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J J Staub

Publications and source records attributed to J J Staub.

At least 19 recordsLinked to original sources

[Evaluation of TSH suppression using a 3d-generation TSH assay: diagnostic and therapeutic consequences].

UNLABELLED: We measured basal and TRH-stimulated TSH values with a 3rd generation assay in patients under suppressive thyroxine (T4) therapy for thyroid carcinoma or goiter and in patients with overt hyperthyroidism. All hyperthyroid patients had undetectable basal TSH levels (< 0.01 mU/l). In patients on suppressive T4 treatment basal TSH values were undetectable in 37.5% (= group A) and measurable in the intermediate range of 0.01-0.05 mU/l in 62.5% (= group B). After TRH administration there was no TSH increase in the hyperthyroid patients (< 0.01 mU/l in 100%). T4-treated patients of group A showed no relevant TSH stimulation in 58% (peak < or = 0.05 mU/l = total TSH suppression). An increase of > 0.05 mU/l could be measured in 42% of group A and 100% of group B (= subtotal TSH suppression). Many of these TSH values measured by a 3rd generation assay are in the undetectable range for most of the commercially available 2nd generation assays (< 0.10 mU/l). CONCLUSION: TSH assay of the 3rd generation decisively improves the diagnosis of hyperthyroidism and probably also borderline hyperthyroidism. Against the background of increased risk of osteoporosis and cardiac function disorders as a result of suppressive T4 treatment, our results suggest the following practical therapeutic guidelines: total TSH suppression with the risk of iatrogenic hyperthyroidism should be confined to high risk patients (eg with metastatic thyroid cancer). Where the risk is low, however (thyroid cancer with favourable prognosis, goiter, goiter prophylaxis), only subtotal TSH suppression is indicated.

Adult

[Long-term follow-up after thyroidectomy: incidence of recurrent goiter and functional results].

We analyzed the postoperative longterm results after strumectomy for sporadic goiter in 26 patients. The follow-up time was 25.1 +/- 14.7 (7-58) years (x +/- SD, extremes). Actual goiter recurrence without need for surgery was observed and sonographically confirmed in 3 patients, and 1 patient without actual recurrence had had a second strumectomy for goiter recurrence in the past. Hence the overall frequency of goiter recurrence in this study is 15% (4/26 patients). The patients with a present recurrence (n = 3) were significantly younger at the time of operation (29 +/- 11, 14-41 years) than those without recurrence (n = 23; 45 +/- 11, 28-60 years; p < 0.001). No patient had clinical endocrine dysfunction. Only four patients had been treated with thyroxine and they all suppressed TSH in the presence of euthyroid FT4 and T3 levels without present recurrence of goiter. 22 patients had no thyroid hormone prophylaxis and in only four of them (18%) was observed a recurrence in the longterm follow-up without endemic iodine deficiency. Prophylaxis with thyroid hormones often is not required in low risk patients operated upon and carefully controlled after strumectomy from non-iodine-deficient regions. Patients at risk for recurrence (second strumectomy, family history, elevated TSH, clinical or sonographic evidence for thyroid growth) should be considered for thyroxine therapy with regular follow-up.

Adolescent

[Does isolated TSH elevation need treatment? Study of risk factors for the development of manifest hypothyroidism].

Isolated elevations of basal TSH levels are frequently observed in the general population. In a prospective study we analyzed the spontaneous evolution of thyroid function over time in such patients. The mean observation period was 5.4 (0.5-12) years. During the follow-up period 20% of these patients developed overt hypothyroidism. The risk of developing hypothyroidism was determined primarily by the initial TSH value and an additive effect was found for the thyroid antibodies and the thyroidal reserve (delta-T3) after TRH stimulation (Cox proportional hazard model). The cumulative risk for overt hypothyroidism after 10 years was only 22% for a mean TSH level of 12 mU/l for patients with negative thyroid antibodies and a good thyroidal reserve (low-risk), but increased to 63% for patients with positive antibodies and impaired T3 reserve (high-risk). Therefore, patients with isolated elevation of TSH can be divided into two subgroups according to the results of TSH, antibody status and T3 reserve: (1) In the "low-risk group" with good prognostic factors the patients should be followed up by periodic laboratory testing only (TSH, FT4, every 2-3 years). (2) In the "high-risk group" with clearly abnormal parameters, however, frequent controls are mandatory (every 6-12 months) or treatment with thyroxine may be indicated.

Adult

Spectrum of subclinical and overt hypothyroidism: effect on thyrotropin, prolactin, and thyroid reserve, and metabolic impact on peripheral target tissues.

