Adrenal Crisis at the Onset of Congenital Adrenal Disease: Case Study

Background. Acute adrenocortical insufficiency (adrenal crisis) is a rare life-threatening condition caused by impaired cortisol synthesis or secretion in adrenal cortex. There are no descriptions of adrenal crisis onset in the first day of life in newborns with congenital adrenal disease in the literature. Case description. Newborn girl had abnormal external genitalia at birth. Pelvic ultrasound revealed uterus and ovaries, and subsequently karyotype 46,XX was confirmed. Blood test showed hypoglycemia and metabolic acidosis with respiratory decompensation, blood sodium and potassium levels were within reference ranges. Diagnosis of congenital adrenal hyperplasia with a salt-wasting crisis has been clinically established. Therapy with hydrocortisone 75 mg/m² intravenously per day was initiated, changing over oral daily administration of hydrocortisone (20-15 mg/m²) and fludrocortisone (0.1-0.75 mg/day) with positive results. Subsequently, salt-wasting form of congenital adrenal hyperplasia (CAH) was confirmed via molecular genetic study: the previously described pathogenic variant Q318W in the CYP21A2 gene in homozygous state was revealed. Conclusion. CAH, caused by gene alternations involved in cortisol biosynthesis, is the most common cause of primary adrenal insufficiency in newborns. However, there are several difficulties at this age with some of the classic symptoms (typical for adrenal crisis) interpretation: somnolence, nausea or vomiting, hypotension, hypoglycemia, hyponatremia. It leads to late disease diagnosis and is associated with higher risk of complications and death. Newborns with adrenal crisis symptoms require immediate medical help, including parenteral glucocorticoid administration.

1. Pervichnaya nadpochechnikovaya nedostatochnost’: Clinical guidelines. Association of Endocrinologists of Russia. Ministry of Health of Russian Federation; 2025. 74 p. (In Russ). Доступно по: https://www.rae-org.ru. Ссылка активна на 04.06.2025.

2. Bancos I, Hahner S, Tomlinson J, Arlt W. Diagnosis and management of adrenal insufficiency. Lancet Diabetes Endocrinol. 2015;3(3):216-226. doi: https://doi.org/10.1016/S2213- 8587(14)70142-1

3. Ovejero García MT, Saez Gallego B, Barreda Bonis AC, et al. Primary adrenal insufficiency: case study IN 5 tertiary hospitals. An Pediatr (Engl Ed). 2024;101(5):303-309. doi: https://doi.org/10.1016/j.anpede.2024.10.008

4. Rushworth RL, Torpy DJ, Stratakis CA, Falhammar H. Adrenal Crises in Children: Perspectives and Research Directions. Horm Res Paediatr. 2018;89(5):341-351. doi: https://doi.org/10.1159/000481660

5. Abrigo E, Munarin J, Bondone C, et al. Adrenal insufficiency management in the pediatric emergency setting and risk factors for adrenal crisis development. Ital J Pediatr. 2023;49(1):63. doi: https://doi.org/10.1186/s13052-023-01475-y

6. Rushworth RL, Chrisp GL, Bownes S, et al. Adrenal crises in adolescents and young adults. Endocrine. 2022;77(1):1-10. doi: https://doi.org/10.1007/s12020-022-03070-3

7. Tseretopoulou X, Ali SR, Bryce J, et al. Temporal Trends in Acute Adrenal Insufficiency Events in Children With Congenital Adrenal Hyperplasia During 2019-2022. J Endocr Soc. 2024;8(10):bvae145. doi: https://doi.org/10.1210/jendso/bvae145

8. Claahsen-van der Grinten HL, Speiser PW, Ahmed SF, et al. Congenital Adrenal Hyperplasia-Current Insights in Pathophysiology, Diagnostics, and Management. Endocr Rev. 2022;43(1):91-159. doi: https://doi.org/10.1210/endrev/bnab016

9. Capalbo D, Moracas C, Cappa M, et al. Primary Adrenal Insufficiency in Childhood: Data From a Large Nationwide Cohort. J Clin Endocrinol Metab. 2021;106(3):762-773. doi: https://doi.org/10.1210/clinem/dgaa881

10. Rushworth RL, Torpy DJ, Falhammar H. Adrenal Crisis. N Engl J Med. 2019;381(9):852-861. doi: https://doi.org/10.1056/NEJMra1807486

