Typing of inflammatory lesions of the pituitary.

Inflammatory pituitary lesions account for 1.8% of all specimens from the German Pituitary Tumor Registry. They occure in 0.5% of the autoptical specimens and in 2.2% of the surgical cases. Women are significantly more often affected than men and are often younger when first diagnosed. In general, primary and secondary inflammation can be distinguished, with secondary types occurring more frequently (75.1%) than idiopathic inflammatory lesions (15.4%). In primary inflammation, the lymphocytic type is more common (88.5%) than the granulomatous type of hypophysitis (11.5%). The most common causes of secondary inflammation are Rathke's cleft cysts (48.6%), followed by tumors (17.4%) such as the craniopharyngioma (9.1%), adenoma (5.5%) or germinoma (2.0%). More causes are tumor-like lesions (7.1%) such as xanthogranuloma (3.5%) or Langerhans histiocytosis (3.5%), abscesses (5.5%), generalized infections (5.1%), spreaded inflammations (4.7%) and previous surgeries (4.0%). In 1.6% of all specimens the reason for the inflammation remains unclear. The described classification of hypophysitis is important for specific treatment planning after surgery.

Fractionated radiotherapy and radiosurgery in acromegaly: analysis of 352 patients from the German Acromegaly Registry.

BACKGROUND: If biochemical control of acromegaly is not achieved by operation and medication, radiotherapy may be indicated. OBJECTIVE: To describe fractionated radiotherapy (FRT) and stereotactic radiosurgery (SRS) regarding excess of IGF-1 and pituitary function. DESIGN AND METHODS: A retrospective analysis of 352 patients (4126 patient-years) from the German Acromegaly Registry was performed. Follow-up was 1.0-45.1 years after radiotherapy. Therapeutic success was defined by low or normal IGF-1 according to center-specific reference ranges without (= remission) or on (= controlled disease) suppressive medication. RESULTS: Time between radiotherapy and last follow-up was 13.0 ± 8.2 years for FRT (n = 233) and 8.9 ± 5.0 years for SRS (n = 119, P < 0.001). Median (IQR) basal growth hormone before radiotherapy was 6.3 (2.9-16.2) ng/mL for FRT and 3.5 (1.8-6.9) ng/mL for SRS (P < 0.001). Mean time in uncontrolled state was 3.0 years after FRT and 2.1 years after SRS (95% CI for the difference is 0.1 to 1.6 years, P = 0.021). The 10-year calculated remission rate was 48% for FRT and 52% for SRS (95% CI for the difference is -18 to 26% age points, P = 0.74) and the respective controlled disease rate was 23 and 26%. The odds ratio for adrenocorticotropic or thyreotropic insufficiency was 0.54 (95% CI: 0.30-1.00, P = 0.049) in SRS compared to FRT patients. CONCLUSION: Both after FRT and SRS about 75% of patients with acromegaly are in remission or controlled after 10 years. A slightly faster achievement of target values was observed after SRS. The rate of pituitary insufficiency in FRT patients is significantly higher.

Clinical Impact of the Current WHO Classification of Pituitary Adenomas.

WHO classifications should be used for comparing the results from different groups of pathologist and clinicians by standardized histopathological methods. Our present report describes the important parameters of pituitary adenoma pathology as demand of the WHO classification for correlation to endocrine data and prognosis. The combination of HE stain based structures with immunostainings for pituitary hormones allows subclassification of adenomas as the best method not only for correlations to clinical hyperfunctions but also for statements to the sensitivity of drug therapies (somatostatin analogs, dopamine agonists). GH-, PRL- and ACTH-secreting pituitary adenomas are further classified based on the size and number of their secretory granules by electron microscopy, or as is mostly the case nowadays by cytokeratin staining pattern, into densely and sparsely granulated. Granulation pattern may be considered for the prediction of treatment response in patients with GH-secreting adenomas, since the sparsely granulated subtype was shown to be less responsive to somatostatin analog treatment. For prognosis, it is important to identify aggressive adenomas by measurements of the Ki-67 index, of the number of mitoses, and of nuclear expression of p53. Among the criteria for atypical adenomas, high Ki-67 labeling index and invasive character are the most important adverse prognostic factors. Promising molecular markers have been identified that might supplement the currently used proliferation parameters. For defining atypical adenomas in a future histopathological classification system, we propose to provide the proliferative potential and the invasive character separately.

