The Corticotropin-Releasing-Hormone Test Versus the High-Dose Dexamethasone Test in the Differential Diagnosis of Cushing's Syndrome

Hermus, A. R. M. M.; Pesman, G. J.; Benraad, Theo J.; Pieters, G. F. F. M.; Smals, A. G. H.; Kloppenborg, P W

doi:10.1016/s0140-6736(86)90113-3

Cited by 78 publications

(22 citation statements)

References 14 publications

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“…Some authors found that when CRH test results are combined with information obtained from low-or highdose dexamethasone suppression tests, the accuracy of the diagnosis is better than when each test is used alone (27,28); other authors disagree, however (16). The combined use of CRH and desmopressin stimulation in the differential diagnosis of ACTH-dependent CS was first proposed by Newell Price et al (29), and subsequently evaluated by other authors too (25).…”

Section: Discussionmentioning

confidence: 99%

The usefulness of combined biochemical tests in the diagnosis of Cushing’s disease with negative pituitary magnetic resonance imaging

Testa¹,

Albiger²,

Occhi³

et al. 2007

eur j endocrinol

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Objective: The etiological diagnosis of ACTH-dependent Cushing's syndrome is often a problem. In fact, no endocrine or radiological examination can conclusively distinguish the ectopic from the pituitary source of disease. The aim of our study was to evaluate the role of stimulation and suppression endocrine tests in the diagnostic and therapeutic approach of patients with Cushing's disease (CD) and negative pituitary magnetic resonance imaging (MRI), considering their post-surgical outcome in comparison with patients with CD and positive MRI. Patients and methods: We retrospectively analyzed 31 patients (25 women and 6 men, median age 40G 15 years) with a confirmed diagnosis of CD who underwent transsphenoidal pituitary surgery by the same neurosurgeon between 2001 and 2005. Preoperative endocrine assessment included corticotropin-releasing hormone (CRH), desmopressin (dDAVP), and overnight 8 mg dexamethasone suppression tests (8-DST) in all patients. Fifteen patients had a normal pituitary MRI and sixteen had a clearly evident pituitary microadenoma. Bilateral inferior petrosal sinus sampling (BIPSS) was performed in patients with discordant biochemical results or with signs and symptoms highly suggestive of an ectopic source of ACTH. Post-surgical median follow-up was 38.4G22.0 months. Results: Among patients with negative MRI, 60% had concordant positive endocrine tests and underwent neurosurgery without other examinations. BIPSS was performed in three other patients prompted by discordant endocrine tests (negative dDAVP) and in two patients with clinical suspicion of ectopic disease. Among patients with positive MRI, 87% underwent neurosurgery without BIPSS that was performed in two patients because of negative concomitant response to dDAVP and CRH tests. A pituitary adenoma, confirmed by pathological examination, was found in 40 and 81% of patients with negative and positive MRI respectively (P!0.05), corticotroph hyperplasia resulted more frequent in the group with negative MRI. Remission rate was not different between patients with negative and positive MRI (73 and 75% respectively; PZ0.61) and between patients with negative MRI who did not undergo BIPSS and patients with positive MRI (PZ0.56). The recurrence rate was also similar between groups (PZ0.64), but higher, although not statistically different (PZ0.07) in patients with corticotroph hyperplasia at histology. Conclusions: An accurate evaluation of presurgical endocrine tests results enabled us to reduce the number of BIPSS in patients with a negative MRI without any fallout on their post-surgical outcome. In the hands of an expert pituitary surgeon, the outcome after surgery and the subsequent recurrence rate are much the same in patients with negative or positive MRI.European Journal of Endocrinology 156 241-248

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Section: Discussionmentioning

confidence: 99%

The usefulness of combined biochemical tests in the diagnosis of Cushing’s disease with negative pituitary magnetic resonance imaging

Testa¹,

Albiger²,

Occhi³

et al. 2007

eur j endocrinol

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“…1). 19,43,70,73,78 This strategy was based on the assumption that CD is caused by well-differentiated adenomas derived from pituitary corticotrophs and that these adenomas should have receptors for CRH and the cellular constituents necessary to respond to CRH stimulation (a positive response is set arbitrarily at a 50% or more increase in ACTH and 20% or more increase in cortisol). Alternatively, ectopic ACTH-secreting tumors are derived from nonpituitary tissues and generally do not respond to CRH.…”

