Friedhelm Raue - Academia.edu (original) (raw)
Papers by Friedhelm Raue
15th International & 14th European Congress of Endocrinology, May 1, 2012
Experimental and Clinical Endocrinology & Diabetes, Jul 14, 2009
Muscle & Nerve, Jul 1, 1996
A 36‐year‐old woman presented with muscle hypertrophy (particularly of the calves) since puberty,... more A 36‐year‐old woman presented with muscle hypertrophy (particularly of the calves) since puberty, occasional muscle cramps, a musculine habitus, and a loss of subcutaneous fat on limbs and trunk sparing her face, neck, and vulva. Multiple lipomas were found on her trunk, and acanthosis nigricans on her neck. Laboratory testing revealed hyperlipidemia and pathological glucose tolerance with hyperinsulinemia. Physical and laboratory findings are consistent with Köbberling‐Dunnigan syndrome, a rare inherited form of lipoatrophy. The patient's mother had the same body habitus and insulin‐dependent diabetes mellitus. These cases suggest that partial lipodystrophy also affects muscle and is a cause of genuine muscular hypertrophy. © 1996 John Wiley & Sons, Inc.
PubMed, Dec 1, 1992
An essential element in the histological differentiation of medullary thyroid cancer (MTC) from o... more An essential element in the histological differentiation of medullary thyroid cancer (MTC) from other thyroid tumors is the use of immunohistochemical methods. The detection of calcitonin in the tumor cells is decisive. Factors which impair the prognosis of MTC are age (> 40 y), male sex, elevated DNA-content and mitotic activity of the tumor cells, immunoreactivity against dopa decarboxylase, histaminase and Leu-M1-antigen. Family screening is based mainly on calcitonin-stimulation tests (using pentagastrin or calcium) as a genetic marker for routine screening is not available yet. Scintigraphic methods using 99mTc-(V)-DMSA, 201Tl-chloride or 99mTc-anti-CEA antibodies become more important, especially in the detection of recurrent disease. Selective venous blood sampling is another sensitive method for localizing recurrent disease. Surgical treatment plays the dominant role in the management of MTC. Complete thyroidectomy in conjunction with systematic lymphadenectomy is now the primary treatment of choice.
Acta chirurgica Austriaca, Jul 1, 1997
PubMed, Sep 1, 1999
Bone metabolism and thus bone remodelling and bone mineral content are profoundly influenced by m... more Bone metabolism and thus bone remodelling and bone mineral content are profoundly influenced by many hormonal and metabolic factors. This review presents the state of the art procedures for bone mineral absorptiometry and examines the interactions of endocrine and metabolic diseases and bone mineral content. Preventive and therapeutic modalities of osteoporosis are discussed in this context.
Springer eBooks, 1992
Medullary thyroid carcinoma (MTC) was first recognized as a distinct pathological entity by Hazar... more Medullary thyroid carcinoma (MTC) was first recognized as a distinct pathological entity by Hazard et al. (1959), who, out of 600 cases of thyroid cancer, identified 21 cases of this tumor from its histopathological appearance. MTC originates from the thyroid parafollicular C-cells first suggested by Williams (1967) and secretes large amounts of calcitonin, a feature which has been used for diagnosis since 1970. MTC is a rare disease which occurs in a sporadic and a familial form; the familial variant is inherited in an autosomal dominant trait associated with other endocrine tumors (multiple endocrine neoplasia, MEN). The combination of MTC with adrenal medullary tumor and parathyroid tumor (MEN 2A) was first described in 1961 by Sipple. A second variant, MEN 2B, consists of MTC, pheochromocytoma, neural tumors, and a marfanoid habitus. The third variety of MTC is the non-MEN familial MTC, a hereditary MTC without any other endocrinopathies.
PubMed, Aug 1, 1990
Medullary carcinoma of the thyroid (MTC) is exceptional in that the hormone calcitonin produced b... more Medullary carcinoma of the thyroid (MTC) is exceptional in that the hormone calcitonin produced by the tumor cells represents a specific and sensitive tumor marker. Careful screening by serial calcitonin determinations following pentagastrin stimulation allows for the early detection of metastatic disease. We have adopted a method of meticulous modified radical neck dissection to eradicate persistent or recurrent MCT in 11 patients treated over a 15-month period. This surgical approach resulted in potentially curative treatment in two patients. Effective tumor reduction was achieved in another seven. Two patients have persistent or progressive disease despite maximum efforts to eradicate malignant tissue. Follow-up is presently incomplete in one patient. Postoperative complications included recurrent nerve paralysis (n = 3), hypoparathyroidism (n = 2), muscular weakness (n = 2) and Horner's syndrome (n = 3). The majority of nervous complications improved spontaneously. It is concluded that the adopted method of meticulous modified radical neck dissection offers the chance of cure to some patients and results in the removal of substantial tumor mass in the majority of others. Postoperative problems are mostly temporary and are deemed acceptable.
