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Glucocorticoid resistance(GCCR)

MedGen UID:
333960
Concept ID:
C1841972
Disease or Syndrome
Synonyms: Cortisol resistance from glucocorticoid receptor defect; Gccr deficiency; Gcr deficiency; Glucocorticoid receptor deficiency; Glucocorticoid resistance, generalized
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): NR3C1 (5q31.3)
 
Monarch Initiative: MONDO:0014421
OMIM®: 615962
Orphanet: ORPHA786

Definition

Generalized glucocorticoid resistance is an autosomal dominant disease characterized by increased plasma cortisol concentration and high urinary free cortisol, resistance to adrenal suppression by dexamethasone, and the absence of clinical stigmata of Cushing syndrome. The clinical expression of the disease is variable. Common features include hypoglycemia, hypertension, and metabolic alkalosis. In females, overproduction of adrenal androgens has been associated with infertility, male-pattern baldness, hirsutism, and menstrual irregularities. Other features include chronic fatigue and profound anxiety (summary by Chrousos et al., 1983; Donner et al., 2013). [from OMIM]

Clinical features

From HPO
Fatigue
MedGen UID:
41971
Concept ID:
C0015672
Sign or Symptom
A subjective feeling of tiredness characterized by a lack of energy and motivation.
Infertility disorder
MedGen UID:
43876
Concept ID:
C0021359
Finding
Inability to conceive for at least one year after trying and having unprotected sex. Causes of female infertility include endometriosis, fallopian tubes obstruction, and polycystic ovary syndrome. Causes of male infertility include abnormal sperm production or function, blockage of the epididymis, blockage of the ejaculatory ducts, hypospadias, exposure to pesticides, and health related issues.
Irregular menstruation
MedGen UID:
56379
Concept ID:
C0156404
Finding
Abnormally high variation in the amount of time between periods.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Metabolic alkalosis
MedGen UID:
113134
Concept ID:
C0220983
Pathologic Function
Metabolic alkalosis is defined as a disease state where the pH is elevated to greater than 7.45 secondary to some metabolic process.
Hirsutism
MedGen UID:
42461
Concept ID:
C0019572
Disease or Syndrome
Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair).
Increased circulating androstenedione concentration
MedGen UID:
1386637
Concept ID:
C0240995
Finding
Increased concentration of androstenedione in the blood circulation.
Increased circulating ACTH level
MedGen UID:
867375
Concept ID:
C4021740
Finding
An abnormal increased in the concentration of corticotropin, also known as adrenocorticotropic hormone (ACTH), in the blood.
Increased circulating cortisol level
MedGen UID:
871175
Concept ID:
C4025651
Finding
Overproduction of the hormone of cortisol by the adrenal cortex, resulting in a characteristic combination of clinical symptoms termed Cushing syndrome, with truncal obesity, a round, full face, striae atrophicae and acne, muscle weakness, and other features.
Increased serum testosterone level
MedGen UID:
892551
Concept ID:
C4072885
Finding
An elevated circulating testosterone level in the blood.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGlucocorticoid resistance

Professional guidelines

PubMed

Matsumura Y
J Int Med Res 2023 Jun;51(6):3000605231175746. doi: 10.1177/03000605231175746. PMID: 37296513Free PMC Article
Zuo X, Guo X, Gu Y, Zheng H, Zhou Z, Wang X, Jiang S, Wang G, Xu C, Wang F
Int J Mol Sci 2022 Nov 20;23(22) doi: 10.3390/ijms232214427. PMID: 36430906Free PMC Article
Ghiciuc CM, Vicovan AG, Stafie CS, Antoniu SA, Postolache P
Mar Drugs 2021 Oct 20;19(11) doi: 10.3390/md19110586. PMID: 34822457Free PMC Article

Recent clinical studies

Etiology

Sarno J, Domizi P, Liu Y, Merchant M, Pedersen CB, Jedoui D, Jager A, Nolan GP, Gaipa G, Bendall SC, Bava FA, Davis KL
Nat Commun 2023 May 22;14(1):2935. doi: 10.1038/s41467-023-38456-y. PMID: 37217509Free PMC Article
Palumbo ML, Prochnik A, Wald MR, Genaro AM
Clin Ther 2020 Jun;42(6):993-1006. Epub 2020 Mar 26 doi: 10.1016/j.clinthera.2020.03.002. PMID: 32224031
Vitellius G, Trabado S, Bouligand J, Delemer B, Lombès M
Ann Endocrinol (Paris) 2018 Jun;79(3):98-106. Epub 2018 Apr 20 doi: 10.1016/j.ando.2018.03.001. PMID: 29685454
Vandewalle J, Luypaert A, De Bosscher K, Libert C
Trends Endocrinol Metab 2018 Jan;29(1):42-54. Epub 2017 Nov 20 doi: 10.1016/j.tem.2017.10.010. PMID: 29162310
Xia N, Li H
Antioxid Redox Signal 2018 Mar 20;28(9):837-851. Epub 2017 Oct 23 doi: 10.1089/ars.2017.7312. PMID: 28903579Free PMC Article