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confidence: 99%

“…However, there is an approximately 10% incidence of false-negative and false-positive results in ectopic tumors with CRH stimulation testing. 43,73 High-dose dexamethasone suppression testing also can be used to distinguish between ACTH-dependent causes of CS. 19,43,54,70,73 Similar to the biological basis for CRH stimulation testing, dexamethasone suppression testing takes advantage of the presence of cellular constituents necessary to respond to dexamethasone (suppression) in the pituitary adenoma corticotroph cells and the lack of the negative feedback response in ectopic nonpituitary tumors that secrete ACTH (Fig.…”

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confidence: 99%

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Cushing's disease: pathobiology, diagnosis, and management

Lonser

Nieman

Oldfield

2017

JNS

151

114

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Cushing's syndrome (CS) is caused by prolonged supraphysiological levels of circulating cortisol. Cushing's disease (CD) is the most common etiology (70%-80% of CS cases) of endogenous CS. It is caused by a pituitary adenoma that secretes adrenocorticotropic hormone (ACTH), which stimulates secretion of cortisol by the adrenal glands. If not effectively treated, CD is associated with hypertension, diabetes, obesity, osteoporosis, vascular disease, and shortened life span. Successful resection of a CD-associated ACTH-secreting pituitary adenoma results in immediate biochemical remission and preservation of pituitary function. Early identification of CD by clinical findings, endocrinological evaluation, and imaging studies is critical for diagnosis and effective surgical management. endocrinological and Clinical Features endocrinological Features Normal PhysiologyInsight into the normal and pathophysiological mechanisms of control of the hypothalamic-anterior pituitaryadrenal axis is critical to understanding the pathologic, diagnostic, and therapeutic features of CD (Fig. 1). 52 Under normal physiological conditions (circadian rhythm, where cortisol levels peak in early morning and nadir late at night), systemic inflammation (cytokine), or stress (physiological or psychological), corticotropin-releasing hormone (CRH; a 41-amino acid peptide) is released from the paraventricular hypothalamic nucleus via the median eminence. From the median eminence, CRH is transported in the hypophyseal portal venous system to the pituitary gland, where it binds to the CRH receptor-1 (CRH-R1) on pituitary corticotroph cells. CRH binding to CRH-R1 receptors activates adenylate cyclase and stimulates proopiomelanocortin (POMC) gene expression in the corticotroph cells.17,66 Proopiomelanocortin preprohormone is processed into ACTH (a 39-amino acid peptide) and b-lipotropin (a 93-amino acid peptide). Products of b-lipotropin include b-endorphin and a-lipotropin. ACTH is secreted into the systemic circulation and binds to receptors in the adrenal cortex, where it stimulates production and secretion of glucocorticoids, including cortisol. 83 Under normal conditions, circulating cortisol provides physiological control of this endocrine axis by its negative feedback inhibition on hypothalamic CRH and pituitary ACTH secretion. Cushing's disease (CD) is the result of excess secretion of adrenocorticotropic hormone (ACTH) by a benign monoclonal pituitary adenoma. The excessive secretion of ACTH stimulates secretion of cortisol by the adrenal glands, resulting in supraphysiological levels of circulating cortisol. The pathophysiological levels of cortisol are associated with hypertension, diabetes, obesity, and early death. Successful resection of the CD-associated ACTH-secreting pituitary adenoma is the treatment of choice and results in immediate biochemical remission with preservation of pituitary function. Accurate and early identification of CD is critical for effective surgical management and optimal prognosis. The authors review the cu...

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“…Whilst it is generally accepted that the CRF test is unnecessary in patients with adrenocortical tumours, since they are indicated by undetectable basal plasma ACTH levels in the presence of hypercortisolaemia and easily confirmed by computerized tomography (Howlett et al, 1986;Kendall-Taylor & Bayliss, 1986), the role of the C R F test in differentiating pituitary ACTH-dependent Cushing's disease from ectopic ACTH secretion is currently under examination. Assessments of the diagnostic accuracy of the CRF test in patients with Cushing's syndrome showed it to be comparable to the high-dose dexamethasone test (Hermus et al, 1986;Nieman et al, 1986, Grossman et al, 1987 all groups advocating a combined-test strategy to yield improved diagnostic accuracy since the two tests assess different aspects of pituitary-adrenal function. Nevertheless, Howlett et al (1986) urge caution in the interpretation of the CRF test, pointing out that some ectopic ACTH-secreting carcinoid tumours suppress with dexamethasone and may in addition also show responses to CRF, leading to the incorrect diagnosis of pituitary-dependent disease.…”

Section: Crf Stimulation In Cushing's Syndromementioning

confidence: 99%