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Reversible central adrenal insufficiency in survivors of COVID-19: results from a 24-month longitudinal study

Saroj Kumar Sahoo

Saroj Kumar Sahoo Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
Division of Endocrinology, Mid and South Essex NHS Trust, Broomfield, UK

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Jayakrishnan C Menon

Jayakrishnan C Menon Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Nidhi Tripathy

Nidhi Tripathy Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Monalisa Nayak

Monalisa Nayak Department of Liver Intensive Care Unit, King’s College Hospital, London, UK

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Subhash Yadav

Subhash Yadav Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

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Objective

We studied the temporal course of hypothalamic–pituitary–adrenal (HPA) dysfunction in patients with coronavirus disease 2019 (COVID-19).

Methods

Three hundred and two patients (median age 54 years (interquartile range (IQR) 42–64), 76% males) were recruited. The HPA axis was evaluated by morning cortisol and adrenocorticotrophic hormone (ACTH) at admission (n = 232). Adrenal insufficiency (AI) during acute illness was defined using a morning cortisol <83 nmol/L. AI at 12 months follow-up was defined using a peak cortisol <406 nmol/L in the ACTH stimulation test (APST) (n = 90). Those with AI at 12 months were further assessed by APST every 6 months for recovery of hypoadrenalism.

Results

The median morning cortisol and ACTH levels during COVID-19 were 295 (IQR 133–460) nmol/L and 3.9 (0.8–6.9) pmol/L, respectively. AI was present in 33 (14%) patients; ACTH was elevated in three and low or inappropriately normal in the rest 30 patients. At 12 months, AI was seen in 13% (12/90) patients, with all cases being hypothalamic–pituitary in origin; five (42%) of them had not met the diagnostic criteria for AI during COVID-19. AI diagnosed at admission persisted at 12 months in seven patients and recovered in seven; the remaining 19 patients were lost to follow-up. The presence of AI at 12 months was independent of severity and steroid use during COVID-19. A morning cortisol <138 nmol/L during COVID-19 predicted the presence of AI at 12 months. All patients showed recovery of the HPA axis in the ensuing 12 months.

Conclusion

Central AI was common during acute COVID-19 and at 12 months of follow-up. AI can be late onset, developing after recovery from COVID-19, and was transient in nature.