Cardiovascular complications of Cushings syndrome: Impact on morbidity and mortality

Transsphenoidal surgery is the first-line treatment for Cushing's disease to selectively remove the tumor. The rate of postoperative remission is estimated around 70%-80% in expert centers. However, the long-term remission rate is lower because of recurrence during follow-up that can be observed in 15% to 25% of the patients depending on the studies and duration of follow-up. There is no significant predictive factor of recurrence before surgery, but postoperative corticotroph insufficiency and its duration has been found to be a protective factor for recurrence in many studies.The persistence of a positive response to desmopressin after surgery is associated with a higher rate of recurrence. Long term monitoring for recurrence with annual clinical and hormonal investigations after the hypothalamic-pituitary-adrenal axis postoperative recovery is advised. The biological tests used for the diagnosis of Cushing's syndrome (24 h-urinary-free cortisol [UFC], late-night salivary or serum cortisol, 1 mg dexamethasone suppression test) can be used to screen for recurrence.Several studies report that increased late night cortisol and alterations of dynamic testing can be observed before the increased 24 h-UFC. For this reason it is suggested that late-night salivary cortisol would be a very sensitive tool to diagnose recurrence, pending the realization of several assays in case of borderline or discrepant result. This review will summarize the knowledge about recurrence of Cushing's disease after pituitary surgery and the current recommendations for its monitoring and diagnosis.

Section: Discussionmentioning

confidence: 99%

Long‐term follow‐up and predictors of recurrence of Cushing's disease

Guignat

Bertherat

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][43]…”

Section: Discussionmentioning

confidence: 99%

Medical management of Cushing's disease: When and how?

Castinetti

2022

Transsphenoidal surgery is the first‐line treatment of Cushing's disease. However, medical treatment can be given in a high proportion of patients with this rare condition. This is especially the case in severe hypercortisolism for which medical treatment will be given for a short period of time to prepare the patient for surgery, or on a long‐term basis after failed transsphenoidal surgery, or when waiting for the maximal beneficial effect of radiation techniques. These different situations all require that hypercortisolism be perfectly controlled. Severe hypercortisolism is frequently treated by a block and replace approach during which a substitutive treatment is given after the induction of adrenal insufficiency. Mild hypercortisolism, the most frequent situation, is usually treated with a titration approach with a progressive dose increase. This approach requires certainty of eucortisolism because patients may be treated for a prolonged period. This review details the main situations during which medical treatment should be considered, as well as the way in which to monitor them to avoid the long‐term consequences of mild hypo‐ or hypercortisolism.

“…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.