scholarly journals Recent evidence sets therapeutic targets for levothyroxine-treated patients with primary hypothyroidism based on risk of death

2021 ◽  
Vol 184 (2) ◽  
pp. C1-C3
Author(s):  
Petros Perros ◽  
Krishnarajah Nirantharakumar ◽  
Laszlo Hegedüs
Keyword(s):  
Large Population ◽  
Indirect Evidence ◽  
Thyroid Stimulating Hormone ◽  
Primary Hypothyroidism ◽  
Normal Serum ◽  
Normal Range ◽  
Ample Evidence ◽  
Risk Of Death ◽  
Hypothyroid Patients ◽  
Serum Tsh

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.

Is There Compensated Hypothyroidism in Infancy?

PEDIATRICS ◽  
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.

scholarly journals Age-Related Serum Thyroid-Stimulating Hormone Reference Range in Older Patients Treated with Levothyroxine: A Randomized Controlled Feasibility Trial (SORTED 1)

2019 ◽  
Vol 9 (1) ◽  
pp. 40-48 ◽  
Author(s):  
Salman Razvi ◽  
Vicky Ryan ◽  
Lorna Ingoe ◽  
Simon H. Pearce ◽  
Scott Wilkes
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Bone Resorption ◽  
Cardiovascular Risk Factors ◽  
Reference Range ◽  
Thyroid Stimulating Hormone ◽  
Adverse Impact ◽  
Feasibility Trial ◽  
Hypothyroid Patients ◽  
Serum Tsh

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.

The nocturnal thyroid-stimulating hormone surge is absent in overt, present in mild primary and equivocal in central hypothyroidism

1992 ◽  
Vol 126 (3) ◽  
pp. 206-212 ◽  
Author(s):  
Ria Adriaanse ◽  
Johannes A Romijn ◽  
Erik Endert ◽  
Wilmar M Wiersinga
Keyword(s):  
Positive Relationship ◽  
Thyroid Stimulating Hormone ◽  
Relative Increase ◽  
Primary Hypothyroidism ◽  
Overt Hypothyroidism ◽  
Central Hypothyroidism ◽  
Pituitary Disease ◽  
Hypothyroid Patients ◽  
Nocturnal Rise ◽  
Central Lesions

The nocturnal TSH surge was studied in controls, in 34 patients with hypothalamic/pituitary disease and in 21 patients with primary hypothyroidism. It was absent in 5/12 hypothyroid patients and in 5/22 euthyroid patients with hypothalamic/pituitary disease (42% vs 23%. NS). Central hypothyroidism relative to euthyroidism was associated with a lower absolute (0.3±0.4 vs 0.9±1.0 mU/l, p<0.05) and relative (24±31 vs 63±51%, p<0.05) nocturnal rise in TSH. In primary hypothyroidism, the nocturnal TSH surge was absent in eight often patients with overt, in one of five patients with mild and in none of six patients with subclinical hypothyroidism. The relative nocturnal rise in TSH was normal in mild (54±33%) and subclinical (92±69%), but decreased in overt hypothyroidism (2±10%). Plasma T4 was positively and 09.00 plasma TSH negatively related to the relative nocturnal TSH surge in primary hypothyroidism, but not in central lesions. In both conditions, however, a positive relationship was observed between the relative nocturnal TSH surge and the relative increase of TSH to TRH. In conclusion: (a) The nocturnal TSH surge is usually absent in overt hypothyroidism but present in mild primary hypothyroidism and equivocal in central hypothyroidism. This limits its usefulness as an adjunct in the diagnosis of central hypothyroidism. (b) The magnitude of the nocturnal TSH surge in patients with hypothalamic/pituitary disease or primary hypothyroidism is directly related to the TSH response to TRH, and thus appears to be determined by the directly releasable TSH pool of the pituitary.

Urine TRH immunoreactivity in hypothyroid and hyperthyroid patients

1984 ◽  
Vol 105 (4) ◽  
pp. 482-486 ◽  
Author(s):  
Anna-Stina Suhonen ◽  
Juhani Leppäluoto ◽  
Jorma Salmi
Keyword(s):  
Healthy Subjects ◽  
Ammonium Acetate ◽  
Polar Solvent ◽  
Primary Hypothyroidism ◽  
Exchange Chromatography ◽  
Reverse Phase ◽  
Before And After ◽  
Hypothyroid Patients ◽  
Hyperthyroid Patients ◽  
Serum Tsh

