Background
Klotho is a new identified anti‐ageing gene with tumour suppressor activities. Current data suggest that there is a tight relationship between Klotho protein and growth hormone ...(GH)/insulin‐like growth factor‐1 (IGF‐1) axis.
Purpose
This study aimed to investigate the possible association of Klotho gene polymorphisms with acromegaly and to assess whether these polymorphisms contribute to clinical characteristics, comorbidities and biochemical variables in these patients.
Methods
The study included 52 patients with acromegaly and 52 unrelated healthy subjects. The Klotho G395A and C1818T polymorphisms were assessed by Sanger sequencing. Serum levels of sKlotho were determined by ELISA method.
Results
Subjects carrying GA genotype of Klotho G395A polymorphism had 3.27 times higher risk of developing acromegaly odds ratio (OR), 3.27; 95% confidence interval (CI): 1.37–7.81; p = .023. The A allele of G395A was significantly associated with acromegaly risk (OR, 2.27; 95% CI: 1.1–4.72; p = .022). No association was observed between the studied polymorphisms and disease characteristics including age at acromegaly diagnosis, size of adenoma, baseline GH and IGF‐1 concentrations, and final outcome. G395A polymorphism was associated with the presence of malignancy (OR, 2.24, 95% CI: 1.63–3.08; p = .019) and colorectal polyps (OR, 1.99; 95% CI: 1.02–3.88; p = .047) in patients with acromegaly. Serum sKlotho levels were significantly higher and correlated with GH and IGF‐1 levels among acromegaly patients. There was no association between the studied polymorphisms and sKlotho levels.
Conclusions
Klotho G395A polymorphism is associated with acromegaly susceptibility and increased risk of malignancy and colorectal polyps in these patients.
Diabetic autonomic neuropathy Vinik, Aaron I.; Erbas, Tomris
Handbook of Clinical Neurology,
2013, 2013-00-00, Letnik:
117
Book Chapter, Journal Article
Recenzirano
Autonomic neuropathy, once considered to be the Cinderella of diabetes complications, has come of age. The autonomic nervous system innervates the entire human body, and is involved in the regulation ...of every single organ in the body. Thus, perturbations in autonomic function account for everything from abnormalities in pupillary function to gastroparesis, intestinal dysmotility, diabetic diarrhea, genitourinary dysfunction, amongst others. “Know autonomic function and one knows the whole of medicine!” It is now becoming apparent that before the advent of severe pathological damage to the autonomic nervous system there may be an imbalance between the two major arms, namely the sympathetic and parasympathetic nerve fibers that innervate the heart and blood vessels, resulting in abnormalities in heart rate control and vascular dynamics. Cardiac autonomic neuropathy (CAN) has been linked to resting tachycardia, postural hypotension, orthostatic bradycardia and orthostatic tachycardia (POTTS), exercise intolerance, decreased hypoxia-induced respiratory drive, loss of baroreceptor sensitivity, enhanced intraoperative or perioperative cardiovascular lability, increased incidence of asymptomatic ischemia, myocardial infarction, and decreased rate of survival after myocardial infarction and congestive heart failure. Autonomic dysfunction can affect daily activities of individuals with diabetes and may invoke potentially life-threatening outcomes. Intensification of glycemic control in the presence of autonomic dysfunction (more so if combined with peripheral neuropathy) increases the likelihood of sudden death and is a caveat for aggressive glycemic control. Advances in technology, built on decades of research and clinical testing, now make it possible to objectively identify early stages of CAN with the use of careful measurement of time and frequency domain analyses of autonomic function. Fifteen studies using different end points report prevalence rates of 1% to 90%. CAN may be present at diagnosis, and prevalence increases with age, duration of diabetes, obesity, smoking, and poor glycemic control. CAN also cosegregates with distal symmetric polyneuropathy, microangiopathy, and macroangiopathy. It now appears that autonomic imbalance may precede the development of the inflammatory cascade in type 2 diabetes and there is a role for central loss of dopaminergic restraint on sympathetic overactivity. Restoration of dopaminergic tone suppresses the sympathetic dominance and reduces cardiovascular events and mortality by close to 50%. Cinderella’s slipper can now be worn!
