Case Presentation: A 61 year old female with Chronic Obstructive Lung Disease (COPD) on inhaled steroids underwent left lower lobectomy for Stage 1 Lung Adenocarcinoma in August 2017. While recovering, her house was flooded by Hurricane Harvey, in Houston, Texas. She was directly exposed to flood waters and subsequently lived with mold in her home. One year later, she was hospitalized for dyspnea and cough, not responsive to treatment for COPD exacerbation. Scattered pulmonary nodules were found on chest imaging. Biopsy with PCR revealed Mucormycosis. A one year course of Posaconazole was prescribed. In June 2019, the patient was hospitalized with new hypertension, fatigue, headache, and nausea. Physical exam was remarkable only for a blood pressure of 177/75 mm Hg. Initial laboratory evaluation including thyroid function tests and CT scan of the brain were unremarkable. CT chest revealed resolving Mucormycosis. A random cortisol was 3.0 µg/dL (normal 3.7-19.4). An adrenocorticotropic hormone (ACTH) stimulation test was performed which revealed a baseline ACTH <5 pg/mL (normal 6-50) and peak cortisol of 9.8 µg/dl at 60 minutes. The constellation of her symptoms and concomitant use of Posaconazole with inhaled steroids led to the diagnosis of Iatrogenic Tertiary Adrenal Insufficiency. Hydrocortisone was initiated with symptom improvement, and Posaconzaole was discontinued.

Discussion: Flood victims can develop a variety of disaster-related infections and complications, often presenting months after the initial event. Mucormycosis, while rare in patients without immunocompromise, has been described in natural disasters as the cause of soft tissue, pulmonary, and rhino-orbital infections. In this case, the patient’s recent surgery in combination with use of inhaled steroids predisposed her to infection.Azole antifungals, including Posaconazole, inhibit the activity of the Cytochrome P450 enzyme CYP3A4 which metabolizes corticosteroids. Concomitant use of Posaconazole with steroids (systemic or inhaled) causes increase serum levels of steroids and subsequent suppression of the hypothalamic-pituitary-adrenal axis which results in Tertiary Adrenal Insufficiency.This patient developed new hypertension, due to Posaconazole. It has been theorized that this medication blocks 11-beta hydroxylase in the adrenal gland, leading to a buildup of 11-deoxycorticosterol, a potent mineralocorticoid causing hypertension. Treatment strategies include reduction or cessation of the antifungal and mineralocorticoid antagonists such as spironolactone or eplerenone.

Conclusions: Patients who suffer through flooding may have delayed presentations of fungal infection, including atypical fungi such as Mucormycosis. Hospitalists are often on the front line of seeing patients during an event and must remain cognizant of their prolonged health consequences. Additionally, patients taking azole antifungals with inhaled or other forms of steroids can present with simultaneous hypertension and signs of adrenal insufficiency. A careful history and medication review can assist in the diagnosis of endocrine abnormalities.

IMAGE 1: Mucormycosis presenting as multiple (>15), scattered pulmonary nodules on CT chest