Genetics and clinical significance of thyroxine binding globulin deficiency, an analysis of seven families

Abstract. Seven families, ascertained through probands with undetectable levels of thyroxine binding globulin (TBG) were studied from clinical and genetic points of view. The blood levels of TBG, thyroxine binding prealbumin (TBPA), thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were determined in altogether 128 family members. The concentration of free thyroxine (FT4) was calculated from the concentrations of T4, TBG and TBPA. Only men (n = 15) were found to have total TBG deficiency. Their TSH levels were within normal range and they did not show any clinical symptoms of thyroid dysfunction. The mothers and daughters of the affected men had significantly lower TBG levels than control women. Segregation analysis performed on 46 nuclear families showed significant evidence for an X-linked additive mode of transmission and an additional multifactorial component with heritability 0.47.

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FAMILIAL THYROXINE-BINDING GLOBULIN DEFICIENCY IN ASSOCIATION WITH NON-TOXIC GOITRE

Acta Endocrinologica ◽

10.1530/acta.0.0910070 ◽

1979 ◽

Vol 91 (1) ◽

pp. 70-76 ◽

Cited By ~ 1

Author(s):

Paul Bratusch-Marrain ◽

Hannes Haydl ◽

Werner Waldhäusl ◽

Robert Dudczak ◽

Wolfgang Graninger

Keyword(s):

Clinical Evidence ◽

Autosomal Dominant ◽

Serum Concentrations ◽

Dominant Inheritance ◽

Normal Range ◽

Thyroxine Binding Globulin ◽

The Family ◽

High Incidence ◽

Total Thyroxine ◽

Mode Of Transmission

ABSTRACT A kindred is presented in which 4 members in 3 generations showed absent or reduced serum concentrations of thyroxine-binding globulin (TBG). TBG was undetectable by radioimmunoassay in one male and decreased to varying extent in 3 female patients (4.0, 4.2 and 8.6 μg/ml; normal range 12.5–26.0 μg/ml). Total thyroxine serum concentrations in the affected subjects were well in the hypothyroid range without clinical evidence of hypothyroidism. The mode of transmission of the trait was consistent with X-chromosome linkage. A high incidence of non-toxic goitre was also present in most of the family members examined irrespective of TBG levels. The transmission of the goitre trait was compatible with autosomal dominant inheritance. Thus its association with transmission of TBG deficiency was interpreted as not causal but coincidental.

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Comparison Study Between Local TSH IRMA Kit (CRRT) and Imported TSH IRMA Kit (Riakey, Korea)

JKPK (Jurnal Kimia dan Pendidikan Kimia) ◽

10.20961/jkpk.v4i2.29756 ◽

2019 ◽

Vol 4 (2) ◽

pp. 77

Author(s):

Gina Mondrida ◽

Triningsih Triningsih ◽

Kristina Dwi Purwanti ◽

Sutari Sutari ◽

Sri Setyowati ◽

...

Keyword(s):

False Negative ◽

Thyroid Stimulating Hormone ◽

The Body ◽

True Positive ◽

Comparison Study ◽

Complex Matrix ◽

Normal Range ◽

True Negative ◽

Immunoassay Technique ◽

Tsh Levels

<p><em>Thyroid Stimulating Hormone</em> (TSH) is one of hormones that our body need for growth of brains, bones and other tissues and regulate the metabolism in the body. Normal range of TSH for adult is from 0.3 to 5.5 µIU/ml, whereas for baby ranged from 3 to 18 µIU/ml. An Immunoradiometricassay (IRMA) is one of immunoassay technique using radionuclide as the tracer to detect low quantity of analyte. This technique is suitable for determine TSH levels in human blood serum which has complex matrix and various concentration. The Center for Radioisotope and Radiopharmaceutical Technology (CRRT)-BATAN has developed a reagent of TSH IRMA kit. The aim of this research is to compare between local TSH IRMA kit (CRRT-BATAN) and imported TSH IRMA kit (Riakey, Korea) toward 110 adult samples obtained from PTKMR - BATAN. The results showed 97 samples as true negative, 5 samples as true positive, 1 sample as false negative and 7 samples false positive. The comparison study gave diagnostic sensitivity as much as 83.33 %, diagnostic spesificity as much as 93.27 % and accuracy as much as 92.72 %.</p>

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Relation between thyroid-stimulating hormone and the occurrence of cardiovascular events and mortality in patients with manifest vascular diseases

European Journal of Preventive Cardiology ◽

10.1177/1741826711416045 ◽

2011 ◽

Vol 19 (4) ◽

pp. 864-873 ◽

Cited By ~ 15

Author(s):

Jan Westerink ◽

Yolanda van der Graaf ◽

Daniël R Faber ◽

Wilko Spiering ◽

Frank LJ Visseren

Keyword(s):