Objective The pituitary gland is responsible for hormonal balance in the body, and disruption of hormonal balance in patients with pituitary adenoma (PA) indirectly affects the quality of life. This ...study aimed to examine the effects of yoga and combined aerobic and strength training (A+ST) on quality of life and related parameters such as sleep, fatigue, emotional state, sexual function, and cognitive status in women with PA. Design Ten women with PA were included in this randomized crossover study. Group 1 (n = 5, mean age: 52 ± 13.5 years) received A+ST for the first 6 weeks, a 2-week washout period, and yoga for the second 6 weeks. Group 2 (n = 5, mean age: 41.8 ± 14 years) received the yoga program first, followed by the A+ST program. Methods Participants were assessed using the following tools before and after each exercise intervention: Functional Assessment of Cancer Therapy–Brain (FACT-Br) (quality of life), Pittsburg Sleep Quality Index, Fatigue Severity Scale (FSS), Female Sexual Function Index (FSFI), Hospital Anxiety and Depression Scale (HADS), and Montreal Cognitive Assessment Scale (MOCA). Results FACT-Br scores were higher after the yoga program, HADS anxiety score was lower after the A+ST program, and MOCA scores increased after both exercise programs (P < 0.05). FSS score decreased after both exercise programs, but not significantly. In addition, nonsignificant decreases in HADS anxiety and depression scores and increased FSFI scores were observed after the yoga program. Conclusion A+ST and yoga have positive effects on the quality of life in PA. We recommend yoga and A+ST as a supportive therapy for this population that may face comorbidities after surgical and medical treatment. Our results indicate these patients may benefit from physiotherapist-guided exercise programs.
Hyperprolactinemia has negative impacts on metabolism and musculoskeletal health. In this study, individuals with active prolactinoma were evaluated for nonalcoholic fatty liver disease (NAFLD) and ...musculoskeletal health, which are underemphasized in the literature.
Twelve active prolactinoma patients and twelve healthy controls matched by age, gender, and BMI were included. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) was used to evaluate hepatic steatosis and magnetic resonance elastography (MRE) to evaluate liver stiffness measurement (LSM). Abdominal muscle mass, and vertebral MRI-PDFF was also evaluated with MRI. Body compositions were evaluated by dual energy X-ray absorptiometry (DXA). The skeletal muscle quality (SMQ) was classified as normal, low and weak by using "handgrip strength/appendicular skeletal muscle mass (HGS/ASM)" ratio based on the cut-off values previously stated in the literature.
Prolactin, HbA1c and CRP levels were higher in prolactinoma patients (p<0.001, p=0.033 and p=0.035, respectively). The median MRI-PDFF and MRE-LSM were 3.0% (2.01-15.20) and 2.22 kPa (2.0-2.5) in the prolactinoma group and 2.5% (1.65-10.00) and 2.19 kPa (1.92-2.54) in the control group, respectively and similiar between groups. In prolactinoma patients, liver MRI-PDFF showed a positive and strong correlation with the duration of disease and traditional risk factors for NAFLD. Total, vertebral and pelvic bone mineral density was similar between groups, while vertebral MRI-PDFF tended to be higher in prolactinoma patients (p=0.075). Muscle mass and strength parameters were similar between groups, but HGS/ASM tended to be higher in prolactinoma patients (p=0.057). Muscle mass was low in 33.3% of prolactinoma patients and 66.6 of controls. According to SMQ, all prolactinoma patients had normal SMQ, whereas 66.6% of the controls had normal SMQ.
Prolactinoma patients demonstrated similar liver MRI-PDFF and MRE-LSM to controls despite their impaired metabolic profile and lower gonadal hormone levels. Hyperprolactinemia may improve muscle quality in prolactinoma patients despite hypogonadism.
We have investigated the role of a cardiomyokine, follistatin-like 1 (FSTL1), and its single nucleotide polymorphism on acromegalic cardiomyopathy.
The study was performed as a cross-sectional case ...research in a Tertiary Referral Centre. Forty-six patients with acromegaly (29 F-17 M, mean age: 50.3 ± 12.1 years) were included. FSTL1 levels were measured and the rs1259293 region of the FSTL1 gene was subjected to polymorphism analysis. 1.5 Tesla MRI was used to obtain cardiac images.
