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D K Lüdecke

Publications and source records attributed to D K Lüdecke.

At least 37 records · Page 2Linked to original sources

Lymphocytic hypophysitis with central diabetes insipidus and consequent panhypopituitarism preceding a multifocal, intracranial germinoma in a prepubertal girl.

UNLABELLED: We report the clinical course of a prepubertal girl with central diabetes insipidus (DI) and consequent panhypopituitarism evolving over a period of 10 years due to lymphocytic hypophysitis and subsequent germinoma. Two years after the diagnosis of central DI was established, MRI revealed a thickened pituitary stalk. Later pituitary enlargement and increasing thickening of the pituitary stalk impinging on the optic chiasm required a trans-sphenoidal biopsy which disclosed active hypophysitis with lymphocytic infiltrates and necrosis. High dose dexamethasone treatment only temporarily halted the disease process. Therefore, stereotactic radiation therapy was performed as a rescue treatment and MRI findings almost reversed. However, the subsequent MRI showed multiple intracranial lesions identified histologically as a germinoma and a standard chemotherapy and radiation was performed. CONCLUSION: The diagnosis of diabetes insipidus in children requires long-term follow up beyond the pubertal age in order to establish the underlying cause. In contrast to lymphocytic hypophysitis in adults, lymphocytic hypophysitis in prepubertal children may represent the first sign of a host reaction to an occult germinoma.

Brain Neoplasms↗

Mucocele-like formation leading to neurological symptoms in prolactin-secreting pituitary adenomas under dopamine agonist therapy.

BACKGROUND: Mucocele-like formation associated with pituitary adenomas, to the best of our knowledge, has been paid little attention. We report three adult male patients with a mucocele-like formation that developed behind the tumor and led to neurological symptoms in prolactin-secreting pituitary adenomas (prolactinomas) under dopamine agonist therapy. CLINICAL PRESENTATION: Three adult male patients with prolactinomas developed hyperprolactinemia and new neurological symptoms during dopamine agonist treatment. In each case, the pathogenesis of these symptoms was due in part to a mass enlargement with development of a mucocele-like formation behind a prolactinoma. In our patients, a prolactinoma with a suprasellar extension originally filled the sphenoid sinus. When dopamine agonist therapy became ineffective, new symptoms, such as progressive visual impairment other than typical hemianopsia or headache, developed and mass enlargement was found on MRI. MRI demonstrated two different components: an enhancing prolactinoma and a nonenhancing mucocele-like formation behind the tumor. Two patients had compression of the optic nerves by a mass. Transnasal removal of mucoceles and adenomas led to resolution of the neurological symptoms. CONCLUSION: Early suspicion of a mucocele-like formation under dopamine agonist therapy for prolactinomas is important in order to avoid a delay in surgery, because a change in medical treatment will be ineffective.

Aged↗

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.

Adenoma↗

Folliculo-stellate cells in pituitary adenomas of patients with acromegaly.

Pituitary adenoma tissue from patients with acromegaly (n = 286) was obtained by surgery and examined for folliculo-stellate cells by immunostaining for S100 protein. The number of immunostained cells varied from one adenoma to another. A hundred and ninety-eight pituitary adenomas (69%) contained S100 protein positive cells corresponding to folliculo-stellate cells (FSC): in 100 cases (35%), only few sparse FSC were found, in 43 cases (15%) FSC were scattered throughout the adenoma, and in 55 cases (19%) there was an abundance of FSC. There were no significant differences regarding sex or age of the patients. The relative amount of FSC vaired among different adenoma types. Plurihormonal adenomas showed the highest FSC density, whereas the majority of monohormonal adenomas contained only few or no FSC. Patients with pituitary adenomas containing scattered FSC had a significantly higher preoperative mean GH level than patients with pituitary adenomas not having FSC. There was a negative correlation between the FSC density in adenoma tissue and the preoperative mean PRL level. There was no correlation between the tumour size and the amount of FSC. Our data indicate no effect of the duration of symptoms on the FSC density and do not suggest a correlation between FSC density and the percentage of a certain hormone-secreting cell type.

Acromegaly↗

Markers of function and proliferation in non-invasive and invasive bi- and plurihormonal adenomas of patients with acromegaly: an immunohistochemical study.

