Endocrine Abstracts

Background: Neuropsychiatric symptoms and cognitive dysfunction are common in Cushing´s disease (CD), and seem only partly reversible after biochemical remission has been achieved.

Aim: To investigate prescription of drugs associated with neuropsychiatric morbidity in a large national cohort of CD patients.

Methods: Patients in the Swedish Pituitary Registry, diagnosed with CD between July 2006 and January 2018 were included, n = 179 (139 women), median age at diagnosis 45 years (range 11–81). Each CD patient was matched with four controls from the background population, by sex, age and living area. Data on dispensed antidepressants, sleeping pills/tranquilizers, opioids, anti-hypertensive and anti-diabetic drugs including insulin was collected from the Swedish Prescribed Drug Registry. Dispense of each drug was investigated from 5 years before diagnosis, during active disease, and at 5- and 10-year follow-up. Chi-square and logistic regression analyses were employed.

Results: In active disease 30% of CD patients vs 16% of controls were on antidepressants, OR 2.29, (95% CI 1.57–3.35); sleeping pills/tranquilizers 32% vs 10%, OR 4.16 (2.80–6.17); opioids 49% vs 12%, OR 6.75 (4.67–9.75). 130 CD patients (remission n = 110, not remission n = 16, remission status unknown n = 4) were available for a 5-year follow-up. Use of antidepressants remained high, 27% in all CD patients regardless of disease control (in remission 26%), sleeping pills/tranquilizers, 24% (in remission 23%) and opioids, 35% (in remission 35%), whereas use of anti-diabetic drugs decreased from 28% at diagnosis to 13% (in remission 13%), RAS-blockade from 56% to 28% (in remission 25%), Ca-antagonists from 38% to 12% (in remission 8%). At 10-year follow-up of CD in remission (n = 52), use of antidepressants and sleeping pills/tranquilizers still remained high, 25% and 21% respectively. In subjects eligible for analysis before diagnosis (CD n = 103, controls n = 412), 32% of CD vs 17% of controls, OR 2.39 (1.46–3.89) had been prescribed an antidepressant on at least one occasion; sleeping pills/tranquilizers 24% vs 17%, OR 1.62 (0.96–2.73); opioids 49% vs 25%, OR 2.91 (1.86–4.54). Notably, the CD vs control difference in use of antidepressants was apparent already 5 years before CD diagnosis.

Conclusions: This prospective registry study shows that a high rate of patients with CD were on drugs for neuropsychiatric morbidity and pain from at least 5 years before diagnosis. Regardless of remission status the rate remained high, suggesting non reversible effects on mental health and a need for long-term follow-up.