Growth Hormone & Igf Research最新文献

Patients with growth hormone deficiency (GHD) have many clinical features in common with Cushing's syndrome (glucocorticoid excess) – notably visceral obesity, insulin resistance, muscle myopathy and increased vascular mortality. Within key metabolic tissues, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone to the active glucocorticoid, cortisol (11-dehydrocorticosterone and corticosterone in rodents respectively), and thus amplifies local glucocorticoid action.

We hypothesize that 11β-HSD1 expression is negatively regulated by growth hormone (GH), and that GHD patients have elevated 11β-HSD1 within key metabolic tissues (leading to increased intracellular cortisol generation) which contributes to the clinical features of this disease.

To identify the impact of GH excess/resistance on 11β-HSD1 in vivo, we measured mRNA expression in key metabolic tissues of giant mice expressing the bovine GH (bGH) gene, dwarf mice with a disrupted GH receptor (GHRKO) gene and mice expressing a gene encoding a GH receptor antagonist (GHA). Additionally, we assessed urine steroid markers of 11β-HSD1 activity in both GHRKO and bGH animals.

11β-HSD1 expression was decreased in gastrocnemius muscle (0.43-fold, p < 0.05), subcutaneous adipose (0.53-fold, p < 0.05) and epididymal adipose tissue (0.40-fold, p < 0.05), but not liver, in bGH mice compared to WT controls. This was paralleled by an increased percentage of 11-DHC (inactive glucocorticoid) present in the urine of bGH mice compared to WT controls (2.5-fold, p < 0.01) - consistent with decreased systemic 11β-HSD1 activity. By contrast, expression of 11β-HSD1 was increased in the liver of GHRKO (2.7-fold, p < 0.05) and GHA mice (2.0-fold, p < 0.05) compared to WT controls, but not gastrocnemius muscle, subcutaneous adipose tissue or epididymal adipose tissue.

In summary, we have demonstrated a negative relationship between GH action and 11β-HSD1 expression which appears to be tissue specific. These data provide evidence that increased intracellular cortisol production within key tissues may contribute to metabolic disease in GHD patients.

Objective

To identify and characterize a novel deletion at the LHX4 gene locus in a proband with growth hormone deficiency (GHD).

Methods

Long range polymerase chain reaction (PCR) amplification was used to confirm the suspected deletion and to identify the rough locations of the end points. Sanger sequencing was carried out to identify the exact end points of the deletion.

Results

Suspected deletion was confirmed via long range PCR amplification. Sanger sequencing identified the end points of the deletion within three nucleotide repeat sequences (“CTT”). The total length of the deleted segment was 12 127 base pairs and it includes complete exon 5 and exon 6 of the LHX4 gene. Therefore the homeodomain motif coded by exons 4 and 5, might be affected.

Conclusion

We have identified a novel deletion that spans exon 5 and exon 6 of the LHX4 gene that could have occurred via microhomology mediated non-recurrent rearrangement. The deletion characterized does not appear to have been reported before. To our knowledge this novel deletion is the first identified LHX4 variant from Sri Lanka and it explains the phenotype of the proband characterized by growth hormone deficiency, hypoplastic anterior pituitary and subsequent deficiency of thyroid stimulating hormone and adrenocorticotropic hormone (ACTH).

Objectives

Pituitary diseases may cause psychiatric and personality alterations. We aimed to compare the personality traits of acromegalic patients with those of patients with non-functioning pituitary adenomas and a healthy control group.

Design

Fifty-eight acromegalic patients, 45 patients with non-functioning adenoma, and 40 healthy subjects were enrolled in the study. Cloninger's Temperament and Character Inventory (TCI), Beck Depression Inventory, Beck Anxiety Inventory, and Rosenberg Self-Esteem Scale (RSES) were used to assess personality, depression, anxiety, and self-esteem.

Results

Depression score was higher in acromegaly and non-functioning adenoma groups than healthy controls. RSES scores were similar among the three groups. Regarding the scales of TCI, only novelty-seeking was significantly reduced in acromegaly and non-functioning adenoma than the control group. Pairwise comparisons revealed that the difference was due to the difference between acromegalic patients and controls. Scales of TCI were correlated with depression and anxiety in patients with acromegaly and non-functioning adenoma but not in healthy controls.

Conclusion

This study showed that novelty-seeking was reduced in patients with acromegaly. Both the hormonal lack and excess and structural changes can lead to cognitive and personality changes in acromegaly. More studies are needed to be carried out about personality characteristics in pituitary diseases.

