Biomedical subjects
J J Staub
Publications and source records attributed to J J Staub.
[In vitro and in vivo diagnosis of borderline hyperthyroidism].
The evaluation of "preclinical hyperthyroidism" includes laboratory and in vivo tests. The measurements of circulating total thyroxine (T4) and total triiodothyronine (T3) depend on the plasma concentration of thyroid hormone binding proteins. A simple approach, the calculation of the free T3 index (FT3I) and the augmented FT3I (aFT3I) from total T3 and T3-resin uptake corrects the total serum T3 for variation in thyroid hormone binding capacity. In a group of 95 patients with border-line elevated T3 levels we have correlated the results of FT3I and aFT3I with clinical, biochemical and radioisotope findings. It was shown that in patients with moderate elevation of T3 the FT3I and aFT3I are capable of distinguishing clearly between the euthyroid and hyperthyroid range. To detect an imbalance in the hypothalamic-pituitary-thyroid axis either the T4-suppression test or the TRH-test could be used. In 60 patients with "preclinical hyperthyroidism" we have compared both of them. In 77% of the patients the T4-suppression test and i.v. TRH-test provided concomitant results. In 13 patients without response to the i.v. TRH-test 7 showed a definite (more than 50%) and 6 a partial suppression (10-40%) of radioiodine uptake. This suggests that there is no sharp distinction between hyper- and euthyroidism.
[Diagnosis and therapy of pituitary adenomas].
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[A case from general practice (7)].
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[Thyroid hormones and thyroid reserve in preclinical hypothyroidism].
Preclinical hypothyroidism (i.e. basal thyroxine within the normal laboratory range, basal TSH normal or elevated and exaggerated TSH response to TRH) is a biochemical constellation of uncertain clinical relevance. The oral TRH test with simultaneous measurements of TSH and thyroid hormones before and 3 h after 40 mg TRH provides information about both pituitary and thyroid reserve. In a group of female patients with preclinical hypothyroidism, basal thyroxine but not triiodothyronine was found to be clearly diminished compared with a group of healthy female controls, indicating a slight thyroid hormone deficiency. Furthermore, a progressively reduced thyroid reserve of T4 and especially of T3 was seen to be closely related to elevation of basal TSH as an expression of thyroid cell insufficiency. These data emphasize the clinical importance of TSH elevation despite normal thyroxine levels as a better individual sign of impending primary hypothyroidism.
[Lipid changes as a possible risk factor in preclinical hypothyroidism. Preliminary report].
In a prospective study the lipids have been investigated in patients with preclinical hypothyroidism (normal values for thyroxine and free thyroxine index but exaggerated response to oral TRH and normal or elevated basal TSH). This group was compared with euthyroid normal subjects and patients with overt hypothyroidism. Cholesterol and triglycerides were normal in patients with preclinical hypothyroidism, in contrast to the increased levels in overt hypothyroidism. HDL cholesterol showed no difference in either group. Lipid electrophoresis on agarose with densitometric analysis revealed elevation of low density lipoproteins (LDL) and diminution of high density lipoproteins (HDL) in both groups of hypothyroid patients. The changes in LDL and HDL are both known coronary risk factors and could explain the reported prevalence of coronary disease in the early stages of thyroid failure. These preliminary findings need further confirmation.
[Atrioventricular block after carotid pressure in hypothyroidism: normalisation after substitution treatment (author's transl)].
Severe auto-immune hypothyroidism, probably after hyperthyroidism, was diagnosed in a 79-year-old woman with hypothyroidism (T3 and T4 immeasurably low) without the classical signs of myxoedema heart. On carotid sinus pressure transitory first degree AV block occurred and, on one occasion, complete AV block. This response disappeared after substitution treatment for four weeks with 50 microgram L-thyroxine. Further examination half a year later, on a maintenance of 75 microgram thyroxine, also gave a negative response to carotid sinus pressure.
Ectopic hormone production by endocrine tumors: localization of hormones at the cellular level by immunocytochemistry.
Clinical and laboratory data, histologic, electron microscopic and immunocytochemical findings of the tumors of eight patients suffering from Cushing's syndrome and of one patient with hypercalcemia are described. The unlabeled antibody enzyme method was used for the detection of insulin, glucagon, somatostatin, pancreatic polypeptide, corticotropin, beta-lipotropin, calcitonin, parathyroid hormone, and gastrin. Ectopic Cushing's syndrome was caused by pancreatic endocrine tumors, medullary thyroid carcinoma, a bronchial, a gastric and a thymic carcinoid, and a carcinoid of the mediastinum. Hypercalcemia in one patient was related to a pancreatic endocrine tumor. After surgery the clinical symptoms disappeared in two patients, but persisted or relapsed in five patients. ACTH-immunoreactivity could be demonstrated in six of eight tumors; calcitonin-immunoreactivity was found in the tumor of the patient suffering from hypercalcemia. ACTH-immunoreactivity could be localized to secretory granules by immunoelectron microscopy, and the presence of ACTH and beta-LPH in the same tumor cells could be shown in one pancreatic tumor. A combination of production of orthotopic and ectopic hormones was found in one, and secretion of two ectopic hormones was detected in another pancreatic endocrine tumor.
[Effect of a standardized ginseng extract on general well-being, reaction time, lung function and gonadal hormones].
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[Metabolic evaluation and etiology of "preclinical hypothyroidism": a preliminary report].
