Metyrapone pre‐treated inferior petrosal sinus sampling in the differential diagnosis of ACTH‐dependent Cushing's syndrome

Cuneo, Ross C.; Lee, Winnifred; Harper, John; Mitchell, K. L.; Ward, Greg; Atkinson, R. Leigh; Salkield, Ian; Cameron, Donald P.

doi:10.1046/j.1365-2265.1997.1971007.x

Cited by 13 publications

(3 citation statements)

References 21 publications

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“…In the present study, the ACTH and F responses to hCRH were similar in patients bearing micro-and macroadenomas, but those to HEX were strikingly lower in patients with macroadenoma than in those with ACTH-secreting microadenoma. On the other hand, discrepancies between magnetic resonance imaging and surgical findings have been recently reported (28). It may be hypothesized that in patients with macroadenoma an impaired function of the hypothalamo-pituitary unit is present; were this the case, in patients with microadenoma, but not in those with macroadenoma, synergy between endogenous CRH and HEX on corticotroph cells could theoretically have occurred.…”

Section: Effects Of Hexarelin On Hpa Axis In Cushing's Disease 4209mentioning

confidence: 99%

Adrenocorticotropin and Cortisol Hyperresponsiveness to Hexarelin in Patients with Cushing’s Disease Bearing a Pituitary Microadenoma, But Not in Those with Macroadenoma¹

Arvat

Giordano

Ramunni

et al. 1998

The Journal of Clinical Endocrinology & Metabolism

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We previously reported that in Cushing's disease (CD) the ACTH- and cortisol (F)-releasing activity of Hexarelin (HEX), a GH secretagogue, is exaggerated with respect to that in normal subjects and is higher than that of human CRH (hCRH), but it is absent in Cushing's syndrome. Our aim was to extend the study about the effects of HEX (2.0 microg/kg, iv) on ACTH and F secretion in 21 patients with CD (3 men and 18 women, 16-68 yr old). Based on magnetic resonance imaging, 15 CD patients had pituitary microadenoma, and 6 had macroadenoma. The results in CD patients were compared with those in 27 normal age-matched controls (NS; 10 men and 17 women, 24-69 yr old). Basal ACTH and F levels in CD were similar in patients with microadenom (mean+/-SEM, 78.3+/-7.2 pg/mL and 237.1+/-23.6 microg/L, respectively) and macroadenoma (57.4+/-9.0 pg/mL and 196.9+/-20.1 microg/L, respectively) and were higher (P < 0.001) than those in NS (17.7+/-2.0 pg/mL and 115.3+/-6.7 microg/L, respectively). In microadenoma CD patients, HEX induced marked ACTH and F increases (delta peak, mean+/-SEM: 261.2+/-77.6 pg/mL and 226.1+/-87.2 microg/L, respectively), which were higher (P < 0.04) than those induced by hCRH (45.6+/-16.9 pg/mL and 84.6+/-25.7 microg/L, respectively). Moreover, in microadenoma CD patients, the ACTH and F responses to HEX were higher (P < 0.001) than those in NS (18.5+/-4.0 pg/mL and 36.1+/-6.8 microg/L, respectively). In macroadenoma CD patients, HEX induced a slight, but significant increase (P < 0.02) in ACTH and F levels (33.9+/-18.0 pg/mL and 89.6+/-34.3 microg/L, respectively), which was not significantly different from that elicited by hCRH (20.0+/-7.0 pg/mL and 54.8+/-21.3 microg/L, respectively). In macroadenoma CD patients, the ACTH and F responses to HEX and hCRH were, in turn, similar to those in NS. In conclusion, our findings demonstrate that the ACTH and F hyperresponsiveness to HEX is present in Cushing's disease with micro-, but not macro- ACTH-secreting pituitary adenoma. This finding agrees with other evidence pointing toward differences in the hormonal behavior between micro- and ACTH-secreting pituitary macroadenomas.

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Section: Effects Of Hexarelin On Hpa Axis In Cushing's Disease 4209mentioning

confidence: 99%

Adrenocorticotropin and Cortisol Hyperresponsiveness to Hexarelin in Patients with Cushing’s Disease Bearing a Pituitary Microadenoma, But Not in Those with Macroadenoma¹

Arvat

Giordano

Ramunni

et al. 1998

The Journal of Clinical Endocrinology & Metabolism

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“…Following hCRH and desmopressin injection, a post-stimulation central:peripheral ACTH ratio of > 2.0 produced a sensitivity of 97.9% and specificity of 100% for Cushing's disease (34). Pre-treatment with metyrapone for 24 to 48 hours prior to BIPSS, to increase pituitary ACTH output, has been explored and may increase sensitivity when CRH is not available (35).…”

Section: Bipss In the Diagnosis Of Cushing's Syndromementioning

confidence: 99%

The role of bilateral inferior petrosal sinus sampling in the diagnosis of Cushing's syndrome

