17 alpha-hydroxylase deficiency differential diagnosis: Difference between revisions

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Latest revision as of 11:52, 23 October 2017

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]

Overview

17 alpha-hydroxylase deficiency must be differentiated from diseases that present with primary amenorrhea and female external genitalia such as pregnancy, androgen insensitivity syndrome, 3beta-hydroxysteroid dehydrogenase type 2 deficiency, gonadal dysgenesis, testicular regression syndrome, LH receptor defects, 5-alpha-reductase type 2 deficiency, mullerian agenesis, primary ovarian insufficiency, hypogonadotropic hypogonadism and turner syndrome.

Differentiating 17 alpha-hydroxylase deficiency from other Diseases

17 alpha-hydroxylase deficiency must be differentiated from diseases that present with primary amenorrhea and female external genitalia such as pregnancy, androgen insensitivity syndrome, 3beta-hydroxysteroid dehydrogenase type 2 deficiency, gonadal dysgenesis, testicular regression syndrome, LH receptor defects, 5-alpha-reductase type 2 deficiency, mullerian agenesis, primary ovarian insufficiency, hypogonadotropic hypogonadism and turner syndrome. .^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]

Differential diagnosis for primary amenorrhea:

Disease name	Cause	Differentiating
Disease name	Cause	Findings	Uterus	Breast development	Testosterone	LH	FSH	Karyotyping
17-alpha-hydroxylase deficiency	CYP17A1 gene mutation	Female external genitalia Primary amenorrhea Hypertension Absence of secondary sexual characteristics Minimal body hair	No	No	↓	Normal	Normal	XY
3 beta-hydroxysteroid dehydrogenase deficiency	HSD3B2 gene mutation	Undervirilization in 46,XY individuals due to a block in testosterone biosynthesis Mild virilization in 46,XX individuals	Yes in female	Yes in female	↓	Normal	Normal	XY and XX
Gonadal dysgenesis	Mutations in SRY, FOG2/ZFPM2, and WNT1	Female external genitalia Intact Mullerian ducts Streak gonads	Yes	Yes	↓	↑	↑	XY
Testicular regression syndrome	Loss of testicular function and tissue early in development	Female phenotype with atrophic Mullerian ducts	No	No	↓	↑	↑	XY
LH receptor defects	LH receptor gene mutation on chromosome 2	Female external genitalia Lack a uterus and fallopian tubes Epididymis and vas deferens may be present Laboratory: Unresponsiveness to hCG Normal levels of testosterone precursors (produced in the adrenal glands)	No	No	↓	↑	↑	XY
5-alpha-reductase type 2 deficiency	Autosomal recessive	Female external genitalia or ambiguous Bilateral testes and normal testosterone formation Impaired external virilization during embryogenesis Defective conversion of testosterone to DHT Testosterone:DHT ratio is >10:1	No	No	Normal male range	High to normal	High to normal	XY
Androgen insensitivity syndrome	Androgen receptor defect	Female external genitalia Resistant to testosterone	No	Yes	Normal male range	Normal	Normal	XY
Mullerian agenesis	Mutations in WNT4	Normal female genitalia Normal breast development	No	Yes	Normal female range	Normal	Normal	XX
Primary ovarian insufficiency	Genetic defects such as turner syndrome, fragile X syndrome, some other chromosomal defects	Normal female genitalia	Yes	Yes	Normal female range	↑	↑	XX
Hypogonadotropic hypogonadism	Functional, sellar masses	Normal female genitalia Delayed puberty	Yes	No	Normal female range	Low	Normal	XX
Turner syndrome	Chromosomal	Normal female external genitalia	Yes	Yes	Normal female range	↑	↑	45 XO

17 alpha-hydroxylase deficiency must be differentiated from diseases that cause ambiguous genitalia:^[9]^[10]

Disease name	Steroid status		Important clinical findings
Disease name	Increased	Decreased	Important clinical findings
17-α hydroxylase deficiency	Deoxycorticosterone Corticosterone Progesterone	Cortisol Aldosterone	Ambiguous genitalia in male Hypertension Primary amenorrhea Absence of secondary sexual characteristics Minimal body hair
Classic type of 21-hydroxylase deficiency	17-hydroxyprogesterone Progesterone Androstenedione DHEA	Aldosterone Corticosterone (salt-wasting) Cortisol (virilization)	Ambiguous genitalia in female Virilization in female Salt-wasting Hypotension and hyperkalemia
11-β hydroxylase deficiency	Deoxycorticosterone 11-Deoxy-cortisol 17-hydroxyprogesterone (mild elevation)	Cortisol Corticosterone Aldosterone	Ambiguous genitalia in female Hypertension and hypokalemia Virilization
3 beta-hydroxysteroid dehydrogenase deficiency	Dehydroepiandrosterone 17-hydroxypregnenolone Pregnenolone	Cortisol Aldosterone	Vomiting, volume depletion, hyponatremia, and hyperkalemia 46-XY infants often show undervirilization, due to a block in testosterone synthesis
Gestational hyperandrogenism	High maternal serum androgen concentrations (usually testosterone and androstenedione) If virilization is caused by exogenous hormone administration, the values may be low because the offending hormone is usually a synthetic steroid not measured in assays for testosterone or other androgens		Androgen excess in mother History of androgen containing medication consumption during pregnancy in mother Virilization in a 46,XX individual with normal female internal anatomy Causes include maternal luteoma or theca-lutein cysts, and placental aromatase enzyme deficiency

