The anorectic adolescent: definition, prevalence and risk factors

Most eating disorders can be classified into four different diagnostic categories:

• –
  

  anorexia nervosa (AN), characterised by a drive for thinness, weight loss and amenorrhoea

  
  
• –
  

  bulimia nervosa (BN), with weight phobia, binge eating and compensatory behaviour (self- induced vomiting and the misuse of laxatives or diuretics)

  
  
• –
  

  eating disorder not otherwise specified (EDNOS): sub-threshold cases of AN or BN or other abnormal feeding or weight control practices, which represent the most common forms of eating disorder.

  
  
• –
  

  binge-eating disorder (BED), without compensatory behaviour and extremely negative body image.

The essential features of anorexia nervosa, according to the latest revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR), of the American Psychiatric Association, are presented in Table 1 .

DSM-IV furthermore recognises two clinical subtypes of AN:

• 1.
  

  restricting type – during the current episode of AN, the person has not regularly engaged in binge-eating or purging behaviour and accomplishes weight loss primarily through fasting or excessive exercise;

  
  
• 2.
  

  binge-eating/purging type – during the current episode of AN, the person has regularly engaged in binge-eating or purging behaviour (self-induced vomiting or the misuse of laxatives, diuretics or enemas).

Amenorrhoea is considered a diagnostic criterion for the disease, although several studies have reported few differences, from a psychopathological point of view, between patients who satisfy all the criteria for AN and those who satisfy all but amenorrhoea. Amenorrhoea primarily reflects the effects of low weight and energy availability on the endocrine system, rather than representing a diagnostic tool.

The incidence of AN is about four to eight per 100 000 persons per year. The prevalence among women in late adolescence and early adulthood is estimated at between 0.5% and 1.0%. However, studies on the prevalence of eating disorders have generally been conducted in clinical settings and are consequently underestimated, since far from all cases are detected by the health-care system. The disease is prevalent in industrialised societies, in middle-to-upper class families and in the Caucasian race. Certain activities and professions focussed on body image, such as dance, fashion modelling and sports in which low-fat mass is considered to be advantageous (e.g., distance running), are associated with higher rates of AN.

The pathogenesis of eating disorders, and of AN in particular, appears to be multifactorial: both biological and psychosocial factors are certainly implicated, but the mechanisms underlying the emergence of the disease remain uncertain. Moreover, the factors that determine the onset of AN appear to be different from those responsible for its maintenance. While previously AN was viewed as a disorder primarily influenced by sociocultural factors, more recently family studies have consistently demonstrated that a genetic vulnerability to the disease does exist, assumed to be due to multigenic effects modulated by environmental influences. Patients often have a positive familiar history of AN or BN: first-degree female relatives and monozygotic twin offspring of patients with AN feature a higher incidence of eating disorders. It has been estimated that children of patients with AN have a lifetime risk for AN that is tenfold that of the general population (5%).Twin studies have underscored the contribution of specific genetic factors to familial aggregation. Current studies are analysing gene coding for heritable personality traits associated with the disease, including perfectionism, harm avoidance and early neuroticism; moreover, genetic association studies have focussed on polymorphisms in serotonin (5-HT)-related genes, since this neurotransmitter system is important in the regulation of eating and mood, identifying a susceptibility locus on chromosome 1 including the coding regions for both the serotonin 1D and delta 1 opioid receptors.

Clinical studies on risk factors for the development of AN have implicated both parenting characteristics, antecedent life events and personality traits ( Table 2 ).

It is well known that females are 10 times more likely than males to suffer from AN. Puberty itself may be a risk factor: psychological reactions to the maturing body, changing peer relationships and new life challenges could play a role in the development of AN. Furthermore, oestrogen and other reproductive hormones affect mood and feeding behaviour.

Family psychiatric problems and traumatic pre-morbid experiences are associated with many psychiatric disorders, while the quality of parenting proves to be more specific. Difficult life events as proximal triggers for the emergence of the disease are not specific either, while critical comments about weight, shape or eating constitute the only variable contributing to the onset of symptoms. Personality traits, such as an elevated degree of perfectionism and negative affectivity, are considered central to the pathogenesis of AN. Problems with feeding and eating are also present in infants and children, and an early onset of the disorders typical of adolescent age is also possible, but it is unclear whether eating disorders, and overweight in infancy in particular, should be considered. Cultural factors that propose a specific ideal of beauty may contribute to the onset of the disease: compared with this ideal, a subject with low self-esteem feels inadequate, develops an extreme fear of gaining weight and may begin severe dieting or excessive physical exercise. The physiological consequences of starvation, including delayed gastric emptying and prolonged gastrointestinal transit, exacerbate restrictive eating patterns since they result in early satiety and chronic constipation. Finally, starvation is associated with changes in the neurotransmitters of the central nervous system, promoting hyperactivity and depression.

