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Panagiotis Nomikos, Michael Buchfelder and Rudolf Fahlbusch

Background and aim: The aim of this study was to illustrate the present role of transsphenoidal surgery as primary therapy in GH-secreting adenomas, and to compare the results concerning control of disease with previous series using older criteria of cure.

Method: We report on a consecutive series of 688 acromegalic patients treated over a time period of 19 years. Biochemical cure was defined as normalisation of basal GH level, suppression of GH levels to below 1 ng/ml during an oral glucose load and normalisation of IGF-I levels. Of the 506 patients undergoing primary transsphenoidal surgery, a total of 57.3% postoperatively fulfilled the criteria used.

Results: The rate of biochemical ‘cure’ correlated with the magnitude of the initial GH levels, the tumour size and invasion. The overall complication rate was below 2%. Mortality in this series was 0.1% (1 of 688). During a follow-up period of 10.7 years only two recurrences (0.4%) occurred. However, in the patients treated by transcranial surgery and by repeat surgery the cure rate was found to be relatively low (5.2 and 21.3% respectively).

Conclusions: These data suggest that surgery remains with very few exceptions the primary treatment of acromegaly for (i) a high cure rate, (ii) low morbidity, (iii) low recurrence rate and (iv) immediate decline of GH. Based on current criteria of cure, recurrences are uncommon. However, cure by surgery alone is improbable in patients harbouring extended, invasive tumours with high secretory activity, in whom further adjuvant treatment is mandatory.

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Hanns-Kristian Rjosk, Rudolf Fahlbusch and Klaus von Werder

Abstract.

Spontaneous development of hyperprolactinaemia was investigated by measuring prolactin levels in 34 hyperprolactinaemic females with a normal sella turcica, in 19 females with a radiologically proven prolactinoma, and in 19 females with a histologically proven prolactinoma after transsphenoidal surgery. Prolactin levels remained unchanged or declined in 69 patients followed over a period of up to 6 years. In one patient with a normal sella turcica, prolactin levels increased accompanied by the development of a radiologically detectable microprolactinoma. In one patient with a radiologically proven macroprolactinoma the increase of human prolactin (hPrl) levels was accompanied by infiltrative and parasellar prolactinoma growth. One patient showed a dramatic increase of post-operative persisting elevated hPrl levels without radiological changes. These findings suggest that prolactinomas in general have a limited growth potential which should be considered in the management of hyperprolactinaemic patients.

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Hanns-Kristian Rjosk, Rudolf Fahlbusch and Klaus von Werder

Abstract.

Hyperprolactinaemic patients desiring pregnancy with a normal sella turcica or radiological evidence for a microprolactinoma without suprasellar extension were treated with bromocriptine. Females desiring pregnancy with large adenomas or suprasellar extension were treated by transsphenoidal surgery and in most instances post-operatively with bromocriptine. This differentiated management allowed the outcome of 65 pregnancies with delivery at term without complications related to the sella turcica.

Considerable variations of prolactin levels during pregnancy suggesting different oestrogen sensitivity of the prolactinoma cells were encountered. However, a rapid fall of the prolactin levels in 60 patients after termination of pregnancy indicated that oestrogen stimulation does not cause persisting growth of the adenoma. In contrast, in 10% of pregnancies of hyperprolactinaemic patients a reduction of the prolactin levels has been observed leading to spontaneous ovulatory cycles in 5 patients.

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Wolfgang Saeger, Dieter K Lüdecke, Michael Buchfelder, Rudolf Fahlbusch, Hans-Jürgen Quabbe and Stephan Petersenn