Utz

2007

Arq Bras Endocrinol Metab

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Adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome is most often due to a pituitary corticotroph adenoma, with ectopic ACTH-secreting tumors representing approximately 15% of cases. Biochemical and radiological techniques have been established to help distinguish between these two entities, and thus aid in the localization of the neoplastic lesion for surgical resection. The test that offers the highest sensitivity and specificity is bilateral inferior petrosal sinus sampling (BIPSS). BIPSS is an interventional radiology procedure in which ACTH levels obtained from venous drainage very near the pituitary gland are compared to peripheral blood levels before and after corticotropin hormone (CRH) stimulation. A gradient between these two locations indicates pituitary Cushing's, whereas the absence of a gradient suggests ectopic Cushing's. Accurate BIPSS results require hypercortisolemia to suppress normal corticotroph ACTH production and hypercortisolemia at the time of the BIPSS to assure excessive ACTH secretion. In some cases, intrapituitary gradients from side-to-side can be helpful to localize small corticotroph adenomas within the sella. BIPSS has rare complications and is considered safe when performed at centers with experience in this specialized technique.

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“…In most studies, a peak stimulated central to peripheral ratio of 3.0 or more, which usually occurs between 3 and 5 min post-CRH, is indicative of Cushing’s disease [36, 119, 120, 124, 125, 126, 128, 129, 130]. Recently, metyrapone pretreatment has been used with success to enhance the central to peripheral gradient [131], suggesting it may have a role when CRH is not available. Interestingly, the criterion which was validated in the largest published series from the NIH [119]required revision downward to maintain ‘100% sensitivity’ in their childhood series, since although 42 of 43 patients with Cushing’s disease had stimulated values of ≥3.0, one patient with Cushing’s disease had a stimulated ratio of 2.5, whilst all six with the ectopic ACTH syndrome had basal and stimulated ratios ≤2.2 [35].…”

Section: Differential Diagnosis Of Acth-dependent Cushing’s Syndromementioning

confidence: 99%

The Diagnosis and Differential Diagnosis of Cushing’s Syndrome<footref rid="foot01"><sup>1</sup></footref>

Newell‐Price

Jørgensen²,

Grossman³

1999

Horm Res Paediatr

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Cushing’s syndrome is defined as the symptoms and signs of glucocorticoid excess, but the precise diagnosis may be difficult to establish and harder to localise. The clinicial, biochemical and imaging features of the syndrome are discussed in the light of our own extensive experience and the published literature. We describe the optimal diagnostic routines currently recommended in major centres, and analyse the sensitivities and specialities of the various tests employed. Only by means of establishing a precise diagnosis can the disorder be successfully treated.

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Metyrapone pre‐treated inferior petrosal sinus sampling in the differential diagnosis of ACTH‐dependent Cushing's syndrome

Abstract: Metyrapone pre-treated inferior petrosal sinus sampling is safe, and appears to induce high ACTH output from pituitary corticotroph adenomas. The technique has allowed accurate localization and treatment of pituitary corticotroph microadenomas.

Cited by 13 publications

References 21 publications

Adrenocorticotropin and Cortisol Hyperresponsiveness to Hexarelin in Patients with Cushing’s Disease Bearing a Pituitary Microadenoma, But Not in Those with Macroadenoma¹

Adrenocorticotropin and Cortisol Hyperresponsiveness to Hexarelin in Patients with Cushing’s Disease Bearing a Pituitary Microadenoma, But Not in Those with Macroadenoma¹

The role of bilateral inferior petrosal sinus sampling in the diagnosis of Cushing's syndrome

The Diagnosis and Differential Diagnosis of Cushing’s Syndrome<footref rid="foot01"><sup>1</sup></footref>

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Metyrapone pre‐treated inferior petrosal sinus sampling in the differential diagnosis of ACTH‐dependent Cushing's syndrome

Abstract: Metyrapone pre-treated inferior petrosal sinus sampling is safe, and appears to induce high ACTH output from pituitary corticotroph adenomas. The technique has allowed accurate localization and treatment of pituitary corticotroph microadenomas.

Cited by 13 publications

References 21 publications

Adrenocorticotropin and Cortisol Hyperresponsiveness to Hexarelin in Patients with Cushing’s Disease Bearing a Pituitary Microadenoma, But Not in Those with Macroadenoma1

Adrenocorticotropin and Cortisol Hyperresponsiveness to Hexarelin in Patients with Cushing’s Disease Bearing a Pituitary Microadenoma, But Not in Those with Macroadenoma1

The role of bilateral inferior petrosal sinus sampling in the diagnosis of Cushing's syndrome

The Diagnosis and Differential Diagnosis of Cushing’s Syndrome<footref rid="foot01"><sup>1</sup></footref>

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Product

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Adrenocorticotropin and Cortisol Hyperresponsiveness to Hexarelin in Patients with Cushing’s Disease Bearing a Pituitary Microadenoma, But Not in Those with Macroadenoma¹

Adrenocorticotropin and Cortisol Hyperresponsiveness to Hexarelin in Patients with Cushing’s Disease Bearing a Pituitary Microadenoma, But Not in Those with Macroadenoma¹