PubMed, Jun 1, 1999
The high sensitivity of pentagastrin stimulation in detecting primary or metastatic medullary thy... more The high sensitivity of pentagastrin stimulation in detecting primary or metastatic medullary thyroid cancer (MTC) suggests widespread expression of the corresponding receptor type on human MTC. Indeed, autoradiographic studies have demonstrated cholecystokinin (CCK)-B/gastrin receptors not only in more than 90% of MTCs but also in a high percentage of small cell lung cancers, some ovarian cancers, astrocytomas and potentially a variety of adenocarcinomas. The aim of this study was to systematically screen and optimize, in a preclinical model and a pilot clinical study, suitable radioligands for targeting CCK-B receptors in vivo. Methods: A variety of CCK/gastrin-related peptides, all bearing the C-terminal CCK receptor-binding tetrapeptide sequence Trp-Met-Asp-PheNH2 or derivatives thereof, were studied. They were radioiodinated by the lodogen or Bolton-Hunter procedures. The peptides were members of the gastrin or CCK families, which differ by the intramolecular position of a tyrosyl moiety. Their stability and affinity were studied in vitro and in vivo; their biodistribution and therapeutic efficacy were tested in nude mice bearing subcutaneous human MTC xenografts. Diethylenetriamine pentaacetic acid (DTPA) derivatives of suitable peptides were synthesized successfully, and their preclinical and initial clinical evaluations were performed, labeled with 111In. Results: All members of the CCK or gastrin families were stable in serum (with half-lives of several hours at 37 degrees C); nevertheless, the stability of those peptides bearing N-terminal pGlu residues or D-amino acids was significantly higher. In accordance with their comparably low affinity, nonsulfated members of the CCK family showed fairly low uptake in the tumor and other CCK-B receptor-expressing tissues. Sulfated CCK derivatives performed significantly better but also displayed a comparably high uptake in normal CCK-A receptor-expressing tissues. This effect was probably due to their similar affinity for both CCK-A and CCK-B receptors. Best tumor uptake and tumor-to-nontumor ratios were obtained with members of the gastrin family because of their selectivity and affinity for the CCK-B receptor subtype. Pilot therapy experiments in MTC-bearing animals showed significant antitumor efficacy compared with untreated controls. DTPA derivatives of minigastrin were successfully developed. In a pilot clinical study, radioiodinated and 111In-labeled derivatives showed excellent targeting of physiological CCK-B receptor-expressing organs, as well as all known tumor sites. Conclusion: CCK/gastrin analogs may be a useful new class of receptor-binding peptides for diagnosis and therapy of CCK-B receptor-expressing tumors, such as MTC or small cell lung cancer. Nonsulfated gastrin derivatives may be preferable because of their CCK-B receptor selectivity, hence lower accretion in normal CCK-A receptor-expressing organs.
