of IMP3, nucleophosmin, and correlation of these markers with Ki-67 proliferation index in papillary thyroid carcinoma and benign neoplasms of thyroid gland. The aim was also to investigate whether there is a difference between papillary and micropapillary carcinomas with regard to clinicopathologic parameters beside IMP3, nucleophosmin, and Ki-67 proliferation index. It was concluded that IMP3 and nucleophosmin cannot be a routine diagnostic marker for discrimination of papillary carcinomas and benign lesions. IMP3 positive staining was quite scarce in IMP3 positive papillary carcinomas although specifity of IMP3 is 100%. A statistically significant correlation was not detected between nucleophosmin, IMP-3, and Ki-67 proliferation index. A statistically significant correlation was found between tumor size, lymphovascular embolism, and Ki-67 proliferation index. There was also significant correlation between tumor size and lymphovascular embolism.

Heel Pain and Comorbid Conditions in Obese Patients

Abstract Objectives: Plantar heel pain [PHP] is one of the most common musculoskeletal disorders of the foot, yet its etiology is poorly understood. Although obesity is the most common cause of PHP, there is little information available about the prevalence and associated factors in obese patients with PHP. The aim of this study was to investigate the prevalence of obesity associated co-morbidities in people with and without PHP. Methods: Obese and overweight patients with or without PHP were sought for this study. The two groups were then compared with regard to weight, hormone, and blood parameters. Diabetes mellitus, chronic obstructive lung disease, asthma, smoking, varix, hemorrhoid, lumbago, constipation, osteoporosis, hormone replacement therapy, goiter, and gastroesophageal reflux. Findings: One hundred forty nine obese and overweight patients agreed to participate [34 with PHP and 115 without PHP]. Statistical analyses demonstrated that the PHP group had a longer duration of obesity than those without PHP. The PHP group had an increased prevalence of chronic obstructive lung disease, [p < 0.01], hemorrhoid [p < 0.01], lumbago [p < 0.01], constipation [p < 0.01], and gastroesophageal reflux [P < 0.05], By contrast, the prevalence of asthma [p < 0.05], and varix [p < 0.01] were decreased in the PHP[+] group. No statistically significant difference in group prevalence was found for diabetes mellitus, coronary heart disease, smoking, osteoporosis, hormone replacement therapy, or goiter. Conclusions: The results of this study suggest that the duration of the obesity in obese patient may be important to the development of PHP in obese patients. The longer duration of obesity in the PHP group may also help to explain its association with co-morbidities such as chronic obstructive lung disease, hemorrhoid, lumbago, constipation, and gastroesophageal reflux.