Emerging Histopathological and Genetic Parameters of Pituitary Adenomas: Clinical Impact and Recommendation for Future WHO Classification.

The review assesses immunohistochemical findings of somatostatin receptors and of metalloproteinases in different pituitary adenoma types and the significance of molecular genetic data. Current evidence does not support routine immunohistochemical assessment of somatostatin or dopamine receptor subtype expression on hormone-secreting or nonfunctioning pituitary adenomas. Further prospective studies are needed to define its role for clinical decision making. Until then we suggest to restrict membrane receptor profiling to individual cases or for study purposes. The problems of adenoma expansion and invasion are discussed. Despite partially contradictory publications, proteases clearly play a major role in permission of infiltrative growth of pituitary adenomas. Therefore, detection of at least MMP-2, MMP-9, TIMP-2, and uPA seems to be justified. Molecular characterization is important for familial adenomas, adenomas in MEN, Carney complex, and McCune-Albright syndrome and can gain insight into pathogenesis of sporadic adenomas.

Ultrasound-assisted microsurgery for Cushing's disease.

OBJECTIVE: Localization of microadenomas in Cushing's disease may be difficult as in up to 45% of patients sellar MRI fails to detect a pituitary tumor. Intraoperative transsphenoidal ultrasound may identify microadenomas as hyperechoic structures. We report on the first 18 consecutive cases with intraoperative use of a new device for direct contact high-frequency-ultrasound in patients with Cushing's disease. PATIENTS AND TECHNIQUE: 18 patients (14 female, 4 male, age 24-71 years) with typical endocrinological findings for Cushing's disease were included in the study. One macroadenoma and 13 microadenomas were suspected or identified preoperatively by MRI. In 4 cases, two of them with recurrent disease, sellar MRIs were negative. During transsphenoidal microsurgery an end fire ultrasound-probe (B-mode frequency range 7.5-13 Mhz, field of view 5 mm, penetration 20 mm) was introduced after opening of sellar floor. The pituitary gland was scanned in direct contact to the capsule. RESULTS: In 13 out of 17 cases (77%) with later on proven microadenomas high-frequency-ultrasound identified the tumors as hyperechoic masses, including 3 of the 4 cases with negative preoperative MRI. In 2 cases ultrasound correctly localized the tumor at a site different from MRI finding (MRI false positive). In the macroadenoma, identification of the border between tumor and anterior pituitary gland was not possible. In all 18 patients postoperative early decline of serum cortisol to subnormal levels confirmed remission of hypercortisolism (100%). Other pituitary functions were unaltered in 17 cases (94%). CONCLUSIONS: Intraoperative scanning of the pituitary gland with high-frequency-ultrasound probes may identify intrapituitary anatomy and pathologies even in MRI-negative cases. This may prevent extensive exploration of the gland with the risk of subsequent hypopituitarism.

Assessment of normal perisellar anatomy in 1.5 T T2-weighted MRI and comparison with the anatomic criteria defining cavernous sinus invasion of pituitary adenomas.

OBJECTIVE: The study aimed to evaluate the anatomical relations of sellar and perisellar structures with T2-weighted MRI and to apply criteria for cavernous sinus (CS) invasion by pituitary adenomas to normal sellar anatomy. METHODS: Thin slice (3 mm) coronal T2-weighted MR-images (1.5 Tesla) were obtained in 117 individuals (234 CS) without pituitary disorders (58 females, 59 males; age 17 months to 87 years). In 99 cases data indicating the presence of arterial hypertension (AH) were available, 25 with AH, 74 without AH. RESULTS: The medial wall of the cavernous sinus was detectable in 33% of cases. The inferior rim of the horizontal part of the ICA was located at the level of the sellar floor in 33%, below in 47%, and above in 20%. The mean distance between the both ICAs was 17.8 mm (range, 7-38 mm). The mean distance between the pituitary and the ICA in AH was significantly shorter than in patients without AH (Chi-square, p=0.01). There was contact between the gland and the ICA in 41.5% of the cases. In 16.7% (39 sides) of all 234 SCs investigated, the area of contact between the ICA and the gland was at least 25% of the vessel's circumference. The medial intercarotid line (ICL) was crossed by the pituitary gland in 9% (21 of 234 CS), the central ICL was touched in another 5% (11 of 234 CS), lateral ICL was never reached. There was a weak correlation with age: a more extensive lateral extension of the gland was seen in individuals older than 40 years compared to younger individuals (Chi-square, p=0.03). There was a marked difference in the anatomical findings between both sides in 41.9% of cases. CONCLUSION: Inter- and intra-individual variations of the perisellar anatomy and its relation to the pituitary gland exist, which are partly related to age and AH. This must be remembered when the invasiveness of pituitary adenomas is assessed in MRI.

