RELATIONSHIP BETWEEN PEROXIDASE ACTIVITY AND SERUM TSH, T4 AND T3 LEVELS IN RATS IN THE COURSE OF IODINE DEFICIENCY

1978 ◽  
Vol 88 (3) ◽  
pp. 499-505 ◽  
Author(s):  
B. M. Nataf ◽  
P. Fragu ◽  
S. Ben Othman

ABSTRACT The relationship between peroxidase activity and serum TSH, T4 and T3 levels was investigated in the course of iodine deficiency in rats. Rats were maintained either on a control diet with a relatively high iodine content (600 μg/kg of 127I), or on a low iodine diet (30 μg/kg of 127I). Twenty days after the low iodine treatment, the thyroid iodine [127I] concentration was half that of control value (647 ± 52 and 1241 ± 72 μg/g of wet weight, respectively). However, no significant changes in serum T4, T3, TSH were found at 20 days even though an early increase in peroxidase activity was observed. It was only at 35 days of iodine deficiency, when the concentration of iodine in the gland averaged 260 μg/g of wet weight that serum T4 and TSH levels started to be significantly modified. From day 35 to day 70, a significant and progressive decrease of plasma T4 concentration was observed, and it levelled off thereafter. The changes of serum T3 were much smaller than those of T4. A significant increase in serum TSH level was noted at 35 days. Thereafter TSH levels increased rapidly and progressively (205 % increase over control at 70 days and 643 % at 80 days). From day 35 until day 80 of the low iodine treatment, the thyroid peroxidase activity and the serum TSH level varied concomitantly. Our results suggest that for an iodine content between 5 and 2 μg per thyroid gland, the high cellular peroxidase activity observed could be correlated with an increase in circulating TSH, due to a decrease of T4. In contrast, in the early period of iodine deficiency, no correlation was found between peroxidase activity and serum T4, T3 and TSH levels.

1979 ◽  
Vol 91 (3) ◽  
pp. 462-472
Author(s):  
P. Fragu ◽  
S. Ben Othman ◽  
B. M. Nataf

ABSTRACT The evolution of peroxidase activity was followed in relation to other parameters of thyroid function in rats when PTU was added to a low iodine diet (LID). Ten days of PTU treatment brings about an equivalent increase in thyroid weight and iodide peroxidase activity at whatever time PTU was added to LID (10, 35, 54 and 80 days). It is shown that the effect of PTU treatment on thyroid weight and peroxidase activity is proportionately higher when PTU is added after 10 days of LID alone than after 80 days. The effect of various durations of PTU treatment was studied more closely when the addition began on day 10 of LID. On day 1 after addition of PTU thyroid weight increased significantly and no significant change was found in peroxidase activity. In contrast 5 days of PTU induced a significant elevation in enzymatic activity which is greater than that of thyroid weight. For a longer period of PTU treatment (10 days or more), the per cent increase of thyroid weight and peroxidase activity evolved parallely. Already on day 1 of PTU treatment very rapid change were noted on T4, T3 and TSH levels; there was a decrease in T3 level (26 ± 5.6 %), while an increase in T4 level (26.4 ± 4.7 %) and TSH level (30 ± 5 %) was observed when the iodine content was still high (about 11 μg/thyroid gland). Thereafter T3 and T4 decreased and stayed at the same level after 10 days of PTU, while TSH increased rapidly and reached a plateau between 18 and 35 days. When PTU was added to LID treatment the increase in TSH was mostly due to a decrease of T3. The per cent increase in serum TSH level is always higher than that of thyroid peroxidase activity.


1987 ◽  
Vol 116 (4) ◽  
pp. 537-548 ◽  
Author(s):  
D. Stübner ◽  
R. Gärtner ◽  
W. Greil ◽  
K. Gropper ◽  
G. Brabant ◽  
...  

Abstract. Goitre growth was investigated in rats receiving a low iodine diet (< 0.1 μg iodine/g) and either 1 g/l KClO4 or 1 g/l propylthiouracil (PTU), or a combination of KClO4 or PTU with 50.82 nmol/l T3 in tap water for 3 weeks. To investigate goitre involution, rats with iodine-deficient goitres were treated for 3 weeks either with T3 (0.5 μg T3/day = 0.768 nmol/day), iodide (0.5 or 2.7 μg KI/day) or a combination of T3 with both iodide doses. Histology together with total DNA distinguished between hypertrophy and hyperplasia of the gland. During goitre growth there was a highly significant correlation between goitre weight and TSH serum level (r = 0.93, P < 0.001). Thyroid total DNA, however, was only weakly correlated to TSH but was inversely related to the degree of iodine deficiency. During goitre regression, TSH levels were normalized, histological signs of hypertrophy had disappeared, and thyroid weight was nearly normalized in all therapy groups. Total DNA, however, was normalized only with 2.7 μg KI/day (95 ± 18 μg DNA/gland), and still elevated in all other groups. The highest DNA levels were found under T3 therapy (143 ± 21 μg DNA/gland) and under 0.5 μg KI/day (161 ± 19 μg DNA/gland). Reduction of total DNA was independent of TSH, but followed replenishment of the iodine content of the glands. We conclude that TSH mainly induces hypertrophy, whereas thyroid hyperplasia is mainly regulated by the intracellular iodine content.