PURPOSE: Subclinical hypothyroidism is found in about 7.5% of females and in about 3% of males. It appears to be a risk factor for atherosclerosis and for coronary heart disease and can affect various other target organs. The morbidity and clinical significance of subclinical hypothyroidism are controversial. Therefore, we evaluated the metabolic impact of progressive thyroid failure in patients with various degrees of hypothyroidism compared with control subjects. PATIENTS AND METHODS: We investigated 86 female patients with the whole spectrum of subclinical hypothyroidism (n = 69) and of overt hypothyroidism (n = 17) and 52 euthyroid women as controls. All subjects underwent full medical and endocrine evaluations (including measurements of thyrotropin [TSH], TSH beta- and alpha-subunits, and prolactin before and after oral administration of thyrotropin-releasing hormone [TRH]) as well as lipid profiles and different tests of peripheral thyroid hormone action. All hypothyroid patients were divided into five categories according to disease severity: grades I to III (subclinical hypothyroidism, with normal thyroxine [T4] levels) and grades IV and V (overt hypothyroidism, with diminished T4). RESULTS: In grade I subclinical hypothyroidism (basal TSH below 6 mU/L), we found significant changes in the clinical index (p less than 0.05), apoprotein A-I level (p less than 0.05), and stimulated prolactin level after oral TRH (p less than 0.001). The findings were similar in grade II (TSH 6 to 12 mU/L). Further changes could be demonstrated in grade III (TSH above 12 mU/L) with a definite elevation of ankle reflex time (p less than 0.001), serum myoglobin level (p less than 0.01), and, to a lesser extent, creatine kinase (p greater than 0.1). The mean low-density lipoprotein cholesterol (LDL-C) level showed an increase of 18%, which was not significant because of marked individual variations (p = 0.15). The frequency of elevated LDL-C levels was definitely higher in patients with grade III disease compared with the controls (42.9% versus 11.4%, p less than 0.05) and with patients with grades I and II disease. Total cholesterol, triglycerides, apoprotein B, and the systolic time intervals (pre-ejection period, corrected for heart rate [PEPc]) were clearly elevated only in overt hypothyroidism (grades IV and V) (p less than 0.01). CONCLUSION: Subclinical hypothyroidism has significant effects on some peripheral target organs at an early stage (grades I and II), but affects LDL-C, skeletal muscle, and myocardial contractility only at a later stage (grades III, IV, and V). Our data of elevated LDL-C in grade III subclinical hypothyroidism provide a likely pathophysiologic explanation for the reported association of coronary heart disease with this syndrome. The impact of increased prolactin secretion, observed in subclinical hypothyroidism, on gonadal function and infertility has yet to be clarified. Therapy with thyroxine should be recommended in at least some patients with subclinical hypothyroidism. Patients with high TSH levels (above 12 mU/L) will require treatment because of the metabolic effects on several target organs. Before treatment is advocated in all patients with subclinical hypothyroidism, the benefits and long-term side effects of thyroid hormone therapy should be clarified by prospective studies in larger groups of patients.

Administration, Oral

[The diagnosis of Cushing's syndrome. Results of diagnostic assessment of 20 patients with Cushing's syndrome of variable etiology (1979-1989)].

In the light of 20 cases of Cushing's syndrome the currently used diagnostic strategies are presented. For initial screening the classical dexamethasone suppression test using 1 mg dexamethasone p.o. and 24-hour urinary extraction of free cortisol were used, and diagnosis was confirmed using the 2 mg dexamethasone suppression test for two days. All three tests had a sensitivity of 100% in these 20 patients. Etiological evaluation was performed using basal ACTH plasma concentration measurement and the more recently available stimulation tests using corticotropin-releasing factor (CRF): in cases with suspected pituitary-hypothalamic etiology, selective catheterisation of the sinus petrous inferior with simultaneous blood sampling for measurement of plasma ACTH concentration was performed. Detailed etiological diagnosis is important in Cushing's syndrome since therapeutic measures differ widely: the etiologies in the 20 patients with Cushing's syndrome were: central Cushing's disease (microadenoma in 11, pituitary carcinoma in 1), adrenal carcinoma (3), adrenal adenoma (1), adrenal hyperplasia (1), ectopic ACTH production (2) and alcohol-induced Cushing's syndrome (1). The stepwise procedure in screening and diagnosis of the various etiologies of Cushing's syndrome are presented and the results of the 20 patients compared with the literature.

Adrenal Cortex Function Tests

Thyroglobulin production by malignant thyroid tumors. An immunocytochemical and radioimmunoassay study.

