Recurrence after pituitary surgery in adult Cushing’s disease: a systematic review on diagnosis and treatment

Abstract

Purpose Recurrence after pituitary surgery in Cushing’s disease (CD) is a common problem ranging from 5% (minimum) to 50% (maximum) after initially successful surgery, respectively. In this review, we give an overview of the current literature regarding prevalence, diagnosis, and therapeutic options of recurrent CD. Methods We systematically screened the literature regarding recurrent and persistent Cushing’s disease using the MESH term Cushing’s disease and recurrence. Of 717 results in PubMed, all manuscripts in English and German published between 1980 and April 2020 were screened. Case reports, comments, publications focusing on pediatric CD or CD in veterinary disciplines or studies with very small sample size (patient number < 10) were excluded. Also, papers on CD in pregnancy were not included in this review. Results and conclusions Because of the high incidence of recurrence in CD, annual clinical and biochemical follow-up is paramount. 50% of recurrences occur during the first 50 months after first surgery. In case of recurrence, treatment options include second surgery, pituitary radiation, targeted medical therapy to control hypercortisolism, and bilateral adrenalectomy. Success rates of all these treatment options vary between 25 (some of the medical therapy) and 100% (bilateral adrenalectomy). All treatment options have specific advantages, limitations, and side effects. Therefore, treatment decisions have to be individualized according to the specific needs of the patient.

Corticotroph tumor progression after bilateral adrenalectomy (Nelson’s syndrome): systematic review and expert consensus recommendations

“…Rates for persistence of CD or recurrence after initial remission were reported with a great variability depending on the ratio of micro-/macroadenoma, the experience of the surgeons and the definition for persistence and recurrence (1,2). Based on meta-analyses the rates for persistence and recurrence after initial TSS ranged from 22 to 24% (persistence) (3,4,5) and 10-12% (recurrence) (4), respectively. Studies with a longer follow-up showed higher recurrence rates.…”

“…Studies with a longer follow-up showed higher recurrence rates. Although the highest risk for recurrent disease is observed in the first five years (6), it can occur as late as several decades after surgery and lifelong surveillance for recurrence is essential. Second-line treatments in persistent and recurrent CD include repeat transsphenoidal surgery, fractionated pituitary radiation and radiosurgery, medical therapy targeting ACTH and cortisol excess, and bilateral adrenalectomy (BADX).…”

Signs, symptoms and biochemistry in recurrent Cushing disease: a prospective pilot study

“…Regular follow-ups after first successful surgery are recommended [5,13,14] but a unifying consensus on specific clinical and biochemical testing and follow-up intervals has not been established so far. Also, recurrence criteria are not universally agreed on [15].…”

Treatment and outcomes of recurrent/persistent Cushing’s disease: a single-center experience

“…Our remission criteria for RCD and PCD were as follows: (I) The 24 UFC level was reduced to eucortisolism levels (20-100 µg/24 hour), including hypocortisolism levels (<20 µg/24 hour) and undetectable 24 UFC (10). (II) Serum cortisol levels decreased to within or below the normal range (5.0-25.0 µg/dL) and values lower than 5 or 3 µg/dL were specified (10,11). Data were obtained after withdrawal of glucocorticoids.…”