17 alpha-hydroxylase deficiency can cause low reninemic hypertension and should be differentiate from other causes of pseudohyperaldosteronism (low renin):

Pseudohyperaldosteronism causes	Disease	Etiology	Clinical features	Labratory				Treatment
Pseudohyperaldosteronism causes	Disease	Etiology	Clinical features	Elevated mineralocorticoid	Renin	Aldosterone	Other	Treatment
Endogenous causes	17 alpha-hydroxylase deficiency	Mutations in the CYP17A1 gene	Ambiguous genitalia in male Hypertension Primary amenorrhea Absence of secondary sexual characteristics Minimal body hair	Deoxycorticosterone (DOC)	↓	↓	Cortisol ↓	Corticosteroids
	11β-hydroxylase deficiency	Mutations in the CYP11B1 gene	Ambiguous genitalia in female Hypertension and hypokalemia Virilization	Deoxycorticosterone (DOC)	↓	↓	Cortisol ↓	Corticosteroids
	Apparent mineralocorticoid excess syndrome (AME)	Genetic or acquired defect of 11-HSD gene Cortisone decreases and cortisol accumulates and binds to aldosterone receptors	Severe juvenile hypertension Hypercalciuria, nephrocalcinosis, polyuria (due to hypokalemia-induced nephrogenic diabetes insipidus) Renal failure	Cortisol has mineralocorticoid effects	↓	↓	Urinary free cortisone ↓↓	Dexamethasone and/or mineralocorticoid blockers
	Liddle’s syndrome (Pseudohyperaldosteronism type 1)	Mutation of the epithelial sodium channels (ENaC) gene in the distal renal tubules	Hypertension Hypokalemia	No extra mineralocorticoid presents, and mutations in Na channels mimic aldosterone mechanism	↓	↓	Cortisol ↓	Amiloride or triamterene
	Cushing’s syndrome	Excess cortisol which saturates 11-HSD2 activity Allows cortisol to bind mineralocorticoid receptor	Rapid weight gain, particularly of the trunk and face with limbs sparing (central obesity) Proximal muscle weakness A round face often referred to as a"moon face" Excess sweating Headache	Cortisol has mineralocorticoid effects	↓	↓ if excess cortisol saturates 11-HSD2 enzyme activity ↑ in direct activation of renin angiotensin system activation by glucocorticoids	Urinary free cortisol markedly ↑↑	Pasireotide, Cabergoline, Ketoconazole, and Metyrapone Adrenalectomy
	Insensitivity to glucocorticoids (Chrousos syndrome)	Mutations in glucocorticoid receptor (GR) gene	Hypertension Adrenal hyperandrogenism	Deoxycorticosterone (DOC)	↓	↓	Cortisol	Dexamethasone
	Cortisol-secreting adrenocortical carcinoma	Multifactorial	Rapid weight gain, particularly of the trunk and face with limbs sparing (central obesity) Proximal muscle weakness A round face often referred to as a "moon face" Excess sweating Headache	Cortisol has mineralocorticoid effects	↓	↓ if excess cortisol saturates 11-HSD2 enzyme activity ↑ in direct activation of renin angiotensin system activation by glucocorticoids	Urinary free cortisol markedly ↑↑	Surgery
	Geller’s syndrome	Mutation of mineralocorticoid (MR) receptor that alters its speciﬁcity and allows progesterone to bind MR	Severe hypertension particularly during pregnancy	Progesterone has mineralocorticoid effects	↓	↓	-	Mineralocorticoid blockers
	Gordon’s syndrome (Pseudohypoaldosteronism type 2)	Mutations of at least four genes have been identiﬁed, including WNK1 and WNK4	Hypertension Hyperkalemia Normal renal function	No excess mineralocorticoid; an increased activity of the thiazide-sensitive Na–Cl co-transporter in the distal tubule	↓	Normal	Hyperkalemia	Thiazide diuretics and/or dietary sodium restriction
Exogenous causes	Corticosteroids with mineralocorticoid activity	Fludrocortisone or ﬂuoroprednisolone can mimic the action of aldosterone	Hypertension Hypokalemia	Medications such as fludrocortisone	↓	↓	-	Change the treatment
	Licorice ingestion	Glycyrrhetinic acid that binds mineralocorticoid receptor and blocks 11-HSD2 at the level of classical target tissues of aldosterone	Hypertension Hypokalemia	-	↓	↓	Moderate ↑ in urinary free cortisol	Discontinue licorice
	Grapefruit	High assumption of naringenin, a component of grapefruit, can also block 11-HSD (11β-hydroxysteroid dehydrogenase)	Hypertension	-	↓	↓	-	Discontinue grapefruit
	Estrogens	Estrogens can retain sodium and water by different mechanisms, causing: Increased blood pressure values and suppressing the renin aldosterone system, on the other side inducing secondary hyperaldosteronism due to the stimulation of the synthesis of angiotensinogen	Hypertension Headache Edema Weight gain	-	↓	↓	-	Discontinue estrogens

