Anorexia nervosa (AN) is a chronic childhood psychiatric illness that involves a reduction in caloric intake, loss of weight and amenorrhea, either primary or secondary. The diagnostic criteria for AN have been established by the American Psychiatric Association. The prevalence of this disease amongst adolescents and young adults is between 0.5 and 1% and the incidence of new cases per year is approximately 5-10/100,000 between 15 and 19 years of age.A number of endocrine and metabolic disturbances have been described in patients with AN including amenorrhea-oligomenorrhea, delayed puberty, hypothyroidism, hypercortisolism, IGF-I deficiency, electrolyte abnormalities, hypoglycemia and hypophosphatemia, among others. In addition to prolonged amenorrhea, osteopenia and osteoporosis are the most frequent complications leading to clinically relevant fractures and increased fracture risk throughout life. Patients exhibit an alteration in the hypothalamic-pituitary-gonadal axis, which is responsible for the menstrual disorders. The increase in gonadotropin secretion that can be observed after ponderal recuperation suggests that malnutrition could be the most important mechanism involved in the decrease in gonadotropin secretion.The loss of fat tissue as a consequence of nutrient restriction has been associated with hypoleptinemia and abnormal secretion of peptides implicated in food control (neuropeptide Y, melanocortins and corticotropin-releasing factor, among others).A review of the endocrine abnormalities, disturbances in neurotransmitters, as well as a detailed analysis of bone markers and bone mineral density in patients with AN is described.
MT Munoz and J Argente
V Barrios, J Argente, MT Munoz, J Pozo, JA Chowen and M Hernandez
OBJECTIVE: To analyze the possible utility of measuring acid-labile subunit (ALS) in some types of pathologies in which the IGF system is altered and to compare it with the clinical implications of measurements of other components of this axis. DESIGN AND METHODS: We studied serum ALS concentrations in 20 children with normal variants of short stature (NVSS) at diagnosis and 24 with growth hormone deficiency (GHD), 18 obese patients and 18 girls with anorexia nervosa at diagnosis and during a follow-up period. RESULTS: In patients with GHD and anorexia nervosa, mean ALS concentrations were significantly reduced, but there was a high percentage of overlap with control values. At diagnosis, ALS concentrations were normal in obese patients and children with NVSS. During follow-up, these values normalized in children with GHD who were treated with GH, tended to normalize in those with anorexia nervosa who showed weight gain, and did not change in obese children upon weight loss. However, ALS measurement was less accurate than that of IGF-I or IGF binding protein (IGFBP)-3 in diagnosis of GHD. The correlations found between ALS and some IGF system components at diagnosis either decreased or were non-significant during follow-up of these clinical conditions. CONCLUSION: ALS adds little information to that obtained with IGF-I and IGFBP-3 determinations.
MT Munoz, G Morande, JA Garcia-Centenera, F Hervas, J Pozo and J Argente
OBJECTIVE: Profound osteopenia is a serious complication of anorexia nervosa (AN). The aim of this work was to study the effect of prolonged AN on lumbar spine bone mineral density (BMD) and to determine whether oral estrogen administration prevents bone loss in women with this disorder. SUBJECTS AND METHODS: Thirty-eight amenorrheic women with AN (mean age: 17.3 years) were treated with estrogen (50 microg of ethinyl estradiol) and gestagen (0.5 mg of norgestrel) during 1 year. Clinical variations, biochemical indices and BMD were studied at three different time points, including after a period of amenorrhea of at least 12 months (n=38), after the administration of estrogens for 1 year (n=22), and after a 1-year follow-up period (n=12). RESULTS: Initial mean BMD was significantly lower than normal (-2.1+/-0.8 s.d.) and less than -2.5 s.d. below normal in 38% of the women with AN. The estrogen-treated group had no significant change in BMD even after the follow-up period and partial recovery of weight. Estradiol and total IGF-I levels were significantly lower throughout the study. All subjects had normal thyroxine (T(4)) and TSH levels and calcium metabolism. However, total tri-iodothyronine (T(3)) was decreased in all anorexic subjects in the first and second study points and were within normal limits after the follow-up period. CONCLUSIONS: (1) Estrogen replacement alone cannot prevent progressive osteopenia in young women with AN. (2) Other factors, such as the loss of weight, the duration of the amenorrhea and the low levels of total insulin-like growth factor-I (IGF-I) could contribute to the loss of bone mass in women with this disorder.
MT Munoz, C de la Piedra, V Barrios, G Garrido and J Argente
OBJECTIVE: Our aim was to compare physical activity and biochemical markers with bone mineral acquisition in rhythmic gymnasts and ballet dancers. METHODS: Weight, height, body mass index, nutritional intake, bone age and menstrual histories were analyzed in nine rhythmic gymnasts, twelve ballet dancers and fourteen controls. Bone mineral density (BMD) was assessed by X-ray absorptiometry at the lumbar spine, hip and radius. Bone alkaline phosphatase (bAP) and amino-terminal propeptide of procollagen I (PNIP) in serum and urinary alpha-isomer of the carboxy-terminal telopeptide of collagen I (alpha-CTX) were measured. RESULTS: Bone age was delayed 2 years and mean age at menarche was 15+/-0.9 years in rhythmic gymnasts and 13.7+/-1 years in ballet dancers, compared with 12.5+/-1 years in controls. Trocanteric and femoral neck BMD was significantly higher in rhythmic gymnasts compared with ballet dancers and controls. Right forearm (non-loaded zone) BMD was significantly decreased in rhythmic gymnasts and ballet dancers compared with controls. All subjects had normal bAP and PNIP levels, but the alpha-CTX/creatinine (Cr) ratio was increased in rhythmic gymnasts (P<0.001) with an inverse correlation between right forearm BMD and the alpha-CTX/Cr ratio (r=-0.74, P<0.001). Serum leptin levels were decreased in rhythmic gymnasts and ballet dancers. Rhythmic gymnasts had a positive correlation between right forearm BMD and leptin levels (r=0.85, P<0.001). CONCLUSIONS: Decreased bone mass in rhythmic gymnasts could be partially explained by an increase in bone resorption. Serum leptin levels could be implicated in the pubertal delay and be a good marker of bone mass in these subjects.