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 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital adrenal hyperplasia is a general term applied to several disorders caused by inherited recessive defects of cortisol synthesis. The most common form is 21-hydroxylase deficiency, accounting for 95% of cases. The classical forms have an incidence of one in 15,000 and the non-classical forms about one in 1,000. The classical or severe phenotype presents in the newborn period or early infancy with virilization and adrenal insufficiency, with or without salt-losing; the non-classical or mild phenotype presents in late childhood or early adulthood with signs of hyperandrogenism. This wide range of clinical expression is explained by genetic variation. Although there is a certain amount of genotype-phenotype correlation, discrepancies have been described. During the last 30 years there has been a substantial improvement in diagnosis and treatment of this disease, and patients with CAH now reach adulthood. Treatment of this condition is intended to reduce excessive corticotropin secretion and replace glucocorticoids and mineralocorticoids as physiologically as possible. Clinical management is often complicated by periods of inadequately treated hyperandrogenism, iatrogenic hypercortisolism, or both. Long-term consequences in adult life may include short stature, obesity, diminished bone mass, gonadal dysfunction with low fertility rates and psychosexual dysfunction in females. New treatment approaches are under investigation, such as the use of anti-androgens, inhibitors of estrogen production and adrenalectomy for severely resistant cases.
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PMID:Childhood-onset congenital adrenal hyperplasia: long-term outcome and optimization of therapy. 1513 1

Recent international agreement on the definitions of polycystic ovary syndrome (PCOS) has helped to clarify the clinical approach to diagnosis of PCOS. However, in the precise assessment of an individual patient it is still necessary for a detailed history of menstrual disorder (especially oligo- and amenorrhoea and anovulatory dysfunctional uterine bleeding), infertility or miscarriage, hyperandrogenism (mainly acne, hirsutism and scalp hair loss, distinguished from virilization) and obesity supplemented by the demonstration of polycystic ovaries on transvaginal ultrasound scanning. Assessment of endocrine changes in serum levels of luteinizing hormone, follicle stimulating hormone, oestradiol and prolactin, plus appropriate measures of circulating androgens (especially total and free testosterone, sex hormone binding globulin, 17 hydroxy-progesterone, dehydro-epiandrosterone sulphate and sometimes a 24-hour urinary free control) might help in further defining the abnormalities. Assessment of ovulatory status, obesity (body mass index and waist-hip ratio) and insulin resistance (oral glucose tolerance test with serum insulin levels) are also important in most cases. PCOS is a highly variable condition and investigation and management needs to be individualized. Long-term follow-up is also to a great extent dictated by the constellation of symptoms and clinical features of individual patients, but potential long-term hazards should be defined and patients warned of these.
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PMID:Current recommendations for the diagnostic evaluation and follow-up of patients presenting with symptomatic polycystic ovary syndrome. 1538 Jan 49

A 50-year-old woman, who presented with progressive androgenization, central obesity and severe hypertension, was initially suspected to have an adrenal virilizing tumor. Her serum testosterone level was in the male range (9.3-11.6 ng/ml) and was not suppressed with dexamethasone. Although no pathological abdominal or pelvic mass was detected, total hysterectomy and bilateral salpingo-oophorectomy was performed. Histopathological examination revealed a theca-cell tumor of the right ovary. Postoperatively the testosterone level returned to normal and the patient had regression of virilism. Our case illustrates that a virilizing ovarian tumor can be small and elude imaging studies, but may be detected by means of well-considered clinical management.
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PMID:Ovarian thecoma with androgenic manifestations in a postmenopausal woman. 1686 53

Both hypergonadotropic hypogonadism and myasthenia gravis can be parts of type II autoimmune polyendocrine syndrome and association between the two disorders has been reported in few cases. A 14 year old male patient with a personal history of bilateral cryptorchidism and ptosis was referred for delayed puberty. Clinical examination revealed eunuchoid habitus, small, soft testes, gynecomastia, ptosis, a myasthenic deficit score of 22.5 points and an IQ of 84 points. Decreased testosterone (0.064 ng/mL) and elevated LH (64.5 mUI/mL) were consistent with hypergonadotropic hypogonadism and karyotype was normal: 46,XY. Thyroid function, haematologic evaluation, BUN, electrolytes, and glycemia were in the normal range. Therapy consisted of anticholinesterase inhibitors, immunosuppressants, corticotherapy, testosterone; thoracoscopic thymectomy was performed showing thymic lymphoid hyperplasia on histopathologic examination. Myasthenic score improved (12.5 points), progressive virilization occurred, and a year later the patient presented with cushingoid features and obesity.
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PMID:46,XY hypergonadotropic hypogonadism and myasthenia gravis. 1730 92