Myocardial Infarction ◽

Vascular Disease ◽

Vascular Diseases ◽

Thyroid Stimulating Hormone ◽

Tissue Thickness ◽

Normal Range ◽

Increased Risk ◽

All Cause Mortality ◽

Visceral Adipose ◽

Tsh Levels

Aims: To investigate whether levels of thyroid-stimulating hormone (TSH) within the normal range are associated with an increased risk of new vascular events and mortality in patients with clinical manifest vascular diseases and whether this relation is influenced by adiposity. Methods and results: Prospective cohort study in 2443 patients (1790 men and 653 women) with clinical manifest vascular disease and TSH levels in the normal range. Median follow up was 2.7 (interquartile range 1.4–3.9) years. Clinical endpoints of interest were: myocardial infarction, stroke, vascular death, and all-cause mortality. In patients with manifest vascular disease, the prevalence of (subclinical) hypothyroidism was 5.7%, while 3.6% had (subclinical) hyperthyroidism. An increase in 1 unit of TSH was associated with a 33% higher risk (HR 1.33; 95% CI 1.03–1.73) for the occurrence of myocardial infarction, adjusted for age, gender, renal function, and smoking. In patients with a body mass index (BMI) below the median of 26.7 kg/m2 the HR per unit TSH for myocardial infarction was 1.55 (95% CI 1.08–2.21) compared to 1.18 (95% CI 0.81–1.71) in patients with a BMI ≥26.7 kg/m2. Visceral adipose tissue thickness below the median (≤8.8 cm) was associated with higher HR per unit TSH for myocardial infarction (HR 1.69; 95% CI 1.21–2.35) compared to visceral adipose tissue thickness >8.9 cm (HR 1.00; 95% CI 0.66–1.49). There was no relation between TSH and risk of stroke, vascular death, the combined endpoint, or all-cause mortality. Conclusion: Higher TSH levels within the normal range are associated with an increased risk of myocardial infarction, in patients with clinical manifest vascular disease. This relation is most prominent in patients without visceral obesity.

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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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P1536Does free thyroxine (fT4) predict risk of atherosclerotic cardiovascular disease (ASCVD)?

European Heart Journal ◽

10.1093/eurheartj/ehz748.0298 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

J L Anderson ◽

V Jacobs ◽

H T May ◽

T L Bair ◽

B A Benowitz ◽

...

Keyword(s):

Thyroid Stimulating Hormone ◽

Atherosclerotic Cardiovascular Disease ◽

Reference Ranges ◽

Rotterdam Study ◽

Normal Range ◽

Hormone Levels ◽

Prevalent Disease ◽

Artery Disease ◽

Intermountain Healthcare ◽

Tsh Levels

Abstract Background Thyroid hormones are associated with arrhythmic risk, but their relationship to ASCVD is unclear. The Rotterdam Study* reported associations of higher fT4 and lower thyroid stimulating hormone (TSH) levels with ASCVD, including within the euthyroid range. Free T3 (fT3) was not assessed. Methods We tested whether fT4, fT3, and TSH levels were associated with ASCVD in Intermountain Healthcare. All patients >18 y old with an fT4 level in the electronic medical record database were included. The hormone reference ranges were divided into quartiles (Q), and associations with prevalent and incident ASCVD were assessed by multivariable regression and trend tests. Results A total of 212,202 patients (age = 64.4±11.2 y; 66.6% women) were included and followed for 6.1±4.4 y. Of these, 8.3%, 86.6%, and 5.1% had fT4 levels below, within, and above the reference range. CAD was prevalent in 18.9% of fT4 Q1 patients. The adjusted odds ratio (OR) for coronary artery disease (CAD) increased through (Q4/Q1 OR=1.36) and beyond (High/Q1 OR=1.71) the normal range, p-trend<0.001 (Table). Smaller incremental risks were noted for fT3 (Q4/Q1 OR=1.13; High/Q1 OR=1.25). The frequencies of incident MI (Q1=2.5%) and stroke (Q1=5.4%) were low and did not show a concentration-related risk gradient. Incident all-cause death (Q1=24.3%) increased slightly for Q4 and high fT4 (OR=1.05, 1.06) but not fT3; death also increased with low fT4 (OR=1.28). TSH showed no consistent gradient within the normal range for prevalent or incident events; however, mortality increased with both high and low TSH. Thyroid Hormone Levels and Prevalent CAD Prevalent CAD (adjusted OR) Low Normal Q1 Normal Q2 Normal Q3 Normal Q4 High fT4 (n=212,202) OR=1.08, p=0.02 OR=1.00 referent OR=1.11, p<0.001 OR=1.21, p<0.001 OR=1.36, p<0.001 OR=1.71, p<0.001 fT3 (n=30,200) OR=1.12, p<0.001 OR=1.00 referent OR=0.98, p=0.61 OR=1.02, p=0.53 OR=1.13, p<0.001 OR=1.25, p<0.001 TSH (n=183,227) OR=1.39, p<0.001 OR=1.00 referent OR=0.93, p=0.42 OR=0.88, p=0.15 OR=0.92, p=0.35 OR=1.73, p<0.001 Reference Q 1–4 are: fT4: 0.75–0.90; 0.91–1.01; 2.02–1.14; 1.15–1.50 ng/dL; TSH: 0.54–1.30; 1.31–2.04; 2.05–3.68; 3.69–6.80 uIU/mL; fT3: 2.40–2.60; 2.70–2.80; 2.90–3.10; 3.20–4.20 pg/dL. Conclusions Consistent with the Rotterdam Study, we found an increase in prevalent CAD with increasing fT4 levels within and beyond the normal range and, uniquely, a more modest relationship with fT3. We could not confirm a normal-range relationship between hormone levels and incident events or between TSH and prevalent disease. The relationship of fT4 levels to ASCVD is intriguing, is deserving of further study, and may have important implications for ASCVD prevention. *A Bano, et-al. Circ Res 2017; 121:1397–1400

