Pneumocystis carinii pneumonia associated with a rapid reduction of cortisol level in a patient with ectopic ACTH syndrome treated by octreotide and ketoconazole

Summary

A case is herein reported of pneumocystis carinii pneumonia in a 60-year-old female patient with ectopic production of ACTH at a position 2 cm superior to her right clavicle, revealed in an octreotide scan. Her extremely high plasma ACTH and cortisol levels (460 pg/ml and 80 μg/dl, respectively) were markedly decreased with the combined treatment of octreotide (300 μg/d) and ketoconazole (600 mg/d). As her serum cortisol concentration decreased, pneumocystis carinii pneumonia occurred on the third day of treatment. A secondary E. coli infection was superimposed and the patient died of disseminated intravascular coagulation and adult respiratory distress syndrome. This case suggests that primary prophylaxis for pneumocystis carinii infection should be initiated before cortisol lowering therapy, especially when the plasma cortisol concentration is excessively high, and that early adjunctive glucocorticoid therapy can reduce the acute mortality in patients with endogenous Cushing's syndrome and Pneumocystis carinii pneumonia. This case study would also like to point out that plasma ACTH and cortisol levels were decreased effectively by the combination of octreotide and ketoconazole in this instance of ectopic ACTH syndrome.

Pneumocystis carinii pneumonia - ectopic ACTH syndrome - Cushing's syndrome - octreotide - ketoconazole

References

• 1 Bakker R C, Gallas P RJ, Romijn J A, Wiersinga W M. Cushing's syndrome complicated by multiple opportunistic infections.  J Endocrinol Invest. 21 329-333 1998; 
• 2 Bertagna X, Favrod-Coune C, Escourolle H, Beuzeboc P, Christoforov B, Girard F, Luton J P. Suppression of ectopic adrenocorticotropin secretion by the long-acting somatostatin analog octreotide.  J Clin Endocrinol Metab. 68 988-991 1989; 
• 3 Blunt S B, Sandler L M, Burrin J M, Joplin G F. An evaluation of the distinction of ectopic and pituitary ACTH dependent Cushing's syndrome by clinical features, biochemical tests and radiological findings.  Q J Med. 283 1113-1133 1990; 
• 4 Bozzette S A, Sattler F R, Chiu J, Wu A W, Gluckstein D, Kemper C, Bartok A, Niosi J, Abramson I, Coffman J. A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome.  N Engl J Med. 323 1451-1457 1990; 
• 5 De Vita V, Goodell B, Hubbard S, Geelhoed G W, Young R C. Pneumocystis pneumonia in patients with cancer: Clinical setting.  Natl Cancer Inst Monogr. 43 41-46 1976; 
• 6 Diop S N, Warnet A, Duet M, Firmin C, Mosse A, Lubetzki J. Longterm treatment of Cushing's disease using ketoconazole. Possibility of therapeutic escape.  Presse Med. 18 1325-1328 1989; 
• 7 Engelhardt D, Weber M M, Miksch T, Abendipour F, Jaspers C. The influence of ketoconazole on human adrenal steroidogenesis: incubation studies with tissue slices.  Clin Endocrinol (oxf). 35 163-168 1991; 
• 8 Frenkel J K, Good J T, Schultz J A. Latent pneumocystis infection of rats, relapse and chemotherapy.  Lab Immun. 15 1559-1577 1966; 
• 9 Fulkerson W J, Newman J H. Endogenous Cushing's syndrome complicated by pneumocystis carinii pneumonia.  Am Rev Respir Dis. 129 188-189 1984; 
• 10 Graham B S, Tucker W S. Opportunistic infections in endogenous Cushing's syndrome.  Annals of Internal Medicine. 101 334-338 1984; 
• 11 Hendley J O, Weller T H. Activation and transmission in rats of infection with pneumocystis.  Proc Soc Exp Biol Med. 137 1401-1404 1971; 
• 12 Lamberts S WJ, Tilanus H W, Klooswijk A IJ, Bruining H A, Van der Lely A J, De Jong F H. Successful treatment with SMS 201-995 of Cushing's syndrome caused by ectopic adrenocorticotropin secretion from a metastatic gastrin-secreting pancreatic islet cell carcinoma.  J Clin Endocrinol Metab. 68 988-991 1988; 
• 13 Loli P, Berselli M E, Tagliaferri M. Use of ketoconazole in the treatment of Cushing's syndrome.  J Clin Endocrinol Metab. 63 1365-1371 1986; 
• 14 Montaner J S, Lawson L M, Levitt N, Belzberg A, Schechter M T, Ruedy J. Corticosteroids prevent early deterioration in patients with moderately severe pneumocystis carinii pneumonia and the acquired immunodeficiency syndrome.  Ann Intern Med. 113 14-20 1990; 
• 15 Natale R B, Yagoda A, Brown A, Singer C, Singer C, Stover D, Bajorunas D. Combined pneumocystis carinii and Nocardia asteroides pneumonitis in a patient with an ACTH-producing carcinoid.  Cancer. 47 2933-2935 1981; 
• 16 Phlipponneau M, Nocaudie M, Epelbaum J, De Keyzer Y, Lalau J D, Marchandise X, Bertagna X. Somatostatin analogue for the localization and preoperative treatment of an adrenocorticotropin-secreting bronchial carcinoid tumor.  J Clin Endocrinol Metab. 78 20-24 1994; 
• 17 Rosen P, Armstrong D, Ramos C. Pneumocystis carinii pneumonia: a clinico-pathologic study of twenty patients with neoplastic disease.  Am J Med. 53 426-436 1972; 
• 18 Sieber S C, Dandurand R, Gelfman N, Iannini P, Braza F. Three opportunistic infections associated with ectopic corticotropin syndrome.  Arch Intern Med. 149 2589-2591 1989; 
• 19 Singer C, Armstrong D, Rosen P P, Schottenfeld D. Pneumocystis carinii pneumonia: A cluster of eleven cases.  Ann Intern Med. 82 772-777 1975; 
• 20 Vignati F, Loli P. Additive effect of ketoconazole and octreotide in the treatment of severe adrenocorticotropin-dependent hypercortisolism.  J Clin Endocrinol Metab. 81 2885-2890 1996; 

1 Oct; octreotide, Ket; ketoconazole, CXR; chest X-ray, ARDS; adult respiratory distress syndrome

1 Blood samples for ACTH, cortisol and K were obtained from plasma at 6 AM.

2 *, cortisol level under hydrocortisone injection.

3 **, cephalosporine and aminoglycoside were given a whole period.