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Avoid desiccated (natural) thyroid extract products for hypothyroidism

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Topics: Adverse effectsEndocrine system disordersLevothyroxine · Primary Care and PCNsUnlicensed medicines ·

Levothyroxine is the standard of care for treating hypothyroidism. Desiccated or natural thyroid extracts (DTE) are not routinely recommended.

Contents
  1. National guidance
    1. NHS England
    2. NICE
    3. RMOC
    4. British Thyroid Association Executive Committee
  2. About desiccated thyroid extract
    1. Composition
    2. Bioequivalence
  3. Benefits of levothyroxine
  4. Actions for prescribers in primary care
    1. Requests for DTE products
    2. Switching from DTE products
  5. Clinical considerations
    1. Licensed status
    2. Lack of evidence
    3. Safety concerns
  6. Bibliography

National guidance

National guidance does not recommend routine use of desiccated or natural thyroid extracts (DTE) for management of hypothyroidism. Levothyroxine is the preferred option.

NHS England

NHS England guidance on items which should not routinely be prescribed in primary care lists Armour Thyroid (a DTE product). It is listed because of the clinical concerns, cost and lack of evidence of superiority of DTE over levothyroxine.

NICE

NICE guidance on the assessment and management of thyroid disease  felt that there is not enough evidence that DTE products offer benefit over levothyroxine and advised that its long-term adverse effects are uncertain.

RMOC

RMOC guidance on the Prescribing of Liothyronine does not recommended DTE products as their safety, quality and efficacy cannot be assured.

British Thyroid Association Executive Committee

The British Thyroid Association Executive Committee state that the routine use of DTE is not recommended advising that prescribing should be reserved for use by endocrinologists prescribing in individual patients (under exceptional circumstances).

About desiccated thyroid extract

Until the advent of levothyroxine in the 1970’s, the mainstay of thyroid hormone replacement therapy was desiccated thyroid extract (DTE) prepared from animal thyroid glands.

Composition

Commercially available DTE products are derived from cleaned, dried and powdered pig thyroid glands formulated into doses called ‘‘grains’’.

One grain contains 38 micrograms of thyroxine (T4) and 9 micrograms of liothyronine (T3) per 65mg of the labelled amount of thyroid.

Bioequivalence

Generally 1mg of DTE is equivalent to1.667 micrograms of levothyroxine (a synthetic form of T4) but the amounts of T4 and T3 in each natural thyroid extract product can vary.

Benefits of levothyroxine

Levothyroxine (synthetic T4) is the preferred the standard of care because:

  • It is licensed for management of hypothyroidism.
  • There is good quality evidence to support use of levothyroxine for hypothyroidism.
  • It is de-iodinated in body tissues to form physiologically appropriate levels of the active form of thyroid hormone, triiodothyronine (T3).
  • It has a relatively long half-life (1 week) giving relatively stable blood levels with minimal daily fluctuations in T4.

Actions for prescribers in primary care

Requests for DTE products

When patients request DTE products

  • Follow local guidance and policy on prescribing of DTE products
  • Do not initiate DTE products for management of hypothyroidism
  • Explain the clinical concerns around DTE to patients who ask about it

Switching from DTE products

When patients are already taking DTE products

  • Consider referring these patients to a consultant NHS endocrinologist who will consider switching to levothyroxine where clinically appropriate

Clinical considerations

There are concerns around use of DTE products

Licensed status

DTE products are not licensed in the UK, which means their efficacy, safety, consistency and quality cannot be assured. However, some DTE products remain commercially available (e.g. Armour Thyroid, Westhroid. ‘Nature-Throid’ and Erfa).

Lack of evidence

There is little published data comparing the clinical effectiveness and safety of DTE products with levothyroxine monotherapy against objective outcome measures in people with hypothyroidism.

Published studies are relatively small, of short duration (less than 6 months) and none are randomised controlled trials. These studies found no significant differences between DTE products and levothyroxine with respect to their impact on thyroid symptoms, quality of life and tolerability.

Evidence

  • A randomised, double-blinded, 16-week crossover trial (n=70) reported no significant difference between a DTE product and levothyroxine on reported thyroid symptoms, quality of life, memory or depression. Weight reduction was greater with DTE.
  • A prospective, randomised, double-blind, 12-week crossover trial (n=75) and a prospective, randomised, double-blind, 22-week crossover study (n=75) compared a DTE product, levothyroxine and a combination of liothyronine and levothyroxine. Both studies reported no significant differences between groups with respect to thyroid symptom scores, weight changes, general health, depression, memory, lipid levels and thyroid function tests.
  • A retrospective matched-cohort trial also reported no differences in the stability of thyroid hormone levels in adults using levothyroxine (n=435) or DTE products (n=435) over 3 years.
  • Across the studies, there was no overall difference for patient preference, although some subgroups were more likely to prefer DTE; including those most symptomatic on levothyroxine, patients with Hashimoto’s disease and those who experienced greater weight loss and subjective improvement with DTE.

Safety concerns

There are concerns about safety of DTE. Healthy human thyroid glands secrete T4 and T3 in a ~14:1 ratio whereas the ratio of T4 to T3 in DTE preparations is ~4:1. Using these products could lead to:

  • Symptoms of hyperthyroidism and greater risk of thyrotoxicosis
  • Long term adverse effects such as osteoporosis and arrhythmia
  • More difficulty adjusting the dose to the desired therapeutic effect
  • Fluctuating levels of thyroid hormones throughout the day (T3 has a shorter half-life than T4 meaning thyroid hormone levels can fluctuate more)

Evidence

Published data which illustrates some of these safety concerns includes the 22-week cross-over study which reported a small increase in heart rate caused by DTE. In addition, a published case report describes a patient with thyrotoxicosis caused by bovine thyroid supplements.