References

↑ Maimoun L, Philibert P, Cammas B, Audran F, Bouchard P, Fenichel P, Cartigny M, Pienkowski C, Polak M, Skordis N, Mazen I, Ocal G, Berberoglu M, Reynaud R, Baumann C, Cabrol S, Simon D, Kayemba-Kay's K, De Kerdanet M, Kurtz F, Leheup B, Heinrichs C, Tenoutasse S, Van Vliet G, Grüters A, Eunice M, Ammini AC, Hafez M, Hochberg Z, Einaudi S, Al Mawlawi H, Nuñez CJ, Servant N, Lumbroso S, Paris F, Sultan C (2011). "Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients". J. Clin. Endocrinol. Metab. 96 (2): 296–307. doi:10.1210/jc.2010-1024. PMID 21147889.
↑ Moreira AC, Leal AM, Castro M (1990). "Characterization of adrenocorticotropin secretion in a patient with 17 alpha-hydroxylase deficiency". J. Clin. Endocrinol. Metab. 71 (1): 86–91. doi:10.1210/jcem-71-1-86. PMID 2164530.
↑ Heremans GF, Moolenaar AJ, van Gelderen HH (1976). "Female phenotype in a male child due to 17-alpha-hydroxylase deficiency". Arch. Dis. Child. 51 (9): 721–3. PMC 1546244. PMID 999330.
↑ Biglieri EG (1979). "Mechanisms establishing the mineralocorticoid hormone patterns in the 17 alpha-hydroxylase deficiency syndrome". J. Steroid Biochem. 11 (1B): 653–7. PMID 226795.
↑ Saenger P (1996). "Turner's syndrome". N. Engl. J. Med. 335 (23): 1749–54. doi:10.1056/NEJM199612053352307. PMID 8929268.
↑ Bastian C, Muller JB, Lortat-Jacob S, Nihoul-Fékété C, Bignon-Topalovic J, McElreavey K, Bashamboo A, Brauner R (2015). "Genetic mutations and somatic anomalies in association with 46,XY gonadal dysgenesis". Fertil. Steril. 103 (5): 1297–304. doi:10.1016/j.fertnstert.2015.01.043. PMID 25813279.
↑ Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE (1974). "Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism". Science. 186 (4170): 1213–5. PMID 4432067.
↑ Schnitzer JJ, Donahoe PK (2001). "Surgical treatment of congenital adrenal hyperplasia". Endocrinol. Metab. Clin. North Am. 30 (1): 137–54. PMID 11344932.
↑ Hughes IA, Nihoul-Fékété C, Thomas B, Cohen-Kettenis PT (2007). "Consequences of the ESPE/LWPES guidelines for diagnosis and treatment of disorders of sex development". Best Pract. Res. Clin. Endocrinol. Metab. 21 (3): 351–65. doi:10.1016/j.beem.2007.06.003. PMID 17875484.
↑ White PC, Speiser PW (2000). "Congenital adrenal hyperplasia due to 21-hydroxylase deficiency". Endocr. Rev. 21 (3): 245–91. doi:10.1210/edrv.21.3.0398. PMID 10857554.

[pmid21147889-1] Maimoun L, Philibert P, Cammas B, Audran F, Bouchard P, Fenichel P, Cartigny M, Pienkowski C, Polak M, Skordis N, Mazen I, Ocal G, Berberoglu M, Reynaud R, Baumann C, Cabrol S, Simon D, Kayemba-Kay's K, De Kerdanet M, Kurtz F, Leheup B, Heinrichs C, Tenoutasse S, Van Vliet G, Grüters A, Eunice M, Ammini AC, Hafez M, Hochberg Z, Einaudi S, Al Mawlawi H, Nuñez CJ, Servant N, Lumbroso S, Paris F, Sultan C (2011). "Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients". J. Clin. Endocrinol. Metab. 96 (2): 296–307. doi:10.1210/jc.2010-1024. PMID 21147889.

[pmid2164530-2] Moreira AC, Leal AM, Castro M (1990). "Characterization of adrenocorticotropin secretion in a patient with 17 alpha-hydroxylase deficiency". J. Clin. Endocrinol. Metab. 71 (1): 86–91. doi:10.1210/jcem-71-1-86. PMID 2164530.