Objective

An intrauterine device (IUD) is one of the most effective reversible contraceptive methods currently available. Women who use IUDs may become pregnant, albeit rarely, and many such women continue to use IUDs. Because it is difficult to remove or it may cause miscarriage. This study measured the changes in human leucocyte antigen-G (HLA-G) and insulin-like growth factor II (IGF-II) levels in the decidua and villi to explore the effect of a copper IUD on embryonic development.

Design

A total of 54 samples of decidual and villus tissue were collected from pregnant women with IUDs (27 samples) or without IUDs (27 samples). Hematoxylin-eosin staining was used to identify morphological characteristics. Immunohistochemistry was used to detect HLA-G and IGF-II; the protein expression levels were measured via Western blotting.

Results

HLA-G was expressed on the membranes of trophoblasts of villus tissues and the glandular epithelium, and in stromal cells of decidual tissues, in both the IUD and control groups. IGF-II was expressed in the glandular epithelium and cytoplasm of trophoblasts and decidual cells in both groups. Compared to the control group, IGF-II expression was significantly reduced in villus tissues of the IUD group (p < 0.05). The mean sac diameter was significantly positively correlated with IGF-II expression in the villi (p < 0.05).

Conclusions

A copper IUD may affect embryonic development by regulating the expression of villus IGF-II.

Objective

Cardiovascular (CV) disease is still a major cause of excessive morbidity and mortality in patients with active acromegaly, which may be attributed to a high prevalence of associated pro-atherosclerotic risk factors. However, a direct effect of GH/IGF-1 excess on the vasculature has been previously suggested, warranting further investigation. The present study was designed to investigate whether chronic GH/IGF-1 excess is associated with an increased prevalence of subclinical atherosclerosis in patients with acromegaly.

Design

We measured carotid intima-media thickness (cIMT) and assessed carotid plaques by ultrasonography along with classical CV risk factors in 54 acromegaly patients (34 females, 50 ± 12 years and compared those with 62 (42 females, 53 ± 13 years) age-, sex- and CV risk factors- matched controls. In order to compare cIMT measurements between patients and controls we analyzed common carotid artery far wall data as well as a combined measurement result, which consisted of the mean value of the six different measurements, three at each side.

Results

mean ± SD serum GH and IGF-1 levels were 2.76 ± 4.65 ng/mL and 1.7 ± 1.25 x ULN, respectively, in all acromegaly patients. Age, body mass index, blood pressure, lipid levels, fasting glucose and Framingham's global cardiovascular risk score classification were similar comparing patients and controls. Combined median [IQR] cIMT measurements were similar in acromegaly patients and matched controls (0.59 [0.52–0.66] mm vs. 0.59 [0.52–0.69] mm; P = 0.872) as well as in acromegaly patients with active and controlled disease (0.59 [0.51–0.68] mm vs. 0.60 [0.54–0.68] mm; P = 0.385). No significant correlations were observed between cIMT measurements and GH (Spearman r = 0.1, P = 0.49) or IGF-1 (Spearman r = 0.13, P = 0.37) levels in patients with acromegaly. Carotid atherosclerotic plaques prevalence was similar in patients and controls (26% vs. 32%; P = 0.54) as well as in patients with active and controlled acromegaly (22% vs. 30%; P = 0.537).

Conclusions

Our data suggest that GH/IGF-1 excess itself is not one of the main drivers of subclinical morphological atherosclerosis changes in patients with acromegaly and that optimal control of acromegaly-associated CV risk factors may preserve vasculature structure even when strict biochemical control is not achieved.

Purpose

To investigate anterior segment parameters (ASPs) and dry eye disease (DED), including the status of the meibomian glands, in patients with acromegaly.

Methods

In this cross-sectional, comparative study, 36 acromegaly patients and 40 healthy sex- and age-matched controls were included. Participants received a comprehensive ophthalmological examination, including intraocular pressure measurements with Goldmann applanation tonometry (IOP_GAT) and central corneal thickness corrected intraocular pressure (IOP_CCT) measurements, and were evaluated for ASPs and DED. For ASPs, white-to-white (WTW), apical (ACT) and thinnest corneal thickness (TCT), corneal volume (CV), keratometry readings (K₁, K₂, and K_mean), anterior chamber depth (ACD) and volume (ACV), and iridocorneal angle (ICA) were obtained via Sirius topography. DED was assessed with Schirmer's test, tear breakup time (TBUT), and Ocular Surface Disease Index (OSDI) scores. Meibography scores (MSs) were obtained with the Sirius topography device.

Results

Patients had higher mean IOP_GAT (P = .006), IOP_CCT (P = .01), ACT (P = .024), and TCT (P = .005) but narrower ICA (P = .014) than controls. Although Schirmer's test did not differ between the groups (P = .442), patients had higher OSDI (P < .001), higher MS (P = .001), and shorter TBUT (P = .002).

