Anorexia nervosa, which belongs to the group of the most severe pathologies, is always accompanied by loss of kilograms up to the exhaustion, which is expressed in the functional imbalance of various organs and systems. In children, anorexia of neurogenic nature occurs in 4% of all cases of nervous disorders and occurs most often in adolescence. You will learn about the mechanism of development of the pathology, its main forms from the article.
- The most common types of the disease.
- Bone mineralization.
The most common types of the disease
When anorexia nervosa develops, there is a disruption in the secretion of hormones that control virtually the entire life cycle of the human body. This is a compensatory-adaptive reaction against the background of a significant loss of kilograms. The essence of the process is the replenishment of energy resources, which are necessary to maintain the vital functions of the internal organs. The mechanism and causes of hormonal failures are presented below.
Children and adults with anorexia nervosa have an acquired resistance to somatotropic hormone. This is manifested by low levels of IGF-1, an insulin-like growth factor, with normal or high concentrations of somatotropic hormone in the blood. Some girls, especially those in adolescence, cannot cope with this situation due to increased basal secretion of growth hormone as a result of the increased frequency and amplitude of somatotropic hormone synthesis by the pituitary gland. In this case, the pituitary-affiliated leptin aggravates the problem, since its minimization in combination with increased secretion of growth factor and ghrelin further increases the hormonal load on the pituitary.
The decrease in IGF-1 despite high levels of growth hormone in patients with anorexia nervosa is explained by the minimization of hepatic synthesis. At the same time, growth hormone synthesis by the feedback principle contributes to this. This is not observed in boys, possibly because girls have already partially realized their growth potential at puberty.
In most cases of anorexia nervosa, various hypothalamic-pituitary abnormalities are noted. They are most often associated with abnormal feedback regulation. Of particular importance is increased cortisol associated with markers of bone resorption and decreased muscle mass. Excessive glucocorticoids activate gluconeogenesis and are correlated with fasting glycemia levels.
This suggests the functional nature of hypercorticism as an adaptation mechanism that aims to increase blood glucose levels. Increased ghrelin also increases serum cortisol levels, due to active ACTH secretion. Weight gain in anorexia nervosa automatically causes a minimization of pulse ACTH secretion, but high serum cortisol concentrations persist for a long time. Leptin in this case is able to act as an antagonist of ghrelin, and only.
Adipokines and appetite
In anorexia nervosa, the levels of hormones that synthesize adipose tissue change markedly: leptin and adiponectin. In addition, the bioactive components that control eating behavior correlate with each other: ghrelin and YY peptides. Ghrelin is responsible for the orexigenic effect and peptide for the anorexigenic effect. Adolescents with anorexia nervosa also have low leptin concentrations due to the minimal amount of adipose tissue and aim to reduce anorexigenic stimuli.
Leptin is necessary for normal functioning of the hypothalamic-pituitary-gonadal system. Its minimization blocks the secretion of gonadotropins by the pituitary gland. The circulating hormone in the bloodstream activates cortical bone anabolism, while central leptin affects bone indirectly, through the sympathetic nervous system. In healthy individuals, a minimum of leptin is associated with a minimum of bone formation markers. Research on adiponectin in this direction is inconsistent.
An increase in ghrelin is typical in adolescents with anorexia nervosa; it activates growth hormone and ACTH secretion, reducing gonadotropin synthesis. Increased ghrelin is an adaptive reaction aimed at stimulating appetite, increasing the concentration of cortisol and growth hormone. The purpose of this reaction is to mobilize glucose as an energy potential in case of alimentary deficiency. High levels of peptide YY are affiliated with minimal markers of bone formation in adolescents.
Hypogonadotropic hypogonadism is the main trigger of menstrual irregularities and amenorrhea in adolescent girls with anorexia nervosa. Sex hormones in the serum of such patients are also reduced. Hypoleptemia and low IGF-1 levels further minimize spontaneous pulsatile LH secretion. Excess ghrelin and cortisol also suppress pituitary gonadotropin secretion.
In other words, there is simply no chance of normal periods in asthenic adolescents or those who weigh less than 50 pounds. When weight is gained, normalization of the menstrual cycle is quickly noted in adults, while in adolescents the correction takes six months or a year. Resumption of menstruation may occur as soon as you gain +2 kg over the weight when amenorrhea began.
Estrogens have an antiresorptive effect, minimizing osteoclast activity. Testosterone also contributes to bone formation. Its low level has an adverse effect on bone density, and its increase is associated with weight gain. Estrogen replacement therapy in physiological doses has a positive effect on behavior, relieves anxiety, and improves body composition.
Most patients with anorexia nervosa are characterized by low levels of thyrotropins: TTH, T4 and T3 in the free state. Moderate decrease in thyroid function is considered to be an adaptation in conditions of energy deficiency of alimentary nature and is accompanied by minimization of intensity of basic metabolism without load, with a minimum of physical effort.
In women with a neurogenic appetite disorder a decrease of brown fat is noted, which gives the possibility to minimize the energy potential of daily expenses due to blocking of active thermogenesis outside the contractility of muscles.
One of the most negative complications of anorexia nervosa is minimization of minerals in bone tissue. In adolescent girls with neurogenic loss of appetite, this problem is registered in the tubular bones of the skeleton. In boys, the femoral head is more often involved in pathological changes. In cases of anorexia nervosa, not only a decrease in bone mineralization is recorded, but also a change in their architectonics. The frequency of fractures in adolescents with this disease exceeds similar problems of their peers with normal weight. Young women have a 60% increased risk of developing fractures. This trend also applies to patients with a history of anorexia nervosa.
Noteworthy contributing factors are:
- decreased BMI;
- minimization of sex hormones and leptin;
- functional increase in the release of adrenal cortex hormones into the bloodstream.
Weight gain corrects bone density scores.
Low estrogen levels are a major trigger for the development of osteoporosis in anorexia nervosa in women. Estrogen monotherapy improves the situation in adolescent girls. Correction of osteoporosis with drugs includes resorptive therapy with bisphosphonates and Denosumab, a preparation of human monoclonal antibodies, and therapy with anabolics such as Teriparatide. There are no data on similar correction in anorexia nervosa.
Thus, the involvement of leptin in the control of weight and energy metabolism in anorexia nervosa in adolescents can be considered absolutely reasonable. Its correction can partially normalize the situation, but much depends on the eating behavior and habits of patients.