Endocrine profile and medical complications in adolescents with AN

From an endocrine aspect, AN is characterised by several adaptive responses to the deficit of nutrients. Metabolic impairment and psychological distress interact at the hypothalamic level activating the chronic stress response: the hyperactivity of the corticotropin-releasing hormone (CRH)– adrenocorticotropic hormone (ACTH)–adrenal axis induces an increase in the daily production of cortisol and arginin–vasopressin and inhibits gonadotropin-releasing hormone (GnRH) pulsatile release and, consequently, pituitary luteinising hormone (LH) production and ovarian function. The LH release becomes similar to that of the prepubertal period, with the characteristic increase during the night and, in the advanced states of disease, practically undetectable. The follicle-stimulating hormone (FSH) levels are generally normal, except for cases of extreme weight loss, in which they too are reduced. Ovarian follicles are no longer stimulated and so oestradiol concentrations regress to prepubertal values. Other factors contributing to hypo-oestrogenism are the reduction in adipose tissue that determines an important decrease of extra-ovarian oestrogen production and the alterations in liver metabolism. At liver level, the production of inactive metabolites is increased and relatively higher levels of sex-hormone-binding globulin (SHBG) are present, so that it can be considered a reliable nutritional index. Higher levels of cortisol are secondary to increased production and to decreased hepatic clearance. Reduced adrenal androgen production, together with the impairment of ovarian production of androstenedione, contributes to low levels of circulating androgens. The increase in cathecolamines is probably responsible for the impairment in peripheral thyroid hormone metabolism, with generalised induction of type 3 deiodinase and a reduction of type 1 deiodinase contributing to the low T3 state associated with the sparing of energy-consuming processes. Induction of type 2 deiodinase in the hypothalamus may explain the lack of compensatory increase in thyroid-stimulating hormone. Sympathetic activation also promotes the recruitment of leucocytes and proinflammatory cytokines: these act in synergy with low T ₃ levels, reducing hepatic protein synthesis, in particular insulin growth factor-1(IGF-1). In anorectic subjects the release of GH is elevated, consequent on the low intake of carbohydrates; but the decrease in GH liver receptors and the reduction of serum Gh-binding protein (GhBP) induce a resistance to GH with IGF-I and IGF-binding protein (IGFBP)-3 levels significantly decreased. Thus, in subjects with amenorrhoea related to weight control, serum LH levels, free T ₃ and IGF-1 are low or in the lower reference range, while mean concentration of cortisol tends to exceed the standard range, especially when measured in the evening ( Table 3 ). Naturally, the levels of all the hormones related to energy availability are reduced. Leptin is a protein hormone secreted by adipocytes, and its circulating levels are correlated with the extension of the fat deposits: leptin secretion can centrally suppress appetite and acts as a connecting signal between energy stores and reproductive function, with a threshold effect on gonadotropin production. Leptin acts on appetite regulation by inhibition of hypothalamic neuropeptide Y (NPY) and stimulation of proopiomelanocortin (POMC). The stimulating effect on GnRH release, as in many animal models, is probably mediated by a group of peptides called kisspeptins, their production is regulated by the kisspeptin-1 (KISS-1) gene, whose expression is leptin dependent. Leptin stimulates KISS-1 gene expression in hypothalamic cells increasing kisspeptin secretion. The down-regulation of kisspeptin consequent on the decrease in leptin levels is thought to be responsible for amenorrhoea. Moreover, a direct effect of leptin on GnRH and on ovarian function has been demonstrated by administering recombinant-metHuLeptin at replacement doses to women with hypothalamic amenorrhoea related to strenuous exercise or low weight: this treatment rapidly improved LH pulse frequency and mean concentrations, as well as ovarian function. Insulin is a key hormone in regulating short-term energy homeostasis and long-term responses to energy-deprivation states, and undoubtedly plays a role in the link between metabolic state and reproductive function. Basal activity of pancreatic beta cells is reduced, with consequent lowering of insulin levels, as documented by low levels of C-peptide dosage (sensitive marker of pancreatic secretion). Alongside the reduction of insulinaemia, as an effect of the caloric and protein deficit, a reduction of peripheral sensitivity to the hormone is also detected, with lower uptake of glucose from the cells, especially in muscle and adipose tissue.

