Background: Female Cushing's disease (CD) patients with active disease present more frequently with depression compared to their male co-sufferers. This study investigated whether the gender difference prevails after remission and whether gender-specific factors contributing to mental health exist. Methods: 72biochemically cured CD patients (11 male, mean age 45.9 ± 13.7 years) who underwent transsphenoidal tumour removal filled out the Symptom Checklist-90-Revised inventory on average 42.1 ± 32.9 months after surgery. Multiple regression analyses included the following independent factors: (i) age, (ii) presence of comorbidities, (iii) presence of hypocortisolism, (iv) presence of hypopituitarism, (v) disease duration until diagnosis, (vi) time elapsed since surgery, and (vii) postoperative radiotherapy to predict postoperative psychopathology. Results: Regarding the Global Severity Index, 23.0% of the female and 27.3% of the male CD patients presented with abnormal scores. In all nine dimensions, psychopathological abnormalities were present in both female and male patients with the same frequency and intensity (each p > 0.05). Prolonged time to diagnosis was a strong predictive factor for worse psychopathological status only in male patients. Among female patients, only the presence of comorbidities and to some extent pituitary deficiencies were related to psychopathological status. Conclusions: During the remission phase of CD, female and male patients present with similar psychopathological profiles. In males, long-term biochemical effects of previous hypercortisolism seem to be salient for psychopathology. In contrast, in females, the presence of comorbidities/stressors they have to cope with is the predictive factor for psychopathology. The results underline gender differences in CD and the need to separate them on various issues.

1.
Starkman MN, Schteingart DE: Neuropsychiatric manifestations of patients with Cushing's syndrome. Relationship to cortisol and adrenocorticotropic hormone levels. Arch Intern Med 1981;141:215-219.
[PubMed]
2.
Trethowan WH, Cobb S: Neuropsychiatric aspects of Cushing's syndrome. AMA Arch Neurol Psychiatry 1952;67:283-309.
[PubMed]
3.
Sonino N, Fava GA, Raffi AR, Boscaro M, Fallo F: Clinical correlates of major depression in Cushing's disease. Psychopathology 1998;31:302-306.
[PubMed]
4.
Dorn LD, Burgess ES, Friedman TC, Dubbert B, Gold PW, Chrousos GP: The longitudinal course of psychopathology in Cushing's syndrome after correction of hypercortisolism. J Clin Endocrinol Metab 1997;82:912-919.
[PubMed]
5.
Kelly WF, Kelly MJ, Faragher B: A prospective study of psychiatric and psychological aspects of Cushing's syndrome. Clin Endocrinol 1996;45:715-720.
[PubMed]
6.
Loosen PT, Chambliss B, DeBold CR, Shelton R, Orth DN: Psychiatric phenomenology in Cushing's disease. Pharmacopsychiatry 1992;25:192-198.
[PubMed]
7.
Dorn LD, Burgess ES, Dubbert B, Simpson SE, Friedman T, Kling M, Gold PW, Chrousos GP: Psychopathology in patients with endogenous Cushing's syndrome: ‘atypical' or melancholic features. Clin Endocrinol 1995;43:433-442.
[PubMed]
8.
Espinosa-de-Los-Monteros AL, Sosa E, Martinez N, Mercado M: Persistence of Cushing's disease symptoms and comorbidities after surgical cure: a long-term, integral evaluation. Endocr Pract 2013;19:252-258.
[PubMed]
9.
Milian M, Teufel P, Honegger J, Gallwitz B, Schnauder G, Psaras T: The development of the Tuebingen Cushing's disease quality of life inventory (Tuebingen CD-25). Part II: Normative data from 1,784 healthy people. Clin Endocrinol 2012;76:861-867.
[PubMed]
10.
Ferrari AJ, Somerville AJ, Baxter AJ, Norman R, Patten SB, Vos T, Whiteford HA: Global variation in the prevalence and incidence of major depressive disorder: a systematic review of the epidemiological literature. Psychol Med 2013;43:471-481.
[PubMed]
11.
Kuehner C: Gender differences in unipolar depression: an update of epidemiological findings and possible explanations. Acta Psychiatr Scand 2003;108:163-174.
[PubMed]
12.
Baxter AJ, Scott KM, Vos T, Whiteford HA: Global prevalence of anxiety disorders: a systematic review and meta-regression. Psychol Med 2013;43:897-910.
[PubMed]
13.
Pecori Giraldi F, Moro M, Cavagnini F, Study Group on the Hypothalamo-Pituitary-Adrenal Axis of the Italian Society of E: Gender-related differences in the presentation and course of Cushing's disease. J Clin Endocrinol Metab 2003;88:1554-1558.
[PubMed]
14.
