Endocrine Abstracts

Case history: A 51 year old lady was referred to Endocrinology with low plasma cortisol, hyperprolactinaemia and galactorrhoea. Extensive past medical history included primary hypothyroidism, B12 deficiency, diaphragmatic paralysis requiring NIV, recurrent aspergillomas, sino-atrial node disease with PPM, immunodeficiency, inflammatory arthropathy and autoimmune pancreatic insufficiency. She took numerous medications:- Itraconazole 100 mg daily, Levothyroxine 75 μg daily, Creon 10 mg tds, Risendronate 35 mg, Carbocisteine 750 mg 2 tds, Hydroxychloroquine 200 mg daily, Domperidone 10 mg tds, Lansoprazole 30 mg daily, Uniphyllin 200 mg bd, intermittent IVIG infusions and Prednisolone 7.5 mg daily. She was Cushingoid, normotensive with no postural hypotension, had expressible galactorrhoea and normal visual fields to confrontation.

Investigations: Serum electrolytes were normal. Prolactin was markedly elevated at 4585 mu/l (normal range 100–500). Short synacthen test showed undetectable ACTH and cortisol of <20 nmol/l at baseline, 60 nmol/l at 30 minutes and 74 nmol/l at 60 minutes. Basal pituitary function was otherwise normal. CT pituitary, performed due to MRI incompatible PPM, was normal with no macroadenoma or haemorrhage.

Results and treatment: Exogenous Cushing’s Syndrome with adrenal suppression secondary to interaction between Itrazconazole and chronic corticosteroids and hyperprolactinaemia secondary to interaction between Itraconazole and Domperidone were diagnosed. Prolactin rapidly normalised on stopping domperidone. Attempts to wean glucocorticoid treatment, to improve Cushing’s and promote adrenal recovery, were hampered by flares of arthritis. Follow-up short synacthen test demonstrated persistent hypoadrenalism. She developed an episode of florid Cushing’s syndrome with proximal myopathy following administration of intra-articular steroid for joint pain by her rheumatologist. With glucocorticoid weaning (total hydrocortisone 20 mg daily) she developed postural hypotension. Electrolytes remained normal but aldosterone was undetectable (<60 pmol/l). This could represent primary adrenal insufficiency (on a background of autoimmunity) or adrenal atrophy with loss of mineralocorticoid, becoming symptomatic on switch from prednisolone to hydrocortisone and dose weaning. Plasma renin was not interpretable as she was taking Propranolol. Adrenal antibodies were negative. Fludrocortisone was introduced, but very small doses required as higher doses caused hypertension.

Conclusions and points for discussion: This case illustrates endocrine presentations of drug interactions. Itraconazole inhibits microsomal enzymes including CYP3A4, resulting in delayed metabolism of drugs including domperidone and steroids. In our patient this caused galactorrhoea, hyperprolactinaemia and symptomatic Cushing’s syndrome. We are developing patient alert cards to warn of such interactions. Itraconazole may also inhibit enzymes of steroidogenesis. Polypharmacy and co-morbidity can cause difficulties in diagnosis and management. MRI pituitary was contraindicated due to pacemaker and renin was uninterpretable due to propranolol.