Langenbeck's Archives of Surgery, Nov 9, 1998
Introduction: A national registry for medullary thyroid carcinoma (MTC) and multiple endocrine ne... more Introduction: A national registry for medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia type 2 (MEN2) was set up to evaluate epidemiological, clinical and prognostic factors of the sporadic and hereditary forms of MTC. Patients and methods: Coded data from 1217 patients with MTC from 57 participating centers in Germany were registered and statistically analyzed. The series included 515 (42%) males (mean age 43.1±16.1 years) and 702 (58%) females (mean age 44.4±17.6 years), with a mean follow-up of 5.2 years; 865 (71%) exhibited the sporadic form and 352 (29%) the familial form (244 MEN2a, 32 MEN2b, 76 FMTC). The mean age at diagnosis was 49 years for sporadic and 30 years for the familial form. Results: Of the patients, 17% presented at stage I, according to the UICC, and 30%, 45%, and 8% presented at stages II, III, and IV, respectively. There were 12% of patients who died of the disease. The overall adjusted survival rate was 87% at 5 years, and 76% at 10 years. In a univariate analysis, the stage of disease at diagnosis, age, gender, and form were relevant prognostic factors. In a multivariate proportional-hazards analysis, the difference between patients with sporadic and familial disease disappeared. Conclusion: As the tumor stage at presentation is the major prognostic factor, early diagnosis and surgical intervention before cervical lymph node metastases appear is necessary to improve survival especially in sporadic cases. Key words Medullary thyroid carcinoma • Multiple endocrine neoplasia type 2 • Pognostic factors Tumor stage Patients and methods A national registry was set up by the German MTC study Group in 1988 [9]. A questionnaire asking for personal and medical data
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Jul 17, 2013
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Oct 26, 2012
Deutsche Medizinische Wochenschrift, Mar 25, 2008
Recent results in cancer research, 1990
Medullary thyroid carcinoma (MTC) is a neoplasm of the calcitonin-secreting parafollicular, or C ... more Medullary thyroid carcinoma (MTC) is a neoplasm of the calcitonin-secreting parafollicular, or C cells, of the thyroid gland; it comprises 5%–10% of all cases of thyroid cancer. In contrast to the follicular cells of the thyroid gland that metabolize iodine and produce the classical thyroid homones T3 and T4, the C cells produce and secrete calcitonin (CT) and related peptides. During embryogenesis the C cells migrate from the neural crest to the last branchial pouch and ultimately to the thyroid. The neural crest origin of the C cells is one explanation for the production of a wide variety of bioactive substances similar to other neuro-endocrine cells, but also for the association of MTC with other tumors of neural crest origin. Another important clinical feature of MTC is its familial occurrence with an autosomal dominant pattern, its multifocal development of C cell hyperplasia prior to malignant transformation, and its association with other endocrine tumors (e.g., bilateral pheochromocytoma).
Recent results in cancer research, 1994
Hypercalcemia can be caused by many disorders, but is most commonly due to primary hyperparathyro... more Hypercalcemia can be caused by many disorders, but is most commonly due to primary hyperparathyroidism and to malignant disease. Together, these account for more than 90% of all cases. Many patients with primary hyperparathyroidism are asymptomatic and ambulant when hypercalcemia is first recognized by routine measurement of serum calcium levels. However, the incidence of hypercalcemia of cancer, which has been estimated to be about 150 new cases per million persons per year, is not as high as the annual incidence rate of primary hyperparathyroidism (approximately 250 new cases per year) (Burkhardt and Kistler 1981; Heath et al. 1980; Mundy et al. 1980, 1984).
15th International & 14th European Congress of Endocrinology, May 1, 2012
Experimental and Clinical Endocrinology & Diabetes, Jul 14, 2009
Muscle & Nerve, Jul 1, 1996
A 36‐year‐old woman presented with muscle hypertrophy (particularly of the calves) since puberty,... more A 36‐year‐old woman presented with muscle hypertrophy (particularly of the calves) since puberty, occasional muscle cramps, a musculine habitus, and a loss of subcutaneous fat on limbs and trunk sparing her face, neck, and vulva. Multiple lipomas were found on her trunk, and acanthosis nigricans on her neck. Laboratory testing revealed hyperlipidemia and pathological glucose tolerance with hyperinsulinemia. Physical and laboratory findings are consistent with Köbberling‐Dunnigan syndrome, a rare inherited form of lipoatrophy. The patient's mother had the same body habitus and insulin‐dependent diabetes mellitus. These cases suggest that partial lipodystrophy also affects muscle and is a cause of genuine muscular hypertrophy. © 1996 John Wiley & Sons, Inc.
PubMed, Dec 1, 1992
An essential element in the histological differentiation of medullary thyroid cancer (MTC) from o... more An essential element in the histological differentiation of medullary thyroid cancer (MTC) from other thyroid tumors is the use of immunohistochemical methods. The detection of calcitonin in the tumor cells is decisive. Factors which impair the prognosis of MTC are age (> 40 y), male sex, elevated DNA-content and mitotic activity of the tumor cells, immunoreactivity against dopa decarboxylase, histaminase and Leu-M1-antigen. Family screening is based mainly on calcitonin-stimulation tests (using pentagastrin or calcium) as a genetic marker for routine screening is not available yet. Scintigraphic methods using 99mTc-(V)-DMSA, 201Tl-chloride or 99mTc-anti-CEA antibodies become more important, especially in the detection of recurrent disease. Selective venous blood sampling is another sensitive method for localizing recurrent disease. Surgical treatment plays the dominant role in the management of MTC. Complete thyroidectomy in conjunction with systematic lymphadenectomy is now the primary treatment of choice.
