Mild clinical expression of myasthenia gravis associated with autoimmune thyroid disease.
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Biomedical subjects
Publications and source records attributed to M Weissel.
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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.
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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.
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This paper tries to evaluate the importance of IFN-alpha induced thyroid dysfunction. Based on our own experience and reported data we present the results obtained in a total of 588 patients, in whom thyroid function and thyroid antibody occurrence was monitored during therapy with IFN-alpha: About 10% of these patients developed thyroid dysfunction during IFN-alpha treatment. Half of them reacted with hypothyroidism, 3% with hyperthyroidism and in 2% a biphasic (hyperthyroidism followed by hypothyroidism) pattern of reaction was observed. The frequency of these thyroid dysfunctions was increased in female patients and in patients with preexisting thyroid antibodies. The risk to develop thyroid dysfunction is reduced to 7% in patients with no pretherapeutic thyroid antibodies. The evolution of the thyroid ailment is variable and therefore unpredictable. In many patients there is no need to stop treatment with IFN-alpha nor to treat the thyroid dysfunction specifically. IFN-alpha induced autoimmune- phenomena seem to be etiologically important for the development of thyroid disease during IFN-alpha. The reported data allow in our view some basic recommendations for the clinician: thyroid function and thyroid antibodies should be evaluated before the start of treatment with IFN-alpha. During therapy with IFN-alpha these parameters should be regularly (eg every 4 months) monitored. In patients with thyroid autoantibodies or dysfunction already before IFN-alpha the control intervals should not be longer than every two months.
Fluoride salts are widely used in Europe in the treatment of established osteoporosis with crush fractures for their ability to increase trabecular bone mass. However, in the United States fluorides are still regarded as an experimental drug. In a prospective, randomized study we compared the fluoride pharmacokinetics of enteric-coated sodium fluoride and disodium monofluorophosphate calcium carbonate (MFP-Ca) over the period of 76 h. Twenty subjects (12 females, 8 males), aged 35-80 years, free of gastrointestinal disorders, renal impairment, and liver disease and without prior fluoride intake entered the study. Ten subjects received NaF (11.3 mg fluoride) twice a day and the other ten MFP-Ca (13.2 mg fluoride) twice a day. During the study period of 76 h the patient's usual food intake was not changed. Serum fluoride levels were determined using an ion sensitive electrode. After intake of a single drug preparation of MFP-Ca or NaF, MFP-Ca showed a significantly shorter lag time of absorption and a significantly higher maximal serum fluoride concentration than NaF (P < 0.01). A comparison of fluoride cumulative characteristics of both drugs showed virtually identical serum fluoride levels before intake of the morning dose on all 4 study days, whereas serum fluoride concentrations measured 4 h afterwards were significantly higher for MFP-Ca than for NaF. These data provide evidence of high "peak" serum fluoride levels for MFP-Ca, whereas only small peak-to-trough fluctuations are seen for NaF.
