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. 2019 Apr;64(1):157-168.
doi: 10.1007/s12020-018-1819-6. Epub 2018 Nov 22.

Factors predicting long-term comorbidities in patients with Cushing's syndrome in remission

Marie Helene Schernthaner-Reiter  1 , Christina Siess  1 , Alois Gessl  1 , Christian Scheuba  2 , Stefan Wolfsberger  3 , Philipp Riss  2 , Engelbert Knosp  3 , Anton Luger  1 , Greisa Vila  4
Affiliations

Factors predicting long-term comorbidities in patients with Cushing's syndrome in remission

Marie Helene Schernthaner-Reiter et al. Endocrine. 2019 Apr.

Erratum in

Abstract

Purpose: In Cushing's syndrome, comorbidities often persist after remission of glucocorticoid excess. Here, we aim to identify factors predicting long-term comorbidities in patients with Cushing's syndrome in remission.

Methods: In a retrospective cross-sectional study, 118 patients with Cushing's syndrome in remission (52 pituitary, 58 adrenal, 8 ectopic) were followed for a median of 7.9 years (range 2-38) after the last surgery. Associations between baseline anthropometric, metabolic, hormonal parameters at diagnosis, and comorbidities (obesity, diabetes, hyperlipidemia, hypertension, osteoporosis, depression) at last follow-up, were tested by uni- and multivariate regression analysis.

Results: In patients with manifest comorbidities at diagnosis, remission of Cushing's syndrome resolved diabetes in 56% of cases, hypertension in 36% of cases, hyperlipidaemia in 23%, and depression in 52% of cases. In a multivariate regression analysis, age, fasting glucose, BMI, and the number of comorbidities at diagnosis were positive predictors of the number of long-term comorbidities, while baseline 24-h urinary free cortisol (UFC) negatively correlated with the persistence of long-term comorbidities. The negative relationship between baseline UFC and long-term comorbidities was also found when pituitary and adrenal Cushing's cases were analyzed separately. Baseline UFC was negatively related to the time of exposure to excess glucocorticoids.

Conclusions: Long-term comorbidities after remission of Cushing's syndrome depend not only on the presence of classic cardiovascular risk factors (age, hyperglycemia, BMI), but also on the extent of glucocorticoid excess. Lower baseline UFC is associated with a higher number of long-term comorbidities, possibly due to the longer exposure to excess glucocorticoids in milder Cushing's syndrome.

Keywords: Cushing’s disease; Diabetes; Hypercortisolism; Hypertension; Obesity; Remission.

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Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human subjects were in accordance with the ethical approval standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study format, consent is not required.

Figures

Fig. 1
Fig. 1
Differences between pituitary and adrenal Cushing’s syndrome at diagnosis (baseline) and last follow-up. Twenty-four hour urinary free cortisol (UFC) at diagnosis a and basal and 1 mg dexamethasone (dex) suppressed morning serum cortisol at diagnosis b. Prevalence of comorbidities (hypertension, hyperlipidemia, overweight, obesity, prediabetes, diabetes, osteoporosis and depression) at baseline and follow-up in percent (of cases with known status) in pituitary c and adrenal Cushing’s syndrome d. Frequency of patients according to number of comorbidities (including hypertension, hyperlipidemia, obesity, diabetes mellitus, osteoporosis and depression) at time of diagnosis e and at last follow-up f. Significances indicate comparisons between pituitary and adrenal Cushing’s syndrome. Differences between groups were tested by independent samples Mann–Whitney-U-tests (a and b) or Pearson’s Chi-squared test (c and d). n.s. not significant, *p < 0.05, **p < 0.005, ***p < 0.001
Fig. 2
Fig. 2
Levels of baseline 24-hour urinary free cortisol (UFC) in relation to long-term comorbidities. a, b Levels of baseline UFC in relation to the number of long-term comorbidities (including hypertension, hyperlipidemia, obesity, diabetes mellitus, osteoporosis, and depression) at last follow-up in the whole cohort a and shown separately in pituitary and adrenal Cushing’s syndrome b. c–e Differences in UFC of patients with comorbidities that resolved or newly manifested during follow-up. c Differences in baseline UFC concentrations between patients with hypertension at baseline, whose hypertension persisted (present, n = 50) or resolved (absent, n = 33) at long-term follow-up. d Differences in baseline UFC between patients with prediabetes or diabetes at baseline, depending on the presence (persistent, n = 13) or absence of prediabetes/diabetes (resolved, n = 24) at long-term follow-up. e Differences in baseline UFC between patients with normal BMI at baseline, who sustained normal BMI (sustained normal, n = 15) or became overweight/obese (n = 9) at long-term follow-up. Differences between means were tested with independent samples Kruskal–Wallis test a, with two-way ANOVA b or with independent samples Mann–Whitney-U-tests c–e. *p < 0.05, **p<0.005
Fig. 3
Fig. 3
Logistic regression analyses of different comorbidities [Hypertension post a, Hyperlipidemia post b, Obesity post c, and Diabetes mellitus post d] at last follow-up (dependent variable) with predicting parameters at initial diagnosis (pre). OR odds ratio, CI confidence interval
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