Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence and clinical characteristics of hypoparathyroidism (Hypo) were evaluated in 8188 hemodialysis (HD) and 1207 CAPD patients treated in 65 hospitals or clinics in Japan. Hypo was defined by an intact parathyroid hormone (PTH) level below 160 pg/ml, which corresponded to the low normal limit of intact PTH to maintain a normal osteoblastic surface in 40 bone biopsy specimens of Japanese dialysis patients, and patients were classified into two groups: absolute Hypo (A-Hypo), intact PTH < 60 pg/ml, and relative Hypo (R-Hypo), 60 pg/ml < or = intact PTH < 160 pg/ml. A total of 2537 (31.0%) and 2736 (33.4%) HD patients were classified into A- and R- Hypo, and 401 (31.3%) and 379 (31.4%) CAPD patients occupied A- and R-Hypo, respectively. A high incidence of Hypo was observed in the HD patients with diabetes mellitus (DM) and old age (> or = 70 years old) compared with that of a nationwide epidemiological report for dialysis patients by Japanese Society for Dialysis Therapy. Hypo patients who were treated by CAPD had a background of being younger, having a shorter duration on dialysis, and were less frequently diagnosed with DM than in those Hypo patients on HD. Bone pain and metastatic calcification were observed in approximately 20% and 25% of Hypo patients, respectively. No difference was observed in the background factors and the prevalence of signs and symptoms between the A- and R-Hypo groups, regardless of the mode of treatment (HD or CAPD). These results suggest that a very high incidence and specific backgrounds (DM and aging) of Hypo exist in Japanese dialysis patients.
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PMID:Incidence and clinical characteristics of hypoparathyroidism in dialysis patients. 935 Jun 86

Diabetes mellitus is the most frequent endocrinopathy associated with mitochondrial disorders, particularly in patients with duplications of mitochondrial DNA (mtDNA). Although hypoparathyroidism has also been described in mitochondrial diseases, there have been few molecular studies in these cases, most of which identified the presence of single mtDNA deletions in the patients' tissues. We studied muscle DNA of a 12-yr-old patient with incomplete Kearns-Sayre syndrome and hypoparathyroidism. Southern analysis showed that muscle DNA contained three populations of mtDNA: wild type (26%), deleted (65%), and duplicated (9%). To determine the sequence of the breakpoint region from deleted and duplicated mtDNA independently, we isolated the deleted and duplicated mtDNA by gel fractionation of a PstI-digested total DNA. The breakpoint was located at mtDNA positions 5788 and 15,448 for both duplicated and deleted molecules. Our study reinforces the concept that endocrinopathies other than diabetes can be associated with a duplication of mtDNA and gives additional support to the hypothesis that the duplication and deletion of mtDNA are generated from the same recombination event.
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PMID:Mitochondrial encephalomyopathy and hypoparathyroidism associated with a duplication and a deletion of mitochondrial deoxyribonucleic acid. 943 28

In 11 MEN 2A gene carriers prophylactic thyroidectomy was carried out between the age of 4 to 17 years. All gene carriers had pathological basal and/or pentagastrin stimulated serum calcitonin levels. On histological examination in five patients C-cell hyperplasia (CCH) and in 6 patients medullary microcarcinoma (< 1 cm, mostly multifocally) was shown. No patient had lymph node involvement. There was no recurrent laryngeal nerve damage in these 11 patients and no permanent hypoparathyroidism. After prophylactic thyroidectomy all 11 patients were cured, they showed normal basal and pentagastrin stimulated calcitonin levels. In the follow-up (mean 19 months) under thyroxine substitution therapy in 9 of these 11 patients TSH was at least at one examination out of the normal range. In 2 patients TSH was suppressed, in 1 of these FT3 was slightly elevated. In 7 patients TSH was elevated between 4.9 to 147 microU/ml. The application of genetic testing is save concerning diagnostic accuracy. If prophylactic thyroidectomy is done at early ages cure rate is 100%. Despite this encouraging results thyroxine substitution therapy in the follow-up carries some problems concerning optimal dosage and non-compliance. Therefore TSH has to be estimated in the follow-up every 3 months.
Exp Clin Endocrinol Diabetes 1997
PMID:Results and follow-up in eleven MEN 2A gene carriers after prophylactic thyroidectomy. 943 23

