Although classical overt primary hypothyroidism presents with a constellation of physical symptoms and signs confirmed by an elevated thyroid-stimulating hormone (TSH), many patients have no symptoms or vague symptoms that are not specific to hypothyroidism.[1]Chaker L, Bianco AC, Jonklaas J, et al. Hypothyroidism. Lancet. 2017 Sep 23;390(10101):1550-62.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619426
http://www.ncbi.nlm.nih.gov/pubmed/28336049?tool=bestpractice.com
[26]Siskind SM, Lee SY, Pearce EN. Investigating hypothyroidism. BMJ. 2021 Apr 27;373:n993.
https://www.bmj.com/content/373/bmj.n993.long
http://www.ncbi.nlm.nih.gov/pubmed/33906834?tool=bestpractice.com
Clinical evaluation
Symptoms of hypothyroidism include lethargy, fatigue, depression, change in voice, cold intolerance, menstrual irregularity, constipation, and weight gain.[1]Chaker L, Bianco AC, Jonklaas J, et al. Hypothyroidism. Lancet. 2017 Sep 23;390(10101):1550-62.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619426
http://www.ncbi.nlm.nih.gov/pubmed/28336049?tool=bestpractice.com
Physical signs include slow speech and movement; coarse, dry skin; eyelid oedema; bradycardia; hypertension; and delayed tendon reflexes.[1]Chaker L, Bianco AC, Jonklaas J, et al. Hypothyroidism. Lancet. 2017 Sep 23;390(10101):1550-62.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619426
http://www.ncbi.nlm.nih.gov/pubmed/28336049?tool=bestpractice.com
[27]Carlé A, Pedersen IB, Knudsen N, et al. Hypothyroid symptoms and the likelihood of overt thyroid failure: a population-based case-control study. Eur J Endocrinol. 2014 Nov;171(5):593-602.
http://www.ncbi.nlm.nih.gov/pubmed/25305308?tool=bestpractice.com
[28]Canaris GJ, Steiner JF, Ridgway EC. Do traditional symptoms of hypothyroidism correlate with biochemical disease? J Gen Intern Med. 1997 Sep;12(9):544-50.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1497160
http://www.ncbi.nlm.nih.gov/pubmed/9294788?tool=bestpractice.com
Goitre is generally uncommon. It is more common in areas of iodine deficiency.[1]Chaker L, Bianco AC, Jonklaas J, et al. Hypothyroidism. Lancet. 2017 Sep 23;390(10101):1550-62.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619426
http://www.ncbi.nlm.nih.gov/pubmed/28336049?tool=bestpractice.com
[9]Zimmermann MB, Andersson M. Global endocrinology: global perspectives in endocrinology: coverage of iodized salt programs and iodine status in 2020. Eur J Endocrinol. 2021 Jun 10;185(1):R13-21.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240726
http://www.ncbi.nlm.nih.gov/pubmed/33989173?tool=bestpractice.com
Goitre may also be present in autoimmune (Hashimoto) thyroiditis.[15]Ragusa F, Fallahi P, Elia G, et al. Hashimotos' thyroiditis: epidemiology, pathogenesis, clinic and therapy. Best Pract Res Clin Endocrinol Metab. 2019 Dec;33(6):101367.
http://www.ncbi.nlm.nih.gov/pubmed/31812326?tool=bestpractice.com
Diagnostic testing
TSH is the most sensitive and specific for diagnosing primary hypothyroidism. It should be ordered in the initial work-up if there is a clinical suspicion of hypothyroidism.[1]Chaker L, Bianco AC, Jonklaas J, et al. Hypothyroidism. Lancet. 2017 Sep 23;390(10101):1550-62.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619426
http://www.ncbi.nlm.nih.gov/pubmed/28336049?tool=bestpractice.com
Normal TSH range is 0.4 to 4.0 mIU/L (there may be some variation in laboratory norms). TSH levels are elevated in primary hypothyroidism, although in sub-clinical disease levels may only be mildly elevated.
Free thyroxine (T4) should then be obtained to quantify the degree of hypothyroidism or if suspicion of disorders other than primary hypothyroidism.[1]Chaker L, Bianco AC, Jonklaas J, et al. Hypothyroidism. Lancet. 2017 Sep 23;390(10101):1550-62.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619426
http://www.ncbi.nlm.nih.gov/pubmed/28336049?tool=bestpractice.com
Normal free T4 range is 9.00 to 23.12 picomol/L (0.8 to 1.8 nanograms/dL). In cases where the TSH is only mildly elevated, the patient is not symptomatic and the serum free T4 is normal, the diagnosis is sub-clinical hypothyroidism.[2]Cooper DS, Biondi B, Cappola AR. Subclinical hypothyroidism: a review. JAMA. 2019 Jul 9;322(2):153-60.
http://www.ncbi.nlm.nih.gov/pubmed/31287527?tool=bestpractice.com
Auto-antibody testing is not necessary for diagnosis, but helps distinguish autoimmune primary hypothyroidism.[1]Chaker L, Bianco AC, Jonklaas J, et al. Hypothyroidism. Lancet. 2017 Sep 23;390(10101):1550-62.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619426
http://www.ncbi.nlm.nih.gov/pubmed/28336049?tool=bestpractice.com
It is recommended that pregnant women with TSH concentrations >2.5 mIU/L should be evaluated for thyroid peroxidase antibody (TPOAb) status.[29]Alexander EK, Pearce EN, Brent GA, et al. 2017 guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017 Mar;27(3):315-89.
http://online.liebertpub.com/doi/pdfplus/10.1089/thy.2016.0457
http://www.ncbi.nlm.nih.gov/pubmed/28056690?tool=bestpractice.com
It is prudent to obtain TSH, full blood count, and fasting blood glucose in patients who present with non-specific fatigue and weight gain. One study found patients with hypothyroidism had a higher risk of anaemia compared with euthyroid participants and suggested that a reduced thyroid function at baseline increased the risk of developing anaemia during the study follow-up; however, the underlying mechanisms of this link is unclear.[30]Wopereis DM, Du Puy RS, van Heemst D, et al. The relation between thyroid function and anemia: a pooled analysis of individual participant data. J Clin Endocrinol Metab. 2018 Oct 1;103(10):3658-67.
https://www.doi.org/10.1210/jc.2018-00481
http://www.ncbi.nlm.nih.gov/pubmed/30113667?tool=bestpractice.com
Total cholesterol and low density lipoprotein, concentrations may be elevated in hypothyroidism.[1]Chaker L, Bianco AC, Jonklaas J, et al. Hypothyroidism. Lancet. 2017 Sep 23;390(10101):1550-62.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619426
http://www.ncbi.nlm.nih.gov/pubmed/28336049?tool=bestpractice.com