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Exceptionally elevated creatine kinase levels in a laryngectomized patient: hypothyroid myopathy

The Journal of Laryngology & Otology ◽

10.1258/0022215041917934 ◽

2004 ◽

Vol 118 (8) ◽

pp. 651-652 ◽

Cited By ~ 2

Author(s):

Udi Cinamon

Keyword(s):

Creatine Kinase ◽

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Thyroid Stimulating Hormone ◽

Blood Levels ◽

Normal Range ◽

Laboratory Findings ◽

Laryngectomized Patient ◽

Hypothyroid Myopathy

We present a laryngectomized patient with unspecific complaints of fatigue whose laboratory findings were out of proportion with the clinical presentation. The enormously high blood levels of creatine kinase (CPK) (8000 IU/l, normal range 30–190 IU/l) and thyroid-stimulating hormone (100 mU/l, normal range 0.5–4.5 mU/l) led to diagnosis and treatment of and recovery from hypothyroid myopathy. Hypothyroidism reduces the ability of the muscle to maintain its adequate energetic economy, via several suggested mechanisms. This may lead to injury (myopathy) that allows enzymes such as CPK to leak out of cells and causes elevation of their serum levels. To our knowledge, this is the first reported case of a patient previously treated for head and neck cancer who developed hypothyroid myopathy, presenting with exceptionally elevated CPK levels. This is noteworthy, since hypothyroidism may be easily avoided by a comprehensive follow-up of patients treated for head and neck cancer.

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Yagya Therapy for Sub-Clinical Hypothyroidism: A Case Study

Interdisciplinary Journal of Yagya Research ◽

10.36018/ijyr.v1i2.13 ◽

2018 ◽

Vol 1 (2) ◽

pp. 31-36 ◽

Cited By ~ 1

Author(s):

Shilpi Verma ◽

Pawan Kumar ◽

Alka Mishra ◽

Vandana Shrivastava

Keyword(s):

Thyroid Stimulating Hormone ◽

Normal Range ◽

Hormonal Balance ◽

Effective Option ◽

Low Levels ◽

Traditional Approaches ◽

In Fire ◽

Very High ◽

Tsh Levels

Sub-clinical hypothyroidism (SCH) is a condition in which Thyroid Stimulating Hormone (TSH) levels are increased, Thyroxine (T4) level is normal to low, and Triiodothyronine (T3) level is normal. Daily use of the synthetic thyroid hormone such as levothyroxine has been a standard approach to SCH. However, most modern approaches are unable to revert the condition to its normal level. Traditional approaches such as Yagya-Therapy can be an effective option in this regard. Yagya-Therapy provides pulmonary inhalation of medicinal-smoke of multiple herbs (generated through oblation in fire along with chanting of Vedic hymns), which have the potential for hormonal balance A case study is being reported wherein a patient (Male/60 years), who had been suffering from SCH since past 2 years and 4 months (pre-data), had been continuously taking allopathic medication for SCH, B12 complex and high blood pressure, and all this time TSH never became normal. The patient continued with the aforesaid medication, and took Yagya-Therapy for 3 months as an add-on therapy. Subsequently, after 4 months of completing Yagya-Therapy, post-data was recorded. Before Yagya-Therapy, TSH levels were very high, i.e. 4.79-11.82 µ/ml, which became normal (3.0 µ/ml) after the Yagya-Therapy. The earlier low levels of B12 (238-326 pg/ml) also increased to the upper side of the normal range (1034 pg/ml). Patient's other complaints such as tiredness, weakness, sleep issues were also resolved completely. Thus, the present study indicates the effectiveness of Yagya-Therapy in the treatment of SCH.