The high incidence of cardiac mortality in type 1 diabetic patients is further increased when diabetic nephropathy is present. Since microalbuminuria (albumin excretion rate > 30 mg/day) represents an incipient stage of diabetic nephropathy, we decided to investigate whether incipient renal changes correlate with early diastolic cardiac dysfunction, known to preceed systolic dysfunction. To test this hypothesis, 13 normotensive type 1 diabetics with incipient nephropathy (mean age 37.8 +/- 3.5, diabetes duration 18.8 +/- 2.6 years), 13 type 1 diabetics without nephropathy (matched for age, diabetes duration and metabolic control) or other microangiopathic changes and 13 normal controls were studied. Diseases known to affect left ventricular performance were ruled out before investigation. Right and left ventricular parameters were assessed by M-mode and Doppler echocardiography. While parameters for left ventricular systolic function stayed within the normal range and did not differ between the two diabetic groups (ejection fraction 69.3 +/- 2.4 vs. 69.6 +/- 1.4%; fractional shortening 40.3 +/- 2.2 vs. 38.5 +/- 1.1%), diastolic function was significantly impaired in diabetic patients with microalbuminuria. This is expressed by an inversed early and late peak flow velocity ratio in patients with microalbuminuria (0.988 +/- 0.04 vs. 1.362 +/- 0.1; p < 0.05) and a significant percentual increase in late (atrial) filling (39.1 +/- 1.7 vs. 29.9 +/- 1.4% when compared to whole filling; p < 0.05) despite a similar rate-corrected isovolumetric relaxation period in both diabetic groups (98.4 +/- 5.8 vs. 95.5 +/- 6.2).(ABSTRACT TRUNCATED AT 250 WORDS)
Insulin resistance, hyperinsulinemia, and dyslipidemia are common characteristics of patients with untreated hypertension. However, the link between the vascular and metabolic disturbances is still unclear. To provide further insights into the metabolic picture of subjects with hypertension, we evaluated insulin resistance, pancreatic secretion, and hepatic extraction of the hormone in 16 untreated patients with essential hypertension before and after 12-16 weeks of drug treatment in comparison with 16 age-, sex-, and body weight-matched normotensive control subjects. All subjects underwent an oral and a frequently sampled intravenous glucose tolerance test. Metabolic parameters were calculated by the minimal model technique. The hypertensive patients exhibited a highly reduced tissue insulin sensitivity (2.6 +/- 0.4 versus 9.6 +/- 1.9 10(4) min-1/[microunits/mL]; p < 0.001). The basal secretion rate (70 +/- 11 versus 35 +/- 5 pmol/L per minute) and the total amount of prehepatically secreted insulin (32 +/- 4 versus 16 +/- 2 nmol/L in 4 hours) were significantly increased in the hypertensive patients compared with the control subjects (p < 0.01), whereas the posthepatic insulin delivery rate was not significantly different between the two groups (4.9 +/- 0.6 versus 3.5 +/- 0.3 nmol/L in 4 hours). Hepatic insulin extraction was found to be significantly elevated in the hypertensive patients compared with control subjects (81 +/- 4% versus 69 +/- 3%, p < 0.04). Increased hepatic insulin extraction partially ameliorated B cell hypersecretion in hypertensive patients. After 12-16 weeks of drug treatment, the blood pressure was normalized, but the metabolic profile of the patients remained unchanged. We conclude that elevated insulin extraction in the liver is a specific characteristic of individuals with essential hypertension and partially compensates pancreatic B cell hypersecretion.
Self-administration of very high doses of androgenic anabolic steroids is common use in power athletes because of their favorable effect on performance. Since androgenic steroids decrease serum T4-binding globulin (TBG) concentrations dramatically, we were interested in the effects of this procedure on thyroid function: we performed TRH tests (200 micrograms Relefact, i.v.), with blood withdrawal before and for 180 min after injection, for determination, using RIA kits, of serum concentrations of total and free T4, total T3, TSH, and TBG in 13 young (20-29 yr old) male body builders with clinically normal thyroid glands, who were all in the same state of training. Five of these athletes admitted taking androgenic anabolic steroids at an average total dose of 1.2 g/week for at least 6 weeks before the tests. TBG, total T4, and total T3 were significantly (P < 0.001) decreased, whereas basal TSH and free T4 were not significantly different from the values of the other 8 without androgenic steroids. The maximum TSH increase after TRH administration (mean +/- SE, 16 -/+ 6 vs. 9 -/+ 4 mU/L; P < 0.05) was relatively increased, whereas the T3 response to TRH (0.61 -/+ 0.10 vs. 1.13 -/+ 0.13 nmol/L; P < 0.05) was relatively decreased in the group receiving androgens. The 5 patients taking androgens had significantly greater weight (114 vs. 90 kg; P < 0.01) and higher total cholesterol levels (6.3 -/+ 1.3 vs. 3.8 -/+ 0.3 mmol/L; P < 0.05) together with very low high density lipoprotein cholesterol levels (0.20 -/+ 0.03 vs. 1.03 -/+ 0.10; P < 0.001) than the controls. PRL levels were normal and similar in both groups. We conclude from our results that high dose androgenic anabolic steroid administration leads to a relative impairment (within the normal range) of thyroid function. Whether this is due to a direct thyroid hormone release (or synthesis?)-blocking effect of these steroids needs further investigation.
