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TSH vs FT4
Investigating thyroid function
Reminder

Full colour PDF of ‘TSH vs FT4’ Reminder May 2007.
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New Zealand GPs choose TSH for testing and monitoring thyroid function

A campaign detailing the guidelines for testing thyroid function was distributed by bpac in October 2005, to all GPs in New Zealand. The key message of the campaign was to promote TSH as the sole initial test for establishing and monitoring thyroid function, in preference to FT4 and FT3 in most situations.

Figure 1: Total number of TSH and FT4 + FT3 tests performed
(October 2004 and October 2006)
Fig 1

In the twelve months following the campaign, requests for FT3 and FT4 tests decreased on average by 27% and 30% respectively, compared with the preceding year. TSH tests remained relatively unchanged over this time period, with a small average decrease of 2% (Figure 1).

Figure 2: Referrals for thyroid function tests
Fig 1

Requests for simultaneous testing of TSH with FT4 and/or FT3 decreased by 17%. Figure 2 shows the thyroid test referrals in the 12 months preceding and following the bpac campaign. After the campaign there was a shift towards sole use of TSH and away from simultaneous testing.

50% of older patients receiving lithium may develop hypothyroidism

Lithium increases the already existing risk of hypothyroidism, in the view of the authors the side effect is so common that it should be discussed with women who are considering lithium treatment.

Lithium has been in clinical use since the 1950s as an effective treatment for people with bipolar disorder. It is known to be associated with thyroid dysfunction, especially hypothyroidism. The main risk factors are female gender and starting lithium later in life, but the reported prevalence of hypothyroidism in patients taking lithium varies widely. In this study, 274 patients treated with lithium who had normal baseline thyroid function were observed for between 1 and 7 years.

17 percent of the women and 3 percent of the men had onset of hypothyroidism during lithium therapy. The incidence of hypothyroidism in women in this study (27 per 1000 person-years of follow up) was about eight times that among women in general. The frequency of hypothyroidism in the study group was low before 45 years of age, but it increased progressively to approximately 50 percent in women 65 years of age, while increasing only slightly in men.

The authors reported that while antibodies are a good predictor for the development of hypothyroidism, they are not useful in the monitoring of patients on lithium. Many patients with positive TPO-Ab remained euthyroid and a negative antibody status did not rule out the development of hypothyroidism years later.

As the occurrence of hypothyroidism is increased when women take lithium, the risks should be discussed with those who are considering lithium treatment. It is also recommend that patients do not stop their lithium if hypothyroidism is diagnosed, instead thyroxine replacement should be started.

Reference:

Kirov G, Tredget J, John R, et al. A cross-sectional and a prospective study of thyroid disorders in lithium-treated patients. J Affect Dis 2005;87:313-7.

Small changes in thyroxine do not produce measurable changes in hypothyroid symptoms, well-being or quality of life

Some people believe that patients with primary hypothyroidism feel better when thyroxine doses are adjusted to push TSH levels into the lower end of the reference range, and a number of authorities now recommend that this be the usual target for the treatment of hypothyroidism. However, this approach has never been tested in a clinical trial, and there is no good evidence that the treatment target for primary hypothyroidism should in fact differ from the general laboratory reference range.

A trial was conducted to determine whether adjustment of thyroxine dose (aiming for a target serum TSH in the lower part of the reference range or below) resulted in improved well-being and reduced symptoms of ill health compared with a target TSH in the upper part of the reference range.

At baseline, all patients had stable thyroxine doses and TSH levels between 0.1 and 4.8 mU/L.

Patients with hypothyroidism were treated with slightly varying doses of thyroxine. Through a complex scheme that involved placebos and individualised adjustments in thyroxine dosing, each patient received three randomly ordered 8-week courses of high, medium, and low dose thyroxine, designed to achieve target TSH levels of <0.3 mU/L, 0.3–1.99 mU/L, and 2.0–4.8 mU/L, respectively.

Extensive assessment of cognitive function, quality of life, and thyroid symptoms at the end of each 8-week treatment course revealed no differences between groups, whether analysed by dose (high, medium, or low) or by TSH level actually attained.

Reference:

Walsh JP, Ward LC, Burke V, et al. Small changes in thyroxine dosage do not produce measurable changes in hypothyroid symptoms, well-being, or quality of life: Results of a double-blind, randomised clinical trial. J Clin Endocrinol Metab 2006 Jul; 91:2624-30.

When requesting thyroid function tests, bpacnz recommends

  1. No testing for thyroid dysfunction unless specifically indicated
  2. TSH is used as the sole initial test of thyroid function in most situations

Key points when requesting thyroid function tests

Testing asymptomatic patients

  • No testing for thyroid dysfunction unless specifically indicated
  • The return of positive results is low and there is controversy around the value of treatment in apparently healthy people

Monitoring patients on thyroxine

Non-pregnant patients:

  • Wait at least 6 weeks to test TSH after adjusting thyroxine dose
  • Monitor stable patients annually with TSH only

Pregnant patients:

  • Check TSH of hypothyroid women who are planning pregnancy
  • Check TSH and FT4 early in pregnancy, and at the start of trimesters two and three
  • Check thyroid function more frequently if there is a change in thyroxine dose

Monitoring anti-thyroid medication

  • Test TSH and FT4 until TSH normalises, then
  • Monitor every 2 months using TSH only

Untreated subclinical hypo- and hyperthyroidism

  • An abnormal TSH should be confirmed several months later
  • If still abnormal, monitor the TSH every 12 months unless symptoms develop
  • Consider treatment if TSH becomes persistently unmeasurably low
  • Patients with positive thyroid antibodies may need closer monitoring

Unwell patients

  • During illness, there may be transient changes in TSH, FT4 and FT3
  • Try to defer thyroid function testing until the illness has resolved

Patients on other drugs

  • Amiodarone: Patients on long term therapy should have 6-monthly TSH and FT4 tests
  • Lithium: Use TSH six monthly to check thyroid function

When to request both TSH and FT4

  • During pregnancy
  • Suspected non-adherence to thyroid replacement regimen
  • When a patient is suspected of having pituitary failure both TSH and FT4 should be requested, as often the patient has a normal TSH with a decreased FT4

TSH or FT4?

TSH FT4
Results affected by:
When no specific indication tick tick
Initial testing
Suspicion of hypothyroidism tick tick
Suspicion of hyperthyroidism tick tick
Monitoring
Untreated subclinical hypothyroidism tick tick
Untreated subclinical hyperthyroidism tick tick
Anti-thyroid Rx tick tick
Thyroxine Rx tick tick
Lithium Rx tick tick
Amiodarone Rx tick tick
Special situations
Commencing anti-thyroid Rx tick tick
Pregnant hypothyroid tick tick
Suspected central hypothyroidism (rare) tick tick
Non compliance with therapy tick tick

For more detailed material please see “Investigating Thyroid Function”.