Biomedical subjects
M Weissel
Publications and source records attributed to M Weissel.
[Hyperthyroidism and heart].
This review discusses the clinically relevant effects of thyroid hormone excess on the heart. Tachycardia and atrial fibrillation are usually reversible after euthyroidism is restored. Atrial fibrillation may, however, take several months to return to sinus rhythm. The increase in contractility leads to an increase of cardiac output. The development of a relative myocardial hypertrophy following long-term high-dose therapy with thyroid hormones is controversial. Cardiac failure at stress in spite of an increased cardiac output at rest is a phenomenon typical for thyrotoxicosis. Reports of dilated cardiomyopathy associated with Graves' disease and evidence for TSH-receptors in the human myocardium suggest a relationship between these two diseases. Endomyocardial biopsy studies have, however, failed to prove this hypothesis. Mitral valve prolapse is more frequent in hyperthyroid patients than in normals. Thyroid hormone excess as well as the autoimmune origin of the disease are suggested as etiology for this phenomenon. The frequently observed angina pectoris seems to be a consequence of the increase in consumption of oxygen in the presence of an unchanged oxygen supply rather than of obstruction of coronary circulation. Well documented cases of myocardial infarction patients with thyroid hormone excess and normal coronary arteries in angiography substantiate this theory. Finally diagnostic and therapeutic options of the two forms of thyrotoxicosis induced by the antiarrhythmic drug amiodarone are presented.
Emergency angioplasty and stent deployment for acute occlusion of an anomalous single coronary artery (all three coronary arteries from one ostium in the right sinus of Valsalva).
A single coronary ostium is traditionally considered to be of little clinical significance. We report a case of a single ostium in the right sinus of Valsalva, giving rise to the right coronary artery, from which the left main coronary artery originated. Sudden death occurred seven days after acute gastrointestinal bleeding and subsequent interruption of aspirin therapy. Acute coronary angiography following successful resuscitation revealed an ascending thrombus in the right coronary artery. The patient underwent a complex percutaneous coronary angioplasty with stent deployment. We conclude that coronary artery disease may lead to severe ischemia with a large area at risk and major complications in patients with coronary anomalies. Patients with acute stent implantation might benefit from platelet aggregation even in cases of recent intestinal bleeding.
[Conservative therapy in endocrine orbitopathy: "State of the art"].
This review describes the state of the art of the conservative therapeutical approach of thyroid associated eye disease. Radiotherapy, surgery and ablative therapy of thyroid ophthalmopathy are discussed elsewhere in this issue of Acta Med Austriaca. All forms of therapy have to be adjusted to the severeness of the eye disease. The assessment of the severeness of this ailment can be difficult. Therefore, the impact of scoring systems like the "Clinical Activity Score" is pointed out. Treatment of thyroid dysfunction is the widely accepted first therapeutic measure. Additional supportive local therapy is usually sufficient in patients with only mild activity of endocrine ophthalmopathy. Glucocorticoids applied via different routes in various dose regimens are the therapy of first choice in (moderately) severe forms of the disease. Reported response rates for the oral form of therapy are about 63%, for the intravenously applied very high doses (given only in very severe forms of the disease) nearly 77%. Cyclosporin has been shown to be more efficient in combination with oral glucocorticoids in patients with moderately severe eye disease than glucocorticoids alone. Patients need a close follow up since both drugs have considerable side effects. An alternative treatment with high-dose intravenous immunoglobulins seems to have less side effects, but has the disadvantage of bearing the danger of serious infections as all plasma derived products and of being extremely expensive. Finally, preliminary data of new treatment modalities with the immunomodulators pentoxifylline and methotrexat are presented. These drugs have been tested so far with good success in patients with severe endocrine ophthalmopathy and unresponsive to other forms of treatment.
Dermatitis herpetiformis is associated with atrophic but not with goitrous variant of Hashimoto's thyroiditis.
BACKGROUND: Dermatitis herpetiformis (DH) is a gluten-sensitive skin disease that is associated with a variety of autoimmune disorders. Several investigations demonstrated an association between DH and autoimmune thyroid disease. However, it has not been shown if DH is associated with atrophic or goitrous variant of Hashimoto's thyroiditis. MATERIALS AND METHODS: We investigated a cohort of 41 DH patients (18 male, 23 female) and a control group (11 male, 19 female; sex and age matched healthy volunteers) to find out which variant of Hashimoto's thyroiditis is associated with DH. All patients had thyroid hormones and antibodies measured. In addition to that, thyroid sonography as well as detailed history-taking of previous thyroid disease were performed. RESULTS: In the control group no individual with elevated levels of thyroid antibodies nor abnormal thyroid hormones nor thyroid atrophy was found. Median thyroid volume in the control group was 11 mL (range 4.8-24.7 mL). However, in nine DH patients (22%) elevated levels of antithyroid microsomal (TM) antibodies were seen (P < 0.01). Three of them had abnormal thyroid hormones (7%). In the group of DH patients a significantly smaller thyroid volume was found (median 8 mL, range 1. 6-25.2 mL; P < 0001). Thyroid atrophy (volume < 4.4 mL) was found in 10 DH patients (24%) of whom 9 were females. All patients with elevated levels of TM antibodies or abnormal thyroid hormones and all patients with a history of previous hypothyroidism had a thyroid volume < 7 mL. Goitrous variant of Hashimoto's thyroiditis was not seen in any of the DH patients. CONCLUSIONS: Our findings demonstrate that DH is associated with atrophic but not with goitrous variant of Hashimoto's thyroiditis.
