Transsphenoidal surgery for Cushing's disease: a review of success rates, remission predictors, management of failed surgery, and Nelson's Syndrome

Kelly, Daniel F.

doi:10.3171/foc.2007.23.3.7

Cited by 100 publications

(37 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…05%)-EDTA (0 . 53 mM) as described previously (van Koetsveld et al 2006). All incubations were performed in quadruplicate and the cell line experiments were performed at least twice.…”

Section: Cell Culturementioning

confidence: 99%

See 1 more Smart Citation

Fluconazole inhibits human adrenocortical steroidogenesis in vitro

Pas¹,

Hofland²,

Hofland³

et al. 2012

Journal of Endocrinology

View full text Add to dashboard Cite

The antifungal agent ketoconazole is often used to suppress cortisol production in patients with Cushing's syndrome (CS). However, ketoconazole has serious side effects and is hepatotoxic. Here, the in vitro effects of ketoconazole and fluconazole, which might be less toxic, on human adrenocortical steroidogenesis were compared. The effects on steroidogenesis were examined in primary cultures of nine human adrenocortical tissues and two human adrenocortical carcinoma cell lines. Moreover, the effects on mRNA expression levels of steroidogenic enzymes and cell growth were assessed. Ketoconazole significantly inhibited 11-deoxycortisol (H295R cells; maximum inhibition 99%; EC 50 0 . 73 mM) and cortisol production (HAC15 cells; 81%; EC 50 0 . 26 mM and primary cultures (mean EC 50 0 . 75 mM)). In cultures of normal adrenal cells, ketoconazole increased pregnenolone, progesterone, and deoxycorticosterone levels, while concentrations of 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol, DHEA, and androstenedione decreased. Fluconazole also inhibited 11-deoxycortisol production in H295R cells (47%; only at 1 mM) and cortisol production in HAC15 cells (maximum inhibition 55%; EC 50 35 mM) and primary cultures (mean EC 50 67 . 7 mM). In the cultures of normal adrenals, fluconazole suppressed corticosterone, 17-hydroxypregnenolone, and androstenedione levels, whereas concentrations of progesterone, deoxycorticosterone, and 11-deoxycortisol increased. Fluconazole (1 mM) slightly increased STAR mRNA expression in both cell lines. Neither compound affected mRNA levels of other steroidogenic enzymes or cell number. In conclusion, by inhibiting 11b-hydroxylase and 17-hydroxylase activity, pharmacological concentrations of fluconazole dose dependently inhibit cortisol production in human adrenocortical cells in vitro. Although fluconazole seems less potent than ketoconazole, it might become an alternative for ketoconazole to control hypercortisolism in CS. Furthermore, patients receiving fluconazole because of mycosis might be at risk for developing adrenocortical insufficiency.

show abstract

“…05%)-EDTA (0 . 53 mM) as described previously (van Koetsveld et al 2006). All incubations were performed in quadruplicate and the cell line experiments were performed at least twice.…”

Section: Cell Culturementioning

confidence: 99%

“…CS is associated with significant morbidity and, when uncontrolled, an increased mortality (De Martin et al 2006, Newell-Price et al 2006, Kelly 2007. In most cases of CS, the primary choice of treatment is surgery.…”

Section: Introductionmentioning

confidence: 99%

Fluconazole inhibits human adrenocortical steroidogenesis in vitro

Pas¹,

Hofland²,

Hofland³

et al. 2012

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…The treatment options for Cushing's corticotrophinomas that are refractory to transsphenoidal surgery (TSS) include i) repeat TSS; ii) drugs that block cortisol production; iii) pituitary irradiation and iv) TBA (11). Although generally out of favour (12), laparoscopic TBA can be useful when a corticotrophinoma is undetectable, surgically unresectable or there is recurrence following TSS.…”

Section: Introductionmentioning

confidence: 99%

“…Although generally out of favour (12), laparoscopic TBA can be useful when a corticotrophinoma is undetectable, surgically unresectable or there is recurrence following TSS. In these cases, TBA offers 85-100% success rate in controlling hypercortisolaemia (3,11) and is particularly useful in patients with life-threatening manifestations of hypercortisolism (13). Although TBA is usually a definitive form of treatment for refractory Cushing's disease with immediate control of hypercortisolaemia, a limitation is the potential for the subsequent development of Nelson's syndrome (14).…”

