Clinical Characteristics of Nine Case of Adrenal Tuberculosis and Literature Review

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Methods We report on nine patients diagnosed with adrenal tuberculosis at the Shanghai Public Health Clinical Center between January 2014 and June 2024. Additionally, we reviewed 206 cases from 60 published reports. We comparatively analyzed the clinical characteristics, laboratory findings, and treatment outcomes. Results Among the nine patients in this hospital, All nine patients underwent anti-tuberculosis therapy, and three also received corticosteroid treatment. Follow-up outcomes showed that four patients were lost to follow-up, while five were cured. Of the 206 cases reported in the literature, Among 160 cases detailing treatment regimens, 152 cases (95%) underwent anti-tuberculosis therapy, and eight were treated with adrenalectomy alone. Cortisol replacement therapy was administered to 106 cases (66%). Prognostic data from 119 cases reported that 40 patients (34%) were cured and 79 (66%) improved. Conclusion Adrenal tuberculosis predominantly affects both adrenal glands. Pathological findings are granulomatous inflammation and caseous necrosis. The diagnosis of adrenal tuberculosis relies on evidence of adrenal cortical insufficiency, extra-adrenal tuberculosis, laboratory confirmation of tuberculosis infection, characteristic imaging features, pathological examination, and diagnostic anti-tuberculosis therapy. Adrenal tuberculosis Adrenal cortical insufficiency Clinical features Cortisol replacement therapy Figures Figure 1 Introduction Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (M.tb), remains a significant global health challenge. According to data from the World Health Organization released in 2022, around 10.6 million new cases of TB were reported worldwide, with the disease leading to an estimated 1.3 million deaths that same year. China ranks third in the world for TB incidence [ 1 ] .TB primarily affects the pulmonary system, with extrapulmonary TB accounting for only 15% of cases [ 2 ] . Among extrapulmonary manifestations, Adrenal TB commonly arises from hematogenous or lymphatic dissemination of M.tb from primary infection sites to the adrenal glands [ 3 ] . Bilateral adrenal involvement is more frequently observed than unilateral involvement, while isolated adrenal TB constitutes merely 2% of cases [ 4 ] . Adrenal tuberculosis lacks typical symptoms in its early stages, and bacteriological diagnosis is challenging, often requiring high-risk invasive tests for confirmation. This frequently leads to delayed diagnosis or misdiagnosis. These factors highlight the necessity of enhancing clinical awareness and understanding of this rare disease. This study retrospectively analyzed clinical data from nine cases of adrenal TB treated at the Shanghai Public Health Clinical Center, along with 206 cases from the literature. It aims to summarize the clinical features of the disease to improve diagnostic and therapeutic approaches for clinicians. Case Report of Nine Adrenal TB Patients Study Participants From 2014 to 2024, nine cases of adrenal TB were recorded in the electronic medical recording system at the Shanghai Public Health Clinical Center, representing approximately 0.6/1,000 newly diagnosed TB cases. Among the nine patients were four males and five females, with a mean age of 47.11 ± 9.43 years. Three cases were confirmed through adrenal biopsy, while the remaining six were clinically diagnosed based on symptoms, imaging findings, and their response to diagnostic anti-TB therapy. Clinical Characters and laboratory findings Out of nine patients, eight displayed symptoms of adrenal insufficiency. The symptoms included skin hyperpigmentation in three cases, poor appetite, nausea, weight loss in seven cases, and dizziness and fatigue in three cases. Additionally, tuberculosis-related symptoms were observed, including fever in six cases, night sweats in three cases, cough in two cases, and chills in one case. Bilateral adrenal lesions were observed in eight out of nine cases, with only one case showing left-sided involvement. Isolated adrenal TB was rare, occurring in two out of nine cases. Seven patients had concurrent extra-adrenal TB, which included pulmonary TB (four cases), spinal TB (two cases), urinary system TB (one case), tuberculous meningitis (one case), cerebral tuberculoma (one case), and thyroid TB (one case) (see Table 1 ). Table 1 Clinical Characteristics of Nine Adrenal TB Cases SN Gender Age (years) Diagnostic method Co-existing TB Lesion location Symptoms 1 Male 52 Clinical diagnosis Spinal TB Bilateral Poor appetite, emaciation, fever 2 Male 54 Clinical diagnosis Urinary and pulmonary TB Bilateral Pigmentation, fever, fatigue, chills, dizziness, cough, nausea 3 Male 58 Pathologically confirmed Pulmonary TB Bilateral Fever, poor appetite 4 Female 34 Pathologically confirmed Pulmonary TB, TB meningitis Bilateral Fatigue, poor appetite, fever, night sweats, weight loss 5 Female 44 Clinical diagnosis - Bilateral Pigmentation 6 Female 33 Pathologically confirmed Cerebral tuberculoma Bilateral Fever 7 Female 52 Clinical diagnosis Pulmonary and thyroid TB Bilateral Pigmentation, fever, poor appetite, nausea, night sweats, cough 8 Male 41 Clinical diagnosis Spinal TB Bilateral Emaciation, fatigue 9 Female 56 Clinical diagnosis - Left side Night sweats, weight loss Out of nine patients, five exhibited elevated levels of Adrenocorticotropic Hormone (ACTH), while two showed decreased cortisol levels. Additionally, hyponatremia was present in six cases, and all nine patients had an elevated Erythrocyte Sedimentation Rate (ESR). Seven patients tested positive for interferon-gamma release assays. Pathological findings were available for three patients: one had a positive acid-fast bacilli smear, another tested positive by PCR, and two displayed typical granulomatous inflammation with caseous necrosis. Adrenal ultrasound results showed hypoechoic masses in one patient, mixed echogenicity masses in another, and irregular hypoechoic areas in a third. Adrenal Computed Tomography(CT) scans revealed nodular changes in four cases, liquefactive necrosis in one case, mass-like lesions in two cases, adrenal thickening in one case, and calcification in one case. Outcomes All nine patients received tailored anti-TB therapy based on their clinical histories, comorbidities, and drug resistance profiles. Three patients also received corticosteroid therapy, resulting in overall improvement. Four patients were lost to follow-up during the follow-up period, although they appeared stable at their final visit. Five patients were cured, with treatment durations ranging from 12 to 24 months. Additionally, one patient underwent an adrenalectomy after 18 months of therapy and continued treatment for another six months due to persistent lesions. Review of previously published studies Cases involved in the analysis A thorough literature review was conducted using the search terms "adrenal tuberculosis" and "tuberculous adrenalitis" in various public medical databases, including PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan-Fang Medical Network. The search yielded 61 English articles and 58 Chinese articles published between January 1, 2014, and June 1, 2024. After excluding duplicates, review articles, and studies with incomplete clinical data, 28 Chinese articles and 32 English articles were selected for analysis. This selection provided data on 206 patients diagnosed with adrenal TB. The collected data were systematically analyzed to assess these patients' clinical characteristics, diagnostic processes, and treatment regimens (see Fig. 1 ). Clinical Characteristics of 206 Adrenal TB Patients from Published Literature Among the 206 patients analyzed [ 5 – 64 ] , 134 cases (65%) were male, and 72 cases (35%) were female. The age range of the cohort was 20–86 years. The majority of 187 cases (91%) were reported from China, with additional cases from the United Kingdom (3), India (3), Indonesia (3), South Korea (3), Peru (2), Morocco (1), Japan (1), Greece (1), Vietnam (1), and the Islamic Republic of Pakistan (1). Sixty cases (29%) were confirmed with TB by biopsy, and the remaining 146 patients (71%) were clinically diagnosed with adrenal TB. The most commonly reported symptoms were skin pigmentation (131 cases, 64%) and systemic weakness or fatigue accompanied by poor appetite (131 cases, 64%). Extra-adrenal TB was noted in 120 cases (58%), with pulmonary TB being the most prevalent form (84 cases, 70% of extra-adrenal TB cases (see Table 2). Laboratory Findings Hyponatremia was observed in 77 cases (37%), hyperkalemia in 36 cases (17%), and elevated ESR in 57 cases (28%). Tuberculin Skin Test (TST) testing was positive in 65 cases (32%), T-cell Enzyme-Linked ImmunoSPOT for Tuberculosis(T-SPOT.TB) in 23 cases (11%), and QuantiFERON-TB Gold(QFT) in 4 cases (2%). Adrenal insufficiency was diagnosed in 144 cases (70%), with an adrenal crisis occurring in 12 cases (6%). Among the 55 cases with pathological data, 40 cases (73%) showed granulomatous inflammation, 28 cases (51%) had caseous necrosis or proliferation, and 14 cases (25%) presented with Langhans giant cells (see Table 2). Imaging Findings Adrenal CT scans showed that 167 cases (81%) involved both adrenal glands, while 39 cases (19%) had unilateral involvement. Among the findings, there were 90 cases (44%) of adrenal masses, 35 cases (17%) of thickening, 40 cases (20%) of nodules, and 103 cases (50%) of calcifications. Out of the total, 77 cases (37%) underwent adrenal-enhanced CT scans. Among these, 12 cases (16%) displayed uneven or homogeneous enhancement, 25 cases (32%) showed peripheral ring-like or septal enhancement, and 16 cases (21%) exhibited no enhancement (see Table 2). Treatment and Outcomes Among the 206 patients, treatment regimens were documented for 160 individuals, while 46 cases did not specify their therapeutic approach. Of those with documented treatments, 152 patients (95%) received anti-TB therapy, primarily a standard first-line regimen, which includes isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E). The remaining eight patients underwent adrenalectomy without subsequent anti-TB therapy. Cortisol replacement therapy was administered to 106 patients (66%), while 54 patients (34%) did not receive this therapy. The main medications used for cortisol replacement included hydrocortisone tablets, prednisone acetate, and prednisone. Prognostic data were available for 119 patients, indicating that 40 individuals (34%) achieved complete recovery, while 79 patients (66%) showed clinical improvement (see Table 2). Discussion The first observations of adrenal TB date back to 1855, when Thomas Addison described the characteristics of Primary Adrenal Insufficiency (PAI). He identified M. tb as a causative agent in six out of eleven cases involving the destruction of the adrenal cortex. In 1856, Trousseau formally defined adrenal insufficiency as Addison's disease, which is characterized by decreased cortisol levels and elevated levels of ACTH [ 65 , 66 ] . In most developed countries, autoimmune adrenal disease, associated with the presence of 21-hydroxylase autoantibodies, is recognized as the primary cause of PAI [ 67 ] . In developing countries, however, adrenal TB remains the leading etiology of PAI [ 68 ] . Clinical Manifestations The adrenal glands' rich vascularization facilitates hematogenous dissemination of M. tb to the adrenal glands, typically a secondary manifestation of TB in other organ systems, most commonly pulmonary and genitourinary TB. Reactivation of primary adrenal TB is rare, and bilateral adrenal involvement is observed more frequently than unilateral involvement. Adrenal TB often presents with a combination of systemic TB symptoms and manifestations of Addison's disease. Common clinical symptoms include systemic symptoms (fatigue, weight loss, hyperpigmentation), gastrointestinal disturbances (nausea, vomiting, diarrhoea, abdominal pain, loss of appetite), circulatory system symptoms (dizziness, palpitations, hypovolemia) and metabolic disorders (hyponatremia, hyperkalemia, hypercalcemia, and hypoglycemia) [ 69 ] .In the present study, eight out of nine cases from our hospital exhibited bilateral adrenal involvement, while one case involved a left-sided lesion. Seven patients had concurrent TB in other sites, including pulmonary TB (four cases). Similarly, literature analysis of 206 cases revealed bilateral lesions in 81% of cases, with unilateral involvement in 19%. Male patients (65%) predominated, indicating that adrenal TB is more common in males. The principal clinical symptoms were skin hyperpigmentation, fatigue, and poor appetite. Additionally, extra-adrenal TB was reported in 58% of cases, most commonly pulmonary TB (70% of extra-adrenal TB cases). Laboratory Tests Laboratory tests for adrenal TB typically include assessments of adrenal function and TB-specific indicators. Adrenal function tests involve plasma ACTH measurements, cortisol rhythm evaluations, and ACTH stimulation tests, with decreased cortisol levels or disrupted rhythm and elevated ACTH levels being key diagnostic criteria for PAI [ 70 ] . TB immunological testing includes the TST test, T-SPOT.TB assay, and QFT. Positive results indicate prior exposure to M.tb or latent infection. However, these tests cannot differentiate latent TB from active disease, and negative results do not exclude TB infection. Low sensitivity and contamination rates limit acid-fast bacilli smear microscopy and M.tb culture methods [ 71 , 72 ] . The Xpert MTB/RIF assay, an advanced nucleic acid amplification test, rapidly detects TB and rifampicin resistance. Despite its utility, negative results do not entirely exclude TB. Molecular detection methods such as deoxyribonucleic acid probe technology are less suited for monitoring active TB due to their inability to distinguish live from dead bacteria [ 73 – 75 ] . Among the cases analyzed, five out of nine patients from our hospital were diagnosed with adrenal insufficiency. In the literature, 70% of cases were identified as adrenal insufficiency and 6% experienced adrenal crisis. Imaging Studies Imaging plays a pivotal role in the diagnosis of adrenal TB. Ultrasonography of adrenal TB often reveals unilateral or bilateral adrenal masses, providing an initial assessment. CT offers superior visualization of adrenal structures and is particularly sensitive to detecting calcifications, making it one of the most widely used modalities for diagnosing adrenal TB. Key CT features include mass-like enlargement, calcifications, central hypodensity, and peripheral rim enhancement [ 76 , 77 ] . Peripheral rim enhancement observed on CT images can be instrumental in diagnosing early or active TB, where prompt initiation of appropriate therapy may be critical for restoring adrenal function [ 78 ] . Magnetic resonance imaging (MRI) is another valuable tool for evaluating pathological changes in adrenal TB. MRI findings often parallel CT observations, including bilateral involvement, mass-like enlargement, hypointensity in the central region on T2-weighted images, and rim enhancement [ 79 ] . While CT is more effective in visualizing calcifications, MRI excels in depicting granulomas and areas of caseous necrosis. In this study, CT imaging of nine patients revealed nodular changes in four cases, mass-like changes in two cases, liquefactive necrosis in one case, adrenal thickening in one case, and calcifications in one case. Among the 206 patients reported in domestic and international literature, CT findings were consistent with the characteristic features of adrenal TB, including calcifications in 103 cases, mass-like changes in 90 cases, nodular changes in 40 cases, and adrenal thickening in 35 cases. Post-contrast enhancement patterns varied and included heterogeneous enhancement, homogeneous enhancement, peripheral rim enhancement, and septal-like enhancement. Pathological Examination Pathological examination via adrenal