SEPHADEX GEL FILTRATION ANALYSIS OF IMMUNOREACTIVE THYROTROPHIC HORMONE IN HUMAN URINE

1974 ◽  
Vol 62 (3) ◽  
pp. 657-662
Author(s):  
S. F. KUKU ◽  
P. HARSOULIS ◽  
J. L. YOUNG ◽  
N. D. QUE ◽  
T. R. FRASER

SUMMARY To assess whether urinary immunoassayable thyroid-stimulating hormone (TSH) differed from pituitary and serum TSH, urinary concentrates from two hypothyroid subjects were analysed by Sephadex G-100 gel filtration. The elution profiles, measured by radioimmunoassay, were then compared with those of neat sera from hypothyroid patients and human pituitary TSH preparations. The pituitary preparations and the hypothyroid serum were eluted as a comparable single symmetrical peak corresponding to that obtained from a highly purified radio-iodinated human TSH of pituitary origin; no evidence of 'big' TSH emerged. In contrast, however, the material eluted from the hypothyroid urine concentrates not only revealed an asymmetrical peak corresponding to that described above but several other minor peaks eluting later and probably corresponding to fragments of TSH. When human pituitary TSH was infused into two normal subjects, gel filtration analysis of concentrates from urinary samples obtained during and at fixed periods after the infusion revealed a single peak during the infusion but more peaks appeared with the later samples.

1974 ◽  
Vol 62 (3) ◽  
pp. 645-655 ◽  
Author(s):  
S. F. KUKU ◽  
P. HARSOULIS ◽  
J. L. YOUNG ◽  
T. R. FRASER

SUMMARY The urinary excretion of thyroid-stimulating hormone (TSH) has been measured by double antibody radioimmunoassay after concentration by dialysis followed by lyophilization. Among 30 normal subjects, the excretion was 5·6 ± 0·31 (s.e.m.) μu./h. No diurnal variation nor differences between sexes were discerned. In 14 primary hypothyroid subjects the urinary excretion was raised (P < 0·001) to 25·1 ± 3·3 μu./h. In 14 hyperthyroid and 7 hypopituitary subjects subnormal levels of 2·6 ± 0·2 and 2·5 ± 0·22 μu./h (P < 0·001) respectively, were found. Serum and urinary TSH concentrations were measured before, during and after an infusion of human pituitary TSH (MRC 70/9) in two subjects and showed a correlation. Urinary TSH measurement is thus a good discriminant between normal and hyperthyroid or hypopituitary patients.


2019 ◽  
Vol 9 (1) ◽  
pp. 40-48 ◽  
Author(s):  
Salman Razvi ◽  
Vicky Ryan ◽  
Lorna Ingoe ◽  
Simon H. Pearce ◽  
Scott Wilkes

Introduction: Serum thyroid-stimulating hormone (TSH) increases with age but target TSH is similar in younger and older hypothyroid patients on treatment. It is unknown if quality of life (QoL), hypothyroid symptoms and cardiovascular risk factors change in older hypothyroid patients treated to an age-appropriate reference range. Objective: To assess if a higher target serum TSH of 4.01–8.0 mU/L is feasible in, and acceptable to, older treated hypothyroid patients. Methods: A single-blind (participant) randomised controlled feasibility trial involving 48 hypothyroid patients aged ≥80 years on established and stable levothyroxine (LT4) therapy with serum TSH levels within the standard reference range (0.4–4.0 mU/L) was conducted. Standard (0.4–4.0 mU/L) or higher (4.1–8.0 mU/L) TSH target (standard TSH [ST] or higher TSH [HT] groups) LT4 for 24 weeks was administered. The outcome measures evaluated were thyroid function tests, QoL, hypothyroid symptoms, cardiovascular risk factors and serum marker of bone resorption in participants that completed the trial (n = 21/24 ST group, n = 19/24 HT group). Results: At 24 weeks, in the ST and HT groups, respectively, median (interquartile range) serum TSH was 1.25 (0.76–1.72) and 5.50 (4.05–9.12) mU/L, mean (± SD) free thyroxine (FT4) was 19.4 ± 3.5 and 15.9 ± 2.4 pmol/L, and daily LT4 dose was 82.1 ± 26.4 and 59.2 ± 23.9 µg. There was no suggestion of adverse impact of a higher serum TSH in the HT group with regard to any of the outcomes assessed. Conclusions: In hypothyroid patients aged ≥80 years on LT4 therapy for 24 weeks, there was no evidence that a higher target serum TSH was associated with an adverse impact on patient reported outcomes, cardiovascular risk factors or bone resorption marker over 24 weeks. Longer-term trials assessing morbidity and mortality outcomes and health-utility in this age group are feasible and should be performed.


