11β-hydroxylase deficiency differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2] Syed Hassan A. Kazmi BSc, MD [3]

Overview

11β-hydroxylase deficiency must be differentiated from diseases that cause ambiguous genitalia such as 21-hydroxylase deficiency, 17 alpha-hydroxylase deficiency, 3 beta-hydroxysteroid dehydrogenase deficiency and Gestational hyperandrogenism.

Differentiating 11β-hydroxylase deficiency from other diseases

11-hydroxylase deficiency must be differentiated from diseases that cause ambiguous genitalia:[1][2]

Disease name Steroid status Important clinical findings
Increased Decreased
Classic type of 21-hydroxylase deficiency
11-β hydroxylase deficiency
17-α hydroxylase deficiency
3 beta-hydroxysteroid dehydrogenase deficiency
Gestational hyperandrogenism

11β-hydroxylase deficiency must be differentiated from diseases that cause virilization and hirsutism in female:[3][2][4]

Disease name Steroid status Other laboratory Important clinical findings
Non-classic type of 21-hydroxylase deficiency Increased:
  • No symptoms in infancy and male
11-β hydroxylase deficiency Increased:

Decreased:

3 beta-hydroxysteroid dehydrogenase deficiency Increased:

Decreased:

Polycystic ovary syndrome
Adrenal tumors
  • Variable levels depends on tumor type
  • Older age
  • Rapidly progressive symptoms
Ovarian virilizing tumor
  • Variable levels depends on tumor type
  • Older age
  • Rapidly progressive symptoms
Cushing's syndrome
Hyperprolactinemia

11β-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
Elevated mineralocorticoid Renin Aldosterone Other
Endogenous causes 17 alpha-hydroxylase deficiency Mutations in the CYP17A1 gene Deoxycorticosterone (DOC) Cortisol Corticosteroids
11β-hydroxylase deficiency Mutations in the CYP11B1 gene Cortisol
Apparent mineralocorticoid excess syndrome (AME) Genetic or acquired defect of 11-HSD gene 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 No extra mineralocorticoid presents, and mutations in Na channels mimic aldosterone mechanism Cortisol Amiloride or triamterene
Cushing’s syndrome
  • Due to excess cortisol which saturates 11-HSD2 activity
Rapid weight gain, particularly of the trunk and face with limbs sparing (central obesity) Cortisol has mineralocorticoid effects
  • ↓ if excess cortisol saturates 11-HSD2 enzyme activity
Urinary free cortisol markedly ↑↑
  • Adrenalectomy
Insensitivity to glucocorticoids (Chrousos syndrome) Mutations in glucocorticoid receptor (GR) gene Deoxycorticosterone (DOC) Cortisol Dexamethasone
Cortisol-secreting adrenocortical carcinoma Multifactorial

Rapid weight gain, particularly of the trunk and face with limbs sparing (central obesity)

Cortisol has mineralocorticoid effects
  • ↓ if excess cortisol saturates 11-HSD2 enzyme activity
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
  • 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 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 - Urinary free cortisol Moderate ↑ Discontinue licorice
Grapefruit High assumption of naringenin, a component of grapefruit, can also block 11-HSD - - 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
- - Discontinue estrogens

Other differentials

11- beta hydroxylase deficiency should be differentiated from other diseases causing hypertension and hypokalemia for example:[5][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]

 
 
 
 
 
 
 
 
Hypertension and Hypokalemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Plasma renin activity
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normal or High (Plasma Renin/Aldosterone ratio <10
 
 
 
 
 
 
 
 
 
 
 
Suppressed (Plasma Renin/Aldosterone ratio >20
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Renin-secreting tumors
*Diuretic use
*Renovascular hypertension
*Coarctation of aorta
*Malignant phase hypertension
 
 
 
 
 
 
 
 
 
 
 
Urinary aldosterone
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Elevated
 
Normal
 
 
Low
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conn's syndrome (Primary aldosteronism)
 
Profound K+ depletion
 
 
• 17 alpha hydroxylase deficiency
• 11 beta hydroxylase deficiency
• Liddle's syndrome
• Licorice ingestion
• Deoxycortisone producing tumor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Add Mineralocrticoid antagonist for 8 weeks
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BP response
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No BP response
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Deoxycorticosterone excess( Tumor, 17 alpha hydroxylase and 11 beta hydroxylase deficiency)
• Licorice ingestion
•Glucocorticoid resistance
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Liddle's syndrome)
Differential Diagnoses Clinical features History Findings Laboratory Findings
Headache and hypertension Nausea and vomiting Palpitations Shortness of breath Diminished pulses Fatigue Constipation Visual abnormalities Pruritis Polyuria Ambiguous genitalia
Renin-Secreting tumors

(Due to hypertension)

- - - - - - -
  • Drug-resistant hypertension
  • Chronic headaches
Coarctation of aorta - - - - -
11-beta hydroxylase deficiency ✔ (Hypertensive crisis due to increased 11-deoxycorticosterone-11-DOC) - - - - - -
17-alpha hydroxylase deficiency - - - - - - -
Uremia - - - -
Liddle's syndrome - - - - - - -

