The classical trias in Cushing's disease, normal or moderately elevated plasma ACTH, significant suppression of cortisol in the high-dose dexamethasone test, and stimulation of ACTH and cortisol in the CRH test, confirms the diagnosis in most cases. However, as a referral centre for complex Cushing's disease cases, we are confronted with problems in the differentiation of pituitary and ectopic Cushing's syndrome and with problems in the localisation of minute ACTH-secreting pituitary adenomas. In this study, cavernous sinus sampling (CSS) was evaluated as a diagnostic tool in complex Cushing's disease cases. Thirty-five patients were transferred to our unit for the treatment of Cushing's disease between January 1999 and August 2000. Of those, 17 patients (including five children) had the combination of equivocal results in endocrinological testing and negative MRI prior to admission. In these cases, CSS was performed preoperatively to confirm the diagnosis and to obtain further information about the localisation of pituitary microadenomas. Twelve of these 17 patients showed the classical trias for Cushing's disease after equivocal tests were repeated. A central-peripheral gradient was also found using CSS. In ten of the 11 patients, where CSS could be successfully performed, the lateralisation of the ACTH-adenoma was correctly predicted (91%). In the eleventh case, a right ACTH-gradient was found in a stalk tumour. In one patient (a child), the catheterisation of the cavernous sinus failed due to anatomical reasons. Eleven of these 12 patients successfully underwent transnasal adenomectomy. In two of the 17 patients, active Cushing's syndrome was excluded. In the remaining three cases, ectopic Cushing's syndrome was suspected based on CSS results. Therefore, these patients did not undergo pituitary exploration. In complex cases, we recommend CSS for diagnostic purposes, especially for the localisation of ACTH-secreting microadenomas within the pituitary. In our experience, CSS has a higher accuracy than inferior petrosal sinus sampling (IPSS) in the localisation of ACTH-adenomas.

In order to clarify the mechanism by which prolactin-secreting adenomas reduce in size during treatment with dopamine agonists (DA), we studied altogether 18 chromophobe pituitary adenomas by carrying out light microscopical cell counting of necrobiotic alterations and necroses in photographs of semi-thin sections. Depending on hormonal activity and preoperative treatment of the patients 3 groups of adenomas were formed: 6 prolactin producing adenomas were treated with bromocriptine and lisuride (group 3). 8 cases remained preoperatively without medical treatment (group 2). For comparison, we studied 4 cases of clinically inactive pituitary adenomas (group 1). All adenomas were immunohistologically positive for prolactin. By classifying each tumor cell in one of four stages of necrotic alteration (stage 1: intact cell, stage 2: slightly condensed nucleus and shrunken cytoplasm, stage 3: necrotic cell with still visible nuclear membrane, stage 4: cell debris) we arrived at an index for necrobiotic alterations of the 18 adenomas. We found a significantly higher rate of cell necroses in DA-treated tumors compared with preoperatively untreated prolactinomas and inactive adenomas. Previous investigations in this field have revealed that a reduction in cell size may well cause the shrinkage of the prolactinomas after DA-therapy. The results presented in this paper indicate, however, that the role of necroses now needs to be given much closer attention as an additional factor.

Acromegaly is a rare disease caused by a growth-hormone-secreting pituitary adenoma. Symptoms include enlargement of the hands, feet, and jaw with growing dental interspaces, as well as hypertrophy of the tongue and nasal and sinusoidal mucosa. The two latter symptoms are mostly responsible for the accompanying obstructive sleep apnea syndrome. Besides these "cosmetic" symptoms, the disease is associated with hypertension and diabetes mellitus, as well as with an increased risk for adenomas and carcinomas of the colon. The average time span from first symptom to diagnosis is well over 6 years; a single determination of insulin-like growth factor 1 in serum can confirm the disease. The treatment of choice remains surgical resection of the adenoma in suitable patients, whereas in extensive disease with invasion of surrounding tissue, drug therapy and/or radiotherapy may be necessary.

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