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Primary hypothyroidism – issues in diagnosis and management

Primary hypothyroidism – issues in diagnosis and management

Advanced nurse practitioner in general practice Helen Lewis explains the key features of primary hypothyroidism, as well as diagnosis and management in primary care

Primary hypothyroidism is defined as low levels of blood thyroid hormones due to destruction of the thyroid gland, usually caused by autoimmunity or an intervention such as surgery, radioiodine or radiation.

The thyroid gland is located in the anterior of the neck, just below the Adam’s apple. It is a butterfly shaped gland made up of two lobes, one on either side of the windpipe, joined in the centre by the isthmus. The thyroid secretes two main hormones into the blood stream: thyroxine which contains four atoms of iodine and is often called T4. This is converted into the second hormone, tri-iodothyronine (T3), which contains three atoms of iodine.

The T3 is biologically active and regulates the body’s metabolism. The amount of T3 and T4 hormone within the blood is regulated via a negative feedback system controlled by the pituitary gland. This is a small bean-shaped gland located at the base of the brain and is the control centre for the release of thyroid stimulating hormone (TSH) when levels of circulating hormone drop.1

Diagnosis of this condition can be troublesome as the signs and symptoms may be mild and non-specific, especially in the elderly, but clinicians should be mindful of the condition when clinical features are discussed with patients. With the current climate of telephone triage, it is particularly important to listen to the soft markers in the patient’s narrative.

The following clinical features may lead to a suspicion and possible diagnosis of hypothyroidism: 

Patient assessment is crucial to enable the clinician to decide on the most appropriate blood tests to investigate possible hypothyroidism, as some test results may be misleading.

For example, menopausal symptoms such as low mood, poor concentration, dry skin and anxiety that are also associated with hypothyroidism can skew the diagnostic process. Whereas TSH gives a definitive result with regard to hypothyroidism, the use of follicle stimulating hormone (FSH) and luteinizing hormone (LH) is not reliable in terms of menopause and the effects of women’s menses are more significant.     

Often patients experience palpitations with hypothyroidism, and with this in mind any patient who is newly diagnosed with atrial fibrillation should also have their thyroid bloods checked. 

Diabetes is an endocrine disease, classified into type 1 or type 2 diabetes, both of which can linked to thyroid disease. Patients with diabetes will undergo annual blood tests and the inclusion of thyroid blood tests is recommended for this group.

It is important that clinical judgement is used when interpreting results.2 For example, recovery of suppressed TSH levels can be delayed following treatment for hyperthyroidism.

To investigate possible hypothyroidism, blood tests for TSH and free T4, and sometimes free T3, are usually requested. Some laboratories still measure total T3 and total T4; in such cases an estimate of the concentration of thyroid-binding protein concentrations must be made to calculate the free T3 or T4 level.

Typically the following reference ranges are used in adults:1

Thyroid stimulating hormone (TSH)0.4-4.5 mU/l
Free T4 (FT4)9.0-25.0 pmol/l
Free T3 (FT3)3.5-7.8 nmol/l
Total T4 (TT4)60-160 nmol/l
Total T3 (TT3)1.2-2.6 nmol/l

Interpretation of results

The following summarises how the combination of blood test results should be interpreted to guide diagnosis and management.

A TSH level which is slightly raised but in combination with a normal free T4 is not a condition which requires treatment and is described as subclinical hypothyroidism. However, this may develop into hypothyroidism and should be monitored for timely intervention. In this situation, thyroid antibody levels can be measured to help determine the patient’s risk of developing hypothyroidism.3 

Changes in thyroid antibody levels can indicate thyroid dysfunction; suspicion of autoimmune thyroid disease such as thyrotoxicosis (Graves’ disease) where patients will present with a goitre, along with large and protruding eyeballs, should also lead to a test for thyroid antibodies.

