This month marks the first Thyroid Awareness Month in Australia. This campaign is supported by the Australian Thyroid Foundation and aims to raise awareness of thyroid health. Symptoms of thyroid disorders are often varied and non-specific, and it is thought that many cases go undiagnosed. Some of the more common features of thyroid disorders are shown in Table 1.
Table 1. Features of thyroid disorders
Hypothyroidism | Hyperthyroidism |
Fatigue | Tremor |
Weight gain | Weight loss |
Cold intolerance | Heat intolerance |
Constipation | Muscle weakness |
Dry skin | Palpitations |
The two main hormones produced by the thyroid gland are triiodothyronine (T3) and thyroxine (T4). These hormones play an important role in regulating the basal metabolic rate. They also contribute to brain maturation and overall growth in children. The levels of T3 and T4 are tightly maintained via feedback from the pituitary gland in the form of thyroid stimulating hormone (TSH).
Thyroid disorders can be classified as primary, secondary, or tertiary. Primary thyroid disorders are those that are caused by a problem within the thyroid gland itself. The negative feedback response to T4 and T3 remain intact in primary disease. Therefore, primary hypothyroidism is associated with elevated TSH and primary hyperthyroidism is associated with suppression of TSH.
In contrast, secondary and tertiary disorders arise in structures outside of the thyroid. Secondary disease is caused by problems in the anterior pituitary gland, which affects the release of TSH. Tertiary disease is caused by a problem in the hypothalamus. This affects the release of thyroid releasing hormone, which then affects the production of TSH. Primary and secondary thyroid disorders are collectively known as central thyroid disorders. In central thyroid disorders, the feedback responses are impaired. For example, serum levels of T3 and T4 will be low in secondary hypothyroidism, but TSH levels may be normal or low.
The Therapeutic Guidelines publish a guide for interpretation of thyroid laboratory results.
Medications affecting thyroid hormones
Many medications can affect thyroid function, thyroid function tests, and therapies to treat thyroid disorders.
Iodine is one of the main building blocks of T3 and T4 and is found in many foods in the form of inorganic iodide. The Australian recommended daily intake (RDI) is 150mcg for adults, with an upper level of intake of 1,100mcg per day. Iodine excess can have a significant impact on thyroid function and can exacerbate both hypothyroidism and hyperthyroidism.
Excess iodine exposure may occur due to the administration of iodinated contrast media or iodine-containing medicines, such as amiodarone. Each molecule of amiodarone contains two iodine atoms which equates to around 75mg of iodine per 200mg tablet. Deiodination that occurs during metabolism releases approximately 6mg of iodine per 200mg tablet, which is significantly higher than the RDI.
Topical iodinated antiseptics (i.e. povidone-iodine) have been associated with thyroid dysfunction. This may be particularly relevant in neonates and when topical preparations are used long-term. Some complementary medicines also contain iodine. Cases of thyroid dysfunction have been reported with products containing kelp (sometimes labelled as Fucus vesiculosus).
Other medications that can affect thyroid hormones are shown in Table 2.
Table 2. Medications that can affect thyroid hormones
Medications | Effect |
Lithium, interferon alfa, interleukin-2, tyrosine kinase inhibitors (e.g. sunitinib, sorafenib), immune checkpoint inhibitors (e.g. ipilimumab, nivolumab, pembrolizumab, atezolizumab) | Hypothyroidism |
Interferon alfa, interleukin-2, alemtuzumab | Thyrotoxicosis |
Colestyramine, sucralfate, ferrous sulfate, aluminium hydroxide, sevelamer, calcium carbonate, soy preparations | Reduced absorption of levothyroxine when administered together |
Phenytoin, barbiturates, carbamazepine, rifampicin | Induces metabolism of levothyroxine |
Biotin (vitamin B7), dopamine, glucocorticoids | May alter diagnostic test results |
Critical illness is likely to exacerbate the above medication-induced effects on thyroid function. The endocrine response during critical illness is complex and may also impact thyroid hormone levels on its own. The result is typically reduced levels of T3 and increased levels of the inactive form, reverse T3 (rT3). Therefore, thyroid test results should be interpreted with caution during critical illness. In the absence of clinical features of thyroid dysfunction, it is not recommended to start therapy for a thyroid disorder in such a patient.
Thyroid disorders affecting medications
Thyroid dysfunction can also alter the effects of some medications, including:
- Digoxin – patients with hypothyroidism may be more sensitive to the effects of digoxin, and patients with hyperthyroidism may be less sensitive. Digoxin doses may need to be modified;
- Diabetes medications – blood glucose should be regularly monitored and reviewed in patients with diabetes when therapy for hypothyroidism is initiated. As thyroid function is corrected, the patient’s requirement for insulin or oral hypoglycaemic agent may increase. This effect is typically delayed as levothyroxine has a slow onset of action, with peak therapeutic effect taking up to four weeks; and
- Warfarin – the INR may require more frequent monitoring when therapy for thyroid disorders is started or changed. The warfarin dose may need to be reduced when therapy for hypothyroidism is initiated and increased when therapy for hyperthyroidism is started.
Summary
It is estimated that over one million Australians have an undiagnosed thyroid disorder. Raising awareness of some of the more common signs and symptoms may improve diagnosis by encouraging people to speak to their doctor.
Many medications can affect thyroid function, with regular testing recommended for some patients. Correcting thyroid function can also affect medicines the patient may already be taking. Careful monitoring and dose adjustments of concomitant medicines may be required when thyroid therapy is initiated, the dose changed, or when thyroid therapy is ceased.
References:
- Bone and Metabolism Expert Group. Therapeutic Guidelines: Bone and Metabolism. Melbourne: Therapeutic Guidelines; 2019.
- Boonen E, Van den Berghe G. Endocrine responses to critical illness: novel insights and therapeutic implications. J Clin Endocr Metab. 2014; 99(5): 1560-82.
- Cordarone X 200® (Amiodarone Hydrochloride) Australian approved product information. Macquarie Park: Sanofi-aventis Australia. Approved June 2020.
- Leung AM, Braverman LE. Consequences of excess iodine. Nat Rev Endocrinol. 2014; 10(3): 136-42.
- National Health and Medical Research Council. Iodine. Canberra: Australian Government; 2017.
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