Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002453 (amenorrhea)
 6,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a female patient who was diagnosed and treated at birth for a classic form of salt-losing congenital adrenal hyperplasia. At 17 years of age, against medical advice, she discontinued both mineralocorticoid and glucocorticoid replacement with no resulting clinical symptoms other than the occurrence of amenorrhoea. Steroid metabolites revealed significant abnormalities of the renin-angiotensin-aldosterone axis, as well as of pituitary-adrenal function. Analysis of our patient's DNA showed only one deleterious CYP21 mutation, an intron 2 base pair change activating a cryptic splice site. We speculate that expression of this patient's CYP21 genes may be altered by the effects of ageing or by changes in the steroid milieu.
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PMID:Phenotypic evolution of classic 21-hydroxylase deficiency. 879 46

21-hydroxylase (21-OH) deficiency accounts for the vast majority of nonclassic (NC) forms of congenital adrenal hyperplasia (CAH), and is associated with symptoms detectable either in childhood (precocious puberty) or sometimes only later in adulthood (hirsutism, acne, amenorrhea). While the severe forms of the disease responsible for salt wasting or simple virilization have been extensively studied, the NC 21-OH deficiency is less well characterized, especially in adults. We studied the 21-OH gene (CYP21) in a population of 69 unrelated hyperandrogenic subjects suspected to be homozygous or heterozygous for NC 21-OH deficiency, based on basal and adrenocorticotrophin (ACTH)-stimulated plasma 17-hydroxyprogesterone (17-OHP, 17-OHPSI) and 21-desoxycortisol (21-DOF, 21-DOFSI) levels. To identify all mutations involved, determination of the whole gene sequence, including exons, exon-intron junctions, and promoter region, was performed, followed by a study of large rearrangements and identification of compound heterozygotes. Alterations were identified in at least one allele of 55 hyperandrogenic subjects. Two NC alterations, Val282Leu and Pro454Ser, were detected in 68% and 7% of the affected alleles, respectively, whereas mutations involved in severe forms were identified in 21% of them. These results document the utility of a molecular diagnosis in hyperandrogenic women suspected of being either heterozygous or homozygous for NC 21-OH deficiency and clearly indicate the importance of genetic counseling in such a population.
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PMID:Exhaustive screening of the 21-hydroxylase gene in a population of hyperandrogenic women. 938 70

A 31-yr-old woman presenting with a history of hirsutism, amenorrhea, and infertility was previously assumed to have polycystic ovary syndrome. A new gynecological-endocrine evaluation demonstrated elevated testosterone/SHBG ratio, serum 17-hydroxyprogesterone (17-OHP), and urinary pregnantriol. She was diagnosed with non-classic congenital adrenal hyperplasia. In spite of treatment with dexamethasone and fludrocortisone in doses that suppressed adrenal androgens and 17-OHP into normal range or below, she did not ovulate. Clomiphene citrate and then FSH/hCG treatment in several cycles gave no consistent ovulation. Progesterone levels remained elevated throughout the cycles indicating a possible contribution from the adrenals. Oral glucose tolerance was normal, but the homeostasis model assessment index indicated insulin resistance. With metformin 1500 mg daily the index decreased remarkably from 2.77 to 0.96 with a few ovulations but no pregnancy occurred. Three cycles of IVF treatment thereafter were unsuccessful. Three months after the last in vitro fertilization (IVF) cycle, still on dexamethasone, fludrocortisone, and metformin, her menstruations became regular and she thereafter became pregnant. During pregnancy metformin was discontinued and dexamethasone replaced with prednisolone. Mild gestational diabetes developed and insulin was given. A healthy boy was born at term by elective Cesarean section. A CYP21- gene analysis had not indicated any of the known mutations but after gene sequencing a novel mutation was found, namely R233G. This case confirms the necessity of adding an analysis of 17-OHP when evaluating women with hirsutism and menstrual disturbances and if an elevated value is found, the advantage of performing a mutation analysis to facilitate counseling and decisions on treatment.
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PMID:A 31-year-old woman with infertility and polycystic ovaries diagnosed with non-classic congenital adrenal hyperplasia due to a novel CYP21 mutation. 1836 11

Non-classic adrenal hyperplasia (NCAH) is a disease in which a partial deficiency of the steroidogenic enzyme 21-hydroxylase produces mild to moderate hyperandrogenemia, hirsutism, polycystic ovaries, oligomenorrhea or amenorrhea, insulin resistance, male pattern baldness and subfertility. The resemblances between NCAH and polycystic ovary syndrome (PCOS) are manifest, and a relation between the two has been sought by many authors trying to identify subtle alterations in the CYP21 gene transcription end-products as the cause or a contributing cause of PCOS. On the other hand, the differences that may differentiate these two diseases have also been the focus of research by many groups, searching for clinical markers that might help to distinguish the two conditions. Insulin resistance or the polycystic ovarian morphology once thought to be hallmarks of PCOS have been proven to exist also in NCAH. Obesity, not being a diagnostic criterion of either but being very prevalent in PCOS women is also present in many NCAH women, and hence is not helpful in the distinction between the two. And if it is a fact that women with NCAH have a higher prevalence of normal ovulation and lower likelihood of having an LH/FSH ratio >2 or polycystic ovaries, in comparison to PCOS, it is also true that even in those parameters overlap does exist. Besides 17-OH-progesterone, progesterone, androstenedione and testosterone are elevated in most NCAH cases, similarly to what occurs in PCOS patients. The only exception in fact is the level of 17-OH-progesterone and progesterone that are not significantly elevated in PCOS, at least not to the levels attained in NCAH. Our recommendation, thus, is that NCAH should be excluded in all women presenting with hirsutism, oligomenorrhea and infertility. A basal follicular phase 17-hydroxyprogesterone level should be used as a screening tool, regardless of the presence of polycystic ovaries or metabolic dysfunction; in the case of doubt, an ACTH stimulation test is recommended. Levels above 10 ng/ml (30 nmol/l), either basal or after stimulation should be considered as diagnostic of NCAH, and some of those patients, particularly the ones that are planning to conceive, should be genotyped, mainly with the purpose of genetic counseling. Treatment of NCAH women normally requires the use of the same anti-androgenic weapons as PCOS but some may benefit from the administration of small doses of glucocorticoids. Curiously, some studies have demonstrated that PCOS cases too may benefit from the administration of glucocorticoids.
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PMID:Non-classic adrenal hyperplasia due to the deficiency of 21-hydroxylase and its relation to polycystic ovarian syndrome. 2400 12