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Objective: Patients with growth hormone deficiency (GHD) have abnormalities of cardiac structure and function. Growth hormone replacement (GHR) therapy can induce an increase in cardiac mass and improvement in left ventricular ejection fraction. B-type natriuretic peptide (BNP) levels have been successfully used to identify patients with heart failure and they correlate with both disease severity and prognosis. Design: To investigate the effect of growth hormone replacement on BNP and inflammatory cardiovascular risk factors in adults with GHD we determined NT-proBNP and high sensitive C-reactive protein (CrP) before, 6 and 12 months after GHR. Patients: Thirty adults (14 males, 16 females) with GHD [mean age: 41.7±14.5 years (range: 17.2 to 75.4 years)] were recruited from the German KIMS cohort (Pfizer's International Metabolic Database). Results: During 12 months of GHR, a significant increase of IGF-1 (85.4 ± 72.1 vs. 172.0±98 μg/dl; p = 0.0001; IGF-1 SDS mean ± SD: -3.85 ± 3.09 vs. -0.92±1.82) was detectable. Mean baseline NT-proBNP was 112±130 pg/ml (range: 7 to 562). Twelve patients had normal BNP, whereas 18 revealed NT-proBNP values corresponding to those of patients with heart failure NYHA classification I (n = 10), NYHA II (n = 6) and NYHA III (n = 2), respectively. Baseline BNP levels correlated significantly (p = 0.044) with increased baseline CrP values. After 12 months of GHR, a significant decrease (p = 0.001) in NT-proBNP levels [mean: 68 ± 81 pg/ ml (range: 5 to 395)] was detectable, associated with an improvement in NYHA performance status in 10 of the 18 with increased baseline NT-proBNP. Conclusions: Based on our study, approximately two-thirds of patients with GHD have increased NT-proBNP levels which may be useful as screening/diagnostic laboratory parameter for heart failure in such patients. GHR therapy decreases BNP levels in most patients with GHD.

Early diagnosis of medullary thyroid carcinoma (MTC) can improve long-term prognosis. MTC can be detected at an early stage by calcitonin screening in all patients with thyroid nodules. This approach, however, is controversial due to high costs and a limited specificity of calcitonin. It was the aim of the present study to investigate whether ultrasonography may contribute to the diagnosis of MTC in patients with thyroid nodules. The study included 19 patients with newly diagnosed MTC. Ten patients had sporadic MTC, 7 had multiple endocrine neoplasia (MEN) type 2A, and 2 patients had MEN 2B. In all subjects conventional ultrasound, and in 14 patients color Doppler sonography were performed before primary surgery. For comparison, ultrasound appearance of 139 benign thyroid nodules was evaluated. In conventional ultrasound, MTC in 17/19 (89%) patients were hypoechoic, contained intranodular calcifications, and had no "halo sign". The combination of these criteria were found in only 8/139 (6%) of benign thyroid nodules. Intranodular blood flow was found in 11/14 patients with MTC (79%), perinodular blood flow in 7/14 MTC (50%). In conclusion, conventional ultrasound reveals a combination of hypoechogenicity, intranodular calcifications, and absence of "halo sign" in the vast majority of MTC. Since this sonographic pattern only rarely occurs in benign thyroid nodules, the results indicate that thyroid ultrasound can contribute to the diagnosis of MTC. In addition, the findings may have implications for calcitonin screening in nodular thyroid disease.

Es wird uber die erfolgreiche endoskopische Exstirpation von insgesamt 6 extraadrenalen Phaochromocytomen bei 3 Patienten berichtet. Ein Tumor lag retrocaval, zwei interaortocaval, zwei paraaortal und einer parailiacal. Die Entfernung erfolgte einmal uber den posterioren retroperitoneoskopischen Zugang, ansonsten laparoskopisch. Der intra- und postoperative Verlauf war jeweils komplikationslos.

Einem 61jahrigen Patienten wurden unter dem Krankheitsbild einer Immunthyreoiditis 25 μg/d Levothyroxin appliziert. Hierdurch manifestierte sich eine zuvor latente Nebennierenrindeninsuffizienz, so das ein Schmidt-Syndrom diagnostiziert werden konnte. Nach Elektrolyt- und Corticoid-Ausgleich erfolgte eine erneute Substitution mit Levothyroxin. Um die Provokation einer Addison-Krise zu vermeiden, sollten daher bei Patienten mit thyreoidaler Autoimmunopathie auch weitere endokrine Erkrankungen abgeklart werden. Pathogenetisch handelt es sich bei polyglandularen Autoimmunsyndromen um systemische, multifaktorielle Immunerkrankungen mit genetischer Pradisposition, einer Dominanz von Th2-Zellen und einer Freisetzung krankheitsspezifischer Autoantikorper.