The use of postoperative ACTH levels as a marker for successful transsphenoidal microsurgery in Cushing's disease.

OBJECTIVES: The declines of ACTH and other POMC metabolites immediately after tumor extirpation do not predict the complete tumor removal of an ACTH-secreting pituitary adenoma in Cushing's disease. However, the pituitary surgeon should be in a position to evaluate the surgical result as soon as possible for the eventual planning of early repeat surgery. So far, subnormal serum cortisol levels after surgery are widely accepted as the criterion for cure. We investigated whether the early postoperative ACTH concentration is a reliable marker for the initial surgical outcome as well as the long-term remission. METHODS: In a prospective study, 147 patients undergoing primary transsphenoidal microsurgery for Cushing's disease between 1990 and 1996 were investigated. The early postoperative ACTH courses were reviewed and compared with the long-term outcome. ACTH measurements were performed immediately after tumor excision, 1, 2, 4, 8, and 12 hours later, and the following morning. Further ACTH levels were determined on various days of the hospital stay. Glucocorticoids were not given until hypocortisolism was proven. RESULTS: Ninety-five patients (65 %) presented with subnormal ACTH levels (< 10 ng/l) during their postoperative stay, of whom two patients (2 %) experienced recurrence of disease after 66 and 100 months. Of 29 procedures with early postoperative ACTH levels ranging from 10-20 ng/l (20 %), one patient received further treatment for persistent (3.5 %) and one patient for recurrent Cushing's disease (3.5 %). Of 12 patients (8 %) with early postoperative ACTH levels in between 20 to 30 ng/l, one patient received further treatment for persistent (8 %) and four patients for recurrent disease (33 %). ACTH levels of more than 30 ng/l, found in 11 patients (7 %), were accompanied by persistent (8 patients, 73 %) or recurrent (2 patients, 18 %) Cushing's disease. CONCLUSION: Subnormal (< 10 ng/l) or low normal (< 20 ng/l) postoperative ACTH levels within the first 7 days after surgery can be regarded as early markers for complete removal of an ACTH adenoma as well as indicators for long-term outcome in Cushing's disease. The risks of persistence or recurrence of Cushing's disease rise with the level of early postoperative ACTH values. Normal ACTH levels should result into further evaluation of the ACTH-cortisol secretion, for example by stimulation- or suppression tests.

Cavernous sinus sampling in selected cases of Cushing's disease.

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.

Cushing's disease: a surgical view.

The management of adrenocorticotropic hormone (ACTH)-dependent Cushing's disease implies difficulties in the differential diagnosis, in the detection of minute pituitary adenomas, as well as in the radical removal of invasive adenomas. Magnetic resonance imaging (MRI) is unspecific and often negative in minute adenomas of three or less millimeters diameter. The trias of detectable ACTH, suppression of cortisol in the high-dose dexamethasone test, and stimulation in the corticotropin-releasing-hormone (CRH)-test has a high accuracy to prove pituitary dependency. In unclear cases, the use of inferior petrosal sinus sampling (IPSS) or cavernous sinus sampling (CSS) for the exclusion of ectopic ACTH-syndrome is currently advised especially in cases where cranial MRI is negative. The reliability of these methods to localize the mostly lateralized microadenomas is still discussed. Transsphenoidal microsurgical adenomectomy, the accepted primary therapy of Cushing's disease, has been published from experienced pituitary centers with remission rates ranging from 70% to 98% in the last decade. False diagnosis (pseudo-Cushing, ectopic ACTH-syndrome), incorrect adenoma localization by IPSS or CSS, and the rate of minute or non-resectable invasive tumors influence the results. The handling of minute specimen implies problems for surgeon and pathologist. Intraoperative tumor localization was improved by ACTH measurement from the cavernous sinus and the adenoma itself, by cytology, and frozen sections. The histology of the anterior lobe (rate of Crooke's cells) bears information of clinical relevance. Invasive macroadenomas may deserve repeat microsurgery, medical treatment, and radiosurgery.

