Endocrine Abstracts

Background: Iatrogenic adrenal insufficiency (AI) refers to primary, secondary, or tertiary hypoadrenalism associated with drug administration, surgery, or irradiation. The most common cause of secondary adrenal insufficiency is exogenous glucocorticoids. Hepatic metabolism of inhaled corticosteroids (ICS) takes place via cytochrome P450 3A4. Nevertheless, it can be decreased by enzyme inhibitors such as itraconazole or ritonavir, thus leading to an increase in the bioavailability of ICS. This can result in an accumulation of the steroid drug and a Cushing’s syndrome whilst also leading to suppression of adrenocorticotropic hormone (ACTH) and hypoadrenalism. We report here a case of coexisting secondary adrenal insufficiency and iatrogenic Cushings syndrome from combined inhaled steroid therapy and Itraconazole.

Case: A 45-year-old female with known bronchiectasis, childhood asthma, atopic eczema and Allergic bronchopulmonary aspergillosis (ABPA) was taking Itraconazole 200mg twice daily for her ABPA for over three years. In addition, she was also on combined therapy with Symbicort (budesonide /formoterol) 200/6 inhaler, Mometasone 50 mg nasal spray and topical Hydrocortisone 1% cream. She presented to her general practitioner initially with a few months’ history of fragile, paper-thin skin and developing easy bruising. She had also had central weight gain and had developed puffy, rounded facial features. Her symptoms had progressively worsened over the previous one year. Her initial investigations were two 9am serum cortisol levels of <28 nmol/l. An ACTH stimulation (Short Synacthen) Test demonstrated both basal and 30 minute cortisol values of <28nmol/l. Her combined therapy was complicated by profound adrenal shutdown and impairment of inhaled steroid clearance which resulted in paradoxical Cushingoid features.

Discussion: This case emphasises the importance of considering assessing the hypothalamic-pituitary-adrenal-axis, when considering combined therapy with Itraconazole and inhaled steroid treatment. Clinicians should be aware of the potential occurrence of iatrogenic Cushing syndrome and secondary adrenal insufficiency due to the association of inhaled corticosteroids with itraconazole.