The clinical manifestation of the disease is largely dependent on the type and degree of enzyme deficiency [4]. As has been indicated above, the majority of cases results from mutations of the gene encoding for 21-hydroxylase [2]. This enzyme is required for corticosteroid and aldosterone synthesis, and affected individuals present with combined deficiencies. In contrast, CYP11B1 defects causing the 11β-hydroxylase deficiency, an uncommon form of AS, are related to decreased levels of corticosteroids while the release of aldosterone is largely unaltered [3]. Accordingly, 21-hydroxylase deficiency is related to the so-called salt-losing form of AS, whereas reduced activity of 11β-hydroxylase provokes the simple virilizing form of the disease. Less common, non-classical forms of AS are associated with disturbances of sex steroid production.

About two-thirds of AS patients are classified as "salt wasters" [5]. These individuals usually present with symptoms of adrenal insufficiency shortly after birth or within the first month of life [6]. Lethargy, feeding difficulties, vomiting, and weight loss are common symptoms [7]. Further examinations may reveal dehydration, hyponatremia, and hyperkalemia. If left untreated, life-threatening metabolic decompensation and shock may occur. Moreover, female neonates typically have ambiguous genitalia comprising an enlarged clitoris, partly fused labia majora, and a common urogenital sinus instead of separated urethra and vagina [4]. Boys may show penile enlargement and hyperpigmentation.

Simple virilizing AS is less severe than salt-losing disease and may not manifest until puberty. In young women, the disease is associated with early pubarche, hirsutism, amenorrhea, and polycystic ovaries [4]. Acne is commonly observed. Simple virilizing AS may cause precocious puberty in boys, who are also more prone to develop testicular tumors [8] [9]. Adult patients are usually of short stature. In the long term, enhanced concentrations of sex steroids may cause hypogonadotropic hypogonadism [10] [11].

• Virilization

  Human Phenotype Ontology (HPO) The Human Phenotype Ontology Project, 2021 Adrenal virilism is a syndrome in which excessive adrenal androgens cause virilization. [openmd.com]

  Abstract After reviewing the causes of virilization in the newborn and grown female child, the Authors describe a case of congenital adrenal hyperplasia (S.A.G.C.) due to 21-hydroxylase deficiency in a newborn and a case of virilizing adrenal tumor in [ncbi.nlm.nih.gov]

  Clinically, the children may present in two forms: “simple virilization” or “salt wasting.” At birth, female infants appear virilized with clitoral enlargement, labial fusion, and/or urogenital sinus. [accessanesthesiology.mhmedical.com]

  The three basic clinical types are: (1) simple virilism, (2) virilism and adrenal insufficiency, and (3) virilism and hypertension. [ajronline.org]

  Virilization The clinical features of adrenogenital syndromes relate to _____ excess. Androgen _____ should be suspected in any neonate with ambiguous genitalia. [quizlet.com]

• Infertility

  It is the most important cause of infertility in adult male congenital adrenal hyperplasia. [ncbi.nlm.nih.gov]

  In women it results primarily in excess growth of facial hair, decreased frequency or cessation of menstrual periods, and infertility. [britannica.com]

  […] manifestations of AGS are quite polymorphic: phenomenon of gipokortitsizm; violation of the nature and pace of sexual development; bilateral increasing of adrenal glands; hypercorticotropinemia, sensitive to dexamethasone; oligo- or amenorrhea; anovulatory infertility [lib.iitta.gov.ua]

  […] virilizing adrenal hyperplasia exists as a phenotypic spectrum - at one end the alarming manifestation of the salt-losing form of female hermaphroditism - and at the other end the mildest form of the troublesome triad of hirsuitism, oligomenorrhea and infertility [jhu.pure.elsevier.com]

• Short Stature

  Adult patients are usually of short stature. In the long term, enhanced concentrations of sex steroids may cause hypogonadotropic hypogonadism. [symptoma.com]