The phenotypes of the polycystic ovarian syndrome (PCOS) and congenital adrenal hyperplasia syndrome (CAHS) present a number of similarities. The main symptoms of PCOS are obesity, menstrual disorders, hirsutism, and low fertility in which the pituitary and adrenal glands are spared. The CAHS is a group of various entities all characterised by different degrees of malfunction of the 21-hydroxylase (CYP21) enzyme. The consequences are a downfall of the levels of aldosterone and cortisol, and the hyperproduction of adrenal androgen hormones. It is capital to be able to recognise these 2 entities in terms of identification of high risk families because the female foetuses suffering from CAHS will undergo severe virilization of there genitals in utero, which can efficiently be prevented by a administration of corticotherapy to the mother throughout the pregnancy.
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PMID:[Polycystic ovary syndrome and congenital adrenal hyperplasia: a different entity for comparable phenotypes?]. 1772 72

Endocrine disrupting chemicals can induce malformations and impairment of reproductive function in experimental animals and may have similar effects in humans. Recently, the environmental obesogen hypothesis was proposed, suggesting that environmental chemicals contribute to the development of obesity and insulin resistance. These effects could be related to chemical interaction with nuclear receptors such as the peroxisome proliferator activated receptors (PPARs). As several testosterone-reducing drugs are PPAR activators, we aimed to examine whether four PPAR agonists were able to affect fetal testosterone production and masculinization of rats. Additionally, we wished to examine whether these chemicals affected fetal plasma levels of insulin and leptin, which play important roles in the developmental programming of the metabolic system. Pregnant Wistar rats were exposed from gestation day (GD) 7-21 to diisobutyl phthalate (DiBP), butylparaben, perfluorooctanoate, or rosiglitazone (600, 100, 20, or 1 mg/kg bw/day, respectively). Endocrine endpoints were studied in offspring at GD 19 or 21. DiBP, butylparaben and rosiglitazone reduced plasma leptin levels in male and female offspring. DiBP and rosiglitazone additionally reduced fetal plasma insulin levels. In males, DiBP reduced anogenital distance, testosterone production and testicular expression of Insl-3 and genes related to steroidogenesis. PPARalpha mRNA levels were reduced by DiBP at GD 19 in testis and liver. In females, DiBP increased anogenital distance and increased ovarian aromatase mRNA levels. This study reveals new targets for phthalates and parabens in fetal male and female rats and contributes to the increasing concern about adverse effects of human exposure to these compounds.
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PMID:Impact of diisobutyl phthalate and other PPAR agonists on steroidogenesis and plasma insulin and leptin levels in fetal rats. 1860 67

Congenital adrenal hyperplasia (CAH) due to deficiency of the enzyme 21-hydroxylase (21-OH), is distinguished in its classical and nonclassical form and is one of the most common autosomal recessive inherited diseases in humans. The classical form appears between 1:5000 and 1:15000 among the live neonates of North America and Europe, whereas the nonclassical form occurs in approximately 0.2% of the general white populations. Three alleles are associated with the 21-OH locus and can be combined in various ways to individuals who are either unaffected, heterozygote carriers, or affected with the classical or nonclassical disease. Variable signs and symptoms of hyperandrogenism are common to both types of the disorder. In women with CAH, hyperandrogenism may be present, extending from virilization of external genitalia and salt-wasting in classical (C)-CAH cases, to menstrual irregularity, obesity, short stature, infertility or subfertility and skin disorders such as hirsutism, in nonclassical (NC)-CAH cases. These clinical characteristics of NC-CAH cases do not differ unmarkedly from those shown in patients with polycystic ovary syndrome, idiopathic hirsutism, or hyperinsulinemia. The significant advances in molecular biology and gene analysis over the past 2 decades have led to the development of novel sensitive methods of DNA analysis and study, including polymerase chain reaction and Southern blot analysis. Thus it has been revealed that the 21-OH gene (CYP21A2) and its nonfunctional pseudogene (CYP21A1P) are located on chromosome 6 (6p21.3), sharing a high homology of about 98%. Inactivating mutations occur as complete gene deletions, large gene conversions and pseudogene-derived mutations.
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PMID:Congenital adrenal hyperplasia because of 21-hydroxylase deficiency. A genetic disorder of interest to obstetricians and gynecologists. 1922 39

