The effects of long-term growth hormone and insulin-like growth factor-1 exposure on the development of cardiovascular, cerebrovascular and metabolic co-morbidities in treated patients with acromegaly

Jayasena, Channa N.; Comninos, Alexander; Clarke, Holly; Donaldson, Mandy; Meeran, Karim; Dhillo, Waljit S.

doi:10.1111/j.1365-2265.2011.04019.x

Cited by 51 publications

(33 citation statements)

References 36 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The most striking functional disturbance in acromegalic cardiomyopathy is the inadequate ventricular filling capacity, as demonstrated by the decrease of E/A and the prolongation of the IVRT, configuring diastolic dysfunction [4,51]. Long disease duration has been associated with higher prevalence of hypertension and diabetes [4,62] as well as cardiac complications, including diastolic and systolic dysfunction, valvulopathy, and arrhythmias [63,64].…”

Section: Discussionmentioning

confidence: 99%

Effects of long-term combined treatment with somatostatin analogues and pegvisomant on cardiac structure and performance in acromegaly

et al. 2016

View full text Add to dashboard Cite

To date, no data are available on the effects of long-term combined treatment with somatostatin analogues (SA) and pegvisomant (PEG) on cardiovascular complications in acromegaly. The current study aimed at investigating the effects of long-term SA + PEG on cardiac structure and performance. Thirty-six patients (14 M, 22 F, aged 52.3 ± 10.2 years) entered this study. Weight, BMI, systolic (SBP) and diastolic (DBP) blood pressure, IGF-I, fasting glucose (FG), fasting insulin (FI), HOMA-IR, HbA, and lipids were evaluated at baseline (T0), after long-term (median 36 months) SA (T1), after 12 (T12) and 60 (T60) months of SA + PEG, and at last follow-up (LFU, median 78 months). At each time point, all patients underwent echocardiography. At T1, induced a slight but not significant decrease in IGF-I (p = 0.077), whereas FI (p = 0.004), HOMA-IR (p = 0.013), ejection fraction (EF, p = 0.013), early (E) to late (A) ventricular filling velocities (E/A, p = 0.001), and isovolumetric relaxation time (IVRT, p = 0.000) significantly improved. At T12, IGF-I (p = 0.000) significantly reduced compared to T0, and FI (p = 0.001), HOMA-IR (p = 0.000), LVMI (p = 0.000), and E/A (p = 0.006) further improved compared to T1. At T60, FI (p = 0.027), HOMA-IR (p = 0.049), and E/A (p = 0.005) significantly improved as compared to T1. At LFU IGF-I normalized in 83.3 %, FI (p = 0.000), HOMA-IR (p = 0.000), LVMi (p = 0.000), and E/A (p = 0.005) further improved as compared to T1. PEG dose significantly correlated with LVMi at T12 (r = 0.575, p = 0.000) and T60 (r = 0.403, p = 0.037). Long-term PEG addition to SA improves cardiac structure and performance, particularly diastolic dysfunction, in acromegalic patients resistant to SA.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of long-term combined treatment with somatostatin analogues and pegvisomant on cardiac structure and performance in acromegaly

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In patients with acromegaly alterations in glucose tolerance, such as impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and overt type 2 diabetes mellitus (DM), are more frequent than in the general population. The prevalence of DM or other carbohydrate metabolism disturbances in acromegaly ranges from 19 to 56% [3] and the presence of these comorbidities correlates with cardiovascular morbidity and mortality in acromegaly [4][5][6]. The therapeutic options for acromegaly include surgery, radiotherapy and medical therapies, such as dopamine agonists, somatotropin release-inhibiting factor receptor ligand (SRIF-RL) and the GH receptor antagonist pegvisomant [7].…”