The value of intraoperative cytology during transsphenoidal surgery for ACTH-secreting microadenoma.

BACKGROUND: Microsurgical selective adenomectomy is the best established method available for the treatment of Cushing's disease. However, this surgical method warrants still more efforts to improve the results in minute microadenomas. In this paper the authors evaluate a method of intraoperative cytological investigations during transsphenoidal surgery. METHOD: Between January 1997 and September 1999, transsphenoidal surgery was performed in 75 patients with the diagnosis of Cushing's disease. Fifty-one cases of proven microadenomas were reviewed. FINDINGS: Of 51 cases, 33 tumors were 3 mm or less in diameter, here after called minute adenomas. In 49 of 51 (96.1%) microadenomas, adenoma tissue was identified by intraoperative cytological techniques. Postoperatively, only 35 of 51 ACTH-secreting microadenomas (68.6%) were confirmed by immunostaining methods. This lower percentage was most probably due to the small amount of tissue obtained. Therefore, in 14 cases (including 12 minute adenomas) the presence of the adenoma was only proven by cytological preparation and clinical outcome. The sensitivity of cytological preparations in cases of confirmed Cushing's disease was 100%. INTERPRETATION: The method described here was particularly well suited for the intraoperative discrimination and documentation of minute adenomas. Cytological preparation appears to be effective in improving the adenoma finding rate and the surgical outcome in cases of Cushing's disease.

Correlates of long-term hypocortisolism after transsphenoidal microsurgery for Cushing's disease.

In Cushing's disease, selective total removal of a corticotroph tumor of the pituitary regularly results in subnormal ACTH- and cortisol plasma levels. The duration of secondary adrenocortical insufficiency varies widely, with an average of 17 months in our patients. The goal of this study is to elucidate the underlying causes for the variation in duration of postoperative hypocortisolism. In this retrospective study, we evaluated 35 patients with postoperative hypocortisolism lasting more than 36 months, and compared them to 51 patients with a duration of less than 36 months. Preoperative data, intraoperative findings, and postoperative results with follow-up evaluations are presented. Extensive pituitary exploration, medial localization of the tumor, and a higher age were associated with increased risk for isolated secondary long-term hypocortisolism. The histological examination of paraadenomateous tissue identified a significantly larger amount of Crooke's cells in long-term cortisol insufficient patients. Previous pituitary surgery increased the risk for hypopituitarism. In some of our patients, the long-term adrenocortical insufficiency resolved after a period of over five years.

Direct intraoperative micromethod for hormone measurements of pituitary tissue in Cushing's disease.

BACKGROUND: During transsphenoidal surgery (TSS) for Cushing's disease, the surgeon depends on experience to find minute adenomas. Cytological slide preparations or frozen sections, even when successful, are not specific concerning the hormone activity. In an attempt to improve accurate localization of minute ACTH adenomas, we evaluated a new intraoperative method of ACTH measurements in adenoma and anterior lobe microsamples. As most ACTH adenomas are monohormonal, the possible benefit of a GH measurement was investigated. METHODS: We included pituitary tissue of 32 patients, 22 with Cushing's disease and 10 endocrine inactive pituitary adenomas as control. All patients underwent TSS by one surgeon. Preoperative data, intraoperative and perioperative hormone measurements of homogenized, weighed pituitary tissue samples, and histological findings are presented. RESULTS: In ACTH adenomas, the median ACTH content was found to be 1,688 ng/mg, minimum 345 ng/mg. The median GH was measured at 36 ng/mg. Anterior lobe tissue contained median 80 ng ACTH/mg, maximum 279 ng/mg. Median GH was 2,200 ng/mg. In hormonally inactive adenomas ACTH was less than 0.1 ng/mg, median GH was 5.5 ng/mg. There was no overlap of ACTH content in the tissues investigated. Therefore, by adopting 300 ng ACTH/mg as a cutoff level, a clear discrimination is given. Additional GH measurements are not necessary. CONCLUSION: This new intraoperative method permits a clear differentiation between adenoma and pituitary tissue. In addition to intraoperative cytology and histology, this method can serve as a specific proof that the ACTH adenoma has been identified during surgery. This may be valuable in difficult cases with unclear intraoperative findings, especially after previously negative exploration.

