How do muscles change?

Note: Muscle weakness affects the quality of life in people with acromegaly.  Doctora Elena Valassi takes a fascinating look at what happens to muscles when exposed to excess Growth Hormone.  Her work is of paramount importance for those people suffering from acromegaly wishing to maintain a healthy lifestyle with exercise and proper nutrition.  Stay tuned for a podcast interview with Dr. Valassi coming up soon in which we will expand on the subject.  Our heartfelt thanks to Dr. Valassi and Dr. Luciana Martel-Duguech for contributing this article.

From Dr. Elena Valassi, M.D., Ph.D. – Hospital de la Santa Creu i Sant Pau, Barcelona, Spain  –  Patients with acromegaly commonly complain of muscle weakness and musculoskeletal pain which may persist long-term after disease control is achieved, severely affecting physical function, psychological state, and, ultimately, quality of life.
Because growth hormone (GH) and insulin-like growth factor type 1 (IGF-I) have anabolic effects on muscle, stimulating protein formation and inhibiting protein breakdown, one may speculate that muscle mass and strength are normal or even increased in patients exposed to GH excess due to acromegaly.
Elena Valassi, M.D., Ph.D.

However, while treatment with physiological doses of GH increases muscle mass and normalizes both muscle strength and function in patients with muscle loss associated with GH deficiency (GHD), the effect on muscle of excessive levels of this hormone, such as those observed in acromegaly, has not been clearly established.

It is important to emphasize that hormone levels should be rigorously maintained within a “physiological window” in our body, in that either an excessive hormone production or a deficient availability may impair our health.

As a matter of fact, an increase in the size of type 1 fibers (the “slow-twitch” ones, which are resistant to fatigue and are needed for low-intensity, long-duration activities) and decrease in size of type 2 fibers (the “fast-twitch” ones, which contract quickly and powerfully, and are needed for high-intensity, short-duration activities)  have been documented in the muscle of patients with GH excess due to acromegaly who underwent muscle biopsies, while muscle mass did not appear to significantly change.  Interestingly, a study of body composition using dual-energy x-ray absorptiometry (DXA) demonstrated that fat-free mass, which consists of body water and muscle mass, was significantly greater in patients with active acromegaly as compared with healthy subjects. However, this increase was mainly due to water retention in soft tissues, rather than to an increase in the number of muscle cells. Likewise, a study using magnetic resonance imaging (MRI) demonstrated that the muscle mass of patients with active acromegaly was similar to that of healthy controls. Of note, muscle mass decreased two years after control of GH excess in male patients, as compared with that found at diagnosis in the same individuals, suggesting that loss of muscle tissue associated with chronic exposure to GH may occur regardless of the biochemical control of the disease.

It is noteworthy that proximal muscle strength, measured by electromyography, was also found to be lower in patients with controlled acromegaly as compared with both healthy subjects and patients with active acromegaly.

Luciana María Martel Duguech M.D., Ph.D. student.

All these findings suggest that muscles in patients with acromegaly may be larger but functionally weaker than those in healthy subjects. Moreover, it appears that both losses of muscle mass and muscle weakness worsen over time in patients previously exposed to high levels of GH, despite remission of hormone excess.

It should be noted that muscle impairment contributes to the development of arthropathy, one of the most frequent and disabling complications of acromegaly, leading to irreversible degeneration of osteoarticular structures. Musculoskeletal disorders are associated with deterioration of the patient’s quality of life, which may persist for more than 10 years since disease control is reached.

While the mechanisms underlying this progressive deterioration of muscle functionality are still to be determined, efforts should be made to prevent and, possibly, revert it through the adoption of a healthy lifestyle.

The beneficial effects of exercise on physical and mental health are well known. A sedentary lifestyle has been associated with poor muscle performance and significant alterations of muscle composition and quality (i.e. excessive accumulation of fat within the muscle) in elderly people. A structured physical training program positively changed muscle composition in them, which was associated with significant amelioration of physical performance and, if continued, even prevented the age-related decline of muscle function.

A 12-week therapist-oriented home rehabilitation program improved general fatigue, muscle strength, performance on function testing, and quality of life in seventeen patients with acromegaly. Patients underwent a structured three sessions a week’s exercise program consisting of  1-hour combined warm-up, muscle strengthening, and resistance exercises, followed by balance aerobic training, and stretching.

Thus, physical activity should be considered as an important intervention integrating and supporting other therapies, such as surgery and drugs, aimed at treating the negative effects of GH excess on patient’s health.  Exercise trainers should be part of the multidisciplinary health care team accompanying patients during all the phases of their disease.

Before starting the exercise program, the trainer should have an extensive interview with the patient in order to assess her/his motivation, objectives, fears, and personal attitude towards physical activity. Moreover, the trainer should collect rigorous information on patient’s habits, lifestyle, and medical history with particular regard to the presence of concomitant conditions (e.g. type 2 diabetes, hypertension, osteoporosis, arthropathy), in order to prepare a program specifically tailored to patient’s needs. It is highly recommendable that the trainer and the physician engaged in patient care talk to each other to develop a common strategy for each patient so that the personalized exercise program is effective and safe. Indeed, the physical activity program should be carefully designed in order to avoid pain, control fatigue, and reinforce motivation through fun and self-esteem enhancement.

In conclusion, to normalize decreased functional capacity and musculoskeletal impairment in patients with acromegaly is paramount. To develop a customized exercise program, within an integrated multidisciplinary team approach, may be one of the milestones leading to fulfilling and long-lasting lifestyle changes.

 

About Dr. Valassi – Graduated “Summa Cum Laude) at the University of Pavia (Italy) and completed her specialty in Endocrinology at the University of Modena (Italy) and her Ph.D. in Endocrinology at the University of Milan.  She was a research fellow in the Neuroendocrine Unit of Massachusetts General Hospital, Harvard Medical School, and is currently a postdoctoral pituitary disease investigator at CIBERER, Sant Pau Hospital, Barcelona, Spain, and consultant endocrinologist at the Hospital General de Catalunya.

About Dr. Martel-Duguech – Graduated at the National University of Tucumán (Argentina) and completed her specialty in Endocrinology at the University of Buenos Aires. She is currently a Ph.D. student in Endocrinology at the Autonomous University of Barcelona, Sant Pau Hospital, Barcelona Spain. Her research is focused on residual morbidity as a consequence of persistent musculoskeletal impairment and its underlying mechanisms in patients with Cushing’s syndrome and acromegaly.

 

Bibliography:

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