The main thyroid antibody test routinely requested is thyroid stimulating hormone receptor antibody (TSHR Ab). Due to the nature of this type of blood sample, there is no standard range and patients suspected of this autoimmune condition should be referred to endocrinology for specialist review and guidance with regard to treatment.

Treatment

Levothyroxine is the first line treatment for adults, children and young people diagnosed with primary hypothyroidism. Treatment will ensure further complications of hypothyroidism are prevented, such as:

  • Depression
  • Hair loss or thinning
  • Memory loss
  • Menorrhagia
  • Oedema around the face and eyes
  • Normocytic anaemia caused by a decrease in red cell mass
  • Reduced renal blood flow and glomerular filtration rate resulting in a reduced water excretion and resulting in fluid retention and oedema
  • Bradycardia resulting in reduced cardiac output.

Starting on levothyroxine can take up to six months for levels to settle and may require repeat blood tests to ensure that the correct dose is being given.4 Consider measuring TSH every three months until the level is stabilised, as evidenced by two similar measurements with the reference range, three months apart. Once the TSH is stable annual bloods should be sufficient to monitor patients.

Principles of levothyroxine treatment for primary hypothyroidism (4,5)

Adults under 65 (and no history of cardiovascular disease): Initially 1.6 mcg/kg once daily, adjusted according to response. Round dose to the nearest 25 mcg. Dose to be taken preferably 30-60 minutes before breakfast, caffeine-containing liquids (eg, coffee, tea) or other medication.

Elderly (and younger adults with history of cardiovascular disease): Initially 25-50 mcg once daily; adjusted in steps of 25 mcg every four weeks and adjusted according to response. Maintenance 50-200 mcg once daily. Dose to be taken preferably 30-60 minutes before breakfast, caffeine-containing liquids (eg, coffee, tea), or other medication.

Monitoring: Consider measuring thyroid stimulating hormone (TSH) level every three months until stabilised (two similar measurements within the reference range, three months apart), then yearly thereafter.

Consider measuring free thyroxine (FT4) if symptoms of hypothyroidism persist after starting levothyroxine.

Clinicians should consider monitoring FT4 and TSH in children and young people more regularly. This means in those aged two years and over measuring levels every six to twelve weeks until the TSH is stable (again, two similar measurements with range, three months apart) initially, then every four to six months until puberty is achieved and then annually.5 Consider seeking specialist opinion if a TSH within the reference range is not achieved despite medication compliance; this is especially important in children especially in the under two years age group.

Treatment plans and the success of the plan can only be achieved when the patient understands both the condition and the implications of not using the medication correctly.  With this in mind, it is essential that treatment plans are discussed in order that shared decision making can be realised. Thyroid disease usually responds well to treatment, to alleviate symptoms and align thyroid function within or as near to the normal reference range as possible.

Conclusion

Nurses working in primary care and the community should:

  • Be aware that in women symptoms of hypothyroidism may be mistaken for menopause
  • Consider testing for thyroid dysfunction in adults, children and young people with depression or unexplained anxiety
  • Offer tests routinely to all patients who have been diagnosed with type 1 diabetes or with new-onset atrial fibrillation
  • Consider seeking specialist opinion if normal TSH is not achieved despite medication compliance; this is especially important in children especially in the under 2 years age group.

References

1. Association for Clinical Biochemistry, British Thyroid Association. UK guidelines for the use of Thyroid Function Tests www.british-thyroid-association.org/sandbox/bta2016/uk_guidelines_for_the_use_of_thyroid_function_tests.pdf

2. Chaker L, Bianco A, Jonklaas J, Peters R. Hypothyroidism. Lancet 2017; 390: 1550-1562

3. Bekkering GE, Agoritsas I, Lytvyn et al. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ 2019; 365: 1-9

4. Datapharm Communications Ltd. SPC for Levothyroxine 25 micrograms tables. Electronic Medicines Compendium www.medicines.org.uk/emc/product/6441/smpc

5. NICE. Thyroid Disease: assessment and management www.nice.org.uk/guidance/NG145

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