Section: Introductionmentioning

confidence: 99%

Clinical and metabolic effects of first-line treatment with somatostatin analogues or surgery in acromegaly: a retrospective and comparative study

et al. 2011

View full text Add to dashboard Cite

To evaluate the metabolic effects of first-line somatostatin analogues or surgery in acromegaly. Retrospective, comparative, 12-month follow-up. Two hundred and thirty one patients (123 men, age 47.32 ± 14.63 years) with active acromegaly, first line treatments were somatostatin analogues in 151 (65.4%) and surgery in 80 (34.6%). Metabolic syndrome (MS) parameters, glucose, insulin and GH during oral glucose tolerance test, stimulated insulin sensitivity by insulin sensitivity index (ISI Matsuda), early and total insulin-secretion rate by insulinogenic index and AUC INS , visceral adiposity function, expressed by visceral adipose index (VAI). Somatostatin analogues treatment improved all MS parameters and significantly reduced fasting glucose (P \ 0.001), HbA1c (P = 0.014) and the prevalence of DM (P = 0.003) when disease control was achieved. Both somatostatin analogues and surgery improved ISI Matsuda (P \ 0.001) and reduced AUC INS (P \ 0.001) and VAI (P \ 0.001 and P = 0.003, respectively). Only in controlled somatostatin analogues-treated patients a significant reduction in insulinogenic index (P = 0.010) was observed. ISI Matsuda showed a significant independent correlation with IGF-1 levels (b = -0.258; P = 0.001) and VAI score (b = -0.430; P \ 0.001). VAI was independently correlated with IGF-1 (b = 0.183; P = 0.004). Both somatostatin analogues and surgery can safely be used as first-line therapy in acromegaly, without any untoward effects on glucose tolerance. The control of acromegaly is the main determinant of beneficial effects on general features of insulin sensitivity. VAI could represent an additional link between disease control and insulin sensitivity.

show abstract

“…Poorly controlled acromegaly is associated with a twoto threefold increase in mortality and significant morbidity (20,21). With adequate control (posttherapy GH !2.5 mg/l, 'safe' levels), mortality is comparable to that of the general population (22).…”

Section: Gh-secreting Adenomas Exist As Distinct Morphological Subtypesmentioning

confidence: 99%

Granulation pattern, but not GSP or GHR mutation, is associated with clinical characteristics in somatostatin-naïve patients with somatotroph adenomas

Larkin

Reddy

Karavitaki

et al. 2013

European Journal of Endocrinology

116

View full text Add to dashboard Cite

Objective: Somatotroph adenomas causing acromegaly are histologically classified into densely granulated (DG) and sparsely granulated (SG) subtypes with different morphology, clinical characteristics and treatment outcomes. Granulation pattern has been reported to co-segregate with a recurrent mutation at codon 49 in growth hormone receptor (GHR) and GSP oncogene. This study examines response to the octreotide suppression test (OST) in relation to granulation pattern and mutation in GHR and GSP. Design: This is a retrospective, single-centre study of 52 patients with pathologically confirmed somatotroph adenoma who were naïve to medical therapy presenting between January 2001 and October 2010. Methods: Clinical, radiological and hormonal data at diagnosis were recorded. GHR and GSP were genotyped, granulation pattern determined and response to the OST measured. Results: SG adenomas were larger (PZ0.038), occurred in younger patients (PZ0.029), were more common in females (PZ0.026) and were more invasive (P!0.0001 and PZ0.001), with diminished responses to the OST (PZ0.007) compared with DG adenomas. GSP mutation was unrelated to granulation pattern but associated with smaller tumours (PZ0.027), producing more GH (PZ0.048) that responded better to the OST (PZ0.022). Codon 49 of GHR was not mutated. Conclusions: Adenoma histological phenotype, not genotype, corresponds to clinical and biochemical characteristics and response to the OST. SG adenomas constitute a clinically more unfavourable subtype but are not associated with GHR mutations in our series. Ascertainment of the adenoma subtype may become an important consideration in the management of acromegaly.

show abstract

The effects of long-term growth hormone and insulin-like growth factor-1 exposure on the development of cardiovascular, cerebrovascular and metabolic co-morbidities in treated patients with acromegaly

Cited by 51 publications

References 36 publications

Effects of long-term combined treatment with somatostatin analogues and pegvisomant on cardiac structure and performance in acromegaly

Effects of long-term combined treatment with somatostatin analogues and pegvisomant on cardiac structure and performance in acromegaly

Clinical and metabolic effects of first-line treatment with somatostatin analogues or surgery in acromegaly: a retrospective and comparative study

Granulation pattern, but not GSP or GHR mutation, is associated with clinical characteristics in somatostatin-naïve patients with somatotroph adenomas

Contact Info

Product

Resources

About