Glucocorticoid Resistance Syndrome: A Systematic Review of the Genotypes, Phenotypes, and Their Relationships

Wang, S; Su, W; Duan, L; Gong, F; Chen, S; Wang, L; Pan, H; Lu, L; Zhu, H

doi:10.1016/j.eprac.2025.09.199

Adrenal disease

Glucocorticoid Resistance Syndrome: A Systematic Review of the Genotypes, Phenotypes, and Their Relationships

Endocr PractPublished 30 Sep 2025Systematic review

Read the original article ↗PubMed

Cite

Authors' conclusion

This study provided the most comprehensive quantitative synthesis to date of glucocorticoid resistance syndrome, highlighting genotype-phenotype correlations and advancing understanding of its clinical and hormonal spectrum.

Study context

Population: Cases of generalized glucocorticoid resistance syndrome caused by NR3C1 mutations; 43 unrelated families, 39 distinct NR3C1 mutations33 published reports + 4 unreported cases
Participants: 71 participants

Comparison: Homozygous/compound heterozygous vs heterozygous NR3C1 mutations
Outcome: Clinical, biochemical and genetic features

Methodological detailsincludes 4 unreported cases from Peking Union Medical College Hospital

Includes 4 unreported cases from Peking Union Medical College Hospital

Pooled result

As reported in the abstract

Symptoms of androgen excess: 43.3%
Mineralocorticoid excess: 38.8%
Glucocorticoid deficiency: 14.9%
Elevated post-low-dose dexamethasone suppression test cortisol: 97.8%
Adrenal CT hyperplasia or adenomas (evaluated patients): 68.8%

Further pooled results

Age at presentation · earlier presentation with homozygous/compound heterozygous

P = 0.007

Homozygous/compound heterozygous19.9 year old

Heterozygotes35.5 year old

Outcome	Homozygous/compound heterozygous	Heterozygotes	← Lower odds with Homozygous/compound heterozygous ←→ Higher odds with Homozygous/compound heterozygous →	OR (95% CI)	P value
Hypertension/hypokalemia	90.9%	28.6%	0.050.21520	25.00 (2.95–211.61)	P < 0.001
			0.050.21520Odds ratio (log scale)

Cortisol · higher with homozygous/compound heterozygous

P = 0.002

Homozygous/compound heterozygous3.20 × ULNinterval 1.19–2.63

Heterozygotes1.40 × ULNinterval 0.59–1.20

ACTH · higher with homozygous/compound heterozygous

P = 0.001

Homozygous/compound heterozygous4.81 × ULNinterval 1.71–13.00

Heterozygotes1.04 × ULNinterval 1.00–1.76

Testosterone · higher with homozygous/compound heterozygous

P = 0.047

Homozygous/compound heterozygous1.84 × ULNinterval 1.34–2.79

Heterozygotes0.89 × ULNinterval 0.55–1.77

Sensitivity analyses and correlations

Sensitivity analyses restricted to probands confirmed these associations
Clinical manifestations correlated with elevated cortisol
Lower renin in patients with hypertension/hypokalemia

Original publication

Glucocorticoid Resistance Syndrome: A Systematic Review of the Genotypes, Phenotypes, and Their Relationships. Endocr Pract. Published 30 September 2025. doi:10.1016/j.eprac.2025.09.199

Read the original article ↗

Composed by AI from the published abstract and checked against it. How Briefs are made →