Purpose
Whether the renin–angiotensin–aldosterone system plays a role or not in the development of cardiovascular morbidity in acromegaly patients is unknown. The aim of the study was to investigate ...the association between ACE (I/D) and AGT (M235T) gene polymorphisms and cardiovascular and metabolic disorders in the acromegaly.
Methods
The study included one hundred and seventeen acromegalic patients (62 F/55 M, age: 50.2 ± 12.3 years) and 106 healthy controls (92 F/14 M, age: 41.4 ± 11.3 years). PCR method was used to evaluate the prevalence of ACE and AGT genotype.
Results
The genotypes of ACE polymorphism in acromegalic patients were distributed as follows; 41.0% (n: 48) for DD, 44.4% (n: 52) for ID and 14.5% (n: 17) for II genotype. The control group had significantly different distribution of the ACE polymorphism 48.1% (n: 51) for DD, 25.5% (n: 27) for ID and 26.4% (n: 28) for II genotypecompared to acromegalic group. Regarding AGT polymorphism, AGT-MT genotype was seen in 88.9% of the acromegalic patients while MM and TT genotype (9.4% and 1.7%, respectively) were present in the rest. The controls had similar distribution of the AGT genotype with the acromegaly group (80.2% MT genotype, 15.1% MM genotype and 4.7% TT genotype). Due to the small number of patients with TT allele (n: 2), T carriers for AGT genotype (AGT-MT+TT) were subgrouped and compared to those with AGT-MM group. ACE-DD, ID and II groups had similar anthropometric measures, blood pressure values and baseline GH and IGF-1 levels. Significantly higher baseline GH levels were found in AGT-MM group compared to T allele carriers 40 (16–60) vs. 12 (5–36) µg/L, p < 0.05. The compared groups in both polymorphisms had similar fasting plasma glucose levels. Patients with ACE-II genotype had significantly higher HDL-C levels compared to those with ACE-DD and ACE-ID polymorphisms (p < 0.05) whereas there was no significant difference in lipid profile between AGT-MM group and AGT-T allele carriers. Moreover, the compared groups in both polymorphisms had similar distribution of hyperlipidemia, hypertension, impaired glucose metabolism (prediabetes or type 2 diabetes mellitus) and coronary artery disease. In terms of echocardiographic parameters, systolic and diastolic function was similar among the groups in ACE and AGT genotypes. Interestingly, AGT-MM group had higher mitral inflow A
peak
values than T allele carriers (0.94 ± 0.46 vs. 0.73 ± 0.20; p = 0.051). No significant difference was observed in LV mass index values in acromegalic patients among the groups in both polymorphisms.
Conclusions
Both ACE (I/D) and AGT (M235T) gene polymorphisms do not seem to have a significant effect on the development of clinical properties or cardiovascular comordities of acromegalic patients.
The aim of the study was to investigate whether lifestyle factors modify the association between fat mass and obesity-associated (FTO) gene single nucleotide polymorphisms (SNPs) and obesity in a ...Turkish population. The study included 400 unrelated individuals, aged 24-50 years recruited in a hospital setting. Dietary intake and physical activity were assessed using 24-hour dietary recall and self-report questionnaire, respectively. A genetic risk score (GRS) was developed using FTO SNPs, rs9939609 and rs10163409. Body mass index and fat mass index were significantly associated with FTO SNP rs9939609 (p = 0.001 and p = 0.002, respectively) and GRS (p = 0.002 and p = 0.003, respectively). The interactions between SNP rs9939609 and physical activity on adiponectin concentrations, and SNP rs10163409 and dietary protein intake on increased waist circumference were statistically significant (P
interaction
= 0.027 and P
interaction
= 0.044, respectively). Our study has demonstrated that the association between FTO SNPs and central obesity might be modified by lifestyle factors in this Turkish population.
Limited data on microvascular complications in patients with post-transplant diabetes (PTDM) is an obstacle to developing follow-up algorithms.
To evaluate diabetic microvascular complications in ...patients with long-standing PTDM.
This study included patients with at least a five-year history of PTDM and age-matched renal transplant recipients without PTDM (NDM). Diabetic peripheral neuropathy (PN) was evaluated using the Michigan Neuropathy Screening Instrument (MNSI), the CASE IV device, and in vivo corneal confocal microscopy (CCM). Cardiac autonomic neuropathy (CAN) tests were performed using the heart rate variability. Nephropathy (DN) screening was assessed using spot urine albumin/creatinine ratio and eGFR calculation. Diabetic retinopathy (DR) was evaluated by fundus examination and photography, and optical coherence tomography.