puncture biopsy or surgical tissue specimen analysis is fundamental in diagnosing adrenal TB. Early or active TB pathology includes caseous necrosis and tuberculous granulomas caused by the destruction of the adrenal cortex by M.tb .Among the nine patients analyzed, pathological results indicated granulomatous inflammation in two cases and caseous necrosis in one case. Literature analysis of 206 cases revealed that granulomatous or granulomatous inflammation with necrosis was present in 73% of cases, while caseous necrosis or proliferation was identified in 51%. Treatment of Adrenal TB The primary treatment options for adrenal TB include drug therapy and, in selected cases, surgical intervention. Drug therapy consists of early, regular, full-course, and combined anti-TB treatment, often accompanied by long-term hormone replacement therapy for patients with adrenal insufficiency. As adrenal TB is a form of extrapulmonary TB, experts recommend a standard 12-month anti-TB regimen, such as 2H-R-Z-E/10H-R-E or 3H-R-Z-E/9H-R-E, for most cases [ 80 – 82 ] . In cases of drug resistance, recurrence, or treatment failure, extended regimens lasting 18 to 24 months are advised [ 83 ] . For patients with PAI, glucocorticoid replacement therapy is critical [ 84 ] . Attention must be given to the potential adverse effects of anti-TB drugs and their interactions with corticosteroids. Rifampin, for example, increases cortisol catabolism and may induce hepatitis, leading to reduced enzymatic conversion of hydrocortisone to cortisol. Consequently, higher hydrocortisone doses may be necessary when using rifampin, or rifampin may be substituted with rifabutin, which has a less pronounced impact on glucocorticoid metabolism [ 85 , 86 ] . Early diagnosis and prompt treatment are essential to improving outcomes and reducing the high mortality rate associated with adrenal TB [ 87 ] . Surgical intervention is not typically a first-line treatment for adrenal TB. However, resection may be considered for large adrenal lesions (> 2 cm) or when malignancy cannot be ruled out, provided there is no evidence of active TB progression and the patient can tolerate surgery. Among the nine patients in our institution, all received anti-TB therapy, and three also received corticosteroid therapy. Four patients were lost to follow-up, while five were cured. Among the cured patients, treatment duration ranged from 12 to 24 months. One patient underwent adrenalectomy after persistent adrenal lesions failed to respond to 18 months of therapy, followed by an additional six months of anti-TB treatment before discontinuation. In the analysis of 206 patients reported in domestic and international literature, 160 cases included treatment details. Among these, 152 (95%) underwent anti-TB therapy, while the remaining eight cases underwent adrenalectomy without additional anti-TB treatment. Cortisol replacement therapy was administered to 106 patients (66%). Two patients treated with HRZE anti-TB therapy and prednisone acetate demonstrated significant improvement in systemic symptoms but continued to experience nausea, vomiting, and hyponatremia. These symptoms were attributed to an interaction between rifampin and prednisone acetate, which resolved after switching from rifampin to rifabutin. Prognostic data were reported for 119 patients. Of these, 40 (34%) achieved a cure, and 79 (66%) demonstrated clinical improvement. Notably, two patients who underwent laparoscopic adrenalectomy without subsequent anti-TB therapy or cortisol replacement showed no metastasis or recurrence during follow-up periods of 20 months and 3 years, respectively. Conclusion Adrenal TB is characterized by subtle and nonspecific symptoms, often involving both adrenal glands and showing a higher prevalence among males. The clinical manifestations predominantly arise from adrenal cortical insufficiency. CT imaging commonly reveals adrenal nodules, masses, thickening, and calcifications, while pathological findings are primarily granulomatous inflammation and caseous necrosis. A comprehensive diagnosis of adrenal TB relies on recognizing symptoms of adrenal cortical insufficiency, identifying evidence of extra-adrenal TB, laboratory confirmation of TB infection, characteristic CT imaging findings, and pathological examination of adrenal biopsy or surgical specimens. Diagnostic anti-TB drug therapy also plays a crucial role in confirming the condition. Management strategies should include standardized anti-TB therapy alongside adrenal corticosteroid replacement therapy, particularly in cases presenting with PAI. Close monitoring is essential to address potential drug interactions between rifampin and adrenal cortical hormones, thereby reducing the risk of adrenal crisis. Declarations Acknowledgments Not applicable. Funding This study was funded by the Intramural Project of the Shanghai Public Health Clinical Center (Grant No. KY-GW-2024-25). Competing interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Data availability statement The data generated in the present study may be requested from the corresponding author. Ethics statement This study complied with ethical guidelines, and the protocol was reviewed and approved by the Ethics Committee of the Shanghai Public Health Clinical Center (approval number: 2024-S021-01). For the retrospective analysis of medical records, the Ethics Committee waived the requirement for informed consent, as the study did not involve direct patient intervention. All procedures adhered to ethical standards outlined by the Declaration of Helsinki and local regulations. Availability of data and materials The datasets used and analysed during the current study are available from the corresponding author on reasonable request. Authors’ contributions DY was responsible for manuscript writing, editing, and data collection. ZTF, HRL and NG performed data analysis and interpretation. DY, ZTF, HRL and NG confirm the authenticity of all raw data used in the study. YY contributed significantly to the study's concept and design. XHL and LX were responsible for conceptualizing the study, supervising it, and critically revising the manuscript for intellectual content. All authors reviewed and approved the final version of the manuscript. ORCIDs: Dan Ye: 0009-0007-4272-1403 Yang Yang: 0000-0002-9864-1353 Lu Xia: 0000-0002-5646-2648 References World Health Organization. Global Tuberculosis Report 2023. https://www.who.int/teams/global-tuberculosisprogramme/tb-reports/global-tuberculosis-report-2023. Chakaya J, Khan M, Ntoumi F, Aklillu E, Fatima R, Mwaba P, Kapata N, et al. Global Tuberculosis Report 2020 - Reflections on the Global TB burden, treatment and prevention efforts. 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Adrenal tuberculosis misdiagnosed as adrenal tumor: a case report [Chinese]. Journal of Modern Urology. 2016;21(1):78. Yang TY. Diagnosis and treatment of adrenal tuberculosis with Addison's disease: a case report [Chinese]. Tibetan Medicine. 2016;37(1):95-96. Gorla AK, Gupta K, Sood A, Biswal CK, Bhansali A, Mittal BR. Adrenal tuberculosis masquerading as disseminated malignancy: A pitfall of (18)F-FDG PET/CT Imaging. Rev Esp Med Nucl Imagen Mol. 2016 Jul-Aug;35(4):257-9. English, Spanish. doi: 10.1016/j.remn.2015.11.008. Epub 2016 Feb 4. PMID: 26853485. Chen YC, Hsu YH. Solitary adrenal tuberculosis. Tzu Chi Med J. 2016 Jul-Sep;28(3):132-133. doi: 10.1016/j.tcmj.2016.04.003. Epub 2016 Jun 3. PMID: 28757741; PMCID: PMC5442921. Zou LP, Chen L, Li X. Adrenal tuberculosis complicated with Addison's disease: a case report [Chinese]. Journal of Clinical Pulmonary Medicine. 2015;20(2):386-387. Xiao PY. A case report of adrenal tuberculosis [Chinese]. Modern Medical Imaging. 2015;24(3):514-515. Long Q, Zhang CJ, Pei B, et al. Primary adrenal insufficiency caused by adrenal tuberculosis: a case report [Chinese]. Chinese Journal of Infectious Diseases. 2015;33(5):319-320. doi:10.3760/cma.j.issn.1000-6680.2015.05.021 Cai FY. Primary adrenal insufficiency caused by adrenal tuberculosis: a case discussion [Chinese]. Celebrity Doctor. 