11. Rushworth RL, Falhammar H, Munns CF, et al. Hospital Admission Patterns in Children with CAH: Admission Rates and Adrenal Crises Decline with Age. Int J Endocrinol. 2016;2016:5748264. doi: https://doi.org/10.1155/2016/5748264

12. Hosokawa M, Ichihashi Y Sato Y, et al. Incidence and Risk Factors for Adrenal Crisis in Pediatric-onset Adrenal Insufficiency: A Prospective Study. J Clin Endocrinol Metab. 2024;109(8): e1602-e1607. doi: https://doi.org/10.1210/clinem/dgad753

13. Eyal O, Levin Y Oren A, et al. Adrenal crises in children with adrenal insufficiency: epidemiology and risk factors. Eur J Pediatr. 2019;178(5):731-738. doi: https://doi.org/10.1007/s00431-019-03348-1

14. Hahner S, Loeffler M, Bleicken B, et al. Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010;162(3):597-602. doi: https://doi.org/10.1530/EJE-09-0884

15. Ishii T, Adachi M, Takasawa K, et al. Incidence and Characteristics of Adrenal Crisis in Children Younger than 7 Years with 21-Hydroxylase Deficiency: A Nationwide Survey in Japan. Horm Res Paediatr. 2018;89(3):166-171. doi: https://doi.org/10.1159/000486393

16. Geraldes Paulino S, Porto Guerra Vasconcelos A, Ferreira S, et al. Adrenal Hypoplasia: A Diagnostic and Clinical Challenge. Cureus. 2025;17(1):e78074. doi: https://doi.org/10.7759/cureus.78074

17. Miller BS, Spencer SP Geffner ME, et al. Emergency management of adrenal insufficiency in children: advocating for treatment options in outpatient and field settings. J Investig Med. 2020;68(1):16-25. doi: https://doi.org/10.1136/jim-2019-000999

18. Reisch N, Willige M, Kohn D, et al. Frequency and causes of adrenal crises over lifetime in patients with 21-hydroxylase deficiency. Eur J Endocrinol. 2012;167(1):35-42. doi: https://doi.org/10.1530/EJE-12-0161

19. Enikeeva SR, Chugunov IS, Kareva MA, et al. Adrenal insufficiency as part of X-linked adrenoleukodystrophy. Problems of Endocrinology. 2024;70(3):83-92. (In Russ). doi: https://doi.org/10.14341/probl13335

20. Orlova EM, Kareva MA, Melikian MA, et al. Familial isolated glucocorticoid deficiency: three clinical cases and a brief overview of the current literature. Problems of Endocrinology. 2013;59(3):30-35. (In Russ).

21. Falhammar H, Frisén L, Norrby C, et al. Increased mortality in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2014;99(12):E2715-E2721. doi: https://doi.org/10.1210/jc.2014-2957

22. Allolio B. Extensive expertise in endocrinology. Adrenal crisis. Eur J Endocrinol. 2015;172(3):R115-R124. doi: https://doi.org/10.1530/EJE-14-0824

23. Tschaidse L, Wimmer S, Nowotny HF, et al. Frequency of stress dosing and adrenal crisis in paediatric and adult patients with congenital adrenal hyperplasia: a prospective study. Eur J Endocrinol. 2024;190(4):275-283. doi: https://doi.org/10.1093/ejendo/lvae023

24. Vrozhdennaya disfunktsiya kory nadpochechnikov: Clinical guidelines. Association of Endocrinologists of Russia. Ministry of Health of Russian Federation; 2025. 65 p. (In Russ). Доступно по: https://www.rae-org.ru. Ссылка активна на 04.06.2025.

25. Speiser PW, Arlt W, Auchus RJ, et al. Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(11):4043-4088. doi: https://doi.org/10.1210/jc.2018-01865

26. Order of the Ministry of Health of the Russian Federation dated April 21, 2022 No. 274н “Ob utverzhdenii Poryadka okazaniya meditsinskoi pomoshchi patsientam s vrozhdennymi i (ili) nasledstvennymi zabolevaniyami". (In Russ). Доступно по: https://base.garant.ru/404987183. Ссылка активна на 04.06.2025.

27. Merke DP Auchus RJ. Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency. N Engl J Med. 2020;383(13): 1248-1261. doi: https://doi.org/10.1056/NEJMra1909786

28. Nokoff NJ, Buchanan C, Barker JM. Clinical Manifestations and Treatment Challenges in Infants and Children With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency. J Clin Endocrinol Metab. 2025;110(Suppl 1):S13-S24. doi: https://doi.org/10.1210/clinem/dgae563