  Prognosis of Congenital Adrenal Hyperplasia (Adrenogenital syndromes) The outcome is usually associated with good health, but short stature may result even with treatment. Males have normal fertility. [myvmc.com]

  Both genders can experience other symptoms such as early onset of puberty, fast body growth, and premature completion of growth leading to short stature, if they are not diagnosed and treated in early life. [rarediseases.org]

• Poor Feeding

  Poor feeding or vomiting Dehydration Electrolyte changes (abnormal levels of sodium and potassium in the blood) Abnormal heart rhythm Girls with the milder form will usually have normal female reproductive organs (ovaries, uterus, and fallopian tubes) [medlineplus.gov]

  Infants with salt-wasting CAH usually show some of the following features within the first few weeks of life: Poor feeding Listlessness and drowsiness Vomiting Diarrhea Dehydration Weight loss Low blood pressure Low blood salt (low blood sodium level) [newbornscreening.info]

• Fatigue

  Hypothyroidism signs and symptoms opposite of hyperthyroidism. fatigue, drowsy, sensitive to cold, thin nails, brittle hair, excessive weight gain, physically and mentally sluggish. an individual with myxedema can exhibit all these symptoms as well as [quizlet.com]

  Case 1 A 43-year-old woman has had fatigue, muscle weakness, facial puffiness, and easy bruising for 18 months. Physical examination reveals hypertension, round facies, muscle wasting, and numerous purpuric lesions. [ucsdlabmed.wikidot.com]

• Hypertension

  Deficiency of 17-hydroxylase leads to deficiency of estrogens and androgens and to excess deoxycorticosterone, causing sexual infantilism and hypertension. [britannica.com]

  The three basic clinical types are: (1) simple virilism, (2) virilism and adrenal insufficiency, and (3) virilism and hypertension. [ajronline.org]

  There is significant phenotypic heterogeneity, and some individuals never develop hypertension (Stowasser et al., 2000). [ncbi.nlm.nih.gov]

• Hirsutism

  A 23-year-old Japanese woman had her male-like musculature, hirsutism, the absence of breast development and marked clitoromegaly. [ncbi.nlm.nih.gov]

  Marked regression of hirsutism, advanced somatic and muscular development, deep voice and elevated urinary 17-ketosteroids followed removal of an adrenocortical adenoma. [pediatrics.aappublications.org]

  Acne subsided and hirsutism decreased one month after the initiation of cortisone therapy in addition to the subtotal adrenal resection. [koreamed.org]

  Non-classic or late-onset AGS is characterized by less pronounced hyperandrogenemia, which can appear for the first time in adult women with symptoms including hirsutism, menstrual cycle disorders, low voice pitch and acne. [medicover-genetics.com]

  In young women, the disease is associated with early pubarche, hirsutism, amenorrhea, and polycystic ovaries. Acne is commonly observed. Simple virilizing AS may cause precocious puberty in boys, who are also more prone to develop testicular tumors. [symptoma.com]

• Receding Hairline

  Other signs of the syndrome are directly due to the overproduction of androgens, and may include an increase in body hair, particularly on the face, chest, back, and other areas, receding hairline, deepening of the voice, enlargement of the clitoris; [rarediseases.org]

• Advanced Bone Age

  Advanced bone age may be diagnosed employing plain radiography. In patients with ambiguous genitalia, karyotyping should be carried out. Diagnostic imaging is recommended to assess the condition of internal reproductive organs. [symptoma.com]

• Amenorrhea

  Girls with Adrenogenital Syndrome usually have amenorrhea (absence of periods) or rare irregular periods which could be a cause of infertility. Abnormal female external genitals during Adrenogenital syndrome should be operated in childhood. [women-info.com]

  Phenotypic manifestations of AGS are quite polymorphic: phenomenon of gipokortitsizm; violation of the nature and pace of sexual development; bilateral increasing of adrenal glands; hypercorticotropinemia, sensitive to dexamethasone; oligo- or amenorrhea [lib.iitta.gov.ua]

