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Consider compounding for hypothyroid sufferers

Compounding can be more cost-effective for people with hypothyroidism, says Najma Easa and Paaven Patel

Hypothyroidism occurs due to inadequate production of thyroid hormones by the thyroid gland. Although it is easily diagnosed and managed, if untreated, it can cause serious adverse health effects and in severe cases can be fatal. Clinical manifestations include fatigue, weakness, dry skin, cold intolerance, weight gain and voice changes1.

The thyroid gland produces two main hormones: inactive thyroxine (T4) and physiologically active triiodothyronine (T3). Both are synthesised in response to thyroid stimulating hormone (TSH) from the pituitary by follicular cells in the thyroid gland2. About 20 per cent of T3 is produced by the thyroid gland; the remainder is produced through conversion of T4 in peripheral tissue.

Hypothyroidism is treated using thyroid hormone replacement therapy. NICE guidelines recommend T4 as first-line therapy (as levothyroxine). Liothyronine (T3) treatment for hypothyroidism either alone or in combination with T4 is no longer recommended by the NHS3, although activist groups fought the removal of T3 from prescription and continue to lobby for better treatment for sufferers.  


Historically, patients were treated with desiccated thyroid extracts (DTE) derived from the porcine gland, which contained T4, T3 and other compounds. Patients treated with DTE occasionally did not feel well, despite adequate T4 dosing, but in a randomised, double-blinded, crossover study, nearly half (34/70) of patients expressed preference for DTE over T4 therapy4. In another study of 12,146 hypothyroid patients, the overall degree of satisfaction from respondents was highest among patients on DTE, followed by the combination T4 and T3 group. The T4 monotherapy group exhibited the lowest satisfaction5

With the discovery of synthetic T4 (levothyroxine), therapy shifted towards the use of the purified synthetic drug, and successive synthesis of T3 (liothyronine) led to the introduction of a combination T4 and T3 therapy, which for numerous decades was considered the acceptable standard. However, to avoid the risk of hyperthyroidism, T4 monotherapy became widely used because of its long half-life of six to seven days compared to only one to two days for T3. With effective peripheral conversion, a low risk of hyperthyroidism, and less frequent dosing, T4 is widely considered a much more convenient and effective therapy for patients6,7.

Nevertheless, dissatisfaction with T4 monotherapy is high. Some five to 10 per cent of patients experience persistent symptoms, such as impaired wellbeing, physiological distress and cognitive disturbances, even when the patients have normal thyroid-stimulating serum (TSH) levels8. The challenge for hypothyroid sufferers, or those whose thyroid has been destroyed by radiation, is getting a product that better mimics their requirement for a mix of thyroid hormones.


With T3 and DTE not generally prescribed on the NHS, patients have taken to private prescriptions. Liothyronine is a licensed product, but is not recommended by the NHS for reasons of cost – the pack price increased by more than 1,100 per cent from £20 in 2009 to £248 in 2017. The huge increase in prices eventually led to the NHS not recommending the use of liothyronine9. Prices have since reduced, but are still reasonably high, with a pack of 28 capsules costing £100 or more, depending on strength and supplying pharmacy. 

Compounding pharmacies might be expected to be expensive due to the work involved in producing customised treatments, but charges for liothyronine capsules at compounding pharmacies such as Specialist Pharmacy can be a third or less of the cost of the licensed version. 

Although prescribing unlicensed compounded therapies involves greater responsibility and risk, the cost implications should be considered for patients, especially as the high costs could potentially result in intentional non-adherence or patients buying medicines from the internet, which could be of greater risk.

Patients should be given options, outlining the risks and benefits, particularly those who are not fully responding to treatment with T4 or licensed doses of T3. In certain patients, compounded formulations can avoid excipients that can cause adverse reactions; slow-release T3 capsules can be prescribed for patients who experience unwanted side-effects, such as anxiety, tachycardia, sweating, increased bowel motility, and menstrual irregularities, due to the short half-life of T3, which results in peak serum levels within 3–4 hours following oral administration. It may also lead to less frequent dosing of T310

Compounding can also offer alternative dosage forms such as oral liquids for patients unable to swallow pills/capsules and sublingual formulations for patients with refractory hypothyroidism that may be due to issues with gastric absorption. 

Treatment with T4 is suitable for many hypothyroid patients, but there are a high number who require or prefer treatment with T3 or DTE. The compounding route can be associated with higher costs as it is tailored to individual needs, but it can be more cost-effective in achieving a desired outcome compared to commercially available alternatives.  

Najma Easa PhD is senior pharmacist and Paaven Patel is operations and quality assurance pharmacist at Specialist Pharmacy, the first compounding pharmacy of its kind in the UK, producing custom-made medications across a wide range of treatment areas. 


1. L Chaker, AC Bianco, J Jonklaas and RP Peeters, 'Hypothyroidism', The Lancet (London, England), 390, p1550 (2017) doi: 10.1016/S0140-6736(17)30703-1

2. SM Kansagra, CR McCudden and MS Willis, 'The Challenges and Complexities of Thyroid Hormone Replacement', Lab. Med., 41, pp338–348, (2010) doi: 10.1309/LMB39TH2FZGNDGIM

3. NICE, Thyroid disease: assessment and management NICE Guideline [NG145], NICE (2019). (accessed May 31, 2022)

4. TD Hoang, CH Olsen, VQ. Mai, PW Clyde and MKM Shakir, 'Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study', J. Clin. Endocrinol. Metab., 98, pp1982–1990 (2013) doi: 10.1210/JC.2012-4107

5. SJ Peterson et al., 'An Online Survey of Hypothyroid Patients Demonstrates Prominent Dissatisfaction', Thyroid, 28, p707, (2018) doi: 10.1089/THY.2017.0681

6. MH Brakke, 'Treatment guidelines for hyperthyroidism and hypothyroidism', JAMA, 274, pp1011b – 1011, (1995) doi: 10.1001/JAMA.274.13.1011B

7. EMC, Liothyronine Sodium BP 20micrograms Tablets - Summary of Product Characteristics (SmPC), (2019), (accessed May 31, 2022)

8. WM Wiersinga, L Duntas, V Fadeyev, B Nygaard, and MPJ Vanderpump, '2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism', Eur. Thyroid J., 1, pp55–71, (2012), doi: 10.1159/000339444

9. Competition and Markets Authority, 'CMA fines pharma firm over pricing of crucial thyroid drug - GOV.UK', (2021), (accessed May 31, 2022)

10. M Milner, 'Hypothyroidism: Optimizing Therapy with Slow-Release Compounded Thyroid Replacement', IJPC, Human Hormone Replacement Therapy, (2005)

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