Soluble tumour necrosis factor-alpha receptor I and interleukin-6 as markers of activity in thyrotoxic Graves' disease.

Autoimmune thyroid diseases are thought to be mediated by pro-inflammatory cytokines such as TNFalpha and IL-6. Serum levels of cytokines may indicate activity levels of immune functions. We investigated serum levels of IL-6 and of the soluble receptor of TNFalpha in patients with newly diagnosed onset of Graves' hyperthyroidism. The predominantly female group consisted of 39 patients, mean fT4 was 47.6 pg/ml (normal values 7.5=19.0 pg/ml). After diagnosis, all patients were treated with anti-thyroid drugs. Soluble Tumour Necrosis Factor Receptor I (TNF-RI) serum levels were found significantly increased (mean 3.7+/-1.3 ng/ml; p<0,01) compared to a matched group of apparent healthy individuals (mean sTNF-RI 1.8+/-0.5 ng/ml) and to a matched group of patients with treated Graves' disease (mean sTNF-RI 1.9+/-0.6 ng/ml). When IL-6 was assessed only 4 of the 39 patients exhibited increased serum levels. Our finding may indicate that sTNF-RI and possibly its ligand, TNFalpha, could play an important role in the onset of the acute stage of Graves' disease.

Recurrent hyperparathyroidism after total parathyroidectomy due to multiple ectopic parathyroid glands in a patient with long-term haemodialysis.

We report the rare case of a recurrent hyperparathyroidism after total parathyreoidectomy due to multiple ectopic glands in a patient on long-term haemodialysis. In a today 47 years old man with membranoproliferative glomerulonephritis intermittent haemodialysis therapy was started in 1975. In 1982 an advanced secondary hyperparathyroidism with a parathormone (PTH) level > 500 pg/l was diagnosed; later on PTH concentration increased to 2,550 pg/ml. In 1987 total parathyroidectomy with parathyroid autograft into the left forearm was performed. After parathyroidectomy the PTH level fell to 150 pg/ml. In 1993 PTH concentration increased again to 1,750 pg/ml. There was no evidence for recurrent parathyroid glands in the neck or forearm. Therefore, we investigated the substernal region by 99mTc-tetrofosmin scintigraphy and magnetic resonance imaging. Both investigations showed evidence for two ectopic parathyroid glands in the anterior mediastinum. In June 1999 in an open thoracic surgical procedure only the greater parathyroid gland in the anterior mediastinum was isolated, but a second gland was detected in the posterior mediastinum. Both parathyroid glands were resected (histologically hyperplastic parathyroid gland tissue). After surgery the PTH level decreased to 340 pg/ml, but later on PTH increased again to > 1,000 pg/ml in January 2001. A control 99mTc-tetrofosmin scan showed evidence for a third ectopic parathyroid gland in the anterior mediastinum. Recurrent secondary hyperparathyroidism can rarely be caused by recurrent ectopic parathyroid glands in the mediastinum.

[Therapy with somatostatin analogs in patient with orbitopathy and positive Octreoscan]. / Therapie der endokrinen Orbitopathie mit Somatostatin-Analoga bei Patienten mit positivem Octreo-Scan.

We prospectively evaluated 28 persons with active endocrine ophthalmopathy and positive sonographic criteria (A-mode) on extraocular eye muscles. To evaluate somatostatin-receptor status SPECT of the orbits was performed with a double-headed rotating gamma camera after application of 110 MBq 111-In-Pentreotide. 9 patients (12/56 eyes respectively) showed a marked uptake ratio (> 2 in circular ROIs by semiquantitative calculation) and were selected for lanreotide (30 mg i.m. every 14 d) treatment. 5 individuals had control scan after clinical progression which became positive in two of them. All but one tolerated modest side-effects of lanreotide treatment (diarrhea). Therapy was discontinued after 3-10 months when thyroid eye disease had lead to fibrotic stage. This subgroup, with the exception of two women, who received corticosteroids additionally, presented stable disease. One of those had to be sent to surgery because of endangered optical nerve. Clinical ophthalmological control showed promising results in patients receiving somatostatin analogues at early stage when positive on octreo-scan.

