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Biomedical subjects

J J Staub

Publications and source records attributed to J J Staub.

At least 19 recordsLinked to original sources
PubMed2001

Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease.

The influence of thyroid failure on haemostasis is controversial, both hypocoagulable and hypercoagulable states have been reported. Since both subclinical and overt hypothyroidism have been associated with atherosclerosis, a hypercoagulable state in addition might represent a risk factor for thromboembolic disease. We investigated various haemostatic variables in 42 women with subclinical hypothyroidism and compared them to 66 euthyroid controls. Prothrombin time, activated partial thromboplastin time, fibrinogen, factor VII activity (FVII:C), factor VII antigen (FVII:Ag), factor VIII activity, von Willebrand factor (vWF), antithrombin III, heparin cofactor II, protein C, protein S, plasminogen, antiplasmin, plasminogen activator inhibitor and tissue plasminogen activator, as well as common lipid variables, were measured. Factor VII:C (P < 0.02) and the ratio FVII:C/FVII:Ag (P < 0.01) were significantly increased in subclinical hypothyroid patients compared to the control group. Both parameters remained higher in hypothyroid patients after exclusion of 18 women on oestrogen replacement therapy. No differences were found between the groups with respect to vWF or the other haemostatic and lipid variables tested. Patients with subclinical hypothyroidism had significantly higher levels of FVII:C. The greater increase in FVII:C compared to that of FVII:Ag, as shown by the increase in their ratio, might reflect the presence of activated FVIIa. This might mean a hypercoagulable state, which could contribute to the increased prevalence of coronary heart disease reported in such patients. A hypercoagulable state might be another argument in favour of thyroxine replacement treatment in subclinical hypothyroidism, especially in patients with additional risk factors for vascular disease.

Adult↗
PubMed2000

[Amiodarone-induced thyrotoxicosis].

Amiodarone is the most important drug in the treatment of ventricular arrhythmias and is widely used for atrial fibrillation. Thyrotoxicosis, a classical side effect, was thought to be iodine induced, but recent evidence suggests that other mechanisms play an important role (toxic effect on thyreocytes, immunological effects). Thyrotoxicosis due to amiodarone is difficult to treat and is further complicated by the pro-arrhythmic potential of thyrotoxicosis and the fading antiarrhythmic effect after amiodarone withdrawal. The mechanism, diagnosis and therapy of amiodarone-induced thyrotoxicosis are discussed in the light of the available literature.

Amiodarone↗
PubMed1999

[Functional dynamics of impending overt hypothyroidism: spontaneous evolution in patients in the years before the beginning of treatment].

The syndrome of subclinical hypothyroidism, with its clinical and metabolic consequences, is frequent. Only a minority of these patients will eventually become overtly hypothyroid. It was the aim of the present study to analyse the spontaneous evolution over 10 years of 27 patients with subclinical hypothyroidism who became overtly hypothyroid (group A). For comparison, 27 patients remaining subclinically hypothyroid and matched for their TSH concentrations were characterised (group B). In group A, continuous increase of TSH concentrations was observed over the whole observation period (p = 0.002; ANOVA). The concentrations of fT4 remained initially stable, and only fell at a late stage in the three years before overt hypothyroidism (p = 0.0001; ANOVA). The concentrations of total T3 remained normal throughout the observation period. Thyroid reserve was already impaired at the beginning and during the whole study period. In contrast, these thyroid parameters of patients of group B remained unchanged over 10 years, and thyroid reserve remained normal. The pathogenesis of overt hypothyroidism is a graded process. Increasing concentrations of TSH, a decrease of fT4 and impaired thyroid reserve are predictors of overt thyroid failure.

Analysis of Variance↗
PubMed1999

Reversible cerebral ischemia in patients with pheochromocytoma.

Cerebral ischemia and symptoms of stroke can occur as a rare manifestation in patients with pheochromocytoma. We describe a 45-year-old woman who was admitted because of a right-sided hemiparesis due to an ischemic lesion in the left hypothalamus. The clinical diagnosis of a pheochromocytoma was proven by highly elevated urinary catecholamines and confirmed histologically after operation. The successful removal of the tumor led to the almost complete recovery of the neurological deficiencies. It is of vital importance to know this atypical presentation of pheochromocytoma. The diagnosis of pheochromocytoma should be suspected in patients with focal cerebral symptoms, particularly in the presence of intermittent hypertension or other paroxysmal symptoms suggestive of pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1999

[Malignant pheochromocytoma in the 17th week of gestation].