[pmid999330-3] Heremans GF, Moolenaar AJ, van Gelderen HH (1976). "Female phenotype in a male child due to 17-alpha-hydroxylase deficiency". Arch. Dis. Child. 51 (9): 721–3. PMC 1546244. PMID 999330.

[pmid226795-4] Biglieri EG (1979). "Mechanisms establishing the mineralocorticoid hormone patterns in the 17 alpha-hydroxylase deficiency syndrome". J. Steroid Biochem. 11 (1B): 653–7. PMID 226795.

[pmid8929268-5] Saenger P (1996). "Turner's syndrome". N. Engl. J. Med. 335 (23): 1749–54. doi:10.1056/NEJM199612053352307. PMID 8929268.

[pmid25813279-6] Bastian C, Muller JB, Lortat-Jacob S, Nihoul-Fékété C, Bignon-Topalovic J, McElreavey K, Bashamboo A, Brauner R (2015). "Genetic mutations and somatic anomalies in association with 46,XY gonadal dysgenesis". Fertil. Steril. 103 (5): 1297–304. doi:10.1016/j.fertnstert.2015.01.043. PMID 25813279.

[pmid4432067-7] Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE (1974). "Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism". Science. 186 (4170): 1213–5. PMID 4432067.

[pmid11344932-8] Schnitzer JJ, Donahoe PK (2001). "Surgical treatment of congenital adrenal hyperplasia". Endocrinol. Metab. Clin. North Am. 30 (1): 137–54. PMID 11344932.

[pmid17875484-9] Hughes IA, Nihoul-Fékété C, Thomas B, Cohen-Kettenis PT (2007). "Consequences of the ESPE/LWPES guidelines for diagnosis and treatment of disorders of sex development". Best Pract. Res. Clin. Endocrinol. Metab. 21 (3): 351–65. doi:10.1016/j.beem.2007.06.003. PMID 17875484.

[pmid10857554-10] White PC, Speiser PW (2000). "Congenital adrenal hyperplasia due to 21-hydroxylase deficiency". Endocr. Rev. 21 (3): 245–91. doi:10.1210/edrv.21.3.0398. PMID 10857554.