Recurrent infectious mononucleosis caused by Epstein-Barr virus with persistent splenomegaly.

We present the clinical case of a 20-year-old male soldier who appeared in general good physical condition. He suffered from infectious mononucleosis caused by Epstein-Barr virus that had recurred 2 years after the first serologically documented episode. The detected splenomegaly persisted in the healthy young man, who otherwise showed no apparent immune deficiency. To our knowledge, this is an extremely rare condition.

Enterovirus infection--a possible trigger for Graves' disease?

Viruses are potential environmental factors in autoimmune disease. Some evidence suggests a relationship between enteroviral infection (especially Coxsackie B virus) and autoimmunity. We investigated 21 individuals with recent onset of Graves' hyperthyroidism in regard of (subclinical) enterovirus infection. Thyrotoxic symptoms had started about two months before blood sample collection. The patients were from Upper Austria and mainly female (17/21). Their mean free thyroxin levels in blood were twice the maximum normal value and the majority achieved a euthyroid state 1 1/2 years later, after antithyroid medication. We employed a nested PCR reaction with primers of the enterovirus genome on blood samples. All were negative for RNA of the enterovirus group. Coxsackie and related viruses were not identified as a trigger factor in autoimmune thyrotoxic disease.

[The insufficiency fracture of the sacrum. An often unrecognized cause of low back pain: results of bone scanning in a major hospital]. / Die sakrale Insuffizienzfraktur. Eine häufig unerkannte Ursache für Lumbo-Sakralgien: Ergebnisse der Knochenszintigraphie in einem Schwerpunktkrankenhaus.

AIM: The insufficiency fracture of the sacrum is often radiographically occult. Bone scintigraphy is a method of reference for the diagnosis; the results have been analysed retrospectively. METHODS: Bone scintigraphy was done on patients who, predominantly after minor trauma, suffered from lower back pain and whose radiographic findings were negative. RESULTS: During a 24 month period, a sacral insufficiency fracture was diagnosed in 102 patients. H-shaped hyperfixation of the tracer--described as typical--was present in only 19.6% of the cases. Tracer accumulation was found as follows: located uni/bilateral in the sacral wings (32.4%/6.9%), horizontal (27.4%) and half H-shaped (13.7%). In 85% of the cases there were further fractures with main localisations in the public bone, in the spine and the ribs. CONCLUSION: The insufficiency fracture of the sacrum as cause of lower back pain is not uncommon, especially in postmenopausal women with risk factors. Bone scintigraphy is not only an adequate procedure for the detection of often radiographically occult sacral fractures, but also an easy method to reveal the often concomitant fractures.

[Clinical value of FDG PET using coincident gamma cameras in staging and restaging of malignant lymphoma--compared with convenitonal diagnostic methods]. / Klinische Wertigkeit der Befunde von FDG-PET mittels Koinzidenz-Gammakamera beim Staging and Restaging maligner Lymphome--ein Vergleich zu konventioneller Diagnostik.

UNLABELLED: AIM of the present retrospective study was to validate the clinical value of F-18-FDG PET imaging in lymphoma patients with a dual head camera modified for coincidence detection. Staging before and after oncological treatment was compared with a conservative diagnostic approach. METHODS: 48 patients (28 non-Hodgkin lymphoma, 20 Hodgkin's disease) received FDG-Hybrid-PET scans. Pretherapeutic staging was realized in 28 patients, 9 of them had control studies after they had completed therapy. Totally 29 persons were examined for post-therapeutic restaging. Computed tomography imaging and lymph node sonography was performed in all cases. Results were validated by clinical follow-up, in three cases a recidive was proven by biopsy. RESULTS: CT and ultrasound detected 77 lesions in 28 patients compared with 100 visualized by PET, but this difference in pretherapeutic staging did not reach significance at p > 0.05 by Fisher's t-test. Hybrid-PET obtained a sensitivity of 93%, a specificity of 79%, a positive of 82% and a negative predictive value of 92% for detection of residual disease. The values for CT + US were 87%, 64%, 72% and 88% respectively. CONCLUSION: FDG Hybrid-PET is as or even more accurate than standard morphologic diagnostic methods for prestaging in malignant lymphoma. Additionally, there is a substantial benefit for therapy monitoring of residual disease using coincidence detection PET with a 3/4-inch crystal gamma camera.