In 1996, the German Registry of Pituitary Tumors was founded by the Pituitary Section of the German Society of Endocrinology as a reference center for collection and consultant pathohistological studies of pituitary tumors. The experiences of the first 10 years of this registry based on 4122 cases will herein be reported. The data supplement former collections of the years 1970–1995 with 3480 surgically removed tumors or lesions of the pituitary region. The cases were studied using histology, immunostainings and in some cases also molecular pathology or electron microscopy. The adenomas were classified according to the current World Health Organization classification in the version of 2004. From 1996 on 3489 adenomas (84.6%), 5 pituitary carcinomas (0.12%), 133 craniophar-yngiomas (3.2%), 39 meningiomas (0.94%), 25 metastases (0.6%), 22 chordomas (0.5%), 115 cystic non-neoplastic lesions (2.8%), and 46 inflammatory lesions (1.1%, 248 other lesions or normal tissue (6.0%)) were collected by us. The adenomas (100%) were classified into densely granulated GH cell adenomas (9.2%), sparsely granulated GH cell adenomas (6.3%), sparsely granulated prolactin (PRL) cell adenomas (8.9%), densely granulated PRL cell adenomas (0.3%), mixed GH/PRL cell adenomas (5.2%), mammosomatotropic adenomas (1.1%), acidophilic stem cell adenomas (0.2%), densely granulated ACTH cell adenomas (7.2%), sparsely granulated ACTH cell adenomas (7.9%), Crooke cell adenomas (0.03%), TSH cell adenomas (1.5%), FSH/LH cell adenomas (24.8%), null cell adenomas (19.3%), null cell adenoma, oncocytic variant (5.8%), and plurihormonal adenomas (1.3%). Following the WHO classification of 2004, the new entity ‘atypical adenoma’ was found in 12 cases in 2005. Various prognostic parameters and clinical implications are discussed.

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Rudolf Fahlbusch, Boris v Keller, Oliver Ganslandt, Jürgen Kreutzer and Christopher Nimsky

Objective: The aim of the study was to evaluate the effect of intraoperative high-field (1.5 Tesla) magnetic resonance imaging (MRI) on the results of transsphenoidal surgery of GH-secreting pituitary macroadenomas.

Methods: Twenty-three acromegalic patients (mean tumor size, 25 ± 12 mm; untreated preoperative GH, 4.2–159 μg/l; IGF-I, 349–1111 μg/l) were investigated by intraoperative high-field MRI. If intraoperative imaging depicted an accessible tumor remnant, resection was continued.

Results: In five patients intraoperative MRI led to further tumor removal, two of these met the consensus criteria for endocrine remission after 3 months. In two patients basal GH and oral glucose tolerance test (OGTT) were <2 μg/l, only IGF-I was slightly elevated, and in one patient GH was <5 μg/l and OGTT was 2 μg/l, with elevated IGF-I. Final intraoperative MRI showed no tumor remnants in 14 patients; eight of them met the consensus criteria for remission of acromegaly. In the patients with MRI showing incomplete removal (four suspect findings and five patients with intended partial removal) none was normalized.

Conclusion: With regard to the patients with a tumor configuration in whom complete tumor removal was considered (n = 18), intraoperative MRI increased the rate of endocrine normalization from 33 to 44% applying the consensus criteria, and improved endocrine outcome to ‘nearly normalization’ in another 17%. With regard to preoperative GH levels and tumor size, intraoperative MRI can help to achieve endocrine remission in patients who are normally considered not to be curable. However, taking GH as the tumor marker, even intraoperative high-field MRI was not able to detect tumor remnants in every case.

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Hans-Udo Schweikert, Horst Lorenz Fehm, Rudolf Fahlbusch, Rainer Martin, Rainer Kolloch, Miyoko Higuchi and Friedrich Krück

Abstract. A 55 year old woman with an unusual form of Cushing's disease was studied. During several periods (periods lasting up to 84 days) evidence of cortisol hypersecretion with cycles occurring every 6 days was found. Suppression of plasma cortisol through orally administered dexamethasone (up to 32 mg per day) could not be achieved either during periods of cyclic cortisol hypersecretion or during apparent remission with normal cortisol secretion. Marked suppression of plasma ACTH was measured in response to an iv infusion of 50 mg cortisol over a period of 55 min whereas a similar test with 2 mg dexamethasone (iv bolus) did not suppress ACTH secretion. Transsphenoidal exploration of the sella revealed a tumour surrounding the anterior pituitary. Examination of the pituitary showed a few tiny tumour structures embedded in normal tissue which could not be removed, when the tumour was resected selectively under preservation of normal appearing tissue. Post-operatively, clinical and chemical remission (normal response to 1 mg dexamethasone) was observed for about 4 months. Thereafter, cortisol hypersecretion occurred again necessitating bilateral adrenalectomy.

Our results are compatible with the assumption that normal hypothalamic-pituitary-adrenal suppressibility with cortisol, but not with dexamethasone, was caused by the loss of feedback receptors for dexamethasone in the presence of cortisol receptors in the cells which secrete ACTH or CRF.

The combination of cyclic hypercortisolism with dexamethasone non-suppressible Cushing's syndrome has not been reported before and thus represents a new variant of Cushing's syndrome.