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@@ Line 4: / Line 4: @@
 {{CMG}}; {{AE}} {{MJ}}
 ==Overview==
-alpha-hydroxylase deficiency must be differentiated from diseases with [[primary amenorrhea]] and female [[external genitalia]]. Some of these causes include [[Pregnancy]], [[androgen insensitivity syndrome]], 3beta-hydroxysteroid dehydrogenase type 2 deficiency, 17-alpha-hydroxylase deficiency,  gonadal dysgenesis, [[testicular regression syndrome]],  [[LH receptor|LH receptor defects]], [[5-alpha-reductase deficiency|5-alpha-reductase type 2 deficiency]], [[mullerian agenesis]], [[Ovarian insufficiency|primary ovarian insufficiency]], [[hypogonadotropic hypogonadism]] and [[turner syndrome]].
+alpha-hydroxylase deficiency must be differentiated from diseases that present with [[primary amenorrhea]] and female [[external genitalia]] such as [[pregnancy]], [[androgen insensitivity syndrome]], 3beta-hydroxysteroid dehydrogenase type 2 deficiency, gonadal dysgenesis, [[testicular regression syndrome]],  [[LH receptor|LH receptor defects]], [[5-alpha-reductase deficiency|5-alpha-reductase type 2 deficiency]], [[mullerian agenesis]], [[Ovarian insufficiency|primary ovarian insufficiency]], [[hypogonadotropic hypogonadism]] and [[turner syndrome]].
 ==Differentiating 17 alpha-hydroxylase deficiency from other Diseases==
-alpha-hydroxylase deficiency must be differentiated from diseases with [[primary amenorrhea]]. Some of these causes include [[androgen insensitivity syndrome]], [[3 beta-hydroxysteroid dehydrogenase deficiency]],  gonadal dysgenesis, [[testicular regression syndrome]], [[LH receptor|LH receptor defects]], [[5-alpha-reductase deficiency|5-alpha-reductase type 2 deficiency]], [[mullerian agenesis]], [[Ovarian insufficiency|primary ovarian insufficiency]], [[hypogonadotropic hypogonadism]] and [[turner syndrome]].<ref name="pmid21147889">{{cite journal |vauthors=Maimoun L, Philibert P, Cammas B, Audran F, Bouchard P, Fenichel P, Cartigny M, Pienkowski C, Polak M, Skordis N, Mazen I, Ocal G, Berberoglu M, Reynaud R, Baumann C, Cabrol S, Simon D, Kayemba-Kay's K, De Kerdanet M, Kurtz F, Leheup B, Heinrichs C, Tenoutasse S, Van Vliet G, Grüters A, Eunice M, Ammini AC, Hafez M, Hochberg Z, Einaudi S, Al Mawlawi H, Nuñez CJ, Servant N, Lumbroso S, Paris F, Sultan C |title=Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients |journal=J. Clin. Endocrinol. Metab. |volume=96 |issue=2 |pages=296–307 |year=2011 |pmid=21147889 |doi=10.1210/jc.2010-1024 |url=}}</ref><ref name="pmid2164530">{{cite journal |vauthors=Moreira AC, Leal AM, Castro M |title=Characterization of adrenocorticotropin secretion in a patient with 17 alpha-hydroxylase deficiency |journal=J. Clin. Endocrinol. Metab. |volume=71 |issue=1 |pages=86–91 |year=1990 |pmid=2164530 |doi=10.1210/jcem-71-1-86 |url=}}</ref><ref name="pmid999330">{{cite journal |vauthors=Heremans GF, Moolenaar AJ, van Gelderen HH |title=Female phenotype in a male child due to 17-alpha-hydroxylase deficiency |journal=Arch. Dis. Child. |volume=51 |issue=9 |pages=721–3 |year=1976 |pmid=999330 |pmc=1546244 |doi= |url=}}</ref><ref name="pmid226795">{{cite journal |vauthors=Biglieri EG |title=Mechanisms establishing the mineralocorticoid hormone patterns in the 17 alpha-hydroxylase deficiency syndrome |journal=J. Steroid Biochem. |volume=11 |issue=1B |pages=653–7 |year=1979 |pmid=226795 |doi= |url=}}</ref><ref name="pmid8929268">{{cite journal |vauthors=Saenger P |title=Turner's syndrome |journal=N. Engl. J. Med. |volume=335 |issue=23 |pages=1749–54 |year=1996 |pmid=8929268 |doi=10.1056/NEJM199612053352307 |url=}}</ref><ref name="pmid25813279">{{cite journal |vauthors=Bastian C, Muller JB, Lortat-Jacob S, Nihoul-Fékété C, Bignon-Topalovic J, McElreavey K, Bashamboo A, Brauner R |title=Genetic mutations and somatic anomalies in association with 46,XY gonadal dysgenesis |journal=Fertil. Steril. |volume=103 |issue=5 |pages=1297–304 |year=2015 |pmid=25813279 |doi=10.1016/j.fertnstert.2015.01.043 |url=}}</ref><ref name="pmid4432067">{{cite journal |vauthors=Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE |title=Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism |journal=Science |volume=186 |issue=4170 |pages=1213–5 |year=1974 |pmid=4432067 |doi= |url=}}</ref><ref name="pmid11344932">{{cite journal |vauthors=Schnitzer JJ, Donahoe PK |title=Surgical treatment of congenital adrenal hyperplasia |journal=Endocrinol. Metab. Clin. North Am. |volume=30 |issue=1 |pages=137–54 |year=2001 |pmid=11344932 |doi= |url=}}</ref>
