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SUMMARY The diagnostic specificity of recombinant 21-hydroxylase autoantibodies (21OH-Ab) for Addison's disease was tested in adult patients with either Graves' disease (GD), insulin-dependent diabetes mellitus (IDDM), or polyendocrinopathy, as well as in healthy controls. Using a radiobinding assay with in vitro translated recombinant human 21-hydroxylase, we found 21OH-Ab in 24/28 (86%) idiopathic Addison patients, and using an immunofluorescence assay we found adrenal cortex autoantibodies (ACA) in 12/28 (43%) patients (P =0.002). All the 12 ACA-positive sera were also positive for 21OH-Ab and ACA were found in 11/15 (73%) patients with less than 15 years and in 1/13 (8%) patients with 15–38 years of disease duration (P = 0.002). 21OH-Ab were present in 3/92 (3%) patients with GD, in 1/180 (0.6%) with IDDM and in 0/106 healthy subjects. The 21OH-Ab-positive GD and IDDM patients were also positive for ACA. None of 17 patients with polyendocrinopathy, but without Addison's disease, had 21OH-Ab. None of the 180 Belgian IDDM patients had Addison's disease or developed an adrenal insufficiency at follow up. In two out of three Graves patients, the presence of 21OH-Ab was associated with clinical and biochemical signs of adrenal insufficiency. Of the 89 21OH-Ab-negative patients with GD none had Addison's disease at the time of blood sampling, and 79 were followed up for 5.6–7.5 years and none developed clinical signs of adrenal insufficiency. We conclude that the presence of 21OH-Ab in patients with endocrine autoimmune diseases is highly specific for Addison's disease.

The hereditary multiple endocrine neoplasia syndromes types 2A and B (MEN 2A and B) were recently linked to germline mutations in the RET proto-oncogene, altering one of five cysteine residues in exon 10 or 11 (MEN 2A), or substituting a methionine for a threonine at codon 918 in exon 16 (MEN 2B). The latter mutation also occurs somatically in some sporadic medullary thyroid carcinomas (MTC), and has in a previous study been correlated with a less favorable clinical outcome. In the present study, 46 MTCs were selected for investigation of the codon 918 mutation. The mutation was found in 29 tumors (63%), and was significantly correlated with a poor outcome, with regard to distant metastasis or tumor recurrence (p < 10(-4)). Two tumors showed multifocal growth and C-cell hyperplasia, and these patients were therefore also investigated for germline mutations in exons 10, 11 and 16. The codon 918 mutation was found only in the tumors, thus of somatic origin. The RET codon 918 mutation may have prognostic impact, and therefore preoperative assessment may influence decision-making in the treatment of patients suffering from MTC.

To study the effects and serum levels of glibenclamide (Gb) and its active metabolites in patients on chronic Gb medication on different daily doses.Fifty patients with type 2 diabetes on regular Gb therapy (1.75-14.0 mg daily). Blood samples were taken immediately before and 90 min after regular Gb intake. A standardized breakfast was served 30 min after drug intake. Serum insulin and proinsulin levels were determined by ELISA methods without cross-reactivities. Serum drug levels were determined by HPLC. Fischer's R to Z-test (correlation coefficients) and paired Student t-tests were used when comparing values within the entire group and unpaired non-parametric Mann-Whitney tests were used when comparing high and low dose levels. A p-value0.05 was considered significant.There were significant correlations between daily Gb dose, on the one hand, and, on the other, HbAlc (r = 0.55), Delta-insulin (r = - 0.59) and Delta-proinsulin (r = - 0.52) levels. Significant correlations between Gb therapy duration and insulin (r = - 0.40) and proinsulin (r = - 0.34) secretion and between Gb dose and ratio proinsulin/insulin (RPI) at both time points (r = 0.32 and 0.30) were also found. The RPI was lower after Gb intake. In patients onor = 10.5 mg steady state serum metabolite levels (Ml and Ml + M2) were higher (29(0-120) and 33 (0-120) ng/ml) than those of Gb itself (18(0-64) ng/ml). A great inter-subject variability in Gb levels at both time points was seen.Our results indicate that, in patients on chronic medication, Gb is capable of stimulating both insulin and proinsulin secretion; the effect on insulin release is relatively greater. The effect was more pronounced in patients on a low Gb dose, either because of less impaired beta-cells in those receiving low doses, or due to reduced sulphonylurea sensitivity in those on high dosage (down-regulation). In patients on a daily dose of 10.5 mg or more, serum metabolite levels of clinical relevance were demonstrated; the metabolites may contribute to hypoglycaemic events.