2015;6(7):145. Kim YY, Park SY, Oh YT, Jung DC. Adrenal tuberculosis mimicking a malignancy by direct hepatic invasion: emphasis on adrenohepatic fusion as the potential route. Clin Imaging. 2015 Sep-Oct;39(5):911-3. doi: 10.1016/j.clinimag.2015.04.019. Epub 2015 May 7. PMID: 26001658. Zhao R, Xie JL, Chang XH. Adrenal crisis caused by adrenal tuberculosis with pulmonary tuberculosis: a case report and literature review [Chinese]. Clinical Misdiagnosis & Mistherapy. 2014;27(4):4-6. Mochizuki T, Sanjo H, Hirai K, Horita A, Saito I. [Unilateral adrenal tuberculosis: a case report]. Hinyokika Kiyo. 2014 Dec;60(12):611-4. Japanese. PMID: 25602476. Biswas Shrestha et al. Successfully treated unusual case of primary adrenal and spinal tuberculosis with three years follow up. Pan African Medical Journal. 2014;17:108. doi: 10.11604/pamj.2014.17.108.2575 Addison T. On the Constitutional and Local Effects of Disease of the Supra-Renal Capsules. Br Foreign Med Chir Rev. 1856 Oct;18(36):404-413. PMID: 30164929; PMCID: PMC5199675. Betterle C, Dal Pra C, Mantero F, Zanchetta R. Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr Rev. 2002 Jun;23(3):327-64. doi: 10.1210/edrv.23.3.0466. Erratum in: Endocr Rev. 2002 Aug;23(4):579. PMID: 12050123. Kinjo T, Higuchi D, Oshiro Y, Nakamatsu Y, Fujita K, Nakamoto A, et al. Addison's disease due to tuberculosis that required differentiation from SIADH. J Infect Chemother. 2009 Aug;15(4):239-42. doi: 10.1007/s10156-009-0690-z. Epub 2009 Aug 18. PMID: 19688243. Laway BA, Khan I, Shah BA, Choh NA, Bhat MA, Shah ZA. Pattern of adrenal morphology and function in pulmonary tuberculosis: response to treatment with antitubercular therapy. Clin Endocrinol (Oxf). 2013 Sep;79(3):321-5. doi: 10.1111/cen.12170. Epub 2013 May 20. PMID: 23414172. Charmandari E, Nicolaides NC, Chrousos GP. Adrenal insufficiency. Lancet. 2014 Jun 21;383(9935):2152-67. doi: 10.1016/S0140-6736(13)61684-0. Epub 2014 Feb 4. PMID: 24503135. Barthel A, Benker G, Berens K, Diederich S, Manfras B, Gruber M, et al. An Update on Addison's Disease. Exp Clin Endocrinol Diabetes. 2019 Feb;127(2-03):165-175. doi: 10.1055/a-0804-2715. Epub 2018 Dec 18. PMID: 30562824. Gupta S, Ansari MAM, Gupta AK, Chaudhary P, Bansal LK. Current Approach for Diagnosis and Treatment of Adrenal Tuberculosis-Our Experience and Review of Literature. Surg J (N Y). 2022 Mar 3;8(1):e92-e97. doi: 10.1055/s-0042-1743523. PMID: 35252566; PMCID: PMC8894089. Subramanyam B, Sivaramakrishnan G, Sangamithrai D, Ravi R, Thiruvengadam K, Vijayaragavan V, et al. Reprocessing of Contaminated MGIT 960 Cultures to Improve Availability of Valid Results for Mycobacteria. Int J Microbiol. 2020 Jul 18;2020:1721020. doi: 10.1155/2020/1721020. PMID: 32733570; PMCID: PMC7383301. Pandey S, Congdon J, McInnes B, Pop A, Coulter C. Evaluation of the GeneXpert MTB/RIF assay on extrapulmonary and respiratory samples other than sputum: a low burden country experience. Pathology. 2017 Jan;49(1):70-74. doi: 10.1016/j.pathol.2016.10.004. Epub 2016 Nov 29. PMID: 27913043. Wang HY, Lu JJ, Chang CY, Chou WP, Hsieh JC, Lin CR, et al. Development of a high sensitivity TaqMan-based PCR assay for the specific detection of Mycobacterium tuberculosis complex in both pulmonary and extrapulmonary specimens. Sci Rep. 2019 Jan 14;9(1):113. doi: 10.1038/s41598-018-33804-1. PMID: 30643154; PMCID: PMC6331544. Efremidis SC, Harsoulis F, Douma S, Zafiriadou E, Zamboulis C, Kouri A. Adrenal insufficiency with enlarged adrenals. Abdom Imaging. 1996 Mar-Apr;21(2):168-71. doi: 10.1007/s002619900037. PMID: 8661767. Wang YX, Chen CR, He GX, Tang AR. CT findings of adrenal glands in patients with tuberculous Addison's disease. J Belge Radiol. 1998 Oct;81(5):226-8. PMID: 9880955. Ma ES, Yang ZG, Li Y, Guo YK, Deng YP, Zhang XC. Tuberculous Addison's disease: morphological and quantitative evaluation with multidetector-row CT. Eur J Radiol. 2007 Jun;62(3):352-8. doi: 10.1016/j.ejrad.2006.12.012. Epub 2007 Apr 26. PMID: 17466476. Guo YK, Yang ZG, Li Y, Ma ES, Deng YP, Min PQ, et al. Addison's disease due to adrenal tuberculosis: contrast-enhanced CT features and clinical duration correlation. Eur J Radiol. 2007 Apr;62(1):126-31. doi: 10.1016/j.ejrad.2006.11.025. Epub 2006 Dec 19. PMID: 17182208. Zhang XC, Yang ZG, Li Y, Min PQ, Guo YK, Deng YP, et al. Addison's disease due to adrenal tuberculosis: MRI features. Abdom Imaging. 2008 Nov-Dec;33(6):689-94. doi: 10.1007/s00261-007-9352-8. PMID: 18180983. Denny N, Raghunath S, Bhatia P, Abdelaziz M. Rifampicin-induced adrenal crisis in a patient with tuberculosis: a therapeutic challenge. BMJ Case Rep. 2016 Nov 29;2016:bcr2016216302. doi: 10.1136/bcr-2016-216302. PMID: 27899384; PMCID: PMC5175016. Shrestha B, Omran A, Rong P, Wang W. Successfully treated unusual case of primary adrenal and spinal tuberculosis with three years follow up. Pan Afr Med J. 2014 Feb 13;17:108. doi: 10.11604/pamj.2014.17.108.2575. PMID: 25018843; PMCID: PMC4081147. Manso MC, Rodeia SC, Rodrigues S, Domingos R. Synchronous presentation of two rare forms of extrapulmonary tuberculosis. BMJ Case Rep. 2016 Apr 18;2016:10.1136/bcr-2015-212917. doi: 10.1136/bcr-2015-212917. PMID: 27090536; PMCID: PMC4840700. Kelestimur F. The endocrinology of adrenal tuberculosis: the effects of tuberculosis on the hypothalamo-pituitary-adrenal axis and adrenocortical function. J Endocrinol Invest. 2004 Apr;27(4):380-6. doi: 10.1007/BF03351067. PMID: 15233561. Kusuki K, Watanabe S, Mizuno Y. Tuberculous Addison's disease with increased hydrocortisone requirements due to administration of rifampicin. BMJ Case Rep. 2019 Mar 14;12(3):e228293. doi: 10.1136/bcr-2018-228293. PMID: 30872343; PMCID: PMC6424385. Thijs E, Wierckx K, Vandecasteele S, Van den Bruel A. Adrenal insufficiency, be aware of drug interactions! Endocrinol Diabetes Metab Case Rep. 2019 Oct 3;2019:19-0062. doi: 10.1530/EDM-19-0062. Epub ahead of print. PMID: 31581123; PMCID: PMC6790904. Shah M, Reed C. Complications of tuberculosis. Curr Opin Infect Dis. 2014 Oct;27(5):403-10. doi: 10.1097/QCO.0000000000000090. PMID: 25028786. Zhao N, Gao Y, Ni C, Zhang D, Zhao X, Li Y, et al. An autopsy case of unexpected death due to Addison's disease caused by adrenal tuberculosis. Eur J Med Res. 2021 Dec 4;26(1):137. doi: 10.1186/s40001-021-00611-w. PMID: 34863306; PMCID: PMC8642993. Table 2 Table 2 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table2.xlsx Cite Share Download PDF Status: Published Journal Publication published 10 Nov, 2025 Read the published version in International Urology and Nephrology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7355816","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":509302574,"identity":"2cadd23a-56cc-4188-8927-858e901ea7f3","order_by":0,"name":"Dan Ye","email":"","orcid":"","institution":"Shanghai Public Health Clinical Center","correspondingAuthor":false,"prefix":"","firstName":"Dan","middleName":"","lastName":"Ye","suffix":""},{"id":509302575,"identity":"abb9eaad-3e6f-4f3a-ba8d-5b63edaf6b99","order_by":1,"name":"Yang Yang","email":"","orcid":"","institution":"Shanghai Public Health Clinical Center","correspondingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Yang","suffix":""},{"id":509302576,"identity":"3ee2ff6b-baad-4fad-a6a1-b767489c1c11","order_by":2,"name":"Zhentao Fei","email":"","orcid":"","institution":"Shanghai Public Health Clinical Center","correspondingAuthor":false,"prefix":"","firstName":"Zhentao","middleName":"","lastName":"Fei","suffix":""},{"id":509302578,"identity":"c476958e-8586-400a-bcde-337bbcd8e39c","order_by":3,"name":"Huarui Liu","email":"","orcid":"","institution":"Shanghai Public Health Clinical Center","correspondingAuthor":false,"prefix":"","firstName":"Huarui","middleName":"","lastName":"Liu","suffix":""},{"id":509302580,"identity":"2880111b-15f8-4149-95cf-4a31c6989bb8","order_by":4,"name":"Ning Gan","email":"","orcid":"","institution":"Shanghai Public Health Clinical