Twenty-seven plurihormonal and 21 growth hormone- prolactin- (GH- PRL-) mixed cell adenomas obtained from patients with acromegaly undergoing transnasal-transsphenoidal surgery were investigated immunohistochemically for expression of Epidermal Growth Factor (EGF), Transforming Growth Factor alpha (TGF alpha), Insulin-like Growth Factor-1 (IGF-1), Estrogen Receptor-Related Protein (ERRP), Multidrug Resistance Marker (MDRM), Protein Kinase C (PKC), Gs alpha,. Cathepsin D and p53. Five plurihormonal adenomas grew invasively. The panel of markers used in this study represents a selection of functional and proliferative markers thought to be associated with the function and development of pituitary adenomas. Our results imply that the growth factors (EGF, TGF alpha, IGF-1), the cell signalling protein Gs alpha and the MDRM are expressed by both types of pituitary adenomas in a similar pattern. Non-invasive GH-PRL-mixed cell adenomas showed an increased expression of IGF-1, TGF alpha and MDRM compared to non-invasive plurihormonal adenomas. No factor was found which would reliably distinguish between invasive and non-invasive adenomas. We failed to confirm the findings of others that p53 and cathepsin D might be indicators of tumor aggressiveness. A participation of ERRP and PKC in the development of bi- and plurihormonal adenomas with acromegaly appears unlikely, as the immunostains were all negative.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Lymphocytic hypophysitis masking a suprasellar germinoma in a 12-year-old girl--a case report.

Case history, light and electron microscopic findings of a case of a lymphocytic hypophysitis in coincidence with a suprasellar germinoma in a 12-year-old girl are reported. The girl presented with a long time case history of diabetes insipidus and subsequent panhypopituitarism. Two years after the diagnosis of diabetes insipidus magnetic resonance imaging (MRI) showed a tumorous enlargement of the sellar content and pituitary stalk. A transnasal exploration was initially performed and revealed a lymphocytic hypophysitis. Light microscopy showed a dense infiltration of mature lymphocytes and plasma cells in the interstitium of the anterior pituitary gland. The stalk area could not be exposed to exclude a germinoma. One year later the lesion relapsed despite dexamethason therapy and a second operation by another neurosurgeon had to be performed. Light microscopy showed lymphocytic infiltrates, fibrosis and necrosis. The diagnosis was a lymphocytic hypophysitis again. Though transcranially exposed only pituitary tissue was removed. No infundibular mass became visible at surgery as shown by MRI. The girl developed five months later multiple cerebral lesions, which revealed to be a germinoma. Lymphocytic hypophysitis in children is very rare and a coincidence with a germinoma has not been described from histopathological aspect until now. The origin of the pituitary infiltration is discussed.

Child↗

Proliferation markers in different types of clinically non-secreting pituitary adenomas.

160 clinically non-secreting pituitary adenomas were examined in regard to their expression of the markers PCNA, bcl2, Ki 67 in the mib-1 modification and p53 which are still under investigation for their relevance to cell proliferation. The series contained 60 null cell adenomas, 60 oncocytomas and 40 gonadotroph adenomas. The groups that showed a definitely negative and definitely positive staining were evaluated in regard to their further characteristics such as size, invasiveness and recurrence. PCNA showed a highly represented immunostaining index throughout the groups, but not correlation between the PCNA index and an increased recurrence rate could be found. The staining for bcl2 was only rarely positive and only in a small number of cells. No correlation with the clinical data could be seen. We found a significant higher rate of staining in the invasive adenomas in the group of null cell adenomas and oncocytomas for Ki 67, especially in those adenomas expressing p53. p53 positivity was restricted to the invasive adenomas but was found only in 20% of all invasive adenomas. These data confirm in a sufficiently large series of clinically endocrine inactive pituitary adenomas, that p53 and Ki67 immunohistology is useful in evaluating the aggressive behavior of clinically silent pituitary adenomas. Nevertheless, negative results do not exclude clinically relevant invasive behavior.

Adenoma↗

Recent primary transnasal surgical outcomes associated with intraoperative growth hormone measurement in acromegaly.