Diabetic patients on dialysis have lower levels of parathyroid hormone (PTH); however, there is no data regarding PTH levels with different degrees of chronic renal failure (CRF). We compared 58 diabetic patients with different degrees of CRF with 268 non-diabetic patients with CRF (serum creatinine >1.2 mg/dl). In both groups, we investigated the main biochemical parameters together with plasma calcium, phosphorus, magnesium, PTH and calcitriol. Diabetic patients showed lower levels of PTH than non-diabetics (P=0.003). The differences were observed in patients with creatinine clearance <70ml/min. We also observed differences in phosphorus, magnesium and tubular resorption of phosphate. In the group of diabetic patients, serum glucose correlated inversely with PTH. Our study suggests that poor control of diabetes (hyperglycaemia) may play a role in the pathogenesis of the hypoparathyroidism observed in patients with diabetes and CRF.
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PMID:Is there a lesser hyperparathyroidism in diabetic patients with chronic renal failure? 956 13

It has been shown that an adenine (A) to guanine (G) transition at position 3243 of the mitochondrial transfer RNA(tRNA)leu(UUR) gene is associated with a subgroup of diabetes mellitus. Therefore, we screened for this transition in 86 patients with non-insulin-dependent diabetes mellitus (NIDDM) in which two or three generations were affected with diabetes, in 14 patients with insulin-dependent diabetes mellitus, and in 9 families with diabetes mellitus and/or associated disorders suggesting mitochondrial gene abnormalities. We failed to identify the mutation in 100 diabetic patients, 86 NIDDM and 14 insulin-dependent diabetes mellitus (IDDM). Out of the latter 9 families, we identified an A to G transition in 14 individuals in 5 families. Diabetes mellitus was shown to be maternally inherited in one family. In 9 of 14 patients with the mutation, insulin was required to treat diabetes mellitus, indicating impaired insulin secretion. A hyperglycemic clamp test performed in one subject revealed significant impairment of insulin secretion, whereas euglycemic clamp test showed normal insulin sensitivity in this patient. The heteroplasmy of the mutant mitochondrial DNA (mtDNA) in leukocytes does not appear to correlate with the severity of diabetes in terms of the insulin therapy required. Body mass index of the affected individuals was less than 23.3. In one family, in addition to diabetes mellitus and hearing loss, hypoparathyroidism was associated with the mutation, suggesting that hypoparathyroidism is caused by the impaired processing and/or secretion of proparathyroid hormone due to the mutation. In addition, the affected subjects presented with proteinuria at the time of diagnosis of diabetes mellitus which appeared not to be related with diabetic nephropathy.
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PMID:Clinical manifestations due to a point mutation of the mitochondrial tRNAleu(UUR) gene in five families with diabetes mellitus. 961 61

