Management of Cushings Syndrome

Management of Pituitary Cushing's Disease

Surgery has about 75% immediate remission rate and 65% long-term remission rate (see Brew Atkinson paper for review).

Octreotide and lanreotide are ineffective in Cushing's disease. Corticotroph adenomas predominantly express somatostatin receptor subtype 5 (SST5), whereas octreotide and lanreotide have primary affinity to SST2. Pasireotide has high affinity for SST5, and has shown some efficacy in a clinical trial (Boscaro 2009).

Assessment of efficacy of surgery

No clear consensus on this. Early 0800 cortisol is widely recommended. Endo Soc guidelines indicate that disease is probably cured if <50 nmol/L, and levels >140 nmol/L "require further evaluation".

Belfast protocol (see Brew Atkinson et al) is for a basal day with 24hr-UFC and measurements of cortisol every 2 hours, followed by 48-hr LDDST. Non cure is indicated by raised UFC, non-LDDST suppression or mean basal-day cortisol > about 300 nmol/L.

Treatment of persistent disease after surgery

Re-operation is recommended in most cases. Some centres recommend repeat surgery during the first admission if 0800 cortisol is elevated post-operatively - but perhaps this is too bold, as elevated 0800 cortisol does not appear to be highly specific for persistent disease.

Estrada reported 80% remission rate with radiotherapy after failed surgery. However, cure may be delayed several years, and hypopituitarism is likely.

Medical therapy may be combined with radiotherapy to achieve early reduction in hypercortisolism. Generally, avoid in women seeking fertility. Metyrapone may result in excess DOC and 11-DOC due to 11β-hydroxylase inhibition, and at least one case of pre-eclampsia presumed due to this has been reported. Ketoconazole certainly reduces androgen synthesis and might also reduce ovarian steroidogenesis though I can find no reports of this - in fact there are a few case reports of effective treatment of CD with ketoconazole during pregnancy.

Laparoscopic bilateral adrenalectomy is immediately effective and quite widely recommended. Would be preferred option in women who wish to maintain fertility.