Center","correspondingAuthor":false,"prefix":"","firstName":"Ning","middleName":"","lastName":"Gan","suffix":""},{"id":509302582,"identity":"07d08632-f589-4f72-bbdd-6bf7f0ac3bca","order_by":5,"name":"Xuhui Liu","email":"","orcid":"","institution":"Shanghai Public Health Clinical Center","correspondingAuthor":false,"prefix":"","firstName":"Xuhui","middleName":"","lastName":"Liu","suffix":""},{"id":509302583,"identity":"80065a77-c8cc-4e7a-a93f-e3ae1e0e9bec","order_by":6,"name":"Lu Xia","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxklEQVRIiWNgGAWjYDACZgbGAwwVDAkMDDzEa2E4wHCGJC1AcICxjRQtBseZHxzmnVeXxz+79+AHhop7dg2EtEg2sxkc5t12uFjizrlkCYYzxckEtfAzM4C0HEhsuJFjxsDYlpBM0GFszOwfDvPOqUucT7QWfmYeoC0NzIkboFrsCGqRbOYpODjn2OHEjXfOGEsknElIIKjF4PzxjQ/e1NQlzrvdY/jhQ0WCPUEtCCABxEArEhtI0wIEpNgyCkbBKBgFIwQAAFHjPgqn2es5AAAAAElFTkSuQmCC","orcid":"","institution":"Shanghai Public Health Clinical Center","correspondingAuthor":true,"prefix":"","firstName":"Lu","middleName":"","lastName":"Xia","suffix":""}],"badges":[],"createdAt":"2025-08-12 12:38:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7355816/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7355816/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11255-025-04897-1","type":"published","date":"2025-11-10T15:58:31+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":90543596,"identity":"1001d46d-37e3-48c1-b0c6-0c4d6e03895f","added_by":"auto","created_at":"2025-09-04 00:13:30","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":288045,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of Literature Inclusion\u003c/p\u003e","description":"","filename":"Figure1.FlowchartofLiteratureInclusion.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7355816/v1/1d1382ec47cc1a10a496f1bf.jpg"},{"id":96105830,"identity":"4e8cd77b-37a2-4ee3-9794-5faeada23d4b","added_by":"auto","created_at":"2025-11-17 16:11:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":993172,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7355816/v1/4b739e7d-945f-4ad4-bfbc-8dbafd05f622.pdf"},{"id":90543600,"identity":"8d075f3f-803d-4bd0-95ee-8938c468f1ac","added_by":"auto","created_at":"2025-09-04 00:13:30","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":23405,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7355816/v1/538a543d4dc880743a8477ff.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Characteristics of Nine Case of Adrenal Tuberculosis and Literature Review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (M.tb), remains a significant global health challenge. According to data from the World Health Organization released in 2022, around 10.6\u0026nbsp;million new cases of TB were reported worldwide, with the disease leading to an estimated 1.3\u0026nbsp;million deaths that same year. China ranks third in the world for TB incidence \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e.TB primarily affects the pulmonary system, with extrapulmonary TB accounting for only 15% of cases \u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Among extrapulmonary manifestations, Adrenal TB commonly arises from hematogenous or lymphatic dissemination of \u003cem\u003eM.tb\u003c/em\u003e from primary infection sites to the adrenal glands \u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Bilateral adrenal involvement is more frequently observed than unilateral involvement, while isolated adrenal TB constitutes merely 2% of cases \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Adrenal tuberculosis lacks typical symptoms in its early stages, and bacteriological diagnosis is challenging, often requiring high-risk invasive tests for confirmation. This frequently leads to delayed diagnosis or misdiagnosis. These factors highlight the necessity of enhancing clinical awareness and understanding of this rare disease. This study retrospectively analyzed clinical data from nine cases of adrenal TB treated at the Shanghai Public Health Clinical Center, along with 206 cases from the literature. It aims to summarize the clinical features of the disease to improve diagnostic and therapeutic approaches for clinicians.\u003c/p\u003e"},{"header":"Case Report of Nine Adrenal TB Patients","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Participants\u003c/h2\u003e\u003cp\u003eFrom 2014 to 2024, nine cases of adrenal TB were recorded in the electronic medical recording system at the Shanghai Public Health Clinical Center, representing approximately 0.6/1,000 newly diagnosed TB cases. Among the nine patients were four males and five females, with a mean age of 47.11 ± 9.43 years. Three cases were confirmed through adrenal biopsy, while the remaining six were clinically diagnosed based on symptoms, imaging findings, and their response to diagnostic anti-TB therapy.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eClinical Characters and laboratory findings\u003c/h3\u003e\n\u003cp\u003eOut of nine patients, eight displayed symptoms of adrenal insufficiency. The symptoms included skin hyperpigmentation in three cases, poor appetite, nausea, weight loss in seven cases, and dizziness and fatigue in three cases. Additionally, tuberculosis-related symptoms were observed, including fever in six cases, night sweats in three cases, cough in two cases, and chills in one case. Bilateral adrenal lesions were observed in eight out of nine cases, with only one case showing left-sided involvement. Isolated adrenal TB was rare, occurring in two out of nine cases. Seven patients had concurrent extra-adrenal TB, which included pulmonary TB (four cases), spinal TB (two cases), urinary system TB (one case), tuberculous meningitis (one case), cerebral tuberculoma (one case), and thyroid TB (one case) (see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinical Characteristics of Nine Adrenal TB Cases\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSN\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDiagnostic method\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCo-existing TB\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLesion location\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSymptoms\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eClinical diagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSpinal TB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBilateral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePoor appetite, emaciation, fever\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eClinical diagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eUrinary and pulmonary TB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBilateral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePigmentation, fever, fatigue, chills, dizziness, cough, nausea\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePathologically confirmed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePulmonary TB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBilateral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eFever, poor appetite\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePathologically confirmed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePulmonary TB, TB meningitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBilateral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eFatigue, poor appetite, fever, night sweats, weight loss\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eClinical diagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBilateral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePigmentation\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePathologically confirmed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCerebral tuberculoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBilateral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eFever\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eClinical diagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePulmonary and thyroid TB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBilateral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePigmentation, fever, poor