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; OMIM *240300, also called APS 1,) is a rare autosomal recessive disorder that is more frequent in certain isolated populations. It is generally characterized by two of the three major clinical symptoms that may be present, Addison's disease and/or hypoparathyroidism and/or chronic mucocutaneous candidiasis. Patients may also have a number of other clinical symptoms including chronic gastritis, gonadal failure, and rarely, autoimmune thyroid disease and insulin-dependent diabetes mellitus. We and others have recently identified the gene for APECED, which we termed AIRE (for autoimmune regulator). AIRE is expressed in thymus, lymph nodes, and fetal liver and encodes a protein containing motifs suggestive of a transcriptional regulator, including two zinc finger motifs (PHD finger), a proline-rich region, and three LXXLL motifs. Six mutations, in cluding R257X, the predominant Finnish APECED allele, have been defined. R257X was also observed in non-Finnish APECED patients occurring on different chromosomal haplotypes suggesting different mutational origins. Here we present mutation analyses in an extended series of patients, mainly of Northern Italian origin. We have detected 12 polymorphisms, including one amino acid substitution, and two additional mutations, R203X and X546C, in addition to the previously described mutations, R257X, 1096-1097insCCTG, and a 13-bp deletion (1094-1106del). R257X was also the common mutation in the Northern Italian patients (10 of 18 alleles), and 1094-1106del accounted for 5 of 18 Northern Italian alleles. Both R257X and 1094-1106del were both observed in patients of four different geo-ethnic origins, and both were associated with multiple different haplotypes using closely flanking polymorphic markers showing likely multiple mutation events (six and four, respectively). The identification of common AIRE mutations in different APECED patient groups will facilitate its genetic diagnosis. In addition, the polymorphisms presented provide the tools for investigation of the involvement of AIRE in other autoimmune diseases, particularly those affecting the endocrine system.
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PMID:Common mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients of different origins. 971 37

We describe two patients with liver kidney microsomal antibody type 1 (LKM1)-positive autoimmune hepatitis (AIH) with associated endocrinopathies. The first patient had insulin-dependent diabetes (IDDM), and the second patient had Addison's disease and hypoparathyroidism, and is also positive for islet cell antibodies, without overt diabetes. To account for the existence of multiple endocrinopathy in these patients, we investigated whether there is sequence similarity between the target of LKM1 antibodies, cytochrome P4502D6 (CYP2D6), and other human proteins, and if so, whether this structural similarity produces a detectable cross-reactive immune response. Our database search identified two proteins, carboxypeptidase H, an autoantigen in insulin-dependent diabetes, and 21-hydroxylase, the major autoantigen in Addison's disease, that share sequence similarity to the second major LKM1 epitope on CYP2D6. We tested the reactivity of sera from these patients to the homologous regions of the three autoantigens using an enzyme-linked immunosorbent assay (ELISA). The cut-off for positivity was established by testing sera from 22 healthy children. To determine the significance of reactivity to the peptide homologues of the three autoantigens, we investigated 16 additional patients with LKM1 AIH and 20 children with chronic hepatitis B virus infection as pathological controls. We found that reactivity to the second major epitope of CYP2D6 is significantly associated with reactivity to the homologous regions of carboxypeptidase H (CPH) and 21-hydroxylase (21-OHase) in patients with LKM1 AIH, and that this simultaneous recognition is cross-reactive. We suggest that a cross-reactive immune response between homologous autoantigens may contribute to the development of multiple endocrinopathies in LKM1 AIH.
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PMID:Immunological cross-reactivity to multiple autoantigens in patients with liver kidney microsomal type 1 autoimmune hepatitis. 979 98

The operative therapy of the autonomous thyroid deals almost exclusively with nodular goiters. There are only rare situations with purely diffuse autonomy in surgical patients. The endpoint of operative therapy is permanent elimination of clinically relevant autonomous function and thereby irreversible abolition of thyrotoxicosis, even in their latent form. Clinically relevant autonomous function normally ist linked to nodular structures of different size and different distribution, so that this aim corresponds automatically with the aim of complete removal of nodular structures, both in autonomous and in non-autonomous goiters. Function is best preserved by leaving a homogenous remnant of considerable size. In different particular clinical situations (for example pregnancy, suspicion of malignancy, recurrent goiter, intrathoracic goiter, thyrotoxic crisis, Marine-Lenhart-syndrome) the basic principal of operative strategy is varied according to the respective situations. Unsatisfactory operative results are mainly caused by incomplete removal of nodules, based on insufficient surgical performance of morphological and functional diagnostics, which is related to operative uniformity. An operative strategy, which ist "fitted to morphology" and "regarding function" and which we call "selective strategy", in our opinion ist highly appropriate, to avoid remnant nodules and remnant autonomy and to preserve an normal remnant, even in different position and of different size. This selective surgery ist applicable both to autonomous and non-autonomous goiter. Compared with the classic subtotal, uniform procedure the incidence of remnant nodules is reduced from about 50% to about 5 %. Remnant autonomy is almost excluded, when mistakes are avoided (about 1%). The incidence of recurrent goiter and recurrent thyrotoxicosis is lowered to under 5%--but up to now there are too few reliable long-term follow-up studies. The selective surgery strategy demands flexibility regarding operative tactics, which can be simply classified into 5 basic situations, which we relate to the operative procedure per thyroid lobe. It requires experience and competence in carefully dissecting and--when necessary--manipulating the recurrent laryngeal nerve und the parathyroid glands. Under these conditions it is followed by a comparatively low rate of complications (permanent recurrent laryngeal nerve paralysis and hypoparathyroidism under 1%, respectively). Thus, the old dilemma of thyroid surgery can be solved, which consists of radical operation with higher morbidity and lower frequency of recurrent disease on the one hand and more limited operative procedures with fewer complications but more frequent recurrencies on the other hand.
Exp Clin Endocrinol Diabetes 1998
PMID:Differentiated operative therapy of thyroid autonomy (Plummer's disease). 986 4