Acta chirurgica Austriaca, Jul 1, 1997
PubMed, Sep 1, 1999
Bone metabolism and thus bone remodelling and bone mineral content are profoundly influenced by m... more Bone metabolism and thus bone remodelling and bone mineral content are profoundly influenced by many hormonal and metabolic factors. This review presents the state of the art procedures for bone mineral absorptiometry and examines the interactions of endocrine and metabolic diseases and bone mineral content. Preventive and therapeutic modalities of osteoporosis are discussed in this context.
Springer eBooks, 1992
Medullary thyroid carcinoma (MTC) was first recognized as a distinct pathological entity by Hazar... more Medullary thyroid carcinoma (MTC) was first recognized as a distinct pathological entity by Hazard et al. (1959), who, out of 600 cases of thyroid cancer, identified 21 cases of this tumor from its histopathological appearance. MTC originates from the thyroid parafollicular C-cells first suggested by Williams (1967) and secretes large amounts of calcitonin, a feature which has been used for diagnosis since 1970. MTC is a rare disease which occurs in a sporadic and a familial form; the familial variant is inherited in an autosomal dominant trait associated with other endocrine tumors (multiple endocrine neoplasia, MEN). The combination of MTC with adrenal medullary tumor and parathyroid tumor (MEN 2A) was first described in 1961 by Sipple. A second variant, MEN 2B, consists of MTC, pheochromocytoma, neural tumors, and a marfanoid habitus. The third variety of MTC is the non-MEN familial MTC, a hereditary MTC without any other endocrinopathies.
PubMed, Aug 1, 1990
Medullary carcinoma of the thyroid (MTC) is exceptional in that the hormone calcitonin produced b... more Medullary carcinoma of the thyroid (MTC) is exceptional in that the hormone calcitonin produced by the tumor cells represents a specific and sensitive tumor marker. Careful screening by serial calcitonin determinations following pentagastrin stimulation allows for the early detection of metastatic disease. We have adopted a method of meticulous modified radical neck dissection to eradicate persistent or recurrent MCT in 11 patients treated over a 15-month period. This surgical approach resulted in potentially curative treatment in two patients. Effective tumor reduction was achieved in another seven. Two patients have persistent or progressive disease despite maximum efforts to eradicate malignant tissue. Follow-up is presently incomplete in one patient. Postoperative complications included recurrent nerve paralysis (n = 3), hypoparathyroidism (n = 2), muscular weakness (n = 2) and Horner's syndrome (n = 3). The majority of nervous complications improved spontaneously. It is concluded that the adopted method of meticulous modified radical neck dissection offers the chance of cure to some patients and results in the removal of substantial tumor mass in the majority of others. Postoperative problems are mostly temporary and are deemed acceptable.
PubMed, Jun 1, 1999
The high sensitivity of pentagastrin stimulation in detecting primary or metastatic medullary thy... more The high sensitivity of pentagastrin stimulation in detecting primary or metastatic medullary thyroid cancer (MTC) suggests widespread expression of the corresponding receptor type on human MTC. Indeed, autoradiographic studies have demonstrated cholecystokinin (CCK)-B/gastrin receptors not only in more than 90% of MTCs but also in a high percentage of small cell lung cancers, some ovarian cancers, astrocytomas and potentially a variety of adenocarcinomas. The aim of this study was to systematically screen and optimize, in a preclinical model and a pilot clinical study, suitable radioligands for targeting CCK-B receptors in vivo. Methods: A variety of CCK/gastrin-related peptides, all bearing the C-terminal CCK receptor-binding tetrapeptide sequence Trp-Met-Asp-PheNH2 or derivatives thereof, were studied. They were radioiodinated by the lodogen or Bolton-Hunter procedures. The peptides were members of the gastrin or CCK families, which differ by the intramolecular position of a tyrosyl moiety. Their stability and affinity were studied in vitro and in vivo; their biodistribution and therapeutic efficacy were tested in nude mice bearing subcutaneous human MTC xenografts. Diethylenetriamine pentaacetic acid (DTPA) derivatives of suitable peptides were synthesized successfully, and their preclinical and initial clinical evaluations were performed, labeled with 111In. Results: All members of the CCK or gastrin families were stable in serum (with half-lives of several hours at 37 degrees C); nevertheless, the stability of those peptides bearing N-terminal pGlu residues or D-amino acids was significantly higher. In accordance with their comparably low affinity, nonsulfated members of the CCK family showed fairly low uptake in the tumor and other CCK-B receptor-expressing tissues. Sulfated CCK derivatives performed significantly better but also displayed a comparably high uptake in normal CCK-A receptor-expressing tissues. This effect was probably due to their similar affinity for both CCK-A and CCK-B receptors. Best tumor uptake and tumor-to-nontumor ratios were obtained with members of the gastrin family because of their selectivity and affinity for the CCK-B receptor subtype. Pilot therapy experiments in MTC-bearing animals showed significant antitumor efficacy compared with untreated controls. DTPA derivatives of minigastrin were successfully developed. In a pilot clinical study, radioiodinated and 111In-labeled derivatives showed excellent targeting of physiological CCK-B receptor-expressing organs, as well as all known tumor sites. Conclusion: CCK/gastrin analogs may be a useful new class of receptor-binding peptides for diagnosis and therapy of CCK-B receptor-expressing tumors, such as MTC or small cell lung cancer. Nonsulfated gastrin derivatives may be preferable because of their CCK-B receptor selectivity, hence lower accretion in normal CCK-A receptor-expressing organs.