appetite, nausea, night sweats, cough\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eClinical diagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSpinal TB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eBilateral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eEmaciation, fatigue\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eClinical diagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eLeft side\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNight sweats, weight loss\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eOut of nine patients, five exhibited elevated levels of Adrenocorticotropic Hormone (ACTH), while two showed decreased cortisol levels. Additionally, hyponatremia was present in six cases, and all nine patients had an elevated Erythrocyte Sedimentation Rate (ESR). Seven patients tested positive for interferon-gamma release assays. Pathological findings were available for three patients: one had a positive acid-fast bacilli smear, another tested positive by PCR, and two displayed typical granulomatous inflammation with caseous necrosis. Adrenal ultrasound results showed hypoechoic masses in one patient, mixed echogenicity masses in another, and irregular hypoechoic areas in a third. Adrenal Computed Tomography(CT) scans revealed nodular changes in four cases, liquefactive necrosis in one case, mass-like lesions in two cases, adrenal thickening in one case, and calcification in one case.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eAll nine patients received tailored anti-TB therapy based on their clinical histories, comorbidities, and drug resistance profiles. Three patients also received corticosteroid therapy, resulting in overall improvement. Four patients were lost to follow-up during the follow-up period, although they appeared stable at their final visit. Five patients were cured, with treatment durations ranging from 12 to 24 months. Additionally, one patient underwent an adrenalectomy after 18 months of therapy and continued treatment for another six months due to persistent lesions.\u003c/p\u003e"},{"header":"Review of previously published studies","content":"\u003ch2\u003eCases involved in the analysis\u003c/h2\u003e\u003cp\u003e A thorough literature review was conducted using the search terms \"adrenal tuberculosis\" and \"tuberculous adrenalitis\" in various public medical databases, including PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan-Fang Medical Network. The search yielded 61 English articles and 58 Chinese articles published between January 1, 2014, and June 1, 2024. After excluding duplicates, review articles, and studies with incomplete clinical data, 28 Chinese articles and 32 English articles were selected for analysis. This selection provided data on 206 patients diagnosed with adrenal TB. The collected data were systematically analyzed to assess these patients' clinical characteristics, diagnostic processes, and treatment regimens (see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003ch2\u003eClinical Characteristics of 206 Adrenal TB Patients from Published Literature\u003c/h2\u003e\u003cp\u003eAmong the 206 patients analyzed \u003csup\u003e[\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37 CR38 CR39 CR40 CR41 CR42 CR43 CR44 CR45 CR46 CR47 CR48 CR49 CR50 CR51 CR52 CR53 CR54 CR55 CR56 CR57 CR58 CR59 CR60 CR61 CR62 CR63\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e–\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e]\u003c/sup\u003e, 134 cases (65%) were male, and 72 cases (35%) were female. The age range of the cohort was 20–86 years. The majority of 187 cases (91%) were reported from China, with additional cases from the United Kingdom (3), India (3), Indonesia (3), South Korea (3), Peru (2), Morocco (1), Japan (1), Greece (1), Vietnam (1), and the Islamic Republic of Pakistan (1). Sixty cases (29%) were confirmed with TB by biopsy, and the remaining 146 patients (71%) were clinically diagnosed with adrenal TB. The most commonly reported symptoms were skin pigmentation (131 cases, 64%) and systemic weakness or fatigue accompanied by poor appetite (131 cases, 64%). Extra-adrenal TB was noted in 120 cases (58%), with pulmonary TB being the most prevalent form (84 cases, 70% of extra-adrenal TB cases (see Table\u0026nbsp;2).\u003c/p\u003e\u003ch3\u003eLaboratory Findings\u003c/h3\u003e\u003cp\u003eHyponatremia was observed in 77 cases (37%), hyperkalemia in 36 cases (17%), and elevated ESR in 57 cases (28%). Tuberculin Skin Test (TST) testing was positive in 65 cases (32%), T-cell Enzyme-Linked ImmunoSPOT for Tuberculosis(T-SPOT.TB) in 23 cases (11%), and QuantiFERON-TB Gold(QFT) in 4 cases (2%). Adrenal insufficiency was diagnosed in 144 cases (70%), with an adrenal crisis occurring in 12 cases (6%). Among the 55 cases with pathological data, 40 cases (73%) showed granulomatous inflammation, 28 cases (51%) had caseous necrosis or proliferation, and 14 cases (25%) presented with Langhans giant cells (see Table\u0026nbsp;2).\u003c/p\u003e\u003ch3\u003eImaging Findings\u003c/h3\u003e\u003cp\u003eAdrenal CT scans showed that 167 cases (81%) involved both adrenal glands, while 39 cases (19%) had unilateral involvement. Among the findings, there were 90 cases (44%) of adrenal masses, 35 cases (17%) of thickening, 40 cases (20%) of nodules, and 103 cases (50%) of calcifications. Out of the total, 77 cases (37%) underwent adrenal-enhanced CT scans. Among these, 12 cases (16%) displayed uneven or homogeneous enhancement, 25 cases (32%) showed peripheral ring-like or septal enhancement, and 16 cases (21%) exhibited no enhancement (see Table\u0026nbsp;2).\u003c/p\u003e\u003ch2\u003eTreatment and Outcomes\u003c/h2\u003e\u003cp\u003eAmong the 206 patients, treatment regimens were documented for 160 individuals, while 46 cases did not specify their therapeutic approach. Of those with documented treatments, 152 patients (95%) received anti-TB therapy, primarily a standard first-line regimen, which includes isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E). The remaining eight patients underwent adrenalectomy without subsequent anti-TB therapy. Cortisol replacement therapy was administered to 106 patients (66%), while 54 patients (34%) did not receive this therapy. The main medications used for cortisol replacement included hydrocortisone tablets, prednisone acetate, and prednisone. Prognostic data were available for 119 patients, indicating that 40 individuals (34%) achieved complete recovery, while 79 patients (66%) showed clinical improvement (see Table\u0026nbsp;2).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe first observations of adrenal TB date back to 1855, when Thomas Addison described the characteristics of Primary Adrenal Insufficiency (PAI). He identified M. tb as a causative agent in six out of eleven cases involving the destruction of the adrenal cortex. In 1856, Trousseau formally defined adrenal insufficiency as Addison's disease, which is characterized by decreased cortisol levels and elevated levels of ACTH \u003csup\u003e[\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e, \u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e]\u003c/sup\u003e. In most developed countries, autoimmune adrenal disease, associated with the presence of 21-hydroxylase autoantibodies, is recognized as the primary cause of PAI\u003csup\u003e[\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e]\u003c/sup\u003e. In developing countries, however, adrenal TB remains the leading etiology of PAI \u003csup\u003e[\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eClinical Manifestations\u003c/h2\u003e\u003cp\u003eThe adrenal glands' rich vascularization facilitates hematogenous dissemination of \u003cem\u003eM. tb\u003c/em\u003e to the adrenal glands, typically a secondary manifestation of TB in other organ systems, most commonly pulmonary and genitourinary TB. Reactivation of primary adrenal TB is rare, and bilateral adrenal involvement is observed more frequently than unilateral involvement. Adrenal TB often presents with a combination of systemic TB symptoms and manifestations of Addison's disease. Common clinical symptoms include systemic symptoms (fatigue, weight loss, hyperpigmentation), gastrointestinal disturbances (nausea, vomiting, diarrhoea, abdominal pain, loss of appetite), circulatory system symptoms (dizziness, palpitations, hypovolemia) and metabolic disorders (hyponatremia, hyperkalemia, hypercalcemia, and hypoglycemia) \u003csup\u003e[\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e]\u003c/sup\u003e.In the present study, eight out of nine cases from our hospital exhibited bilateral adrenal involvement, while one case involved a left-sided lesion. Seven patients had concurrent TB in other sites, including pulmonary TB (four cases). Similarly, literature analysis of 206 cases revealed bilateral lesions in 81% of cases, with unilateral involvement in 19%. Male patients (65%) predominated, indicating that adrenal TB is more common in males. The principal clinical symptoms were skin hyperpigmentation, fatigue, and poor appetite. Additionally, extra-adrenal TB was reported in 58% of cases, most commonly pulmonary TB (70% of extra-adrenal TB cases).