OBJECTIVE: Since 1983, we have measured GH intraoperatively to improve the surgical outcome for acromegalic patients with GH secreting pituitary adenomas. Here, we present the recent results of primary surgery in patients with acromegaly to examine the effect of improved surgical techniques and experience. PATIENTS AND MEASUREMENT: Intraoperative GH concentrations were measured in 78 consecutive acromegalic patients who had not previously undergone surgery between May 1992 and April 1994 (45 females and 33 males, age range, 21-70 years, mean, 47.1 +/- 1.3). All patients were followed for at least 3 years. Direct transnasal tumour extirpation was performed. Intraoperative GH measurements were assayed 0, 20 and 60 min after tumour removal. A plasma GH level < or = 4.5 micrograms/l at 60 min after initial tumour removal was used as a criterion of radical tumour removal. In cases with intraoperative plasma GH concentrations > or = 40 micrograms/l prior to tumour resection, the half-life of the GH concentration at 20 min was used to assess completeness of tumour removal. In these cases, it was defined as having achieved a 50% reduction in plasma GH at 20 min compared to 0 min after tumour resection. To obtain intraoperative GH measurements, mild anaesthesia was continued for an average of 82 +/- 23 min. RESULTS: Radical tumour removal was determined intraoperatively in 51 patients and subsequently confirmed in 50 patients (98.0%). In 18 of 27 patients with incomplete tumour removal, immediate reoperation was performed under continous anaesthesia. In 11 of these 18 patients, endocrinological remission was achieved (14.1%; 11/78). None of the remaining nine patients who did not undergo secondary surgery achieved remission. Secondary surgery improved the remission rate from 85.7% (12/14) to 92.9% (13/14) in microadenomas and from 70.1% (38/54) to 88.9% (48/54) in non-invasive macroadenomas. Remission was not observed in patients with imageproven extrasellar extension. CONCLUSIONS: Secondary surgery based on intraoperative GH measurement improves the outcome of tumour resection in patients with non-invasive GH secreting macroadenomas.

Acromegaly↗

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.

Adenoma↗

Transnasal surgery for infradiaphragmatic craniopharyngiomas in pediatric patients.

OBJECTIVE: Transnasal surgery has been performed in only a small number of cases of pediatric craniopharyngiomas, and its efficacy is still a matter of debate. METHODS: We analyzed the results of transnasal surgery performed in 11 pediatric patients (6 male and 5 female patients) with infradiaphragmatic craniopharyngiomas who were younger than 15 years at the time of surgery (age range, 7.7-14.9 yr) and who were treated between 1985 and 1996, when more refined diagnostic and surgical techniques were available. Two of the patients had undergone primary surgery elsewhere. The transnasal approach was chosen because of sellar enlargement and the presence of an infradiaphragmatic tumor. The duration of the clinical follow-up period was at least 1 year. RESULTS: Five patients required drilling of incompletely pneumatized sphenoid sinuses to reach the sella, but in no cases were the anatomic differences related to patient age or size thought to be a limiting factor in the transnasal procedure. The normal pituitary gland was incised to expose a dorsally located tumor in each of eight patients (72.7%). This surgical procedure has never provoked any major functional damage to the anterior pituitary gland. Complete tumor resection was achieved in three patients (27.3%) and subtotal removal in eight (72.7%). Twenty-two (95.7%) of 23 normal functions were preserved after subtotal tumor removal. In contrast, only one of four normal functions was maintained after complete tumor resection. Persistent diabetes insipidus occurred after total tumor resection in one patient. Tumor regrowth occurred in two patients. No tumor recurrence was observed during the follow-up period. CONCLUSION: Based on the present findings, transnasal surgery seems to be indicated for most infradiaphragmatic craniopharyngiomas occurring in pediatric patients. Transnasal surgery is as safe to perform in pediatric patients as it is in adult patients. The concept of subtotal tumor removal with preservation of pituitary function, avoiding damage to hypothalamic structures and excessive cerebrospinal fluid leakage, seems to be justified in pediatric patients.

Adolescent↗

Growth hormone-secreting pituitary adenomas in childhood and adolescence: features and results of transnasal surgery.

OBJECTIVE: Pituitary tumors causing gigantism are rare in childhood and adolescence. In a review of 2367 patients with pituitary adenomas who were treated between 1970 and 1997, we found 15 cases (0.63%, 9 male and 6 female patients) of growth hormone-secreting pituitary adenomas in patients who were less than 20 years of age at the time of surgery, and we compared their characteristics with those of adenomas in an adult group. METHODS: Patients were grouped according to their ages at the first operation, with five patients (33.3%) in the prepubescent group (0-11 yr), eight (53.3%) in the pubescent group (12-17 yr), and two (13.3%) in the postpubescent group (18-19 yr). All 15 patients exhibited the typical symptoms of growth hormone oversecretion. The incidence of hyperprolactinemia among patients with prepubescent onset was 66.7%. Radiological examinations demonstrated microadenomas in 4 patients (26.7%) and macroadenomas in 11 patients (73.3%). The mean follow-up period was 73.5 months. RESULTS: Direct transnasal explorations were performed for all patients. Tumor invasion into the cavernous sinus was observed in six patients (40%). Radical tumor resection was performed for four patients (80%) in the prepubescent group, for five patients (62.5%) in the pubescent group, and for neither patient in the postpubescent group. Surgical morbidity was caused by permanent diabetes insipidus in three patients (20%). Rapid growth was postoperatively improved in 80% of the prepubescent age group. The recurrence rate was 13.3% (2 of 15 patients). CONCLUSION: Transnasal pituitary surgery was found to be as safe in pediatric patients with gigantism as in adults. Growth hormone-secreting pituitary adenomas in childhood and adolescence were more likely to be invasive or aggressive than were those in adulthood. The clinical biological characteristics for children were different from those for adults.

