Applicability of the third-generation, thyroid-stimulating hormone assay in pregnancy

Summary Familial nonautoimmune hyperthyroidism (FNAH) is rare and occurs due to a constitutively activating thyroid-stimulating hormone receptor (TSHR) germline mutation. Forty-one families with FNAH have been reported so far. In the study, 17 of 41 families were not diagnosed with FNAH until three generations or more were described with hyperthyroidism. We report a case of FNAH diagnosed in the third generation. The index patient was diagnosed with hyperthyroidism at age 3. Large fluctuations in thyroid hormone levels occurred during anti-thyroid drug treatment, and he developed a goiter. The patient’s mother had similar history, requiring two surgical interventions and radioiodine treatment. The younger brother of the index patient did not experience large thyroid hormone level fluctuations, nor increased thyroid growth. A heterozygous TSHR c.1357A>G mutation, resulting in a M453V amino acid exchange, was detected in all three patients leading to FNAH diagnosis, with complete genotype–phenotype segregation. Based on Sorting intolerant from tolerant (SIFT) and PolyPhen2 scores of 0.01 and 0.99, respectively, an effect on protein function can be assumed. As illustrated by this family with FNAH, total thyr oidectomy is necessary for patients with nonautoimmune hyperthyroidism. Development of goiter is common, anti-thyroid drug treatment is often difficult, and remission of hyperthyroidism does not occur after discontinuation of anti-thyroid drug treatment. Thus, early diagnosis and appropriate treatment of FNAH is necessary to avoid predictable, unnecessary complications and further surgical interventions. Learning points In the study, 19/42 cases of familial nonautoimmune hyperthyroidism (FNAH), including the reported case, were not diagnosed as FNAH until the third generation; this lead to suboptimal treatment and frequent relapses of nonautoimmune hyperthyroidism (NAH). Detection of thyroid-stimulating hormone receptor (TSHR) mutations in patients with suspected FNAH to confirm diagnosis is essential to ensure proper treatment for the patient and further affected family members. NAH will persist without proper treatment by total thyroidectomy. Symptoms and age of onset may vary between family members All family members with a TSHR germline mutation should be monitored with thyroid-stimulating hormone and for symptoms throughout their lives.

Download Full-text

Thyroid Stimulating Hormone Measurement Using a Third Generation Immunometric Assay

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456329503200308 ◽

1995 ◽

Vol 32 (3) ◽

pp. 307-313 ◽

Cited By ~ 5

Author(s):

Christine R Squire ◽

William D Fraser

Keyword(s):

Second Generation ◽

Light Emission ◽

Standard Procedure ◽

Thyroid Stimulating Hormone ◽

Third Generation ◽

Assay Sensitivity ◽

Thyroxine Therapy ◽

The Third ◽

Assay Performance ◽

Stimulating Hormone

After an initial evaluation of the standard procedure for performance of a third generation TSH (thyroid stimulating hormone) assay (Amerlite TSH-30) modifications were made to standardize the timing of measurement of light emission following signal reagent addition. By adopting this optimized procedure, a significant improvement in assay sensitivity was achieved when compared to a second generation TSH assay (DAKO). Using the optimized assay the sensitivity was 0·003 mU/L (20 replicates of zero) or 0·009 mU/L [22% CV (coefficient of variation) from the precision profile]. Recovery of added TSH and parallelism of the assay were good. A significant negative bias was detected for the Amerlite TSH-30 assay when compared to the DAKO assay (log y = 0·92 log x − 0·33, n = 210). Excellent discrimination was achieved between euthyroid, hypothyroid and thyrotoxic subjects. A high percentage of thyrotoxic patients had undetectable TSH and the spread of values between thyrotoxic and euthyroid was greater with the third generation assay. In patients receiving thyroxine therapy a higher percentage had detectable TSH values. The optimized Amerlite TSH 30 assay offers improved assay performance when compared to a second generation assay.