2018 ◽  
Vol 178 (2) ◽  
pp. 189-197 ◽  
Author(s):  
Flora Veltri ◽  
Pierre Kleynen ◽  
Lidia Grabczan ◽  
Alexandra Salajan ◽  
Serge Rozenberg ◽  
...  

ObjectiveIn the recently revised guidelines on the management of thyroid dysfunction during pregnancy, treatment with thyroid hormone (LT4) is not recommended in women without thyroid autoimmunity (TAI) and TSH levels in the range 2.5–4.0 mIU/L, and in a recent study in that particular group of pregnant women, more complications were observed when a treatment with LT4 was given. The objective of the study was therefore to investigate whether variation in thyroid function within the normal (non-pregnant) range in women free of thyroid disease was associated with altered pregnancy outcomes?DesignCross-sectional data analysis of 1321 pregnant women nested within an ongoing prospective collection of pregnant women’s data in a single centre in Brussels, Belgium.MethodsThyroid peroxidase antibodies (TPO-abs), thyroid-stimulating hormone (TSH), free T4 (FT4) and ferritin levels were measured and baseline characteristics were recorded. Women taking LT4, with TAI and thyroid function outside the normal non-pregnant range were excluded. Pregnancy outcomes and baseline characteristics were correlated with all TSH and FT4 levels within the normal range and compared between two groups (TSH cut-off < and ≥2.5 mIU/L).ResultsTobacco use was associated with higher serum TSH levels (OR: 1.38; CI 95%: 1.08–1.74);P = 0.009. FT4 levels were inversely correlated with age and BMI (rho = −0.096 and −0.089;P < 0.001 and 0.001 respectively) and positively correlated with ferritin levels (rho = 0.097;P < 0.001). Postpartum haemorrhage (>500 mL) was inversely associated with serum FT4 levels (OR: 0.35; CI 95%: 0.13–0.96);P = 0.040. Also 10% of women free of thyroid disease had serum TSH levels ≥2.5 mIU/L.ConclusionsVariation in thyroid function during the first trimester within the normal (non-pregnant) range in women free of thyroid disease was not associated with altered pregnancy outcomes. These results add evidence to the recommendation against LT4 treatment in pregnant women with high normal TSH levels and without TPO antibodies.


2022 ◽  
Vol 11 (1) ◽  
Author(s):  
Georgiana Sitoris ◽  
Flora Veltri ◽  
Pierre Kleynen ◽  
Malika Ichiche ◽  
Serge Rozenberg ◽  
...  

Objective It is unknown if foetal gender influences maternal thyroid function during pregnancy. We therefore investigated the prevalence of thyroid disorders and determined first-trimester TSH reference ranges according to gender. Methods A cross-sectional study involving 1663 women with an ongoing pregnancy was conducted. Twin and assisted pregnancies and l-thyroxine or antithyroid treatment before pregnancy were exclusion criteria. Serum TSH, free T4 (FT4) and thyroid peroxidase antibodies (TPOAb) were measured at median (interquartile range; IQR) 13 (11–17) weeks of gestation. Subclinical hypothyroidism (SCH) was present when serum TSH levels were >3.74 mIU/L with normal FT4 levels (10.29–18.02 pmol/L), and thyroid autoimmunity (TAI) was present when TPOAb were ≥60 kIU/L. Results Eight hundred and forty-seven women were pregnant with a female foetus (FF) and 816 with a male foetus (MF). In women without TAI and during the gestational age period between 9 and 13 weeks (with presumed high-serum hCG levels), median (IQR range) serum TSH in the FF group was lower than that in the MF group: 1.13 (0.72–1.74) vs 1.24 (0.71–1.98) mIU/L; P = 0.021. First-trimester gender-specific TSH reference range was 0.03–3.53 mIU/L in the FF group and 0.03–3.89 mIU/L in the MF group. The prevalence of SCH and TAI was comparable between the FF and MF group: 4.4% vs 5.4%; P = 0.345 and 4.9% vs 7.5%; P = 0.079, respectively. Conclusions Women pregnant with an MF have slightly but significantly higher TSH levels and a higher upper limit of the first-trimester TSH reference range, compared with pregnancies with a FF. We hypothesise that this difference may be related to higher hCG levels in women pregnant with a FF, although we were unable to measure hCG in this study. Further studies are required to investigate if this difference has any clinical relevance.