Conclusion

Patients with acromegaly have greater IOP, greater corneal thickness, but narrower ICA than healthy individuals, as well as DED with increased MSs, which suggests meibomian gland dysfunction.

Aims

Describe the local characteristics, methodology and results of the registry of acromegalic patients in Colombia (RAPACO).

Methods

Multicenter, retrospective study based on the registry of acromegalic patients in Colombia: RAPACO. The data collected included: demographics, diagnosis, approximate time of disease evolution, data on weight, height, body mass index (BMI), neck circumference (NC) abdominal circumference (AC) hip circumference (HC) and waist/hip ratio (WHR); clinical and biochemical data at the time of diagnosis, etiology, immunohistochemistry of the tumor and information related to types of treatment. Descriptive analytics were employed.

Results

A total of 201 patients (60% females) with an average age at registration of 49.5 ± 14.6 years and an average time of evolution of the disease of 6.96 ± 4.5 years. Average weight was 75.1 Kg ± 12.98, with an average BMI of 28.11 ± 4.33. The most frequent symptoms mentioned at the time of diagnosis were extremity enlargement and headache. The most frequent comorbidity was arterial hypertension in 50.3% of the cases. 78.6% of cases were caused by macroadenoma. 80.1% received surgical treatment, 77.6% were under medical treatment, of which 95.7% were receiving somatostatin analogues. 26.4% of patients were treated with radiation therapy. Of the patients who received any type of clinical treatment, only 2.5% reported biochemical control at registration.

Conclusion

It is important to recognize the local epidemiological, clinical, biochemical and treatment characteristics in order to assist in further understanding this pathology to implement local measures to improve both the quality of life as well as the prognosis of the patients diagnosed.

Objective

It was the aim of this study to evaluate illness-related burdens and support needs of patients with acromegaly to identify hitherto unadressed research questions and to open up avenues for improvements in patient care. This was done by using the focus group approach as a qualitative research method.

Design

Seven patients with acromegaly took part in a focus group moderated by an external medical communication specialist. The discourse focused on topics such as impact of the illness on everyday life, support needs and personal resources. The discussion was recorded and transcribed and analyzed by qualitative content analysis.

Results

Participants reported a huge impact of acromegaly on daily life, ranging from time expenditure for managing their illness, to bodily and mental sequelae and strain caused by physical disfigurement. Patients' coping strategies included family support, physical activities and humor. The participants wished for a sound patient-doctor relationship, more interdisciplinary and holistic treatment, medical rehabilitation services with special knowledge on acromegaly-related morbidity, a stable contact person in the medical process and reliable information material for themselves and their relatives.

Conclusions

The results provide multi-facetted impressions of the overwhelming impact of acromegaly and unmet support needs of the afflicted patients. Further quantitative research is necessary to examine the generalisibility of the present results in order to implement tailored support measures. We suggest to develop standardized questionnaires to explore the prevalence and severity of the addressed problems in a large patient sample and to establish screening instruments to monitor disease burden in clinical practice.

Introduction

Goiter is very common in patients with acromegaly; its development is correlated to the duration of the disease. Thyroid cells express the IGF-1 receptor and the TSH/IGF-1 interaction has been demonstrated to have a synergistic effect in thyroid cell growth. There is a correlation between IGF-1 levels and the thyroid volume of patients with acromegaly. The aim of this study was to evaluate, in a retrospective case-cohort study of patients with acromegaly, the associated risk factors for thyroid nodules disease in this population.

Methods

This was a case-cohort study matched by age, gender, and growth hormone at diagnosis. Cases consisted of acromegalic patients that developed thyroid nodules during the follow up, and controls consisted in acromegalic patients without thyroid nodules. A Cox proportional hazard estimation was carried out for measure the associated risk factors for thyroid nodules disease in acromegalic patients. A nodular thyroid disease-free survival analysis was estimated using the Kaplan-Meier analysis.

Results

We recruited 49 cases and 56 controls. In a multivariate Cox proportional hazard analysis age and IGF-1 ≥ 2.2 x ULN were significantly related with the presence of thyroid nodules [HR of 2.21 (95% CI; 1.15–4.25, p = 0.01)]. Nodularity-free survival rates in patients who had an IGF-1 X ULN ≥ 2.2 was found to be lower in comparison to those who had IGF-1 X ULN < 2.2, according to a Kaplan-Meier survival analysis.

Conclusions

Our findings support that exist more probability to develop thyroid nodular disease in patients with acromegaly that present IGF-1 X ULN ≥ 2.2, suggesting a possible direct effect between the time of exposure to the IGF-1 axis hyperactivity and the genesis of thyroid nodules.