The thyroid is a small, butterfly-shaped gland located at the base of the neck. It secretes hormones which regulate the heart, brain, liver, kidneys and skin, among other organ systems. The thyroid gland also regulates calcium. Thyroid disease is estimated to affect 20 million people in the United States, with up to 60% being undiagnosed. The risk for women to develop thyroid disease is 5 to 8-fold greater when compared with men. Most causes of thyroid disease are unknown. Typically, thyroid disease is managed by an endocrinologist after diagnosis. Although there are many health conditions that may impact the thyroid, this article will focus on hyperthyroidism, hypothyroidism, and available testing.
Hyperthyroidism is a medical condition where excess thyroid hormones are produced by the thyroid. Hyperthyroidism may manifest as heart palpitations, fatigue, tremors, anxiety, sleep problems, weight loss, heat intolerance, or sweating. Clinical presentation is influenced by patient demographics such as age, sex, comorbidities (such as pregnancy), duration of disease, certain medications, and etiology. In contrast, hypothyroidism is where not enough thyroid hormones are secreted by the thyroid gland. Symptoms may include fatigue, lethargy, cold intolerance, weight gain, constipation, change in voice, increased bleeding tendency and dry skin. Similarly, symptoms and severity may be impacted by patient demographics. If undiagnosed and therefore, untreated, symptoms can even be fatal. Hypothyroidism is found at a higher prevalence in people with autoimmune disease, Down syndrome, or Turner syndrome.
Screening for thyroid disease has been available for decades and may involve testing for thyroid stimulating hormone (TSH); thyroxine (T4), tri-iodothyronine (T3); and thyroid peroxidase (TPO) antibodies. TSH is secreted by the pituitary gland, which is located at the base of the brain. It signals the thyroid gland to produce hormones. T4 and T3 are the main hormones produced by the thyroid and assist in regulating blood pressure, body temperature, heart rate, and metabolism. TPO antibody testing is a way for clinicians to determine if there is an autoimmune condition that may be causing hypothyroidism.
Interestingly, TSH results may be confounded by circadian fluctuations (e.g. – time of day the specimen was drawn) and is prone to seasonal variations, depending on the time of year. Reference ranges for TSH may be impacted by age, sex, and patient ethnicity; and have been the topic of debate and discussion in the literature. Even with these caveats, TSH is an exceptionally reliable screening tool to assess a patient for thyroid disease.
Typically, cascade testing is used when screening for thyroid disease. Depending on results, other reflex tests are ordered. Although specific reference ranges can vary among labs, the usual algorithm is as follows:
- Perform TSH testing.
- If TSH is in the normal range, no further testing is warranted.
- If TSH is high, check T4 and TPO antibodies.
- If TSH is high and T4 is low, then hypothyroidism may be diagnosed.
- If TPO is high, an autoimmune condition such as Hashimoto’s disease or Graves’ disease may be the underlying cause of the hypothyroidism.
- If TSH is low, check T4.
- If T4 is low, check T3
- If TSH is low, and T4/T3 is high, then hyperthyroidism may be diagnosed.
There may be unique combinations of test results that may be indicative of subclinical thyroid disease. This small subgroup of patients may be more challenging to diagnose and manage for the endocrinologist.
Additionally, there are other tests available to the clinician. Thyroid radioactive iodine uptake test may also be used to screen for hyperthyroidism and thyrotoxicosis (excess circulating thyroid hormones, regardless of the source), but is contraindicated when the patient is diagnosed with Graves’ disease. Other tests available for thyroid disease include ultrasound and TSH-receptor antibodies (TRAb). These methods are preferred in Europe, Japan, and Korea.
Of note, there are specific risks of hypothyroidism to consider for the patient who is pregnant. Hypothyroidism during pregnancy is associated with an increased risk for preterm labor/delivery, miscarriage, fetal death, placental abruption, and postpartum hemorrhage. There is also evidence in the literature that maternal hypothyroidism may adversely affect child neuropsychological and intellectual development. Therefore, screening for patients who desire to become pregnant should be part of routine pre-conception and prenatal care.
On the surface, diagnosis and management of patients with thyroid disease may seem straight-forward. However, there may be many nuances to thyroid disease, as described here. Fortunately, thyroid disease screening and testing is available to clinicians when caring for their patients. It is important for clinical staff members to rely upon the expertise of the reference lab performing the thyroid screening when troubleshooting difficult cases. It is also important for the patients to communicate their symptoms to their medical provider, to facilitate diagnosis and a treatment plan for the thyroid disease.
- American Association of Clinical Endocrinology: https://www.aace.com/disease-and-conditions/thyroid/all-about-thyroid. Accessed 10/19/2020
- American Thyroid Association: https://www.thyroid.org/media-main/press-room/#:~:text=An%20estimated%2020%20million%20Americans,thyroid%20disorder%20during%20her%20lifetime. Accessed 10/19/2020
- Koulouri O, Moran C, Halsall D, Chatterjee K, Gurnell M. Pitfalls in the measurement and interpretation of thyroid function tests. Best Pract Res Clin Endocrinol Metab. 2013 Dec;27(6):745-62. doi: 10.1016/j.beem.2013.10.003. Epub 2013 Oct 17. PMID: 24275187; PMCID: PMC3857600.
- De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet. 2016 Aug 27;388(10047):906-918. doi: 10.1016/S0140-6736(16)00278-6. Epub 2016 Mar 30. PMID: 27038492; PMCID: PMC5014602.
- Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet. 2017 Sep 23;390(10101):1550-1562. doi: 10.1016/S0140-6736(17)30703-1. Epub 2017 Mar 20. PMID: 28336049; PMCID: PMC6619426.
- Mayo Clinic Laboratories: Endocrinology Catalog. Thyroid Function Cascade, Serum. https://endocrinology.testcatalog.org/show/THSCM. Accessed 10/17/2020.
- Mayo Clinic Laboratories: Thyroid Function Ordering Algorithm. https://www.mayocliniclabs.com/it-mmfiles/Thyroid_Function_Ordering_Algorithm.pdf. Accessed 10/17/2020.
- Squizzato A, Romualdi E, Büller HR, Gerdes VE. Clinical review: Thyroid dysfunction and effects on coagulation and fibrinolysis: a systematic review. J Clin Endocrinol Metab. 2007 Jul;92(7):2415-20. doi: 10.1210/jc.2007-0199. Epub 2007 Apr 17. PMID: 17440013.
Insights / December 18, 2020 / by beaconlbs
It is estimated that about 50% of the variability in patient antidepressant response is due to genetic factors.
Insights / July 03, 2019 / by beaconlbs
BeaconLBS has invited the Labs-of-Choice™ to provide some more information about themselves for a blog series featuring each of the Labs-of-Choice. The following content was provided by the featured lab, Dermpath Diagnostics.