Current researches are studying the role of gastrointestinal peptides in situations of weight control. High levels of ghrelin, a peptide of 28 amino acids synthesised predominantly by the stomach and the gut, which not only activates the type 1a growth hormone (GH) receptor but also stimulates feeding behaviour and osteoblast function, have been demonstrated in subjects with energy restraint. Increased plasma levels of peptide YY (PYY), an anorexigenic peptide derived primarily from the intestine, which also plays a role in regulating bone mass, have also been found.

The medical complications of AN involve different organs and systems, with serious consequences depending on the degree of illness and the duration of the symptoms. Most of the complications are reversed by restoration of healthy eating habits, but a few apparatuses and organs, such as bones, tooth enamel, the liver and kidneys, may be compromised permanently in some subjects despite nutritional rehabilitation. We focus on the complications specifically studied in adolescent populations with AN.

The cardiovascular apparatus: cardiac involvement is present even in the early stages of the disorder. The most commonly reported complications include bradycardia, orthostatic hypotension, increased vagal tone and a variety of electrocardiographic changes (decreased voltage and extension of the QT interval). Arrhythmia may be caused by electrolytic disturbances such as hypokalaemia, hypomagnesaemia and altered acid–base balance and, in some cases, it may cause sudden death by unexpected cardiac failure. Poor myocardial contractility, mitral valve prolapse (MVP), reduction in left ventricular wall thickness and silent pericardial effusion can also be present. The need for early identification and prompt treatment of these complications should be emphasised. Gradual weight restoration with careful cardiac monitoring would re-establish normal cardiac function. During inpatient treatments, special attention must be paid to the so-called ‘refeeding syndrome’: this is a severe shift in fluid and electrolyte levels, particularly phosphates, from extracellular to intracellular spaces in severely malnourished patients who undergo overly rapid refeeding. The adverse consequences of hypophosphataemia include muscle weakness, immune dysfunction, congestive heart failure and sometimes death.

The gastro-enteric apparatus: gastrointestinal symptoms include constipation, fullness after eating and bloatedness due to delayed gastric emptying; oesophagitis, oesophageal erosions and ulcers are the result of frequent exposure to gastric acid in those anorexics who also induce vomiting. Other complications include hepatic steatosis related to mobilisation of fat from stores in the absence of sufficient energy for their metabolism; the reduced hepatic function explains hypercholesterolaemia, raised serum carotene and the reduction in the metabolic clearance rate of many steroid hormones (e.g., androgens and cortisol). More rarely, there is pancreatic involvement, with occasional cases of acute pancreatitis reported in the refeeding phase.

The musculoskeletal apparatus: the main complications are hypotrophy, especially of the trunk muscles, as a result of catabolism of structural proteins caused by energy demands. A very frequent complication is osteopaenia due to reduction in bone mineral content resulting from the uncoupling between bone formation and bone resorption, with an increased probability of fractures. The mechanisms implied in the pathogenesis of bone loss are multifactorial: undernutrition (with low intake of calcium and vitamin D), oestrogen deficiency, low IGF-1 levels, decreased ovarian and adrenal androgen production, hypercortisolism, reduced leptin levels, increased adrenergic tone and altered production of neuroendocrine gastrointestinal-derived peptides regulating food intake. Impaired linear growth and the possibility of permanent short stature are significant medical complications in younger adolescents with AN, especially related to the dramatic alterations in the Gh–IGF-1 axis. Although various studies have demonstrated a catch-up growth following nutritional intervention, these subjects generally do not reach their full genetic height potential.

Urinary apparatus: renal complications are the consequence of electrolytic abnormalities: hypokalaemic nephropathy occurs in anorexia as a result of chronic abuse of diuretics or laxatives, and it is associated with the development of chronic renal failure; other renal complications are decreased glomerular filtration rate and concentration capacity, increased blood urea and pitting oedema.