The TRH test, using synthetic TRH (TSH-releasing hormone) is the most sensitive test for the assessment of thyroid function. It may show elevated basal TSH and/or an exaggerated TSH response to TRH, despite normal thyroid hormone levels (T4, FT4I, T3). This condition is termed "preclinical hypothyroidism" (pc hypo). Thyroid hormone levels, the clinical index of Billewicz and metabolic impact on target tissues were studied prospectively in 38 pc hypo women and compared with 20 controls matched for age, weight and sex and 9 patients with overt hypothyroidism. For metabolic evaluation at the tissue site two new metabolic tests were developed and standardized, the systolic time intervals (STI) and sex-hormone-binding globulin (SHBG), which were used in conjunction with the ankle reflex time (ART) and lipids (cholesterol and triglycerides). The thyroid hormones T4, FT4I and T3 in pc hypo (77.8 +/- 2.0 nmol/l; 71.8 +/- 2.3; 1.92 +/- 0.07 nmol/l respectively; mean +/- SEM) were within the normal range (by definition), but significantly lower in comparison with the normal controls (105.5 +/- 3.3 nmol/l; 97.8 +/- 3.1; 2.91 +/- 0.12 nmol/l respectively; p less than 0.001). The clinical index and metabolic parameters SHBG and ART showed significant hypothyroid changes. STI (measured as preejection period) and lipids were not yet significantly different from the controls despite a hypothyroid tendency in many single individuals. The etiology in 144 patients with pc hypo (out of 2969 TRH tests) was analysed and the following causes identified: a) treated hyperthyroidism (38 after radioiodine, 5 after partial thyroidectomy, 5 after antithyroid drugs, 5 after radioiodine and partial thyroidectomy); b) simple goiter (7 without and 21 after partial thyroidectomy); c) autoimmune thyroiditis (27); d) other causes such as subacute thyroiditis (10); Riedel's thyroiditis (2), dyshormogenesis (2), drugs (6), treated toxic adenomas (2); e) etiology unknown or not identified (14).
[Dyspnea and thyroid gland diseases].
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[Improved thyroid diagnosis in borderline hyperthyroidism by determination of free T3 index].
The measurements of circulating total thyroxine (T4) and total triiodothyronine (T3) depend on the concentrations of thyroid hormone binding proteins, especially TBG. A simple approach, the calculation of free T3 index (FT3I) and augmented FT3I (aFT3I) from total T3 and T3-resin uptake, corrects the total serum T3 for variation in thyroid hormone binding capacity. In a group of 95 patients with borderline elevated T3 levels (3.0-4.5 nmol/l) we have correlated the results of FT3I and aFT3I with clinical, biochemical and radioisotope findings: in a subgroup of 23 euthyroid females taking oestrogens (group A1) and in 22 other patients with TBG elevations (independent of oestrogens, group A2) the results for total T3 were within the slightly hyperthyroid range (3.32 +/- 0.3 and 3.26 +/- 0.24 nmol/l respectively), but FT3I was always within the normal range. In contrast, FT3I was clearly elevated in 50 hyperthyroid patients (group B) compared to the total T3 (4.6 +/- 0.6 and 3.9 +/- 0.4 nmol/l respectively). An even better discrimination was obtained by calculation of augmented FT3I. It is concluded that in patients with moderate elevations of T3 the FT3I and aFT3I are capable of distinguishing clearly between the euthyroid and hyperthyroid range. The estimation is thus indicated in all patients with changes in thyroid hormone binding protein concentration and is of great value in confirming or ruling out the diagnosis of T3-toxicosis, T4-toxicosis and in all cases of "preclinical" or borderline hyperthyroidism.
[Effect of the dopamin antagonist metoclopramide on the TSH response after oral TRH in the TSH suppression syndrome ("preclinical hyperthyroidism"). Preliminary report].
The TSH response to exogenous TRH may be diminished or absent not only on overt hyperthyroidism but also in other situations, e.g. obesity, old age, multinodular goiter and depression. To elucidate the possible role of dopaminergic control of the TSH response to TRH in such patients, the oral TRH test (40 mg) was performed with and without simultaneous administration of metoclopramide (10 mg i.v.) in 20 patients known to have diminished or absent response to oral TRH (delta TSH < 1.0 mU/l). All patients had euthyroid basal levels of FT4-index and T3, and may thus be assumed to have "preclinical hyperthyroidism" (TSH suppression syndrome). In 11 patients the history suggested they were free of symptoms of mental depression, while 9 patients were considered by two independent examiners to have various degrees of depression. The TSH response to TRH in depressive patients was significantly increased when the dopamine-receptor-blocker metoclopramide (MCL) wad added. The delta TSH rose from 0.6 +/- 0.3 mU/l (SEM) without MCL to 8.8 +/- 1.8 mU/l with MCL (p < 0.002). In contrast, MCL failed to enhance the TSH response in non-depressive patients: the delta TSH was 0.7 +/- 0.3 mU/l without MCL, and with MCL 2.1 +/- 0.9 mU/l (n.s.). Thus the dopaminergic system appears to play a major role in modulating the sensitivity of the pituitary to TRH stimulation. In clinically doubtful situations, the combined metoclopramide-TRH test may be used to distinguish patients with a diminished or absent TSH response as a consequence of depression (central dopaminergic suppression) from patients with "preclinical hyperthyroidism" where the TSH response is suppressed by feedback control of TSH by thyroid hormones (thyroid autonomy).
Thyrotropin secretion in carcinoma of the thyroid.
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[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.
[Clinical aspects and physiopathology of ectopic hormone production].
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[Advantages of the oral TRH test for the diagnosis of thyroid gland diseases].
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[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.