Biller BM, Grossman AB, Stewart PM, Melmed S, Bertagna X, Bertherat J, Buchfelder M, Colao A, Hermus AR, Hofland LJ, Klibanski A, Lacroix A, Lindsay JR, Newell-Price J, Nieman LK, Petersenn S, Sonino N, Stalla GK, Swearingen B, Vance ML, Wass JA, Boscaro M: Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab 2008;93:2454-2462.
[PubMed]
15.
Derogatis L: SCL-90-R, Administration, Scoring & Procedures Manual-I for the R(evised) Version. Baltimore, John Hopkins University School of Medicine, 1977.
16.
Franke GH: SCL-90-R - die Symptom-Checkliste von L.R. Derogatis (2. vollständig überarbeitete und neu normierte Auflage). Göttingen, Beltz Test, 2002.
17.
Van Aken MO, Pereira AM, Biermasz NR, van Thiel SW, Hoftijzer HC, Smit JW, Roelfsema F, Lamberts SW, Romijn JA: Quality of life in patients after long-term biochemical cure of Cushing's disease. J Clin Endocrinol Metab 2005;90:3279-3286.
[PubMed]
18.
Milian M, Honegger J, Teufel P, Wolf A, Psaras T: Tuebingen CD-25 is a sensitive tool to investigate health-related quality of life in Cushing's disease patients in the course of the disease. Neuroendocrinology 2013;98:188-199.
[PubMed]
19.
Lindsay JR, Nansel T, Baid S, Gumowski J, Nieman LK: Long-term impaired quality of life in Cushing's syndrome despite initial improvement after surgical remission. J Clin Endocrinol Metab 2006;91:447-453.
[PubMed]
20.
Webb SM, Badia X, Barahona MJ, Colao A, Strasburger CJ, Tabarin A, van Aken MO, Pivonello R, Stalla G, Lamberts SW, Glusman JE: Evaluation of health-related quality of life in patients with Cushing's syndrome with a new questionnaire. Eur J Endocrinol 2008;158:623-630.
[PubMed]
21.
Santos A, Resmini E, Martinez-Momblan MA, Crespo I, Valassi E, Roset M, Badia X, Webb SM: Psychometric performance of the Cushing QoL questionnaire in conditions of real clinical practice. Eur J Endocrinol 2012;167:337-342.
[PubMed]
22.
Nolen-Hoeksema S, Larson J, Grayson C: Explaining the gender difference in depressive symptoms. J Pers Soc Psychol 1999;77:1061-1072.
[PubMed]
23.
Billings AG, Moos RH: Coping, stress, and social resources among adults with unipolar depression. J Pers Soc Psychol 1984;46:877-891.
[PubMed]
24.
Mazure CM, Maciejewski PK: The interplay of stress, gender and cognitive style in depressive onset. Arch Womens Ment Health 2003;6:5-8.
[PubMed]
25.
Orth DN: Cushing's syndrome. N Engl J Med 1995;332:791-803.
[PubMed]
26.
Heald AH, Ghosh S, Bray S, Gibson C, Anderson SG, Buckler H, Fowler HL: Long-term negative impact on quality of life in patients with successfully treated Cushing's disease. Clin Endocrinol 2004;61:458-465.
[PubMed]
27.
Tiemensma J, Biermasz NR, Middelkoop HA, van der Mast RC, Romijn JA, Pereira AM: Increased prevalence of psychopathology and maladaptive personality traits after long-term cure of Cushing's disease. J Clin Endocrinol Metab 2010;95:E129-E141.
[PubMed]
28.
Tiemensma J, Kaptein AA, Pereira AM, Smit JW, Romijn JA, Biermasz NR: Coping strategies in patients after treatment for functioning or nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 2011;96:964-971.
[PubMed]
29.
Miettunen J, Veijola J, Lauronen E, Kantojarvi L, Joukamaa M: Sex differences in Cloninger's temperament dimensions - a meta-analysis. Compr Psychiatry 2007;48:161-169.
[PubMed]
30.
Cloninger CR, Svrakic DM, Przybeck TR: Can personality assessment predict future depression? A twelve-month follow-up of 631 subjects. J Affect Disord 2006;92:35-44.
[PubMed]
31.
Dimopoulou C, Ising M, Pfister H, Schopohl J, Stalla GK, Sievers C: Increased prevalence of anxiety-associated personality traits in patients with Cushing's disease: a cross-sectional study. Neuroendocrinology 2013;97:139-145.
[PubMed]
32.
McHenry J, Carrier N, Hull E, Kabbaj M: Sex differences in anxiety and depression: role of testosterone. Front Neuroendocrinol 2014;35:42-57.
[PubMed]
You do not currently have access to this content.