Clinical significance of autoimmune thyroid disease in myasthenia gravis.
We investigated thyroid function and autoimmunity in 74 (61% females) consecutive patients with MG. 30 of these patients were tested twice: the time between the investigations ranging from 1 to 4 years. MG was diagnosed on the basis of typical clinical symptoms, a positive tensilone-test, and/or detectable acetylcholine antibodies and/or repetetive stimulation tests. Eye involvement was present in 86%, concurrent thymomas in 56%. The following parameters were measured in the serum of these patients by commercially available kits: free and total T4, TSH, TSH-Receptor-Antibodies ("TRAB"), antibodies against thyroglobulin (Tg-Ab), against thyroid microsomes (M-Ab) and against acetyl-choline-receptors . An age matched group of 50 patients (54% females) with no known thyroid disease from a cardiological ward and from the neurological outpatient department served as control. There was only 1 MG patient with overt thyroid dysfunction (iodine induced thyrotoxicosis in a patient with autonomous adenoma and no circulating thyroid autoantibodies detected at the second investigation). There were, moreover, 1 euthyroid MG-patient on L-thyroxine therapy with a history of Hashimoto's disease and positive thyroid autoantibodies and 1 other MG-patient with mildly elevated TSH without elevated thyroid antibodies, who has had subtotal thyroidectomy without substitution therapy years before for unknown reasons. Tg-Ab were positive (>360 IU/ml) in 5%, M-Ab were positive (>154 IU/ml) in 15% of the MG patients. The control group had 4% Tg-Ab and 6% M-Ab. TRAB levels were normal in all patients and controls. The relative increase in M-Ab frequency was not statistically significant (x-square test). We conclude from our results, that autoimmune thyroid disease may be associated with MG but that the occurrence of thyroid dysfunction induced by autoimmunity is a very rare phenomenon in MG.
Fatal liver failure after high-dose glucocorticoid pulse therapy in a patient with severe thyroid eye disease.
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[Spontaneous healing of retroperitonea fibroasis after successful therapy of sigmoid carcinoma].
In a 64 year old man sigma cancer was diagnosed unexpectedly during an operation for retroperitoneal fibrosis (histologically benign fibrosis), that had caused unilateral hydronephrosis. In the following hemicolectomy this tumor of the colon turned out to be a medium high grade adenocarcinoma (tumor staging pT2, pN1, DUKES C). Chemotherapy with 450 mg/m2 5-FU once a week and a concomitant therapy with laevamisol was added for 6 months. Computer-tomography revealed a significant reduction of the retroperitoneal masses already before induction of chemotherapy. One year after termination of chemotherapy retroperitoneal fibrosis was no longer detectable. The course of events makes us assume that the retroperitoneal fibrosis of our patient was paraneoplastic and therefore completely reversible by successful removal of the underlying tumor.
[Administration of thyroid hormones in therapy of psychiatric illnesses].
This review tries to give the state of the art of the therapeutic use of thyroid hormones in psychiatric disorders, mainly in depression. Four hypotheses suggest an effect in these ailments: 1) a local relative T4 excess present (or better postulated to be present) in the brain of depressed patients is lowered by triiodothyronine (T3), by lowering serum levels of thyroxine (T4), 2) the effect of a depression-mediated cerebral lack of catecholamines is compensated by the T3/T4 induced activation of beta-receptors, 3) a postulated depression-induced local cerebral hypothyroidism can be counteracted by T3 and T4. 4) thyroid hormones increase the cerebral content of serotonin. This may be beneficial in depression, where shortage of serotonin in the brain is accused to be etiologically important. Thyroid hormones have been used so far in the following ways: 1) as T3 monotherapy in depression; 2) initial additive T3 for acceleration of the response to treatment with tricyclic antidepressants (TCA); 3) additive T3 for augmentation of the response to TCA in therapy-resistant patients with depression, 4) as high-dose (250-500 micrograms/die) T4-treatment of "rapid cycling bipolar disorder". Low dose (5-50 mg/die) T3 "augmentation therapy" is the best documented form of treatment with thyroid hormones in depression. The results suggest a convincing benefit for a varying percentage of non responders to therapy with TCA. For the other forms of treatment placebo-controlled double blind studies are not yet available or give conflicting results.
Culture of human insulinoma cells: development of a neuroendocrine tumor cell- and human pancreatic islet cell-specific monoclonal antibody.
