Background: Endogenous Neonatal Cushing's syndrome (CS) is a rare condition with around 100 cases reported worldwide. Pneumocystis Jiroveci pneumonitis (PJP) is a well described, albeit rare, complication of exogenous CS (i.e. CS resulting from external glucocorticoids). The pneumonitis usually occurs following reduction of glucocorticoid dosage and is therefore thought to be triggered by an inappropriate immune reaction evident after glucocorticoids withdrawal, treatment of which includes both antibiotics and glucocorticoids. PJP has not been hitherto described in neonatal endogenous CS.
Objective: To describe the problems associated with therapy of life-threating PJP in a baby with active neonatal CS with particular attention to glucocorticoid levels.
Case presentation: A 3-month old female infant presented with failure of linear growth and mild hirsutism. She was diagnosed with CS, with high fasting cortisol levels (893 nmol/l). After low dose (15 mcg/kg) dexamethasone- cortisol paradoxically increased to 1350 nmol/l- consistent with micronodular adrenal disease. Adrenal size was normal for age by computerized tomography. Within days of diagnosis of CS, she developed hypoxemia and severe respiratory distress requiring mechanical ventilation. A chest x-ray typical of severe pneumonitis provoked performance of a broncho alveolar lavage by which Pneumocystis Jiroveci infection was diagnosed.
In order to prevent further exacerbation of pneumonitis, treatment of the CS was postponed and corticosteroids were administered. Despite antibiotic and steroidal treatment and maximum mechanical ventilatory therapy, the baby's pulmonary status continued to deteriorate. Extracorporeal membranous oxygenation (ECMO) was commenced a week after the diagnosis of PJP pneuomonitis. The combined antibiotics and glucocorticoids treatment was associated with successful eradication of PJP from bronchio-alveolar lavage fluid but also with an increase in cortisol levels to above 3000 nmol/l (probably part of her paradoxical response to external glucocorticoids) and hypokalemia and hypertension appeared. Therefore, combined therapy with Ethomidate (0.15 mg/kg/h) and Metyrapone (50mg*6/d) was initiated and cortisol levels were successfully titrated to approximate expected stress levels of 700-1000 nmol/l. However, the pulmonary damage was irreversible and after 97 days on ECMO The infant died.
Conclusion: PJP complicating endogenous CS is a severe life-threatening condition. It is not clear how best to take care of glucocorticoid levels during therapy. This case shows that despite early diagnosis of both CS and PJP, outcome can be fatal. We present this case with the hope that accumulation of experience of this condition may help develop a successful therapeutic strategy for future cases.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology