Cushing's Syndrome due to Ectopic Production of Corticotropin-Releasing Factor

Belsky, Joseph L.; Cuello, Beatriz; Swanson, L. W.; Simmons, Donna M.; Jarrett, Robert M.; Braza, Frank

doi:10.1210/jcem-60-3-496

Cited by 106 publications

(21 citation statements)

References 16 publications

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“…False-positive results in IPSS can be caused by periodic hormonogenesis in ectopic tumors as has been reported by Yamamoto (50) in two patients harboring ACTH-secreting bronchial carcinoids or also by CRH-producing ectopic tumors which are already reported (51,52).…”

Section: Discussionmentioning

confidence: 73%

Ectopic ACTH syndrome: our experience with 25 cases

Fragoso²,

et al. 2006

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Objective: Ectopic ACTH syndrome (EAS) occurs in about 5-10% of all patients with ACTH-dependent hypercortisolism with most of them caused by intrathoracic neoplasms. It may be associated with overt malignancies or with occult and indolent tumors. We assessed the accuracy of dynamic tests, inferior petrosal sinus sampling (IPSS) using desmopressin, and imaging in the work-up diagnosis of EAS. Design and subjects: Tumor markers, imaging, and outcome data from 25 patients (13F/12M) aged 18-72 years. High dexamethasone suppression test (HDDST), desmopressin test, GHRP-6 test, corticotropin-releasing hormone (CRH) test, IPSS, computed tomography (CT), magnetic resonance imaging (MRI), and 111 In-pentetreotide scintigraphy were revised. Results: In 5 out of 20 patients HDDST was positive. In 13 patients who underwent desmopressin test, ACTH-and cortisol-positive responses were seen in six and five patients respectively. GHRP-6 test was positive in two out of three cases. Two patients underwent CRH test with negative response. In the seven patients submitted to IPSS using desmopressin in six of them, none had ACTH gradients. CT was positive in 15 out of 21 patients and MRI in 8 out of 17 cases.111 In-pentetreotide scintigraphy was positive in three out of five patients. Fourteen patients had intrathoracic tumors, five had pheochromocytomas, three had pancreatic tumors, one had a glomic tumor, and had three occult tumors. Six out of 11 patients with metastasis died and 3 others without metastasis died. Conclusions: IPSS with desmopressin was helpful for differential diagnosis. Patients initially harboring occult carcinoids may also exhibit severe hypercortisolism and those harboring tymic carcinoids had poor prognoses when compared with bronchial carcinoids and pheocromocytomas.European Journal of Endocrinology 155 725-733

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Section: Discussionmentioning

confidence: 73%

Ectopic ACTH syndrome: our experience with 25 cases

Fragoso²,

et al. 2006

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“…Few reports on a false positive outcome in ectopic CS have been published. Some tumors co-secrete CRH which thereby could counteract a suppression of normal pituitary corticotrophs during hypercortisolism (36)(37)(38)(39)(40). In these reports, CRH levels in peripheral blood were found to be clearly elevated in two of the patients (38,40) and within the normal range in one case (38).…”

Section: Discussionmentioning

confidence: 98%

Dual bronchial carcinoids and Cushing's syndrome with a paradoxical response to dexamethasone and a false positive outcome of inferior petrosal sinus sampling