The nervous system: a diminution of the osteotendinous reflexes and possible peripheral neuropathy due to caloric and vitamin deficit has been described. Investigations into brain structure in AN have demonstrated a reduction in cerebral mass with ventricular enlargement probably due to the reduction of intracellular liquid and to hypercortisolism, which has been related to concentration and memorisation deficits. Studies of functional neuroimaging have provided evidence of limbic dysfunction and, more recently, in subjects with early-onset anorexia, a unilateral reduction of blood flow in the temporal region associated with impaired visual–spatial ability, impaired visual memory and enhanced speed of information processing.

The haematological and immune systems: pancytopaenia is common in severe AN, with mild normocytic normochromic anaemia and thrombocytopenia reported in about one-third of patients and leucopoenia with related lymphocytosis in up to two-thirds. Specific suppression of the antigen presenting cell–T cell–CD4+ lymphocyte axis has been demonstrated in anorectic patients.

Endocrine profile and medical complications in adolescents with AN

From an endocrine aspect, AN is characterised by several adaptive responses to the deficit of nutrients. Metabolic impairment and psychological distress interact at the hypothalamic level activating the chronic stress response: the hyperactivity of the corticotropin-releasing hormone (CRH)– adrenocorticotropic hormone (ACTH)–adrenal axis induces an increase in the daily production of cortisol and arginin–vasopressin and inhibits gonadotropin-releasing hormone (GnRH) pulsatile release and, consequently, pituitary luteinising hormone (LH) production and ovarian function. The LH release becomes similar to that of the prepubertal period, with the characteristic increase during the night and, in the advanced states of disease, practically undetectable. The follicle-stimulating hormone (FSH) levels are generally normal, except for cases of extreme weight loss, in which they too are reduced. Ovarian follicles are no longer stimulated and so oestradiol concentrations regress to prepubertal values. Other factors contributing to hypo-oestrogenism are the reduction in adipose tissue that determines an important decrease of extra-ovarian oestrogen production and the alterations in liver metabolism. At liver level, the production of inactive metabolites is increased and relatively higher levels of sex-hormone-binding globulin (SHBG) are present, so that it can be considered a reliable nutritional index. Higher levels of cortisol are secondary to increased production and to decreased hepatic clearance. Reduced adrenal androgen production, together with the impairment of ovarian production of androstenedione, contributes to low levels of circulating androgens. The increase in cathecolamines is probably responsible for the impairment in peripheral thyroid hormone metabolism, with generalised induction of type 3 deiodinase and a reduction of type 1 deiodinase contributing to the low T3 state associated with the sparing of energy-consuming processes. Induction of type 2 deiodinase in the hypothalamus may explain the lack of compensatory increase in thyroid-stimulating hormone. Sympathetic activation also promotes the recruitment of leucocytes and proinflammatory cytokines: these act in synergy with low T ₃ levels, reducing hepatic protein synthesis, in particular insulin growth factor-1(IGF-1). In anorectic subjects the release of GH is elevated, consequent on the low intake of carbohydrates; but the decrease in GH liver receptors and the reduction of serum Gh-binding protein (GhBP) induce a resistance to GH with IGF-I and IGF-binding protein (IGFBP)-3 levels significantly decreased. Thus, in subjects with amenorrhoea related to weight control, serum LH levels, free T ₃ and IGF-1 are low or in the lower reference range, while mean concentration of cortisol tends to exceed the standard range, especially when measured in the evening ( Table 3 ). Naturally, the levels of all the hormones related to energy availability are reduced. Leptin is a protein hormone secreted by adipocytes, and its circulating levels are correlated with the extension of the fat deposits: leptin secretion can centrally suppress appetite and acts as a connecting signal between energy stores and reproductive function, with a threshold effect on gonadotropin production. Leptin acts on appetite regulation by inhibition of hypothalamic neuropeptide Y (NPY) and stimulation of proopiomelanocortin (POMC). The stimulating effect on GnRH release, as in many animal models, is probably mediated by a group of peptides called kisspeptins, their production is regulated by the kisspeptin-1 (KISS-1) gene, whose expression is leptin dependent. Leptin stimulates KISS-1 gene expression in hypothalamic cells increasing kisspeptin secretion. The down-regulation of kisspeptin consequent on the decrease in leptin levels is thought to be responsible for amenorrhoea. Moreover, a direct effect of leptin on GnRH and on ovarian function has been demonstrated by administering recombinant-metHuLeptin at replacement doses to women with hypothalamic amenorrhoea related to strenuous exercise or low weight: this treatment rapidly improved LH pulse frequency and mean concentrations, as well as ovarian function. Insulin is a key hormone in regulating short-term energy homeostasis and long-term responses to energy-deprivation states, and undoubtedly plays a role in the link between metabolic state and reproductive function. Basal activity of pancreatic beta cells is reduced, with consequent lowering of insulin levels, as documented by low levels of C-peptide dosage (sensitive marker of pancreatic secretion). Alongside the reduction of insulinaemia, as an effect of the caloric and protein deficit, a reduction of peripheral sensitivity to the hormone is also detected, with lower uptake of glucose from the cells, especially in muscle and adipose tissue.

