Within-Person Variation in Serum Thyrotropin Concentrations: Main Sources, Potential Underlying Biological Mechanisms, and Clinical Implications

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.

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Homeopathic Treatment of Subclinical Hypothyroidism—A Series of 19 Cases

Homeopathy ◽

10.1055/s-0041-1734028 ◽

2021 ◽

Author(s):

Luiz Carlos Esteves Grelle ◽

Luiz Antonio Bastos Camacho

Keyword(s):

Subclinical Hypothyroidism ◽

Clinical Importance ◽

Clinical Problem ◽

Thyroid Stimulating Hormone ◽

Exclusion Criteria ◽

The Mean ◽

Common Clinical Problem ◽

Prompt Diagnosis ◽

Serum Tsh ◽

Tsh Levels

Abstract Background Subclinical hypothyroidism (SCH) is a common clinical problem. Controversy surrounds the definition, clinical importance, and need for prompt diagnosis and treatment of the mild form of SCH. Aim The aim of the study was to analyze the evolution of serum thyroid stimulating hormone (TSH) levels after a therapeutic homeopathic intervention in women older than 40 years with SCH. Methods This study is a retrospective series of 19 cases of SCH, with serum TSH levels between 5 and 10 mIU/L, treated exclusively with homeopathic medicines prescribed on an individualized basis. Results Nineteen patients were included according to the inclusion and exclusion criteria. Their mean age was 56 years, they were followed for a mean duration of 69 months, the mean number of serum TSH level measurements was 18, and the intervention was successful for 13 patients. Conclusion The homeopathic therapeutic intervention was successful in 68% of the patients, with serum TSH levels back within the normal range (0.5–5.0 mIU/L).

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Effects of thyroid hormone and depression on common components of central obesity

Journal of International Medical Research ◽

10.1177/0300060519851624 ◽

2019 ◽

Vol 47 (7) ◽

pp. 3040-3049 ◽

Cited By ~ 1

Author(s):

Fu-Man Du ◽

Hong-Yu Kuang ◽

Bin-Hong Duan ◽

Da-Na Liu ◽

Xin-Yang Yu

Keyword(s):

Central Obesity ◽

Low Density Lipoprotein ◽

Fasting Blood Glucose ◽

Density Lipoprotein ◽

Epidemiological Studies ◽

Thyroid Stimulating Hormone ◽

Model Assessment ◽

Free Triiodothyronine ◽

Serum Tsh ◽

Tsh Levels

Objective We investigated the prevalence of abnormal thyroid function and depression in centrally obese participants, and to analyze the relationship of thyroid hormones and depression with components of central obesity. Methods We randomly selected 858 centrally obese participants and 500 non-obese controls in this study. For all participants, we measured serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), body mass index (BMI), waist–hip ratio (WHR), fasting blood glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid concentrations, and blood pressure. Depression was assessed using the Center for Epidemiological Studies-Depression (CES-D) scale. Results Centrally obese participants had a higher prevalence of hypothyroidism and depression than non-obese controls. Serum FT4 levels negatively correlated with BMI and serum TSH levels and positively correlated with BMI, WHR, total triglycerides (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C). After excluding participants with hypothyroidism and hyperthyroidism, serum FT4 levels showed negative correlation and serum TSH levels showed positive correlation with BMI in the remaining centrally obese participants. CES-D scores positively correlated with BMI. Conclusion We found high prevalences of hypothyroidism and depression among centrally obese participants. FT4 and TSH are important in weight regulation. Depression positively correlated with obesity.

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THE INFLUENCE OF METHALLIBURE (ICI 33,828) ON SERUM AND PITUITARY THYROID-STIMULATING HORMONE LEVELS IN THE RAT

Journal of Endocrinology ◽

10.1677/joe.0.0490569 ◽

1971 ◽

Vol 49 (4) ◽

pp. 569-572

Author(s):

J. R. BOURKE ◽

S. W. MANLEY ◽

R. W. HAWKER

Keyword(s):

Thyroid Stimulating Hormone ◽

Feedback Mechanism ◽

Seminal Vesicles ◽

Endocrine Organs ◽

System 1 ◽

Dose Levels ◽

Higher Doses ◽

Serum Tsh ◽

Tsh Levels ◽

Stimulating Hormone

SUMMARY The effect of methallibure (ICI 33,828), a non-steroidal pituitary inhibitor, on serum and pituitary thyroid-stimulating hormone (TSH) levels has been investigated. A biphasic action of the drug on serum TSH levels was observed, the greatest falls occurring with the lowest doses (2mg/day). Increasing dose and period of administration induced progressive decreases in pituitary TSH content. These results are interpreted in terms of three actions on the thyroid—pituitary system: (1) inhibition of the release of TSH from the pituitary, (2) inhibition of TSH synthesis evident only at higher doses, and (3) a thyroid-blocking action, which is also only observed at the higher dose levels, with consequent pituitary stimulation via the thyroid—pituitary feedback mechanism. Effects upon body weight and weight of endocrine organs are reported, that upon the seminal vesicles being the most marked.