This study included 41 patients with PTDM and 45 patients in the NDM group. The median follow-up was 107.5 months in the PTDM group. PN was significantly higher in the PTDM group than in the NDM group (p = 0.02). In the PTDM patients with PN, the corneal nerve fiber density examined by CCM was significantly lower than in the PTDM patients without neuropathy (p = 0.001). Parasympathetic involvement was observed in 58.5% of the PTDM group and 22% of the NDM group (p = 0.001). Sympathetic involvement was present in 65.9% of the PTDM group and 29.3% of the NDM group (p = 0.001). Retinopathy was observed in 19.5% of patients in the PTDM group, while none were in NDM patients (p < 0.001). Renal functions were similar between the study groups.
CAN and DR can affect patients with PTDM at a high rate. DR was found to be a threat to the vision of PTDM patients. Diabetic PN can be detected early in PTDM patients by CCM.
The Secret Behind Anemia in Patients With Acromegaly Firlatan, Busra; Sendur, Suleyman Nahit; Oguz, Seda Hanife ...
Journal of the Endocrine Society,
05/2021, Letnik:
5, Številka:
Supplement_1
Journal Article
Recenzirano
Odprti dostop
Abstract
Introduction: The GH/IGF-1 axis has regulatory effects on erythropoiesis. GH deficiency is associated with normocytic anemia in adults, and hemoglobin (Hb) concentrations are normalized ...after GH replacement. Little is known about the significance of anemia in acromegalic patients. The aim of this study is to evaluate the factors associated with anemia in patients with acromegaly.
Methods: A single-center retrospective cohort study was conducted. A total of 381 acromegalic patients who admitted to the University Hospital from 1980 to 2018 were included. Information regarding the demographic features, the pre-operative and follow-up hormone levels, radiological features of adenoma, treatment modalities, comorbidities, presence of cancer, colonoscopy results, medication history, presence and type of anemia together with the CBC, iron parameters, 25(OH)D, and vitamin B12 levels at the time of anemia detected were retrieved from the patient record system. Anemia was defined as Hb levels <12.0 g/dL in women and <13.0 g/dL in men.
Results: Of 381 acromegalic patients (120F/98M, age: 44±13yr/45±12 yr); 218 cases (57.2%) were diagnosed with anemia (67% normocytic, 33% microcytic) at a median duration of 6 months after the diagnosis of acromegaly. Hb values were 11.1±0.9 g/dL in women and 12.1±1.0 g/dL in men. Serum levels of ferritin and transferrin saturation were lower in anemic patients (p<0.001). The levels of 25(OH)D and vitamin B12 were lower in the anemic group, but the differences were not statistically significant. Anemia was detected more likely in patients who had macroadenoma (p=0.001), suprasellar extension (p=0.001), and cavernous sinus invasion (p<0.001) on pre-op MRI and residue tumor (p<0.001) on post-op MRI. Patients with anemia had higher GH, IGF-1 and PRL levels (p<0.01), and there was a significant difference related to the use of octreotide (p<0.001). Anemia was observed more frequently in patients with a history of radiotherapy (29% vs. 10%, p<0.001). Hypopituitarism was seen in 63 (29%) patients in the anemic group and 21 (13%) patients in the non-anemic group (p<0.001). Cancer prevalence in the study population was 14.2%, and the most commonly diagnosed cancers were thyroid, bladder, prostate, and breast. Although not statistically significant, the prevalence of cancer was higher in anemic patients compared to non-anemic patients (17% vs. 10%). There was no significant difference regarding the presence of colorectal polyps between groups, and only two anemic patients were diagnosed with colon cancer.
Conclusion: This is the first study highlighting that anemia is a common comorbidity in patients with acromegaly, and that anemia can be related to characteristics of the tumor, hormonal status, type of treatment, and the presence of cancer in addition to nutritional factors. Therefore, a comprehensive evaluation is required for anemia in acromegalic patients.
