Benefit of Combined Triiodothyronine (LT3) and Thyroxine (LT4) Treatment in Athyreotic Patients Unresponsive to LT4 Alone

AbstractDespite some reports, the usefulness of levothyroxine ( LT4) and levotriiodothyronine (LT3) combination therapy in hypothyroidism remains controversial. The objective of this paper is to study a benefit of additional LT3 in athyreotic patients who failed to normalize TSH on LT4 alone even with hyperthyroid serum T4 values.In a survey of 200 athyreotic patients treated between 2006 and 2009, about 7% failed to normalize serum TSH levels following treatment with LT4, though serum T4 values in the hyperthyroid range were achieved. These patients (characterized by serum T4≥160 nmol/L and TSH≥5.0 mIU/L), were additionally treated with 10 μg b. i. d LT3. LT3 and LT4 combination therapy resulted in decreased serum TSH levels into the normal range (12.8 vs. 1.22 mIU/L; p<0.01) and reduced LT4 dose (153.3 vs. 117.5 μg; p<0.01) required for normalization of serum T4 values (170.6 vs. 123.3 nmol/L; p<0.01). Serum T3 values were higher (1.3 vs. 2.26 nmol/L; p<0.01) than those during monotherapy with LT4.Our results indicate a subpopulation of athyreotic patients that could significantly benefit from combined LT4 + LT3 therapy in restoring normal TSH and thyroid hormone patterns. Further research should be undertaken to provide a genetic basis for these findings.

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Inhibition of pituitary type 2 deiodinase by reverse triiodothyronine does not alter thyroxine-induced inhibition of thyrotropin secretion in hypothyroid rats

Acta Endocrinologica ◽

10.1530/eje.1.01984 ◽

2005 ◽

Vol 153 (3) ◽

pp. 429-434 ◽

Cited By ~ 7

Author(s):

P Cettour-Rose ◽

T J Visser ◽

A G Burger ◽

F Rohner-Jeanrenaud

Keyword(s):

Specific Inhibitor ◽

Adult Rats ◽

Reverse T3 ◽

Brown Adipose ◽

Tsh Secretion ◽

Serum T3 ◽

Serum T4 ◽

Serum Tsh ◽

Tsh Levels

Objectives: Intrapituitary triiodothyronine (T3) production plays a pivotal role in the control of TSH secretion. Its production is increased in the presence of decreased serum thyroxine (T4) concentrations and the enzyme responsible, deiodinase type 2 (D2), is highest in hypothyroidism. In order to document the role of this enzyme in adult rats we developed an experimental model that inhibited this enzyme using the specific inhibitor, reverse T3 (rT3). Methods: Hypothyroidism was induced with propylthiouracil (PTU; 0.025 g/l in drinking water) which in addition blocked deiodinase type 1 (D1) activity, responsible for the rapid clearance of rT3 in vivo. During the last 7 days of the experiment, the hypothyroid rats were injected (s.c.) for 4 days with 0.4 or 0.8 nmol T4 per 100 g body weight (bw) per day. For the last 3 days, the same amount of T4 was infused via s.c. minipumps. In additional groups, 25 nmol rT3/100 g bw per day were added to the 3-day infusion of T4. Results: Infusion of 0.4 nmol T4/100 g bw per day did not affect the high serum TSH levels, 0.8 nmol T4/100 g bw per day decreased them to 57% of the hypothyroid values. The infusions of rT3 inhibited D2 activity in all organs where it was measured: the pituitary, brain cortex and brown adipose tissue (BAT). In the pituitary, the activity was 27%, to less than 15% of the activity in hypothyroidism. Despite that, serum TSH levels did not increase, serum T4 concentrations did not change and the changes in serum T3 were minimal. Conclusions: We conclude that in partly hypothyroid rats, a 3-day inhibition of D2 activity, without concomitant change in serum T4 and minimal changes in serum T3 levels, is not able to upregulate TSH secretion and we postulate that this may be a reflection of absent or only minimal changes in circulating T3 concentrations.

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Is There Compensated Hypothyroidism in Infancy?