References

  1. 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.
  2. 2.0 2.1 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.
  3. Hohl A, Ronsoni MF, Oliveira M (2014). "Hirsutism: diagnosis and treatment". Arq Bras Endocrinol Metabol. 58 (2): 97–107. PMID 24830586. Vancouver style error: initials (help)
  4. Melmed, Shlomo (2016). Williams textbook of endocrinology. Philadelphia, PA: Elsevier. ISBN 978-0323297387.=
  5. 5.0 5.1 Wada N, Jin S, Hui SP, Yanagisawa K, Kurosawa T, Chiba H (2014). "[Differential diagnosis of primary aldosteronism by measurement of hybrid steroids using mass spectrometry]". Rinsho Byori (in Japanese). 62 (3): 276–82. PMID 24800505.
  6. Nielsen ML, Pareek M, Andersen I (2012). "[Liquorice-induced hypertension and hypokalaemia]". Ugeskr. Laeg. (in Danish). 174 (15): 1024–5. PMID 22487411.
  7. Chow KM, Ma RC, Szeto CC, Li PK (2012). "Polycystic kidney disease presenting with hypertension and hypokalemia". Am. J. Kidney Dis. 59 (2): 270–2. doi:10.1053/j.ajkd.2011.08.020. PMID 21962616.
  8. Sarafidis PA, Georgianos PI, Germanidis G, Giavroglou C, Nikolaidis P, Lasaridis AN, Madias NE (2012). "Hypertension and symptomatic hypokalemia in a patient with simultaneous unilateral stenoses of intrarenal arteries and mesangioproliferative glomerulonephritis". Am. J. Kidney Dis. 59 (3): 434–8. doi:10.1053/j.ajkd.2011.11.001. PMID 22154539.
  9. Khosla N, Hogan D (2006). "Mineralocorticoid hypertension and hypokalemia". Semin. Nephrol. 26 (6): 434–40. doi:10.1016/j.semnephrol.2006.10.004. PMID 17275580.
  10. Weiner ID (2013). "Endocrine and hypertensive disorders of potassium regulation: primary aldosteronism". Semin. Nephrol. 33 (3): 265–76. doi:10.1016/j.semnephrol.2013.04.007. PMC 3748390. PMID 23953804.
  11. Martell-Claros N, Abad-Cardiel M, Alvarez-Alvarez B, García-Donaire JA, Pérez CF (2015). "Primary aldosteronism and its various clinical scenarios". J. Hypertens. 33 (6): 1226–32. doi:10.1097/HJH.0000000000000546. PMID 25715092.
  12. Franse LV, Pahor M, Di Bari M, Somes GW, Cushman WC, Applegate WB (2000). "Hypokalemia associated with diuretic use and cardiovascular events in the Systolic Hypertension in the Elderly Program". Hypertension. 35 (5): 1025–30. PMID 10818057.
  13. Rossi E, Farnetti E, Nicoli D, Sazzini M, Perazzoli F, Regolisti G, Grasselli C, Santi R, Negro A, Mazzeo V, Mantero F, Luiselli D, Casali B (2011). "A clinical phenotype mimicking essential hypertension in a newly discovered family with Liddle's syndrome". Am. J. Hypertens. 24 (8): 930–5. doi:10.1038/ajh.2011.76. PMID 21525970.
  14. Ruecker B, Lang-Muritano M, Spanaus K, Welzel M, l'Allemand D, Phan-Hug F, Katschnig C, Konrad D, Holterhus PM, Schoenle EJ (2015). "The Aldosterone/Renin Ratio as a Diagnostic Tool for the Diagnosis of Primary Hypoaldosteronism in Newborns and Infants". Horm Res Paediatr. 84 (1): 43–8. doi:10.1159/000381852. PMID 25968592.
  15. Ardhanari S, Kannuswamy R, Chaudhary K, Lockette W, Whaley-Connell A (2015). "Mineralocorticoid and apparent mineralocorticoid syndromes of secondary hypertension". Adv Chronic Kidney Dis. 22 (3): 185–95. doi:10.1053/j.ackd.2015.03.002. PMID 25908467.
  16. Iglesias P, Tajada P, Martínez I, Díez JJ (2009). "[Salt-wasting congenital adrenal hyperplasia associated to hyperreninemic hyperaldosteronism]". Med Clin (Barc) (in Spanish; Castilian). 132 (2): 80–1. doi:10.1016/j.medcli.2008.09.002. PMID 19174076.
  17. Kikuta Y, Sanjo K, Nakajima K, Ashizawa I, Ojima M (1988). "Primary aldosteronism in childhood due to primary adrenal hyperplasia". Tohoku J. Exp. Med. 155 (1): 57–70. PMID 3413779.
  18. Hassan-Smith Z, Stewart PM (2011). "Inherited forms of mineralocorticoid hypertension". Curr Opin Endocrinol Diabetes Obes. 18 (3): 177–85. doi:10.1097/MED.0b013e3283469444. PMID 21494136.
  19. Bartter FC, Henkin RI, Bryan GT (1968). "Aldosterone hypersecretion in "non-salt-losing" congenital adrenal hyperplasia". J. Clin. Invest. 47 (8): 1742–52. doi:10.1172/JCI105864. PMC 297334. PMID 4299011.