Mast cell disorders are defined by an abnormal accumulation of tissue mast cells in one or more organ systems. In systemic mastocytosis, at least one extracutaneous organ is involved by definition. ...Although, systemic mastocytosis usually represents with skin lesion called urticaria pigmentosa, in a small proportion, there is extracutaneous involvement without skin infiltration. Other manifestations are flushing, tachycardia, dyspepsia, diarrhea, hypotension, syncope, and rarely fever. Various medications have been used but there is not a definite cure for systemic mastocytosis. The principles of treatment include control of symptoms with measures aimed to decrease mast cell activation. We describe a case of systemic mastocytosis presenting with hypotension, syncope attacks, fever, and local flushing. In bone marrow biopsy, increased mast cell infiltration was demonstrated. She had no skin infiltration. A good clinicopathological response was obtained acutely with combination therapy of glucocorticoid and cyclosporine.
Comparison of metoclopramide and erythromycin in the treatment of diabetic gastroparesis.
T Erbas ,
E Varoglu ,
B Erbas ,
G Tastekin and
S Akalin
Department of Internal Medicine, Medical Faculty, ...Hacettepe University, Ankara, Turkey.
Abstract
OBJECTIVE--To compare the effects of erythromycin and metoclopramide on gastric emptying and symptoms of gastroparesis in
diabetic patients with delayed gastric emptying. RESEARCH DESIGN AND METHODS--The study group consisted of 13 patients with
symptoms of severe gastroparesis and delayed gastric emptying. Gastric emptying was evaluated using a radionuclide method,
and gastrointestinal symptoms were scored. The patients were given either erythromycin (250 mg 3 times/day) or metoclopramide
(10 mg 3 times/day) in random order for 3 wk, and after a washout period of 3 wk they were crossed-over to the other medication
for another 3 wk. Parameters of gastric emptying were assessed before treatment and after both erythromycin and metoclopramide
administration. RESULTS--The half-time of gastric emptying in diabetic subjects was 110 (77-120) min before treatment. At
60 and 90 min, the median value of residual isotope activity was 66.5 (55-83.5) and 55% (43-74.3), respectively. The half-time
decreased to 55 min (28.6-115) after 3 wk of treatment with erythromycin and percentages of meal retention in the stomach
at 60 and 90 min were 49.9 (38.4-70) and 40.5% (29.7-60), respectively. After taking metoclopramide, the median value of half-time
was 67 min (15-115) and percentages of meal retention at 60 and 90 min were 51 (34.5-93.9) and 42% (24-71.2), respectively.
When compared with baseline values a significant difference in gastric emptying parameters was found after both erythromycin
and metoclopramide. A significant improvement of the total score for gastrointestinal symptoms was observed with both drugs,
but this improvement was more pronounced with erythromycin. CONCLUSIONS--Erythromycin, a macrolide antibiotic and a motilin
receptor agonist, appears to stimulate intestinal motility and seems to be an alternative agent for the treatment of gastroparesis
caused by diabetic autonomic neuropathy.
The clinical features of pituitary hemorrhage vary from asymptomatic to catastrophic. We aimed to evaluate the frequency, symptoms, outcome and risk factors of clinical and subclinical pituitary ...apoplexy (PA) patients. In a retrospective analysis, charts of 547 pituitary adenoma patients from 2000 to December 2011 were reviewed. The patients were classified as clinical or subclinical PA. We compared the results with a control group without PA. Anterior pituitary hormones for endocrine dysfunction, histology, Ki-67 labeling index (LI), and p53 positivity of the tumor and pituitary imaging by magnetic resonance imaging were evaluated. Thirty-two patients (5.8 %) were diagnosed as clinical and 81 patients (14.8 %) as subclinical PA. Among PA patients, 85 patients (75.2 %) had a macroadenoma, 8 patients (7.1 %) had a microadenoma. The most frequent symptoms at presentation in PA patients were visual loss and headache. The patients with macroadenoma had a significantly increased risk for PA (
p
< 0.05). Hormone inactive tumors were significantly associated with the development of clinical PA (
p
= 0.05). Dopamine agonist use was significantly higher in subclinical PA patients (
p
= 0.001). Sex, Ki-67 LI, p53 positivity, diabetes mellitus, hypertension, somatostatin analogue and anticoagulant use did not predispose to PA whereas cavernous sinus invasion predisposed patients to PA (
p
< 0.01). The incidence of subclinical PA is higher than that of clinical PA. The development of PA is associated with macroadenomas. Clinically non-functioning tumors predispose to clinical PA. Cavernous sinus invasion of the tumor may be a sign of increased risk of bleeding.