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Histopathology of vasculitis

Reumatismo ◽

10.4081/reumatismo.2018.1096 ◽

2018 ◽

pp. 155-164 ◽

Cited By ~ 1

Author(s):

G. Bajocchi ◽

A. Cavazza

Keyword(s):

Clinical Practice ◽

Clinical Assessment ◽

Gold Standard ◽

Sampling Error ◽

Systemic Vasculitis ◽

Clinical Implications ◽

Disease Evolution ◽

Changes Over Time ◽

Broad Complex ◽

Over Time

The range of pathologies that are related to primitive vasculitis is broad, complex and not as typical as we would expect. Clinicians should be aware that several forms of primitive and systemic vasculitis, regardless of the size of the affected vessel, may exhibit identical histological alterations. This observation has important clinical implications as it means that cases of vasculitis do not correspond clinically and histologically. Thus, while histology remains the diagnostic gold standard, it can be used only as part of the most complete clinical assessment possible. Another point worth of the clinician’s attention is that vasculitis histology changes over time, as do disease evolution and activity, even without considering the masking effects of treatment and the possibility of sampling error due to the patchy occurrence of vasculitis. The purpose of this review is to identify the most common forms of vasculitis in clinical practice, and to provide guidance to the clinician on the pathology of the vessels.

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Syndrome of'inappropriate secretion of thyroid-stimulating hormone' by partial target organ resistance to thyroid hormones

Acta Endocrinologica ◽

10.1530/acta.0.0970361 ◽

1981 ◽

Vol 97 (3) ◽

pp. 361-368 ◽

Cited By ~ 4

Author(s):

J. Salmerón De Diego ◽

C. Alonso Rodriguez ◽

A. Salazar Orlando ◽

P. Sanchez Garcia Cervigon ◽

E. Caviola Mutazzi ◽

...

Keyword(s):

Thyroid Hormones ◽

Elevated Serum ◽

Pituitary Tumour ◽

Thyroid Stimulating Hormone ◽

Target Organ ◽

Resistance To Thyroid Hormones ◽

Serum Thyroid Hormone ◽

Serum Tsh ◽

Tsh Levels ◽

Stimulating Hormone

Abstract. A 74 year old woman was found to have elevated serum thyroid-stimulating hormone (TSH) levels and elevated serum thyroid hormone levels, with clinical euthyroidism. There was no evidence of a pituitary tumour. TSH levels increased substantially during methimazole therapy. Administration of dexamethasone was followed by a prompt fall in serum TSH levels. Triiodothyronine (T3) was administered over a period of 20 days in doses from 25 μg to as much as 100 μg daily causing a rise in serum T3 above 700 ng/100 ml, a decline of T4 and a blunting of the response to thyrotrophinreleasing hormone (TRH), with normal metabolic responses (pulse rate, photomotogram, cholesterol). These results suggest that the patient's disorder is due to partial target organ resistance to thyroid hormones.

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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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Does foetal gender influence maternal thyroid parameters in pregnancy?

European Thyroid Journal ◽

10.1530/etj-21-0001 ◽

2022 ◽

Vol 11 (1) ◽

Author(s):

Georgiana Sitoris ◽

Flora Veltri ◽

Pierre Kleynen ◽

Malika Ichiche ◽

Serge Rozenberg ◽

...

Keyword(s):

Reference Range ◽

Thyroid Autoimmunity ◽

First Trimester ◽

Thyroid Peroxidase ◽

Reference Ranges ◽

Free T4 ◽

Cross Sectional ◽

Maternal Thyroid ◽

Serum Tsh ◽

Tsh Levels

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.

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Maternal TSH levels at first trimester and subsequent spontaneous miscarriage: a nested case–control study

Endocrine Connections ◽

10.1530/ec-19-0316 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1288-1293 ◽

Cited By ~ 4

Author(s):

Jiashu Li ◽

Aihua Liu ◽

Haixia Liu ◽

Chenyan Li ◽

Weiwei Wang ◽

...

Keyword(s):

Case Control Study ◽

First Trimester ◽

Case Control ◽

Thyroid Stimulating Hormone ◽

Free Thyroxine ◽

Thyroid Peroxidase ◽

Spontaneous Miscarriage ◽

Control Study ◽

Tsh Levels ◽

Stimulating Hormone

Thyroid dysfunction is a frequently found endocrine disorder among reproductively aged women. Subclinical hypothyroidism is the most common condition of thyroid disorders during pregnancy and is defined as manifesting a thyroid-stimulating hormone concentration exceeding the trimester-specific reference value, with a normal free thyroxine concentration. Here, we evaluated the prospective association between spontaneous miscarriage and first-trimester thyroid function. We conducted a case–control study (421 cases and 1684 controls) that was nested. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroid-peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) status were measured. We found that higher TSH was related to spontaneous miscarriage (OR 1.21; 95% CI, 1.13–1.30, P < 0.001). Compared with women with TSH levels of 0.4–<2.5 mIU/L, the risk of miscarriage was increased in women with TSH levels of 2.5–<4.87 mIU/L (OR 1.47; 95% CI, 1.16–1.87) and TSH greater than 4.87 mIU/L (OR 1.97; 95% CI, 1.22–3.18). After controlling for the confounding factor, TPOAb positivity status and FT4, the results were similar. The present study showed that higher TSH was associated with miscarriage in early pregnancy. In fact, TSH levels between 2.5 and 4.87 mIU/L increased the risk for miscarriage, with TSH greater than 4.87 mIU/L increasing the risk even further.

