Adrenal insufficiency (AI) can be classified into three distinct categories based on its underlying causes: primary adrenal disorders, secondary deficiencies in adrenocorticotropin, or hypothalamic suppression from external factors, most commonly glucocorticoid medications used for anti-inflammatory therapy. The hallmark clinical features of AI include fatigue, appetite loss, unintentional weight loss, low blood pressure, and hyponatremia. Individuals with primary AI additionally manifest skin hyperpigmentation, hyperkalemia, and salt craving. The diagnosis of AI is frequently delayed due to the non-specific symptoms and signs early in the disease course, which poses a significant challenge to its early detection prior to an adrenal crisis. Despite the widespread availability of lifesaving glucocorticoid medications for decades, notable challenges persist, particularly in the domains of timely diagnosis while simultaneously avoiding misdiagnosis, patient education for averting adrenal crises, and the determination of optimal replacement therapies. This article reviews recent advancements in the contemporary diagnostic strategy and approaches to optimal treatment for AI.
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Background Monitoring adults with classical 21-hydroxylase deficiency (21OHD) is challenging due to variation in clinical and laboratory settings. Moreover, guidelines for adrenal imaging in 21OHD are not yet available. We evaluated the relationship between adrenal morphology and disease control status in classical 21OHD.
Methods This retrospective, cross-sectional study included 90 adult 21OHD patients and 270 age- and sex-matched healthy controls. We assessed adrenal volume, width, and tumor presence using abdominal computed tomography and evaluated correlations of adrenal volume and width with hormonal status. We investigated the diagnostic performance of adrenal volume and width for identifying well-controlled status in 21OHD patients (17α-hydroxyprogesterone [17-OHP] <10 ng/mL).
Results The adrenal morphology of 21OHD patients showed hypertrophy (45.6%), normal size (42.2%), and hypotrophy (12.2%). Adrenal tumors were detected in 12 patients (13.3%). The adrenal volume and width of 21OHD patients were significantly larger than those of controls (18.2±12.2 mL vs. 7.1±2.0 mL, 4.7±1.9 mm vs. 3.3±0.5 mm, P<0.001 for both). The 17-OHP and androstenedione levels were highest in patients with adrenal hypertrophy, followed by those with normal adrenal glands and adrenal hypotrophy (P<0.05 for both). Adrenal volume and width correlated positively with adrenocorticotropic hormone, 17-OHP, 11β-hydroxytestosterone, progesterone sulfate, and dehydroepiandrosterone sulfate in both sexes (r=0.33–0.95, P<0.05 for all). For identifying well-controlled patients, the optimal cut-off values of adrenal volume and width were 10.7 mL and 4 mm, respectively (area under the curve, 0.82–0.88; P<0.001 for both).
Conclusion Adrenal volume and width may be reliable quantitative parameters for monitoring patients with classical 21OHD.
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Interactive metabolic signatures of testicular testosterone with bilateral adrenalectomy in mice Hae Lim Cho, Ji-Hoon Kim, Seuk-Min Ryu, Jongsung Noh, Sang Won Lee, Man Ho Choi The Journal of Steroid Biochemistry and Molecular Biology.2023; 231: 106333. CrossRef
Construction of a novel clinical nomogram to predict cancer-specific survival in patients with primary malignant adrenal tumors: a large population-based retrospective study Mingzhen Li, Xiaoying Duan, Di You, Linlin Liu Frontiers in Medicine.2023;[Epub] CrossRef
The anti-platelet drug cilostazol enhances heart rate and interrenal steroidogenesis and exerts a scant effect on innate immune responses in zebrafish Wei-Chun Chang, Mei-Jen Chen, Chung-Der Hsiao, Rong-Ze Hu, Yu-Shan Huang, Yu-Fu Chen, Tsai-Hua Yang, Guan-Yi Tsai, Chih-Wei Chou, Ren-Shiang Chen, Yung-Jen Chuang, Yi-Wen Liu, Mohammed Fouad El Basuini PLOS ONE.2023; 18(10): e0292858. CrossRef
Regulation of Morphogenetic Processes during Postnatal Development and Physiological Regeneration of the Adrenal Medulla S. S. Obernikhin, N. V. Yaglova, E. P. Timokhina, S. V. Nazimova, V. V. Yaglov Bulletin of Experimental Biology and Medicine.2023; 175(4): 549. CrossRef
Distinct HAND2/HAND2-AS1 Expression Levels May Fine-Tune Mesenchymal and Epithelial Cell Plasticity of Human Mesenchymal Stem Cells Rachel Vazana-Netzarim, Yishay Elmalem, Shachar Sofer, Hod Bruck, Naama Danino, Udi Sarig International Journal of Molecular Sciences.2023; 24(22): 16546. CrossRef
An Update on Genetics of Adrenal Gland and Associated Disorders Chester Gauss, Dustin Rowland, Berrin Ergun-Longmire Endocrines.2022; 3(2): 187. CrossRef
Immune dysfunction after spinal cord injury – A review of autonomic and neuroendocrine mechanisms Kyleigh A. Rodgers, Kristina A. Kigerl, Jan M. Schwab, Phillip G. Popovich Current Opinion in Pharmacology.2022; 64: 102230. CrossRef
Clinical and Technical Aspects in Free Cortisol Measurement Man Ho Choi Endocrinology and Metabolism.2022; 37(4): 599. CrossRef
Surrénalectomies Isabelle Valin, Dan Rosenberg Le Nouveau Praticien Vétérinaire canine & féline.2022; 19(82): 50. CrossRef
Adrenal medulla development and medullary-cortical interactions Nicole Bechmann, Ilona Berger, Stefan R. Bornstein, Charlotte Steenblock Molecular and Cellular Endocrinology.2021; 528: 111258. CrossRef
Theory: Treatments for Prolonged ICU Patients May Provide New Therapeutic Avenues for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Dominic Stanculescu, Lars Larsson, Jonas Bergquist Frontiers in Medicine.2021;[Epub] CrossRef
Unravelling Polycystic Ovary Syndrome and Its Comorbidities Kyung-Wook Kim Journal of Obesity & Metabolic Syndrome.2021; 30(3): 209. CrossRef
Adrenocortical carcinoma is often functional and presents with signs and symptoms of adrenal steroid hormone excess. Adrenal insufficiency secondary to bilateral adrenocortical carcinoma is a particularly rare complication. We recently encountered a case of bilateral adrenocortical carcinoma complicated by adrenal insufficiency. A 52-year-old male was transferred to this hospital complaining of general weakness and weight loss. A bilateral adrenal mass was detected on abdomen CT. Plasma cortisol and aldosterone failed to rise during the rapid ACTH stimulation test. The CT-guided adrenal biopsy revealed findings consistent with adrenocortical carcinoma. Left hemiparesis was developed and brain metastasis was detected via brain MRI. Despite the application of gamma knife surgery and chemotherapy, the disease progressed and the patient died.
A Case of Bilateral ACTH-independent Adrenal Adenomas with Cushing's Syndrome Treated by Ipsilateral Total and Contralateral Partial Laparoscopic Adrenalectomy Seung Ah Park, Dong min Jung, Soon young Kim, Nan Young Choi, Tae-jun Kim, Yong kyun Kim, Seong kyun Na, Chul Sik Kim, Seong Jin Lee, Sung-Hee Ihm, Jun Goo Kang The Korean Journal of Obesity.2013; 22(4): 254. CrossRef