Correspondence
Cabergoline plus Lanreotide for Ectopic Cushing's Syndrome
N Engl J Med 2005; 352:2457-2458June 9, 2005
- Article
To the Editor:
The ectopic corticotropin syndrome, a rare cause of chronic endogenous hypercortisolism, accounts for 15 to 20 percent of corticotropin-dependent Cushing's syndrome and 5 to 10 percent of cases of Cushing's syndrome overall.1,2 This syndrome is often associated with corticotropin-secreting lung carcinoid tumors. The treatment of choice in cases in which the syndrome is associated with lung carcinoid is surgery, but the success rate of surgery is limited owing to the persistence of tumor remnants,3 which frequently necessitate palliative medical treatment to inhibit adrenal cortisol secretion. Somatostatin analogues have been observed to be effective in controlling carcinoid corticotropin secretion4; in contrast, dopamine agonists have not been used in treatment of the ectopic corticotropin syndrome. In this report, we describe a patient with the ectopic corticotropin syndrome due to a lung carcinoid tumor. After surgery failed, the condition was successfully managed with a long-acting somatostatin analogue, together with a long-acting dopamine agonist.
A 35-year-old man had a clinical picture suggestive of the ectopic corticotropin syndrome related to a carcinoid tumor; biochemical and hormonal tests confirmed the diagnosis. Somatostatin-receptor scintigraphy revealed abnormal uptake in the anterobasal region of the left lung, and computed tomography (CT) revealed a lung tumor. Thoracotomy was performed, and the presence of a corticotropin-positive, atypical carcinoid tumor was confirmed. After surgical removal of the tumor, Cushing's syndrome persisted, with increased plasma cortisol levels and increased urinary cortisol excretion. Somatostatin-receptor scintigraphy showed persistently abnormal uptake in the left lung, although chest CT revealed no abnormalities. Since reoperation was not an option, therapy with the somatostatin analogue lanreotide (90 mg per month) was begun, on the basis of the positive findings on scintigraphy. After six months, corticotropin and cortisol secretion decreased but then stopped responding to treatment, and after one year, the lanreotide therapy was stopped. Since reverse-transcriptase–polymerase-chain-reaction analysis of somatostatin-receptor and dopamine-receptor expression in a tumor sample revealed dopamine D2 receptor expression in addition to expression of somatostatin receptor subtype 5, dopamine-agonist therapy with cabergoline (7 mg per week) was initiated. After six months, corticotropin and cortisol secretion normalized but then stopped responding again, and the administration of cabergoline was stopped after one year. In a final attempt at medical therapy, combined treatment with cabergoline and lanreotide was started on the basis of the documented interaction between the dopamine D2 receptor and the somatostatin receptor subtype 5.5 Corticotropin and cortisol secretion rapidly normalized and remained normal, as did plasma corticotropin and urinary cortisol levels (Figure 1Figure 1
Urinary Cortisol Levels after Various Treatments in a Patient with the Ectopic Corticotropin Syndrome Associated with a Corticotropin-Secreting Lung Carcinoid.).This case documents the long-term effectiveness of combined treatment with a somatostatin analogue and a dopamine agonist in a patient who no longer had a response to either agent alone and supports the hypothesis that somatostatin and dopamine receptors interact and that somatostatin and dopamine agonists may potentiate actions.
5 ReferencesRosario Pivonello, M.D., Ph.D.
Federico II University, 80131 Naples, Italy
rpivone@tin.it Diego Ferone, M.D., Ph.D.
University of Genoa, 16132 Genoa, ItalySteven W.J. Lamberts, M.D., Ph.D.
Erasmus Medical Center, 3015 GD Rotterdam, the NetherlandsAnnamaria Colao, M.D., Ph.D.
Federico II University, 80131 Naples, Italy1
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Richard A. Feelders, Leo J. Hofland, Dik J. Kwekkeboom, StevenW. Lamberts, Wouter W. de Herder. 2012. Neuroendocrine Tumors. , 761-778.
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F. Gatto, L. J. Hofland. (2011) The role of somatostatin and dopamine D2 receptors in endocrine tumors. Endocrine Related Cancer 18:6, R233-R251
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Oscar D. Bruno, Karina Danilowicz, Marcos Manavela, Daniela Mana, Maria A. Rossi. (2010) Long-Term Management with Octreotide or Cabergoline in Ectopic Corticotropin Hypersecretion: Case Report and Literature Review. Endocrine Practice 16:5, 829-834
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Krystallenia I. Alexandraki, Ashley B. Grossman. (2010) The ectopic ACTH syndrome. Reviews in Endocrine and Metabolic Disorders 11:2, 117-126
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Cristina Claret, Juan J. Chillarón, Juana A. Flores, David Benaiges, Rafael Aguiló, Mar García, Guadalupe Aguilar, Alberto Goday, Juan F. Cano-Pérez. (2010) Carcinoid tumor of the thymus associated with Cushing′s syndrome and dysgeusia: case report and review of the literature. Endocrine 37:1, 1-5
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Giorgio Arnaldi, Marina Cardinaletti, Laura Trementino, Giacomo Tirabassi, Marco Boscaro. (2009) Pituitary-directed medical treatment of Cushing’s disease. Expert Review of Endocrinology & Metabolism 4:3, 263-272
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