Abstract. Urine samples from 8 healthy subjects, from 16 patients with primary hypothyroidism and 8 patients with Graves' hyperthyroidism were pre-purified in SP-Sephadex-C-25 cation-exchange-chromatography, subjected to reverse phase high-pressure liquid chromatography (HPLC) with 0.01 M ammonium acetate pH 4 as a polar and propanol as a non-polar solvent with a 1%/min gradient and assayed in our TRH radioimmunoassay. Urine TRH-immunoreactivity levels were measured before and after 3 months of treatment with thyroxine or methimazole. The urine TRH-levels in healthy subjects were 5.5 ± 1.4 ng/l (mean ± sem, n = 8). In the hypothyroid patients, the urine TRH levels were 50.6 ±40 ng/l before and 71.7 ± 45.3 ng/l after 3 months of treatment with thyroxine. These values did not significantly differ from those in healthy subjects. The large variations were due to highly elevated values in 3 patients. In 2 hypothyroid patients with initially high urine TRH values, 67 and 657 ng/l, urine TRH was measured 5 and 18 months later and was found to have decreased to 5 and 11 ng/l. In the hyperthyroid patients, urine TRH levels were 10.3 ± 3.9 ng/l before and 8.9 ± 3.3 ng/l after the treatment with methimazole and did not differ significantly from the levels in healthy subjects. After 3 months of treatment, the hyper- and the hypothyroid patients were euthyroid. Our results show, that, except in 2 hypothyroid patients, there does not appear to be any relationship between urine TRH levels and serum TSH or thyroid hormone levels in hypothyroid and hyperthyroid patients.

SUBCLINICAL HYPOTHYROIDISM IN ADDISON'S DISEASE

1979 ◽  
Vol 91 (4) ◽  
pp. 674-679 ◽  
Author(s):  
Jens Faber ◽  
Dorte Cohn ◽  
Carsten Kirkegaard ◽  
Morten Christy ◽  
Kaj Siersbæk-Nielsen ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Mean Value ◽  
Normal Serum ◽  
Control Group ◽  
Addison's Disease ◽  
Normal Range ◽  
Microsomal Antibody ◽  
The Mean ◽  
Thyroid Microsomal Antibodies ◽  
Serum Tsh

ABSTRACT Fourteen patients with Idiopatic Addison's disease (IAD) were studied in order to detect a possible subclinical hypothyroid state. All were clinically euthyroid with normal serum thyroxine (T4) and serum 3,5′,3′-triiodothyronine (T3). Eleven had circulating thyroid microsomal antibodies in blood. The mean basal serum TSH was significantly higher than that of the control group but only three patients had values above the upper normal range. The mean value of serum T4 was decreased as compared to that of the normal persons, while serum 3,3′,5′-triiodothyronine was elevated. 7.5 mU bovine thyrotrophin per kilogram body weight injected intravenously caused a rise in serum T3 not different from the response in normals. However, as well increasing serum TSH as increasing microsomal antibody titer correlated significantly to decreasing thyroidal release of T3. Our results suggest that clinically euthyroid patients suffering from IAD might have a beginning thyroidal insufficiency because of a progressive immunological damage of the thyroid.

Low but detectable serum thyroid-stimulating hormone concentrations in ambulant subjects not receiving thyroxine

2003 ◽  
Vol 40 (6) ◽  
pp. 639-642 ◽  
Author(s):  
S Chatterjee ◽  
BP O'Malley ◽  
DE Price ◽  
AM Fielding ◽  
R Aitken
Keyword(s):  
Reference Range ◽  
Thyroid Stimulating Hormone ◽  
Normal Serum ◽  
Third Generation ◽  
Assay Sensitivity ◽  
Free Thyroid Hormones ◽  
Isotope Scanning ◽  
Detectable Serum ◽  
Serum Tsh ◽  
Stimulating Hormone

Background: In laboratories employing 'front-line' sensitive thyroid-stimulating hormone (TSH) measurement, it is generally accepted that a fully suppressed serum TSH concentration (third-generation assay) alongside normal serum concentrations of free thyroid hormones indicates subclinical hyperthyroidism. However, other explanations are often provided for low but detectable serum TSH concentrations, such as drug effects or non-thyroidal illness. Methods: We investigated 25 consecutive ambulant individuals, identified over an 18-month period as having low but not fully suppressed TSH concentrations (third-generation assay; sensitivity 0.003 mIU/L) with additional free thyroxine (T4), free tri-iodothyronine (T3) and thyroid microsomal antibody estimations and thyroid isotope scanning (technetium). Results: Concentrations of serum hormones (median, inter-quartile range) were: TSH, 0.23, 0.17-0.26 mIU/L (reference range 0.34-5.6 mIU/L); free T4, 14.6, 10.6- 17.6 pmol/L (reference range 10-25 pmol/L); free T3, 6.1, 5.7-6.6 pmol/L (reference range 4.5-7.5 pmol/L). Thyroid antibodies were negative in all but one individual. On isotope scanning, nine individuals had hot nodules and ten individuals had multinodular goitres (MNG). Of the six with normal scans, ultrasound scanning showed a definite MNG ( n = 1) and early MNG ( n = 2). Conclusions: A low but detectable serum TSH concentration, obtained using a third-generation assay, found in an ambulant individual, is frequently a pointer to underlying thyroid disease.