Adenoma↗

Reduced expression levels of the cell-cycle inhibitor p27Kip1 in human pituitary adenomas.

The molecular mechanisms leading to increased cellular proliferation rates and, thus, tumor formation in the anterior pituitary gland are poorly understood. The cyclin-dependent kinase inhibitor p27Kip1 is a key molecule regulating the G1 phase of the cell cycle in many cell types. Furthermore, it was shown that p27 knock-out mice develop pro-opiomelanocortin-positive pituitary tumors. In an effort to clarify the role of p27 in the normal and tumorous human pituitary, we studied the expression of p27 by immunohistochemistry, using a highly specific mouse monoclonal anti-human p27 antibody. Normal pituitaries and 54 pituitary adenomas (twelve somatotrope adenomas, nine prolactinomas, twelve corticotrope adenomas, three TSH-producing tumors, six gonadotrope adenomas, six null cell adenomas, and six oncocytomas) were analyzed. p27 expression was determined semiquantitatively with regard to both the percentage of positive cells and the intensity of the staining. Normal human pituitaries showed strong expression of p27 in most nuclei. In contrast, the levels of p27 were reduced in the majority of the tumors analyzed. Twenty-two tumors (six somatotrope adenomas, five prolactinomas, four corticotrope adenomas, two TSH-producing tumors, two gonadotrope adenomas, and three null cell adenomas) were completely p27-negative. In 18 tumors, p27 expression was found in < or = 10% of the cells. In the other ten tumors, 11-80% of the cells were p27-positive. In summary, we were able to demonstrate reduced expression levels of the cell-cycle inhibitor p27 in tumors derived from all pituitary cell types. Our data indicate that p27 may be an important regulator of cellular proliferation in the anterior pituitary, the underexpression of which could play a role in pituitary tumorigenesis.

Adenoma↗

Ganglioglioma of the neurohypophysis with secretion of vasopressin.

A patient with a ganglioglioma of the neurohypophysis developed the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We present the case and describe its microscopic and ultrastructural features. Malignant neoplasms were thought to be the main cause of ectopic production of vasopressin. Head trauma, infection, or drugs, however, can also induce hypersecretion of vasopressin. Mechanical compression of the pituitary stalk can lead to an excessive antidiuretic hormone (ADH) release by affecting the inhibitory system. Primary neuroendocrine tumors of the hypothalamic-neurohypophyseal system are extremely rare. We demonstrate the presence of vasopressin in the tumor cells by immunocytochemistry. This represents the first case of SIADH caused by a tumor of the neurohypophysis.

Aged↗

Clinically nonsecreting pituitary adenomas in childhood and adolescence.

OBJECTIVE AND PATIENTS: Clinically nonsecreting pituitary adenomas are rare in childhood and adolescence. We analyzed five cases of clinically nonsecreting pituitary adenomas in patients (4 male and 1 female patient) under 20 years of age at surgery (0.22%), identified by a review of 2288 patients with pituitary adenomas treated from 1970 to 1996 at the Hamburg University. CLINICAL PRESENTATION AND RESULTS: Patient age at the onset of symptoms ranged from 8 to 13 years (mean, 10.8 yr), and age at surgery ranged from 12.5 to 19.5 years (mean, 15.5 yr). Two patients presented with endocrine symptoms, two with headache only, and one with a visual field defect. Endocrinological examinations showed pituitary insufficiency in two patients with endocrine symptoms. The serum prolactin level was normal in all patients. Radiological investigations demonstrated resectable macroadenomas with ring enhancement in four patients and a nonresectable macroadenoma with parasellar extension in one. Transnasal explorations achieved radical tumor resection except in one patient. The latter underwent a transcranial resection and radiotherapy because of parasellar tumor rest. Surgical morbidity consisted of left oculomotor nerve palsy after transcranial exploration. In two patients, normal pituitary function was preserved by transnasal surgery. Follow-up duration was 2 to 23 years (mean, 10.9 yr). There was no recurrence except for one parasellar adenoma. Immunohistological diagnosis was null cell adenoma in two patients, silent prolactinoma in two, and silent gonadotroph adenoma in one. The proliferative activity measured by Ki-67 (as the antibody MIB-1) and p53 expression revealed a positive reaction in one adenoma with parasellar extension. CONCLUSION: Clinically nonsecreting pituitary adenomas in childhood and adolescence cause different endocrine symptoms from those in adults. They caused pubertal and growth delay and/or primary amenorrhea in the patients investigated in this study. Transnasal surgery in childhood and adolescence is as safe as in adults. The characteristics of nonsecreting pituitary adenomas in this age group, including 20 patients cited from the literature, do not differ from those in adults.

