====== Pituitary corticotroph adenoma recurrence ======

Recurrent Cushing's disease occurs when the symptoms of the disease return after successful treatment. This can happen for a variety of reasons, including:

Incomplete surgical removal of the [[pituitary tumor]]: If the entire tumor is not removed during surgery, it can continue to produce cortisol and cause a recurrence of symptoms.

Regrowth of the tumor: Even if the tumor is completely removed, it can sometimes regrow and cause a recurrence of symptoms.

Ectopic production of [[ACTH]]: In rare cases, [[Cushing's disease]] can be caused by a tumor outside the pituitary gland that produces ACTH, which then stimulates [[cortisol]] production.
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There is no consensus on the remission criteria for [[Cushing's disease]] or on the definition of disease recurrence after [[transsphenoidal surgery]], and comparison of the different published series is therefore difficult. A long-term recurrence rate of Cushing's disease ranging from 2%-25% has been reported. Predictors of long-term remission reported include: 1) adenoma-related factors (aggressiveness, size, preoperative identification in MRI), 2) surgery-related factors, mainly neurosurgeon experience, 3) clinical factors, of which dependence on and duration of glucocorticoid treatment are most important, and 4) biochemical factors. 

Abellán-Galiana et al. propose an ACTH value <15 pg/mL as a good long-term prognostic marker in the postoperative period of [[Cushing's Disease]]. Reaching the ACTH nadir in less time is associated to a lesser recurrence rate
((Abellán-Galiana P, Fajardo C, Riesgo-Suárez P, Pérez-Bermejo M, Ríos-Pérez C, 
Gómez-Vela J. Prognostic usefulness of ACTH in the postoperative period of
Cushing's disease. Endocr Connect. 2019 Aug 1. pii: EC-19-0297.R1. doi:
10.1530/EC-19-0297. [Epub ahead of print] PubMed PMID: 31394502.
)).
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Low postoperative [[cortisol]] levels, less than 2 mcg/dL predict for disease remission. However, even when undetectable plasma cortisol levels are present, long-term recurrence may still occur and lifetime follow-up is required. Abellán Galiana et al. report the preliminary results of the first 20 patients with Cushing's disease operated on at our hospital using nadir cortisol levels less than 2 mcg/dl as remission criterion
((Abellán Galiana P, Fajardo Montañana C, Riesgo Suárez PA, Gómez Vela J,
Escrivá CM, Lillo VR. [Predictors of long-term remission after transsphenoidal
surgery in Cushing's disease]. Endocrinol Nutr. 2013 Oct;60(8):475-82. doi:
10.1016/j.endonu.2012.09.009. Epub 2012 Dec 23. Spanish. PubMed PMID: 23266144.
)).

Patients in long-term remission of Cushing's syndrome (CS) commonly report impaired quality of life (QoL). The CushingQoL questionnaire is a disease-specific QoL questionnaire for patients diagnosed with CS. The developers of the CushingQoL recommend using a global (total) score to assess QoL.

If doctors or researchers would like to tease apart physical and psychosocial issues, the 2-subscale scoring solution would be recommended, since this solution showed to be optimal in scoring the CushingQoL. Regardless of the scoring solution used, the CushingQoL has proven to be a valuable resource for assessing health-related QoL in patients with CS
((Tiemensma J, Depaoli S, Felt JM. Using subscales when scoring the Cushing's
quality of life questionnaire. Eur J Endocrinol. 2016 Jan;174(1):33-40. doi:
10.1530/EJE-15-0640. Epub 2015 Oct 2. PubMed PMID: 26431845.
)).

===== References =====