Current researches are studying the role of gastrointestinal peptides in situations of weight control. High levels of ghrelin, a peptide of 28 amino acids synthesised predominantly by the stomach and the gut, which not only activates the type 1a growth hormone (GH) receptor but also stimulates feeding behaviour and osteoblast function, have been demonstrated in subjects with energy restraint. Increased plasma levels of peptide YY (PYY), an anorexigenic peptide derived primarily from the intestine, which also plays a role in regulating bone mass, have also been found.

The medical complications of AN involve different organs and systems, with serious consequences depending on the degree of illness and the duration of the symptoms. Most of the complications are reversed by restoration of healthy eating habits, but a few apparatuses and organs, such as bones, tooth enamel, the liver and kidneys, may be compromised permanently in some subjects despite nutritional rehabilitation. We focus on the complications specifically studied in adolescent populations with AN.

The cardiovascular apparatus: cardiac involvement is present even in the early stages of the disorder. The most commonly reported complications include bradycardia, orthostatic hypotension, increased vagal tone and a variety of electrocardiographic changes (decreased voltage and extension of the QT interval). Arrhythmia may be caused by electrolytic disturbances such as hypokalaemia, hypomagnesaemia and altered acid–base balance and, in some cases, it may cause sudden death by unexpected cardiac failure. Poor myocardial contractility, mitral valve prolapse (MVP), reduction in left ventricular wall thickness and silent pericardial effusion can also be present. The need for early identification and prompt treatment of these complications should be emphasised. Gradual weight restoration with careful cardiac monitoring would re-establish normal cardiac function. During inpatient treatments, special attention must be paid to the so-called ‘refeeding syndrome’: this is a severe shift in fluid and electrolyte levels, particularly phosphates, from extracellular to intracellular spaces in severely malnourished patients who undergo overly rapid refeeding. The adverse consequences of hypophosphataemia include muscle weakness, immune dysfunction, congestive heart failure and sometimes death.

The gastro-enteric apparatus: gastrointestinal symptoms include constipation, fullness after eating and bloatedness due to delayed gastric emptying; oesophagitis, oesophageal erosions and ulcers are the result of frequent exposure to gastric acid in those anorexics who also induce vomiting. Other complications include hepatic steatosis related to mobilisation of fat from stores in the absence of sufficient energy for their metabolism; the reduced hepatic function explains hypercholesterolaemia, raised serum carotene and the reduction in the metabolic clearance rate of many steroid hormones (e.g., androgens and cortisol). More rarely, there is pancreatic involvement, with occasional cases of acute pancreatitis reported in the refeeding phase.

The musculoskeletal apparatus: the main complications are hypotrophy, especially of the trunk muscles, as a result of catabolism of structural proteins caused by energy demands. A very frequent complication is osteopaenia due to reduction in bone mineral content resulting from the uncoupling between bone formation and bone resorption, with an increased probability of fractures. The mechanisms implied in the pathogenesis of bone loss are multifactorial: undernutrition (with low intake of calcium and vitamin D), oestrogen deficiency, low IGF-1 levels, decreased ovarian and adrenal androgen production, hypercortisolism, reduced leptin levels, increased adrenergic tone and altered production of neuroendocrine gastrointestinal-derived peptides regulating food intake. Impaired linear growth and the possibility of permanent short stature are significant medical complications in younger adolescents with AN, especially related to the dramatic alterations in the Gh–IGF-1 axis. Although various studies have demonstrated a catch-up growth following nutritional intervention, these subjects generally do not reach their full genetic height potential.

Urinary apparatus: renal complications are the consequence of electrolytic abnormalities: hypokalaemic nephropathy occurs in anorexia as a result of chronic abuse of diuretics or laxatives, and it is associated with the development of chronic renal failure; other renal complications are decreased glomerular filtration rate and concentration capacity, increased blood urea and pitting oedema.

