Adrenal Infarction Secondary to COVID-19 Infection: Etiology, Pathophysiology, Imaging, Treatment, and Prognosis Introduction

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Since the outbreak of COVID-19, clinicians and researchers have become increasingly aware of its far-reaching systemic effects. While the respiratory tract remains the primary site of infection, the coagulation abnormalities and multi-organ involvement have highlighted the virus’s systemic impact. One such complication—adrenal infarction secondary to COVID-19 infection—has been reported in select cases, underscoring the vulnerability of adrenal glands to ischemic damage under hypercoagulable states.

This article provides an in-depth, expert-level analysis of the etiology, pathophysiology, epidemiology, clinical presentation, imaging findings, treatment, and prognosis of adrenal infarction associated with COVID-19. It also references a real clinical case (Figures 1–4) and offers an educational quiz for readers.

Case Reference and Imaging

A 68-year-old woman with hypertension and hypercholesterolemia presented with fever, left-sided chest pain, cough, and dyspnea. Additional symptoms included fatigue, abdominal pain, vomiting, and diarrhea. Laboratory results revealed lymphopenia, elevated C-reactive protein (CRP), and hyponatremia. Imaging studies revealed findings consistent with COVID-19 pneumonia and acute non-hemorrhagic adrenal infarction.

Imaging Features


Figure 1. Chest X-ray (P-A view): Bilateral, patchy, central and basal airspace consolidations consistent with COVID-19 pneumonia.

Figure 2. Abdominal CT, Coronal c+ portal venous phase: Enlarged adrenal gland with poor enhancement, suggesting acute infarction.

Figure 3. Abdominal CT, Axial c+ portal venous phase: Blurred adrenal margins with periadrenal fat stranding, typical for infarction.

Figure 4. CT of lung bases (lung window): Peripheral ground-glass opacities and parenchymal bands consistent with viral pneumonia.

Etiology and Cause

Adrenal infarction is a rare but critical condition, typically arising from thrombosis or embolism within the adrenal venous outflow or its microvascular supply. In COVID-19, several mechanisms converge:

  1. Hypercoagulability: COVID-19 is associated with heightened inflammatory responses (cytokine storm) leading to upregulation of clotting cascades. Elevated IL-2 and TNF-α are implicated.

  2. Endothelial Injury: SARS-CoV-2 enters endothelial cells via ACE2 receptors, found in the adrenal vasculature. Endothelial dysfunction promotes thrombosis.

  3. Adrenal Vascular Anatomy: The adrenal glands are supplied by multiple arterial branches but drained by a single central vein, making them prone to venous thrombosis and ischemic infarction.

  4. Systemic Risk Factors: Hypertension, hypercholesterolemia, and systemic inflammation further exacerbate thrombotic risks.

Pathophysiology

The pathophysiological cascade involves:

  • Cytokine-driven hypercoagulability → thrombus formation.

  • Microvascular thrombosis in adrenal sinusoids and venules.

  • Ischemia and necrosis of adrenal tissue.

  • Potential secondary hemorrhage following infarction, particularly with anticoagulation therapy.

COVID-19 therefore, acts both as a direct endothelial toxin and an indirect pro-thrombotic trigger, leading to adrenal infarction.

Epidemiology

Although adrenal infarction is uncommon, autopsy and radiological studies suggest underdiagnosis:

  • In COVID-19 ICU patients, 31% develop thrombotic complications despite prophylaxis, with venous thromboembolism being most common.

  • Adrenal infarction has been reported in both severe and moderate COVID-19 cases.

  • Pregnant women and patients with antiphospholipid syndrome are at a higher baseline risk for adrenal infarction.

Because abdominal pain and hyponatremia are often nonspecific, adrenal infarction may be missed unless imaging is performed.

Clinical Presentation

Symptoms vary but may include:

  • Systemic: Fever, fatigue, weakness.

  • Abdominal: Pain, distension, nausea, vomiting, diarrhea.

  • Respiratory: Cough, chest pain, dyspnea (due to concurrent pneumonia).

  • Endocrine: Hyponatremia, adrenal insufficiency symptoms (fatigue, hypotension, weight loss).

In the presented case, hyponatremia was the key biochemical clue. Cortisol and ACTH remained normal initially, consistent with partial adrenal infarction.

Imaging Findings

Radiological confirmation is essential:

  • X-ray: Bilateral patchy consolidations, typical of COVID-19 pneumonia.

  • CT Chest (lung window): Peripheral ground-glass opacities.

  • CT Abdomen (portal venous phase): Enlarged, poorly enhancing adrenal glands with periadrenal fat stranding.

  • Differential diagnosis: adrenal hemorrhage, metastasis, abscess.

CT remains the gold standard for diagnosis. MRI may also detect ischemia, but is less commonly used acutely.

Treatment

Management combines COVID-19 supportive care and adrenal-specific therapy:

  1. COVID-19 Management: Oxygen support (if needed), antiviral/anti-inflammatory therapies depending on guidelines.

  2. Adrenal Insufficiency Management: IV hydrocortisone (200 mg bolus, then 50 mg q6h), fluid restriction for hyponatremia, sodium supplementation.

  3. Anticoagulation: Warfarin or low molecular weight heparin to prevent further thrombotic events.

  4. Long-term: Transition to oral hydrocortisone on discharge.

Prognosis

The outcome depends on:

  • Extent of infarction: Partial infarction may preserve adrenal function, while bilateral infarction risks Addisonian crisis.

  • Timeliness of therapy: Early steroid and anticoagulant therapy improves outcomes.

