الفهرس 
Chronic obstructive pulmonary disease
COPD and somatotropic axisOnly 14 pages are availabe for public view
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Abstract
Chronic obstructive pulmonary disease (COPD) is no longer considered to affect only the lungs and airways but also the rest of the body. The systemic manifestations of COPD include a number of endocrine disorders, such as those involving the pituitary, the thyroid, the gonads, the adrenals, the pancreas and the renin–angiotensin–aldosterone system. The mechanisms by which COPD alters endocrine function are incompletely understood but likely involve hypoxaemia, hypercapnia, systemic inflammation and glucocorticoid administration that may be used in its treatment. Altered endocrine function can worsen the clinical manifestations of COPD through several mechanisms, including decreased protein anabolism, increased protein catabolism, nonenzymatic glycosylation and activation of the rennin–angiotensin–aldosterone system. Systemic effects of endocrine disorders include abnormalities in control of breathing, decreases in respiratory and limb-muscle mass and function, worsening of respiratory mechanics, impairment of cardiac function and disorders of fluid balance. Downregulation of the GH/IGF-I system is usually due to; advanced age, malnutrition, inactivity and administration of glucocorticoids, energy imbalance, hormonal insufficiency (GH, IGF-I and testosterone), systemic inflammation and oxidative stress. Systemic inflammation is involved in the genesis of cachexia in COPD. The molecules receiving the greatest amount of attention are TNF-α, IL-1β, IL-6, C-reactive protein, ROS, RNS and low leptin levels. In contrast, hypoxaemia and hypercapnia probably increase GH levels in patients with COPD. The high prevalence of decreased IGF-I in several investigations raises the possibility that a depression of the somatotropic axis may contribute to the decreased muscle mass in some patients with COPD. In patients with COPD, decreased muscle mass reduces respiratory muscle function, limb muscle function, exercise capacity and life expectancy. Depression of the somatotropic axis may contribute to decreased muscle mass in COPD and administration of recombinant human GH has produced mixed positive and negative results, so it is difficult to find a rationale for the use of GH in COPD at this time. Many different approaches to treating cachexia had been attempted, such as, active nutritional support and appetite stimulation, exercise training, correcting arterial hypoxaemia with supplemental anti-inflammatory drugs, anabolic hormones and noninvasive positive pressure ventilation. The prevalence of hypogonadism was equivalent in men with COPD to that in healthy subjects. Several risk factors that may decrease testosterone in patients with COPD had been reported. These include aging, hypoxaemia, hypercapnia, chronic disease, smoking, administration of glucocorticoids, systemic inflammation and obesity. COPD and late-onset hypogonadism can lead to many functional consequences as; decrease quality of life, depression, sexual difficulties, quadriceps muscle weakness and excess cardiovascular risk in men. Administration of a relatively low dose of testosterone to males and females with COPD; increases the lean body mass, body weight and respiratory muscle strength were observed. Circulating levels of DHEAS are decreased in COPD. This may be due to: aging, severe airway obstruction, hypoxaemia and hypercapnia. Lower DHEA levels are associated with decreased bone-mineral density. DHEA supports lung function in individuals with COPD, while in elderly patients without COPD, DHEA administration has no significant benefit. COPD was found to increase the risk of type 2 diabetes mellitus. The mechanisms through which COPD might induce type 2 diabetes include systemic inflammation, oxidative stress, smoking and administration of glucocorticoids, hypoxia, hypercapnia, insulin resistance, obesity and sleep disorders. In patients who do not necessarily have COPD, diabetes can negatively affect respiratory muscle function, pulmonary mechanics, gas exchange and respiratory drive. Patients with diabetes are also at increased risk of infections and cardiovascular complications. Diabetes therapy in COPD, should be the same as for diabetic patients without COPD except of inhaled insulin which can cause small but significant decreases in diffusing capacity and FEV1. In addition, absorption of inhaled insulin in COPD is unpredictable and, at least in ex-smokers, it may increase the rate of bronchogenic carcinoma. Impaired thyroid function can present as subclinical hypothyroidism, overt hypothyroidism and nonthyroidal illness syndrome. Of these, nonthyroidal illness syndrome is the most common in COPD. This may be due to severe airway obstruction, hypoxaemia, systemic inflammation and glucocorticoids. Hypothyroidism can decrease respiratory drive, respiratory muscle function, exercise capacity, and increase the risk for sleep disordered breathing in COPD. Hyperthyroidism may be more prevalent in COPD than in the general population and it may impair respiratory muscle function, respiratory mechanics and exercise capacity in COPD. Both hypothyroidism and hyperthyroidism in patients with COPD should be treated in the same manner as in patients without COPD. COPD often exhibits impaired excretion of sodium and water, which is aggravated when oedema is present. This may be due to upregulation of the renin–angiotensin–aldosterone system and vasopressin in COPD. Increased renin–angiotensin–aldosterone may contribute to sodium retention and increased vasopressin may contribute to hyponatraemia and water retention. Diuretics should be postponed in COPD as it can aggravate retention of sodium and water through several pathways including hypoventilation-induced hypochloraemic metabolic alkalosis. Angiotensin-converting enzyme inhibitors can increase sodium excretion.