Panhypopituitarism Induced by COVID-19 Infection

Coronavirus disease 2019 (COVID-19) infection has led to multiple endocrinopathies.   We present a case of panhypopituitarism induced by COVID -19 infection.

Case Description :

76 yo male with history of type 2 diabetes, hypertension, and 1.5 cm stable, nonfunctioning, pituitary macroadenoma diagnosed in 2017 had multiple admissions for altered mental status and hyponatremia following COVID-19 infection in April 2020. Workup revealed low free T4 0.60 ng/dL (0.8-1.8), low random cortisol 1.8 mcg/dL(2.9-19.4), high prolactin 33.5 ng/mL (2-18), low total testosterone < 10 ng/dl (175-781), SHBG 32.7 nmol/L (13.3-89.5), and low gonadotropins.

While hospitalized, he was diagnosed with pan-hypopituitarism and started on glucocorticoids and levothyroxine.  Repeat MRI pituitary done after discharge, documented stability of the macroadenoma without hemorrhage.

To date, the patient remains on glucocorticoid replacement and thyroid hormone replacement in stable state. 

Discussion :

Hypopituitarism from any etiology has an incidence of 4.2 per 100,000. Hormone replacement therapy remains the mainstay of treatment. This case represents a patient who had unexplained recurrent hyponatremia after COVID-19 infection and later diagnosed with pan-hypopituitarism.

Given the continued pandemic, more endocrinopathies related to the COVID-19 infection have been reported. We have data for other viral infections, such as SARS and Dengue, documenting pituitary dysfunction.  Review of literature documents SARS infection leading to post infectious hypophysitis with resulting secondary hypocortisolism and hypothyroidism. The cause was thought to be virus binding to pituitary angiotensin-converting enzyme 2 (ACE2) receptors. There is also data supporting COVID-19 infection leading to pituitary apoplexy and hypophysitis, though the number of cases reported is limited.

The pathophysiology is thought to be the COVID 19 virus binding to pituitary ACE2 receptors for which it has a 10-20-fold higher affinity. Furthermore, the hypothalamus also expresses ACE2 receptors making it a target for the virus.  The binding leads to cellular destruction and autoimmune collateral damage. Hypothalamic pituitary dysfunction could be due to direct effect of virus.  The virus can also lead to reversible hypophysitis.