  This 27-year-old patient, first evaluated at the age of 18, had a masculine figure, abnormal external genitalia, and primary amenorrhea. Clitoridectomy was performed. [journals.lww.com]

  In young women, the disease is associated with early pubarche, hirsutism, amenorrhea, and polycystic ovaries. Acne is commonly observed. Simple virilizing AS may cause precocious puberty in boys, who are also more prone to develop testicular tumors. [symptoma.com]

• Clitoromegaly

  For preservation of postoperative sensitivity of the glans clitoris, clitoroplasty for clitoromegaly due to adrenogenital syndrome is reported. [ncbi.nlm.nih.gov]

  […] pubic hair and rapid growth in childhood Precocious puberty or failure of puberty to occur (sexual infantilism: absent or delayed puberty) Excessive facial hair, virilization, and/or menstrual irregularity in adolescence Infertility due to anovulation Clitoromegaly [en.wikipedia.org]

• Primary Amenorrhea

  This 27-year-old patient, first evaluated at the age of 18, had a masculine figure, abnormal external genitalia, and primary amenorrhea. Clitoridectomy was performed. [journals.lww.com]

• Irregular Menstruation

  Women with CAH normally have normal health, but they are usually shorter than normal, experience irregular menstruation, may not experience menstruation at all (amenorrhea), could experience psychological problems if they do not undergo plastic surgery [docdoc.com.sg]

• Laboratory analyses of blood samples are required to determine electrolyte levels and concentrations of ACTH, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, cortisol, aldosterone, and renin. High levels of 17-hydroxyprogesterone in a randomly timed blood sample are diagnostic of 21-hydroxylase deficiency [4].
• An ACTH stimulation test may be required to identify AS not related to the 21-hydroxylase deficiency.
• Urine samples may be analyzed for their contents of adrenal hormones and metabolites like 17-ketosteroids, although these studies have been largely replaced by serum analyses.
• Advanced bone age may be diagnosed employing plain radiography.
• In patients with ambiguous genitalia, karyotyping should be carried out [12]. Diagnostic imaging is recommended to assess the condition of internal reproductive organs.
• Genetic analyses are usually not required to diagnose AS. However, corresponding results greatly facilitate genetic counseling and possibly prenatal testing in family members.

OBJECTIVE: To discuss the treatment of male adrenogenital syndrome. [ncbi.nlm.nih.gov]

Later the main treatment for Adrenogenital Syndrome will be hormonal compensation and hormonal replacement therapy – the main goal of treatment is to return hormone levels to normal. [women-info.com]

Too much sex hormone secretion can cause bones to age more rapidly, and treatment can slow this progression, if caught early. Standard Therapies Treatment Treatment of CAH varies greatly depending on the type and severity. [rarediseases.org]

Treatment[edit] Treatment of all forms of CAH may include any of: Supplying enough glucocorticoid to reduce hyperplasia and overproduction of androgens or mineralocorticoids Providing replacement mineralocorticoid and extra salt if the person is deficient [en.wikipedia.org]

Benign prognosis. (Despite atypical nuclei with pleomorphism) DDX: Leydig cell tumor: usually painless, unilateral, most lacks nuclear pleomorphism, and a third has Reinke crystalloid. [auanet.org]

Besides 21-hydroxylase deficiency, other enzyme defects may account for AS. All forms known to date are inherited as an autosomal recessive trait.

