Abstract
The diagnosis of Cushing’s syndrome (CS) may sometimes be cumbersome. In particular, in ACTH-dependent CS it may be difficult to distinguish between the presence of an ACTH-secreting pituitary adenoma and ectopic ACTH and/or CRH secretion.In such instances, the etiology of CS may remain unknown despite extensive diagnostic workout, and the best therapeutic option for each patient has to be determined. We report here the case of a 54-yr-old man affected by ACTH-dependent CS in association with a left adrenal adenoma and medullary thyroid carcinoma (MTC). He presented with clinical features and laboratory indexes of hypercortisolism associated with elevated levels of calcitonin. Ectopic CS due to MTC was reported previously. In our case hypercortisolism persisted after surgical treatment of MTC. Thorough diagnostic assessment was performed, in order to define the aetiology of CS. He was subjected to basal and dynamic hormonal evaluation, including bilateral inferior petrosal sinus sampling. Extensive imaging evaluation was also performed. Overall, the laboratory data together with the results of radiological procedures suggested that CS might be due to inappropriate CRH secretion. However, the source of CRH secretion in this patient remained unknown. It was then decided to remove the left adenomatous adrenal gland. Cortisol level fell and has remained within the normal range nine months after surgery. This case well depicts the complexity of the diagnostic workout, which is needed sometimes to correctly diagnose and treat CS, and suggests that monolateral adrenalectomy may represent, at least temporarily, a reasonable therapeutic option in occult ACTH-dependent hypercortisolism.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arnaldi G, Angeli A, Atkinson AB, et al. Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 2003, 88: 5593–02.
Orth DN. Cushing’s syndrome. N Engl J Med 1995, 332: 791–03.
Wajchenberg BL, Mendonca BB, Liberman B, et al. Ectopic adrenocorticotropic hormone syndrome. Endocr Rev 1994, 15: 752–87.
Invitti C, Pecori Giraldi F, De Martin M, Cavagnini F. The Study Group of the Italian Society of Endocrinology on the pathophysiology of the hypothalamic-pituitary-adrenal axis. Diagnosis and management of Cushing’s syndrome: results of an Italian multicentre study. J Clin Endocrinol Metab 1999, 84: 440–8.
Oldfield EH, Doppman JL, Nieman LK, et al. Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing’s syndrome. N Eng J Med 1991, 325: 897–05.
Kaltsas GA, Giannulis MG, Newell-Price JDC, et al. A critical analysis of the value of simultaneous inferior petrosal sinus sampling in Cushing’s disease and the occult ectopic adrenocorticotropin syndrome. J Clin Endocrinol Metab 1999, 84: 487–92.
Arioglu E, Doppman J, Gomes M, et al. Cushing’s syndrome caused by corticotropin secretion by pulmonary tumorlets. N Engl J Med 1998, 339: 883–6.
Ozbey N, Bozbora A, Kalayci G, et al. Cushing’s syndrome caused by ectopic corticotropin secretion by multiple peripheral pulmonary carcinoids and tumorlets of carcinoid type. J Endocrinol Invest 2000, 23: 536–41.
Peri A, Bemporad D, Parenti G, Luciani P, Serio M, Mannelli M. Cushing’s syndrome due to intermittent ectopic ACTH production showing a temporary remission during a pulmonary infection. Eur J Endocrinol 2001, 145: 605–11.
Thomas CC, Cowan RJ, Albertson DA, Cooper MR. Detection of medullary carcinoma of the thyroid with I-131 MIBG. Clin Nucl Med 1994, 19: 1066–8.
Yamamoto Y, Isobe Y, Nishiyama Y, et al. Iodine-131 MIBG imaging in multiple endocrine neoplasia type 2B. Clin Nucl Med 1998, 23: 13–5.
Boscaro M, Barzon L, Fallo F, Sonino N. Cushing’s syndrome. Lancet 2001, 357: 783–91.
Young J, Deneux C, Grino M, Oliver C, Chanson P, Schaison G. Pitfall of petrosal sinus sampling in a Cushing’s syndrome secondary to ectopic adrenocorticotropin-corticotropin releasing hormone (ACTH-CRH) secretion. J Clin Endocrinol Metab 1998, 83: 305–8.
