A case report today in Pediatrics describes a previously healthy 17-year-old girl with significant encephalopathy later diagnosed as having primary adrenal insufficiency (PAI; Addison disease) as a complication of influenza infection.
PAI, which can be caused by an autoimmune process, is suspected in pediatric patients displaying poor growth, poor weight gain, nausea, vomiting, fatigue, and skin hyperpigmentation. Ill or stressed patients with untreated or undertreated adrenal insufficiency are at risk for adrenal crisis, which can lead to hypotensive shock, lethargy, confusion, coma, and death.
“While primary adrenal insufficiency is reported as a rare cause of encephalopathy, and more rarely encephalitis in adults, it is not known to be associated with encephalitis in children,” wrote the University of Cincinnati study authors.
Rapidly declining neurologic function
The teen patient was seen in the emergency department (ED) after fainting following three days of vomiting. She had an influenza A-H3 infection, altered mental status, hypoglycemia (low blood glucose), low blood pressure, and slow respiration (four breaths per minute), and lab tests showed metabolic acidosis (low blood pH), low blood sodium, elevated lactate levels (indicating a medical emergency), and very high creatinine concentrations (indicating impaired kidney function).
While primary adrenal insufficiency is reported as a rare cause of encephalopathy, and more rarely encephalitis in adults, it is not known to be associated with encephalitis in children.
She was admitted to the intensive care unit. Six days after initial magnetic resonance imaging (MRI), a repeat scan suggested acute leukoencephalopathy, or disease affecting the brain’s white matter, which is responsible for transmitting nerve signals.
After diagnostic delays caused by rapidly declining neurologic function, concern about infectious encephalitis, and unusual electrolyte imbalances, she was eventually diagnosed with adrenal crisis triggered by flu-related encephalitis.
The girl was transferred to an academic children’s hospital for neuroimmunologic and genetic testing. Her family history was notable for multiple autoimmune conditions, including type 1 diabetes, Hashimoto hypothyroidism, multiple sclerosis, vitiligo, and rheumatoid arthritis.
“Given patient and family history, islet cell antibody testing was performed, and results were positive for antibodies against glutamic acid decarboxylase; hemoglobin A1c level was normal at 5.1%,” the researchers wrote. Glutamic acid decarboxylase regulates neural excitability and insulin secretion.
Treatment with fluids, steroid replacement
Intravenous fluids rapidly normalized kidney function. After steroid replacement was started, the patient made “remarkable” functional progress and was able to speak and interact with others, the authors said. She underwent inpatient rehabilitation, and her steroid dosing was slowly reduced.
PAI is a challenging diagnosis, particularly in adolescents, often presenting with subtle and nonspecific symptoms.
After three months in the hospital, the patient was released. At outpatient follow-up a month after hospital release, she was able to carry on a full conversation, make jokes, and walk without assistance. She continues to work on memory, impulsiveness, and fine motor skills.
“It remains uncertain whether PAI-associated encephalopathy results from autoimmune or inflammatory processes, steroid deficiency, or both,” the authors wrote. “This case contributes to the growing literature of primary adrenal insufficiency in the pediatric patient and demonstrates the important role of glucocorticoids on neurologic function and calcium/phosphate metabolism.”
“PAI is a challenging diagnosis, particularly in adolescents, often presenting with subtle and nonspecific symptoms,” they added. “This case underscores the importance of maintaining suspicion for PAI even in complex presentations and highlights the importance of anticipatory guidance, including stress dosing during illness, to prevent severe outcomes.”
