Difficulty with differential diagnosis on adrenal lesions in congenital adrenal cortex dysfunction: a series of clinical cases
A. Chevais,
N. V. Tarbaeva,
Y. Y. Golubkina,
M. M. Gadzhimuradova,
K. V. Ivashchenko,
D. O. Ladygina,
M. V. Vorontsova,
O. B. Bezlepkina,
G. A. Melnichenko,
N. G. Mokrysheva https://doi.org/10.14341/probl13564
Abstract
Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive disorders characterized by defects in enzymes critical for steroidogenesis, with 21-hydroxylase deficiency due to mutations in the CYP21A2 gene being the most prevalent form.
Since the introduction of replacement therapy and neonatal screening programs in the 1950s, there has been a significant increase in survival rates among newborns diagnosed with CAH. However, despite these advancements, mortality associated with this condition remains disproportionately high. Achieving optimal therapeutic compensation through medication remains a complex challenge, contributing to a range of long-term complications. These complications stem from both the underlying disease and its treatment, impacting key physiological functions, including metabolism, growth and development, cardiovascular health, and fertility. These multifaceted outcomes underscore the need for ongoing research and the refinement of therapeutic approaches to better manage this intricate condition. This article presents a series of four clinical cases of CAH characterized by the absence of sustained compensation for glucoand mineralocorticoid deficiencies. These cases were further complicated by the development of large adrenal masses and ectopic testicular adrenal rest tissue (TART), emphasizing the challenges in achieving long-term disease management.
About the Authors
A. Chevais
Endocrine Research Centre
Russian Federation
Competing Interests:
Russian Federation
Anastassia Chevais, MD, PhD
Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
N. V. Tarbaeva
Endocrine Research Centre
Russian Federation
Competing Interests:
Russian Federation
Natalya V. Tarbaeva, MD, PhD
Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
Y. Y. Golubkina
Endocrine Research Centre
Russian Federation
Competing Interests:
Russian Federation
Yulia Y. Golubkina, MD
Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
M. M. Gadzhimuradova
Endocrine Research Centre
Russian Federation
Competing Interests:
Russian Federation
Mansurat M. Gadzhimuradova, MD
Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
K. V. Ivashchenko
Endocrine Research Centre
Russian Federation
Competing Interests:
Russian Federation
Kseniya V. Ivashchenko, MD
Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
D. O. Ladygina
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Competing Interests:
Russian Federation
Daria O. Ladygina, MD, PhD
Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
M. V. Vorontsova
Endocrine Research Centre; Lomonosov Moscow State University
Russian Federation
Competing Interests:
Russian Federation
Maria V. Vorontsova
Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
O. B. Bezlepkina
Endocrine Research Centre
Russian Federation
Competing Interests:
Russian Federation
Olga B. Bezlepkina, MD, PhD, Professor
Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
G. A. Melnichenko
Endocrine Research Centre
Russian Federation
Competing Interests:
Russian Federation
Galina A. Melnichenko, MD, PhD, Prof, acad.
Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
N. G. Mokrysheva
Endocrine Research Centre
Russian Federation
Competing Interests:
Russian Federation
Natalia G. Mokrysheva, MD, PhD, Prof, acad.
Moscow
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
References
1. Auer MK, Nordenström A, Lajic S, et al. Congenital adrenal hyperplasia. Lancet. 2023;401(10372):227-244. doi: https://doi.ru/10.1016/S0140-6736(22)01330-7
2. Speiser PW, Arlt W, Auchus RJ, et al. Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline [published correction appears in Journal of Clinical Endocrinology & Metabolism 2019 Jan 1;104(1):39-40. doi: 10.1210/jc.2018-02371]. Journal of Clinical Endocrinology & Metabolism. 2018;103(11):4043-4088. doi: https://doi.ru/10.1210/jc.2018-01865
3. Kareva MV. Vrozhdennaya disfunkciya kory nadpochechnikov u detej: epidemiologiya, geneticheskaya osnova, personalizirovannyj podhod k diagnostike i lecheniyu, monitoring somaticheskogo i reproduktivnogo zdorovya. [dissertation] Moscow; 2019. (in Russ.) Доступно по: https://www.endocrincentr.ru/sites/default/files/specialists/science/dissertation/kareva_doctorskaya_ final_26_11_18.pdf
4. Mokrysheva NG, Melnichenko GA, Adamyan LV, et al. Russian clinical practice guidelines «congenital adrenal hyperplasia». Obesity and metabolism. 2021;18(3):345-382. (In Russ.). doi: https://doi.org/10.14341/omet12787
5. Speiser PW, Arlt W, Auchus RJ, et al. Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline [published correction appears in J Clin Endocrinol Metab. 2019 Jan 1;104(1):39- 40. doi: 10.1210/jc.2018-02371]. J Clin Endocrinol Metab. 2018;103(11):4043-4088. doi: https://doi.ru/10.1210/jc.2018-01865
6. Shifman BM, Dzeranova LK, Pigarova EA, et al. Late consequences of classic congenital adrenal hyperplasia and its long-term poor control in men (case report and literature review). Obesity and metabolism. 2019;16(4):90-102. (In Russ.). doi: https://doi.org/10.14341/omet10032