One hundred and eighty-one families with multiple endocrine neoplasia type 2A (MEN-2A) or familial medullary thyroid carcinoma (FMTC) have been investigated for mutations in the ret protooncogene in Germany. In 8 families with FMTC or MEN-2A, no mutation could be detected in the cysteine-rich domain encoded in exons 10 and 11 of the ret protooncogene. DNA sequencing of additional exons (no. 13-15) revealed rare noncysteine mutations in 3 families (codons 631, 768, and 844). In contrast to these rare events, heterozygous missense mutations in exon 13, codons 790 and 791, were found in 5 families (4 with MTC only; 1 family with MTC and pheochromocytoma) and 11 patients with apparently sporadic tumors. Two different mutations in codon 790 (TTG-->TTT, TTG-->TTC; Leu790Phe) and one mutation in codon 791 (TAT-->TTT; Tyr791Phe) created a phenylalanine residue. We conclude that codons 790 and 791 of the ret protooncogene represent a new hot spot for FMTC/MEN-2A causing mutations. With the discovery of these considerably common mutations in codons 790 and 791 and the identification of some rare mutations, 100% of the German FMTC/MEN-2A families could be characterized by a mutation in the ret protooncogene.

HISTORY AND ADMISSION FINDINGS: A seventy-year-old woman was admitted to our hospital under suspicion of an adrenal Cushings's syndrome. Initial laboratory values showed elevated cortisol (834 nmol/l; normal: 180-640) which could not be suppressed after administration of 2 mg dexamethasone (632 nmol/l). Computed tomography of the abdomen showed a 19 x 34 mm mass in the region of the left adrenal gland. INVESTIGATIONS: ACTH levels were normal (42 ng/ml; 17-52). Serum cortisol remained high at 1021 nmol/l after administration of 8 mg dexamethasone. Four more doses of 2 mg dexamethasone were applied on 3 consecutive days, leading to a mild suppression of serum cortisol to 705 nmol/l, with urine cortisol levels dropping from 1915 to 101 nmol/l/24 h. The CRH-test produced a rise of serum cortisol from 895 to 1475 nmol, with ACTH rising from 42 to 68 pg/ml, a laboratory constellation consistent with the diagnosis of centrally located Cushing's syndrome (Cushing's disease). MRI failed to show an adenoma of the pituitary gland so that sinus petrosus sampling was done to confirm the diagnosis (ACTH central/peripheral 7:1; normal range < 2:1). TREATMENT AND COURSE: Serum cortisol rose to 1070 nmol/l and the patient developed pneumonia and contracted tinea. Prior to surgery we lowered the excessive cortisol levels with etomidate and successfully treated the pneumonia with antibiotics. Postoperatively clinical symptoms of Cushing's syndrome disappeared. The patient now presented with total insufficiency of the anterior pituitary. CONCLUSION: Exact hormone testing that may involve sinus petrosus sampling is necessary in diagnosing Cushing's syndrome. Even if radiological procedures cannot show an adenoma of the pituitary, transsphenoidal resection should be considered. Etomidate can lower excessive cortisol levels in seriously ill patients.

An enhanced chemiluminescence immunoassay for the determination of serum human chorionic gonadotropin (HCG) in specimens from oncology patients has been assessed with respect to its cross-reactivity with the free HCG beta-subunit (HCG-beta). The assay, standardized against the First International Reference Preparation 75/537, had a cross-reactivity with the free beta-subunit of 625% (molar basis). Therefore this assay achieves high sensitivity for the detection of either intact HCG or free HCG-beta in serum of patients with seminomatous or nonseminomatous testicular cancers. Results of both assays, the in-house immunoradiometric assay (+HCG-beta) and the Amerlite HCG-60 assay, showed a close correlation (R = 0.854-0.960) when serum samples from tumour patients were analyzed. Moreover, the content of free beta-subunit determined in a specific HCG-beta assay, could be quantitatively measured in the enhanced chemiluminescence immunoassay. Thus, this assay is suitable for oncology use, but also highlights the limitations of measuring HCG in serum samples.