INTRODUCTION: Pheochromocytoma during pregnancy is rare and represents a high risk for mother and fetus. Due to the variable clinical presentation it may be mistaken for preeclampsia. CASE: A 34-year-old primipara with hypertension up to 240/120 mmHg. After diagnosis of a pheochromocytoma its resection together with lymph node metastasis in the 17th week of gestation was performed. CONCLUSION: The definitive diagnosis is confirmed by elevation of serum catecholamines and their metabolites in a 24-h urine collection. Localization during pregnancy can be made by ultrasound and MRI. The definitive treatment is surgical removal after administration of adrenergic blockers. If discovered later in pregnancy, delivery by elective caesarean section followed by tumor resection is recommended. Since about 10 % of pheochromocytomas are malignant, postpartum screening is required to detect and treat extraadrenal or metastatic tumors by MIBG scintigraphy, chemotherapy or surgical procedures.

Adrenal Gland Neoplasms↗
PubMed1999

[Is there a need for treatment in subclinical hypo- and hyperthyroidism?].

Subclinical thyroid dysfunction is characterized by normal levels of thyroid hormones but abnormal values of thyrotropin (TSH) in an asymptomatic individual. Subclinical hypothyroidism is a common disorder with a prevalence of about 7 to 8% in women (most frequently in females over 50 years), and about 3% in men. It is characterized by elevated serum TSH in the presence of normal concentrations of serum thyroxine. Patients with TSH levels about 12 mU/L (and with positive antithyroidal antibodies) have the highest risk for developing overt hypothyroidism. Therefore, these patients will require L-thyroxine treatment. In patients with TSH < 12 mU/L, the indication for therapy depends on the etiology, on risk factors and concomitant diseases (e.g. strumectomy, coronary heart disease, depression, infertility). Subclinical hyperthyroidism (TSH suppression syndrome) is characterized by normal thyroid hormone concentrations but diminished serum TSH. Most frequently, this disorder is caused by exogenous L-thyroxine treatment. The endogenous form of subclinical hyperthyroidism mainly caused by nodular goiter has a prevalence of up to 20% in patients with large goiters. In patients with subclinical hyperthyroidism, there is an increased risk for development of atrial fibrillation and for a decrease in bone mass in postmenopausal women. In the majority of patients measurable TSH levels can be detected before or after stimulation with TRH. This formally excludes overt hyperthyroidism in such patients. Frequently, there is no need for treatment but follow-up is important. However, in patients with subclinical hyperthyroidism associated with atrial fibrillation a therapy with antithyroid drugs, beta-blockers or radioiodine must be considered.

Diagnosis, Differential↗
PubMed1998

[Long-term study of subclinical hypothyroidism: spontaneous course and predictors of manifest hypothyroidism].

The syndrome of subclinical hypothyroidism is frequent and predominantly affects females over 40. Only limited data on its natural course is available. It was the aim of our prospective trial to analyze the spontaneous evolution of this syndrome, to identify risk factors of the development of overt hypothyroidism and to develop guidelines for the management of such patients. 154 female patients were followed over a mean observation period of 10 years. After 10 years, 34% had developed overt hypothyroidism, 57% remained in the subclinical stage, and in 9% thyroid function had normalized. The initial grading of TSH-concentration (< 6 mU/l, 6-12 mU/l, > 12 mU/l) was highly predictive for thyroid failure: 7.3%, 25% and 78%, respectively, overt hypothyroidism occurred. Further risk factors for thyroid failure included an impaired thyroid reserve (T3-stimulation after TRH) and elevated titers of microsomal antibodies. We therefore recommend to controlling patients with a TSH-concentration < 6 mU/l, start thyroxine hormone replacement therapy in patients with a TSH-concentration > 12 mU/l and, depending on the additional risk factors, either controlling or treating patients with a TSH-concentration of 6-12 mU/l.

Adolescent↗
PubMed1998

[Hyperthyroidism and thyroid carcinoma--coincidence or association?].

