Hypothyroidism: tips for GP management and common pitfalls

GPs represent a cornerstone in the management of primary hypothyroidism, the second most common endocrine disorder that GPs will encounter in their day-to-day practice.

Hashimoto’s thyroiditis is generally considered the most common cause of hypothyroidism in iodine-replete regions, such as Australia. In contrast, iodine deficiency is generally the most common cause of hypothyroidism in regions with low levels of dietary iodine.

GPs play a key role in the diagnosis and management of primary hypothyroidism, while referral to an endocrinologist is recommended for secondary hypothyroidism and complex cases of primary hypothyroidism.

There are currently limited Australian data on the prevalence of hypothyroidism, although estimates suggest at least one in 30 adults are living with the condition. Analysis of data from the Blue Mountains Eye Study (1997–2000) found that 4.16% of participants were receiving thyroxine therapy, and unrecognised hypothyroidism (thyroid-stimulating hormone [TSH] levels > 4.5 mIU/L) was reported in 4.1% of participants. These figures are in keeping with more robust international data (here and here).

Hypothyroidism can be a subtle disease. For example, patients may not be able to accurately report their history of hypothyroidism, and this is reflected by the fact that 15.3% of current thyroxine users from an Australian study did not self-report any history of thyroid disease. Hypothyroidism can manifest in a highly variable manner, and apart from thorough history taking, increased awareness among GPs is key to ensuring the timely diagnosis and management of hypothyroidism.

Common symptoms of overt hypothyroidism include lethargy, low mood, weight gain, constipation, cold intolerance, menstrual irregularity, myalgia, muscle weakness, dry skin, thickened/brittle nails, and dry/thinning hair. Women presenting with infertility or subfertility should be assessed for hypothyroidism or autoimmune thyroid disease.

When assessing patients, clinicians should consider factors such as the patient’s age, as well as the aetiology, severity and duration of the hypothyroidism, which can all influence the clinical presentation. If there is any diagnostic uncertainty, we recommend referral to an endocrinologist.

Like the symptoms, the signs of hypothyroidism can also be easy to miss. Common clues that point to underlying low thyroid function include thyroid nodules or goitre; cardiovascular signs, such as bradycardia and diastolic hypertension; carpal tunnel syndrome; and the Woltman sign (delayed relaxation phase of the deep tendon reflexes).

Ordering thyroid function tests and looking to the distinctive pattern of raised TSH with low T4 and/or T3 levels confirms the diagnosis. Antithyroid peroxidase (TPO) antibodies and antithyroglobulin (TG) antibodies should be assessed, and will be elevated in most patients with suspected Hashimoto thyroiditis.

Treatment of hypothyroidism is with thyroid hormone replacement, most commonly levothyroxine, which is similar to endogenous T4.

The various levothyroxine preparations are a common source of confusion for GPs and other clinicians. We will provide a brief summary here and the latest Product Information documents can be accessed via the Therapeutic Goods Administration (TGA) website.

Levothyroxine sodium is available in Australia as Oroxine, Eutroxsig, and Eltroxin (Aspen Pharma), and most recently, Levoxine (Sun Pharma ANZ):

• Oroxine, Eutroxsig, and Levoxine are bioequivalent and interchangeable on a same-dose basis.
• Eltroxin is not bioequivalent on a same-dose basis with Oroxine, Eutroxsig, and Levoxine (see Eltroxin Product Information for more details).
• Both Oroxine and Eutroxsig should be kept refrigerated at all times.
• Eltroxin and Levoxine do not need to be refrigerated, but need to be kept at under 25°
• GPs should routinely advise patients not to switch between Eltroxin and Oroxine/Eutroxsig/Levoxine unless this is an intended change.
• If patients wish to use desiccated thyroid extracts instead of levothyroxine, they should be made aware that desiccated thyroid extracts are not considered a standard therapy, are not available on the Pharmaceutical Benefits Scheme, and are not approved by the TGA.

Common pitfalls in thyroxine replacement are the practical aspects of administration, such as storage and adherence. Clinicians should also explore potential lifestyle factors or other medical conditions that could affect levothyroxine absorption, distribution and metabolism.