Treatment and long-term outcome of pineal nongerminomatous germ cell tumors.

In 1994 we reported on a small series of 3 children with malignant, marker-positive pineal nongerminomatous germ cell tumors treated with a 'sandwich' protocol. Here, we report on the long-term survival of these children. Preoperative chemotherapy consisted of two courses of bleomycin, etoposide, and cisplatin. En bloc resection of the tumors via the supracerebellar, infratentorial route was performed immediately after decline of tumor marker levels. Postoperatively, two courses of vinblastine, ifosfamide, and cisplatin were applied, followed by craniospinal irradiation. The patients showed no major neurological deficits and no evidence (neuroradiologically or with regard to tumor marker levels) of recurrence of disease after 66, 71, and 78 months, respectively. We propose this regimen for children with tumors of the pineal region in whom the tumor markers are positive. It should be started without histological classification of the tumor to avoid possible spillage of malignant tumor cells to the cerebrospinal fluid.

Transnasal microsurgery in children and adolescents with Cushing's disease.

OBJECTIVE: Transnasal adenomectomy is the treatment of choice for Cushing's disease. We review the diagnostic peculiarities, specific surgical problems, and outcome of children and adolescents with Cushing's disease. METHODS: We report on our series of 55 consecutive children and adolescents (range, 4.2-18.9 yr [mean age, 14.4 yr]; female:male = 1.1:1.0; mean follow-up, 54.5 +/- 38.6 mo [standard deviation]) with Cushing's disease on whom we performed surgery since 1980. The indication for transsphenoidal surgery is based on endocrinological parameters and not on neuroradiological findings. RESULTS: Detection rate of the tumor site was 22% using computed tomography and 33% using magnetic resonance imaging. Only 7 of 13 interpetrosal adrenocorticotropic hormone gradients obtained during inferior petrosal sinus sampling correctly lateralized the tumor site preoperatively (53.8%). In cases of incomplete sphenoid pneumatization, adequate exposure is achieved by drilling. The tumor finding rate is 98%. The remission rate is 100% when two early subsequent operations are included. The recurrence rate for 45 primary operations with follow-up of at least 1 year is 15.5%. Seven of nine subsequent operations for recurrent hypercortisolism were successful. One patient needed three more operations until hypercortisolism subsided; one patient achieved remission after additional pituitary irradiation. The surgical morbidity was low in this series, which consisted of two cerebrospinal fluid fistulas. The incidence of hypopituitarism after primary operations (10.3%) is significantly lower than after subsequent operations (45.5%). CONCLUSION: Direct transnasal submucosal surgery for Cushing's disease is successful, and pituitary function can be preserved in most of these young patients.

Persistent and recurrent hypercortisolism after transsphenoidal surgery for Cushing's disease.

After transnasal operations in Cushing's syndrome persisting hypercortisolism either due to negative pituitary exploration or due to subtotal tumor removal, and recurrence of the disease after successful surgery still are challenging. We report on the therapeutic failures among 310 consecutive patients who underwent primary transsphenoidal microsurgery for Cushing's disease. In 287 patients an ACTH-producing pituitary adenoma could be detected (finding rate: 92.6%). In 264 cases remission of hypercortisolism could be attained (remission rate with adenoma 92.0%, for the whole series of primary operations 85.2%). In 23 patients no adenoma could be found despite extensive pituitary exploration (7.4%). Here, we will focus on the management of the 23/287 patients with persistent hypercortisolism after transnasal tumor operation (8.0%) and those 29 cases of the 264 patients with a remission who developed a recurrence of hypercortisolism (11.0%). In recurrent hypercortisolism we recommend transsphenoidal reoperation even when no tumor is visible in MRI. Seventeen of 24 reoperations in recurrent Cushing's disease were successful (70.8%). In persistent hypercortisolism we perform a reoperation during the same hospital stay. Nine of 16 early reoperations led to remission of hypercortisolism (56.3%). If transsphenoidal reoperation fails we indicate radiation therapy of different modalities depending on the extension and location of the tumor remnants. Bilateral adrenalectomy is proposed by us only if all other therapeutic measures failed.