There were 15 active (6 F-9M) and 31 (22 F-9M) controlled patients. Active patients had a higher left ventricular mass (LVM) and left ventricular mass index (LVMi). GH levels were positively correlated with left ventricular end-diastolic volume index (LVEDVi), stroke volume index (SVi), cardiac index (Ci), LVM and LVMi; r = 0.35, 0.38, 0.34, 0.39 and 0.39, respectively. IGF-1 index was positively correlated with LVEDVi, left ventricular end-systolic volume index (LVESVi), SVi, Ci, LVM and LVMi; r = 0.36, 0.34, 0.32, 0.31, 0.42 and 0.42, respectively. Twenty out of 46 patients with acromegaly (43.5%) had myocardial fibrosis. FSTL1 levels were neither correlated with disease activity nor with any functional and structural cardiac parameter. Multivariate linear regression analysis revealed no association between FSTL1 and any study parameters. The rs1259293 variant genotype CC was significantly associated with low left ventricular mass.
Serum FSTL1 levels are not associated with functional and structural measures of myocardium in patients with acromegaly. However, the risk of left ventricular hypertrophy is reduced in CC genotyped individuals of FSTL1.
Abstract Context The paucity of data on microvascular complications in patients with posttransplant diabetes (PTDM) is an obstacle to developing follow-up algorithms. Objective To evaluate diabetic ...microvascular complications in patients with long-standing PTDM. Methods In patients with ≥5-year history of PTDM and age-matched renal transplant recipients without PTDM (NDM), diabetic peripheral neuropathy was evaluated using the Michigan Neuropathy Screening Instrument, the CASE IV device, and in vivo corneal confocal microscopy (CCM). Cardiac autonomic neuropathy tests were performed using heart rate variability. Nephropathy screening was assessed using spot urine albumin/creatinine ratio and eGFR calculation. Diabetic retinopathy was evaluated by fundus examination and photography, and optical coherence tomography. Results This study included 41 patients with PTDM and 45 NDM patients. The median follow-up was 107.5 months in the PTDM group. Peripheral neuropathy was significantly higher in the PTDM group than in the NDM group (P = .02). In the PTDM patients with peripheral neuropathy, corneal nerve fiber density examined by CCM was significantly lower than in PTDM patients without neuropathy (P = .001). Parasympathetic involvement was observed in 58.5% of the PTDM group and 22% of the NDM group (P = .001). Sympathetic involvement was present in 65.9% of the PTDM group and 29.3% of the NDM group (P = .001). Retinopathy was observed in 19.5% of patients in the PTDM group and in none of the NDM patients (P < .001). Renal functions were similar between the study groups. Conclusion Cardiac autonomic neuropathy and diabetic retinopathy can affect patients with PTDM at a high rate. Diabetic retinopathy is a threat to the vision of PTDM patients. Diabetic peripheral neuropathy can be detected early in PTDM patients by CCM.
Purpose
Evaluate periodontal status of acromegalics through clinical and biochemical variables.
Methods
Demographics, hormone and metabolic variables, periodontal variables, gingival crevicular fluid ...(GCF) volume, and content data were collected from 30 patients with acromegaly, 30 patients with periodontitis, and 20 healthy subjects and comparatively analyzed.
Results
GH differences between acromegaly (2.56 ± 4.86) and periodontitis (0.53 ± 0.95) (
p
< 0.001) were statistically significant. IGF-1 was lowest at periodontitis (113.31 ± 45.01) and lower (152.11 ± 45.56) at healthy group compared with acromegalics (220.38 ± 167.62) (
p
< 0.05). GH and IGF-1 had positive correlation (
p
< 0.05). IGF-1 and CAL had negative (
p
< 0.01) correlation except healthy group that showed the same correlation at the opposite direction (
p
< 0.05). Besides similar plaque and gingival indices with periodontitis, acromegalics showed relatively less CAL and GCF volume but except CAL, all their periodontal variables were higher than healthy subjects. GCF GH and prolactin showed higher values in acromegalics while healthy subjects showed relatively high interleukin-1, -10 and carboxyterminal telopeptide of type I collagen compared with others.
Conclusion
Acromegalics have a tendency of slowed periodontal destruction with an influence of GH and IGF-1 to the inflammation- and collage metabolism-related mechanisms rather than bone-associated ones. However, this information must be confirmed with further studies exploring the mechanisms possibly bonded to others.
Abstract
Disclosure: I. Eroglu: None. B. Gonul Iremli: None. I. Idilman: None. D. Yuce: None. I. Lay: None. D. Akata: None. T. Erbas: None.
