Autoantibodies against 21-hydroxylase (P450c21) are common in idiopathic autoimmune Addison's disease. In the present work, we have developed a sensitive radiobinding assay using in vitro translated recombinant human 35S-P450c21. Levels of P450c21 antibodies (P450c21-Ab) were expressed as a relative index (P450c21 index) using a P450c21-Ab positive Addisonian serum and two antibody-negative healthy sera as positive and negative standards in healthy individuals. The upper level of normal was the mean + 3 SD. Positivity for P450c21-Ab was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of immunoprecipitated 35S-P450c21. In 38 Addisonian patients, P450c21-Ab were found in 24/28 (86%) idiopathic, 0/5 post-tuberculosis, 0/3 adrenoleukodystrophy, and 0/2 post-adrenalectomy sera. Among healthy individuals, 1/70 (1.4%) were positive. The P450c21 index, as an estimate of P450c21-Ab levels, correlated inversely with the duration of idiopathic Addison's disease (r = -0.527; P = 0.007): 16/16 (100%) positive in patients with less than 20 yr and 8/12 (67%) positive in patients with more than 20 yr disease duration. The availability of this simple and sensitive radiobinding assay to evaluate levels of P450c21-Ab will permit large clinical studies as well as screening subjects at risk. In addition, the general population can now be screened to evaluate the predictive value of P450c21-Ab for Addison's disease.

The hypothalamic arcuate nucleus is involved in the control of energy intake and expenditure and may participate in the pathogenesis of eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Two systems are of particular interest in this respect, synthesizing ␣-melanocyte-stimulating hormone (␣-MSH) and synthesizing neuropeptide Y, respectively. We report here that 42 of 57 (74%) AN and͞or BN patients studied had in their plasma Abs that bind to melanotropes and͞or corticotropes in the rat pituitary. Among these sera, 8 were found to bind selectively to ␣-MSH-positive neurons and their hypothalamic and extrahypothalamic projections as revealed with immunostaining on rat brain sections. Adsorption of these sera with ␣-MSH peptide abolished this immunostaining. In the pituitary, the immunostaining was blocked by adsorption with ␣-MSH or adrenocorticotropic hormone. Additionally, 3 AN͞BN sera bound to luteinizing hormonereleasing hormone (LHRH)-positive terminals in the rat median eminence, but only 2 of them were adsorbed with LHRH. In the control subjects, 2 of 13 sera (16%) displayed similar to AN͞BN staining. These data provide evidence that a significant subpopulation of AN͞BN patients have autoantibodies that bind to ␣-MSH or adrenocorticotropic hormone, a finding pointing also to involvement of the stress axis. It remains to be established whether these Abs interfere with normal signal transduction in the brain melanocortin circuitry͞LHRH system and͞or in other central and peripheral sites relevant to food intake regulation, to what extent such effects are related to and͞or could be involved in the pathophysiology or clinical presentation of AN͞BN, and to what extent increased stress is an important factor for production of these autoantibodies.A norexia nervosa (AN) and bulimia nervosa (BN) are two officially recognized eating disorders that affect Ϸ3% of women during their lifetime (1). Both illnesses usually make their debut at young age and are characterized by hyperactivity and exaggerated concern about body shape and weight, and they often occur in the same patients (2). AN is manifested by an aversion to food, often resulting in life-threatening weight loss and amenorrhea, whereas BN includes large uncontrolled eating episodes followed by compensatory vomiting without significant change in body weight. Even if the cause(s) of AN and BN is still unclear, a body of data exists suggesting a primary neurobiological origin (3), and neuropeptides also have been implicated in these disorders (4). These assumptions are paralleled by growing evidence for a role of hypothalamic peptidergic neurons in conditions associated with energy deprivation or energy excess, providing a concept for central mechanisms controlling food intake and body weight (5-7). In a search of possible mechanisms implicating hypothalamic peptidergic neurons in the etiology and pathogenesis of AN͞BN, we hypothesized that hypothalamic systems responsible for the regulation of food intake could be targeted by autoantibodies...

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Stereotactic radiosurgery is a safe and effective method in the treatment of patients with adrenocorticotropic hormone-producing pituitary tumors, and the effect of treatment is long-lasting. Stereotactic radiosurgery is mainly a complement to microsurgery because of its gradually appearing effect and the occurrence of pituitary insufficiency. New pituitary deficiencies may be found more than 10 years after treatment.