Prevalence of Adrenal Insufficiency and Adrenal Morphology in Treatment-Naïve Tuberculosis Patients: A Cross-Sectional Study From a High-Burden Region

Background and Objectives

Adrenal insufficiency (AI) is a recognized complication in tuberculosis (TB), with previous studies reporting a highly variable prevalence (0%–76%), primarily during or after antitubercular treatment (ATT). However, data on AI prevalence in treatment-naïve TB patients remains scarce. This study aimed to determine the prevalence of AI and adrenal gland morphology in adult patients with newly diagnosed, treatment-naïve TB.

Materials and Methods

This cross-sectional study included 100 treatment-naïve adult TB patients attending the Revised National Tuberculosis Control Program (RNTCP) clinic at Government Medical College Hospital, Thiruvananthapuram, and Chest Disease Hospital, Pulayanarkotta. Patients with HIV, uncontrolled diabetes, critical illness, or recent steroid use were excluded. Due to the COVID-19 pandemic, patient attendance was limited. Clinical features suggestive of AI were assessed based on symptoms and laboratory findings, including hyponatremia and hyperkalemia. An ACTH stimulation test was performed using 0.5 mL (30 units) of long-acting porcine ACTH (Acton Prolongatum) intramuscularly. Serum cortisol levels were measured at 60 and 120 min after administration. AI was defined as a peak cortisol level below 17 μg/dL at 60 min and below 19.5 μg/dL at 120 min. Contrast-enhanced CT (CECT) Abdomen or Thorax images were analyzed for adrenal morphology in one AI-diagnosed TB patient and a subset of 14 TB patients without AI, and 18 age-matched healthy controls without TB or chronic lung pathology.

Results

Among 100 patients (88% pulmonary TB [PTB], 12% extrapulmonary TB[EPTB]) with a mean age of 50 ± 15.4 years and a male-to-female ratio of 3.1:1, 27 patients (27%) exhibited clinical features suggestive of AI. The mean peak serum cortisol levels were 35.17 ± 10.77 μg/dL at 60 min and 39.67 ± 10.84 μg/dL at 120 min. AI was diagnosed in one patient with EPTB (1%), while none of the patients with PTB had AI. CT analysis revealed significantly reduced right adrenal Hounsfield unit (HU) density (p = 0.02) and lateral limb thickness (p = 0.01) in TB patients versus controls, despite absent adrenal enlargement.

Conclusion

AI is rare (1%) in treatment-naïve TB patients despite the overlapping clinical features in a significant proportion. Subtle adrenal morphological changes without enlargement suggest early TB-related alterations without overt dysfunction. Future research should prioritize larger TB cohorts including Extrapulmonary TB to enhance detection of adrenal pathology while minimizing radiation exposure with detailed immune assessments.