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Hypothyroidism With Thyroxine-Binding Gobulin Excess

PEDIATRICS ◽

10.1542/peds.84.1.197 ◽

1989 ◽

Vol 84 (1) ◽

pp. 197-197

Author(s):

ALEXANDER K. C. LEUNG ◽

ROBERT G. MCARTHUR

Keyword(s):

Clinical Features ◽

Preoperative thyroid-stimulating hormone associated risk of differentiated thyroid cancer in patients with thyroid nodules

Cellular and Molecular Biology ◽

10.14715/cmb/2021.67.3.11 ◽

2021 ◽

Vol 67 (3) ◽

pp. 85-91

Author(s):

Al Essa M

Keyword(s):

Thyroid Cancer ◽

Differentiated Thyroid Cancer ◽

Thyroid Nodules ◽

Conditional Logistic Regression ◽

Care Center ◽

Tertiary Care ◽

Thyroid Stimulating Hormone ◽

Normal Range ◽

Tsh Levels ◽

Stimulating Hormone

In an assessment of risk for differentiated thyroid cancer (DTC) in individuals with human papillary thyroid cancer (PTC) and thyroid nodules a cohort prospective study was undertaken to establish the significance of preoperative thyroid-stimulating hormone (TSH) levels. Confirmed histologically PTC cases in one tertiary care center, and matched healthy individuals were tested for TSH, T3, T4 and T4 free total. The ORs and 95% confidence intervals have been calculated using conditional logistic regression models (CI). The blood TSH levels were related to the higher risk of PTC for men (OR,0,09; 95% Ci, 04–0,21, 95% CI and women) compared with the middle tertile of the TSH levels in the normal range (OR,0,07; 95 percent CI, 0,04–0,1). Over the normal range of TSH levels, an elevated PTC risks were connected amongst women (OR 0,09; 95% CI, 0,04–0,21) but not amongst men (OR,0,07; 95% CI, 0,04–0,1). With an increase in TSH level in the normal range between men and women, the risk for PTC reduced (Ptrend=0.041 and 0.0001). The risk of PTC related to TSH levels has been dramatically elevated above the normal range for men and TSH values below the normal range for women.

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A rare cause of subclinical hypothyroidism: macro-thyroid-stimulating hormone

Diagnosis ◽

10.1515/dx-2019-0026 ◽

2020 ◽

Vol 7 (1) ◽

pp. 75-77

Author(s):

Cem Onur Kirac ◽

Sedat Abusoglu ◽

Esra Paydas Hataysal ◽

Aysegul Kebapcilar ◽

Suleyman Hilmi Ipekci ◽

...

Keyword(s):

Subclinical Hypothyroidism ◽

Thyroid Stimulating Hormone ◽

Overt Hypothyroidism ◽

Normal Range ◽

Free Triiodothyronine ◽

Case Presentation ◽

Chronic Autoimmune Thyroiditis ◽

Levothyroxine Replacement ◽

Tsh Levels ◽

Stimulating Hormone

AbstractBackgroundSubclinical hypothyroidism is a situation in which the thyroid-stimulating hormone (TSH) value exceeds the upper limit of normal, but the free triiodothyronine (T3) and thyroxine (T4) values are within the normal range. The etiology is similar to overt hypothyroidism.Case presentationAn 18-year-old female patient was referred to our endocrinology clinic due to elevated TSH levels detected during a routine examination. She was clinically euthyroid and had a normal thyroid ultrasound pattern. The TSH concentration was measured twice independently, giving values of 5.65 μIU/mL and 5.47 μIU/mL. The polyethylene glycol (PEG) method for TSH measurement was used to determine the concentration of macro-TSH (m-TSH), a macromolecule formed between TSH and immunoglobulin (Ig). Using the same blood samples for which the TSH levels were found to be high, the PEG method found TSH levels to be within a normal range, with values of 1.50 μIU/mL (5.65–1.50 μIU/mL measured; a decrease of 75%) and 1.26 μIU/mL (5.47–1.26 μIU/mL measured; a decrease of 77%), respectively. The TSH values determined by the PEG precipitation test were markedly low, with PEG-precipitable TSH ratios greater than 75%.ConclusionsThe cause of 55% of subclinical hypothyroidism is chronic autoimmune thyroiditis. However, it is necessary to exclude other TSH-elevated conditions for diagnosis. One of these conditions is m-TSH, which should be kept in mind even though it is rarely seen. m-TSH should be considered especially in patients who have a TSH value above 10 μIU/mL without hypothyroidism symptoms or who require a higher levothyroxine replacement dose than expected to make them euthyroid.

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