This study reports our experience with a combined treatment with cyclosporin A (Cy A) and cortisone in patients with Graves' ophthalmopathy (GO), all of whom had compressive optic nerve disease (CON). The therapy was performed in 8 patients (6 females, age range: 40 to 76 years) with normal liver and kidney function and classical Graves' disease, except for 1 male, who had normal thyroid function and no detectable thyroid antibodies. 5 patients were euthyroid on methimazole, 2 patients were off thyrostatic treatment for 5 and 2 years. 3 patients have had high-dose cortisone (100 mg/die) treatment for GO before the study. Visual field defects were reported by the patients 1 week before start of therapy and evaluated by computerized visual field measurements (CVFM). The treatment consisted of Cy A in a dose which aimed at through levels between 100 and 300 ng/ml (RIA method) for 2 to 6 months and of methylprednisolone in a starting dose of 1 mg/kg body weight, tapered gradually to a maintenance dose of 10 mg/day for 6 to 12 months. CON disappeared completely in all patients. The thickening of affected eye muscles decreased in 5 patients, disappeared in 1 and remained unchanged in 2 patients. The shortest period for a measurable effect (either by echography or by CVFM, performed every week the first month and then every 3 months) was 1 week; the longest 1 month. The follow-up of the patients (range 6 months to 2.5 years) showed a relapse only in 1 patient. 2 patients were lost to follow-up 1 year after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Noninvasive assessment of pulmonary artery hypertension would be of great value in patients with chronic obstructive pulmonary disease (COPD). Although continuous wave Doppler echocardiographic measurement of right atrial to right ventricular pressure gradient is the most useful method of noninvasive assessment of pulmonary artery hypertension, this technique is often limited in patients with COPD. In order to evaluate the usefulness of pulsed Doppler echocardiography, for the estimation of pulmonary artery pressure in COPD patients in whom continuous wave Doppler ultrasound has failed, we compared right ventricular systolic time intervals: pre-ejection period (PEP, ms), acceleration time (AT, ms), right ventricular ejection time (RVET, ms), and AT/RVET and PEP/RVET ratios, as measured by pulmonary artery pulsed Doppler traces, in 30 COPD patients, with the time intervals of 15 age- and sex-matched healthy volunteers, using the subcostal approach. In addition, right ventricular systolic time intervals of the COPD patients were correlated with invasive catheterization data (systolic and mean pulmonary artery pressure (PAPs and PAPm). AT and AT/RVET were significantly shorter in COPD patients (AT 92 +/- 4.3 ms; AT/RVET 0.38 +/- 0.03) as compared with healthy volunteers (AT 132 +/- 4.5 ms; p < 0.001; AT/RVET 0.46 +/- 0.02; p < 0.005), whereas RVET, PEP and PEP/RVET were not significantly different in both groups. A significant correlation was demonstrated between AT and PAPs (r = -0.76; p < 0.001) and PAPm (r = -0.82; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
This study was made to evaluate assays for monitoring of low dose heparin thromboprophylaxis and to evaluate its efficacy in reduction of hypercoagulation. Patients with medical diseases scheduled for routine thromboprophylaxis were subcutaneously treated with either 5.000 anti XaU low molecular weight (LMW) heparin once daily (n = 20) or 5.000 IU standard (ST) heparin 3 times daily (n = 19). On days 1,2,3, before, 1 and 4 hours after heparin injection APTT, TCT, anti Xa, Heptest, thrombin-antithrombin complexes (TAT), and D-Dimer levels were measured. In the LMW heparin group, median values of APTT and TCT slightly increased after heparin and the ranges of pre- and postinjection values showed