Free thyroxine, free triiodothyronine, and thyrotropin concentrations in hypothyroid and thyroid carcinoma patients receiving thyroxine therapy

1987 ◽  
Vol 116 (3) ◽  
pp. 418-424 ◽  
Author(s):  
K. Liewendahl ◽  
T. Helenius ◽  
B.-A. Lamberg ◽  
H. Mähönen ◽  
G. Wägar
Keyword(s):  
Thyroid Carcinoma ◽  
Equilibrium Dialysis ◽  
Primary Hypothyroidism ◽  
Free Thyroxine ◽  
Suppressive Therapy ◽  
Free Triiodothyronine ◽  
Thyroxine Therapy ◽  
Thyroxine Replacement ◽  
Hypothyroid Patients ◽  
Serum Tsh

Abstract. Free thyroxine (FT4) and free triiodothyronine (FT3) concentrations in serum were measured by direct equilibrium dialysis methods in patients receiving thyroxine replacement or suppression therapy. Four of 50 hypothyroid patients euthyroid on replacement therapy (mean thyroxine dose 120 μg/day) had supra-normal FT4 concentrations, whereas the FT3 concentrations were normal in all. Forty-one of 56 operated thyroid carcinoma patients on suppressive therapy (mean thyroxine dose 214 μg/day) had raised FT4 concentrations, whereas the FT3 concentration was elevated in only one patient. There was a large difference in mean FT4 values for hypothyroid and thyroid carcinoma patients (17.2 vs 29.5 pmol/l), whereas the difference in mean FT3 values was small (5.0 vs 6.1 pmol/l), suggesting a decreased peripheral conversion of T4 to T3 with increasing concentrations of FT4. Serum TSH concentrations, as determined by an immunoradiometric assay, varied from < 0.02 to 11.9 mU/l in treated hypothyroid patients; 21 patients (42%) had values outside the reference limits. As a single test, serum TSH is therefore not very useful for the assessment of adequate thyroxine dosage in patients with primary hypothyroidism. In thyroid carcinoma patients, the TSH concentrations were < 0.18 mU/l; 45 patients had values < 0.02 mU/l indicating sufficient suppression of TSH secretion in the majority of cases. On the basis of these results we recommend the combination of FT3 and TSH tests for monitoring thyroxine replacement and suppression therapy. FT4 appears less useful than FT3 for this purpose even if special reference values values were adopted for each patient group.

MEASUREMENTS OF SERUM TRIIODOTHYRONINE BY RADIOIMMUNOASSAY

1974 ◽  
Vol 77 (1) ◽  
pp. 71-81 ◽  
Author(s):  
C. Kirkegaard ◽  
Th. Friis ◽  
K. Siersbæk-Nielsen
Keyword(s):  
Binding Proteins ◽  
Normal Serum ◽  
Normal Range ◽  
Dextran Coated Charcoal ◽  
Hypothyroid Patients ◽  
Hyperthyroid Patients

ABSTRACT A radioimmunoassay of serum T3 was developed displacing T3 from the thyroxine binding proteins by merthiolate. Separation of the free and the antibody bound fraction was accomplished by the use of dextran-coated charcoal. The addition of 14 mg BSA was shown to diminish the adsorption of the antibody bound fraction to charcoal. In 90 controls serum T3 was 1.33 ± sd 0.29 ng/ml. None of 94 hyperthyroid patients had serum T3 values within normal range, whereas 12% of 34 hypothyroid patients had normal serum T3 values. The T4:T3 ratio in serum was found to be 67.0 ± sd 11.9 in normals, while the ratio was significantly (P < 0.001) decreased as well in hyperthyroid as in hypothyroid patients. The discriminant value of serum T3 was found to be superior to T4 in the diagnosis of hyperthyroidism, whereas serum T4 was found to be better with regard to hypothyroidism. However, correction of the influence of different TBG levels by calculating free T4 index and free T3 index showed that both parameters almost completely separated normals from patients with untreated hyperthyroidism, respectively hypothyroidism.

scholarly journals Levothyroxine dose adjustment in hypothyroid women achieving pregnancy through IVF

