Endocrine Abstracts

Case history: A 45-year-old female with a background of depression presented with asthma exacerbation. She was taking paroxetine and mirtazapine for depression. Over the preceding six months the patient’s asthma control had deteriorated, resulting in overuse of inhaled beclometasone. On questioning, the patient reported a four stone weight gain in four months with generalised weakness, dizziness and fatigue during simple activities. On examination, the patient appeared overtly Cushingoid.

Investigations: Overnight dexamethasone suppression test revealed 11pm cortisol of 48 and 8am cortisol of less than 27 nmol/L, excluding Cushing’s disease. Early morning cortisol, repeated without dexamethasone suppression, measured 27 nmol/L and short synacthen test supported the diagnosis of adrenal insufficiency. Pituitary profile revealed suppression of further hormones, with normal imaging. Our investigations indicated severe hypothalamic-pituitary adrenal axis suppression with concurrent iatrogenic Cushing’s Syndrome.

Results and treatment: The patient was commenced on hydrocortisone and counselled on her diagnosis. Along with education on inhaler technique and appropriate use, her drug control was optimised. According to the GP, signs and symptoms had developed rapidly over a few months. Overuse of inhaled corticosteroids (ICS) is common, reported in up to 50% of patients and therefore may only provide partial explanation for such severe and rapid progression in this patient. Cytochrome (CYP) 34A is the enzyme responsible for steroid metabolism. It is well documented that concurrent use of an ICS and CYP34A inhibitors, such as antivirals and antifungals, results in rapid development of steroid-related side effects. It is rarely described in patients on commonly prescribed antidepressants. Paroxetine is a strong inhibitor of CYP450 enzymes, with laboratory studies suggesting a moderate inhibitory effect on CYP34A. Additionally, as mirtazapine is also metabolized by the CP34A enzyme, competitive inhibition may result. This drug interaction, whilst significant due to the commonality of such prescriptions, may be under-appreciated. To our knowledge, there is one just existing case in the literature reporting such interaction.

Conclusions: Whilst there are systemically safer ICS available, current national guidelines recommend the least costly drug that is suitable for an individual should be prescribed. This can be problematic with concurrent use of CYP450 inhibitors, which is often overlooked. Therefore, practitioners should be aware of the issues discussed and be able to recognize early presentation of side effects. Additionally, education on inhaler technique and appropriate use could prevent exacerbation of this drug interaction.