1972 ◽  
Vol 71 (4) ◽  
pp. 665-676 ◽  
Author(s):  
Kristian F. Hanssen

ABSTRACT By using a double antibody radio-immunoassay (pre-precipitation technique) for the determination of immunoreactive human growth hormone (IRHGH) in normal human urine concentrated by dialysis and lyophilization, a factor was revealed that displaces 125I-HGH from HGH antibodies. This displacement was neither due to salts nor to glucose; it is suggested that it is due to IRHGH in the urine. A linear relationship between dilution of urine and the measured IRHGH concentration was obtained. Recovery of exogenous HGH was between 70–105%. The recovery of IRHGH from different volumes of urine following dialysis and lyophilization was between 97–110%. Plasma IRHGH and urinary IRHGH was measured simultaneously after HGH injection in a normal subject. A correlation was shown between plasma IRHGH and urinary IRHGH. In 9 normal subjects, the urinary IRHGH ranged from 28–53 ng/24 h. The excretion of urinary IRHGH was increased in acromegaly and was diminished in some, but not in all patients with adult hypopituitarism. The urinary IRHGH was further studied by gel filtration. It was recovered in one peak corresponding to a molecular weight of approximately 20 000 – 30 000. However, in the present work it was not clarified whether the urinary IRHGH represents pituitary HGH excreted in the urine or a metabolite of high molecular weight with retained immunological properties.


2021 ◽  
Vol 184 (2) ◽  
pp. C1-C3
Author(s):  
Petros Perros ◽  
Krishnarajah Nirantharakumar ◽  
Laszlo Hegedüs

Since the introduction of sensitive assays for serum thyroid-stimulating hormone (TSH) clinicians have advised hypothyroid patients to adjust the dose of levothyroxine (L-T4) in order to achieve a normal serum TSH. A minority of patients are dissatisfied with this treatment strategy and experience symptoms. Some indirect evidence suggests that a normal serum TSH may not necessarily reflect euthyroidism at the tissue level in patients treated with L-T4. Increasingly hypothyroid patients demand higher doses of L-T4 or liothyronine (L-T3) or animal thyroid extract, often purchased online, and titrate the dose against symptoms, although ample evidence suggests that combination treatment (L-T4 with L-T3) is no more effective than L-T4 alone. Community surveys show that up to 53% of treated hypothyroid patients at any time have a serum TSH outside the normal range. The recommendation by guidelines that the upper limit of the normal range for serum TSH should not be exceeded is supported by robust evidence and is generally accepted by clinicians and patients. However, until recently the lower limit of serum TSH for optimal L-T4 replacement has been controversial. New evidence obtained by two independent large population studies over the past two years has shown that mortality of hypothyroid patients treated with levothyroxine is increased when the serum TSH exceeds or is reduced outside the normal reference range. It is estimated that the implementation of a policy of normalising serum TSH in hypothyroid patients will reduce the risk of death of 28.3 million people in the USA and Europe alone.


1973 ◽  
Vol 73 (3) ◽  
pp. 455-464 ◽  
Author(s):  
P. A. Torjesen ◽  
E. Haug ◽  
T. Sand

ABSTRACT The rapid iv administration of 0.5 mg of synthetic thyrotrophin-releasing hormone (TRH) increased the serum thyroid-stimulating hormone (TSH) concentration in 20 normal subjects from baseline levels of 2.0 ± 0.5 ng/ml (sem) to peak values of 6.0 ± 0.7 ng/ml (sem) in women and 4.5 ± 0.5 ng/ml (sem) in men. The maximal increase occurred 30 min after TRH. The serum growth hormone (HGH) concentrations increased from baseline levels of 2.6± 1.0 ng/ml (sem) to peak values of 7.8± 1.3 ng/ml (sem) in women. In men there was no rise in the serum HGH concentrations. The serum levels of luteinizing hormone (LH) and folliclestimulating hormone (FSH) did not change significantly. In patients with hyperthyroidism the serum TSH concentrations did not change following TRH. Patients with primary hypothyroidism showed an exaggerated and prolonged increase in serum TSH concentrations after TRH administration. A routine TRH-stimulation test is proposed.