Pivotal studies have demonstrated that pharmacotherapy with pegvisomant (Somavert) is a highly effective treatment for acromegaly. Since clinical experience with the drug was very limited, the Pegvisomant Observational Study was launched in Germany immediately with the drug becoming commercially available to patients early in 2004. Its purpose was to record safety and efficacy data on as many patients as possible. As of 12th August 2008 a total of 371 patients (185 males, 186 females) had been included in the study. They were on pegvisomant therapy for an average of 118 weeks. Median and mean doses of pegvisomant were 15 and 16.4 mg/day respectively. Treatment efficacy was monitored by IGF1 levels and the patients symptoms were evaluated by completion of a questionnaire (patient-assessed acromegaly symptom questionnaire). Safety data included liver function tests, fasting glucose, HbA1c measurements, and tumor size monitoring by repeated magnetic resonance imaging. Normalization of IGF1 ranged from 55.7% of the 273 patients assessed after 6 months to 71.3% of 202 patients assessed after 24 months of treatment. It was 70.7% after 36 months (133 patients), 64.8% at 48 months (71 patients), and 58.4% after 60 months (24 patients). In 39 patients (10.9%) treatment was discontinued due to serious adverse events or adverse events with 25 (6.7%) of these patients having a potential causal relationship with the pegvisomant treatment. Liver function tests became abnormal in 20 patients and another three patients were recorded to have hepatobiliary disorders. Tumor size increase was reported in 20 patients, but only confirmed in nine patients by careful revision of all available images. Local injection site reactions were observed in 12 patients. In conclusion, in this large group of pegvisomant-treated patients, long-term data for up to 5 years of treatment are now available. In 71.3% of patients with previously not sufficiently treatable acromegaly, IGF1 levels were normalized by pegvisomant therapy. Elevated transaminases usually normalized after discontinuation but in half of the affected patients also despite continuation of treatment without dose alteration. Tumor progression was a rare event. It did not exceed the expected rate in patients with acromegaly not treated with pegvisomant. As from this presently largest database of acromegalic patients treated with pegvisomant, long-term results are encouraging. The German data are now merged into the global ACROSTUDY and will constitute a major portion of the international ACROSTUDY project as a continuing global web-based observational study.

In treatment-resistant patients with acromegaly, pharmacotherapy with pegvisomant (Somavert) is a highly effective option. However, safety concerns have been raised related to a potential increase in tumor size during long-term pegvisomant treatment. Therefore, neuroradiological monitoring of tumor extension and volume was performed in the German Pegvisomant Observational Study, which covers 87% of patients treated with pegvisomant in Germany. As of 15 July 2007, a total of 307 patients (156 males and 151 females) had been included in the study and were on pegvisomant therapy for an average of 86.7 weeks. Median and mean doses of pegvisomant were 15 and 16.6 mg/day respectively. Out of these 307 patients, 18 were reported to have tumor-size increases as adverse events. From these 18 patients, all available serial magnetic resonance images were collected. Identical or similar sequences were chosen and the region of interest was magnified and compared across time after the best possible fit had been achieved by size and gray-scale correction. All available images were carefully re-evaluated according to this method. In 10 out of the 18 patients, there was no evidence of tumor-size increase, when the pre-treatment scans were compared with the most recent follow-up investigations. In two out of the remaining eight patients, there was a rebound effect observed after withdrawal of somatostatin analog treatment, but no further progression. In another three out of the eight patients, tumor-size increase had already been documented before pegvisomant treatment was commenced, during preceding somatostatin analog treatment and continued therapy. In the last three patients, tumor progression after the start of pegvisomant treatment was confirmed. All three patients had undergone pituitary surgery as primary treatment, but had not been pre-treated with radiotherapy. In all three cases, the tumor increase was not considered clinically significant and the investigators decided to continue pegvisomant treatment. In conclusion, in this large group of pegvisomant-treated patients, tumor progression was rare. It was reported in between 2 and 3% of patients treated, and did not exceed the expected rate in patients with acromegaly not treated with pegvisomant. In over one-half of patients, reports of tumor increase could not be confirmed by re-evaluation. This was mostly due to non-identical gantry projections. Misjudgements mainly occurred when only images from two individual investigations, rather than the entire series of scans, were compared. Thus, we recommend a careful serial evaluation of all available images to avoid misinterpretations and erroneous alerts. As from this presently largest database of acromegalic patients treated with pegvisomant, tumor-growth rate appears not to be different from patients on other treatment modalities. Although these data are reassuring with regard to the concern of somatotroph adenoma growth under peripheral GH receptor blockade, further study is required.

Human choriogonadotropin (hCG) and free hCG-beta values for 934 serum samples from patients with seminomatous or nonseminomatous testicular cancer were measured by highly specific immunoradiometric assays (IRMAS). In non-seminoma samples, hCG and hCG-beta were highly correlated (r = 0.82, P less than 0.001). Of 112 "marker-positive" seminoma samples, only 46 (41.1%) showed both increased hCG and hCG-beta. In 39 cases (34.8%) only hCG-beta and in 27 cases (24.1%) only dimer-hCG was increased. This makes the determination of hCG and hCG-beta, either by two assays or by a single hCG (+hCG-beta) assay, most reliable in these patients. For all samples, hCG (+hCG-beta) was measured by a polyclonal RIA and a monoclonal IRMA, which differed in their cross-reactivities with hCG-beta (234% and 720%, respectively). The hCG (+hCG-beta) IRMA, as a result of its higher hCG-beta cross-reactivity, was superior to the hCG (+hCG-beta) RIA in detecting slightly increased hCG-beta. Additionally, 11 widely used commercial hCG kits were tested for their hCG-beta cross-reactivities and showed values between less than 3% and 264%.