Section: Introductionmentioning

confidence: 99%

Nelson's syndrome

Barber

Adams²,

Ansorge³

et al. 2010

European Journal of Endocrinology

View full text Add to dashboard Cite

Nelson's syndrome is a potentially life-threatening condition that does not infrequently develop following total bilateral adrenalectomy (TBA) for the treatment of Cushing's disease. In this review article, we discuss some controversial aspects of Nelson's syndrome including diagnosis, predictive factors, aetiology, pathology and management based on data from the existing literature and the experience of our own tertiary centre. Definitive diagnostic criteria for Nelson's syndrome are lacking. We argue in favour of a new set of criteria. We propose that Nelson's syndrome should be diagnosed in any patient with prior TBA for the treatment of Cushing's disease and with at least one of the following criteria: i) an expanding pituitary mass lesion compared with pre-TBA images; ii) an elevated 0800 h plasma level of ACTH (O500 ng/l) in addition to progressive elevations of ACTH (a rise of O30%) on at least three consecutive occasions. Regarding predictive factors for the development of Nelson's syndrome post TBA, current evidence favours the presence of residual pituitary tumour on magnetic resonance imaging (MRI) post transsphenoidal surgery (TSS); an aggressive subtype of corticotrophinoma (based on MRI growth rapidity and histology of TSS samples); lack of prophylactic neoadjuvant pituitary radiotherapy at the time of TBA and a rapid rise of ACTH levels in year 1 post TBA. Finally, more studies are needed to assess the efficacy of therapeutic strategies in Nelson's syndrome, including the alkylating agent, temozolomide, which holds promise as a novel and effective therapeutic agent in the treatment of associated aggressive corticotroph tumours. It is timely to review these controversies and to suggest guidelines for future audit.

show abstract

“…Transsphenoidal surgery (TS) is the first choice of treatment for CD. Although being a safe treatment, with a reported 30-day mortality in experienced hands of less than 1%, surgical cure is not achieved in all patients [1,2,3]. The reported initial success rate for pituitary surgery for CD varies between 60 and 86%, however the true rate tends to be lower since up to 25% of patients suffer from recurrence after apparent remission [4,5,6,7,8,9,10,11,12].…”

Section: Introductionmentioning

confidence: 99%

Biochemical Predictors of Outcome of Pituitary Surgery for Cushing’s Disease

Alwani

Herder²,

Aken³

et al. 2009

Neuroendocrinology

View full text Add to dashboard Cite

Objective: Transsphenoidal surgery (TS) is the primary therapy for Cushing’s disease (CD). The aims of this retrospective study were twofold: (i) investigate early and late results of TS for CD, and (ii) evaluate various postoperative tests in order to predict the outcome of TS. Methods: We reviewed the long-term outcome in 79 patients with CD who underwent TS (median follow-up 84 months, range 6–197). Within 2 weeks after surgery, morning serum cortisol concentrations were obtained (n = 78) and corticotropin-releasing hormone (CRH) (n = 53) and metyrapone tests (n = 72) were performed. Three groups of outcome were identified: sustained remission, early failure (persistent CD), and late relapse. Results: Immediate postoperative remission was achieved in 51 patients (65%), whereas 28 patients (35%) had persistent CD after TS. Ten patients developed recurrent CD after initial remission (20%). Morning cortisol: all relapses but one recorded serum cortisol >50 nmol/l. A cortisol threshold value of 200 nmol/l has a positive predictive value of 79% for immediate surgical failure (negative predictive failure [NPV] 97%). CRH test: CRH-stimulated peak cortisol ≧600 nmol/l predicted early failure in 78% (NPV 100%). All relapses recorded CRH-stimulated peak cortisol ≧485 nmol/l. Metyrapone test: 11-deoxycortisol ≧345 nmol/l predicted an early failure in 86% of cases (NPV 94%). Conclusion: Predictive factors of surgical failure are morning cortisol ≧200 nmol/l, 11-deoxycortisol ≧345 nmol/l after metyrapone and CRH-stimulated cortisol ≧600 nmol/l. CRH and/or metyrapone testing are not superior to morning cortisol concentration in the prediction of outcome of TS. Careful long-term follow-up remains necessary independent of the outcome of biochemical testing.

show abstract

Transsphenoidal surgery for Cushing's disease: a review of success rates, remission predictors, management of failed surgery, and Nelson's Syndrome

Cited by 100 publications

References 74 publications

Fluconazole inhibits human adrenocortical steroidogenesis in vitro

Fluconazole inhibits human adrenocortical steroidogenesis in vitro

Nelson's syndrome

Biochemical Predictors of Outcome of Pituitary Surgery for Cushing’s Disease

Contact Info

Product

Resources

About