2012 ◽  
Vol 167 (2) ◽  
pp. 261-265 ◽  
Author(s):  
Carlo Cappelli ◽  
Mario Rotondi ◽  
Ilenia Pirola ◽  
Barbara Agosti ◽  
Annamaria Formenti ◽  
...  

ObjectiveA retrospective study to evaluate the changes in TSH concentrations in diabetic patients treated or not treated with metformin and/or l-thyroxine (l-T4).MethodsThree hundred and ninety three euthyroid diabetic patients were divided into three groups on the basis of metformin and/or l-T4 treatment: Group (M−/L−), 119 subjects never treated with metformin and l-T4; Group (M+/L−), 203 subjects who started metformin treatment at recruitment; and Group (M+/L+), 71 patients on l-T4 who started metformin recruitment.ResultsThe effect of metformin on serum TSH concentrations was analyzed in relation to the basal value of TSH (below 2.5 mIU/l (Q1) or between 2.51 and 4.5 mIU/l (Q2)). In patients of group M+/L+, TSH significantly decreased independently from the basal level (Q1, from 1.45±0.53 to 1.01±1.12 mU/l (P=0.037); Q2, from 3.60±0.53 to 1.91±0.89 mU/l (P<0.0001)). In M+/L− group, the decrease in TSH was significant only in those patients with a basal high-normal serum TSH (Q2: from 3.24±0.51 to 2.27±1.28 mU/l (P=0.004)); in M−/L− patients, no significant changes in TSH levels were observed. In patients of group M+/L− showing high-normal basal TSH levels, a significant decrease in TSH was observed independently from the presence or absence of thyroid peroxidase antibodies (AbTPO; Q2 AbTPO +: from 3.38±0.48 to 1.87±1.08 mU/l (P<0.001); Q2 AbTPO −: from 3.21±0.52 to 2.34±1.31 mU/l (P<0.001)).ConclusionsThese data strengthen the known TSH-lowering effect of metformin in diabetic patients on l-T4 treatment and shows a significant reduction of TSH also in euthyroid patients with higher baseline TSH levels independently from the presence of AbTPO.


1965 ◽  
Vol 49 (4) ◽  
pp. 610-628 ◽  
Author(s):  
Hugo Studer ◽  
Monte A. Greer

ABSTRACT An extensive study of the temporal sequence of changes in thyroid function after initiation of a low iodine regimen has been made in rats. Variables measured include: thyroid weight, 131I uptake, monoiodotyrosine/diiodotyrosine (MIT/DIT) and triiodothyronine/thyroxine (T3/T4) ratios, iodide clearance, and 127I content. Also measured were protein-bound iodine (PBI), inorganic iodide and thyrotrophin (TSH) levels in the serum. Significant thyroid hypertrophy was produced during the first week and before there was a fall in serum PBI. Temporally related to the appearance of goiter were a rise in 131I uptake, MIT/DIT ratio and iodide clearance and a fall in thyroidal 127I concentration. In contrast, a fall in total thyroidal 127I appeared later and was closely correlated with a decline in serum PBI concentration and a rise in the thyroidal T3/T4 ratio. Manipulations such as hypophysectomy, injections of iodide, thyroxine or TSH, and refeeding a high iodine diet gave results consistent with the view that changes produced by iodine deficiency involve both autonomous and TSH-dependent thyroidal mechanisms. Although elevated serum TSH levels could not be demonstrated until after the first week of the iodine-deficient regimen, the total evidence of these studies permits the conclusion that increased TSH secretion is the most important factor in producing the thyroidal response to iodine deficiency. It is shown that homeostatic mechanisms allow maintenance of a normal level of circulating thyroid hormone in an iodine-deficient state until the body iodine pool becomes too severely depleted to supply adequate iodide substrate to the thyroid. The changes observed closely resemble those found in human iodine-deficient goiters. Although the large goiters produced after several weeks of an iodine-deficient regimen were hyperplastic, they could readily be converted to typical colloid goiters by feeding a high iodine diet for a few days.


2019 ◽  
Vol 3 (12) ◽  
pp. 2385-2396
Author(s):  
Yasuyo Nakajima ◽  
Sayaka Yamada ◽  
Ayaka Nishikido ◽  
Akiko Katano-Toki ◽  
Emi Ishida ◽  
...  