Burman¹,

Lethagen

Ivancev³

et al. 2008

European Journal of Endocrinology

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Context: Establishing the cause of Cushing's syndrome (CS) can be a considerable challenge, in particular in ectopic adrenocorticotropic hormone (ACTH) syndrome, and often requires a combination of biochemical tests and imaging procedures. Subject: A 27-year-old man presented with signs of CS. P-ACTH levels were three times above the upper limit of normal (ULN) and free urinary cortisol around 2000 nmol/24 h. The work-up showed remarkable results. Results: A 2-day low-dose dexamethasone suppression test demonstrated paradoxical increases in cortisol. Sampling from the bilateral inferior petrosal sinus sampling (BIPSS) showed a central to peripheral ACTH ratio of 4.7 after corticotrophin-releasing hormone (CRH) stimulation, i.e. indicated pituitary disease, but magnetic resonance imaging of the pituitary was normal. Computed tomography (CT) scan of the lungs showed two oval-shaped masses, 1.3!1.8 and 1.3!2 cm, in the middle lobe. Both were positive at somatostatin receptor scintigraphy, compatible with tumors or inflammatory lesions. Subsequently, 11 C-5-hydroxytryptophan-PET showed distinct uptake in the tumors but not elsewhere. Two carcinoids situated 3 cm apart, both staining for ACTH, were removed at surgery. Conclusion: This unique case with dual bronchial carcinoids inducing hypercortisolism illustrates the problems with identifying the source of ACTH in CS. Possibly, an abnormal regulation of ACTH production in response to dexamethasone, or steroid-induced tumor necrosis, explains the paradoxical outcome at dexamethasone suppression, and the false positive result at BIPSS reflects an unusual sensitivity of the pituitary corticotrophs to CRH in this patient. The work-up illustrates the great value of 11 C-5-hydroxytryptophan-PET as a diagnostic procedure when other investigations have produced ambiguous results. European Journal of Endocrinology 159 483-488

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“…Nearly all previous cases of ectopic Cushing's syn drome have been reported to be due to secre tion of ACTH by a non-pituitary site [2][3][4], However, a few cases have been described in which ACTH secretion was found in con junction with the secretion of substances with CRF activity [23][24][25] which conceiva bly may have stimulated the pituitary corticotrophs. More recently, however, since an tisera to CRF have become available, cases of Cushing's disease due solely to ectopic production of CRF [6,8] or excessive pro duction of CRF by an intrasellar gangliocytoma [7] have been described. Of these cases, that of Belskey et al [8] most closely resem bles our own patient.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, many cases of Cushing's syn drome due to excessive secretion of ACTH by benign and malignant tumours of a variety of tissues have been described [2][3][4][5], More re cently, Cushing's disease due to ectopic pro duction of corticotrophin-releasing factor (CRF) has been described [6][7][8]. Acromegaly associated with ectopic secretion of growth hormone releasing factor (GRF) has also been reported [9][10][11][12][13][14], We report here the use of a human pituitary cell culture system to diag nose 1 case (case 1) of ectopic CRF secretion, associated with Cushing's syndrome, and I case of ectopic GRF secretion associated with acromegaly (case 2).…”

Section: Introductionmentioning

confidence: 99%

Ectopic Corticotrophin-Releasing-Factor and Growth Hormone Releasing Factor Secretion: Diagnosis Using Human Pituitary Cell Culture

et al. 1987

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Cell culture of human pituitary tissue has been used to diagnose a patient with Cushing’s syndrome due to ectopic secretion of corticotrophin-releasing factor (CRF; case 1) and a case of acromegaly associated with ectopic secretion of a growth-hormone releasing factor (GRF; case 2). In both patients a pituitary tumour was not detected. Case 1 had a small cell carcinoma and symptoms of the ectopic ACTH syndrome, but in culture the carcinoma failed to secrete detectable ACTH. However, the culture medium used to maintain this carcinoma in vitro was found to contain a substance which stimulated ACTH secretion by human pituitary corticotrophs in cell culture. Radioimmunoassays and HPLC indicated that this substance had similar elution characteristics to human CRF and cross-reacted with antiserum to ovine CRF. Case 2 was found to have a lung tumour, the removal of which led to regression of her acromegalic symptoms. In culture, this tumour did not secrete GH, but did secrete a GRF. We conclude that the Cushing’s syndrome and acromegaly, in cases 1 and 2, respectively, were due to ectopic secretion of CRF and GRF leading to hyperstimulation of the pituitary gland.

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Cushing's Syndrome due to Ectopic Production of Corticotropin-Releasing Factor

Cited by 106 publications

References 16 publications

Ectopic ACTH syndrome: our experience with 25 cases

Ectopic ACTH syndrome: our experience with 25 cases

Dual bronchial carcinoids and Cushing's syndrome with a paradoxical response to dexamethasone and a false positive outcome of inferior petrosal sinus sampling

Ectopic Corticotrophin-Releasing-Factor and Growth Hormone Releasing Factor Secretion: Diagnosis Using Human Pituitary Cell Culture

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