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]

  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]

  […] 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]

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

  Some men and woman have short stature, severe acne, and decreased fertility. Diagnosis Diagnostic testing Most forms of CAH can be diagnosed by measuring the amount of specific hormones in a urine sample. [encyclopedia.com]

• Pain

  All patients had resolution of pain at 3-month followup. [ncbi.nlm.nih.gov]

  Most patients present with bilateral testicular pain or masses. Gross: well-circumscribed, unencapsulated, solid and lobulated brown tumor. [auanet.org]

  Barr Volume 31, Issue 5 Objective Sonographic Measures for Characterizing Myofascial Trigger Points Associated With Cervical Pain Jeffrey J. Ballyns, Jay P. Shah, Jennifer Hammond et al. [jultrasoundmed.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]

• Hypertension

  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]

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

  An episode of hypertension occurred in each case, but was preceded and followed by periods of normal blood pressure. These episodes may have been due to accelerated release of desoxycorticosterone from implanted DOCA pellets. [pediatrics.aappublications.org]

• 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]

  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]

  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]

• 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]

• Irritability

  Fecal transplant is used to treat gut infections and is now being studied as a treatment for obesity, urinary tract infections, irritable bowel syndrome and more. [nytimes.com]

  The signs of an adrenal crisis include: Confusion Irritability Rapid heart rate Coma Periods of adrenal crisis due to too little aldosterone can occur as early as one week to one month of age. [newbornscreening.info]

• Amenorrhea

  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]

  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]

  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]

• Testicular Pain

  The only indication of surgery in stage 5 is testicular pain. Copyright © 2017 Elsevier Masson SAS. All rights reserved. [ncbi.nlm.nih.gov]

  Involvement is bilateral and frequently multiple, commonly at testicular hilus. Most patients present with bilateral testicular pain or masses. Gross: well-circumscribed, unencapsulated, solid and lobulated brown tumor. [auanet.org]

• 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]

• 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]

• 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.

• ACTH Increased

  Autosomal recessive A deficiency in cortisol results in a(n) _____ in secretion of adrenocorticotropic hormone (ACTH). Increase True or False: A deficiency in cortisol results in adrenal hypoplasia. [quizlet.com]

• Adrenocortical Hyperplasia

  hyperplasia, see there. ad·re·no·gen·i·tal syn·drome ( ă-drē'nō-jen'i-tal sin'drōm ) Generic designation for a group of disorders caused by adrenocortical hyperplasia or malignant tumors and characterized by masculinization of women, feminization of [medical-dictionary.thefreedictionary.com]

  This review concerns only the form associated with adrenocortical hyperplasia and known to be related to an inherent defect of the normal. .. [nejm.org]

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

Treatment: Treatment of this condition involves hormone replacement. [medigoo.com]

1 Congenital Adrenal Hyperplasia: Innovative Once Daily Dual Release Hydrocortisone Treatment Recruiting NCT03760835 Phase 4 Conventional Glucocorticoids (immediate release hydrocortisone, cortisone acetate, prednisone, prednisolone, dexamethasone);Dual [malacards.org]

Treatment can be stopped if prenatal testing finds that the baby is male or is an unaffected female, otherwise treatment continues until birth. [encyclopedia.com]

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]

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]

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]

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

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

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]

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].

1. Parsa AA, New MI. Steroid 21-hydroxylase deficiency in congenital adrenal hyperplasia. J Steroid Biochem Mol Biol. 2016.
2. Yau M, Khattab A, Poppas D, Ghizzoni L, New M. Congenital Adrenal Hyperplasia: Unresolved Issues. Front Horm Res. 2016; 46:184-195.
3. Peter M, Dubuis JM, Sippell WG. Disorders of the aldosterone synthase and steroid 11beta-hydroxylase deficiencies. Horm Res. 1999; 51(5):211-222.
4. Merke DP, Bornstein SR. Congenital adrenal hyperplasia. Lancet. 2005; 365(9477):2125-2136.
5. Padidela R, Hindmarsh PC. Mineralocorticoid deficiency and treatment in congenital adrenal hyperplasia. Int J Pediatr Endocrinol. 2010; 2010:656925.
6. Al-Agha AE, Ocheltree AH, Al-Tamimi MD. Association between genotype, clinical presentation, and severity of congenital adrenal hyperplasia: a review. Turk J Pediatr. 2012; 54(4):323-332.
7. Heather NL, Seneviratne SN, Webster D, et al. Newborn screening for congenital adrenal hyperplasia in New Zealand, 1994-2013. J Clin Endocrinol Metab. 2015; 100(3):1002-1008.
8. Rich MA, Keating MA, Levin HS, Kay R. Tumors of the adrenogenital syndrome: an aggressive conservative approach. J Urol. 1998; 160(5):1838-1841.
9. Claahsen-van der Grinten HL, Hermus AR, Otten BJ. Testicular adrenal rest tumours in congenital adrenal hyperplasia. Int J Pediatr Endocrinol. 2009; 2009:624823.
10. Merke DP, Poppas DP. Management of adolescents with congenital adrenal hyperplasia. Lancet Diabetes Endocrinol. 2013; 1(4):341-352.
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.
12. Taboada M, Gagliardi P. The challenge of mistaken sex assignment in an 11-year-old with virilizing CAH. Adv Exp Med Biol. 2011; 707:163-168.