We report on the culture of human insulinoma cells derived from a 32-year-old male patient with hyperinsulinism due to an insulinoma of the pancreas. A single-cell suspension was made by passing insulinoma fragments through a fine-gauge stainless-steel mesh. Cluster-forming insulinoma cells resembling pancreatic islets grew in the presence of fibroblasts. The insulinoma cell clusters could be differentiated from fibroblasts by using in situ pan optic staining and specific immunocytochemical staining (anti-human insulin and anti-human insulinoma monoclonal antibody (mAb) D24). mAb D24 was generated using insulinoma cells as antigen for immunization of a Balb/C mouse and cell fusion by the hybridoma cell technique. The anti-insulinoma cell mAb recognized a 32 kDa protein on immunoblot analysis of neuroendocrine tumor cells. D24 mAb also reacted immunohistochemically with normal pancreatic beta-cells and tumors such as vipoma, gastrinoma and carcinoid. Insulinoma cell clusters separated from fibroblasts by micromanipulation and plated into multiwell culture dishes exhibited an insulin-secretion rate of approximately 30 U/100 cells per 24 h with no insulin-secretory response to elevated glucose concentration. Purified insulinoma cells incubated with 1 ng/ml human nerve growth factor expressed neurofilament and neurite extension. These findings together with earlier observations in animal models suggest that human pancreatic beta-cells share some properties with neurons and are related to other neuroendocrine cells in the gastrointestinal tract.
[Thyrotoxic hypokalemic periodic paralysis in a male Kurd].
Thyrotoxic hypokalemic periodic paralysis has been described to occur quite frequently in male Asiatic patients. The syndrome is, however, very rare in patients of Caucasian origin. To our knowledge it has never been described in Austria so far. This is the reason why we present the following case: A 22-year old male patient of Kurdish origin suffered from two periods of typical flaccid paralysis of the extremities after strenuous physical exertion, that were 4 months apart. The periods of paralysis were quickly reversed by substitution with potassium. Graves' disease was retrospectively diagnosed to have existed already during the first period. The patient was treated with an ablative dose of 131-I (25 mCi) and can perform strenuous exercise without symptoms since. This case and the review of the literature clearly illustrates the advantage of screening for thyroid dysfunction in patients with flaccid paralysis: unnecessary further periods of paralysis can be avoided by the correct treatment of thyrotoxicosis in such patients.
Myocardial ischemia with normal coronary arteries associated with thoracic myelitis.
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[Spontaneous remission of an amiodarone-induced pulmonary lesion].
Amiodarone is an effective class-III antiarrhythmic agent. However, during long term therapy 1-10% of patients develop severe adverse pulmonary reactions, which are potentially life threatening. We report the case of a patient who developed dyspnoea and extensive pulmonary infiltrates compatible with amiodarone-associated interstitial lung disease following 6 months of treatment with amdiodarone (300 mg daily) for atrial flutter. On discontinuation of amiodarone treatment the infiltrates impressively resolved almost completely within 8 weeks, without administration of corticosteroids.
Mild clinical expression of myasthenia gravis associated with autoimmune thyroid disease.
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[Post partum thyroiditis: is early detection of risk patients during pregnancy worthwhile?].
This short review summarizes the arguments for and against a screening for post-partum thyroiditis in early pregnancy: Measurement of circulating TPO (thyro-peroxydase) antibodies in early pregnancy seems a valid screening method for detecting persons at risk. TPO positive mothers seem to have, moreover, an increased risk to develop post-partial depression or symptoms of thyroid disease even without alteration of thyroid function. In addition, a higher frequency of miscarriages has been described in such patients. In contrast to these arguments in favour of performing such a screening is the fact that post-partum thyroiditis usually has only mild clinical symptoms and is a self-limiting disease.
Management of acquired bullous skin diseases.
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Factitious hyperthyroidism causing acute myocardial infarction.
Myocardial ischemia is a rare but severe and possibly life threatening manifestation of hyperthyroidism, but does not usually result in persistent ischemia. We report on a 71-year-old woman who had undergone total thyroidectomy with subsequent irradiation because of follicular carcinoma 3 years ago. Since then, she had been maintained on oral levothyroxine replacement therapy at a dose of 0.15 mg alternating with 0.2 mg daily. When latent hypothyroidism became evident despite replacement therapy, the dose of levothyroxine was increased to 0.3 mg a day. Three weeks later, the patient suffered from an acute posterior myocardial infarction, although she had no previous history of coronary artery disease. Subsequent coronary arteriograms revealed no evidence of disease of the major vessels. Myocardial scintigraphy 3 weeks after infarction still revealed a persistent perfusion defect. Since it is known that thyroid hormones increase oxygen demand, the rapid elevation of oxygen utilization caused by thyrotoxicosis factitia is likely to be responsible for this patient's myocardial infarction. The case illustrates that a sudden increase in levothyroxine replacement dose should be avoided.