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder for which the gene (AIRE) has recently been identified on chromosome 21q22.3. We present the mutational analyses of a French-Canadian family with APECED, in which there are two affected siblings, as well as the response to cyclosporine A(CyA) therapy in the index patient, the eldest sibling. Haplotype analysis suggested compound heterozygozity at the AIRE locus. Direct sequencing of exon 8 revealed a previously described mutation, a 13-bp deletion (1085-1097) of maternal origin, found in the index patient, her affected sister, and her unaffected sister. A novel missense mutation characterized by a T-->G transversion at nucleotide position 398, resulting in a leu-->arg amino acid substitution (L93R), was found in exon 2. The mutation was present in the father, the brother, the index patient, and the affected sister. The presence of the mutation in the propositus was verified by cloning of PCR products from genomic DNA. The mutation destroys a PstI restriction enzyme site, as confirmed in the aforementioned patients. Screening of 50 French-Canadian controls with PstI digestion did not show destruction of the restriction-enzyme site. The index patient's phenotype was severe, manifested by classic features of the illness (adrenal insufficiency, hypoparathyroidism, candidiasis, and keratoconjunctivitis with alopecia universalis), as well as by severe exocrine pancreatic insufficiency, diabetes mellitus, hepatic inflammation, growth hormone (GH) deficiency due to lymphocytic hypophysitis, and primary ovarian failure. Oral CyA (5 mg/kg/day) was initiated at 13 yr of age. After 8 months of therapy, stimulated pancreatic lipase increased 24-fold with normalization of stool fat (from 31.5 g/day to 2.5 g/day, normal(N) < 5). There was complete resolution of her photophobia, and considerable hair regrowth was diffusely apparent. Minimal side effects were noted. Our experience supports the use of oral CyA for the treatment of severe APECED-associated exocrine pancreatic failure and keratoconjunctivitis.
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PMID:Severe autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy in an adolescent girl with a novel AIRE mutation: response to immunosuppressive therapy. 1008 59

This review reports evidence showing that the function of the respiratory muscles (RMs) is affected in endocrinopathies and emphasizes that clinicians should look for RM weakness in hormone inbalances. Although there is a potential pathophysiological mechanism for affecting RM in diabetes insipidus, hypoparathyroidism, Cushing's disease, pheochromocytoma, adrenalin deficiency or androgen disorder, no study was found in the available literature. Therefore, investigations are urgently needed in these diseases. Controversial results have been reported in acromegaly, hypopituitarism, diabetes mellitus and steroid-induced (iatrogenic) RM myopathy. Obviously, these are areas for further research. Respiratory muscle dysfunction has been well documented in thyroid disease and there is general agreement that both hypo- and hyperthyroidism are associated with reversible respiratory muscle weakness.
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PMID:Respiratory muscle function in endocrine diseases. 1039 31


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