Abstract
Objective
Data on bacterial diversity and microbiota alterations in acromegaly are currently lacking. The effects of somatostatin receptor analogs on gut microbiota remain unknown. The ...objective of this study was to determine microbiota alterations in patients with acromegaly and to assess the effects of somatostatin receptor analogs on gut microbiota.
Methods
The study was designed as a cross-sectional case-control research and three cohorts, comprising individuals with acromegaly without medical therapy (n=5), acromegaly receiving octreotide acetate (OCT) (n=8) and healthy controls (n=5), were evaluated.
Results
No statistically-supported changes in
Bacteroidetes, Firmicutes, Proteobacteria
and
Actinobacteria
abundance were observed.
Bacteroidaceae, Odoribacteraceae, Porphyromonadaceae, Prevotellaceae
and
Alistipes
families of
Bacteroidetes
and
Bifidobacterium
genus of the
Actinobacteria
phyla were detected, without overt differences. Variations in
Clostridia, Erysipelotrichaceae
and
Veillonellaceae
were not significant, while
Lactobacillales
were increased in individuals receiving OCT. Moreover,
Akkermansia mucinophila
was present in patients under OCT treatment.
Conclusion
Our preliminary results suggest that the bacterial community profile under OCT treatment may facilitate a colonic microenvironment for improved glucose metabolism. Alterations in the gut microbiota may be a factor affecting diabetes development during somatostatin analog treatment in acromegalic patients.
Abstract
The prevalence of growth hormone (GH)-secreting pituitary adenoma is around 11-13% of all pituitary adenomas. Giant GH-secreting pituitary adenomas (≥ 4 cm) are rare tumors, and its ...prevalence of among acromegalic patients is <5%.
This is a retrospective cohort study including patients with giant GH-secreting pituitary adenomas. The study population consisted of 10 patients (5 M/5 F). The mean age at diagnosis was 33.0±12.9 yrs (11-55 yrs). The mean delay between first symptom onset and diagnosis was 2.9 years. The most frequent symptoms were acral enlargement and facial changes (80%), followed by headache (70%) and visual deterioration (50%). One patient had epilepsy. Amenorrhea was presented in three females but obvious galactorrhea in two. The mean adenoma diameter was 42.6±4.7 mm (40-51 mm) at diagnosis. The vast majority of adenomas presented suprasellar extension (100%) or cavernous sinus invasion (80%). Cystic adenomas accounted for 50%. At presentation, mean GH and IGF-1 levels were 40.0±21.4 ng/mL (14.8-51.0) and 2.62±1.09 x ULN (1.08-3.96), respectively. Six patients presented with PRL cosecretion. At diagnosis maximal tumor diameter was not correlated with GH or IGF-1 levels.
All patients underwent pituitary surgery as first-line treatment. Three cases were treated with an endoscopic approach and four cases with a microscopic approach. Transcranial approach was also employed in three cases. Postoperative mean GH and IGF-1 levels were 14.9±16.1 ng/mL (0.6-51.0) and 2.25.±0.82 x ULN (1.48-3.74), respectively. After first surgery, only one patient had more than 50% reduction in IGF-1 levels. Five patients (50%) underwent repeat surgery on two to three procedures because remission was not achieved. Postoperative somatostatin receptor ligands (SRLs) were used by all patients. Six patients were treated with dopamine agonist in combination with SRL. Six patients (60%) received postoperative radiotherapy.
The mean follow-up period was 12.6±5.3 yrs (4-21 yrs). The mean GH and IGF-1 levels were 1.47±1.54 ng/mL (0.08-5.25) and 0.73±0.44 x ULN (0.08-1.56), respectively at the last visit. Residual adenoma was present at the last MRI in eight patients (mean diameter 9.0±3.6 mm). Panhypopituitarism rose from 10% at baseline to 30% at the last visit. During follow-up, one patient diagnosed breast cancer, while another diagnosed thyroid papillary cancer.
Giant GH-secreting pituitary adenomas can have a clinically aggressive behavior with mass effect. Moreover, treatment in patients with giant GH-secreting pituitary adenoma is complex and multimodal therapy is necessary.