Diagnostic value of super-selective bilateral cavernous sinus sampling with hypothalamic stimulating hormone loading in patients with ACTH-producing pituitary adenoma

Abstract Aims: Early diagnosis and early treatment by transsphenoidal surgery is desirable for ACTHproducing pituitary microadenoma, but accurate localization of the functional lesion is not always possible before surgery because magnetic resonance (MR) imaging may provide false negative and/or positive findings. The diagnostic value of super-selective bilateral cavernous sinus sampling with the administration of corticotropin-releasing hormone (CRH) was assessed in patients with functioning ACTH-producing pituitary adenoma. Methods: Fifteen patients with pituitary adenoma (14 with microadenoma) aged from 23 to 74 years (mean 46.7 years) underwent cavernous sinus sampling with or without the CRH loading test and subsequent transsphenoidal surgery in our institute from October 1997 through to November 2002. MR imaging including dynamic scan failed to detect the adenomatous lesion in all patients. To eliminate the bias due to uneven blood flow in the cavernous sinuses and the multi-hormonal response to CRH administration, the ACTH/FSH ratios were evaluated. The inter-cavernous gradient (ICG) was calculated as the higher/lower ACTH venous blood levels in the right and left cavernous sinuses with or without CRH loading. The adjusted ICG was calculated using the ACTH/FSH ratios. The results were compared with the surgical findings. An ICG of 1.4 or greater was considered to indicate the localization of the responsible lesion. Results: Transsphenoidal surgery revealed the functioning lesion on the right in five cases, the left in six, the midline in three and the bilateral lateral wings (double adenoma) in one. Adjusted ICG with CRH loading had a localization accuracy of 93.3% (14/15), which was significantly higher than that of 73.3% (11/15) using ICG without hypothalamic stimulating hormone loading (p=0.0402). Conclusions: Super-selective cavernous sinus sampling with hypothalamic stimulating hormone administration can provide accurate localization of the responsible lesion in patients with ACTH-producing pituitary adenoma.

[1]  T. Yoshimoto,et al.  Transsphenoidal surgery and adjuvant gamma knife treatment for growth hormone-secreting pituitary adenoma. , 2001, Journal of neurosurgery.

[2]  A. Teramoto,et al.  Cavernous sinus sampling in patients with adrenocorticotrophic hormone-dependent Cushing's syndrome with emphasis on inter- and intracavernous adrenocorticotrophic hormone gradients. , 1998, Journal of neurosurgery.

[3]  D. Redelmeier,et al.  Improved diagnostic accuracy of inferior petrosal sinus sampling over imaging for localizing pituitary pathology in patients with Cushing's disease. , 1998, The Journal of clinical endocrinology and metabolism.

[4]  J. Doppman,et al.  The limited ability of inferior petrosal sinus sampling with corticotropin-releasing hormone to distinguish Cushing's disease from pseudo-Cushing states or normal physiology. , 1993, The Journal of clinical endocrinology and metabolism.

[5]  J. Doppman,et al.  Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing's syndrome. , 1991, The New England journal of medicine.

[6]  H. Raff,et al.  Routine inferior petrosal sinus sampling in the differential diagnosis of adrenocorticotropin (ACTH)-dependent Cushing's syndrome: early recognition of the occult ectopic ACTH syndrome. , 1991, The Journal of clinical endocrinology and metabolism.

[7]  A. Tabarin,et al.  Usefulness of the corticotropin-releasing hormone test during bilateral inferior petrosal sinus sampling for the diagnosis of Cushing's disease. , 1991, The Journal of clinical endocrinology and metabolism.

[8]  S. Nussey,et al.  Corticotrophin releasing hormone (CRH1–41) stimulates the secretion of adrenocorticotrophin, vasopressin and oxytocin but not adrenocorticotrophin precursors: evidence from petrosal sinus sampling in man , 1991, Clinical endocrinology.

[9]  B. Allolio,et al.  A multihormonal response to corticotropin-releasing hormone in inferior petrosal sinus blood of patients with Cushing's disease. , 1990, The Journal of clinical endocrinology and metabolism.

[10]  D. Lüdecke Intraoperative measurement of adrenocorticotropic hormone in peripituitary blood in Cushing's disease. , 1989, Neurosurgery.

[11]  D. Hadden,et al.  BILATERAL INFERIOR PETROSAL SINUS SAMPLING AS A ROUTINE PROCEDURE IN ACTH‐DEPENDENT CUSHING'S SYNDROME , 1989, Clinical endocrinology.

[12]  B. Allolio,et al.  SELECTIVE BILATERAL AND SIMULTANEOUS CATHETERIZATION OF THE INFERIOR PETROSAL SINUS: CRF STIMULATES PROLACTIN SECRETION FROM ACTH‐PRODUCING MICROADENOMAS IN CUSHING'S DISEASE , 1988, Clinical endocrinology.

[13]  J. Doppman,et al.  Usefulness of inferior petrosal sinus venous endocrine markers in Cushing's disease. , 1988, Journal of neurosurgery.

[14]  A. Eberle,et al.  CORTICOTROPHIN‐RELEASING FACTOR‐TEST USED WITH BILATERAL, SIMULTANEOUS INFERIOR PETROSAL SINUS BLOOD‐SAMPLING FOR THE DIAGONOSIS OF PITUITARY‐DEPENDENT CUSHING'S DISEASE , 1986, Clinical endocrinology.

[15]  J. Doppman,et al.  Preoperative lateralization of ACTH-secreting pituitary microadenomas by bilateral and simultaneous inferior petrosal venous sinus sampling. , 1985, The New England journal of medicine.

[16]  J. Doppman,et al.  Petrosal sinus sampling for Cushing syndrome: anatomical and technical considerations. Work in progress. , 1984, Radiology.

[17]  R. Santen,et al.  Simultaneous bilateral venous sampling for adrenocorticotropin in pituitary-dependent cushing's disease: evidence for lateralization of pituitary venous drainage. , 1983, The Journal of clinical endocrinology and metabolism.

[18]  J. Earll,et al.  Selective venous sampling to differentiate ectopic ACTH secretion from pituitary Cushing's syndrome. , 1977, The New England journal of medicine.