Steroid hormone profiles and molecular diagnostic tools in pediatric patients with non-CAH primary adrenal insufficiency

Steroid hormone profiles and molecular diagnostic tools in pediatric patients with non-CAH primary adrenal insufficiency. Seven Menevse, T., Kendir Demirkol, Y., Gurpinar Tosun, B., Bayramoglu, E., Yildiz, M., Acar, S., Erisen Karaca, S., Orbak, Z., Onder, A., Sobu, E., Anık, A., Atay, Z., Bugrul, F., Bulus, A. D., Demir, K., Dogan, D., Emeksiz, H. C., Kirmizibekmez, H., Ozcan Murat, N., Yaman, A., Turan, S., Bereket, A., & Guran, T. The Journal of Clinical Endocrinology & Metabolism, January, 2022.

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There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology.Investigation of the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin.Paediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targetedgene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls.Eighteen pediatric endocrinology clinics.Forty-one patients (17 females, median age: 3 months, range: 0-8 years) with non-CAH PAI of unknown etiology.A genetic diagnosis was obtained in 29 (70.7%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to healthy control group, patients showed lower steroid concentrations, most significantly in cortisone, cortisol, and corticosterone (p<0.0001, area under the ROC curve: 0.96, 0.88, 0.87, respectively). Plasma cortisol<4 ng/mL, cortisone<11 ng/mL, and corticosterone<0.11 ng/mL had >95% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology.Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, while they are unlikely to point out a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, while little additional benefit is expected from WES.

@article{seven_menevse_steroid_2022,
	title = {Steroid hormone profiles and molecular diagnostic tools in pediatric patients with non-{CAH} primary adrenal insufficiency},
	issn = {0021-972X},
	url = {https://doi.org/10.1210/clinem/dgac016},
	doi = {10.1210/clinem/dgac016},
	abstract = {There is a significant challenge of attributing specific diagnoses to patients with primary adrenal insufficiency of unknown etiology other than congenital adrenal hyperplasia (non-CAH PAI). Specific diagnoses per se may guide personalized treatment or may illuminate pathophysiology.Investigation of the efficacy of steroid hormone profiles and high-throughput sequencing methods in establishing the etiology in non-CAH PAI of unknown origin.Paediatric patients with non-CAH PAI whose etiology could not be established by clinical and biochemical characteristics were enrolled. Genetic analysis was performed using targetedgene panel sequencing (TPS) and whole-exome sequencing (WES). Plasma adrenal steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls.Eighteen pediatric endocrinology clinics.Forty-one patients (17 females, median age: 3 months, range: 0-8 years) with non-CAH PAI of unknown etiology.A genetic diagnosis was obtained in 29 (70.7\%) patients by TPS. Further molecular diagnosis could not be achieved by WES. Compared to healthy control group, patients showed lower steroid concentrations, most significantly in cortisone, cortisol, and corticosterone (p\&lt;0.0001, area under the ROC curve: 0.96, 0.88, 0.87, respectively). Plasma cortisol\&lt;4 ng/mL, cortisone\&lt;11 ng/mL, and corticosterone\&lt;0.11 ng/mL had \&gt;95\% specificity to ensure the diagnosis of non-CAH PAI of unknown etiology.Steroid hormone profiles are highly sensitive for the diagnosis of non-CAH PAI of unknown etiology, while they are unlikely to point out a specific molecular diagnosis. TPS is an optimal approach in the molecular diagnosis of these patients with high efficacy, while little additional benefit is expected from WES.},
	urldate = {2022-01-20},
	journal = {The Journal of Clinical Endocrinology \& Metabolism},
	author = {Seven Menevse, Tuba and Kendir Demirkol, Yasemin and Gurpinar Tosun, Busra and Bayramoglu, Elvan and Yildiz, Melek and Acar, Sezer and Erisen Karaca, Seda and Orbak, Zerrin and Onder, Asan and Sobu, Elif and Anık, Ahmet and Atay, Zeynep and Bugrul, Fuat and Bulus, Ayse Derya and Demir, Korcan and Dogan, Durmus and Emeksiz, Hamdi Cihan and Kirmizibekmez, Heves and Ozcan Murat, Nurhan and Yaman, Akan and Turan, Serap and Bereket, Abdullah and Guran, Tulay},
	month = jan,
	year = {2022},
	keywords = {Clinical Exome},
	pages = {dgac016},
}

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