1977 ◽  
Vol 85 (3) ◽  
pp. 479-487 ◽  
Author(s):  
J. Lindholm ◽  
H. Dige-Petersen ◽  
L. Hummer ◽  
P. Rasmussen ◽  
O. Korsgaard

ABSTRACT The secretion and biological activity of thyroid stimulating hormone (TSH) were studied in 22 patients with a pituitary tumour (17 acromegalics and 5 patients with a chromophobe adenoma) and in 36 hypophysectomized patients (16 acromegalics and 20 with a chromophobe adenoma). Thyroid function was assessed by serum thyroxine (T4), serum triiodothyronine (T3), and thyroxine-binding globulin (TBG) concentration. Serum TSH was measured before and after injection of TSH releasing hormone (TRH), and in 19 hypophysectomized patients the T3 response after TRH was measured. In addition a TRH test was performed 1–2 weeks after surgery in 11 patients. The basal serum TSH did not differ from euthyroid control values in any of the groups and no late effect of hypophysectomy was observed. Subnormal peak TSH values were seen in 10 out of 37 euthyroid patients, whereas 9 out of 11 hypothyroid patients responded normally. Hypophysectomy caused an immediate but transient decrease in peak TSH in patients with a chromophobe adenoma only. The rise in serum T3 after TRH was significantly lower in hypophysectomized patients than in controls. An increase in TSH was followed by a T3 response in all patients except in 4 out of 8 euthyroid acromegalics. In patients operated on for a chromophobe adenoma the T3 response was correlated with serum T4, whereas this was not the case in acromegalics.


1978 ◽  
Vol 88 (4) ◽  
pp. 691-697 ◽  
Author(s):  
Klaus Johansen ◽  
Jens Mølholm Hansen ◽  
Lis Skovsted

ABSTRACT Serum TSH values and the free concentration of T4 and T3 in serum expressed as the free T4- and T3-indices showed a curvilinear relationship in 24 patients with manifest hypothyroidism mainly due to extremely elevated serum TSH levels associated with very low thyroid hormone levels. The same degree of negative correlation was found between the log serum TSH concentration and serum free T4-index (r = −0.51, P < 0.05) and between log serum TSH concentration and serum free T3-index (r = −0.47, P < 0.05). The correlation coefficients dropped to non-significant levels when the interdependence between the free T3- and T4-indices was taken into account and eliminated by partial correlation analysis. The degree of negative correlation between serum TSH and the thyroid hormones was also of the same order of magnitude in 5 hypothyroid patients studied prospectively during treatment with L-thyroxine (TSH vs. T4: mean r = −0.71; TSH vs T3: mean r = −0.79).


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Naoki Hattori ◽  
Takeshi Matsuda ◽  
Kazuhisa Chihara ◽  
Junko Nishioka ◽  
Selin Elmaoğulları ◽  
...  

Abstract Macro-TSH is mainly a complex of TSH with anti-TSH autoantibodies. Due to its large molecular size (&gt;150 kDa), it accumulates in the circulation resulting in elevated serum TSH concentrations. Because the bioactivity of macro-TSH is low, treatment with thyroxine is not necessary. The prevalence of macro-TSH is no more than 1% in adult patients with subclinical hypothyroidism. However, the prevalence of macro-TSH in children is not known. We report here two cases of macro-TSH in pediatric setting. [Case reports] Case 1. Six-year and eight-month-Japanese boy visited a pediatric hospital because of hyperactivity disorder. Physical examination revealed that he had a slight mental retardation (IQ 63 by Tanaka-Binet test). Thyroid tests showed that fT4 1.21 ng/dL, TSH 120.4 µU/mL, Tg antibody 1.9 IU/mL, TPO antibody &lt;0.1 IU/mL. His serum was sent to our laboratory to examine the causes of inappropriate high serum TSH concentration. Case 2. Eight-year and three-month-Turkish girl was brought to a pediatric hospital by her parents because of her yellowish palms, which was not identified at the hospital. She did not have any complaints and physical signs attributable to thyroid dysfunction. Laboratory data disclosed that fT4 1.5 ng/dL, TSH 19.6 µU/mL, Tg Ab negative, TPO Ab negative. Levothyroxine treatment started but serum TSH concentration was still high (39.0 µU/mL) after two months. Her serum sample was sent to our laboratory to examine the causes of inappropriate high serum TSH concentrations. [Lab. Tests for macro-TSH] When serum was mixed with the same amount of 25% polyethylene glycol (PEG) and γ-globulin fraction was precipitated, TSH concentration in the supernatant decreased significantly from 109.3 µU/mL to 2.3 µU/mL (PEG precipitation ratio 97.9%) in case 1, and from 17.3 µU/mL to 0.15 µU/mL (PEG precipitation ratio 99.1%) in case 2. HAMA blockers did not significantly change TSH concentration in both cases. High proportion of serum TSH bound to a protein G column, which binds IgG, in case 1 (91.3%) and in case 2 (57.7%), indicating that TSH was associated with IgG. Gel filtration chromatography (GFC) revealed that TSH was mostly eluted at the fraction &gt; 150 kDa rather than 28 kDa of authentic TSH in both cases. Serum was incubated with 37.7 µU of TSH for one hour and subjected to GFC. TSH concentration in the fraction of 150 kDa (macro-TSH) increased from 2.8 µU/mL to 5.6 µU/mL in case 1 and from 0.4 µU/mL to 2.0 µU/mL in case 2, suggesting that macro-TSH was produced by the binding of exogenous TSH to anti-TSH autoantibodies. [Conclusion] Macro-TSH exists in children and careful evaluation is required in patients with inappropriate high serum TSH concentrations to avoid unnecessary treatment.


