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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus and late onset congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency were observed in two female siblings aged 51 and 60 years. Not only coincidence but also causality (hyperinsulinism, glucose intolerance due to hyperandrogenism) should be considered when explaining the association of diabetes mellitus with late onset congenital adrenal hyperplasia.
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PMID:Diabetes mellitus associated with late onset congenital adrenal hyperplasia: coincidence or causality? 183 May 36

An effective treatment is now available to prevent the masculinization of female fetuses with congenital adrenal hyperplasia. Some vitamin-responsive inborn errors of metabolism can be treated prenatally by cofactor administration. Maternal phenylketonuria and maternal diabetes mellitus and the prevention of recurrent neural tube defects are also areas where therapeutic advances are being made. It may be possible to carry out chorionic villi sampling before 8 weeks menstrual age if appropriate catheters and guidance systems (probably transvaginal ultrasound) are used. First trimester diagnosis and treatment of fetal cardiac arrhythmias could prove to be very important, as they are later in pregnancy. Future possibilities for progress include gene microinjection into zygotes, classification and treatment of fresh embryos, biopsy and frozen storage of genetically at risk embryos, and therapy of preimplantation embryos by chimera formation or gene introduction by retroviruses.
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PMID:Treatment of the embryo and the fetus in the first trimester: current status and future prospects. 217 15

The changes in normal endocrine physiology which accompany pregnancy result in changes in normal ranges of hormone levels and in specific changes in the course and management of endocrine diseases. This review presents information about the various endocrine diseases and their management in pregnant adolescents. Normal pituitary function during pregnancy is described as is the effect of pregnancy on pituitary tumors such as microadenomas and prolactinomas. The effects of bromocriptine therapy in cases where tumor enlargement occurs during pregnancy are tabulated. Methods of distinguishing placental growth hormone secretion and pituitary growth hormone secretion in patients with acromegaly are presented (with the note that acromegalic patients rarely become pregnant). TSH-secreting, gonadotropin, and nonsecreting tumors are rare in this age group, and there is no evidence that they enlarge during pregnancy. The discussion of the pituitary covers chronic hypopituitarism, Sheehan's Syndrome, lymphocytic hypophysitis, and diabetes insipidus. After reviewing normal changes in thyroid physiology during pregnancy, hyperthyroidism (usually due to Graves' disease), thyroid storm, and hypothyroidism are considered. The adrenal is the next subject, with a brief description of normal changes during pregnancy followed by comments on Cushing's Syndrome, adrenal insufficiency, congenital adrenal hyperplasia, and primary hyperaldosteronism. The symptoms, diagnosis, and treatment of pheochromocytomas, which are uncommon during pregnancy but are associated with high fetal and maternal mortality, are the next topics. After a review of changes in calcium metabolism during pregnancy and hypercalcemia, this report ends with a consideration of diabetes mellitus which includes alterations in maternal carbohydrate metabolism during pregnancy, effects of diabetes on the fetus, and management of insulin-dependent diabetes mellitus during pregnancy (the most likely type to be present in adolescents).
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PMID:Endocrine problems of adolescent pregnancy. 824 53

Close liaison between paediatric and adult endocrinologists is essential for optimum care in a variety of clinical conditions. The increasingly recognized importance of growth hormone deficiency (GHD) in the adult is a further indication for maintaining long-term follow-up of patients with isolated GHD, which remains demonstrable when linear growth is complete, in addition to those patients presenting in childhood with evidence of structural pituitary disease and anterior pituitary failure. Additional areas in which liaison is desirable include congenital adrenal hyperplasia, precocious puberty, gonadal dysgenesis and other disorders of primary and secondary sexual development, thyroid dysfunction, diabetes mellitus, inherited neoplasia syndromes and those conditions, for example Cushing's syndrome, which present in childhood but are more common in adult clinical endocrine practice. In this brief review, the diagnostic spectrum of the paediatric/adult interface is described and the rationale for an integrated approach to treatment and follow-up is outlined.
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PMID:Conditions spanning paediatric and adult endocrine practice--the adult perspective. 940 61