+alpha-hydroxylase deficiency must be differentiated from diseases that present with [[primary amenorrhea]] and female [[external genitalia]] such as [[pregnancy]], [[androgen insensitivity syndrome]], 3beta-hydroxysteroid dehydrogenase type 2 deficiency, gonadal dysgenesis, [[testicular regression syndrome]],  [[LH receptor|LH receptor defects]], [[5-alpha-reductase deficiency|5-alpha-reductase type 2 deficiency]], [[mullerian agenesis]], [[Ovarian insufficiency|primary ovarian insufficiency]], [[hypogonadotropic hypogonadism]] and [[turner syndrome]].
+.<ref name="pmid21147889">{{cite journal |vauthors=Maimoun L, Philibert P, Cammas B, Audran F, Bouchard P, Fenichel P, Cartigny M, Pienkowski C, Polak M, Skordis N, Mazen I, Ocal G, Berberoglu M, Reynaud R, Baumann C, Cabrol S, Simon D, Kayemba-Kay's K, De Kerdanet M, Kurtz F, Leheup B, Heinrichs C, Tenoutasse S, Van Vliet G, Grüters A, Eunice M, Ammini AC, Hafez M, Hochberg Z, Einaudi S, Al Mawlawi H, Nuñez CJ, Servant N, Lumbroso S, Paris F, Sultan C |title=Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients |journal=J. Clin. Endocrinol. Metab. |volume=96 |issue=2 |pages=296–307 |year=2011 |pmid=21147889 |doi=10.1210/jc.2010-1024 |url=}}</ref><ref name="pmid2164530">{{cite journal |vauthors=Moreira AC, Leal AM, Castro M |title=Characterization of adrenocorticotropin secretion in a patient with 17 alpha-hydroxylase deficiency |journal=J. Clin. Endocrinol. Metab. |volume=71 |issue=1 |pages=86–91 |year=1990 |pmid=2164530 |doi=10.1210/jcem-71-1-86 |url=}}</ref><ref name="pmid999330">{{cite journal |vauthors=Heremans GF, Moolenaar AJ, van Gelderen HH |title=Female phenotype in a male child due to 17-alpha-hydroxylase deficiency |journal=Arch. Dis. Child. |volume=51 |issue=9 |pages=721–3 |year=1976 |pmid=999330 |pmc=1546244 |doi= |url=}}</ref><ref name="pmid226795">{{cite journal |vauthors=Biglieri EG |title=Mechanisms establishing the mineralocorticoid hormone patterns in the 17 alpha-hydroxylase deficiency syndrome |journal=J. Steroid Biochem. |volume=11 |issue=1B |pages=653–7 |year=1979 |pmid=226795 |doi= |url=}}</ref><ref name="pmid8929268">{{cite journal |vauthors=Saenger P |title=Turner's syndrome |journal=N. Engl. J. Med. |volume=335 |issue=23 |pages=1749–54 |year=1996 |pmid=8929268 |doi=10.1056/NEJM199612053352307 |url=}}</ref><ref name="pmid25813279">{{cite journal |vauthors=Bastian C, Muller JB, Lortat-Jacob S, Nihoul-Fékété C, Bignon-Topalovic J, McElreavey K, Bashamboo A, Brauner R |title=Genetic mutations and somatic anomalies in association with 46,XY gonadal dysgenesis |journal=Fertil. Steril. |volume=103 |issue=5 |pages=1297–304 |year=2015 |pmid=25813279 |doi=10.1016/j.fertnstert.2015.01.043 |url=}}</ref><ref name="pmid4432067">{{cite journal |vauthors=Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE |title=Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism |journal=Science |volume=186 |issue=4170 |pages=1213–5 |year=1974 |pmid=4432067 |doi= |url=}}</ref><ref name="pmid11344932">{{cite journal |vauthors=Schnitzer JJ, Donahoe PK |title=Surgical treatment of congenital adrenal hyperplasia |journal=Endocrinol. Metab. Clin. North Am. |volume=30 |issue=1 |pages=137–54 |year=2001 |pmid=11344932 |doi= |url=}}</ref>
 === Differential diagnosis for [[primary amenorrhea]]: ===
@@ Line 24: / Line 25: @@
 ! align="center" style="background:#4479BA; color: #FFFFFF;" + |Karyotyping
 |-
-![[3 beta-hydroxysteroid dehydrogenase deficiency]]
+![[17-alpha-hydroxylase deficiency]]
 |
-* HSD3B2  [[gene]] [[mutation]]
+* [[CYP17A1|CYP17A1 gene mutation]]
 |
-* [[Undervirilization]] in 46,XY individuals due to a block in [[testosterone]] biosynthesis.
+* Female [[external genitalia]]
-* Mild [[virilization]] in 46,XX individuals
+* [[Primary amenorrhea]]
+* [[Hypertension]]
+* Absence of secondary [[sexual characteristics]]
+* Minimal [[body hair]]
 | align="center" style="padding: 5px 5px; background: " |
-Yes in [[female]]
+No
 | align="center" style="padding: 5px 5px; background: " |
-Yes in [[female]]
+No
 | align="center" style="padding: 5px 5px; background: " |
 ↓
@@ Line 41: / Line 46: @@
 Normal
 | align="center" style="padding: 5px 5px; background: " |
-[[XY]] and [[XX]]
+[[XY]]
 |-
-![[17-alpha-hydroxylase deficiency]]