PEDIATRICS ◽

10.1542/peds.90.2.207 ◽

1992 ◽

Vol 90 (2) ◽

pp. 207-211

Author(s):

Ramin Alemzadeh ◽

Silvia Friedman ◽

Pavel Fort ◽

Bridget Recker ◽

Fima Lifshitz

Keyword(s):

Screening Program ◽

Thyroid Stimulating Hormone ◽

Normal Serum ◽

Close Monitoring ◽

Normal Range ◽

Thyroid Screening ◽

Serum T4 ◽

Hypometabolic State ◽

Serum Tsh ◽

Tsh Levels

The state-mandated newborn thyroid screening program may uncover infants who exhibit normal thyoxine (T4) levels with various degrees of hyperthyrotropinemia. To elucidate further the thyroid status, the basal metabolic rate (BMR) of 10 infants (7 boys, 3 girls; aged 9 to 63 days) was studied by indirect calorimetry. They were clinically euthyroid and healthy with no evidence of overt biochemical hypothyroidism (low T4, high thyroid-stimulating hormone [TSH]). Confirmatory testing indicated that all infants had normal serum T4 levels for age (mean ± SD: 10.3 ± 3.2 µg/dL). However, serum TSH levels varied from 2.3 to 99.2 µU/mL In 4 infants (2 boys, 2 girls) the BMR was low (38.1 ± 4.1 kcal/kg per day), while the other 6 patients (5 boys, 1 girl) demonstrated BMRs within the normal range (49.6 ± 1.9 kcal/kg per day, P < .001). The serum TSH levels were above 7.0 µU/mL among those infants with a low BMR, whereas the serum TSH levels were always below 6.0 µU/mL among the normometabolic infants. All infants who had a low BMR received thyroid therapy and promptly became normometabolic (BMR: 48.7 ± 1.0 kcal/kg per day) with suppression of TSH levels (3.2 ± 1.3 µU/mL) within 3 weeks of therapy, while their serum T4 levels remained within the normal range. The observed normalization of BMR In parallel to reduction of TSH levels following thyroid replacement therapy strongly suggests that these patients demonstrated a hypometabolic state, despite normal serum T4 levels. Therefore, the assessment of BMR may help define subclinical hypothyroidism in infancy in conjunction with a close monitoring of TSH concentration.

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Serum T3 and T4 Levels in Sick Children

PEDIATRICS ◽

10.1542/peds.58.5.776 ◽

1976 ◽

Vol 58 (5) ◽

pp. 776-776

Author(s):

J. N. Carter ◽

J. M. Corcoran ◽

C. J. Eastman ◽

L. Lazarus ◽

M. O'Halloran

Keyword(s):

Thyroid Hormone ◽

Normal Range ◽

Hormone Levels ◽

Serum T3 ◽

The Mean ◽

Thyroid Hormone Levels ◽

Sick Children ◽

Circulating Levels ◽

Tsh Levels ◽

Sick Euthyroid

We have reported that most adults with severe, chronic, nonthyroidal illnesses (i.e., sick euthyroid patients) have significantly decreased circulating levels of triiodothyronine (T3) and thyroxine (T4), whilst the thyrotropin (TSH) levels are not elevated.1 The T3 levels are usually reduced into the hypothyroid range, whilst the T4 levels generally remain within the normal range. The patients in that study were aged from 21 to 84 years. We have recently concluded a study of circulating thyroid hormone levels in children of various ages and have found that the mean levels of both T3 and T4 are higher than in adults.

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Activation of GLP-1 and Glucagon Receptors Regulates Bile Homeostasis Independent of Thyroid Hormone

Current Molecular Pharmacology ◽

10.2174/1874467212666190212112402 ◽

2019 ◽

Vol 12 (2) ◽

pp. 139-146

Author(s):

Vishal J. Patel ◽

Amit A. Joharapurkar ◽

Samadhan G. Kshirsagar ◽

Brijesh K. Sutariya ◽

Maulik S. Patel ◽

...