Diagnosis

Sarno J, Domizi P, Liu Y, Merchant M, Pedersen CB, Jedoui D, Jager A, Nolan GP, Gaipa G, Bendall SC, Bava FA, Davis KL
Nat Commun 2023 May 22;14(1):2935. doi: 10.1038/s41467-023-38456-y. PMID: 37217509Free PMC Article
Huang H, Wang W
Eur J Clin Invest 2023 Feb;53(2):e13901. Epub 2022 Nov 23 doi: 10.1111/eci.13901. PMID: 36346177
Martins CS, de Castro M
Mol Cell Endocrinol 2021 Jun 15;530:111277. Epub 2021 Apr 14 doi: 10.1016/j.mce.2021.111277. PMID: 33864884
Athimulam S, Lazik N, Bancos I
Endocrinol Metab Clin North Am 2019 Dec;48(4):701-715. Epub 2019 Sep 25 doi: 10.1016/j.ecl.2019.08.003. PMID: 31655771
van Rossum EFC, van den Akker ELT
Endocr Dev 2011;20:127-136. Epub 2010 Dec 16 doi: 10.1159/000321234. PMID: 21164266

Therapy

Khantakova JN, Mutovina A, Ayriyants KA, Bondar NP
Cells 2023 Nov 30;12(23) doi: 10.3390/cells12232749. PMID: 38067176Free PMC Article
Athimulam S, Lazik N, Bancos I
Endocrinol Metab Clin North Am 2019 Dec;48(4):701-715. Epub 2019 Sep 25 doi: 10.1016/j.ecl.2019.08.003. PMID: 31655771
Timmermans S, Souffriau J, Libert C
Front Immunol 2019;10:1545. Epub 2019 Jul 4 doi: 10.3389/fimmu.2019.01545. PMID: 31333672Free PMC Article
Vandewalle J, Luypaert A, De Bosscher K, Libert C
Trends Endocrinol Metab 2018 Jan;29(1):42-54. Epub 2017 Nov 20 doi: 10.1016/j.tem.2017.10.010. PMID: 29162310
Barnes PJ
Handb Exp Pharmacol 2017;237:93-115. doi: 10.1007/164_2016_62. PMID: 27796513

Prognosis

Baumer Y, Pita MA, Baez AS, Ortiz-Whittingham LR, Cintron MA, Rose RR, Gray VC, Osei Baah F, Powell-Wiley TM
Clin Sci (Lond) 2023 Mar 31;137(6):469-494. doi: 10.1042/CS20220304. PMID: 36960908Free PMC Article
Allam VSRR, Pavlidis S, Liu G, Kermani NZ, Simpson J, To J, Donnelly S, Guo YK, Hansbro PM, Phipps S, Morand EF, Djukanovic R, Sterk P, Chung KF, Adcock I, Harris J, Sukkar MB
Thorax 2023 Jul;78(7):661-673. Epub 2022 Nov 7 doi: 10.1136/thorax-2021-218555. PMID: 36344253
Lambrou GI, Adamaki M, Hatziagapiou K, Vlahopoulos S
Curr Drug Res Rev 2020;12(2):131-149. doi: 10.2174/2589977512666200220122650. PMID: 32077838
Wang H, Gou X, Jiang T, Ouyang J
J Cancer Res Clin Oncol 2017 Jun;143(6):1005-1011. Epub 2017 Mar 12 doi: 10.1007/s00432-017-2388-4. PMID: 28286901
Loke TK, Sousa AR, Corrigan CJ, Lee TH
Curr Allergy Asthma Rep 2002 Mar;2(2):144-50. doi: 10.1007/s11882-002-0009-y. PMID: 11892094

Clinical prediction guides

Ostrovskyy MM, Shvets KV, Kulynych-Miskiv MO, Savelikhina IO, Varunkiv OI, Korzh GZ, Zuban AB
Wiad Lek 2023;76(9):1949-1954. doi: 10.36740/WLek202309108. PMID: 37898930
Allam VSRR, Pavlidis S, Liu G, Kermani NZ, Simpson J, To J, Donnelly S, Guo YK, Hansbro PM, Phipps S, Morand EF, Djukanovic R, Sterk P, Chung KF, Adcock I, Harris J, Sukkar MB
Thorax 2023 Jul;78(7):661-673. Epub 2022 Nov 7 doi: 10.1136/thorax-2021-218555. PMID: 36344253
Methkal A, Kuts L
Wiad Lek 2022;75(9 pt 1):2076-2080. doi: 10.36740/WLek202209105. PMID: 36256931
Martins CS, de Castro M
Mol Cell Endocrinol 2021 Jun 15;530:111277. Epub 2021 Apr 14 doi: 10.1016/j.mce.2021.111277. PMID: 33864884
Wang H, Gou X, Jiang T, Ouyang J
J Cancer Res Clin Oncol 2017 Jun;143(6):1005-1011. Epub 2017 Mar 12 doi: 10.1007/s00432-017-2388-4. PMID: 28286901

Recent systematic reviews

Rothe N, Steffen J, Penz M, Kirschbaum C, Walther A
Neurosci Biobehav Rev 2020 Jul;114:232-270. Epub 2020 Feb 20 doi: 10.1016/j.neubiorev.2020.02.024. PMID: 32088345
Nicolaides NC, Charmandari E
Eur J Clin Invest 2015 May;45(5):504-14. Epub 2015 Mar 23 doi: 10.1111/eci.12426. PMID: 25715669
Charmandari E
Horm Res Paediatr 2011;76(3):145-55. Epub 2011 Sep 6 doi: 10.1159/000330759. PMID: 21912096
Charmandari E, Kino T, Ichijo T, Chrousos GP
J Clin Endocrinol Metab 2008 May;93(5):1563-72. Epub 2008 Mar 4 doi: 10.1210/jc.2008-0040. PMID: 18319312Free PMC Article

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