Adenoma↗

Recent results of secondary transnasal surgery for residual or recurring acromegaly.

OBJECTIVE: The results of secondary surgery for either residual or recurring acromegaly have been reported to be unfavorable. To evaluate the effectiveness of recent techniques of secondary transnasal microsurgery, we analyzed the surgical results of remnant or recurring acromegaly in patients who underwent secondary transnasal surgery from 1990 to 1996. METHODS: Secondary transnasal explorations were performed in 28 acromegalic patients (mean age+/-standard error, 39+/-2.3 yr) who had been previously treated with microsurgery (patients at our institutions, n=5; patients at other institutions, n=23). For most of these patients, medical treatment after primary surgery was unsatisfactory. Magnetic resonance imaging demonstrated 18 transnasally resectable tumors (64.3%) and 10 nonresectable grossly invasive tumors (35.7%). Surgical indication was based on elevated plasma growth hormone (GH) levels and evidence of tumor revealed by magnetic resonance imaging. RESULTS: Intraoperative GH measurement was performed in all patients. In 13 of 18 patients with resectable tumors, the surgical assessment with sufficient GH decline intraoperatively was likewise judged as complete and was later proved. In three of five patients with inadequate GH decline, endocrinological remission was achieved by performing further surgery. Thus, an endocrinological remission was achieved in 16 of 18 patients (88.9%) with resectable tumors. In 10 patients with nonresectable tumors, the tumor mass was further reduced. Overall, the endocrinological remission rate was 57.1% (16 of 28 patients). There was no serious morbidity and there was no mortality in this series. CONCLUSION: We conclude that in patients with transnasally resectable tumor residuals or recurrences confirmed by magnetic resonance imaging, endocrinological remissions can be obtained with high probability, even in secondary surgery after an unsuccessful previous operation.

Acromegaly↗

Mutation and expression analysis of corticotropin-releasing factor 1 receptor in adrenocorticotropin-secreting pituitary adenomas.

The present study was designed to investigate a possible role of CRF1 receptors (CRF1-R) in the pathogenesis of Cushing's disease. ACTH-secreting pituitary adenomas and nonsecreting pituitary adenomas have been analyzed for mutations in the CRF1-R gene by PCR and sequencing and been compared with the sequences of normal anterior pituitaries. No mutations affecting the CRF1-R protein have been found in all tumors analyzed. However, we found a significant overexpression of the CRF1-R messenger RNA in ACTH-secreting pituitary adenomas vs. inactive adenomas and normal pituitaries. We conclude that mutations of the CRF1-R are unlikely to be involved in Cushing's disease. We suggest that the overexpression of the CRF1-R messenger RNA may be related to a disturbed receptor regulation in ACTH-secreting pituitary adenomas.

Adenoma↗

[Combined neuronal and endocrine tumors of the sellar region].

Gangliocytomas or gangliogliomas of the sellar region are very rare tumors. In a great proportion of those cases an adenoma of the anterior pituitary develops from the cell type that is hyperstimulated by the releasing hormone produced from the gangliocytoma. Five GHRH secreting gangliocytomas are reported. Four of these were localized adjacent to a GH secreting adenoma. In one case, no adenoma tissue was found beside the ganglicytoma. As only the adenomas can secrete GH, the adenomas and not the gangliocytomas are directly responsible for acromegaly so that such an adenoma has to be present in cases of acromegaly. A CRH secreting gangliocytoma was combined with an ACTH cell adenoma that had induced Cushing's disease. A ganglioglioma of the posterior pituitary had led to an inappropriate secretion of Vasopressin. The morphology of the different tumors is presented.

Acromegaly↗