Keyword(s):

Single Dose ◽

Lipid Metabolism ◽

Thyroid Hormone ◽

Fibroblast Growth Factor 21 ◽

Dose Treatment ◽

Obesity And Diabetes ◽

Serum T3 ◽

Serum T4 ◽

Glucagon Like Peptide 1 ◽

Glucagon Receptors

Background: Balanced coagonists of glucagon-like peptide-1 (GLP-1) and glucagon receptors are emerging therapies for the treatment of obesity and diabetes. Such coagonists also regulate lipid metabolism, independent of their body weight lowering effects. Many actions of the coagonists are partly mediated by fibroblast growth factor 21 (FGF21) signaling, with the major exception of bile homeostasis. Since thyroid hormone is an important regulator of bile homeostasis, we studied the involvement of thyroid hormone in coagonist-induced changes in lipid and bile metabolism. Methods: We evaluated the effect of a single dose of coagonist Aib2 C24 chimera2 at 150 to 10000 µg/kg on tetraiodothyronine (T4) and triiodothyronine (T3) in high-fat diet-induced obese (DIO) mice and chow-fed mice. Repeated dose treatment of coagonist (150 µg/kg, subcutaneously) was assessed in four mice models namely, on lipid and bile homeostasis in DIO mice, propylthiouracil (PTU)-treated DIO mice, methimazole (MTM)-treated DIO mice and choline-deficient, L-amino acid-defined, highfat diet (CDAHFD)-induced nonalcoholic steatohepatitis (NASH). Results: Single dose treatment of coagonist did not alter serum T3 and T4 in chow-fed mice and DIO mice. Coagonist treatment improved lipid metabolism and biliary cholesterol excretion. Chronic treatment of GLP-1 and glucagon coagonist did not alter serum T3 in hypothyroid DIO mice and CDAHFDinduced NASH. Coagonist increased serum T4 in DIO mice after 4 and 40 weeks of treatment, though no change in T4 levels was observed in hypothyroid mice or mice with NASH. Conclusion: Our data demonstrate that coagonist of GLP-1 and glucagon receptors does not modulate bile homeostasis via thyroid signaling.

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Distinct Roles of Deiodinases on the Phenotype of Mct8 Defect: A Comparison of Eight Different Mouse Genotypes

Endocrinology ◽

10.1210/en.2010-0900 ◽

2011 ◽

Vol 152 (3) ◽

pp. 1180-1191 ◽

Cited By ~ 51

Author(s):

Xiao-Hui Liao ◽

Caterina Di Cosmo ◽

Alexandra M. Dumitrescu ◽

Arturo Hernandez ◽

Jacqueline Van Sande ◽

...

Keyword(s):

Growth Response ◽

Pituitary Thyroid Axis ◽

Severe Impairment ◽

Serum T3 ◽

Serum T4 ◽

Thyroid Axis ◽

Mct8 Deficiency ◽

The Brain ◽

Insight Into ◽

Serum Tsh

Mice deficient in the thyroid hormone (TH) transporter Mct8 (Mct8KO) have increased 5′-deiodination and impaired TH secretion and excretion. These and other unknown mechanisms result in the low-serum T4, high T3, and low rT3 levels characteristic of Mct8 defects. We investigated to what extent each of the 5′-deiodinases (D1, D2) contributes to the serum TH abnormalities of the Mct8KO by generating mice with all combinations of Mct8 and D1 and/or D2 deficiencies and comparing the resulting eight genotypes. Adding D1 deficiency to that of Mct8 corrected the serum TH abnormalities of Mct8KO mice, normalized brain T3 content, and reduced the impaired expression of TH-responsive genes. In contrast, Mct8D2KO mice maintained the serum TH abnormalities of Mct8KO mice. However, the serum TSH level increased 27-fold, suggesting a severely impaired hypothalamo-pituitary-thyroid axis. The brain of Mct8D2KO manifested a pattern of more severe impairment of TH action than Mct8KO alone. In triple Mct8D1D2KO mice, the markedly increased serum TH levels produced milder brain defect than that of Mct8D2KO at the expense of more severe liver thyrotoxicosis. Additionally, we observed that mice deficient in D2 had an unexplained marked reduction in the thyroid growth response to TSH. Our studies on these eight genotypes provide a unique insight into the complex interplay of the deiodinases in the Mct8 defect and suggest that D1 contributes to the increased serum T3 in Mct8 deficiency, whereas D2 mainly functions locally, converting T4 to T3 to compensate for distinct cellular TH depletion in Mct8KO mice.