The effects of hypercortisolemia and ACTH on the metabolism of cortisol in congenital adrenal hyperplasia, Cushing's syndrome, and exogenous ACTH and cortisol administration were investigated by analysis of the respective urinary tetrahydro-metabolites of cortisol (THF and aTHF) and cortisone (THE) by capillary gas chromatography. The results for the patients with congenital adrenal hyperplasia establish that ACTH hypersecretion in the absence of an associated marked elevation of plasma cortisol does not cause inhibition of the 11beta-OHSD enzyme. In contrast elevated plasma cortisol levels (adrenal adenoma or intravenous cortisol administration) in the presence of suppressed ACTH secretion leads to significant inhibition of the peripheral conversion of cortisol to cortisone. The latter results are equivalent to the mode of cortisol metabolism noted during clinical states of ACTH hypersecretion and hypercortisolemia (Cushing's disease, ectopic ACTH syndrome and ACTH administration). The overall findings provide convincing evidence that ACTH hypersecretion is not associated with specific in vivo inhibition of 11beta-OHSD enzyme activity.
Exp Clin Endocrinol Diabetes 1998
PMID:Effect of hypercortisolism and ACTH on the metabolism of cortisol. 951 61

Congenital adrenal hyperplasia (CAH) is an inherited recessive disorder of adrenal steroidogenesis caused by mutations in the steroid 21-hydroxylase gene (CYP21) in more than 90% of affected patients. The CYP21 gene is located within the HLA complex locus on chromosome 6 (6p21.3). During a molecular characterisation study of a group of 47 Mexican families with 21-hydroxylase deficiency, we identified nine in which the mutation or mutations found in the patient did not appear to originate from one of the parents. Through DNA fingerprinting, paternity was established in all nine families with a probability of non-paternity in the range of 10(-19) to 10(-23). Among these families, we identified one patient with exclusive paternal inheritance of all eight markers tested on chromosome 6p, despite normal maternal and paternal contributions for eight additional markers on three different chromosomes. We did not identify duplication of paternal information for markers in the 6q region, consistent with lack of expression of transient neonatal diabetes owing to genomic imprinting in this patient. Our results substantiate evidence for the existence of different genetic mechanisms involved in the expression of this recessive condition in a substantial portion (approximately 19%) of affected Mexican families. In addition to the identification of a patient with paternal uniparental disomy, the occurrence of germline mutations may explain the unusual pattern of segregation in the majority of the remaining eight families.
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PMID:Uniparental disomy for chromosome 6 results in steroid 21-hydroxylase deficiency: evidence of different genetic mechanisms involved in the production of the disease. 986 99

Idiopathic Addison's disease develops as a consequence of autoimmune destruction of steroid-producing cells in the adrenal gland. A major autoantigen is 21-hydroxylase (21OH; P450c21), which is involved in the biosynthesis of cortisol and aldosterone in the adrenal cortex. We selected a number of functionally important 21OH amino acid substitutions, found in patients with congenital adrenal hyperplasia, to study their effects on the binding of 21OH autoantibodies (21OHAb) to 21OH. The ability of 21OHAb to bind in vitro transcribed and translated wild-type 21OH and five different 21OH mutant proteins was quantified by liquid-phase assays. Sera from 21OHAb-positive patients with idiopathic Addison's disease (n = 24), Graves' disease (n = 3), and insulin-dependent diabetes mellitus (n = 1) were used. While the P105L, delE196, and G291S mutations had no effect on autoantibody binding, the P453S mutation had a considerable effect, and the R483P mutation almost completely abolished binding. Synthetic peptides corresponding to linear epitopes defined by amino acids 447-461 and 477-491 were unable to compete with wild-type 21OH for binding to autoantibodies. Direct 21OH DNA sequencing could not reveal any specific genetic variation in alleles found in 21OHAb-positive patients. We conclude that the region involving R483 plays a key role in the formation of a three-dimensional epitope in a functionally important C-terminal domain of the enzyme.
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PMID:A conformation-dependent epitope in Addison's disease and other endocrinological autoimmune diseases maps to a carboxyl-terminal functional domain of human steroid 21-hydroxylase. 997 24

The Steroidogenic Acute Regulatory (StAR) protein has been demonstrated to be an indispensable component in the acute regulation of steroid hormone biosynthesis. The StAR protein, which is rapidly synthesized in response to tropic hormone stimulation, apparently functions by mediating the transfer of the substrate for all steroid hormones, cholesterol, from the outer to the inner mitochondrial membrane where it is cleaved to pregnenolone, the first steroid formed. This transfer is the regulated and rate limiting step in steroidogenesis. Mutations in the StAR gene have been shown to be the only cause of the potentially fatal disease, lipoid congenital adrenal hyperplasia, in which the affected individual can synthesize virtually no steroids. One of the most interesting and important areas of studies on this protein encompasses the mechanism whereby the StAR protein mediates the transfer of cholesterol to the inner mitochondrial membrane. While this mechanism remains unknown at this time, this review will attempt to bring this aspect of StAR function up to date.
Exp Clin Endocrinol Diabetes 1999
PMID:An update on the mechanism of action of the Steroidogenic Acute Regulatory (StAR) protein. 1043 61