Abstract Context We previously identified factors affecting thyroid status, including sex, age, and smoking. Objective In the current study, we increased the number of subjects examined and investigated the effects of these factors, particularly smoking and the thyroid peroxidase antibody (TPO-Ab), in Japanese patients with euthyroxinemia and serum free T4 levels within the normal range. Participants A total of 12,289 subjects who underwent health checkups were analyzed in a cross-sectional and longitudinal study. Results The mean age of subjects was 50 ± 10 years (age range: 21 to 88 years). Serum TSH levels and the prevalence of positivity for TPO-Ab increased with age in Japanese subjects with euthyroxinemia. Mean serum TSH levels were significantly lower in the smoking group than in the nonsmoking group except for women older than 50 years. Serum TSH levels were significantly higher in subjects with positivity for TPO-Ab than in those with negativity at all ages and in both sexes; however, smoking did not affect free T4 levels or positivity for TPO-Ab. Among men, the rate of smokers was significantly higher in patients with subclinical hyperthyroidism (25%) than in those with subclinical hypothyroidism (10%; P < 0.05). Furthermore, the results of the longitudinal study revealed a significant decrease in serum TSH levels 1 year after the start of smoking in men (P < 0.05). Conclusion Because smoking appeared to lower serum TSH levels in Japanese subjects with euthyroxinemia, their smoking status warrants careful consideration when evaluating subclinical thyroid function.


2021 ◽  
Vol 12 ◽  
Author(s):  
Evie van der Spoel ◽  
Ferdinand Roelfsema ◽  
Diana van Heemst

BackgroundIndividuals exhibit fluctuations in the concentration of serum thyroid-stimulating hormone (TSH) over time. The scale of these variations ranges from minutes to hours, and from months to years. The main factors contributing to the observed within-person fluctuations in serum TSH comprise pulsatile secretion, circadian rhythm, seasonality, and ageing. In clinical practice and clinical research however, such within-person biological variation in serum TSH concentrations is often not considered. The aim of this review is to present an overview of the main sources of within-person variation in TSH levels, as well as the potential underlying biological mechanisms, and the clinical implications.SummaryIn euthyroid individuals, the circadian rhythm, with a nocturnal surge around 02:00–04:00 h and a nadir during daytime has the greatest impact on variations in serum TSH concentrations. Another source of within-person variation in TSH levels is seasonality, with generally higher levels during the cold winter months. Since TSH is secreted in a pulsatile manner, TSH levels also fluctuate over minutes. Furthermore, elevated TSH levels have been observed with ageing. Other factors that affect TSH levels include thyroid peroxidase (TPO)-antibody positivity, BMI, obesity, smoking, critical illness, and many xenobiotics, including environmental pollutants and drugs. Potential underlying biological mechanisms of within-person variation in TSH levels can be safely concluded from the ability of TSH to respond quickly to changes in cues from the internal or external environment in order to maintain homeostasis. Such cues include the biological clock, environmental temperature, and length of day. The observed increase in TSH level with ageing can be explained at a population level and at an organism level. In clinical practice, the season for thyroid testing can influence a patient’s test result and it occurs frequently that subclinical hypothyroid patients normalize to euthyroid levels over time without intervention.ConclusionsSerum TSH concentrations vary over time within an individual, which is caused by multiple different internal and external factors. It is important to take the within-person variations in serum TSH concentrations into account when testing a patient in clinical practice, but also in performing clinical research.


Endocrinology ◽  
2020 ◽  
Vol 161 (12) ◽  
Author(s):  
Barbara M L C Bocco ◽  
Gustavo W Fernandes ◽  
Tatiana L Fonseca ◽  
Antonio C Bianco

Abstract More than a billion people worldwide are at risk of iodine deficiency (ID), with well-known consequences for development of the central nervous system. Furthermore, ID has also been associated with dyslipidemia and obesity in humans. To further understand the metabolic consequences of ID, here we kept 8-week-old C57/Bl6 mice at thermoneutrality (~28°C) while feeding them on a low iodine diet (LID). When compared with mice kept on control diet (LID + 0.71 μg/g iodine), the LID mice exhibited marked reduction in T4 and elevated plasma TSH, without changes in plasma T3 levels. LID mice grew normally, and had normal oxygen consumption, ambulatory activity, and heart expression of T3-responsive gene, confirming systemic euthyroidism. However, LID mice exhibited ~5% lower respiratory quotient (RQ), which reflected a ~2.3-fold higher contribution of fat to energy expenditure. LID mice also presented increased circulating levels of nonesterified fatty acids, ~60% smaller fat depots, and increased hepatic glycogen content, all indicative of accelerated lipolysis. LID mice responded much less to forced mobilization of energy substrates (50% food restriction for 3 days or starvation during 36 hours) because of limited size of the adipose depots. A 4-day treatment with T4 restored plasma T4 and TSH levels in LID mice and normalized RQ. We conclude that ID accelerates lipolysis and fatty acid oxidation, without affecting systemic thyroid hormone signaling. It is conceivable that the elevated plasma TSH levels trigger these changes by directly activating lipolysis in the adipose tissues.


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