[Primary lymphoma of the thyroid with contralateral recurrence--case report]. / Primäres Lymphom der Schilddrüse mit kontralateralem Rezidiv--Ein Fallbericht.

Primary lymphomas located in the thyroid gland are rare clinical findings. The therapy and the subsequent monitoring of the disease continue to be a subject of debate. We present the case of a 63-year-old female patient in whom a hemi-thyroidectomy was performed because of a growing goiter. Histological examination of the excised tissue revealed a large-cell B-lymphocytic lymphoma which extended to neighboring lymph nodes. The patient received chemotherapy which led to remission of disease for two years. The disease re-occurred in the remaining thyroid lobe. Subsequently, the patient was treated with involved-field radiation therapy which lead to long term remission. We conclude that total thyroidectomy should be considered in the treatment of lymphomas located in the thyroid gland.

[Clinical application of biopsy of the sentinel lymph node in breast carcinoma]. / Klinische Anwendung der Biopsie des leitenden Lymphknotens beim Mammacarcinom.

Sentinel lymph node (SN) biopsy in primary breast cancer seems to be an alternative to complete axillary lymph node dissection for evaluation of the axillary lymph node status in selected patients. Following evaluation of the technique of SN biopsy, we applied SN biopsy clinically to 23 selected patients. A lymphoscintigraphy was performed preoperatively to evaluate lymphatic drainage. The SN was identified in the operating room by use of a hand-held gamma camera and a blue vital dye. The SN was found in all 23 patients. In 17/23 the SN was tumor free and no axillary dissection was performed; 6/23 showed a positive SN and complete axillary dissection was done. Intraoperative lymphatic mapping and SN biopsy may be the treatment of choice for evaluation of axillary node status in selected patients, for it combines accurate nodal staging and low morbidity.

The incidence of hyperthyroidism in Austria from 1987 to 1995 before and after an increase in salt iodization in 1990.

Between 1963 and 1990, Austria had iodized salt prophylaxis of endemic goitre with 10 mg KI (7.5 mg I) per kg. This was obviously insufficient, as urinary iodine excretion ranged from 42 to 78 microg I per g of creatinine and goitre in adults remained in the endemic range of 15%-30%. Therefore salt iodization was doubled in 1990. The aim of this study was to assess the annual incidence of different types of hyperthyroidism (HT) before and after this increase in salt iodization. The incidence of HT was recorded in 14 nuclear medicine centres from 1987 to 1995. In five additional centres data were available from 1992 onwards. Data prior to 1992 were documented retrospectively, while those after 1992 were recorded prospectively. The 14 centres drew patients from an area with a population of approximately 4.23 million while all 19 institutes were estimated to cover an area with a population of 5.4 million (the total population of Austria is 7.86 million). A total of 414232 persons were examined for the first time in the participating centres. HT and the type of HT were defined by clinical examination, serum TSH, thyroid hormone levels in blood, ultrasonography, scintigraphy and serum autoantibody titres. HT was classified into immunogenic HT (Graves' or Basedow's disease, GD) and HT with intrinsic thyroid autonomy (uni-, multinodular or disseminated Plummers' disease, PD). HT was also divided into overt (o) or subclinical (sc) disease. The following data were calculated: annual incidence per 100000 and the relative risk (RR) for HT with 95% confidence intervals (CI). In addition, linear trends were calculated for each type of HT by means of logistic regressions. In the 19 centres a total of 47834 patients with HT were registered from 1987 to 1995. PD accounted for 75% of all cases of HT and GD for 19%, while other types of HT were present in 6%. From 1987 to 1989 (time period T0), the annual incidence of oPD was 30.5 (95% CI 29.6-31.5) per 100000. The RR compared to the baseline period T0 was highest in 1992 (1.37; 1.3-1.45) and decreased to 1.17 (1.1-1.24) in 1995. The annual incidence of scPD in T0 was 27.4 (26.5-28.3) per 100000. The RR was highest in 1991 (1.64; 1.56-1.73) and was 1.60 (1. 51-1.69) in 1995. In oPD and scPD a higher RR was observed in persons older than 50 years of age, particularly in men. The incidence of oGD in T0 was 10.4 (9.8-10.9) per 100000; the maximum RR increased to 2.19 (2.01-2.38) in 1993 and decreased to 1.95 (1.78-2.13) in 1995. The incidence of scGD was 1.9 (1.6-2.1) in T0. The maximum RR was observed in 1994 (2.47; 2.04-3.0) and it was still 2.26 (1.85-2.77) in 1995. The increased incidence of oGD and scGD was evenly distributed in all ages and both sexes. The time course of different types of HT following the increase in salt iodization could be divided into two phases: an increase in the incidences of HT with peaks after 1-4 years and a subsequent decrease, the only exception being scGD. The effect was more pronounced in GD than in PD. PD showed an age and gender dependency over time, while GD did not.

