Long‐term morbidity and mortality in patients with Cushing's syndrome

Patients with Cushing's syndrome have increased morbidity and mortality from cardiovascular causes, most commonly myocardial infarction and stroke, but also aneurysms and pulmonary emboli. 1,2 These are also common causes of death in the general population in developed countries and are age-dependent. It has been estimated that untreated Cushing's syndrome patients have a four-to five-fold higher mortality rate than the general population, with only 50% of patients surviving 5 years from diagnosis. 3 The 5-year survival rate was improved to 86% after bilateral adrenalectomy. 4 The major risk factors for this mortality in the general population are diabetes (DM2), hypertension, smoking, dyslipidaemia, abdominal obesity/metabolic syndrome, and male gender. These same risk factors pertain in all forms of glucocorticoid excess. Here, I focus on endogenous Cushing's syndrome and pertinent to this is that the majority of patients (70%-80%) have adrenocorticotrophic hormone (ACTH)-dependent pituitary Cushing's disease and are frequently women (75% of cases) of premenopausal age, typically between 30 and 55 years old at diagnosis. This sex and age-group has a low incidence of cardiovascular disease in the general population. Furthermore, Cushing's syndrome patients are exposed to excess glucocorticoid for approximately 3-4 years before diagnosis and effective treatment, thereby increasing the likelihood of early development of cardiovascular risk factors.Even more concerning is the fact that, even after 'cure' of the Cushing's syndrome, the risk factors may not fully normalise with adequate amelioration of glucocorticoid excess.

“…This article is part of an update series on the diagnosis and treatment of Cushing's syndrome. [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52]…”

Section: Overall Conclusionmentioning

confidence: 99%

Cardiovascular complications of Cushings syndrome: Impact on morbidity and mortality

Clayton

2022

“…This article is part of an update series on the diagnosis and treatment of Cushing's syndrome. [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42]…”

Section: Discussionmentioning

confidence: 99%

Role of radiosurgery in the treatment of Cushing's disease

Losa

Albano

Bailo

et al. 2022

Radiotherapy is a useful adjuvant treatment for patients with Cushing's disease that is not cured by surgery. In particular, Gamma Knife radiosurgery (GKRS) has been increasingly used worldwide as the preferred radiation technique in patients with persistent or recurrent Cushing's disease. The most widely accepted criterion for hormonal remission after GKRS is normalization of urinary free cortisol (UFC) levels.

“…75,76,82 This article is part of an update series on the diagnosis and treatment of Cushing's syndrome. [117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132][133] AUTHOR CONTRIBUTIONS Julia Simon: Data curation; writingoriginal draft; writingreview and editing. Marily Theodoropoulou: Conceptualization; data curation; funding acquisition; project administration; supervision; writingreview and editing.…”

Section: Discussionmentioning

confidence: 99%

Genetics of Cushing's disease

Simon

Theodoropoulou

2022

Corticotroph tumours are primarily sporadic monoclonal neoplasms and only rarely found in genetic syndromes. Recurrent mutations in the ubiquitin specific protease 8 (USP8) gene are found in around half of cases. Mutations in other genes such as USP48 and NR3C1 are less frequent, found in less than ~20% of cases. TP53 and ATXR mutations are reported in up to one out of four cases, when focusing in USP8 wild type or aggressive corticotroph tumours and carcinomas. At present, USP8 mutations are the primary driver alterations in sporadic corticotroph tumours, TP53 and ATXR mutations may indicate transition to more aggressive tumour phenotype. Next generation sequencing efforts have identified additional genomic alterations, whose role and importance in corticotroph tumorigenesis remains to be elucidated.