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Specific measurement of cyclosporine concentrations in whole blood: radioimmunoassay and fluorescence polarization immunoassay compared

Clinical Chemistry ◽

10.1093/clinchem/37.12.2150a ◽

1991 ◽

Vol 37 (12) ◽

pp. 2150-2152 ◽

Cited By ~ 2

Author(s):

Kathleen A Fuller ◽

Wayne S Brown ◽

John W Koenig ◽

Barbara J Eveland ◽

Mitchell G Scott

Keyword(s):

Thyroid Hormone ◽

Whole Blood ◽

Fluorescence Polarization ◽

Hashimoto Thyroiditis ◽

High Serum ◽

Fluorescence Polarization Immunoassay ◽

Normal Range ◽

Normal Value ◽

Serum T3 ◽

History Of

Letters A 39-year-old woman with a 20-year history of hypothyroidism caused by Hashimoto thyroiditis had been managed adequately with oral thyroxun (T4), 200 mg/day, until a few months before referral, at which time she developed symptoms of hyperthyroidism. Her thyroid hormone proffle at the time of referral is shown in Table 1 (Sample 1). Her normal value for serum thyrotropin (TSH) concentration indicates that she was euthyreid but, because of the high serum triiodothyronune (T3) value, the daily oral doseof T4 was decreased to 100 mg. The serum thyroid tests were repeated four weeks later (Table 1, Sample 2): The decreased T4 and increased TSH show that the patient had become hypothyroid at this dosagé of T4 but the serum T3 concentration was still in the high normal range.

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Pregnancy outcomes are not altered by variation in thyroid function within the normal range in women free of thyroid disease

Acta Endocrinologica ◽

10.1530/eje-17-0628 ◽

2018 ◽

Vol 178 (2) ◽

pp. 189-197 ◽

Cited By ~ 6

Author(s):

Flora Veltri ◽

Pierre Kleynen ◽

Lidia Grabczan ◽

Alexandra Salajan ◽

Serge Rozenberg ◽

...

Keyword(s):

Pregnant Women ◽

Thyroid Function ◽

Pregnancy Outcomes ◽

Thyroid Disease ◽

Thyroid Autoimmunity ◽

Thyroid Peroxidase ◽

Normal Range ◽

Baseline Characteristics ◽

Serum Tsh ◽

Tsh Levels

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.

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A rare mutation of thyroid hormone receptor beta gene in thyroid hormone resistance syndrome

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-21-0023 ◽

2021 ◽

Vol 2021 ◽

Author(s):

Michela Del Prete ◽

Fabrizio Muratori ◽

Irene Campi ◽

Gianleone Di Sacco ◽

Federico Vignati ◽

...

Keyword(s):