7. Nermoen I, Falhammar H. Prevalence and Characteristics of Adrenal Tumors and Myelolipomas in Congenital Adrenal Hyperplasia: A Systematic Review and Meta-Analysis. Endocr Pract. 2020;26(11):1351-1365. doi: https://doi.ru/10.4158/EP-2020-0058
8. El-Maouche D, Hannah-Shmouni F, Mallappa A, et al. Adrenal morphology and associated comorbidities in congenital adrenal hyperplasia. Clin Endocrinol (Oxf ). 2019;91(2):247-255. doi: https://doi.ru/10.1111/cen.13996
9. Reisch N, Scherr M, Flade L, et al. Total adrenal volume but not testicular adrenal rest tumor volume is associated with hormonal control in patients with 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2010;95(5):2065-2072. doi: https://doi.ru/10.1210/jc.2009-1929
10. Kim TM, Kim JH, Jang HN, Choi MH, Cho JY, Kim SY. Adrenal Morphology as an Indicator of Long-Term Disease Control in Adults with Classic 21-Hydroxylase Deficiency. Endocrinol Metab (Seoul). 2022;37(1):124-137. doi: https://doi.ru/10.3803/EnM.2021.1278
11. Calissendorff J, Juhlin CC, Sundin A, et al. Adrenal myelolipomas. Lancet Diabetes Endocrinol. 2021;9(11):767-775. doi: https://doi.ru/10.1016/S2213-8587(21)00178-9
12. Sahlander F, Patrova J, Mannheimer B, Lindh JD, Falhammar H. Congenital adrenal hyperplasia in patients with adrenal tumors: a population-based case-control study. J Endocrinol Invest. 2023;46(3):559-565. doi: https://doi.ru/10.1007/s40618-022-01933-0
13. Łebek-Szatańska A, Nowak KM, Samsel R, et al. Adrenocortical carcinoma associated with giant bilateral myelolipomas in classic congenital adrenal hyperplasia. Pol Arch Intern Med. 2019;129(7-8):549-550. doi: https://doi.ru/10.20452/pamw.14788
14. Libé R, Arlt W, Louiset E, et al. A feminizing adrenocortical carcinoma in the context of a late onset 21-hydroxylase deficiency. J Clin Endocrinol Metab. 2014;99(6):1943-1944. doi: https://doi.ru/10.1210/jc.2014-1342
15. Pakalniskis MG, Ishigami K, Pakalniskis BL, et al. Adrenal collision tumour comprised of adrenocortical carcinoma and myelolipoma in a patient with congenital adrenal hyperplasia. J Med Imaging Radiat Oncol. 2020;64(1):67-68. doi: https://doi.ru/10.1111/1754-9485.12961
16. Gemmel F, Bruinsma H, Oomen P, et al. PET/CT incidental detection of bilateral adrenal myelolipomas in a patient with a huge maxillary sinus carcinoma. Clin Nucl Med. 2010;35(2):132-133. doi: https://doi.ru/10.1097/RLU.0b013e3181c7c007
17. Elaini AB, Shetty SK, Chapman VM, et al. Improved detection and characterization of adrenal disease with PET-CT. Radiographics. 2007;27(3):755-767. doi: https://doi.ru/10.1148/rg.273055031
18. Ludwig V, Rice MH, Martin WH, et al. 2-Deoxy-2-[18F]fluoro-Dglucose positron emission tomography uptake in a giant adrenal myelolipoma. Mol Imaging Biol. 2002;4(5):355-358. doi: https://doi.ru/10.1016/s1536-1632(02)00018-5
19. Castinetti F, Verschueren A, Cassagneau P, et al. Adrenal myelolipoma: an unusual cause of bilateral highly 18F-FDG-avid adrenal masses. J Clin Endocrinol Metab. 2012;97(8):2577-2578. doi: https://doi.ru/10.1210/jc.2012-1713
20. Engels M, Span PN, van Herwaarden AE, et al. Testicular Adrenal Rest Tumors: Current Insights on Prevalence, Characteristics, Origin, and Treatment. Endocr Rev. 2019;40(4):973-987. doi: https://doi.ru/10.1210/er.2018-00258
21. Stikkelbroeck NM, Hermus AR, Suliman HM, et al. Asymptomatic testicular adrenal rest tumours in adolescent and adult males with congenital adrenal hyperplasia: basal and follow-up investigation after 2.6 years. J Pediatr Endocrinol Metab. 2004;17(4):645-653. doi: https://doi.ru/10.1515/jpem.2004.17.4.645
22. Falhammar H, Filipsson H, Holmdahl G, et al. Increased liver enzymes in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr J. 2009;56(4):601-608. doi: https://doi.ru/10.1507/endocrj.k08e-312
Supplementary files
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1. Figure 1. MSCT of the adrenal glands with contrast. | |
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2. Figure 2. Gross specimen of giant myelolipoma of the left adrenal gland in CAH. | |
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3. Figure 3. MSCT of the adrenal glands with contrast. | |
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4. Figure 4. MSCT of the adrenal glands with contrast. | |
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5. Figure 5. MSCT of the adrenal glands, native phase. | |
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6. Figure 6. MSCT of the adrenal glands, native phase. | |
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7. Figure 7. Gross specimen: totally necrotic tumor of the right adrenal gland of a patient with CAH. | |
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8. Figure 8. Potential pathogenetic mechanism of development of myelolipomas of the adrenal glands in CAH. | |
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For citations:
Chevais A., Tarbaeva N.V., Golubkina Y.Y., Gadzhimuradova M.M., Ivashchenko K.V., Ladygina D.O., Vorontsova M.V., Bezlepkina O.B., Melnichenko G.A., Mokrysheva N.G. Difficulty with differential diagnosis on adrenal lesions in congenital adrenal cortex dysfunction: a series of clinical cases. Problems of Endocrinology. 2025;71(2):22-34. (In Russ.) https://doi.org/10.14341/probl13564
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