Experience with chemotherapy in patients with differentiated and undifferentiated thyroid cancer is limited because most recurrent tumors respond well to surgery, radioiodine therapy, or external beam radiation. Cytotoxic drugs are almost exclusively used in patients with tumors that are not surgically resectable, not responsive to 131I, and have already been treated or are not amenable to external beam radiotherapy. The majority of patients with distant metastases that have lost their ability to concentrate 131I die within 5 years. However, even those patients may have stable disease over a period of months or even several years without specific therapy. Chemotherapy in differentiated thyroid cancer should therefore only be given in cases of progressive metastatic disease refractory to radioiodine treatment. Only in poorly differentiated and anaplastic carcinoma can chemotherapy following conventional treatment be approved from the beginning.

OBJECTIVE: Diabetes is associated with coronary microvasculature abnormalities and impaired coronary flow reserve (CFR). CFR is the ratio of coronary flow under maximal vasodilation to basal flow and is a measure for coronary vasoreactivity. Insulin resistance is the central defect in the development of type 2 diabetes, preceding its onset by 10-20 years. Thus, the relationship between insulin sensitivity and CFR in nondiabetic subjects is particularly interesting. The aim of the study was to investigate this relationship. DESIGN: Cross-sectional study. PATIENTS: The study population consisted of 18 non-diabetic subjects without coronary artery stenosis on coronary angiography. We excluded patients with structural heart disease or with conditions affecting CFR or insulin sensitivity such as low density lipoprotein (LDL)-cholesterol ≥ 4.14 mmol/l, smoking, hypertension or obesity with a body mass index (BMI) > 28 kg/m2. MEASUREMENTS AND RESULTS: CFR W8S 3.1 ± 0.8 (range 1.7-4.8), as assessed by intracoronary Doppler measurements in the left anterior descending coronary arteries after adenosine stimulation. Intravascular ultrasound revealed zero to moderate coronary atherosclerotic changes. Whole-body insulin sensitivity (M-value) was 7.5 ± 2.9 mg/kg/min (range 2.2-12.6), as assessed by the hyperinsulinaemic- euglycaemic clamp test. Subjects with low CFR (< 3.0) had a significantly lower M-value than subjects with normal CFR (> 3.0) (6.0 ± 2-5 vs. 9.0 ± 2.5 mg/kg/min, P = 0.021). Univariate linear regression demonstrated a strong correlation between CFR and M-value (r = 0.76, P < 0.001). In multiple regression analysis, the significant association of CFR with M-value was independent of potential confounders (sex, age, BMI, LDL-cholesterol and plaque burden on intravascular ultrasound). Bootstrap analysis corroborated this finding. CONCLUSIONS: Whole-body insulin sensitivity relates to coronary vasoreactivity. Across a wide range of both insulin sensitivity and coronary flow reserve from markedly abnormal to normal values, an increase in insulin sensitivity appears to be associated with an increase in coronary flow reserve. Insulin resistance is therefore associated with coronary microvasculature abnormalities in nondiabetics.

The 825T-allele of the C825T polymorphism in GNB3, the gene for the G protein beta3 subunit, has been reported to be associated with essential hypertension and obesity. Expression of Gbeta3s, the gene product of GNB3 associated with the GNB3 825T-allele, causes increased signal transduction which may contribute to pathogenetic mechanisms ultimately resulting in hypertension and obesity. Given the known involvement of heterotrimeric G proteins in insulin secretion and insulin action on the cellular level, we analysed insulin sensitivity in each 15 young lean normotensive males with TC- and CC-genotypes, respectively. Blood glucose and serum insulin samples were taken during a standard oral glucose tolerance test. Insulin-stimulated glucose disposal was analysed by euglycemic-hyperinsulinemic clamp. Both groups did not differ with regard to the time-courses for glucose or insulin concentrations in the oral glucose tolerance test. Furthermore, insulin-stimulated glucose disposal was virtually independent of genotype. The TC-genotype is not associated with a primary defect in insulin secretion or sensitivity suggesting that obesity and hypertension in carriers of 825T do not likely result from primary alterations in glucose and insulin homeostasis. However, GNB3 825T-associated obesity may predispose to insulin resistance, an issue which remains to be investigated. Furthermore, fasting cholesterol was significantly higher in TC compared to CC genotype (4.71 versus 3.96 mmol/l; p = 0.007) suggesting that enhanced G protein signalling might be associated with alterations of cholesterol metabolism.