"in ways so slipshod as to breach professional standards of medical ethics"[14] and "there were no data on long-term follow-up of physical and metabolic outcomes in children exposed to dexamethasone".[15] Epidemiology[edit] The incidence varies geographically [en.wikipedia.org]

Epidemiological data: There were significantly fewer males (43%) than females (57%), and the percentage of males did not increase during the observation period. Salt wasters (SW) totalled 64.7%, whereas 35.3% had simple virilizing (SV) CAH. [thedoctorsdoctor.com]

Pathophysiology The common finding in all of these cases is an elevated adrenocorticotropic hormone (ACTH) level resulting from significantly decreased negative feedback of cortisol on ACTH secretion in the pituitary gland. [accesspediatrics.mhmedical.com]

Nonclassic adrenogenitalism YOU MIGHT ALSO LIKE... 67 terms Adrenal Cortex + MEN 25 terms Pathophysiology Chapter 40 65 terms Endocrine Disorders OTHER SETS BY THIS CREATOR 57 terms USPSTF Guidelines 132 terms Chapter 6: Musculoskeletal System 140 terms [quizlet.com]

Congenital adrenal hyperplasia, which also dates to the first half of the century, has become the preferred term to reduce ambiguity and to emphasize the underlying pathophysiology of the disorders. [en.wikipedia.org]

Adrenogenital syndrome (TTAGS) Also know as Testicular adrenal rest tumors (TARTs) Biologically, the lesions represent hyperplasia of aberrant rests rather than a true neoplastic tumor Sites Normaly descended testis and adjacent tissues Etiology and Pathophysiology [pathologyoutlines.com]

Dispareunia is prevented by total excision of the corpora cavernosa, including the crura. [ncbi.nlm.nih.gov]

Genetic Disorders and the Fetus: Diagnosis, Prevention and Treatment. John Wiley and Sons. pp. 600–. ISBN 978-1-4051-9087-9. Retrieved 14 June 2010. ^ Richard D. McAnulty, M. [en.wikipedia.org]

Hypothyroidism prevention most cases in US are not preventable because most are due to hashimoto thyroiditis. [quizlet.com]

Virilism and addisonian crises were prevented with fair success in both by cortisone and DOCA. [pediatrics.aappublications.org]

In this form of CAH21 enough enzyme is present to prevent abnormally low levels of salt in the body and to prevent an adrenal crisis. [encyclopedia.com]

The adrenal glands comprise distinct cell populations producing different hormones. In detail:

• Catecholamines are released by cells located in the adrenal medulla.
• Precursors of androgens and estrogens are synthesized by cells of the zona reticularis, the innermost layer of the adrenal cortex.
• Glucocorticoids like cortisol and corticosterone originate from the zona fasciculata.
• The outermost layer of the adrenal cortex, the zona glomerulosa, accounts for synthesis and release of aldosterone.

Adrenal hormone release is primarily controlled by superior centers like pituitary gland and hypothalamus and negative feedback loops assure the preservation of an equilibrium between demands and hormone synthesis. First and foremost, adrenal corticosteroids inhibit adrenocorticotropic hormone (ACTH) release by the pituitary gland. In the case of insufficient corticosteroid synthesis, the pituitary gland releases excess amounts of ACTH, which, in turn, stimulates the production of hormones by functional adrenal tissues [1]. Moreover, any disturbance of aldosterone production interferes with electrolyte balance. In patients suffering from adrenogenital syndrome (AS), both aldosterone and corticosteroid synthesis may be impaired, most commonly due to an inherited 21-hydroxylase deficiency [2]. Accordingly, AS is often referred to as congenital adrenal hyperplasia. The latter term, however, does not consider rare cases of acquired AS. These may be triggered by adrenal or gonadal neoplasms.

Of note, aldosterone release by zona glomerulosa cells is regulated by the renin-angiotensin system and is not part of the hypothalamic-pituitary-adrenal hormone axis [3].

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2. Yau M, Khattab A, Poppas D, Ghizzoni L, New M. Congenital Adrenal Hyperplasia: Unresolved Issues. Front Horm Res. 2016; 46:184-195.
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11. Rohayem J, Tuttelmann F, Mallidis C, Nieschlag E, Kliesch S, Zitzmann M. Restoration of fertility by gonadotropin replacement in a man with hypogonadotropic azoospermia and testicular adrenal rest tumors due to untreated simple virilizing congenital adrenal hyperplasia. Eur J Endocrinol. 2014; 170(4):K11-17.
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