+![[3 beta-hydroxysteroid dehydrogenase deficiency]]
 |
-* [[CYP17A1|CYP17A1 gene mutation]]
+* HSD3B2  [[gene]] [[mutation]]
 |
-* Female [[external genitalia]]
+* [[Undervirilization]] in 46,XY individuals due to a block in [[testosterone]] biosynthesis
+* Mild [[virilization]] in 46,XX individuals
-* [[Primary amenorrhea]]
-* [[Hypertension]]
-* Absence of secondary [[sexual characteristics]]
-* Minimal [[body hair]]
 | align="center" style="padding: 5px 5px; background: " |
-No
+Yes in [[female]]
 | align="center" style="padding: 5px 5px; background: " |
-No
+Yes in [[female]]
 | align="center" style="padding: 5px 5px; background: " |
 ↓
@@ Line 64: / Line 65: @@
 Normal
 | align="center" style="padding: 5px 5px; background: " |
-[[XY]]
+[[XY]] and [[XX]]
 |-
 ![[Gonadal dysgenesis]]
@@ Line 90: / Line 91: @@
 * Loss of [[testicular]] function and tissue early in development
 |
-* Female phenotype with atrophic [[Mullerian ducts]].
+* Female phenotype with atrophic [[Mullerian ducts]]
 | align="center" style="padding: 5px 5px; background: " |
 No
@@ Line 113: / Line 114: @@
 * Laboratory:
 ** Unresponsiveness to [[hCG]]
-** Normal levels of [[testosterone]] precursors (produced in the [[adrenal glands]]).
+** Normal levels of [[testosterone]] precursors (produced in the [[adrenal glands]])
 | align="center" style="padding: 5px 5px; background: " |
 No
@@ Line 135: / Line 136: @@
 * Impaired external [[virilization]] during [[embryogenesis]]
-* Defective conversion of [[testosterone]] to [[DHT]].
+* Defective conversion of [[testosterone]] to [[DHT]]
 * [[Testosterone]]:[[DHT]] ratio is >10:1
 | align="center" style="padding: 5px 5px; background: " |
@@ Line 210: / Line 211: @@
 * Functional, sellar masses
 |
-* Normal [[female genitalia]],
+* Normal [[female genitalia]]
 * Delayed [[puberty]]
@@ Line 254: / Line 255: @@
 ! align="center" style="background:#4479BA; color: #FFFFFF;" + |Increased
 ! align="center" style="background:#4479BA; color: #FFFFFF;" + |Decreased
+|-
+![[17 alpha-hydroxylase deficiency|17-α hydroxylase deficiency]]
+|
+* [[Deoxycorticosterone]]
+* [[Corticosterone]]
+* [[Progesterone]]
+|
+* [[Cortisol]]
+* [[Aldosterone]]
+|
+* [[Ambiguous genitalia]] in male
+* [[Hypertension]]
+* [[Primary amenorrhea]]
+* Absence of [[secondary sexual characteristics]]
+* Minimal [[body hair]]
 |-
 ![[21-hydroxylase deficiency|Classic type of 21-hydroxylase deficiency]]
@@ Line 284: / Line 303: @@
 * [[Hypertension]] and [[hypokalemia]]
 * [[Virilization]]
-|-
-![[17 alpha-hydroxylase deficiency|17-α hydroxylase deficiency]]
-|
-* [[Deoxycorticosterone]]
-* [[Corticosterone]]
-* [[Progesterone]]
-|
-* [[Cortisol]]
-* [[Aldosterone]]
-|
-* [[Ambiguous genitalia]] in male
-* [[Hypertension]]
-* [[Primary amenorrhea]]
-* Absence of [[secondary sexual characteristics]]
-* Minimal [[body hair]]
 |-
 ![[3 beta-hydroxysteroid dehydrogenase deficiency]]
@@ Line 317: / Line 318: @@
 ! Gestational [[hyperandrogenism]]
 | colspan="2" |
-* Maternal serum [[androgen]] concentrations (usually [[testosterone]] and [[androstenedione]]) are high
+* High maternal serum [[androgen]] concentrations (usually [[testosterone]] and [[androstenedione]])
 * If [[virilization]] is caused by exogenous hormone administration, the values may be low because the offending hormone is usually a synthetic [[steroid]] not measured in assays for [[testosterone]] or other [[androgens]]
 |
@@ Line 343: / Line 344: @@
 | rowspan="9" |Endogenous causes
 ![[17 alpha-hydroxylase deficiency]]
-|Mutations in the [[CYP17A1]] gene
+|
+* Mutations in the [[CYP17A1]] gene
 |
 * [[Ambiguous genitalia]] in male
@@ Line 360: / Line 362: @@
 |-
 ![[11β-hydroxylase deficiency]]
-|Mutations in the [[CYP11B1]] gene
+|
+* Mutations in the [[CYP11B1]] gene
 |
 * [[Ambiguous genitalia]] in female
@@ Line 382: / Line 385: @@
 |-
 ![[Liddle's syndrome|Liddle’s syndrome]] (Pseudohyperaldosteronism type 1)
-|Mutation of the epithelial [[sodium]] channels ([[ENaC]]) [[gene]] in the distal [[renal tubules]]
+|
+* Mutation of the epithelial [[sodium]] channels ([[ENaC]]) [[gene]] in the distal [[renal tubules]]
 |
 * [[Hypertension]]
@@ Line 395: / Line 399: @@
 ![[Cushing’s syndrome]]
 |
-* The main pathogenetic mechanism is linked to the excess
+* Excess [[cortisol]] which saturates 11-HSD2 activity
-of [[cortisol]] which saturates 11-HSD2 activity,
+* Allows [[cortisol]] to bind [[mineralocorticoid receptor]]