Cardiac abnormalities, such as cardiomegaly and congestive heart failure, occur frequently in advanced acromegaly. Abnormalities of systolic and diastolic function, mostly associated with left ventricular (LV) hypertrophy, have been reported. The impact of disease activity on LV performance in patients with normal or slightly elevated LV muscle mass has not been demonstrated.Conventional two-dimensional/Doppler echocardiography and tissue Doppler imaging (TDI) of the mitral annulus were performed in 13 patients with active acromegaly (AA) and normal or slightly elevated LV muscle mass (140 g/m2) and in 19 cured/well-controlled patients (CA). A group of 21 volunteers without symptoms or signs of cardiac disease served as controls (CON). The combined myocardial performance index (Tei-Index) was determined in all patients and controls.Muscle mass index of the left ventricle, ejection fraction, fractional shorting, E/ET-ratio, systolic (ST) and late diastolic (AT) annular velocities did not differ significantly between the three groups. In the AA group, the early diastolic annular velocity ET[7.13 +/- 2.11 (AA); 9.83 +/- 3.29 (CA); 10.10 +/- 1.70 m/s (CON); P0.05 AA vs. CA, P0.005 AA vs. CON] and the ET/AT-ratio [0.71 +/- 0.26 (AA); 0.95 +/- 0.33 (CA); 1.00 +/- 0.15 m/s (CON); P0.05 AA vs. CA, P0.005 AA vs. CON] were significantly reduced. Patients with AA had a longer deceleration time [209 +/- 19 (AA); 179 +/- 22 (CA); 185 +/- 26 ms (CON); P0.05]. The Tei-Index was significantly higher in AA in comparison with CON [0.50 +/- 0.15 (AA); 0.48 +/- 0.12 (CA); 0.41 +/- 0.10 (CON); P0.05 AA vs. CON]. Subjects with CA did not differ significantly from controls with respect to 2-D/Doppler echo- and TDI-derived parameters.The data demonstrate that diastolic dysfunction can be verified by tissue Doppler imaging in patients with active acromegaly with normal or slightly elevated muscle mass of the left ventricle and seems to be related to disease activity. The Tei-Index as a sensitive combined myocardial performance index can be used to complete the assessment of systolic and diastolic LV performance in acromegalic patients.

Most patients with functional bowel disorders complain of daytime symptoms while they remain asymptomatic at night. As symptoms are associated with heightened visceral sensitivity, we hypothesized that circadian fluctuations of the visceral sensory function occur. At four different timepoints (06.00, 12.00, 18.00 and 24.00 h), colorectal distensions (CRD) were performed in fasting conscious male Lewis rats using a balloon catheter and a barostat device. The abdominal wall contractions (behavioural pain response) were assessed during colorectal distension by abdominal wall electromyography (EMG). Plasma levels for endogenous cortisol were determined simultaneously at these timepoints. EMG responses to CRD were significantly (P

Overweight and obesity are widespread in industrial countries and are considered to be serious health problems in these countries. Population-based studies in Germany have shown that between 12 and 18 % of the adult population is obese. Overweight and obesity are accompanied by a large spectrum of health disorders and extreme psychosocial burdens. Besides the hereditary disposition, the life style including both intra- and inter-individual aspects determines the complex etiology of obesity. Within the collective sample of the obese, one sub-sample is the "psychogenic obese" i. e. in which psychiatric disorders lead to a change in both eating and exercise behavior, the result then being a continuous positive energy reserve in the form of overweight and obesity. The paper describes the psychosocial problems of obese persons; especially the controverse question with regard to psychiatric morbidity in general and eating disorders in particular are emphasized. The results of past, mainly behavioral oriented treatment concepts are presented and various concepts beyond single school orientation are discussed. Finally, the problems with psychiatric psychological diagnostics in those obese patients with the request for surgical weight reduction within the context of insurance coverage and the surgeons are presented.

Patients with acromegaly have an increased risk of ventricular dysrhythmias and sudden death. Late potentials in a signal-averaged electrocardiogram (SAECG), a predictor of ventricular dysrhythmias, are frequently seen in patients after previous myocardial infarction, but little is known about the prevalence of late potentials in acromegaly. The aim of our study was to investigate the prevalence of late potentials in patients with acromegaly and their relation to the activity of the disease and to myocardial hypertrophy.The study included 48 patients with acromegaly [27 males, 21 females, mean age 52.3 +/- 14.2 years, 16 active disease, 32 cured or 'well controlled', under treatment with sandostatin analogues (12/32)] and 38 healthy volunteers as a control group.Late potentials were detected in 9/16 (56%) patients with active acromegaly vs. 2/32 (6%) with cured/well controlled acromegaly (P = 0.001), defined as normal age-related IGF-1 levels and GH levels suppressible below 1 microg/l after an oral glucose load (75 g). Late potentials were not related to muscle mass index (127 +/- 35 active vs. 123 +/- 34 g/m2 cured/well controlled). The association of disease activity with the detection of late potentials was independent of age, gender, duration of the disease and body mass index. In comparison to the control group, the prevalence of late potentials was significantly higher in patients with acromegaly (23%) than in the control group (0%; P0.001).Late potentials in the SAECG are frequently seen in active acromegaly and may represent an early and sensitive parameter to detect myocardial injury in acromegaly.