Precedenti studi randomizzati hanno suggerito un’associazione tra la terapia con radioiodio per l’ipertiroidismo del morbo di Basedow (MB) e l’oftalmopatia basedowiana (OB). Lo scopo di questo studio era di confrontare la comparsa o il peggioramento della OB in pazienti trattati con radioiodio o con farmaci antitiroidei. Veniva condotto uno studio randomizzato in 96 pazienti con un follow-up di 4 anni. Pazienti con una diagnosi recente di MB con ipertiroidismo venivano randomizzati al trattamento precoce con radioiodio (163 pazienti) o a 18 mesi di terapia con farmaci antitiroidei. Ad entrambi i gruppi veniva somministrata la tiroxina a scopo sostitutivo. Il peggioramento o lo sviluppo di OB erano significativamente piu frequenti nel gruppo trattato con radioiodio (63 pazienti; 38,7%) rispetto al gruppo trattato con antitiroidei (32 pazienti; 21,3%) (p

Hypothyroidism is a clinical entity resulting from deficiency of thyroid hormones or, more rarely, from their impaired activity at tissue level. It is a common condition, with a prevalence of 1.9 per cent in women, and the prevalence increases with age. Hypothyroidism may be congenital or acquired, primary or secondary, chronic or transient. Primary hypothyroidism is caused by disease or treatment which destroys the thyroid gland or interferes with thyroid hormone biosynthesis. Autoimmune thyroiditis is the predominant cause of primary hypothyroidism in countries such as Sweden where severe iodine deficiency is non-existent. Another cause of primary hypothyroidism, chronic or transient, is previous radio-iodine or surgical treatment of hypothyroidism. In secondary or central hypothyroidism, which is very rare, there is a lack of thyroid-stimulating hormone (TSH) or TSH activity, due to a pituitary or hypothalamic cause. The clinical features of hypothyroidism are dependent on the patient's age, the presence of other disease, and the rate at which hypothyroidism develops. As thyroid hormones are universal determinants of organ function, there may be a multiplicity of symptoms. Particularly in the elderly, the clinical features may be atypical, and the diagnosis easily missed. First line tests for hypothyroidism are analyses of the concentrations of free thyroxine (T4) and TSH in serum. In primary hypothyroidism, the serum content of T4 is low and that of TSH high. In central hypothyroidism, the serum content of T4 is low and that of TSH generally low or normal, though slightly increased levels of biologically inactive TSH may also occur. Subclinical hypothyroidism is characterised by a normal serum level of T4, an increased level of TSH, and the absence of clinical symptoms. When a diagnosis of chronic hypothyroidism is confirmed, treatment with laevothyroxine is started, the initial dose being adjusted to the age and general condition of the patient, and the duration and severity of hypothyroidism. As a rule, full thyroxine replacement therapy should bring the serum TSH level into the normal range. In central hypothyroidism, laevothyroxine treatment is similar, but pituitary function must be evaluated and, if necessary, corticosteroid replacement be instituted before laevothyroxine treatment is started.

This study aimed at evaluating the frequency of autoimmune disorders in Addison's disease. We have observed 180 patients (113 females, 67 males, aged 9-74 years) for 1 to 26 years. Tuberculosis was noted in 54 patients. Autoimmune disorders were found in 80 patients (44%); however, 125 (69%) patients were believed to have an autoimmune origin of adrenocortical insufficiency. In 20 patients two or more autoimmune disorders were found to coexist with Addison's disease.

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Eight children with Cushing's disease aged 6-18 years were treated with external radiation to the pituitary gland using 60Co gamma radiation given with stereotactic technique. The dose given varied between 50 and 70 Gy. The observation time was 2.6 to 6.75 years. Seven children had a clinical remission with normal urinary Cortisol excretion. One child had insufficent effect of two irradiations and underwent bilateral adrenalectomy. In the patients in remission the growth velocity increased during the first year after treatment but growth retardation occurred again during the second year. Insufficient growth hormone secretion was demonstrated in all subjects. Two patients were given thyroxine substitution and three showed evidence for secondary hypogonadism. In conclusion, stereotactic pituitary irradiation was effective in normalizing the excessive glucocorticoid production in children with Cushing's disease. However, with the doses used, it was not possible to maintain a normal anterior pituitary function.