Studies which evaluate the psychosocial development and integration of adult female congenital adrenal hyperplasia (CAH) patients are rare but show that patients with the salt wasting form are significantly more virilized and more frequently single and childless. Major complaints are irregular menstruation, hirsutism, acne, obesity, deep voice, and cushingoid features. Surprisingly, a higher prevalence of psychosomatic disorders has not yet been described. Since anorexia nervosa (AN) has not yet been described in patients with CAH, we here report 4 cases of female CAH patients who developed AN during adolescence. Diagnosis of CAH was made between the age of 10 days and 3 years. Three patients suffer from the simple-virilizing form of CAH, one patient has a mild salt wasting CAH. Genital malformation varied from Prader stage II to IV. All 4 patients were compound heterozygotes for mutations/deletions of the CYP21B gene. Control of substitution therapy consisting of hydrocortisone and fluorocortisone was good. AN developed at ages 12, 13, 17, and 21 years (ICD 10 criteria for AN are BMI below 17.5 kg/m2, deliberate weight loss, body image disturbance, and primary or secondary amenorrhoea). Diagnosis of AN was established by psychiatrists and/or psychologists. All four patients showed an impressive and deliberate weight loss between 13 and 20 kg within 6 months, had primary or secondary amenorrhoea, and presented with BMI between 13 and 17.9 kg/m2. All patients received psychological treatment and recovered. However, one patient had a severe relapse of AN. Two patients are now married and one has a healthy son. These cases demonstrate that the diagnosis of CAH is compatible with the development of AN and illustrate the importance of providing treatment for CAH patients that encompasses not only medical but also psychological and social care.
Exp Clin Endocrinol Diabetes 2000
PMID:Anorexia nervosa in congenital adrenal hyperplasia: long-term follow-up of 4 cases. 1102 57

Non-classic congenital adrenal hyperplasia (NCAH) is a rare cause of hirsutism and it results from a defect in the biosynthetic pathway of cortisol and/or aldosterone. 250 microg ACTH test (SDT) is used in the diagnosis of this disease. Our aim was to investigate the responses of 11-deoxycortisol to 1microg ACTH (LDT) test in women with NCAH due to 11-beta hydroxylase (11- beta OH) deficiency and to compare them with the values obtained after SDT in the patients and in the control subjects. Eleven patients with NCAH due to 11- beta OH deficiency and 15 control subjects were involved in the study. The main complaint of the patients with NCAH was hirsutism and the diagnosis was made if the adrenal 11-deoxycortisol response to SDT exceed threefold the 95th percentile of controls. ACTH stimulation tests were carried out consecutively by using 250 microg and 1 microg intravenous ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0,30 and 60 min. Peak cortisol, 17-hydroxyprogesterone (17-OHP) and DHEAS responses were similar in LDT and SDT while 11-deoxycortisol responses to LDT (15.7 +/- 1.8 nmol/L) were significantly (p < 0.005) lower than the results obtained after SDT (76.3 +/- 21.4 nmol/L) in women with 11- beta OH deficiency. Peak cortisol and 17-OHP responses to LDT in patients and control subjects were similar. Peak 11-deoxycortisol responses to LDT were significantly (p < 0.05) higher in NCAH patients (15.7 +/- 1.8 nmol/L) than in the control subjects (6.5 +/- 0.8 nmol/L). However, in LDT, all patients had peak 11-deoxycortisol level lower than threefold the 95th percentile (25.8 nmol/L) of controls. This study represents the first demonstration that LDT gives similar cortisol but not 11-deoxycortisol responses to SDT in patients with 11- beta OH deficiency. This study also showed that LDT can not replace SDT in every clinical situation.
Exp Clin Endocrinol Diabetes 2002 Nov
PMID:The value of low dose (1 microg) ACTH stimulation test in the investigation of non-classic adrenal hyperplasia due to 11beta-hydroxylase deficiency. 1251 47


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