[Hyperthyroidism caused by TSH producing hypophyseal adenoma]. / Hyperthyreose durch ein TSH-produzierendes Hypophysenadenom.

Thyrotropin (TSH-)producing adenomas of the anterior pituitary gland are the least frequently encountered ones and constitute a very rare cause of hyperthyroidism. The case is presented of a 58 year old male patient with a well-known history of hyperthyroidism over a period of at least 9 years growing goiter. Despite different forms of medical treatment he presented a constant clinical pattern consisting of restlessness and paroxysmal tachycardial atrial fibrillation. Laboratory findings revealed elevated levels of circulating thyroid hormones despite inadequately high levels of TSH. MRI scan revealed an adenoma of the pituitary measuring 9 mm in diameter. After microsurgery, consisting of transphenoidal resection of the tumor, the patient recorded no clinical symptoms. Histological examination revealed positive immunohistochemical staining, with antibodies to TSH, but a negative reaction against the GH, PRL, FSH, LH and ACTH hormone antibodies. Moreover, the levels of circulating hormones (GH, PRL, FSH, LH and ACTH) were normal. TSH-alpha subunits were not elevated. Before the correct diagnosis was reached, this patient was treated for nine years with antithyroid drugs. Five months after the operation the patient showed normal values of circulating thyroid hormones and TSH and thus no thyroid-specific medication was necessary.

Autoimmune reactions in patients with silicone breast implants.

Silicone breast implants have been surgical routine for over 30 years. An association between silicone augmentation and immune related diseases has been reported in approximately 100 cases. In a retrospective single center study we investigated 36 non-selected women with silicone breast implants and 36 sex- and age-matched controls. Autoimmune reactions were evaluated by measuring antinuclear antibodies (ANA), rheumatoid factor (RF) and thyroid gland antibodies (TMS), along with angiotensin-converting enzyme (ACE), C-reactive protein (CRP) and other immunological and laboratory parameters. In the controls only 3 (8%) women had an elevated ANA titer and 1 demonstrated thyroid autoantibodies (microsomal), giving a total of 4 (11%) women with detectable autoantibodies. By contrast, 12 (33%) of the 36 women with silicone augmentation had raised ANA titers (> or = 1 : 80), a significantly higher percentage than in the control group (p < 0.02). Of the 12 women, 1 showed antismooth muscle antibodies (ASMA; titer 1 : 40) and 2 of the patients displayed antineutrophilic cytoplasm antibodies (ANCA; 1 : 320 and 1 : 40, respectively), one of the latter also being positive for rheumatoid factor. 2 further women demonstrated thyroid autoantibodies (microsomal), giving a total of 14 (39%) women in whom significant autoantibodies were detectable. Clinical symptoms (musculoskeletal) were present in 1 patient. Most of the observed autoantibodies were organ-unspecific, with a predominance of elevated ANA titers of the heterogeneous type and not related to a distinct clinical entity. However, none of the investigated women with silicone breast implants showed clinical symptoms or signs of connective tissue disease according to ARA criteria.

Serum dehydroepiandrosterone and cortisol measurements in Huntington's chorea.