-* This allows [[cortisol]] to bind [[mineralocorticoid receptor]]
 |Rapid [[Obesity|weight gain]], particularly of the [[trunk]] and [[face]] with [[limbs]] sparing ([[central obesity]])
 * Proximal [[muscle weakness]]
-* A [[round face]] often referred to as a "[[moon face]]"
+* A [[round face]] often referred to as a[[moon face|"moon face]]"
 * Excess [[sweating]]
 * [[Headache]]
@@ Line 416: / Line 419: @@
 |-
 !Insensitivity to [[glucocorticoids]] (Chrousos syndrome)
-|Mutations in [[glucocorticoid receptor]] (GR) gene
+|
+* Mutations in [[glucocorticoid receptor]] (GR) gene
 |
 * [[Hypertension]]
@@ Line 428: / Line 432: @@
 |-
 ![[Cortisol]]-secreting adrenocortical [[carcinoma]]
-|Multifactorial
+|
+* Multifactorial
 |
 Rapid [[Obesity|weight gain]], particularly of the [[trunk]] and [[face]] with [[limbs]] sparing ([[central obesity]])
@@ Line 445: / Line 450: @@
 |-
 !Geller’s syndrome
-|[[Mutation]] of [[mineralocorticoid]] (MR) receptor that alters its speciﬁcity and allows [[progesterone]] to bind MR
+|
-|Severe [[hypertension]] particularly during [[pregnancy]]
+* [[Mutation]] of [[mineralocorticoid]] (MR) receptor that alters its speciﬁcity and allows [[progesterone]] to bind MR
+|
+* Severe [[hypertension]] particularly during [[pregnancy]]
 |[[Progesterone]] has [[mineralocorticoid]] effects
 |↓
 |↓
 | -
-|[[mineralocorticoid]] blockers
+|[[Mineralocorticoid]] blockers
 |-
 !Gordon’s syndrome (Pseudohypoaldosteronism type 2)
-|Mutations of at least four genes have been identiﬁed, including WNK1 and WNK4
+|
+* Mutations of at least four genes have been identiﬁed, including WNK1 and WNK4
 |
 * [[Hypertension]]
@@ Line 461: / Line 469: @@
 * Normal renal function
-|No excess mineralocorticoid; an increased activity of the thiazide-sensitive Na–Cl co-transporter in the distal tubule
+|No excess [[mineralocorticoid]]; an increased activity of the [[thiazide]]-sensitive Na–Cl co-transporter in the [[distal tubule]]
 |↓
 |Normal
-|Hyperkalemia
+|[[Hyperkalemia]]
-|thiazide diuretics and/or dietary sodium restriction
+|Thiazide diuretics and/or dietary sodium restriction
 |-
 | rowspan="4" |Exogenous causes
 !Corticosteroids with mineralocorticoid activity
-|Fludrocortisone or ﬂuoroprednisolone can mimic the action of aldosterone,
+|
+* Fludrocortisone or ﬂuoroprednisolone can mimic the action of aldosterone
 |
 * [[Hypertension]]
@@ Line 481: / Line 490: @@
 |-
 !Licorice ingestion
-|[[Glycyrrhetinic acid]] that binds [[mineralocorticoid]] receptor and blocks 11-HSD2 at the level of classical target tissues of [[aldosterone]]
+|
+* [[Glycyrrhetinic acid]] that binds [[mineralocorticoid]] receptor and blocks 11-HSD2 at the level of classical target tissues of [[aldosterone]]
 |
 * [[Hypertension]]
@@ Line 489: / Line 499: @@
 |↓
 |↓
-|Urinary free cortisol Moderate ↑
+|Moderate ↑ in urinary free cortisol
 |Discontinue licorice
 |-
 !Grapefruit
-|High assumption of naringenin, a component of grapefruit, can also block 11-HSD
+|
+* High assumption of naringenin, a component of grapefruit, can also block 11-HSD (11β-hydroxysteroid dehydrogenase)
 |
 * [[Hypertension]]
@@ Line 504: / Line 515: @@
 ![[Estrogens]]
 |[[Estrogens]] can retain [[sodium]] and water by different mechanisms, causing:
-* Increased blood pressure values and suppressing the [[renin]] [[aldosterone]] system, on the other side inducing secondary hyperaldosteronism due to the stimulation of the synthesis of [[angiotensinogen]]
+* Increased [[blood pressure]] values and suppressing the [[renin]] [[aldosterone]] system, on the other side inducing [[secondary hyperaldosteronism]] due to the stimulation of the synthesis of [[angiotensinogen]]
 |
 * [[Hypertension]]

17 alpha-hydroxylase deficiency differential diagnosis: Difference between revisions

Latest revision as of 11:52, 23 October 2017

Overview

Differentiating 17 alpha-hydroxylase deficiency from other Diseases

Differential diagnosis for primary amenorrhea:

17 alpha-hydroxylase deficiency must be differentiated from diseases that cause ambiguous genitalia:[9][10]

17 alpha-hydroxylase deficiency can cause low reninemic hypertension and should be differentiate from other causes of pseudohyperaldosteronism (low renin):

References

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17 alpha-hydroxylase deficiency must be differentiated from diseases that cause ambiguous genitalia:^[9]^[10]