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Cortisone reductase deficiency 2(CORTRD2)

MedGen UID:
766296
Concept ID:
C3553382
Disease or Syndrome
Synonym: CORTRD2
 
Gene (location): HSD11B1 (1q32.2)
 
Monarch Initiative: MONDO:0013842
OMIM®: 614662

Definition

Cortisone reductase deficiency is a disorder in which there is a failure to regenerate the active glucocorticoid cortisol from cortisone via the enzyme 11-beta-hydroxysteroid dehydrogenase, encoded by the HSD11B1 gene. Purified 11-beta-HSD acts readily as a dehydrogenase, inactivating cortisol to cortisone; however, in the presence of a high NADPH/NADP+ ratio, generated in vivo through the activity of microsomal hexose-6-phosphate dehydrogenase (H6PD; 138090), 11-beta-HSD switches to ketoreductase activity and generates active glucocorticoid. Lack of cortisol regeneration stimulates ACTH-mediated adrenal hyperandrogenism, with males manifesting in early life with precocious pseudopuberty and females presenting later with hirsutism, oligomenorrhea, and infertility. Biochemically, CORTRD is diagnosed through the assessment of urinary cortisol and cortisone metabolites and consists of measuring the ratio of tetrahydrocortisol (THF) plus 5-alpha-THF to tetrahydrocortisone (THE), which in CORTRD patients is typically less than 0.1 (reference range, 0.7 to 1.2) (summary by Lawson et al., 2011). For a discussion of genetic heterogeneity of cortisone reductase deficiency, see CORTRD1 (604931). [from OMIM]

Clinical features

From HPO
Obesity
MedGen UID:
18127
Concept ID:
C0028754
Disease or Syndrome
Accumulation of substantial excess body fat.
Accelerated skeletal maturation
MedGen UID:
154262
Concept ID:
C0545053
Finding
An abnormally increased rate of skeletal maturation. Accelerated skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Insulin resistance
MedGen UID:
43904
Concept ID:
C0021655
Pathologic Function
Increased resistance towards insulin, that is, diminished effectiveness of insulin in reducing blood glucose levels.
Acanthosis nigricans
MedGen UID:
54
Concept ID:
C0000889
Disease or Syndrome
A dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck.
Premature pubarche
MedGen UID:
575093
Concept ID:
C0342541
Disease or Syndrome
The onset of growth of pubic hair at an earlier age than normal.
Low tetrahydrocortisol (THF) plus 5-alpha-THF/tetrahydrocortisone (THE) ratio
MedGen UID:
764632
Concept ID:
C3551718
Finding
The relative concentration of tetrahydrocortisol plus 5-alpha-tetrahydrocortisol relative to that of tetrahydrocortisone is below the lower limit of normal.
Reduced urine retrahydrocortisol plus 5-alpha-THF to tetrahydrocortisone ratio
MedGen UID:
1054488
Concept ID:
CN378428
Finding
Abnormally low ratio of tetrahydrocortisol (THF) plus 5-alpha-THF to tetrahydrocortisone (THE).

Recent clinical studies

Etiology

Zajkowska A, Rydzewska M, Wojtkielewicz K, Pomaski J, Romer T, Bossowski A
Pediatr Endocrinol Diabetes Metab 2017;23(1):42-48. doi: 10.18544/PEDM-23.01.0073. PMID: 29073307
Idkowiak J, Lavery GG, Dhir V, Barrett TG, Stewart PM, Krone N, Arlt W
Eur J Endocrinol 2011 Aug;165(2):189-207. Epub 2011 May 26 doi: 10.1530/EJE-11-0223. PMID: 21622478
Qin K, Rosenfield RL
Steroids 2011 Jan;76(1-2):135-9. Epub 2010 Nov 2 doi: 10.1016/j.steroids.2010.10.001. PMID: 21050867Free PMC Article
Phillipov G, Palermo M, Shackleton CH
J Clin Endocrinol Metab 1996 Nov;81(11):3855-60. doi: 10.1210/jcem.81.11.8923828. PMID: 8923828

Diagnosis

Zajkowska A, Rydzewska M, Wojtkielewicz K, Pomaski J, Romer T, Bossowski A
Pediatr Endocrinol Diabetes Metab 2017;23(1):42-48. doi: 10.18544/PEDM-23.01.0073. PMID: 29073307
Dhayat NA, Frey AC, Frey BM, d'Uscio CH, Vogt B, Rousson V, Dick B, Flück CE
J Steroid Biochem Mol Biol 2015 Nov;154:226-36. Epub 2015 Aug 19 doi: 10.1016/j.jsbmb.2015.07.024. PMID: 26297192
Idkowiak J, Lavery GG, Dhir V, Barrett TG, Stewart PM, Krone N, Arlt W
Eur J Endocrinol 2011 Aug;165(2):189-207. Epub 2011 May 26 doi: 10.1530/EJE-11-0223. PMID: 21622478
White PC, Rogoff D, McMillan DR
Curr Opin Pediatr 2008 Aug;20(4):453-7. doi: 10.1097/MOP.0b013e328305e439. PMID: 18622204
Małunowicz EM, Romer TE, Urban M, Bossowski A
Horm Res 2003;59(4):205-10. doi: 10.1159/000069326. PMID: 12649576

Therapy

Zajkowska A, Rydzewska M, Wojtkielewicz K, Pomaski J, Romer T, Bossowski A
Pediatr Endocrinol Diabetes Metab 2017;23(1):42-48. doi: 10.18544/PEDM-23.01.0073. PMID: 29073307
Małunowicz EM, Romer TE, Urban M, Bossowski A
Horm Res 2003;59(4):205-10. doi: 10.1159/000069326. PMID: 12649576

Prognosis

Zajkowska A, Rydzewska M, Wojtkielewicz K, Pomaski J, Romer T, Bossowski A
Pediatr Endocrinol Diabetes Metab 2017;23(1):42-48. doi: 10.18544/PEDM-23.01.0073. PMID: 29073307

Clinical prediction guides

Qin K, Rosenfield RL
Steroids 2011 Jan;76(1-2):135-9. Epub 2010 Nov 2 doi: 10.1016/j.steroids.2010.10.001. PMID: 21050867Free PMC Article
Smit P, Dekker MJ, de Jong FJ, van den Beld AW, Koper JW, Pols HA, Brinkmann AO, de Jong FH, Breteler MM, Lamberts SW
J Clin Endocrinol Metab 2007 Jan;92(1):359-62. Epub 2006 Oct 24 doi: 10.1210/jc.2006-1349. PMID: 17062770
Draper N, Stewart PM
J Endocrinol 2005 Aug;186(2):251-71. doi: 10.1677/joe.1.06019. PMID: 16079253
San Millán JL, Botella-Carretero JI, Alvarez-Blasco F, Luque-Ramírez M, Sancho J, Moghetti P, Escobar-Morreale HF
J Clin Endocrinol Metab 2005 Jul;90(7):4157-62. Epub 2005 Apr 12 doi: 10.1210/jc.2004-1523. PMID: 15827106

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