2015 ◽  
Vol 173 (4) ◽  
pp. 417-424 ◽  
Author(s):  
Andrea Busnelli ◽  
Guia Vannucchi ◽  
Alessio Paffoni ◽  
Sonia Faulisi ◽  
Laura Fugazzola ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Dose Adjustment ◽  
Thyroid Autoimmunity ◽  
First Trimester ◽  
Primary Hypothyroidism ◽  
Second Trimester ◽  
Third Trimester ◽  
Normal Range ◽  
Detrimental Impact ◽  
Serum Tsh

ObjectiveAbout one out of two women with primary hypothyroidism has to increase the dosage of exogenous levothyroxine (l-T4) during pregnancy. Considering the detrimental impact of IVF on thyroid function, it has been claimed but not demonstrated thatl-T4dose adjustment may be more significant in hypothyroid women who become pregnant after IVF.DesignRetrospective cohort study.MethodsHypothyroid-treated women who achieved a live birth through IVF were reviewed. Women could be included if thyroid function was well compensated withl-T4before the IVF cycle (i.e., serum TSH <2.5 mIU/l and serum free T4within the normal range). Serum TSH and dose adjustment were evaluated at five time points during pregnancy. The trimester ranges for serum TSH considered as reference to adjustl-T4therapy were 0.1–2.5 mIU/l for the first trimester, 0.2–3.0 mIU/l for the second trimester, and 0.3–3.0 mIU/l for the third trimester.ResultsThirty-eight women were selected. During the whole pregnancy 32 women (84%; 95% CI: 72–96%) required an increase in the dose ofl-T4. In most cases (n=28), this occured within the first 5–7 weeks of gestation (74%, 95% CI: 58–85%). At 5–7 weeks of gestation, the median (interquartile range) increase ofl-T4dose for the whole cohort was 26% (0–50%). At 30–32 weeks, it was 33% (14–68%). In order to identify predictive factors of dose adjustment, we compared women who did (n=28) and did not (n=10) adjustl-T4dosage at 5–7 weeks' gestation. Significant differences emerged for thyroid autoimmunity prevalence and for the distribution of hypothyroidism aetiology.ConclusionsThe vast majority of hypothyroid-treated women who achieve pregnancy through IVF need an increase in thel-T4dose during gestation. This requirement tends to occur very early during gestation.

Efficacy and safety of Barg-e-Sahajna (Moringa olifera Lam.) in primary hypothyroidism

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Md Anzar Alam ◽  
Mohd Aleemuddin Quamri ◽  
Nafis Haider
Keyword(s):  
Thyroid Stimulating Hormone ◽  
Primary Hypothyroidism ◽  
Hormone Deficiency ◽  
Efficacy And Safety ◽  
Serum Glutamic Oxaloacetic Transaminase ◽  
Objective Parameter ◽  
Serum T3 ◽  
Safety Parameters ◽  
Serum Tsh

Abstract Objectives Hypothyroidism is the most common disorder arising from hormone deficiency. It frequently affects women than men. The prevalence of overall hypothyroidism has been reported to be 4.8–11%. Levothyroxine is the treatment of choice for all types of hypothyroidism. The purpose of this pilot study was to evaluate the efficacy and safety of Barg-e-Sahajna (Leaves of Moringa olifera Lam.) among diagnosed patients of primary hypothyroidism. Methods This study was an open observational study. A total of 22 patients were screened, out of which 10 were excluded (did not meet inclusion criteria) and 2 refused to consent to be part of the study, rest 10 participants were enrolled after obtaining written informed consent finally 8 subjects completed the study and 2 are dropout in last follow up. The drug was given in the form of decoction at the dose of 5 g fresh leaves twice a day after meal for 45 days. Results The study effects on objective parameter thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were found extremely significant when compared before (16.62 ± 11.49, 132 ± 19.32, 9.28 ± 1.46) and after (4.75 ± 3.12, 150.37 ± 20.68, 11.84 ± 3.81) treatment with a significant decrease in serum TSH level (p<0.0246) and an increase in serum T3 (p<0.0005) and T4 (p<0.0438) levels. The results were analyzed using paired “t” test. Conclusions The improvements in thyroid profiles (TSH, T3 and T4) after consuming ‘Barg-e-Sahajna’ show that the test drug is effective in primary hypothyroidism and the relief was considerable. No significant effect on safety parameters (serum-glutamic-oxaloacetic-transaminase [SGOT], serum glutamic-pyruvic transaminase [SGPT], blood urea, and serum creatinine) was observed. Therefore, it may be concluded that the Barg-e-Sahajna is preliminarily safe and effective in the management of primary hypothyroidism.

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