Fjellestad-Paulsen A, Abrahamsson PA, Bjartell A, et al. Carcinoma of the prostate with Cushing’s syndrome. A case report with histochemical and chemical demonstration of immunoreactive corticotropin-releasing hormone in plasma and tumoral tissue. Acta Endocrinol (Copenhagen) 1988, 119: 506–16.
Vrezas I, Willenberg HS, Mansmann G, Hiroi N, Fritzen R, Bornstein SR. Ectopic adrenocorticotropin (ACTH) and corticotropin-releasing hormone (CRH) production in the adrenal gland: basic and clinical aspects. Microsc Res Tech 2003, 61: 308–14.
Tourniaire J, Rebattu B, Conte-Devolx B, et al. Cushing’s syndrome caused by ectopic production of CRH by a medullary carcinoma of the thyroid body. Ann Endocrinol (Paris) 1988, 49: 61–7.
Tagliabue M, Pagani A, Palestini N, Manieri C, Martina V. Multiple endocrine neoplasia (MEN IIB) with Cushing’s syndrome due to medullary thyroid carcinoma producing corticotropin-releasing hormone. Panminerva Med 1996, 38: 41–4.
Hijzai YM, Nieman LK, Medeiros LJ. Medullary carcinoma of the thyroid as a cause of Cushing’s syndrome: a case with ectopic adrenocorticotropin secretion characterized by double enzyme immunostaining. Hum Pathol 1992, 23: 592–6.
Smallridge RC, Bourne K, Pearson BW, Van Heerden JA, Carpenter PC, Young WF. Cushing’s syndrome due to medullary thyroid carcinoma: diagnosis by proopiomelanocortin messenger ribonucleic acid in situ hybridization. J Clin En-docrinol Metab 2003, 88: 4565–8.
Loli P, Vignati F, Grossrubatscher E, et al. Management of occult adrenocorticotropin-secreting bronchial carcinoids: limits of endocrine testing and imaging techniques. J Clin Endocrinol Metab 2003, 88: 1029–35.
White A, Ray DW, Talbot A, Abraham P, Thody AJ, Bevan JS. Cushing’s syndrome due to phaeochromocytoma secreting the precursors of adrenocorticotropin. J Clin Endocrinol Metab 2000, 85: 4771–5.
Mannelli M, Ferruzzi P, Luciani P, et al. Cushing’s sindrome in a patient with bilateral macronodular adrenal hyperplasia responding to cisapride: an in vivo and in vitro study. J Clin Endocrinol Metab 2003, 88: 4616–22.
Lamas C, Alfaro JJ, Lucas T, Lecumberri B, Barcelò B, Estrada J. Is unilateral adrenalectomy an alternative treatment for ACTH-independent macronodular adrenal hyperplasia?: Long-term follow-up of four cases. Eur J Endocrinol 2002, 146: 237–40.
Landau B, Leiba S, Kaufman H, Servadio C, Wainrach B. Unilateral adrenalectomy and pituitary irradiation in the treatment of ACTH-dependent Cushing’s disease in children and adolescents. Clin Endocrinol (Oxf) 1978, 9: 221 -6.
Nagesser SK, van Seters AP, Kievit J, et al. Treatment of pituitary-dependent Cushing’s syndrome: long-term results of unilateral adrenalectomy followed by external pituitary irradiation compared to transsphenoidal pituitary surgery. Clin Endocrinol (Oxf) 2000, 52: 427–35.
Tsagarakis S, Christoforaki M, Giannopoulou H, et al. A reappraisal of the utility of somatostatin receptor scintigraphy in patients with ectopic adrenocorticotrpin Cushing’s syndrome. J Clin Endocrinol Metab 2003, 88: 4754–8.
Zagar I, Han R, Mitrovic S. Meta-[131I]iodobenzylguanidine in the scintigraphic evaluation of neural crest tumors. Q J Nucl Med 1995, 39: 13–6.
Gao Z, Biersack HJ, Ezzidin S, Logvinski T, An R. The role of combined imaging in metastatic medullary thyroid carcinoma: (111)In-DTPA-octreotide and (131)I/(123)I-MIBG as predictors for radionuclide therapy. J Cancer Res Clin Oncol 2004, 130: 649–56.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Parenti, G., Nassi, R., Silvestri, S. et al. Multi-step approach in a complex case of Cushing’s syndrome and medullary thyroid carcinoma. J Endocrinol Invest 29, 177–181 (2006). https://doi.org/10.1007/BF03344094
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03344094