Langenbeck's Archives of Surgery, Nov 9, 1998
Introduction: A national registry for medullary thyroid carcinoma (MTC) and multiple endocrine ne... more Introduction: A national registry for medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia type 2 (MEN2) was set up to evaluate epidemiological, clinical and prognostic factors of the sporadic and hereditary forms of MTC. Patients and methods: Coded data from 1217 patients with MTC from 57 participating centers in Germany were registered and statistically analyzed. The series included 515 (42%) males (mean age 43.1±16.1 years) and 702 (58%) females (mean age 44.4±17.6 years), with a mean follow-up of 5.2 years; 865 (71%) exhibited the sporadic form and 352 (29%) the familial form (244 MEN2a, 32 MEN2b, 76 FMTC). The mean age at diagnosis was 49 years for sporadic and 30 years for the familial form. Results: Of the patients, 17% presented at stage I, according to the UICC, and 30%, 45%, and 8% presented at stages II, III, and IV, respectively. There were 12% of patients who died of the disease. The overall adjusted survival rate was 87% at 5 years, and 76% at 10 years. In a univariate analysis, the stage of disease at diagnosis, age, gender, and form were relevant prognostic factors. In a multivariate proportional-hazards analysis, the difference between patients with sporadic and familial disease disappeared. Conclusion: As the tumor stage at presentation is the major prognostic factor, early diagnosis and surgical intervention before cervical lymph node metastases appear is necessary to improve survival especially in sporadic cases. Key words Medullary thyroid carcinoma • Multiple endocrine neoplasia type 2 • Pognostic factors Tumor stage Patients and methods A national registry was set up by the German MTC study Group in 1988 [9]. A questionnaire asking for personal and medical data
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Jul 17, 2013
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature, Oct 26, 2012
Deutsche Medizinische Wochenschrift, Mar 25, 2008
Recent results in cancer research, 1990
Medullary thyroid carcinoma (MTC) is a neoplasm of the calcitonin-secreting parafollicular, or C ... more Medullary thyroid carcinoma (MTC) is a neoplasm of the calcitonin-secreting parafollicular, or C cells, of the thyroid gland; it comprises 5%–10% of all cases of thyroid cancer. In contrast to the follicular cells of the thyroid gland that metabolize iodine and produce the classical thyroid homones T3 and T4, the C cells produce and secrete calcitonin (CT) and related peptides. During embryogenesis the C cells migrate from the neural crest to the last branchial pouch and ultimately to the thyroid. The neural crest origin of the C cells is one explanation for the production of a wide variety of bioactive substances similar to other neuro-endocrine cells, but also for the association of MTC with other tumors of neural crest origin. Another important clinical feature of MTC is its familial occurrence with an autosomal dominant pattern, its multifocal development of C cell hyperplasia prior to malignant transformation, and its association with other endocrine tumors (e.g., bilateral pheochromocytoma).
Recent results in cancer research, 1994
Hypercalcemia can be caused by many disorders, but is most commonly due to primary hyperparathyro... more Hypercalcemia can be caused by many disorders, but is most commonly due to primary hyperparathyroidism and to malignant disease. Together, these account for more than 90% of all cases. Many patients with primary hyperparathyroidism are asymptomatic and ambulant when hypercalcemia is first recognized by routine measurement of serum calcium levels. However, the incidence of hypercalcemia of cancer, which has been estimated to be about 150 new cases per million persons per year, is not as high as the annual incidence rate of primary hyperparathyroidism (approximately 250 new cases per year) (Burkhardt and Kistler 1981; Heath et al. 1980; Mundy et al. 1980, 1984).