Four hundred thirty surgical and biopsy specimens of malignant thyroid tumors of 323 patients were analyzed by histologic and immunocytochemical examination for their thyroglobulin (TG) content. Almost 95% of the differentiated thyroid carcinomas of follicular origin contained immunoreactive TG. The authors could not demonstrate TG in anaplastic carcinomas. Postoperative follow-up and serum TG determinations were available for 111 athyroid patients. Serum TG was elevated in five patients with metastatic or recurrent moderately differentiated follicular carcinoma, in two patients with metastasizing papillary, and in one patient with anaplastic carcinoma. Four patients had detectable serum TG levels without clinical and radiologic evidence of recurrence or metastases. In addition to conventional histologic examination, immunocytochemical demonstration of TG is a reliable and valuable aid in the diagnosis, classification, and determination of the grade of differentiation of malignant thyroid tumors. From this the pathologist can provide a pathologic basis for postoperative patient management.

Adenocarcinoma

[Value of the oral TRH test for the evaluation of thyroid function in impaired TSH reserve. Preliminary report].

Oral TRH (40 mg) exerts a marked and protracted stimulatory effect on TSH release. The potency of oral TRH in stimulating TSH and T3 was evaluated in 26 euthyroid patients with absent or impaired TSH response in the i.v. TRH test (200 micrograms). All were given i.v. and oral TRH at an interval of at least 3 days. Based on the response to i.v. TRH, they were divided into "non-responders" (TSH increment less than 1.0 microU/ml) and "low-responders" (TSH increment 1.0--3.7 microU/ml). The results were compared with those in 11 patients with overt hyperthyroidism. 10 "non-responders" were additionally tested with 400 micrograms TRH i.v. to study the effect of a supramaximal dose. Most patients unresponsive to i.v. TRH had a pronounced response to oral TRH (TSH increment 0.1 +/- 0.1 and 4.0 +/- 0.9 microU/ml (mean +/- SEM) respectively, p less than 0.005). The "low-responders" in the i.v. test had a significantly enhanced response to the oral dose (2.4 +/- 0.3 and 7.6 +/- 1.6 respectively, p less than 0.005). The euthyroid patients with treated Graves' disease with a weak response to i.v. TRH showed a distinct response to the oral dose. On the other hand, plasma TSH in patients with overt hyperthyroidism failed to increase either after intravenous or after oral TRH. In contrast to oral TRH, the supramaximal dose of 400 micrograms i.v. TRH did not enhance the TSH-response in the "non-responders". In most patients with absent or impaired response to i.v. TRH, a marked increase in T3 could be demonstrated (0.5 +/- 0.1 ng/ml and 0.6 +/- 0.1 ng/ml in "non-responders" and "low-responders" respectively, p less than 0.01); thus, oral administration allows simultaneous stimulation of TSH and triiodothyronine. Oral TRH can be considered the test of choice for the investigation of patients with diminished TSH reserve.

Administration, Oral

[Ectopic hormone formation and tumor markers in bronchial neoplasms].

Carcinoma of the bronchus can produce several polypeptide hormones and therefore has the capacity to cause most syndromes of endocrine hyperfunction. All pituitary hormones can be synthesized ectopically; furthermore, the production of hormones from the hypothalamus (CRF), the placenta (HCG, HPL) and the C-cells of the thyroid (calcitonin), as well as parathormone and prostaglandins has been described. The paraneoplastic syndrome may often be more dangerous for the patient than the tumor growth itself, and can lead to early death. On the other hand, it may allow the early detection of an unsuspected tumor. The ectopic hormones and other nonendocrine proteins and peptides can be used as tumor markers, and can demonstrate the effect of treatment and early recurrence or metastases. An ideal tumor marker should have the following characteristics: 1. production exclusively by neoplastic tissue, 2. direct correlation with tumor size, 3. substances common to all tumor types ("large spectrum tumor marker") although specific tumor markers for special tumors should be available, 4. the assays must be easy and automation should be possible. At present no tumor marker satisfies all these conditions. The measurement of several tumor markers and the use of discriminant analysis may extend their diagnostic value and open the way for biochemical detection of cancer in the future.

Adrenocorticotropic Hormone

The short metyrapone test: comparison of the plasma ACTH response to metyrapone and insulin-induced hypoglycaemia.