extensive overlap. However, values of anti Xa and Heptest markedly increased, showing complete separation of ranges. In the ST heparin group neither APTT, TCT, anti Xa, nor Heptest were significantly different comparing pre- and postheparin values. Half of the patients in both groups had subclinical hypercoagulation at baseline (TAT greater than 5 ng/ml, D-Dimer greater than 200 ng/ml). On day 3 of prophylaxis this percentage was not significantly decreased. Moreover, several patients in both groups increased in TAT and D-Dimer. In the LMWheparin group, negative correlations between body weight and 4 h postinjection heparin levels were found (anti Xa R = -0.50, Heptest R = -0.31) and between 1 h postinjection heparin and TAT and D-Dimer levels 3 h later (TAT-anti Xa R = -0.58, TAT-Heptest R = -0.64, D-Dimer-anti Xa R = -0.32, D-Dimer-Heptest R = -0.33).(ABSTRACT TRUNCATED AT 250 WORDS)
Forty-five patients with myeloproliferative or myelodysplastic syndromes, treated with recombinant interferon-alpha (rIFN-alpha) for a minimum of 1 up to 4 years, were examined for the occurrence of thyroid autoimmunity. During treatment, the rate of thyroid autoimmunity rose to more than 20%. The decrease in severity and frequency of thyroid autoimmunity after withdrawal of IFN shows that this is a potentially reversible side effect. The key determinant for the manifestation of this IFN-related autoimmune phenomenon seems to be a predisposition for autoimmunity, since patients with initially detectable thyroid antibodies are prone to exacerbations of thyroid autoimmunity. Concurrent with thyroid autoimmunity, hypothyroidism occurred but did not correlate with the levels of thyroid antibodies, although severe hypothyroidism in two patients was accompanied by increased levels of thyroid antibodies. This investigation shows that thyroid autoimmunity and consecutively hypothyroidism must be expected in certain patients treated with rIFN-alpha during long periods. Furthermore, it may be assumed that IFN-alpha does not induce the development of autoimmunity, but rather enhances the levels of pre-existent thyroid antibodies.
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Since pulmonary artery hypertension (PH) complicates advanced stages of cystic fibrosis (CF), we wondered whether plasma concentrations of h-ANP would be increased in adult patients with CF. Furthermore, if only the right ventricle is faced with an increased afterload in these patients, the increased h-ANP plasma levels should stem primarily from the right atrium. To test this hypothesis we studied 12 adult patients with CF in a clinically stable condition using right heart catheterization. Mean pressures were measured in the right atrium (Pra) and pulmonary artery (Ppa), pulmonary capillary wedge (PCWP) position, and blood were drawn from the pulmonary artery and from a peripheral vein to determine h-ANP. Plasma levels in the pulmonary artery were significantly higher than in a peripheral vein (54.3 +/- 6.0 pg/ml vs. 32.2 +/- 4.4 pg/ml; p less than 0.001). Four of the 12 patients had PH (Ppa, 25.8 +/- 2.9 mmHg) whereas 8 patients exhibited normal pulmonary artery pressures (Ppa, 15.9 +/- 0.7 mmHg). Patients with PH had higher Pra (4.2 +/- 0.4 mmHg) than patients with CF without PH (1.9 +/- 0.7 mmHg; p less than 0.05). Plasma h-ANP concentrations were significantly higher in patients with CF with PH (70 +/- 10.4 pg/ml in the pulmonary artery; 42.6 +/- 4 pg/ml in a peripheral vein) than in patients with normal pulmonary artery pressure (43 +/- 3.3 pg/ml in the pulmonary artery; p less than 0.01; 24.7 +/- 5.6 pg/ml in a peripheral vein; p less than 0.05). Although our results are derived from a small group of patients with CF, we conclude from our results that in patients with CF PH may cause increased h-ANP secretion. The right atrium seems to be a major source.