Autoimmune cranial diabetes insipidus: its association with other endocrine diseases and with histiocytosis X.

Thirty-nine patients with idiopathic cranial diabetes insipidus (DI) and 81 secondary to hypothalamic lesions were investigated for the presence both of associated autoimmune diseases and autoantibodies. Eleven (28%) of the idiopathic but none of the secondary DI cases had an overt autoimmune disease. A further two patients with idiopathic DI had associated organ-specific autoantibodies.

Secondary failure to treatment with oral antidiabetic agents in non-insulin-dependent diabetes.

To study the etiopathogenesis of secondary drug failure to treatment with oral antidiabetic agents in patients with non-insulin-dependent diabetes (NIDD) we compared 60 "nonresponders" with 60 "responders" to treatment with oral drugs. Secondary drug failure was defined as mean diurnal blood glucose greater than 12 mmol/L after an initial good response of greater than or equal to 2 yr. The nonresponders were characterized by 50% lower C-peptide concentrations than the responders (P less than 0.

Islet cell antibodies identify latent type I diabetes in patients aged 35-75 years at diagnosis.

One hundred fifty-four selected patients with nonketotic diabetes diagnosed between the ages of 35 and 75 yr and treated with diet or oral hypoglycemic agents for at least 1 yr were investigated for parameters of glycemic control (weight loss, blood glucose, and glycosylated hemoglobin), islet cell function (fasting and glucagon-stimulated C-peptide responses), and immunologic markers of insulitis (total ICA and CF-ICA) or autoimmunity (thyroid and gastric antibodies). These parameters were all repeated in 9 of 22 ICA-positive patients after a 2-yr follow-up and correlated with secondary drug failure. The antibody tests were also done on 51 nondiabetic controls matched for age and body weight.

Autoimmune thyroid disease.

The concept of thyroid autoimmune disease now includes the following clinical entities: 1 degree thyrotoxicosis and goitrous thyroiditis (Hashimoto) with their variants, and 1 degree myxedema (atrophic thyroiditis); some cases of sporadic nontoxic goiters; most cases of neonatal hyperthyroidism; and a proportion of congenital athyreotic cretinism. Endocrine exophthalmos, though clinically associated with Graves' disease, is now considered a separate immunological entity.

Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis. Final results of an international trial.

The effect of azathioprine on survival of patients with primary biliary cirrhosis was studied prospectively in a multinational, double-blind, randomized clinical trial including 248 patients of whom 127 received azathioprine and 121 placebo. There were 57 deaths in the azathioprine group and 62 in the placebo group. The actual survival was slightly longer during azathioprine than during placebo treatment.

Early features of primary biliary cirrhosis: an analysis of 85 patients.

A standardized clinical, laboratory, and histological assessment was carried out on 85 patients with primary biliary cirrhosis within 1 year of developing symptoms. Presenting symptoms included pruritus (n = 30), jaundice (n = 9), variceal bleeding (n = 6), ascites (n = 5), fatigue (n = 4), and abdominal pain (n = 4). Ten patients had symptoms not immediately suggestive of hepatic etiology and a further 17 were asymptomatic, the diagnosis being made fortuitously.

Further studies on thyroid growth-stimulating immunoglobulins in euthyroid nonendemic goiter.

Sixty-two consecutive patients with sporadic euthyroid goiter (57 women and 5 men) from noniodine-deficient areas, including 15 patients with diffuse goiter, 39 patients with multinodular goiter, and 8 patients with a single nodule, were studied for the presence of serum thyroid growth-stimulating immunoglobulins (TGI) by the ultrasensitive cytochemical bioassay based on DNA cytophotometry (Feulgen-cytochemical bioassay). Using strictly specified conditions, 43 patients (67%) were positive. Values tended to be high in diffuse goiter, nodular goiters reccuring after partial thyroidectomy, and those with recent growth.

Aberrant expression of HLA-DR antigens on bileduct epithelium in primary biliary cirrhosis: relevance to pathogenesis.

Direct immunofluorescence with an avidinbiotin system was used to investigate the expression of MHC molecules HLA-DR and HLA-A,B,C on bileducts in cryostat sections from 10 primary biliary cirrhosis (PBC) patients. Needle biopsy specimens from 55 patients with various chronic liver disorders, surgical biopsy specimens from 2 patients with recurrent secondary cholangitis, and 4 normal livers were used as controls. Normal bileducts did not express DR whereas in 8/10 PBC biopsy specimens there were varying degrees of cytoplasmic DR staining in septal or interlobular bileduct epithelium.

