Acromegaly is characterized by growth hormone (GH) and insulin-like growth factor 1 (IGF1) excess and is accompanied by an increased cardiovascular diseases (CVD) risk. As innate immune responses are crucial in CVD development, and IGF1 is linked to subclinical inflammation, we hypothesized that GH/IGF1 excess contributes to CVD development by potentiating systemic inflammation. We aimed to assess the effects of GH/IGF1 on inflammatory cytokine production. Whole blood from acromegaly patients and healthy volunteers and peripheral blood mononuclear cells (PBMCs) from healthy volunteers were stimulated with Toll-like receptor (TLR) ligands, with or without adding GH or IGF1 (in PBMC). Cytokine concentrations were measured by ELISA. The underlying signalling pathways were investigated by the inhibition of downstream targets of the IGF1 receptor. The following results were obtained. GH or IGF1 alone did not influence cytokine production in PBMCs. GH did not affect TLR-induced cytokine production, but co-stimulation with IGF1 dose dependently increased the TLR ligand-induced production of IL6 (P < 0.01), TNF alpha (P = 0.02) and IFNg (P < 0.01), as well as the production of the anti-inflammatory cytokine IL10 (P = 0.01). IGF1 had no effect on IL1B, IL17 and IL22 production. Inhibition of the MAPK pathway, but not mTOR, completely abrogated the synergistic effect of IGF1 on the LPS-induced IL6 and TNF alpha production. In whole blood of acromegaly patients, ex vivo IL6 production was increased (P < 0.01). In conclusion, IGF1, but not GH, has pro-inflammatory effects, probably via the MAPK signalling pathway and might be involved in the pathogenesis of atherosclerosis in acromegaly. The increased IL10 production possibly counteracts the pro-inflammatory effects.

/pdf/igf1-potentiates-the-pro-inflammatory-response-in-human-33fa002vo0.pdf

IGF1 potentiates the pro-inflammatory response in human peripheral blood mononuclear cells via MAPK.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is common in active acromegaly and negatively influences quality of life, morbidity, and mortality. This prospective study with 3 predetermined timepoints and a standardized treatment protocol investigates changes in sleep parameters during the first 2.5 years of acromegaly treatment. METHODS: Before initiation of acromegaly treatment (medical pretreatment followed by surgery), polysomnography (PSG) was performed in 27 consecutive patients with treatment-naive acromegaly. PSG was repeated after 1 year (N = 24) and 2.5 years (N = 23), and anthropometric and biochemical parameters were obtained. RESULTS: At baseline, 74.1% of the patients was diagnosed with OSAS. The respiratory disturbance index (RDI; P = 0.001), oxygen desaturation index (ODI; P = 0.001), lowest oxygen saturation (LSaO2; P = 0.007) and the Epworth Sleepiness Scale (ESS; P < 0.001) improved significantly during treatment, with the greatest improvement in the first year. After 2.5 years of treatment, all patients had controlled acromegaly. Of the 16 patients with repeated PSG and OSAS at baseline, 11 (68.8%) were cured of OSAS. Changes in RDI, ODI, LSaO2, and ESS correlated with insulin-like growth factor 1 levels. CONCLUSION: OSAS has a high prevalence in active acromegaly. There is a substantial decrease in prevalence and severity of OSAS following acromegaly treatment, with the largest improvement during the first year. Most patients recover from OSAS following surgical or biochemical control of the acromegaly. Therefore, a PSG is advised after diagnosis of acromegaly. When OSAS is present, it should be treated and PSG should be repeated during acromegaly treatment.

The Course of Obstructive Sleep Apnea Syndrome in Patients With Acromegaly During Treatment

In acromegalic patients the serum levels of interleukin-33 and Resolvin D1 influence skin perfusion of hands: A pilot study.

Acromegaly is a chronic systemic disease characterized by autonomous and excessive secretion of growth hormone (GH). Acromegaly is most commonly caused by ais a somatotroph adenoma of the anterior pituitary. In acromegaly, mortality primarily results from are cerebrovascular, cardiovascular, respiratory diseases and malignancies. Monocyte/lymphocyte ratio (MLR), neutrophil/lymphocyte ratio (NLR), red cell distribution width (RDW), platelet distribution width (PDW) and delta neutrophil index (DNI) are popular inflammatory markers. This study's purpose was to assess pre/post-treatment levels of NLR, GH, RDW, MLR, PDW and DNI in acromegalic patients and to investigate the impact of acromegaly treatment on these markers.

Akromegali Hastalarında Hematolojik İndekslerin Değerlendirilmesi

Background: Acromegaly is not one disease but an association of clinical, biochemical and radiological features. Altered blood counts are often observed in acromegaly patients. Acromegaly patients presenting with a hematological malignancy are rare. To date, there are several cases that have reported the co-occurrence of these diseases. Summary: The coexistence of the two diseases can be a mere coincidence or may have a common pathogenic mechanism. The rarity of these conditions and the small number of patients makes it difficult to determine the real role of elevated growth hormone and insulin-like growth factor-1 levels in the occurrence of hematological malignancies. Patients with growth hormone (GH) replacement due to GH-deficient acromegaly are at a high risk of developing hematological disorders. Conclusion: In this review, we aim to provide evidence for the correlation between the two disorders.

/pdf/co-occurrence-of-acromegaly-and-hematological-disorders-a-3qmnh3x3bj.pdf

Co-Occurrence of Acromegaly and Hematological Disorders: A Myth or Common Pathogenic Mechanism

Introduction:Cardiovascular, respiratory, and cerebrovascular diseases and malignancies are responsible for morbidity and mortality in acromegaly. Also these diseases are associated with chronic inflammation. The neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are currently gaining interest as new markers of inflammation. Moreover, increased morbidity and mortality are positively correlated with the presence of diabetes and levels of insulin-like growth factor 1 (IGF-1) in acromegaly. The objective of the present study was to investigate the relationship between these markers and acromegaly according to plasma glucose status and serum IGF-1 levels.Materials and Methods:We retrospectively analyzed data from 61 acromegaly patients who were in a newly diagnosed period (35 male, 26 female; mean age 38.13 ± 13.98). Patients with normal plasma glucose (n = 27), impaired fasting glucose (n = 18), and diabetes mellitus (n = 16) were categorized into three different groups. NLR and PLR ...

Evaluation of blood neutrophil to lymphocyte and platelet to lymphocyte ratios according to plasma glucose status and serum insulin-like growth factor 1 levels in patients with acromegaly.

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Evaluation of blood neutrophil to lymphocyte and platelet to lymphocyte ratios according to plasma glucose status and serum insulin-like growth factor 1 levels in patients with acromegaly.