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Age and Menopausal Status Affect Osteoprotegerin and Osteocalcin Levels in Women Differently, Irrespective of Thyroid Function

Clinical Medicine Insights Endocrinology and Diabetes ◽

10.4137/cmed.s15466 ◽

2014 ◽

Vol 7 ◽

pp. CMED.S15466 ◽

Cited By ~ 7

Author(s):

Alexander D. Shinkov ◽

Anna-Maria I. Borissova ◽

Roussanka D. Kovatcheva ◽

lliana B. Atanassova ◽

Jordan D. Vlahov ◽

...

Keyword(s):

Body Mass Index ◽

Thyroid Function ◽

Vascular Function ◽

Thyroid Dysfunction ◽

Bone Cells ◽

Menopausal Status ◽

Thyroid Stimulating Hormone ◽

Multiple Factors ◽

Serum Tsh ◽

Tsh Levels

Osteoprotegerin (OPG) and osteocalcin (OC) are essential bone proteins. Recent studies have demonstrated that they are not secreted solely by bone cells; they play roles in the vascular function and energy metabolism, and they are influenced by multiple factors. The aim of the current study was to investigate the influence of menopause and age on OPG and OC in women with different thyroid-stimulating hormone (TSH) levels. Material and Methods We studied 49 women with elevated TSH, 26 with suppressed TSH, and 67 age-matched euthyroid controls. Of them 64 were menstruating and 78 postmenopausal. Body weight, height, waist circumference (WC), body mass index (BMI), serum TSH, free thyroxin (FT4), OPG, and OC were measured. Results Generally, both OPG and OC were higher in the postmenopausal women than in the menstruating subjects (OPG 3.85 ± 1.49 pmol/L vs. 5.84 ± 2.42 pmol/L, P < 0.001; OC 8.84 ± 3.70 ng/dL vs. 12.87 ± 6.45 ng/dL, P < 0.001), and within the two thyroid dysfunction subgroups and the controls (all P < 0.05). OPG correlated with age (postmenopausal rho = 0.57, P < 0.001; premenopausal rho = 0.31, P = 0.015). Among the premenopausal subjects, OPG was higher in those with low TSH than in the controls ( P = 0.048). OC correlated negatively with BMI and WC in the postmenopausal group (Spearman rho = –-0.25, P = 0.03 and rho = –-0.42, P < 0.001 respectively). OC was higher in the postmenopausal subjects with low TSH than in those with elevated TSH ( P = 0.024), and correlated positively with FT4 (rho = 0.40, P = 0.002) and negatively with TSH (rho = -0.29, P = 0.013). CONCLUSIONS In women, OPG and OC depended differently on age and menopause and, to a lesser extent, on the thyroid function and body composition.

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Does serum TSH level act as a surrogate marker for psychological stress and cardio-metabolic risk among adolescent and young people?

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2021-0021 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Niranjan Gopal ◽

Akash Shivaji Pune ◽

Roshan Takhelmayum ◽

Ashok Kumar Ahirwar

Keyword(s):

Blood Pressure ◽

Metabolic Syndrome ◽

Psychological Stress ◽

Surrogate Marker ◽

Thyroid Stimulating Hormone ◽

First Year ◽

Metabolic Risk ◽

Anthropometric Measures ◽

Serum Tsh ◽

Tsh Levels

Abstract Objectives The incidence of metabolic syndrome is increasing even at younger ages. Metabolic syndrome constitutes a group of cardiovascular risk factors that include high cholesterol, triacylglycerol, hyperglycemia, central obesity, etc., which increases the risk of cardiovascular disease, diabetes mellitus, may be even cancer. Indian students enter colleges just after crossing their adolescent age and will be exposed to greater academic stress. Psychological stress or depression is associated with transient change in thyroid hormones level or dysfunction. To explore an association among serum Thyroid Stimulating Hormone (TSH) levels, fT3:fT4 ratio, psychological stress scores, and selected known cardio-metabolic risk markers. Methods Forty first year MBBS students were included. Their demographic, anthropometric variables, and the blood pressure were documented. Serum TSH, fT3, fT4, and salivary cortisol level was quantified. The stress level was assessed using Cohen Perceived Stress Scale Scoring. Data were expressed in mean ± standard deviation. Data (parametric/non-parametric) were compared by Independent unpaired ANOVA or Kruskal Wallis test whichever is appropriate. Spearmen correlation analysis was performed. Results Serum TSH and Cohen stress score are negatively correlated (r=−0.152), but serum cortisol showed (r=0.763) a positive correlation. TSH levels and the marks obtained in the summative assessments were negatively correlated and the correlation was not statistically significant. Conclusions The psychological stress is associated with low serum TSH, high cortisol, and poor academic performance in first year MBBS students. Blood pressure, plasma glucose, and anthropometric measures were not associated with the psychological stress.

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