A seventy-year-old woman was admitted to our hospital under suspicion of an adrenal Cushings's syndrome. Initial laboratory values showed elevated cortisol (834 nmol/l; normal: 180-640) which could not be suppressed after administration of 2 mg dexamethasone (632 nmol/l). Computed tomography of the abdomen showed a 19 x 34 mm mass in the region of the left adrenal gland.ACTH levels were normal (42 ng/ml; 17-52). Serum cortisol remained high at 1021 nmol/l after administration of 8 mg dexamethasone. Four more doses of 2 mg dexamethasone were applied on 3 consecutive days, leading to a mild suppression of serum cortisol to 705 nmol/l, with urine cortisol levels dropping from 1915 to 101 nmol/l/24 h. The CRH-test produced a rise of serum cortisol from 895 to 1475 nmol, with ACTH rising from 42 to 68 pg/ml, a laboratory constellation consistent with the diagnosis of centrally located Cushing's syndrome (Cushing's disease). MRI failed to show an adenoma of the pituitary gland so that sinus petrosus sampling was done to confirm the diagnosis (ACTH central/peripheral 7:1; normal range2:1).Serum cortisol rose to 1070 nmol/l and the patient developed pneumonia and contracted tinea. Prior to surgery we lowered the excessive cortisol levels with etomidate and successfully treated the pneumonia with antibiotics. Postoperatively clinical symptoms of Cushing's syndrome disappeared. The patient now presented with total insufficiency of the anterior pituitary.Exact hormone testing that may involve sinus petrosus sampling is necessary in diagnosing Cushing's syndrome. Even if radiological procedures cannot show an adenoma of the pituitary, transsphenoidal resection should be considered. Etomidate can lower excessive cortisol levels in seriously ill patients.

We describe the successful endoscopic removal of six extra-adrenal pheochromocytomas in three patients. One neoplasia was located retrocavally, two between the aorta and vena cava, two by the para-aortal, and one by the parailiacal. The tumors were removed by the posterior retroperitoneoscopic or by the anterior laparoscopic approach, respectively. The intraoperative and postoperative courses were uneventful.

Thyroid carcinomas may originate in the thyroid cells (follicular and papillary, carcinoma, so-called differentiated carcinomas, constituting roughly 80-90% of cases), and the calcitonin-producing parafollicular C cells (medullary carcinoma, roughly 10%). The suspected diagnosis is clarified with the aid of ultrasonography, scintigraphy and fine-needle aspiration cytology. Primarily, carcinomas of the thyroid are treated surgically; in the case of differentiated carcinomas, surgery is followed by radio-iodine treatment, and in the follow-up period 131I scintigraphy is performed. During this period, physical examination, ultrasonography of the neck, monitoring of the tumours markers, and treatment with levothyroxine are applied (TSH-suppressive in cases of differentiated carcinoma). In the event of a recurrence showing rapid progression, when surgical and nuclear medical treatment modalities have been exhausted, chemotherapy can be given.

The early detection of metastases from medullary thyroid cancer (MTC) is important because the only curative therapy consists in surgical removal of all tumour tissue. There is no single sensitive diagnostic imaging modality for the localization of all metastases in patients with MTC. Therefore, in many cases several imaging modalities (e.g. ultrasonography, magnetic resonance imaging, computerized tomography and scintigraphy using pentavalent technetium-99m dimercaptosuccinic acid, thallium-201 chloride, indium-111 pentetreotide, anti-CEA antibodies or metaiodobenzylguanidine) must be performed consecutively in patients with elevated calcitonin levels until the tumour is localized. In this prospective study, we investigated the value of fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET) in the follow-up of patients with MTC. [18F]FDG PET examinations of the neck and the chest were performed in 20 patients with elevated calcitonin levels or sonographic abnormalities in the neck. Positive [18F]FDG findings were validated by histology, computerized tomography or selective venous catheterization. [18F]FDG PET detected tumour in 13/17 patients (nine cases were validated by histology, four by computerized tomography). Five patients showed completely negative PET scans (of these cases, one was true-negative and four false-negative). One patient with [18F]FDG accumulation in pulmonary lesions from silicosis and one patient with a neck lesion that was not subjected to histological validation had to be excluded. Considering all validated localizations, [18F]FDG PET detected 12/14 tumour manifestations in the neck, 6/7 mediastinal metastases, 2/2 pulmonary metastases and 2/2 bone metastases. In two patients with elevated calcitonin levels, no diagnostic modality was able to localize a tumour. The sensitivity of [18F]FDG PET in the follow-up of MTC was 76% (95% confidence interval 53%-94%); this is encouraging. [18F]FDG PET promises to be a valuable diagnostic method, especially for the detection of lymph node metastases, surgical resection of which can result in complete remission.