Pituitary surgery in elderly patients with acromegaly.

Because of the common belief that there is an increase in surgical risk and morbidity involved in the surgical therapy of elderly patients with acromegaly, physicians tend to either neglect therapy altogether or choose radiation therapy combined with medical treatment. In consideration of the expected increasing number of elderly patients resulting from social structure change in the coming years, we decided to investigate the outcome in 15 patients with acromegaly (13 women and 2 men) older than 64 years (mean, 68.3 yr) at the time of surgery in the form of a retrospective study. Medical treatment using either dopamine agonists (9 patients) and/or octreotide (4 patients) were attempted in 11 patients. For various reasons, however, medical therapy could not be permanently continued in any of these patients. The mean preoperative growth hormone (GH)-plasma level without medical treatment was 47.4 +/- 64.2 (mean +/- standard deviation) micrograms/L. At the time of operation, 13 of 15 patients had additional diseases, which led to an increased anesthesiological risk. Transnasal tumor removal was performed without anesthesiological or surgical complications in all patients. The radicality of tumor removal was controlled intraoperatively by GH measurements in eight patients. There was no postoperative mortality or serious morbidity. Postoperative basal GH-plasma levels were normal (< 4.5 micrograms/L) in all patients. None of the 13 patients who participated in long-term follow-up examinations (mean, 4.2 yr) revealed signs of definite tumor recurrence. The mean GH-plasma level at follow-up was 1.6 +/- 0.9 (mean +/- standard deviation) micrograms/L. One patient died 2 years after the operation of causes unrelated to pituitary surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Intrastriatal cerebellar grafts: differentiation of cerebellar anlage and sprouting of Purkinje cell axons.

Pieces of cerebellar primordia were obtained from G16 (day 16 of gestation) rat fetuses and stereotaxically injected into the striatum of adult Wistar rats. The transplants were allowed to integrate with the host brain for 2 h up to 6 months after implantation. Ninety four out of 105 transplants perfectly integrated with the host brain (90%) and established the typical trilaminar histoarchitecture of cerebellar cortex. The transplants were sufficiently vascularized. Vessels seen within the grafts provided all ultrastructural elements of a blood-brain barrier. Light microscopic evaluation of graft development showed no considerable retardation of cerebellar histogenesis. Electron microscopic examination disclosed normal ultrastructure of cerebellar neurons, as well as elements of regular synaptic organization. The topic of efferent graft-to-host projections was investigated 2.5 months after transplantation using the monoclonal Purkinje cell marker anti-Leu-4 (CD3). This method allowed us to detect immunoreactive, morphologically intact axons of grafted Purkinje cells running over long distances (at least 500 microns) within the host striatum. Whilst afferent but in no case efferent connections of heterotopic cerebellar transplants had been demonstrated elsewhere, we could now prove the reciprocal modus of graft-host interaction with heterotopic cerebellar grafts.

Autoradiographic demonstration of in vivo 125I-growth hormone-releasing hormone (GHRH) binding by human GH-secreting pituitary adenomas transplanted on athymic nude mice.

This study was designed for the purpose of investigating a method for in vivo tumor labelling of human GH (hGH) secreting pituitary adenomas. Pituitary adenoma tissue removed from four acromegalic patients was transplanted into 62 athymic nude mice. After positive GHRH stimulation tests 125I-GHRH(1-44) NH2 was injected intravenously (i.v.) in ten nude mice. 10 min after 125I-GHRH injection, the nude mice were sacrificed, the transplants excised and prepared for light microscopical autoradiography. The mouse pituitary and skeletal muscle specimens served as controls. After the i.v. injection of 125I-GHRH we observed a marked accumulation of silver grains within the adenoma tissue indicating tumor labelling. This study is a first step in investigating a new method for labelling small residues of hGH secreting pituitary adenomas intraoperatively.