  • COVID-19 severity: Patients with systemic thromboembolism or multiorgan involvement have higher mortality.

The case described showed full recovery of sodium balance and symptom improvement with medical management.

Quiz Section

1. Chest X-ray (Figure 1) most likely shows:
A) Bilateral consolidation
B) Pleural effusion
C) Rib fracture
D) Pneumothorax
E) All of the above

2. Which abdominal structure shows abnormal findings on CT (Figures 2 & 3)?
A) Aorta
B) Kidney
C) Adrenal gland
D) Pancreas
E) Mesentery

3. The pathophysiological mechanism most implicated in adrenal infarction secondary to COVID-19 is:
A) Viral replication in hepatocytes
B) ACE2-mediated endothelial injury and hypercoagulability
C) Autoimmune adrenalitis
D) Hypotension-induced ischemia

4. Which laboratory abnormality is commonly associated with adrenal infarction?
A) Hyperkalemia
B) Hyponatremia
C) Hyperglycemia
D) Leukocytosis

5. Which imaging modality is considered the gold standard for adrenal infarction diagnosis?
A) Ultrasound
B) MRI
C) CT scan
D) PET scan

6. The most appropriate initial treatment for adrenal crisis in COVID-19-associated infarction is:
A) IV insulin
B) Oral NSAIDs
C) IV hydrocortisone
D) IV antibiotics

Answer & Explanation

1. Answer: A) Bilateral consolidation. Explanation: COVID-19 pneumonia typically manifests as patchy, bilateral consolidations.

2. Answer: C) Adrenal gland. Explanation: Poor enhancement and periadrenal fat stranding confirm adrenal infarction.

3. Answer: B) ACE2-mediated endothelial injury and hypercoagulability. Explanation: COVID-19 induces a systemic hyperinflammatory state (“cytokine storm”), with elevated IL-2 and TNF-α activating the coagulation cascade, leading to a prothrombotic condition. At the same time, SARS-CoV-2 enters endothelial cells via ACE2 receptors, which are expressed in the adrenal vasculature. This causes direct endothelial injury and promotes intravascular clot formation. Together, hypercoagulability and endothelial dysfunction lead to adrenal vein/microvascular thrombosis, resulting in subsequent infarction.

4. Answer: B) Hyponatremia. Explanation: The adrenal glands produce mineralocorticoids (e.g., aldosterone), which regulate sodium and fluid balance. In adrenal infarction, impaired hormone production leads to adrenal insufficiency, commonly manifesting as hyponatremia. In the presented case, low serum sodium was a critical biochemical clue, explaining the patient’s nonspecific symptoms such as fatigue, abdominal pain, and nausea.

5. Answer: C) CT scan. Explanation: Contrast-enhanced abdominal CT (portal venous phase) is the gold standard for diagnosing adrenal infarction. Typical findings include:

  • Adrenal enlargement

  • Poor or heterogeneous enhancement

  • Periadrenal fat stranding
    Although MRI can demonstrate ischemia, CT is more widely available and faster in acute settings. Ultrasound is limited for adrenal evaluation, while PET-CT is mainly for oncological purposes.

6. Answer: C) IV hydrocortisone. Explanation: Acute adrenal infarction may precipitate adrenal crisis, which requires urgent steroid replacement therapy. The recommended regimen is:

  • IV hydrocortisone 200 mg bolus, followed by

  • 50 mg IV every 6 hours.
    Once stabilized, patients can be transitioned to oral hydrocortisone.
    In addition, anticoagulation (warfarin or LMWH) is necessary to prevent further thrombotic events, and fluid/sodium management addresses hyponatremia.

Conclusion

Adrenal infarction secondary to COVID-19 represents an under-recognized but potentially life-threatening complication. Clinicians must maintain a high index of suspicion in COVID-19 patients presenting with abdominal pain, hyponatremia, or unexplained hypotension. Early imaging and treatment with corticosteroids and anticoagulants are crucial for achieving favorable outcomes.

The presented case highlights how even patients with relatively mild respiratory symptoms can develop severe systemic thrombotic complications. As COVID-19 continues to evolve, recognizing these extra-pulmonary manifestations is crucial for timely diagnosis and improved patient care.

References

[1] Y. Tang et al., "Cytokine storm in COVID-19: The current evidence and treatment strategies," Front. Immunol., vol. 11, 2020.
[2] F. Zhou et al., "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China," Lancet, vol. 395, pp. 1054–1062, 2020.
[3] M. Klok et al., "Incidence of thrombotic complications in critically ill ICU patients with COVID-19," Thrombosis Research, vol. 191, pp. 145–147, 2020.
[4] A. Varga et al., "Endothelial cell infection and endotheliitis in COVID-19," Lancet, vol. 395, pp. 1417–1418, 2020.
[5] J. Ippolito et al., "Adrenal involvement in COVID-19 patients: A radiological insight," Clin. Imaging, vol. 69, pp. 91–95, 2021.
[6] S. Zuin et al., "Systemic thromboembolic complications in COVID-19: A review," Acta Biomed., vol. 91, no. 4, pp. 1–9, 2020.
[7] C. Bornstein et al., "Practical recommendations for the management of adrenal insufficiency in patients with COVID-19," Lancet Diabetes Endocrinol., vol. 8, pp. 472–474, 2020.
[8] K. Raghavan et al., "COVID-19 and adrenal infarction: Case series and review," Endocrine Practice, vol. 27, no. 5, pp. 505–512, 2021.

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