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eLaboratory Tests\u003c/h2\u003e\u003cp\u003eLaboratory tests for adrenal TB typically include assessments of adrenal function and TB-specific indicators. Adrenal function tests involve plasma ACTH measurements, cortisol rhythm evaluations, and ACTH stimulation tests, with decreased cortisol levels or disrupted rhythm and elevated ACTH levels being key diagnostic criteria for PAI \u003csup\u003e[\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e]\u003c/sup\u003e. TB immunological testing includes the TST test, T-SPOT.TB assay, and QFT. Positive results indicate prior exposure to \u003cem\u003eM.tb\u003c/em\u003e or latent infection. However, these tests cannot differentiate latent TB from active disease, and negative results do not exclude TB infection. Low sensitivity and contamination rates limit acid-fast bacilli smear microscopy and \u003cem\u003eM.tb\u003c/em\u003e culture methods \u003csup\u003e[\u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e, \u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e]\u003c/sup\u003e. The Xpert MTB/RIF assay, an advanced nucleic acid amplification test, rapidly detects TB and rifampicin resistance. Despite its utility, negative results do not entirely exclude TB. Molecular detection methods such as deoxyribonucleic acid probe technology are less suited for monitoring active TB due to their inability to distinguish live from dead bacteria \u003csup\u003e[\u003cspan additionalcitationids=\"CR74\" citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e]\u003c/sup\u003e. Among the cases analyzed, five out of nine patients from our hospital were diagnosed with adrenal insufficiency. In the literature, 70% of cases were identified as adrenal insufficiency and 6% experienced adrenal crisis.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eImaging Studies\u003c/h2\u003e\u003cp\u003eImaging plays a pivotal role in the diagnosis of adrenal TB. Ultrasonography of adrenal TB often reveals unilateral or bilateral adrenal masses, providing an initial assessment. CT offers superior visualization of adrenal structures and is particularly sensitive to detecting calcifications, making it one of the most widely used modalities for diagnosing adrenal TB. Key CT features include mass-like enlargement, calcifications, central hypodensity, and peripheral rim enhancement \u003csup\u003e[\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e, \u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e]\u003c/sup\u003e. Peripheral rim enhancement observed on CT images can be instrumental in diagnosing early or active TB, where prompt initiation of appropriate therapy may be critical for restoring adrenal function \u003csup\u003e[\u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e]\u003c/sup\u003e. Magnetic resonance imaging (MRI) is another valuable tool for evaluating pathological changes in adrenal TB. MRI findings often parallel CT observations, including bilateral involvement, mass-like enlargement, hypointensity in the central region on T2-weighted images, and rim enhancement \u003csup\u003e[\u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e79\u003c/span\u003e]\u003c/sup\u003e. While CT is more effective in visualizing calcifications, MRI excels in depicting granulomas and areas of caseous necrosis. In this study, CT imaging of nine patients revealed nodular changes in four cases, mass-like changes in two cases, liquefactive necrosis in one case, adrenal thickening in one case, and calcifications in one case. Among the 206 patients reported in domestic and international literature, CT findings were consistent with the characteristic features of adrenal TB, including calcifications in 103 cases, mass-like changes in 90 cases, nodular changes in 40 cases, and adrenal thickening in 35 cases. Post-contrast enhancement patterns varied and included heterogeneous enhancement, homogeneous enhancement, peripheral rim enhancement, and septal-like enhancement.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003ePathological Examination\u003c/h2\u003e\u003cp\u003ePathological examination via adrenal puncture biopsy or surgical tissue specimen analysis is fundamental in diagnosing adrenal TB. Early or active TB pathology includes caseous necrosis and tuberculous granulomas caused by the destruction of the adrenal cortex by \u003cem\u003eM.tb\u003c/em\u003e.Among the nine patients analyzed, pathological results indicated granulomatous inflammation in two cases and caseous necrosis in one case. Literature analysis of 206 cases revealed that granulomatous or granulomatous inflammation with necrosis was present in 73% of cases, while caseous necrosis or proliferation was identified in 51%.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003eTreatment of Adrenal TB\u003c/h2\u003e\u003cp\u003eThe primary treatment options for adrenal TB include drug therapy and, in selected cases, surgical intervention. Drug therapy consists of early, regular, full-course, and combined anti-TB treatment, often accompanied by long-term hormone replacement therapy for patients with adrenal insufficiency. As adrenal TB is a form of extrapulmonary TB, experts recommend a standard 12-month anti-TB regimen, such as 2H-R-Z-E/10H-R-E or 3H-R-Z-E/9H-R-E, for most cases \u003csup\u003e[\u003cspan additionalcitationids=\"CR81\" citationid=\"CR80\" class=\"CitationRef\"\u003e80\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR82\" class=\"CitationRef\"\u003e82\u003c/span\u003e]\u003c/sup\u003e. In cases of drug resistance, recurrence, or treatment failure, extended regimens lasting 18 to 24 months are advised \u003csup\u003e[\u003cspan citationid=\"CR83\" class=\"CitationRef\"\u003e83\u003c/span\u003e]\u003c/sup\u003e. For patients with PAI, glucocorticoid replacement therapy is critical \u003csup\u003e[\u003cspan citationid=\"CR84\" class=\"CitationRef\"\u003e84\u003c/span\u003e]\u003c/sup\u003e. Attention must be given to the potential adverse effects of anti-TB drugs and their interactions with corticosteroids. Rifampin, for example, increases cortisol catabolism and may induce hepatitis, leading to reduced enzymatic conversion of hydrocortisone to cortisol. Consequently, higher hydrocortisone doses may be necessary when using rifampin, or rifampin may be substituted with rifabutin, which has a less pronounced impact on glucocorticoid metabolism \u003csup\u003e[\u003cspan citationid=\"CR85\" class=\"CitationRef\"\u003e85\u003c/span\u003e, \u003cspan citationid=\"CR86\" class=\"CitationRef\"\u003e86\u003c/span\u003e]\u003c/sup\u003e. Early diagnosis and prompt treatment are essential to improving outcomes and reducing the high mortality rate associated with adrenal TB \u003csup\u003e[\u003cspan citationid=\"CR87\" class=\"CitationRef\"\u003e87\u003c/span\u003e]\u003c/sup\u003e. Surgical intervention is not typically a first-line treatment for adrenal TB. However, resection may be considered for large adrenal lesions (\u0026gt;\u0026thinsp;2 cm) or when malignancy cannot be ruled out, provided there is no evidence of active TB progression and the patient can tolerate surgery.