Plasma ACTH levels in response to metyrapone and insulin hypoglycaemia were compared in subjects with normal pituitary-adrenal function. After a single dose of 2 g of metyrapone given with a snack at midnight, the ACTH level was 468 ng/l +/- 66 )SEM) at 07.30 h the next morning (mean increment approximately nine fold over normal morning values). After insulin-hypoglycaemia the peak ACTH level was 369 ng/l +/- 31 (SEM). Peak ACTH levels greater than 200 ng/l were achieved in twenty of twenty-one (95%) subjects after metyrapone and twenty of twenty-four (83%) after insulin. No major side effects were noted after metyrapone. It is concluded that the short single-dose metyrapone test produces at least as strong and consistent a stimulus to ACTH release as the standard insulin-hypoglycaemia test in normal subjects. A direct assay of ACTH avoids misinterpretations which are inherent in a judgement based on compound S increase only. The short test has significant practical advantages over the classical metyrapone test, and provides a convenient and sensitive method of assessing the negative feedback ACTH control mechanism. It may be particularly useful in detecting minor degrees of pituitary suppression. The value of this test in clinical practice for the investigation of patients with hypothalamic-pituitary diseases in comparison to the classical tests of ACTH stimulation has yet to be demonstrated.

Adolescent

[Biology of breast cancer: current approaches to new treatment modalities].

After years of progress, there appear to be few new developments in the treatment of breast cancer at the present time. Aspects of breast cancer are discussed which might offer new therapeutic possibilities. The rather schematic management of the patient with breast cancer is less than well matched with the variable biology and the multitude of factors influencing risk and prognosis. Epidemiological, hereditary, and environmental, as well as endocrinological, immunological, and psychoneurological variables are believed to determine the spontaneous course of the disease and the therapeutic results. One way of improving treatment results is better evaluation of such biological factors in a given patient and variation of treatment plans according to individual needs.

Adolescent

[Sex hormone binding globulin (SHBG), a new metabolic in vitro thyroid function test].

SHBG (sex hormone binding globulin) is a carrier protein for the sex hormones testosterone and estradiol with a molecular weight of about 95000 dalton. It can be used as a metabolic test of thyroid function. SHBG was measured by the adsorption method of Mickelson and Petra; the SHBG contained in serum is incubated with 3H-5alpha-dihydrotestosterone and adsorbed to a cellulose filter. Thirty-eight female patients with hyperthyroidism before treatment had markedly elevated levels of SHBG (x +/- SD: 4.85 +/- 2.4 microgram DHT/100 ml) compared with normal controls (1.50 +/- 0.57; p is less than 0.001). A good correlation between the thyroid hormones and SHBG could be domonstrated which was better for T3 than for T4:r =0.76 (p is less than 0.001) for T3 and r= 0.65 (p is less than 0.001) for T4. This agrees with the clinical finding that the circulating T3 level is a better index of the metabolic severity of thyrotoxicosis than T4. After radioiodine treatment SHBG returns to normal values in euthyroid patients (1.38 +/- 0.8; n = 15) and remains elevated in persistent hyperthyroidism (3.99 +/-1,6; n = 67). Even in patients with persistent biochemical hyperthyroidism who are completely euthyroid on clinical examination, SHBG remains high. Despite lack of evidence of clinical hyperthyroidism, this metabolic test demonstrates the biologic significance of merely biochemical hyperthyroidism. Estimation of SHBG as a metabolic thyroid function test in vitro is of special value for the evaluation of patients showing discrepancies between the clinical and biochemical states and for borderline hyperthyroidism.

Carrier Proteins

Thyroid-stimulating hormone (tsh), triiodothyronine (t3) and thyroxine (t4) response to intravenous and oral stimulation with synthetic thyrotropin-releasing hormone (trh) in young healthy adults.

TSH, T3 and T4 response to stimulation with thyrotropin releasing hormone (TRH) has been investigated in 24 young healthy adults after intravenous injection and in 25 young healthy adults upon oral application of 40 mg of TRH. After intravenous injection the TSH concentration raises from a mean of 1.6 to a mean maximum of 11.7 muU/ml. A statistically significant sex difference could not be found. T3 shows a statistically significant increase which is however too small to be of diagnostic value in an individual test. After oral stimulation with 40 mg of TRH, TSH rises to a slightly higher maximum of 13.2 muU/ml after 3 h. The T3 increase from 1.5 to 2.19 ng/ml is significant and considerably higher than after intravenous stimulation. The thyroxin increase is statistically significant. The present results compare well with previously published data for intravenous stimulation. The oral route of TRH application has not yet been widely used and the present series establishes the normal response in young healthy adults. Repetitive stimulation with three times 40 mg of TRH leads to a decrease in TSH stimulation which reaches 5.8 muU/ml 3 h after the third dose. This is in contrast to a comparable increase in plasma T3.

Administration, Oral