A 69-year-old man presented with headache and conscious collapse day 3 into COVID-19 infection, and was admitted with severe hypoosmolar euvolaemic hyponatraemia (serum sodium 119 mmol/L [135-145 mmol/L], calculated serum osmolarity 252 mmol/L) and concentrated urine with inappropriately high urine sodium (urine sodium 98 mmol/L, urine osmolarity 340 mOsmol/kg). Further investigation identified low morning serum cortisol (64 nmol/L [133-540 nmol/L]), prompting initiation of oral hydrocortisone alongside fluid restriction. COVID-19-directed therapy was not indicated. The hyponatraemia resolved day 14 post-COVID-19 infection. A short Synacthen test on day 15 demonstrated a robust cortisol response to ACTH (ACTH 26ng/L [7-60 ng/L] and cortisol 277 nmol/L at baseline, 416 nmol/L 30min, 501 nmol/L 60min post-Synacthen). Hydrocortisone was ceased.
Two years later, the patient was admitted with human metapneumovirus infection, severe hypoosmolar hyponatraemia and concentrated urine with inappropriately high urine sodium (serum sodium 115 mmol/L, calculated serum osmolarity 239 mmol/L, urine sodium 53mmol/L, urine osmolarity 552 mOsmol/kg). Further investigation revealed low morning serum cortisol (81 nmol/L) with inappropriately low serum ACTH (20 ng/L) and an otherwise normal pituitary hormone panel. MRI showed a small pituitary gland. Hyponatraemia resolved within 4 days of fluid restriction and intravenous hydrocortisone. A suboptimal cortisol response (ACTH 22 ng/L, cortisol 70 nmol/L at baseline, 218 nmol/L 30min, 297 nmol/L 60 min post-Synacthen) confirmed the diagnosis of secondary adrenal insufficiency (SAI).
Although primary adrenal insufficiency post-COVID-19 infection was described early in the pandemic, the present case represents one of only a few documented SAI cases. The lag in the abnormal short Synacthen test in our case pinpoints the time of corticotroph insult to the COVID-19 infection. This case notably highlights that COVID-19-associated adrenal insufficiency may be pituitary in origin; hence, early short Synacthen testing may be false negative due to inadequate duration of ACTH deficiency to cause adrenal atrophy.