PC3058: Adrenal Insufficiency in Multisystem Inflammatory Syndrome in Children ( MIS-C)

Introduction: Involvement of endocrine organ system is uncommon in multiple systems affected in MIS-C. We present endocrine dysfunction manifesting as primary adrenal insufficiency in a MIS-C patient.

Case Description: A 5-year-old previously healthy boy presented with 2 days history of fever, sore throat, headache, lethargy, vomiting, and diarrhea. He had 2 episodes of viral illness in the preceding 2 months with multiple family members being ill and had received second dose of mRNA COVID-19 vaccine recently. On arrival, he was hypotensive (blood pressure 69/31 mmHg), hypoglycemic (serum glucose: 10 mg/dL) and hyponatremic (serum sodium: 133 mmol/L). He was treated with 40 ml/kg normal saline bolus, 1 g/kg of dextrose followed by dextrose containing fluids and stress dose steroid therapy (intravenous hydrocortisone: 50 mg/m2/day) on suspicion of acute adrenal insufficiency. Laboratory investigations done at admission showed appropriate levels of growth hormone, fatty acid profile, and ketones. However, it revealed low serum cortisol level at 2.5 µg/dL (Normal range (N): 4.8-19.5 µg/dL). He was diagnosed with MIS-C based on multi-system involvement (neurological, gastrointestinal, cardiac and hematological) and elevated inflammatory markers (CRP: 7.2 mg/L, IL-6: 84.3 pg/mL, absolute neutrophil count: 8800 cells/mcL and NTpro Brain Natriuretic Peptide level: 2979 pg/mL). Additional workup of his endocrine dysfunction revealed poor cortisol response to ACTH stimulation test (serum cortisol: 5.8 µg/dL), low aldosterone level: < 3ng/dL (N: < 36 ng/dL) and low dehydroepiandrosterone level: < 10.5 µg /dL (N: < 85.3 µg/dL), more suggestive of primary adrenal insufficiency. His adrenal antibodies were negative and computerized tomography study of his abdomen revealed normal sized bilateral adrenal glands with no signs of hemorrhage or thrombosis. He was continued on hydrocortisone therapy and fludrocortisone was added based on his endocrine results and persistent borderline blood pressures with good effect. On one-month follow up, he has maintained his serum glucose and blood pressures on this therapy. Further follow up is pending for assessment of complete recovery of his adrenal function.

Discussion: Rare involvement of adrenal gland in MIS-C precludes precise pathophysiology for adrenal insufficiency. Various mechanisms including viral infection of the adrenal gland (due to presence of angiotensin 2 and transmembrane protease serine 2 receptors in adrenal zonae fasciculata and reticularis), molecular mimicry resulting in Anti-ACTH antibody, adrenal vasculopathy resulting in bilateral adrenal non-hemorrhagic or hemorrhagic infarction, immune-mediated injury with immune cell infiltration of different layers of adrenal cortex and surrounding tissue or COVID-19-related cytokine storm that impairs the release and function of ACTH and adrenal cell function have been proposed in adult patients with COVID-19 infection for adrenal insufficiency.

Conclusion: As we continue to learn more about MIS-C, an assessment of adrenal function must be undertaken in MIS-C patients presenting with hypoglycemia, hyponatremia and hypotension.