Adrenal, thyroid function preserved in COVID-19 survivors

Survivors of COVID-19 appear to have normal adrenal and thyroid function at least 3 months following disease presentation, a study has found. Many of these patients have experienced persistent fatigue, but their symptoms are not accounted for by overt adrenal or thyroid gland dysfunction.

“These findings have important implications for the clinical assessment of patients after COVID-19, an emerging field of medicine,” the researchers said.

This prospective, observational study was conducted at the Clinical Research Facility, Imperial College NHS Healthcare Trust, UK, to assess adrenal and thyroid gland function in COVID-19 survivors. Seventy patients aged ≥18 years were included at least 3 months after COVID-19 diagnosis. They attended a research study visit (8:00–9:30 AM), during which a short Synacthen test (250 µg IV bolus) and thyroid function assessments were performed.

All patients had a peak cortisol ≥450 nmol/L following Synacthen test, which indicated adequate adrenal reserve. No difference was noted between basal and peak serum cortisol in relation to disease severity or history of dexamethasone treatment during COVID-19. [J Clin Endocrinol Metab 2021;106:2208-2220]

Likewise, baseline or peak cortisol did not differ after Synacthen test or in thyroid function tests, or thyroid status, among patients with fatigue (n=44) compared to those without (n=26).

“The standard 250-µg Synacthen test remains the most widely used dynamic function test for assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis, and is the gold-standard test for diagnosing primary adrenal insufficiency,” the researchers said. [J Clin Endocrinol Metab 2016;101:364-389; Clin Endocrinol (Oxf) 2018;88:744-751; J Clin Endocrinol Metab 2018;103:3050-3059; Lancet 2014;383:2152-2167]

“Given the pathophysiology of COVID-19, primary, secondary, and tertiary adrenal insufficiency were all distinct clinical possibilities, and thus the standard short Synacthen test provided the most practical way to interrogate the HPA axis in its entirety,” they added.

Previous studies reported that persistent symptoms after COVID-19 affected about 53–63 percent of patients. This was consistent with the present findings, where direct questioning revealed that 62.9 percent of patients experienced persistent fatigue after COVID-19. [Lancet 2021;397:220-232; JAMA 2020;324:603-605]

“Not only is disturbance of the adrenal axis frequently associated with fatigue, but dysfunction of the thyroid axis may frequently present with tiredness,” the researchers said. “Of those patients not already known to have thyroid disease (n=68), thyroid function tests (TSH, fT4, and fT3) were all within the normal range.”

They also demonstrated a small decrease in TSH and FT4 compared to the pre-COVID-19 baseline, as well as recovery to intra-individual set points for FT4 and TSH. Furthermore, no evidence of increase in frequency of hypo- or hyperthyroidism was found in patients with fatigue compared to those without. [J Clin Endocrinol Metab 2021;106:e803-e811]

“Endocrine systems are vulnerable to the effects of COVID-19 as many glands express the angiotensin-converting enzyme 2 receptor, used by the SARS-CoV-2 virion for cellular access,” the researchers noted.