The chemiluminescence assays for detection of autoantibodies to thyroid peroxidase (TPO) and thyroglobulin (Tg) implemented on the IMMULITE 2000 system (Diagnostic Products Corporation) were evaluated. These were immunometric assays with antigen-coated beads and monoclonal murine anti-IgG antibodies conjugated with alkaline phosphatase. Precision was satisfactory with an intraassay precision of 5.3-5.5% for anti-Tg and 4.8-5.3% for anti-TPO and an interassay precision of 5.7-7.3% for anti-TPO and 5.2-7.5% for anti-Tg. The lower detection limit was determined as 5 IU/ml for anti-TPO and 2.2 IU/ml for anti-Tg. The average dilution linearities of 102% for anti-TPO and 100% for anti-Tg and the average recovery of 80-127% for anti-TPO and 93-112% for anti-Tg were acceptable. The findings of the tests were compared with the systems from PharmaciaUpjohn, ORGenTec, Roche Diagnostics, Byk Sangtec Diagnostica and BRAHMS Diagnostica. Taking the respective cutoff value into account, concordance was 87-96% for anti-Tg and 87-97% for anti-TPO. Summarizing all results from the different methods revealed a clinical agreement of 95% for anti-TPO and 93% for anti-Tg. A good agreement was found with the IMMULITE anti-TPO and anti-Tg assays, which are closely related as regards method and biochemistry. Regression analysis gave the following results: anti-TPO IMMULITE 2000 vs anti-TPO IMMULITE: anti-TPO IMMULITE 2000 = 0.99 x IMMULITE anti-TPO - 1.43 IU/ml (r = 0.99, n = 144). anti-Tg IMMULITE 2000 vs anti-Tg IMMULITE: anti-Tg IMMULITE 2000 = 0.98 x IMMULITE anti-Tg + 1.63 IU/ml (r = 0.99, n = 86). Further age-dependent normal ranges were evaluated. A higher prevalence of elevated autoantibody titers was found for patients older than 50 years. The rate of elevated antibody titer can be reduced by using an age-dependent reference range:or = 50 years anti-TPO35 IU/ml, anti-Tg40 IU/ml and50 years anti-TPO100 IU/ml, anti-Tg80 IU/ml. Further samples from clinically diagnosed Hashimoto's thyroiditis and Graves' disease were investigated. The levels of positive anti-Tg values and anti-TPO values accorded with those stated in the literature and were comparable to those measured with a reference assay. In the tested INSTAND e. V. interlaboratory samples there was high-level accordance with the expected clinical results.

Primary adrenal tumors were removed in 24 patients by the posterior retroperitoneoscopic approach, maintaining tumor-free parts of the ipsilateral adrenal gland. These partial adrenal resections did not cause a significantly different operating time or blood loss compared to 58 complete adrenalectomies performed during the same period. All 20 patients with hormonally active tumors are biochemically and clinically cured (mean follow-up 18 months). In selected cases the retroperitoneoscopic subtotal adrenal gland resection is a safe procedure, which can potentially maintain the function of the adrenal gland's cortex.

One hundred and eighty-one families with multiple endocrine neoplasia type 2A (MEN-2A) or familial medullary thyroid carcinoma (FMTC) have been investigated for mutations in the ret protooncogene in Germany. In 8 families with FMTC or MEN-2A, no mutation could be detected in the cysteine-rich domain encoded in exons 10 and 11 of the ret protooncogene. DNA sequencing of additional exons (no. 13-15) revealed rare noncysteine mutations in 3 families (codons 631, 768, and 844). In contrast to these rare events, heterozygous missense mutations in exon 13, codons 790 and 791, were found in 5 families (4 with MTC only; 1 family with MTC and pheochromocytoma) and 11 patients with apparently sporadic tumors. Two different mutations in codon 790 (TTG--TTT, TTG--TTC; Leu790Phe) and one mutation in codon 791 (TAT--TTT; Tyr791Phe) created a phenylalanine residue. We conclude that codons 790 and 791 of the ret protooncogene represent a new hot spot for FMTC/MEN-2A causing mutations. With the discovery of these considerably common mutations in codons 790 and 791 and the identification of some rare mutations, 100% of the German FMTC/MEN-2A families could be characterized by a mutation in the ret protooncogene.

