SUN-008 - The Underrecognized Early Cues for Cushing'S Disease: Mood Disorders and Insomnia

INTRODUCTION
Cushing’s syndrome is associated with increased morbidity and mortality. However, the disease shares features with more common disorders, such as obesity, diabetes mellitus and the metabolic syndrome, leading to underdiagnosis. Clinical suspicion is becoming even more challenging in the current obesity epidemic. We sought to identify additional clinical features that can prompt early evaluation and timely management.

METHODS
We analyzed a total of 112 patients (85 F/27 M, mean + SD age: 50.4 ±15.7 y and BMI: 35.5 ± 8.36 kg/m2) who underwent endoscopic endonasal approach (EEA) transsphenoidal excision of a pituitary adenoma, of which 65 had Cushing’s disease (CD) and 47 had non-functioning (NF) adenomas. We assessed the associations between CD and insomnia, mood disorders, prior venous thromboembolism (VTE), weight change, osteoporosis, and polycystic ovary syndrome (PCOS) using univariate logistic regression followed by multivariable regression adjusted for gender, sex, and insomnia, when appropriate. Osteoporosis was defined as a T-score ≤ -2.5 by dual energy x-ray absorptiometry (DXA) at any site, a history of fragility fracture or an osteoporosis diagnosis code prior to the EEA. Statistical significance was set at p < 0.05.

RESULTS
Patients with CD were younger (CD: 46 ± 15 y, NF: 57 ± 14 y; p < 0.001) and more likely to be female (CD 85%, NF 64%; p= 0.01). Mean BMI (CD: 36.3 ± 9.0 kg/m2, NF: 34.4 ± 7.3 kg/m2) and weight (CD: 100.7 ± 26.0 kg, NF: 97.6 ± 27.9 kg) were similar. Patients with CD had higher odds of insomnia within the 1 year before EEA (OR = 5.03, p-value < 0.001), which remained significant when adjusting for gender (OR = 4.46, p-value = < 0.001). Patients with CD had 5.69 times the odds of having new or worsening anxiety or depression in the 3 years before EEA (CI 95% 2.30-14.04; p-value < 0.001), remaining significant after adjustment for sex and insomnia (OR = 3.53, CI 95% 1.29 - 9.67, p-value = 0.014). The composite outcome of anxiety/depression or new/increased antidepressant or positive PHQ/GAD were correlated with CD diagnosis in the univariate (OR = 4.38, p-value < 0.001) and adjusted model for sex and insomnia (OR = 2.67, CI 95% 1.05-6.76, p-value = 0.038). Prior VTE (p-value = 0.87), weight change in the 6-months prior to EEA (p-value = 0.18), osteoporosis (p-value = 0.62), and the diagnosis of PCOS (p-value = 0.08) were not statistically associated with the diagnosis of Cushing’s disease.

DISCUSSION
Here we demonstrate that anxiety or depression and insomnia are significant predictors of Cushing’s disease in a population with obesity. Screening for mood disorders and insomnia in the appropriate clinical context can potentially help detect Cushing’s earlier, reducing morbidity and improving quality of life.

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