In a series of 617 patients undergoing thyroidectomy, 86 cases (13.9%) were identified as having hyperthyroidism. Forty-nine out of these 86 patients suffered from Graves disease. Histopathologic evaluation revealed a low grade papillary thyroid carcinoma in two out of the 86 specimens from the hyperthyroid patients. Therefore, the incidence of malignancy among all our patients with hyperthyroidism is 2.3% and among those with Graves disease is 4.1%. Patients with hyperthyroidism and concurrent nodular or diffuse goiter are at possible risk for thyroid carcinoma. The indication for surgical resection is given in these cases where the success of thyroistatic treatment is low and where patients are at higher risk for thyroid malignancy. In a short review of the literature, we discuss the coincidence of the two pathologic entities and their possible association.

Carcinoma, Papillary↗
PubMed1998

[Ultrasensitive TSH screening for detection of thyroid gland dysfunctions in women of a medical ambulatory care patient group].

This aim of the study was to identify the prevalence of unsuspected thyroid dysfunction in a female population attending a medical primary care unit (case-finding study). A TSH assay of the third generation was used as a screening test. The overall prevalence of unsuspected thyroid dysfunction in 1061 female patients was 2.5% (0.5% overt hyperthyroidism, 0.3% overt hypothyroidism, 0.5% subclinical hyperthyroidism, and 1.2% subclinical hypothyroidism). The prevalence of thyroid disease is clearly age dependent with 4.3% over the age of 40 and 5.9% for 50-60 year-olds. The ratio for females below 40 and over 40 was 10.75 (Odds ratio, p < 0.0001). We conclude from our study and from the literature that TSH screening as a case-finding strategy is indicated, and also seems cost-effective, in women over 40 years of age.

Adolescent↗
PubMed1997

Estimation of tissue hypothyroidism by a new clinical score: evaluation of patients with various grades of hypothyroidism and controls.

The classical signs and symptoms of hypothyroidism were reevaluated in the light of the modern laboratory tests for thyroid function. We analyzed 332 female subjects: 50 overt hypothyroid patients, 93 with subclinical hypothyroidism (SCH), 67 hypothyroid patients treated with T4, and 189 euthyroid subjects. The clinical score was defined as the sum of the 2 best discriminating signs and symptoms. Beside TSH and thyroid hormones, we measured parameters known to reflect tissue manifestations of hypothyroidism, such as ankle reflex relaxation time and total cholesterol. Classical signs of hypothyroidism were present only in patients with severe overt hypothyroidism with low T3, but were rare or absent in patients with normal T3 but low free T4 or in patients with SCH (normal thyroid hormones but elevated basal TSH; mean scores, 7.8 +/- 2.7 vs. 4.4 +/- 2.2 vs. 3.4 +/- 2.0; P < 0.001). Assessment of euthyroid subjects and T4-treated patients revealed very similar results (mean score, 1.6 +/- 1.6 vs. 2.1 +/- 1.5). In overt hypothyroid patients, the new score showed an excellent correlation with ankle reflex relaxation time and total cholesterol (r = 0.76 and r = 0.60; P < 0.0001), but no correlation with TSH (r = 0.01). The correlation with free T4 was r = -0.52 (P < 0.0004), and that with T3 was r = -0.56 (P < 0.0001). In SCH, the best correlation was found between the new score and free T4 (r = -0.41; P < 0.0001) and TSH (r = 0.35; P < 0.0005). Evaluation of symptoms and signs of hypothyroidism with the new score in addition to thyroid function testing is very useful for the individual assessment of thyroid failure and the monitoring of treatment.

Adult↗
PubMed1996

[Detection of RET-proto-oncogene mutations in the diagnosis of Type 2 endocrine neoplasia (MEN 2)].

