Introduction
Since 2000, several consensus documents have been published on various aspects of acromegaly management [
1‐
7]. In 2003 a consensus on the diagnosis and treatment of acromegaly complications was published [
3], and in March 2011, the Acromegaly Consensus Group that had produced these documents met to revise and update guidelines on acromegaly complications. The meeting was sponsored by the Pituitary Society and the European Neuroendocrinology Association and included experts skilled in acromegaly management.
Patients with acromegaly have a considerable burden of complications and co-existing illnesses, and factors contributing to increased mortality in acromegaly include higher prevalence of hypertension, hyperglycemia or diabetes, cardiomyopathy and sleep apnea [
8]. The diagnosis and management of complications of disease are therefore critical for assuring a favorable long-term outcome for this chronic illness. Current comorbidity issues were discussed by the group and recommendations made for updating the 2003 guidelines.
Recommendations were graded, based on the GRADE system [
9,
10], depending on the quality of evidence as very low quality (VLQ; expert opinion with one or a small number of small uncontrolled studies in support), low quality (LQ; large series of small uncontrolled studies), moderate quality (MQ; one or a small number of large uncontrolled studies or meta-analyses), or high quality (HQ; controlled studies or large series of large uncontrolled studies with sufficiently long follow-up). Recommendations were classed as discretionary recommendations (DR) if based on VLQ or LQ evidence, and as strong recommendations (SR) if based on MQ and HQ evidence.
Cardiovascular complications
Hypertension is highly prevalent, occurring in more than 40 % of patients with acromegaly, and early diagnosis and early aggressive treatment of elevated blood pressure is important irrespective of which acromegaly treatment is employed (HQ) [
11‐
17]. Hypertension in patients with acromegaly is usually mild and readily treated with anti-hypertensive drugs (VLQ) [
3]. The choice of treatment for hypertension should be similar to that in non-acromegaly patients (DR). The effect of different medical treatments for acromegaly on hypertension is as yet unclear (LQ) [
15,
18‐
21]. Sleep apnea, which is present in most patients with acromegaly, exacerbates hypertension (LQ) [
22].
Cardiomyopathy is present in most patients with acromegaly, and baseline echocardiogram is indicated. Arrhythmia is rarely a significant clinical challenge in acromegaly (MQ) [
16,
23]. Treatment of acromegaly improves early and intermediate stage myocardial hypertrophy and cardiac dysfunction (HQ) [
24‐
26]. Improvement depends on age, presence of hypertension and duration of the disease (LQ). Recent data (published after the consensus meeting) show that cabergoline does not aggravate prevalence or incidence of valve regurgitation and remodeling [
27], which are increased in acromegaly (MQ) [
28,
29]. Furthermore, somatostatin receptor ligands (SRLs) may cause asymptomatic bradycardia (LQ) [
30]. Rigorous clinical outcome measures (and not only biochemical goals) should be addressed in research studies.
The following routine baseline assessments are therefore required for patients with acromegaly: electrocardiogram (ECG), echocardiogram, blood pressure measurement, and the Epworth scale or sleep study for sleep apnea (SR) (Table
1). These patients also require assessment of the peripheral arterial system. Particularly in gigantism, there is a need for assessment of vascular disease including peripheral venous disease (DR).
Table 1
Assessment of acromegaly complications at diagnosis and during long-term monitoring
Blood pressure measurement | Every 6 months or when change of treatment (if hypertensive) |
Echocardiography | Annually |
ECG | Annually |
Epworth scale or sleep study | Annually |
Echo Doppler of peripheral arterial and venous system | Annually particularly in gigantism |
OGTT | Fasting blood glucose every 6 months (particularly in uncontrolled disease and during SRL therapy); HbA1c every 6 months if diabetes present |
Total testosterone, SHBG and prolactin (males) | Annually (free testosterone when doubts in interpretation of total testosterone) |
LH, FSH, 17β-estradiol and prolactin (females) | Annually (or when pregnancy is desired) |
AcroQoL | Annually |
DEXA | Every 2 years if patient with osteopenia/osteoporosis |
Thoracic and lumbar spine X-ray | Every 2–3 years if osteoporosis risk factors, kyphosis or symptoms |
Colonoscopy | Every 10 years (more frequently if IGF-I remains persistently elevated or if abnormal colonoscopy or family history of colonic cancer) |
Genetic screening for markers of familial acromegaly (if suspicion) | |
Conclusions
Effective management of acromegaly complications will lead to decreased morbidity and mortality, and improved QoL. Comprehensive multimodal acromegaly management should integrate biochemical monitoring, careful assessment of tumor behavior and clinical features, and comorbidities.
Acknowledgments
The authors thank all participants in the Eighth Acromegaly Consensus Group meeting: Ariel Barkan (USA), Albert Beckers (Belgium), Paolo Beck-Peccoz (Italy), John Bevan (UK), Nienke Biermasz (The Netherlands), Jens Bollerslev (Norway), Vivien Bonert (USA), Francoise Borson-Chazot (France), John Carmichael (USA), Philippe Caron (France), Jens Christiansen (Denmark), David Clemmons (USA), Renato Cozzi (Italy), Maria Vittoria Davi (Italy), Diego Ferone (Italy), Maria Fleseriu (USA), Monica Gadelha (Brazil), Yona Greenman (Israel), Ashley Grossman (UK), Ken Ho (Australia), David Kleinberg (USA), Marta Korbonits (UK), Monica Marazuela Azpiroz (Spain), Gherardo Mazziotti (Italy), Moises Mercado (Mexico), Mark Molitch (USA), Lisa Nachtigall (USA), Stephan Petersenn (Germany), Vera Popovic-Brkic (Serbia), Roberto Salvatori (USA), Janet Schlechte (USA), Michael Sheppard (UK), Gunther Stalla (Germany), Peter Trainer (UK), Mary Lee Vance (USA), Aart Van der Lely (The Netherlands), and Susan Webb (Spain). This study was sponsored by the Pituitary Society and the European Neuroendocrine Association and was supported by an unrestricted grant from Ipsen. We acknowledge the editorial assistance provided by Martin Gilmour of ESP Bioscience (Crowthorne, UK), supported by Ipsen, during the preparation of this manuscript.