Long COVID Case Study: Persistent Hormone Deficiencies

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A case study of a 65-year-old man in Japan with long COVID describes how he recovered from certain impaired hormone deficiencies that persisted for more than a year.

Days after the patient recovered from respiratory failure and came off a ventilator, he had a sudden drop in blood pressure, which responded to hydrocortisone.

The patient was found to have low levels of growth hormone and adrenocorticotropic hormone (ACTH) (hypopituitarism) that persisted for more than a year. He also had low levels of testosterone that remained low at 15 months (the study end).

“An important finding in the present case is the eventual recovery from hypopituitarism over time, but not from hypogonadism,” the researchers write, in their study published in Endocrine Journal.

This is the first published case of secondary adrenal insufficiency after recovery from COVID-19, which was confirmed using an insulin tolerance test Kai Yoshimura, Kakogawa Medical Center, Japan, and colleagues report.

The findings show that “pituitary insufficiency should be considered in patients with prolonged symptoms of COVID-19,” they continue, since it can be treated with hormone supplements that markedly improves symptoms and quality of life.

“It might be worthwhile to screen for endocrine dysfunction in patients with such persistent symptoms after their recovery from the acute disease,” the researchers conclude.

Case Study Timeline

The patient in this study was healthy without obesity, previous endocrine disease, or steroid use. He was admitted to hospital because he had dyspnea and fever for 8 days and a reverse transcription-polymerase chain reaction (RT-PCR) test that was positive for COVID-19.

He received ciclesonide 200 µg/day for 2 days. Then he was put on a ventilator and the drug was discontinued and “favipiravir, ritonavir, and lopinavir, a standard regimen during the early phase of the COVID-19 pandemic, were initiated;” the researchers explain.

On day 25 of his hospital stay the patient had recovered from respiratory failure and was extubated.

On day 31, he had a negative PCR test for COVID-19.

On day 36, the patient’s blood pressure suddenly dropped from 120/80 mmHg to 80/50 mmHg. His plasma ACTH and serum cortisol levels were low, suggesting secondary adrenal insufficiency. The low blood pressure responded to hydrocortisone 100 mg, which was gradually tapered.

At day 96, the patient was discharged from hospital with a dose of 15 mg/day hydrocortisone.

At 3 months after discharge, an insulin tolerance test revealed that the patient’s ACTH and cortisol responses were blunted, suggestive of adrenal insufficiency. The patient also had moderate growth hormone deficiency and symptoms of hypogonadism.

At 6 months after discharge, the patient started testosterone therapy because his dysspermatism had worsened.

At 12 months after discharge, a repeat insulin tolerance test showed that both ACTH and cortisol responses were low but improved. The patient was no longer deficient in growth hormone.

At 15 months after discharge, early morning levels of ACTH and cortisol were now in the normal range. The patient discontinued testosterone treatment, but the symptoms returned so he resumed it.

Long COVID Symptoms, Possible Biological Mechanism

The present case shows how certain COVID-19-associated conditions develop after the onset of, or the recovery from, respiratory disorders, the authors note.

Symptoms of long COVID-19 include fatigue, weakness, hair loss, diarrhea, arthralgia, and depression, and these symptoms are associated with pituitary insufficiency, especially secondary adrenocortical insufficiency.

In addition, an estimated 25% of sexually active men who recover from COVID have semen disorders such as azoospermia and oligospermia.

The underlying mechanism by which COVID-19 might trigger pituitary insufficiency is unknown, but other viral infections such as influenza-A and herpes simplex are also associated with transient hypopituitarism. An exaggerated immune response triggered by SARS-CoV-2 may explain the dysfunction of multiple endocrine organs, the researchers write.  

The researchers have declared no conflicts of interest.

Endocr J. Published online July 14, 2022. Article.

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