The article critically reviews selected, clinically significant, adverse endocrine and metabolic effects associated with psychotropic drug treatments, including hyperprolactinaemia, hyponatraemia, diabetes insipidus, hypothyroidism, hyperparathyroidism, sexual dysfunction and virilization, weight loss, weight gain and metabolic syndrome (type 2 diabetes mellitus, dyslipidaemia and hypertension). Such effects are prevalent and complex, but can be managed clinically when recognized. They encourage continued critical assessment of benefits versus risks of psychotropic drugs and underscore the importance of close coordination of psychiatric and general medical care to improve long-term health of psychiatric patients. Options for management of hyperprolactinaemia include lowering doses, switching to agents such as aripiprazole, clozapine or quetiapine, managing associated osteoporosis, carefully considering the use of dopamine receptor agonists and ruling out stress, oral contraceptive use and hypothyroidism as contributing factors. Disorders of water homeostasis may include syndrome of inappropriate antidiuretic hormone (SIADH), managed by water restriction or slow replacement by hypertonic saline along with drug discontinuation. Safe management of diabetes insipidus, commonly associated with lithium, involves switching mood stabilizer and consideration of potassium-sparing diuretics. Clinical hypothyroidism may be a more useful marker than absolute cut-offs of hormone values, and may be associated with quetiapine, antidepressant and lithium use, and managed by thyroxine replacement. Hyper-parathyroidism requires comprehensive medical evaluation for occult tumours. Hypocalcaemia, along with multiple other psychiatric and medical causes, may result in decreased bone density and require evaluation and management. Strategies for reducing sexual dysfunction with psychotropics remain largely unsatisfactory. Finally, management strategies for obesity and metabolic syndrome are reviewed in light of the recent expert guidelines, including risk assessment and treatments, such as monoamine transport inhibitors, anticonvulsants and cannabinoid receptor antagonists, as well as lifestyle changes.
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PMID:Adverse endocrine and metabolic effects of psychotropic drugs: selective clinical review. 1995 39

Despite decades of different treatment algorithms, the management of congenital adrenal hyperplasia (CAH) remains clinically challenging. This is due to the inherent difficulty of suppressing adrenal androgen production using near physiological dosing of glucocorticoids (GC). As a result, alternating cycles of androgen versus GC excess can occur and may lead to short stature, obesity, virilization, and alterations in puberty. Novel therapeutic alternatives, including new and more physiological means of GC delivery, inhibitors at the level of CRH or ACTH secretion and/or action, as well as "rescue strategies", such as GnRH analogs, anti-androgens, aromatase inhibitors, and estrogen receptor blockers, are available; many of these agents, however, still require active investigation in CAH. Bilateral adrenalectomy is effective but it is also still an experimental approach. Gene therapy and stem cells, to provide functional adrenal cortical tissue, are at preclinical stage but provide exciting avenues for a potential cure for CAH.
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PMID:Alternative strategies for the treatment of classical congenital adrenal hyperplasia: pitfalls and promises. 2065 35

In 1719 Morgagni described a condition, today known as hyperostosis frontalis interna (HFI), as one sign within a triad consisting of HFI, virilism, and obesity. Today, HFI is predominantly found in older women. Although the etiology of HFI has not yet been determined precisely, the condition has been linked to metabolic disorders. HFI is reported to be rare in the archaeological record and the frequency of the condition is thought to have increased during the 19th and 20th centuries. We present preliminary results on the occurrence of HFI in the commingled human bone assemblage from "tomb VII" discovered underneath the Bronze Age royal palace of the ancient city of Qatna, Syria. A preliminary minimal number of individuals of 70 has been estimated for the as yet not fully analyzed skeletal remains. Skull fragments of nine individuals exhibit endocranial bone formations consistent with HFI. Rarity of stress indicators in the skeletons, the rich grave goods, and the burial place within the area of the Royal palace are suggestive of a high social status and an economically favorable situation of the buried individuals. Assuming that their life style included a high calorie diet in combination with little physical activity, acquired metabolic disorders may have been present in many individuals. The comparatively high number of individuals presenting HFI in the studied sample might therefore be viewed as being related to their high social status. Multiple occurrences of HFI in archaeological skeletal assemblages might serve as a proxy for social status.
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PMID:Hyperostosis frontalis interna - a marker of social status? Evidence from the Bronze-Age "high society" of Qatna, Syria. 2123 60


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