We have analyzed 95 blood- and 25 paraffin-derived DNA samples of 120 individuals from Switzerland (MEN 2 family members and patients with medullary thyroid carcinoma or pheochromocytoma) for the presence of RET protooncogene mutations in exons 10, 11, 13, 14 and 16, where recently germline point mutations have been identified in more than 95% of patients with MEN 2A, familial medullary thyroid carcinoma (FMTC) and MEN 2B. Molecular DNA screening of samples was performed by non-radioactive single strand conformation polymorphism (SSCP) and heteroduplex gel electrophoresis method followed by mutation analysis of PCR products by direct cycle sequencing using an automated DNA sequencer. We identified 12 MEN 2A/FMSC and 6 MEN 2B families with 29 gene carriers. Ten different types of mutations were identified in the MEN 2A/FMTC families (620 Cys-->Arg, 618 Cys-->Ser, Gly, 611 Cys-->Tyr; 634 Cys-->Arg, Tyr, Trp, Phe, Ser, Gly) and all 6 MEN 2B families had a 918 Met-->Thr point mutation. Our results indicate that PCR-based DNA testing for RET point mutations is a rapid, accurate and reproducible method of identifying MEN 2 gene carriers using blood or tissue DNA. Early detection of gene carriers allows preventive thyroidectomy without neck dissection or parathyroid transplantation, and non-gene carriers can be released from biochemical testing. Furthermore, it is shown that the distribution and localization of RET mutations in MEN 2 families from Switzerland concur with combined results of larger series and that a "founder effect" of MEN 2 can be excluded for this country.

Adrenal Gland Neoplasms↗
PubMed1995

Impaired action of thyroid hormone associated with smoking in women with hypothyroidism.

BACKGROUND: The effect of smoking on thyroid function is controversial, and its effect on thyroid hormone action is unknown. We investigated the effects of cigarette smoking in women with various grades of hypothyroidism and in normal women. METHODS: We studied 138 normal women and 135 women with primary hypothyroidism, of whom 84 had subclinical hypothyroidism and 51 overt hypothyroidism. Sixty of the women with hypothyroidism were reevaluated during thyroxine therapy. The women were categorized as smokers or nonsmokers according to their responses to a questionnaire. Thyroid function was evaluated by measurements of serum thyrotropin, free thyroxine, and triiodothyronine. Peripheral thyroid hormone action was assessed by a clinical score and measurements of ankle-reflex time and serum lipids and creatine kinase. RESULTS: Among the women with subclinical hypothyroidism, the smokers had a higher mean (+/- SD) serum thyrotropin concentration (21.3 +/- 16.6 vs. 12.7 +/- 7.2 mU per liter, P = 0.004) and a higher ratio of serum triiodothyronine to serum free thyroxine (by 30 percent, P = 0.003) than the nonsmokers. Their serum concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol were higher (by 16 percent, P = 0.013; and 28 percent, P = 0.003, respectively). Among the women with overt hypothyroidism, the serum concentrations of thyrotropin, free thyroxine, and triiodothyronine were similar in the smokers and nonsmokers. As compared with the nonsmokers, the smokers had a clinical score indicating a greater degree of hypothyroidism (P < 0.001), higher serum concentrations of total and LDL cholesterol (by 25 percent, P < 0.001; and 24 percent, P = 0.002, respectively), longer ankle-reflex time (by 25 percent, P < 0.001), and higher serum concentrations of creatine kinase (by 236 percent, P < 0.001). There were dose-response relations between smoking and serum concentrations of total and LDL cholesterol, serum creatine kinase concentrations, and ankle-reflex time in the women with overt hypothyroidism, and between smoking and serum concentrations of total and LDL cholesterol in the women with subclinical hypothyroidism. CONCLUSIONS: Smoking increases the metabolic effects of hypothyroidism in a dose-dependent way. This may be explained by alteration of both thyroid function and hormone action.

Adult↗
PubMed1995

Parathyroidectomy in primary hyperparathyroidism: preoperative localization and routine biopsy of unaltered glands are not necessary.

BACKGROUND: An assessment was made of operative risk and outcome after parathyroidectomy for primary hyperparathyroidism. METHODS: A retrospective study was conducted in a single center university hospital in Switzerland. The 173 patients (130 women and 43 men) ranged from 17 to 89 years of age (mean, 62.0 years). No routine preoperative localization methods were used for primary neck exploration. Parathyroidectomy was performed under general anesthesia. No routine use was made of intraoperative biopsy of glands whose macroscopic appearance was normal. The 173 patients underwent 179 operations (170 primary and 9 secondary interventions). Resection of a single gland was performed in 127 cases (73.4%) and of two glands in 36 cases (20.8%). Subtotal parathyroidectomy (3 1/2 glands) was performed in 10 cases (5.8%). RESULTS: Of 170 patients with primary intervention, 164 (96.5%) were normocalcemic after operation. Six of 170 patients (3.5%) underwent early reexploration. Three additional patients underwent late secondary procedures. These nine secondary operations were successful in seven patients (78%). At follow-up (mean, 24.7 months after operation) normocalcemia was noted in 163 of 171 patients (95.3%). Persistent and recurrent hyperparathyroidism occurred in 1.2% and 3.5% of patients, respectively. Permanent postoperative hypoparathyroidism was noted in 4% (six of seven patients underwent a subtotal parathyroidectomy for multiglandular hyperplasia). Operative morbidity and mortality were 2.3% and 0.6%, respectively. CONCLUSIONS: Our surgical strategy for treatment of primary hyperparathyroidism has proved to be safe with a favorable outcome in more than 95% of patients. This was possible without the routine use of preoperative localization studies and intraoperative biopsy of macroscopically normal glands. Routine biopsy of normal-appearing glands seems to be unnecessary and may increase the risk of hypoparathyroidism.