Thyroid Hormone ◽

Thyroid Hormones ◽

Genetic Test ◽

List Type ◽

Thyroid Function Tests ◽

Resistance To Thyroid Hormone ◽

Hereditary Syndrome ◽

Serum Tsh ◽

Receptor Beta ◽

Tsh Levels

Summary Resistance to thyroid hormone (RTH) is a rare hereditary syndrome with impaired sensitivity to thyroid hormones (TH) and reduced intracellular action of triiodothyronine (T3) caused by genetic variants of TH receptor beta (TRB) or alpha (TRA). RTH type beta (RTHβ) due to dominant negative variants in the TRB gene usually occurs with persistent elevation of circulating free TH, non-suppressed serum TSH levels responding to a thyrotropin-releasing hormone (TRH) test, an absence of typical symptoms of hyperthyroidism and goiter. Here, we present a rare variant in the TRB gene reported for the first time in an Italian patient with generalized RTHβ syndrome. The patient showed elevated TH, with non-suppressed TSH levels and underwent thyroid surgery two different times for multinodular goiter. The genetic test showed a heterozygous mutation in exon 9 of the TRB gene resulting in the replacement of threonine (ACG) with methionine (ATG) at codon 310 (p.M310T). RTHβ syndrome should be considered in patients with elevated TH, non-suppressed TSH levels and goiter. Learning points Resistance to thyroid hormone (RTH) is a rare autosomal dominant hereditary syndrome with impaired tissue responsiveness to thyroid hormones (TH). Diagnosis of RTH is usually based on the clinical finding of discrepant thyroid function tests and confirmed by a genetic test. RTH is a rare condition that must be considered for the management of patients with goiter, elevation of TH and non-suppressed serum TSH levels in order to avoid unnecessary treatments.

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Association between Thyroid Stimulating Hormone and Respiratory Distress Syndrome of Newborn in the Preterm Infants

10.21203/rs.3.rs-40381/v1 ◽

2020 ◽

Author(s):

Young Jin Kim ◽

Byoung Kook Kim ◽

Yong Hyuk Kim

Keyword(s):

Thyroid Hormone ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Gestational Age ◽

Distress Syndrome ◽

Control Group ◽

Lower Serum ◽

Significant Difference ◽

Serum Tsh ◽

Tsh Levels

Abstract Background: Various hormones are known to influence the production and secretion of pulmonary surfactant. But the relationship between respiratory distress syndrome (RDS) and thyroid hormone has yet to be clarified. Methods: 126 infants with gestational age between 24 and 34 weeks who were hospitalized at the neonatal ICU of the Wonju Severance Christian Hospital from April 2017 to February 2019 were included in the study. Infants were divided into 3 groups by gestational age – 24 weeks 0 days to 28 weeks 0 days, 28 weeks 0 days to 31 weeks 0 days, and 31 weeks 0 days to 33 weeks 0 days, each with 18, 34, and 74 subjects, respectively. Among the subjects, there were 56 infants with RDS and 70 infants without RDS.Results: The group with lowest gestational age showed T3 and fT4 level that was lower than those of other groups (p<0.05) on the day of birth but there was no difference in the TSH level (p=0.129). T3 and TSH level were lower in the RDS group compared with the control group on the day of birth (p<0.05). Free thyroxine (fT4) level was higher in the control group on the day of birth but without any significant difference. Multiple logistic regression analysis showed that lower serum TSH levels on the day of birth was associated with a higher incidence of RDS (p<0.05).Conclusion: The incidence of RDS was significantly higher in infants with lower serum TSH levels at birth, but there was no significant difference in RDS incidence according to serum thyroid hormone levels.

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INFLUENCE OF TESTOSTERONE ON THE SECRETION OF THYROTROPHIN IN THE RAT

Acta Endocrinologica ◽

10.1530/acta.0.0500155 ◽

1965 ◽

Vol 50 (1) ◽

pp. 155-160 ◽

Cited By ~ 11

Author(s):

G. P. van Rees ◽

E. L. Noach ◽

J. A. M. J. van Dieten

Keyword(s):

Thyroid Hormone ◽

Testosterone Propionate ◽

Male Rats ◽

Thyroxine Treatment ◽

High Doses ◽

Serum Tsh ◽

Tsh Levels

ABSTRACT Castration of male rats decreases both pituitary and serum TSH-levels. Administration of testosterone propionate increases serum TSH-levels in castrated males, but its effect on pituitary TSH-content appears to be complex: whereas treatment with physiological amounts of testosterone prevents the decrease induced by castration, administration of high doses of testosterone results in low pituitary TSH-contents not unlike those seen in untreated castrated rats. Testosterone administered to thyroxine-maintained thyroidectomized rats had the same effects as mentioned above, but if thyroxine treatment was omitted, no effect of testosterone on pituitary and serum TSH-levels could be observed. It is thought that testosterone interferes with the effect of thyroid hormone on the secretion of TSH.

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