In vitro and in vivo reversal of thyroid epithelial polarity: its relevance for autoimmune thyroid disease.

A method is described for culturing intact human thyroid follicles, based on the study of 40 thyroidectomy specimens from normal (n = 18) and diseased glands (n = 22). Reversal of the normal polarity of thyrocytes, whereby the microvilli move from the colloid edge to the vascular pole of the cells, occurs gradually when the amount of fetal calf serum (FCS) is changed from 0.5% to 10%.

Autoantibodies in highly aged humans.

The presence of 14 different autoantibodies was determined in 65 persons, aged 95 years and older, without overt disease. The prevalence of positive anti-immunoglobulin latex tests, of autoantibodies against nuclear components and against thyroid microsomes was significantly increased. This selective increase of autoantibodies of low titre and without cluster formation is considered to be the result of a loss of control within the immune system due to ageing, rather than as a sign of latent disease.

Aberrant expression of HLA-DR antigen on thyrocytes in Graves' disease: relevance for autoimmunity.

To investigate the expression of class II histocompatibility antigens HLA-DR in the thyrocytes in autoimmune thyroid diseases, 47 thyroidectomy specimens were examined by immunofluorescence with monoclonal antibodies to the nonpolymorphic region of the DR molecule. Aberrant DR expression was most marked in the Hashimoto gland, with the entire section being strongly stained. DR expression was seen in discrete groups of follicles in 20/26 thyroids from patients with Graves' disease, in 2/9 non-toxic nodular goitres, and in none of 11 specimens of "normal" thyroid.

Detection of thyroid growth immunoglobulins (TGI) by [3H]-thymidine incorporation in cultured rat thyroid follicles.

A new bioassay is described for detecting the growth stimulating immunoglobulins (TGI) that contribute to goitre formation in human thyroid autoimmune diseases. It measures the incorporation of tritiated thymidine into intact rat thyroid follicles grown in tissue culture. This radiometric assay demands much less technical skill than the cytochemical bioassays (CBA) previously employed.

[Autoimmune form of central diabetes insipidus with antibodies against vasopressin-producing hypothalamic cells].

Autoantibodies against vasopressin (AVP)-producing cells of the human pituitary gland as well as conventional antibodies were determined in 67 patients with central diabetes insipidus and in 141 controls without diabetes insipidus using an immunofluorescence technique. Eleven out of 30 patients (37%) with nonfamilial idiopathic diabetes insipidus, two out of 28 patients (7%) with symptomatic diabetes insipidus and none of the control persons had AVP-cell antibodies. Antibody titres were between 1 : 2 and 1 : 32, in 8 of the 13 cases the antibodies were complement-binding.

[Possibilities and value of immunofluorescence in the diagnosis of endocrine diseases].

The indirect immunofluorescence (IFL) test is the method of choice for the detection of new organ-specific autoantibodies. It is also the standard method of detection of antibodies to pancreatic islet cells, adrenal cortex, and steroid-producing cells in gonads and placenta. A positive test is the essential diagnostic step to find out the etiology of some endocrine diseases, but the significance of this method varies in different organs.

Etiology of Type I diabetes mellitus: heterogeneity and immunological events leading to clinical onset.

Type I diabetes is a heterogeneous disorder and the causes of pancreatic beta-cell destruction are unknown. In 1-2% of all cases, viruses (e.g.

[Can growth-stimulating immunoglobulins (TGI) explain sporadic euthyroid goiters?].

IgGs capable of stimulating thyroid growth have been demonstrated (thyroid growth stimulating IgG-TGI) using a cytochemical bioassay based upon measurement of DNA synthesis in slices of guinea-pig thyroid. This activity has been confirmed by measurement of 3H-thymidine incorporation into DNA, in rat dispersed thyroid follicles cultured in suspension. Circulating TGI has been observed in patient with "simple" goitre, Graves' disease and more rarely in Hashimoto's thyroiditis.

Autoimmunity to anterior pituitary cells and the pathogenesis of insulin-dependent diabetes mellitus.

An immunofluorescence study using unfixed cryostat sections of human pituitary glands was carried out on sera from patients with type-Ia (juvenile-onset) diabetes (61 recent onset, 48 longstanding). 63 of their selected high-risk first-degree relatives and 117 patients with type-Ib ("polyendocrine") diabetes were tested for comparison. Healthy controls included 48 sera from laboratory staff and students.