Bei 24 Patienten wurden primare benigne Nebennierentumoren retroperitoneoskopisch enfernt und dabei ipsilateral tumorfreie Nebennierenanteile gezielt belassen. Im Vergleich zu den im gleichen Zeitraum durchgefuhrten 58 Adrenalektomien fuhrt dieses Vorgehen weder zu einer Verlangerung der Operationsdauer noch zu groseren Blutverlusten. Nach einer medianen Nachbeobachtungszeit von 18 Monaten sind alle 20 Patienten mit hormonaktiven Neoplasien biochemisch und klinisch geheilt. Die retroperitoneoskopisch durchgefuhrte subtotale Nebennierenresektion ist in ausgesuchten Fallen ein sicheres Operationsverfahren, das potentiell die Funktion der Nebennierenrinde erhalt.

In einer prospektiven Beobachtungsstudie von 1993 bis 1996 wurde bei 85 konsekutiven Erstoperationen wegen primarem Hyperparathyreoidismus der Eingriff dann unilateral beendet, wenn auf dieser Seite ein Adenom (auch histologisch zumindest als Hyperplasie bestatigt) und eine normal kleine Nebenschilddruse aufgefunden wurden. Anderenfalls oder bei notwendigen Simultaneingriffen an der Schilddruse wurde bilateral operiert. Mit dieser Strategie unter Zuhilfenahme von 69,4% richtigen Sonographiebefunden konnte ein Primarerfolg von 95,3% und i.M. eine signifikante Zeitersparnis von 30 Minuten erzielt werden.

Within a prospective case control study from 1993 to 1996, in 85 first operations for primary hyperparathyroidism the neck exploration was ended unilaterally when an adenoma (also histologically proven) and one normally small parathyroid gland were found. Otherwise or in case of simultaneous surgery of the thyroid gland, a bilateral exploration was performed. The primary success rate with this strategy, additionally based on 69.4% correct results of cervical ultrasound, was 95.3%, with a significant saving of an average of 30 min. operating time.

In patients with autoimmune thyroid disease the presence of autoantibodies against several distinct antigens including the TSH receptor, thyroglobulin, and the microsomal antigens (MAg) is well established. The MAg is a glycoprotein of an apparent molecular weight of about 100kDa [1–3], and its major antigenic component is thyroid peroxidase (TPO) [4–7]. Recently published studies have suggested a heterogeneous nature of autoantibodies directed against TPO (anti-TPO-Abs) [8] and reported that anti-TPO-Abs not only bound to TPO but also inhibited its enzymatic activity [9–12]. However, the important question of whether the antigenic determinants of TPO include its catalytic sites is presently controversial, since another study failed to find any inhibition of TPO activity by anti-TPO-Abs [4].

Human choriogonadotropin (hCG) and free hCG-beta values for 934 serum samples from patients with seminomatous or nonseminomatous testicular cancer were measured by highly specific immunoradiometric assays (IRMAS). In non-seminoma samples, hCG and hCG-beta were highly correlated (r = 0.82, P less than 0.001). Of 112 "marker-positive" seminoma samples, only 46 (41.1%) showed both increased hCG and hCG-beta. In 39 cases (34.8%) only hCG-beta and in 27 cases (24.1%) only dimer-hCG was increased. This makes the determination of hCG and hCG-beta, either by two assays or by a single hCG (+hCG-beta) assay, most reliable in these patients. For all samples, hCG (+hCG-beta) was measured by a polyclonal RIA and a monoclonal IRMA, which differed in their cross-reactivities with hCG-beta (234% and 720%, respectively). The hCG (+hCG-beta) IRMA, as a result of its higher hCG-beta cross-reactivity, was superior to the hCG (+hCG-beta) RIA in detecting slightly increased hCG-beta. Additionally, 11 widely used commercial hCG kits were tested for their hCG-beta cross-reactivities and showed values between less than 3% and 264%.

Basal and TRH-stimulated TSH levels were determined in 72 patients with differentiated thyroid cancer on hormonal treatment, using a highly sensitive immunoradiometric assay (IRMAclon, Henning). 43 patients were under treatment with levothyroxine (T4), 29 patients with triiodothyronine (T3). In 33/43 patients (77%) under T4- and in 18/29 patients (62%) under T3-treatment basal TSH levels were below 0.1 mU/l and levels stimulated with 200 µg TRH i.v. were below 0.5 mU/l. 3 patients showed a significant response (to above 0.5 mU/l) in the TRH test despite basal values of less than 0.1 mU/l. In 2 patients with elevated basal TSH levels (0.23 and 0.60 mU/l, resp.) in the IRMAclon, total suppression of TSH secretion was suggested by a failure of TSH to rise after TRH. By retesting these samples in an own TSH IRMA, basal and stimulated TSH values were below 0.1 mU/l. In conclusion, basal and TRH-stimulated TSH levels are well correlated in most patients with thyroid cancer under hormonal treatment. However, in some cases (5/72) determination of basal TSH could not clearly define the degree of thyrotropic suppression. Thus, TRH testing is still necessary to establish definitely complete TSH suppression in patients with thyroid carcinoma under suppressive treatment.