2013 ◽  
Vol 5 (2) ◽  
pp. 67-72
Author(s):  
P Eshita ◽  
B Dharani Priya ◽  
G Sudhakar ◽  
G Paddaiah

Background: Adipocytokines, secreted from the adipose tissues have profound effect on complex metabolic and endocrine functions. Among them, leptin and adiponectin are the most recognized molecules which influence body homeostasis and metabolism. Moreover, patients with thyroid disease usually exhibit disturbances of these metabolic activities. Thus adipocytokines and thyroid hormones may influence similar aspects of metabolic functions. Objective: The main objective of current study was to evaluate the association and impact of leptin and adiponectin on thyroid stimulating hormone (TSH) among hypothyroid patients. Materials and Methods: For the present study a total 350 individuals were enlisted, out of which 200 were hypothyroid patients and 150 age and sex matched healthy controls aged ≥ 12 years. The serum TSH, leptin and adiponectin concentration were measured by CLIA method and results were computed by statistical methods such as mean, standard deviation, standard error and correlation using MS-Excel 2007. Result: Our data showed that hypothyroidism was more prevalent in the age group 30-50(62%) and an elevated TSH level was observed with advancing age among the patients as compared to controls. The inverse relation of leptin and adiponectin has been seen among the patients. When patients were compared with controls, they were with normal values which were in the range of standardized lab values leptin (3.7-13ng/dl) and adiponectin (5-10μg/ml). Conclusion: In conclusion, our data interpreted variations in the level of leptin and adiponectin among the hypothyroid individuals with high TSH level. As abnormal levels of these adipocytokines indicates the risk for other metabolic diseases like cardiovascular disease, obesity etc. DOI: http://dx.doi.org/10.3126/ajms.v5i2.8789 Asian Journal of Medical Science, Volume-5(2) 2014: 67-72


1979 ◽  
Vol 41 (04) ◽  
pp. 718-733 ◽  
Author(s):  
Preben Kok

SummaryThree types of plasminogen activator could be distinguished in extracts from human uterine tissue. The activators differed in thermostability or in mode of inhibition by EACA.All the extracts contained stable as well as labile activators. The saline extracts were uniformly inhibited by increasing concentrations of EACA. Extracts made with 2 M ammonium thiocyanate were either uniformly inhibited by EACA or showed deflections indicating contamination with an activator, which was inhibited in a biphasic manner. It was possible to distinguish between: (1) An activator, abundantly present in the tissue, which was uniformly inhibited and stable. (2) Another uniformly inhibited activator, which was labile. (3) An activator, inhibited in a biphasic manner, similar to urokinase, which was present in varying amounts in uteri with the endometrium in the proliferative phase.Gel filtration of the uterine extracts showed two major activity peaks corresponding to particle sizes of 60,000 dalton and about 10,000 dalton.Antiserum to purified plasminogen activator, prepared from porcine ovaries, inhibited the activity of the human uterine extracts, but not the activities of human urokinase or urine. Urokinase antiserum in a concentration completely inhibiting human urine or urokinase, inhibited only 10% or less of the activities of human uterine extracts.


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