In our experience, improper storage of levothyroxine can result in fluctuations of potency (here and here) and, therefore, in the dosing of Oroxine/Eutroxsig. GPs should also consider other potential causes for fluctuations in the TSH, such as significant weight loss or gain and malabsorption (eg, due to bowel disorders). Medications such as oestrogen and glucocorticoid therapy should also be taken into account when interpreting thyroid function tests.

In terms of medication administration, we usually give the following pragmatic advice:

• levothyroxine should ideally be taken on an empty stomach with water, at least 30 minutes before breakfast;
• avoid taking levothyroxine with other medications/supplements that may interfere with absorption (eg, calcium carbonate, antacids, iron supplements);
• a general rule of thumb would be to take other medications at least 4 hours after taking levothyroxine.

In our experience, suboptimal adherence is often the biggest challenge in the management of hypothyroidism (here and here). The lack of immediate consequences of a skipped dose is a key factor contributing to frequent or persistent medication non-adherence. Given the half-life of levothyroxine is approximately 7 days, dose omission does not result in the rebound or worsening of symptoms the following day (here and here).

When managing medication non-adherence, clinicians should avoid blaming the patient. Instead, adherence can be optimised by improving patient awareness, providing regular patient education, and discussing measures to improve adherence (eg, setting up phone alarms, putting reminders on the fridge). GPs are involved in the management of most patients with primary hypothyroidism, and ongoing patient education from GPs is crucial to achieving stable thyroid function.

Two important goals in the management of primary hypothyroidism are relief of symptoms and attainment of a TSH within the target range appropriate for the patient’s age and clinical context. Thyroid function tests should be repeated no sooner than 4 weeks after dose or regimen adjustments due to the long half-life of T4.

On the other hand, free T4 (not TSH levels) should be used to monitor treatment in individuals with central (secondary or pituitary) hypothyroidism, and management by an endocrinologist is recommended.

Some symptoms attributed to hypothyroidism can be non-specific and may not actually have a causal relationship with the hypothyroidism. For instance, if there is persistent lethargy despite achieving biochemical euthyroidism, alternative causes (eg, coeliac disease, obstructive sleep apnoea, depression) should be considered.

A small number of patients will report persistent symptoms despite achieving biochemical euthyroidism, and sometimes, no other cause for their symptoms can be identified despite extensive investigations. In this situation, patients and clinicians often wonder whether the addition of liothyronine (synthetic T3) could provide symptomatic relief and/or improved clinical outcomes. Referral to an endocrinologist is recommended in this situation.

Clinical trials to date have not shown a consistent benefit with the combination of liothyronine with levothyroxine to treat hypothyroidism, but a select cohort of patients may benefit from combination therapy under specialist management.

In summary, hypothyroidism is a very common condition that can present insidiously, but have a significant impact on quality of life. However, hypothyroidism is generally easily treatable with thyroxine replacement, and GPs represent a cornerstone in the management of primary hypothyroidism. Time and time again, we have seen improved patient satisfaction and outcomes when clinician and patient awareness is optimised, and when a collaborative, dynamic and multitargeted approach is adopted.

Dr Xi May Zhen is an adult endocrinology advanced trainee at Royal Prince Alfred Hospital (RPA), Sydney. She graduated with an MBBS from the University of Queensland in 2015, and completed her basic physician training at RPA.

Dr Ted Wu is Senior Staff Specialist endocrinologist and the Director of the Diabetes Centre, at Royal Prince Alfred Hospital (RPA), Sydney. He is also a Visiting Medical Officer at Dubbo Base Hospital, and an Honorary Professor at the Shijiazhuang Diabetes Hospital in Hebei Province, China. Dr Wu is interested in clinical diabetes, and has a long term interest in both teaching and researching diabetes complications and novel treatments for the disease. He was also instrumental in establishing the RPA Diabetes Centre as an International Diabetes Federation Centre of Education, and the National Association of Diabetes Centres Centre of Excellence. 

The statements or opinions expressed in this article reflect the views of the authors and do not represent the official policy of the AMA, the MJA or InSight+ unless so stated.