\u003c/p\u003e\u003cp\u003eAmong the nine patients in our institution, all received anti-TB therapy, and three also received corticosteroid therapy. Four patients were lost to follow-up, while five were cured. Among the cured patients, treatment duration ranged from 12 to 24 months. One patient underwent adrenalectomy after persistent adrenal lesions failed to respond to 18 months of therapy, followed by an additional six months of anti-TB treatment before discontinuation. In the analysis of 206 patients reported in domestic and international literature, 160 cases included treatment details. Among these, 152 (95%) underwent anti-TB therapy, while the remaining eight cases underwent adrenalectomy without additional anti-TB treatment. Cortisol replacement therapy was administered to 106 patients (66%). Two patients treated with HRZE anti-TB therapy and prednisone acetate demonstrated significant improvement in systemic symptoms but continued to experience nausea, vomiting, and hyponatremia. These symptoms were attributed to an interaction between rifampin and prednisone acetate, which resolved after switching from rifampin to rifabutin. Prognostic data were reported for 119 patients. Of these, 40 (34%) achieved a cure, and 79 (66%) demonstrated clinical improvement. Notably, two patients who underwent laparoscopic adrenalectomy without subsequent anti-TB therapy or cortisol replacement showed no metastasis or recurrence during follow-up periods of 20 months and 3 years, respectively.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAdrenal TB is characterized by subtle and nonspecific symptoms, often involving both adrenal glands and showing a higher prevalence among males. The clinical manifestations predominantly arise from adrenal cortical insufficiency. CT imaging commonly reveals adrenal nodules, masses, thickening, and calcifications, while pathological findings are primarily granulomatous inflammation and caseous necrosis. A comprehensive diagnosis of adrenal TB relies on recognizing symptoms of adrenal cortical insufficiency, identifying evidence of extra-adrenal TB, laboratory confirmation of TB infection, characteristic CT imaging findings, and pathological examination of adrenal biopsy or surgical specimens. Diagnostic anti-TB drug therapy also plays a crucial role in confirming the condition. Management strategies should include standardized anti-TB therapy alongside adrenal corticosteroid replacement therapy, particularly in cases presenting with PAI. Close monitoring is essential to address potential drug interactions between rifampin and adrenal cortical hormones, thereby reducing the risk of adrenal crisis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the Intramural Project of the Shanghai Public Health Clinical Center (Grant No. KY-GW-2024-25).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data generated in the present study may be requested from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study complied with ethical guidelines, and the protocol was reviewed and approved by the Ethics Committee of the Shanghai Public Health Clinical Center (approval number: 2024-S021-01). For the retrospective analysis of medical records, the Ethics Committee waived the requirement for informed consent, as the study did not involve direct patient intervention. All procedures adhered to ethical standards outlined by the Declaration of Helsinki and local regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDY was responsible for manuscript writing, editing, and data collection. ZTF, HRL and NG performed data analysis and interpretation. DY, ZTF, HRL and NG confirm the authenticity of all raw data used in the study. YY contributed significantly to the study\u0026apos;s concept and design. XHL and LX were responsible for conceptualizing the study, supervising it, and critically revising the manuscript for intellectual content. All authors reviewed and approved the final version of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eORCIDs:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDan Ye: 0009-0007-4272-1403\u003c/p\u003e\n\u003cp\u003eYang Yang: 0000-0002-9864-1353\u003c/p\u003e\n\u003cp\u003eLu Xia: 0000-0002-5646-2648\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWorld Health Organization. Global Tuberculosis Report 2023. https://www.who.int/teams/global-tuberculosisprogramme/tb-reports/global-tuberculosis-report-2023.\u003c/li\u003e\n\u003cli\u003eChakaya J, Khan M, Ntoumi F, Aklillu E, Fatima R, Mwaba P, Kapata N, et al. Global Tuberculosis Report 2020 - Reflections on the Global TB burden, treatment and prevention efforts. 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PMID: 34863306; PMCID: PMC8642993.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 2","content":"\u003cp\u003eTable 2 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Adrenal tuberculosis, Adrenal cortical insufficiency, Clinical features, Cortisol replacement therapy","lastPublishedDoi":"10.21203/rs.3.rs-7355816/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7355816/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eTo examine the clinical features of adrenal tuberculosis to improve clinicians' diagnostic accuracy and treatment strategies.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe report on nine patients diagnosed with adrenal tuberculosis at the Shanghai Public Health Clinical Center between January 2014 and June 2024. Additionally, we reviewed 206 cases from 60 published reports. We comparatively analyzed the clinical characteristics, laboratory findings, and treatment outcomes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAmong the nine patients in this hospital, All nine patients underwent anti-tuberculosis therapy, and three also received corticosteroid treatment. Follow-up outcomes showed that four patients were lost to follow-up, while five were cured. Of the 206 cases reported in the literature, Among 160 cases detailing treatment regimens, 152 cases (95%) underwent anti-tuberculosis therapy, and eight were treated with adrenalectomy alone. Cortisol replacement therapy was administered to 106 cases (66%). Prognostic data from 119 cases reported that 40 patients (34%) were cured and 79 (66%) improved.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eAdrenal tuberculosis predominantly affects both adrenal glands. Pathological findings are granulomatous inflammation and caseous necrosis. The diagnosis of adrenal tuberculosis relies on evidence of adrenal cortical insufficiency, extra-adrenal tuberculosis, laboratory confirmation of tuberculosis infection, characteristic imaging features, pathological examination, and diagnostic anti-tuberculosis therapy.\u003c/p\u003e","manuscriptTitle":"Clinical Characteristics of Nine Case of Adrenal Tuberculosis and Literature Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-04 00:13:25","doi":"10.21203/rs.3.rs-7355816/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"edb8d5ab-0dbb-4d2b-99b2-7f55c222bd8a","owner":[],"postedDate":"September 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-17T16:09:08+00:00","versionOfRecord":{"articleIdentity":"rs-7355816","link":"https://doi.org/10.1007/s11255-025-04897-1","journal":{"identity":"international-urology-and-nephrology","isVorOnly":false,"title":"International Urology and Nephrology"},"publishedOn":"2025-11-10 15:58:31","publishedOnDateReadable":"November 10th, 2025"},"versionCreatedAt":"2025-09-04 00:13:25","video":"","vorDoi":"10.1007/s11255-025-04897-1","vorDoiUrl":"https://doi.org/10.1007/s11255-025-04897-1","workflowStages":[]},"version":"v1","identity":"rs-7355816","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7355816","identity":"rs-7355816","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}