Download Full-text

Management of thyroid disease in pregnancy – Room for improvement in the first trimester

Obstetric Medicine ◽

10.1177/1753495x16629773 ◽

2016 ◽

Vol 9 (3) ◽

pp. 126-129 ◽

Cited By ~ 1

Author(s):

Helen Robinson ◽

Philip Robinson ◽

Michael D’Emden ◽

Kassam Mahomed

Keyword(s):

General Practitioner ◽

Thyroid Function ◽

Thyroid Disease ◽

Thyroid Dysfunction ◽

First Trimester ◽

Antenatal Clinic ◽

Thyroid Stimulating Hormone ◽

Thyroid Function Tests ◽

In Pregnancy ◽

Stimulating Hormone

Background First-trimester care of maternal thyroid dysfunction has previously been shown to be poor. This study evaluates early management of thyroid dysfunction in pregnancy in Australia. Methods Patients reviewed by the Obstetric Medicine team for thyroid dysfunction from 1 January 2012 to 30 June 2013 were included. Data were collected on gestation at referral from the patient’s general practitioner to the antenatal clinic, information provided in the referral letter, thyroid function tests and thyroid medications. Results Eighty-five women were included in the study. At the time of general practitioner referral to antenatal services, 19% of women with preexisting thyroid disease had no thyroid function tested. Forty-three percent had an abnormal thyroid-stimulating hormone defined as being outside the laboratory-specific pregnancy reference range if available, or outside the level of 0.1–2.5 mIu/L in the first trimester, 0.2–3.0 mIu/L in the second trimester and 0.3–3.0 mIu/L in the third trimester. Only 21% of women increased their thyroxine dose prior to their first antenatal clinic review. Conclusion This study highlights that a significant proportion of women with known thyroid disease either have untested thyroid function in the first trimester or a thyroid-stimulating hormone outside of levels recommended by guidelines.

Download Full-text

Analytical validation of the LiCA® high-sensitivity human thyroid stimulating hormone assay

Clinical Biochemistry ◽

10.1016/j.clinbiochem.2021.11.018 ◽

2021 ◽

Author(s):

Miao Wang ◽

Jing Li ◽

Youyuan Huang ◽

Tao Chen ◽

Sheng Dong ◽

...

Keyword(s):

High Sensitivity ◽

Thyroid Stimulating Hormone ◽

Human Thyroid ◽

Analytical Validation ◽

Hormone Assay ◽

Stimulating Hormone

Download Full-text

Thyroid Disease I: Hyperthyroidism in Pregnancy

10.2310/obg.19041 ◽

2020 ◽

Author(s):

Robert B. Martin ◽

Brian Casey

Keyword(s):

Hyperemesis Gravidarum ◽

Beta Blockers ◽

Thyroid Stimulating Hormone ◽

Thyroid Storm ◽

Care Level ◽

Hypermetabolic State ◽

Life Threatening ◽

Overt Hyperthyroidism ◽

In Pregnancy ◽

Stimulating Hormone

Thyroid physiologic adaptations in pregnancy may be confused with pathologic changes. Human chorionic gonadotropin rises early in pregnancy, stimulating thyrotropin secretion and suppressing thyroid stimulating hormone. These chemical changes are often seen in hyperemesis gravidarum and gestational transient thyrotoxicosis. Therefore, mild thyrotoxicosis may be difficult to differentiate from early pregnancy thyroxine stimulation. However, overt hyperthyroidism usually includes classic symptoms seen outside of pregnancy in addition to suppressed TSH and T4 levels. Treatment includes thionamides propylthiouracil and methimazole. Thyroid ablation is contraindicated in pregnancy. Often, in affected women, the fetus is euthyroid, but neonates can develop hyper or hypothyroidism with or without a goiter. Lastly, thyroid storm, though rare, is life threatening. Often presenting as a hypermetabolic state with cardiomyopathy and pulmonary hypertension, it generally results from decompensation from preeclampsia, anemia, sepsis, or surgery. Treatment requires intensive care level management, with initiation of thionamides, iodine, and beta blockers. This review contains 2 figures, 4 tables and 38 references. Keywords: Thyroid-releasing hormong, thyroid-stimulating hormone, thyromegaly, thyroid-stimulating immunoglobulins, thryotoxicosis, thionamides, thyroid storm

Download Full-text