Effect of long acting repeatable octreotide on the ACTH secretion in Nelson's syndrome and Cushing's disease

ARREGGER AL, CARDOSO E, TUMILASCI G, CONTRERAS L

Boston

Congreso; Endo 2011; 2011

Endocrine Society

Effect of Long-Acting Repeatable Octreotide on the ACTH Secretion in Nelson Syndrome and Cushing Disease Alejandro Luis Arregger, MD, Estela Maria Cardoso, PhD, Gloria Tumilasci, PhD and Liliana Noemi Contreras, MD Endocrine Research Department (ALA,EMC,GT,LNC), University of Buenos Aires IDIM-CONICET, Buenos Aires Argentina Background: Management of persistent ACTH excess in Nelson's syndrome (NS) and Cushing's disease (CD) remains a challenge. Somatostatin (SS) and its analogs as octreotide decrease ACTH secretion through SS receptors (sst) of pituitary cells. To our knowledge there are no reports on the effect of long-acting repeatable octreotide (oct-lar) in patients with NS and CD who failed conventional therapy. Clinical cases: We studied one woman (AS) with NS and two (LC and GG) with persitent CD. They were all treated with oct-lar (20 mg/monthy i.m.). AS had received radiotherapy twice and underwent trans-cranial pituitary surgery in four different occasions.The pituitary tumor continued extending to the sphenoid sinus .She was on hydrocortisone and fludrocortisone persisting pigmented with left eye blindness and palsy of the third cranial nerve. Monthly oct-lar was prescribed; three months later ACTH levels fell from 1069.0±10pg/ml (normal 50.0 pg/ml, IRMA) to 525.0 ±13.0 pg/ml and to 321.0±4.0 pg/ml after 21months; p=0.001.Pigmentation decreased, visual field remained unchanged with no evidence of tumor growth. In order to determine whether previous radiotherapy was involved in the control of NS oct-lar was discontinued and ACTH increased significantly (1210.0±5.0 pg/ml) p= 0.0001, suggesting the inhibitory role of this analog. LC had remission of CD after selective pituitary adenomectomy relapsing after 5 years. She underwent total pituitary surgery remaining with cortisol excess (UFC =160.0±20.0µg/day; normal 90.0 µg/day; ACTH = 59.0± 4.0 pg/ml) developing toxicity while on ketoconazole. After 4 monthly injections of oct-lar, UFC and ACTH levels did not show differences from baseline (130.0±10.0µg/day and 66.0±17.0 pg/ml, respectively); p0.090 for both. GG persisted with CS after total hypophysectomy and gamma knife radiosurgery. After a 4 month trial with oct-lar UFC 236.0 ±15.0 µg/day and ACTH 85.0±13.0 pg/ml did not differ from baseline (211.0 ±13.8 µg/day and 83.0±8.0 pg/ml; respectively); p0.767 and clinical changes were not observed. Conclusion: Oct-lar therapy reduced ACTH secretion in NS without side effects but failed to control ACTH in CD, probably due to the inhibitory effect of glucocorticoids on sst2 receptor expression. Further trials in CD patients should consider the combination of oct-lar with adrenostatic drugs