ACTH-Dependent Cushing's Syndrome “Cured” By Histoplasmosis-Mediated Destruction of the Adrenal Glands Causing Adrenal Insufficiency

Presentation Number: SAT-410
Date of Presentation: March 7th, 2015

Jorge Javier Figueroa*1, Amy M DeGueme1, Iram Hussain2, Melissa Nelson3, Ugis Gruntmanis4 and Uma Gunasekaran5
1UT Southwestern Medical Center, Dallas, TX, 2University of Texas Southwestern Medical Center, Dallas, TX, 3UT Southwestern Medical Center, 4University of Texas, Southwestern Medical Center and University of Latvia, Dallas, TX, 5UT Southwestern Medical Center, Irving, TX

Abstract

BACKGROUND: Cushing's syndrome can lead to severe morbidity and mortality if untreated. We describe a patient with untreated ACTH-Dependent Cushing’s syndrome who presented with adrenal insufficiency (AI) secondary to adrenal histoplasmosis six years after her initial diagnosis. Disseminated histoplasmosis commonly involves the adrenal cortex causing necrosis and is associated with adrenal enlargement on imaging, with up to 50% of patients developing AI.

CLINICAL CASE: A 55 year old woman with type 2 diabetes and hypertension was initially seen for evaluation of an elevated morning cortisol level of 24.8 mcg/dL (normal: 4.3-22.4 mcg/dL). At the time, her physical examination findings included dorsocervical fat pad, moon facies, abdominal striae, and hirsutism. Further biochemical evaluation revealed a 24 hour urinary free cortisol of 302 mcg/24hr (normal: 3.5-45 mcg/24hr), an inappropriately normal ACTH of 49 pg/mL (normal: 6-58 pg/mL), and a 1-mg overnight dexamethasone suppression test with a cortisol of 31.9 mcg/dL (normal: < 1.8 mcg/dL). An abdominal CT scan showed normal adrenal glands with no hyperplasia or nodules, and a pituitary MRI showed a partially empty sella without evidence of an adenoma. She was lost to follow up so treatment was not initiated for the ACTH-dependent Cushing’s syndrome.

Six years later, she was admitted for septic shock with a morning cortisol level of 3.2 mcg/dL and stress dose steroids were started. Pituitary MRI was negative for pituitary adenoma or hemorrhage. Abdominal CT scan showed diffusely enlarged adrenal glands, each measuring 6 cm. Subsequent abdominal MRI ruled out hemorrhage and confirmed adrenal gland hyperplasia. She was discharged on hydrocortisone for AI but was readmitted one month later for adrenal crisis (morning cortisol: 2.7 mcg/dL) and septic shock secondary to a urinary tract infection. Of note, her calcium level was 15.8 mg/dL (normal: 8.4 - 10.2 mg/dL), which prompted investigations for secondary causes of AI. Testing for tuberculosis, sarcoidosis, multiple myeloma and HIV was negative. Fungal serologies revealed an elevated histoplasma mycelia antibody of 1:64 (normal: < 1:8) and urinary histoplasma antigen was weakly positive, suggesting a chronic infection. An adrenal biopsy showed histoplasmosis infection. Itraconazole was started (with a plan to continue for one year), and hydrocortisone was tapered to home dosing.

CONCLUSION: This is the first case reported in the literature of a patient with ACTH-dependent Cushing’s syndrome that is “cured” by an adrenal histoplasmosis infection. An infection with Histoplasma capsulatum is usually asymptomatic or self-limited, however, this patient was immunocompromised due to hypercortisolemia. This case demonstrates the need to have a high index of suspicion for adrenal insufficiency in patients presenting with septic shock, despite a previous history of Cushing’s syndrome.

 

Nothing to Disclose: JJF, AMD, IH, MN, UG, UG