Outcome of complications in acromegaly patients after long-term disease remission

Abstract

Acromegaly patients suffer from pathologically high growth hormone (GH) and IGF-1 levels that in 99% of cases is due to a GH-producing pituitary adenoma. During active disease, GH excess is associated with a number of pathological conditions, such as hypertension, hypertrophic cardiomyopathy, sleep apnea, arthropathy, vertebral fractures and insulin resistance. After adequate treatment in the form of transsphenoidal surgery, radiotherapy, medical treatment or by a combination of these treatment modalities, several comorbid conditions improve considerably. However, despite long-term biochemical disease control, the prevalence of late manifestations of GH excess is high and significantly impair quality of life. In addition, there is evidence that adequate treatment is not able to normalize mortality risk in these patients. In this review, we critically evaluate the long-term consequences of acromegaly after treatment, focusing on comorbid conditions, quality of life and mortality. We also discuss ongoing challenges in the management of acromegaly patients.

Keywords:

• acromegaly
• arthropathy
• heart disease
• mortality
• quality of life
• remission
• vertebral fractures

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Despite long-term control of growth hormone (GH)/IGF-1 excess, acromegaly patients suffer from a large number of invalidating complications, both physically and psychologically. Several complications are not extensively studied in a long-term controlled setting.

• Results on the effects of adequate disease control on hypertension, sleep apnea and body composition are inconsistent.

• GH control (both achieved by surgery and medical treatment) has positive effects on systolic and diastolic heart function and left ventricle function. In addition, there is limited evidence for stabilization, but not improvement, of cardiac valve function after adequate control of GH excess.

• Adequate disease control, especially by treatment with pegvisomant, is able to normalize GH-induced alterations in glucose homeostasis and insulin sensitivity.

• Despite long-term GH control, patients suffer from a high prevalence of vertebral fractures in the presence of normal bone mineral density, indicating GH-induced alterations in bone quality explaining vertebral fragility.

• Prevalence of arthropathy is high in well-controlled acromegaly, with clinical and radiographic osteoarthritis progression in a large subset of patients. Progression seems to be highest in medically treated patients.

• There is limited evidence for increased prevalence of colonic polyps, diverticulae and dolichocolon in the controlled phase.

• Prevalence of psychological symptoms and ineffective coping strategies is high in controlled patients, significantly impairing quality of life.

• Adequate acromegaly treatment is able to significantly improve mortality risk.