The nervous system: a diminution of the osteotendinous reflexes and possible peripheral neuropathy due to caloric and vitamin deficit has been described. Investigations into brain structure in AN have demonstrated a reduction in cerebral mass with ventricular enlargement probably due to the reduction of intracellular liquid and to hypercortisolism, which has been related to concentration and memorisation deficits. Studies of functional neuroimaging have provided evidence of limbic dysfunction and, more recently, in subjects with early-onset anorexia, a unilateral reduction of blood flow in the temporal region associated with impaired visual–spatial ability, impaired visual memory and enhanced speed of information processing.

The haematological and immune systems: pancytopaenia is common in severe AN, with mild normocytic normochromic anaemia and thrombocytopenia reported in about one-third of patients and leucopoenia with related lymphocytosis in up to two-thirds. Specific suppression of the antigen presenting cell–T cell–CD4+ lymphocyte axis has been demonstrated in anorectic patients.

Diagnostic markers

The physical signs of AN are mostly related to adaptive response to energy deficiency and to progressive malnutrition, and include pale and cold hands and feet, extreme thinness, stunted growth and failure of breast development (if prepubertal in onset), dry skin, fine downy hair ( lanugo ) on the back, forearms and cheeks, due to unbalanced circulating androgen levels, orange discolouration of the skin of the palms and soles in patients with hypercarotenaemia, swelling of the parotid and submandibular glands (especially in bulimic patients), erosion of inner surface of front teeth (perimylolysis) in those who vomit frequently, bradycardia and hypotension; in more compromised situations, dependent oedema (complicating assessment of body weight), and weak proximal muscles (illustrated as difficulty rising from a squatting position). The more frequently referred symptoms are marked sensitivity to cold, gastrointestinal disturbances and poor sleep with early morning wakening. Psychological symptoms frequently include depression and anxiety disorders, irritability, mood swings, impaired concentration, loss of sexual appetite and obsessive features. From a diagnostic point of view, the assessment and monitoring of nutritional status is of vital importance: body mass index (BMI) calculation can be indicative for use in longitudinal evaluation as well as mid-upper arm circumference measurement (MUAC).

Routine analyses are useful in evaluating eventual anaemia, leucopoenia and liver involvement. As regards protein levels, albumin is generally normal or higher in relation to globulins. Total cholesterol, low-density and high-density lipoprotein cholesterol are frequently higher in AN patients, except in subjects with extremely low BMI. If there is a suspicion of compensatory behaviour for binge eating, such as forced vomiting, laxative or diuretic abuse, it is mandatory to check serum electrolytes and amylase. Mild hypokalaemia is a common consequence of excessive loss of potassium, but severe hypokalaemia is extremely dangerous since it can result in cardiac arrhythmia. Hyperamylasemia reflects an overproduction of the enzyme by the salivary glands due to vomiting, but pancreatic involvement may also be possible. The serum parameters useful for endocrine and metabolic evaluation have been summarised in Table 3 .

A thorough study of body composition can be performed by dual-energy X ray absorptiometry (DEXA), which enables the simultaneous evaluation of bone mineral density, total fat mass and lean body mass (both total and related to specific areas of the body). From a diagnostic point of view, the fat mass percentage is strictly related to the restoration of the reproductive function: in a study comparing eumenorrhoeic and amenorrhoeic subjects with eating disorders, a mean value of 20% was observed in the first group. The lean body mass highlights the impact of muscle on total weight and is also strictly related to bone density preservation. Considering the impact of AN on bone metabolism, the direct evaluation of bone mineral density (BMD) in these subjects is also of interest, using age-adjusted software and considering the bias on DEXA-derived measurements related to stature: in short subjects, BMD is generally underestimated. The drawback to the extensive use of DEXA in the follow-up of anorectic subjects is the exposure to radiation, albeit limited, with each examination. Another possible option for the measurement of body composition is the use of bioelectrical impedance analysis (BIA). This simple and non-invasive method is based on a two-compartment model in which proteins, water and minerals are considered together to form the free fat mass (FFM). The application of this method to patients with a BMI <15 kg m ⁻² has been questioned. Another parameter resulting from BIA evaluation, of particular interest in monitoring subjects with serious nutritional deficiency, is the phase angle, which is related to the ratio between intra- and extracellular water as well as to the body cell mass: it decreases in proportion to undernutrition.