Serum levels of dehydroepiandrosterone sulfate (DHEAS), known to antagonize metabolic effects of glucocorticoids in animals, and cortisol (CRT), already shown to be related to cognitive dysfunction in man and animals, were measured in 11 drug-free male subjects with definite Huntington's chorea (HC) and in 25 age-matched male normal controls. Statistical difference was found between DHEAS serum levels (p < 0.05), CRT levels (p < 0.05) and the DHEAS/CRT ratio (p < 0.01) of HC subjects and normal individuals. These findings may indicate a dysfunction of the hypothalamic-pituitary-adrenal axis (HPAA) and possibly suggest a role of DHEAS as an antiglucocorticoid in HC.

[Indications for immunoscintigraphy in orthopedics and its interpretation]. / Indikationen zur Immunszintigraphie in der Orthopädie und deren Deutung.

In the view of an orthopedist the immunscintigraphy is a diagnostic and differential diagnostic enrichment. The MAK BW 250/183 is stored in a lyophiled shape. The MAK is marked with 99m Tc with little expense and in a short time. The advantage of the immunscintigraphy is the high sensitivity for places where granulocytes are gathered. The immunscintigraphy proved to be a very good proceed in recording acute inflammations.

[Kinetics and immunocytochemical staining of 99mTc-labeled monoclonal anti-CEA antibodies against granulocytes following intravenous administration]. / Kinetik und immunzytochemische Färbung monoklonaler 99mTc-markierter Anti-CEA-Antikörper gegen Granulozyten nach intravenöser Applikation.

Until now the clinical identification of the affinity of monoclonal 99mTc-anti-CEA antibodies (MAK BW 250/183) on granulocytes was made with tumor cells carrying the same epitope on NCA-95 and human granulocytes in vitro. As this antibody only binds human granulocytes, animal experiments are impossible. 3 patients had their blood withdrawn within 6 h after injection, another patient had his left hip-joint biopsied after 24 h, the samples undergoing subsequent immunocytochemical dyeing. Dyeing of granulocytes all over the smears was evident whereas lymphocytes, monocytes and erythrocytes did not show any reaction. After 6 h there seemed to be a large difference between a relatively high quantity of 86% unlabelled 99mTc-MAb and 75% of immunocytochemically stainable granulocytes in the blood through an excess of binding epitopes. Six h after injection 27% of the activity were, on average, detectable in whole blood. At this time the activity in blood was reduced to an extent that scintigraphic imaging was feasible.

[Percutaneous pulmonary valvuloplasty in adults]. / Perkutane Pulmonalklappensprengung beim Erwachsenen.

Percutaneous balloon pulmonary valvuloplasty was performed in 6 adult patients (aged 21-59 years, mean age: 43 years) with congenital pulmonary valve stenosis and systolic pressure gradients of 50 to 120 mm Hg (mean: 78 mm Hg). In 5 patients the procedure was successful: mean systolic right ventricular pressure was reduced from 99 +/- 26 to 55 +/- 7 mm Hg and the trans-stenotic pressure gradient from 77 +/- 28 to 31 +/- 12 mm Hg. Valvuloplasty with a 20 mm balloon was not effective in a patient with a wide pulmonary anulus (diameter 25 mm). In 1 patient only, the balloon occlusion led to severe systemic hypotension with syncope. Short-term follow-up (3 months) demonstrated symptomatic improvement and persistent reduction of the pressure gradient in all successfully treated patients. In conclusion, percutaneous balloon pulmonary valvuloplasty appears to be an effective method with low risk of complications for the treatment of pulmonary valve stenosis in adults.

[Aortic valve prolapse]. / Aortenklappenprolaps.

The aortic valve prolapse which can be diagnosed by echocardiography is usually found in patients with the floppy valve syndrome. The clinical symptoms are identical with those of the mitral valve prolapse. The frequency of aortic valve prolapse in 67 cases of mitral valve prolapse was 8.9%, the frequency of aortic insufficiency 5.9%. A main etiological factor of aortic valve prolapse is a myxomatous degeneration of valvular tissue which can affect one or more cardiac valves.