title: Neuropsychiatric and cardiometabolic comorbidities in patients with previously diagnosed Cushing's disease: a longitudinal observational study.
abstract: BACKGROUND
  Only few studies have systematically investigated neuropsychiatric aspects in patients with Cushing's disease (CD). Pain syndromes have been described in patients with pituitary adenomas, but so far no systematical investigation has been conducted in patients with CD. Additionally, CD has an association with cardiometabolic comorbidities which ultimately leads to increased morbidity and mortality. Long-term treatment of the hypercortisolic state cannot prevent the persistence of an unfavourable cardiometabolic risk profile. Finally, chronic hypercortisolism is known to impact the health-related quality of life (HRQoL). We aim to systematically investigate the neuropsychiatric and cardiometabolic comorbidities, as well as assess the HRQoL, in patients with previously diagnosed CD in a longitudinal fashion.
  
  
  METHODS
  In this longitudinal study, we will assess 20 patients with CD displaying biochemical control 24 months after recruitment in the initial cross-sectional study (n=80). This will be a mixed cohort including patients after surgical, after radiation therapy and/or under current medical treatment for CD. Primary outcomes include changes in mean urinary free cortisol and changes in specific pain patterns. Secondary/exploratory neuropsychiatric domains include depression, anxiety, personality, sleep, body image and quality of life. Secondary/exploratory cardiometabolic domains include anthropometric parameters, cardiometabolic risk biomarkers and insulin resistance. Additional domains will be investigated if warranted by clinical indication. Safety assessment under medical therapy will include liver enzymes, ECG abnormalities and hyperglycaemia.
  
  
  BACKGROUND
  Risk of damage from study-conditioned measures is very small and considered ethically justified. Dual-energy X-ray absorptiometry may call for detailed fracture risk assessment. However, the radiation dose is very small and only administered on clinical indication; therefore, it is considered ethically justified. This protocol has been approved by the local medical ethics committee.
authors.affiliation: Department of Neuroendocrinology, Max Planck Institute of Psychiatry (MPIP), Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Dimopoulou
authors.affiliation: Department of Neuroendocrinology, Max Planck Institute of Psychiatry (MPIP), Munich, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Geraedts
authors.affiliation: Department of Neuroendocrinology, Max Planck Institute of Psychiatry (MPIP), Munich, Germany.
authors.forename: G K
authors.initials: GK
authors.lastname: Stalla
authors.affiliation: Department of Neuroendocrinology, Max Planck Institute of Psychiatry (MPIP), Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Sievers
mesh_terms: D000236:Adenoma / Q000150:complications; D000328:Adult; D001007:Anxiety / Q000150:complications / Q000209:etiology; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism; D015897:Comorbidity; D003430:Cross-Sectional Studies; D003863:Depression / Q000209:etiology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007333:Insulin Resistance; D008137:Longitudinal Studies; D008297:Male; D001523:Mental Disorders / Q000209:etiology* / Q000378:metabolism; D010146:Pain / Q000209:etiology*; D010554:Personality Disorders / Q000150:complications; D047748:Pituitary ACTH Hypersecretion / Q000150:complications* / Q000473:pathology / Q000523:psychology; D010902:Pituitary Gland / Q000378:metabolism / Q000473:pathology*; D010911:Pituitary Neoplasms / Q000150:complications / Q000523:psychology; D011788:Quality of Life; D012107:Research Design; D012890:Sleep; D011795:Surveys and Questionnaires
chemical_list: D006854:Hydrocortisone
references.citation: Lancet. 2001 Mar 10;357(9258):783-91
references.pmid: 11253984
references.citation: Clin Endocrinol (Oxf). 2014 Dec;81(6):826-33
references.pmid: 25052342
references.citation: J Clin Endocrinol Metab. 2002 May;87(5):1949-54
references.pmid: 11994323
references.citation: J Clin Endocrinol Metab. 2002 Aug;87(8):3662-6
references.pmid: 12161492
references.citation: J Clin Endocrinol Metab. 1997 Mar;82(3):912-9
references.pmid: 9062506
references.citation: Clin Endocrinol (Oxf). 2004 Dec;61(6):768-77
references.pmid: 15579193
references.citation: Endocrinol Metab Clin North Am. 2005 Jun;34(2):327-39, viii
references.pmid: 15850845
references.citation: J Clin Endocrinol Metab. 2005 Jun;90(6):3279-86
references.pmid: 15741267
references.citation: Brain. 2005 Aug;128(Pt 8):1921-30
references.pmid: 15888539
references.citation: Eur J Endocrinol. 2008 May;158(5):623-30
references.pmid: 18426820
references.citation: J Clin Endocrinol Metab. 2009 Sep;94(9):3365-71
references.pmid: 19509101
references.citation: J Endocrinol Invest. 2012 Apr;35(4):434-48
references.pmid: 22652826
references.citation: Eur J Endocrinol. 2012 Nov;167(5):687-95
references.pmid: 22936421
references.citation: Neuroendocrinology. 2013;97(2):139-45
references.pmid: 22572774
references.citation: Patient. 2013;6(2):113-24
references.pmid: 23575965
references.citation: Clin Endocrinol (Oxf). 2013 Jul;79(1):1-11
references.pmid: 23452135
references.citation: Clin Endocrinol (Oxf). 2013 Nov;79(5):700-7
references.pmid: 23594250
references.citation: Neuroendocrinology. 2013;98(3):188-99
references.pmid: 24080783
references.citation: Osteoporos Int. 2014 Feb;25(2):441-6
references.pmid: 24311114
references.citation: Eur J Endocrinol. 2014 Nov;171(5):581-91
references.pmid: 25117460
references.citation: J Endocrinol Invest. 2014 Oct;37(10):957-65
references.pmid: 25012159
references.citation: Psychoneuroendocrinology. 2002 Apr;27(3):367-83
references.pmid: 11818172