Adolescent↗
PubMed1994

[Combined endocrine autoimmune syndrome--incidence, forms of manifestation and clinical significance].

UNLABELLED: In a retrospective case finding study we collected data from patients with polyglandular autoimmune syndrome type II (PGAS Type II) who had been treated in our endocrine outpatient clinic between 1975 and 1989. 31 adult patients (25 females and 6 males) fulfilled the criteria for PGAS Type II (association of autoimmune endocrine disease with at least one other--usually endocrine--autoimmune disease or autoantibodies against another organ). Among these patients, 18 had hypothyroidism due to autoimmune thyroiditis, 8 were hyperthyroid (Graves' disease), and 4 had silent autoimmune thyroiditis (without thyroid dysfunction). Insulin dependent (type I) diabetes mellitus (IDDM) was seen in 11, Addison's disease in 7, primary hypogonadism in 5, vitiligo in 6 and pernicious anemia in 5 cases. The presence of antiparietal cell antibodies was demonstrated in 21 of 30 investigated patients. These patients also showed other evidence of autoimmune gastritis, such as increased gastrin (in 10 out of 13), diminished vitamin B12 levels (6 out of 13), atrophic gastritis (9 out of 9), pernicious anemia (6 out of 30) and funicular myelosis (2 out of 30). CONCLUSION: The most common endocrine diseases in our patient group were autoimmune thyroid diseases (97%) followed by IDDM (35%) and Addison's disease (23%). A high percentage (70%) of our subjects had elevated titers of antiparietal cell antibodies. Polyglandular autoimmune syndrome must be suspected in all patients with autoimmune endocrine disease, especially in the presence of relatives suffering from PGAS. Patients at risk should be screened regularly by measuring thyrotropin (ultrasensitive assay), fasting blood glucose levels, and by checking red blood count and antiparietal cell antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Surgery in pheochromocytoma. 12-year development].

Hypertension (sustained and/or paroxysmal) is the most common symptom of pheochromocytoma. Correct evaluation nearly always leads to the diagnosis, and complete surgical excision is the definitive treatment. Our study deals with preoperative evaluation, operative morbidity and long-term results after surgery. During the 12-year period (1981-1992) 31 patients (48 years, 25-85) with pheochromocytoma were treated at our institution. The selected preoperative management was reviewed on the basis of patient records. Long-term follow-up was carried out consecutively and personally. All patients received alpha-adrenergic blockers to achieve preoperative normotension and volume repletion. All resections were performed by laparotomy; two of the early cases were extended into the chest. 27 of 29 patients (93.1%) had elevated levels of urinary vanillylmandelic acid; a similar sensitivity was noted in the urinary catecholamines (24/26 = 92.3%). In anatomical localization CT-scan was accurate in 100% (27/27). MIGB scintigraphy was of help in 21 of 23 (91.3%) and, in the most recent patients, MRI was helpful in 3 of 3 (100%). No patient died during the first 30 days after surgery. One patient developed an anaphylactic reaction after cephalosporin administration (morbidity: 3.2%). 2 patients (6.4%) with malignant pheochromocytoma developed a recurrent tumor during the follow-up period. Resection of pheochromocytomas by laparotomy has a low perioperative morbidity and mortality after standardized preparation. A positive MIBG scintigraphy allows extra-adrenal localization. Better resolution and multiplanar imaging are the advantages of MRI. Perioperative management and new imaging techniques--eliminating arteriography and venous sampling among others--have simplified surgical treatment and improved its safety.

Adrenal Gland Neoplasms↗