A 54-year-old woman with no family or personal history of diabetes was referred for assessment of fasting hyperglycemia (7.6 mmol/l) and asthenia. Medical history included recurrent stomatopharyngeal candidiasis, rectal ulcerations because of abuse of analgesic suppositories, depression, and chronic sinusitis. On physical examination, she had facial plethora, diffuse bruises, cutaneous fragility, normal weight, and mildly elevated blood pressure (140/90 mmHg). An oral glucose tolerance test (OGTT) showed a 120-min plasma glucose value of 16.2 mmol/l. Homeostasis model assessment suggested decreased insulin sensitivity (67%) with intact β-cell function (106%). HbA1c value was 6.8% (3–6%). Anti-GAD, anti-IA2 antibodies, and microalbuminuria were negative.
There were no compelling clinical features to suggest either routine type 1 or type 2 diabetes. The clinical impression was suggestive of a chronic glucocorticoid excess and an ACTH-independent Cushing’s syndrome was confirmed by an abolished circadian cortisol rhythm (444 and 492 nmol/l at 8 and 20 h, respectively), elevated free urinary cortisol excretion (147 μg/day, normal limit <60), a low ACTH concentration (3 pg/ml), and a lack of morning plasma cortisol suppression after both low (355 nmol/l)- and high (467 nmol/l)-dose dexamethasone administration. However, adrenal gland imaging was normal. In this context, the possibility of hidden intake of glucocorticoids was considered. The patient admitted that she had been taking nasal drops containing prednisolone (2.5 mg/ml) at a dose of 30–40 ml per week for at least 5 years to relieve symptoms of chronic sinusitis (mean dose 10–14 mg prednisolone acetate/day). This consumption was surreptitiously continued during evaluation of the hypothalamic-pituitary-adrenal (HPA) axis. After discontinuation of nasal drops, the patient developed secondary adrenal insufficiency (low morning cortisol at 43 nmol/l) and required hydrocortisone treatment. Three months later, a reevaluation showed near normoglycemia (fasting glycemia 4.4 mmol/l, at 120 min of OGTT 7.9 mmol/l) and a normal HPA axis (morning cortisol 364 nmol/l, peak-to-ACTH stimulation 628 nmol/l).
This is the first report of overt Cushing’s syndrome induced by hidden chronic nasal prednisolone administration and complicated by diabetes and withdrawal-induced adrenal insufficiency. There are only a few publications concerning cases of Cushing’s syndrome induced by intranasal administration of steroids, and these seem to occur particularly in children and adolescents taking betamethasone or dexamethasone drops (1–3). In our case, the high cross-reactivity (171%) of prednisolone in the immunoassay used for cortisol measurement (Elecsys 2010) (4) resulted in falsely high cortisol concentrations, making the evaluation of the HPA axis even more complex.
Physicians should be aware of the deleterious effects of chronic use of intranasal steroids and the risks of their uncontrolled discontinuation.