Background: Due to their impaired glucose and lipid ...metabolism, acromegaly patients are potentially at risk for NAFLD. However, limited data exist about acromegaly and NAFLD relation. In this study (cross-sectional, case-controlled), we evaluated the risk of NAFLD and hepatic fibrosis in acromegalic patients and its association with noninvasive hepatosteatosis scores (NS) and angiopoietin-like protein-8 (ANGPTL-8) level for the first time in the literature. Methods: Thirty-two (15F/17M - median age=50.15 yrs) acromegalic patients (n=15 active acromegaly - AA and n=17 controlled acromegaly - CA) compared to 19 healthy controls (C) in terms of liver fat ratio (LFR), liver stiffness measurement (LSM), and ANGPTL-8 levels. Subjects had MRI-PDFF to determine LFR and MR elastography to quantify LSM. NAFLD was confirmed in those with LFR of ≥5%, and increased LSM in those with LSM of ≥2.5 kPa. VAI (visceral adipocity index), FLI (fatty liver index), HSI (hepatic steatosis index), and TyG (Triglyceride-glucose index) were calculated as NS. Results: Age, gender and BMI were similiar across groups. The GH and IGF-1 levels in AA group was greater than in CA, and C (p< 0.001). The CA had greater frequency of NAFLD than AA (p<0.001). Increased LSM was detected in three (21.4%) of AA, four (23.5%) of CA, and two (10.5%) of C.The median LFR was 1.75% in the AA group, 6.5% in the CA group, and 3.5% in the control group. LFR was lower in the AA group than in the CA (p=0.026). According to MRI-PDFF results, none of the patients in the AA group were diagnosed with NAFLD, while 58.8% (n=10) in the CA group and 26.3% (n=5) in the control group were diagnosed with NAFLD. The prevalence of NAFLD was found to be higher in the CA group than in the AA group (p<0.001). In acromegaly patients, LFR was positively correlated with TyG (r=0.675, p<0.001), VAI (r=0.508, p=0.004), and FLI (r=0.482, p=0.006). However, no correlation was seen between LFR and traditional risk factors for NAFLD (including BMI, waist circumference, Hba1c, HOMA-IR, and CRP) in acromegalics.ANGPTL-8 was lower in CA group (0.61 ng/mL) than in AA group (0.89 ng/mL) (p=0.006). When all acromegaly patients were evaluated independently, those with NAFLD had lower ANGPTL-8 levels than those without NAFLD (p=0.036). Conclusion: In conclusion, high GH levels seem to be protective against fatty liver in patients with active acromegaly, even if the metabolic profileis impaired. There was no relation observed between LFR and conventional risk factors in acromegaly patients. The strongest connection was found between LFR and TyG index among the noninvasive hepatosteatosis scores. ANGPTL-8 levels were lower in acromegaly patients with NAFLD, suggesting that high levels represent a reaction to insulin resistance rather than a cause of NAFLD. Treatment planning at a level that does not cause GH deficiency while maintaining disease control may be helpful to prevent NAFLD in acromegaly.
Presentation: Thursday, June 15, 2023
Growth retardation is one of the cardinal manifestations of glycogen storage disease type Ia. It is unclear which component of the growth hormone and/or insulin-like growth factor axis is primarily ...disrupted, and management of growth impairment in these patients remains controversial. Here we report the first case in the literature where glycogen storage disease type Ia is associated with pituitary hypoplasia and growth hormone deficiency.
A 20-year-old woman with glycogen storage disease type Ia was admitted to our endocrinology department because of growth retardation. Basal and overnight growth hormone sampling at 2-hour intervals demonstrated low levels; however, provocative testing revealed a relatively normal growth hormone response. A hypoplastic anterior pituitary with preserved growth hormone response to provocative testing suggested the possibility of growth hormone neurosecretory dysfunction and/or primary pituitary involvement.
Pituitary hypoplasia may result from growth hormone-releasing hormone deficiency, a condition generally known as growth hormone neurosecretory dysfunction. It is an abnormality with a spontaneous and pulsatile secretion pattern, characterized by short stature, growth retardation and normal serum growth hormone response to provocative testing. However, in the case described in this report, a normal although relatively low growth hormone response during insulin tolerance testing and pituitary hypoplasia suggested that primary pituitary involvement or growth hormone neurosecretory dysfunction may occur in glycogen storage disease type Ia. This is a potential cause of growth failure associated with a lower somatotroph mass, and may explain the variable responsiveness to growth hormone replacement therapy in people with glycogen storage disease.
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