Viollier : Labor - Laboratoire - Laboratorio

Consultation:

Matter Lukas, MD; Burki Dieter, MD; Pfister Stefan, PharmD

Measurement of thyroid stimulating hormone (TSH), fT4 (free thyroxine) and fT3 (free triiodothyronine) enables differentiation of primary versus secondary disorders of thyroid gland function and subclinical (latent) versus manifest hypo- or hyperthyroidism. If only TSH is measured, there is the danger of missing a secondary or tertiary hypothyroidism.

Thyroid peroxidase (TPO) and thyroglobulin (TG) IgG and also TSH-receptor IgG provide information about the autoimmune pathogenesis of a thyroid disorder (see Section Interpretation, Autoimmunity: Endocrine disorders).

Laboratory diagnosis: hypothyroidism

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Laboratory diagnosis: hyperthyroidism

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Interpretation of thyroid function tests

TSH

fT4

fT3

Frequent cause

Rare cause

–	+	+	Primary hyperthyroidism (Graves' disease, nodular goiter, toxic nodules), transient thyroiditis (postpartum, postviral /de Quervain's thyroiditis)	Thyroxine ingestion, ectopic thyroid gland tissue, iodine-induced, amiodarone, gestational thyrotoxicosis
–	N	N	Subclinical hyperthyroidism, thyroxine ingestion	Steroid therapy, dopamine / dobutamine, non-thyroid disease
– / N	–	–	Non-thyroid disease, recently started antithyroid therapy (TSH still suppressed)	Secondary hypothyroidism, congenital TSH or TRH deficiency
+	–	–	Primary hypothyroidism in chron. autoimmune thyroiditis, after radioiodine therapy or thyroidectomy, hypothyroid phase of transient thyroiditis	After irradiation, amiodarone, lithium, interferon, IL-2, iodine deficiency, amyloid, Riedel's thyroiditis, rare congenital defects
+	N	N	Subclinical autoimmune thyroiditis	Heterophilic antibodies, intermittent T4 therapy in hypothyroidism, amiodarone, sertraline, colestyramine, iodine deficiency, recovery after non-thyroid disease, TSH-R- and other congenital defects
N / +	+	N / +		Interfering antibodies to T3/T4, dysalbuminemia, amiodarone, intermittent T4 therapy, T4-resistance, TSH-secreting pituitary tumor

Key

– decreased; + increased; N normal

Common misinterpretations of thyroid function tests

TSH

fT4

fT3

Situation

Misinterpretation

Correct interpretation

–	–	–	After thyrotoxicosis therapy	Persistent hyperthyroidism	Severe hypothyroidism
–	+	+	Neck pain of recent onset	Thyrotoxicosis	Possible transient thyroiditis
– / N	– / N	– / N	General illness	Hypothyroidism	Non-thyroid disease
N	nd	nd	Pituitary disorder	Euthyroidism	Hypothyroidism possible: measure fT4 and fT3
+	N	N	TSH does not fall under T4 therapy	Compliance error	Interfering antibodies

Key

– decreased; + increased; N normal, nd not done

Physiological and clinical influences on thyroid tests

TSH

fT4

FT3

Neonates	N / +	N / +	N / +
Children	N	N	N / +
Elderly	N / –	N / –	N / –
Period spent at high altitude	N	+
Serious non-thyroid disease	N / – / +	N / –	–
Hyperalbuminemia	N	N / –	N
Increased TBG	N	N	N
Decreased TBG	N	N	N

Key

– decreased; + increased; N normal

Pregnancy

hCG has a weak thyroid-stimulating effect. The very high hCG concentrations in the first trimester therefore suppress TSH secretion and can mimic (subclinical) hyperthyroidism. If TSH is in the lower reference range before conception, it can fall below 0.35 mU/L in the first trimester (with normal fT3 and fT4 levels). Conversely, a normal TSH value can mask (usually subclinical) hypothyroidism in the first trimester, particularly if TPO IgG are present. Pregnant women in the first trimester with TSH > 2.0 mU/L and positive TPO IgG or a family or personal history of thyroid disease frequently exhibit thyroid hypofunction and may require T4 replacement to prevent obstetric complications. Hypothyroidism in pregnant women or in fetuses can affect neural development and is associated with an increased incidence of abortions and premature births.

Effects of drugs on thyroid hormones

Numerous drugs affect thyroid hormones. Of particular practical importance are amiodarone and lithium.

Forms of amiodarone-induced thyroid dysfunction

Amiodarone inhibits 5’-deiodinase and reduces metabolic clearance. Depending on dietary iodine intake, the additional supply of iodine can lead to hyper- or hypothyroidism. A toxic destructive thyroiditis can also develop.

Hyperthyroidism

Hypothyroidism

Type I

Type II

Mechanism	iodine excess	destructive thyroiditis (toxic effect)	iodine excess
Incidence	up to 23%, especially in areas of iodine deficiency		up to 20%, especially if adequate iodine intake
TPO autoantibodies	frequent	usually negative	frequent
Thyroid function	hyperthyroidism	hyperthyroidism	hypothyroidism
Doppler ultrasound	hypervascularised, blood flow normal or increased	blood flow reduced	variable
Therapy	antithyroid drugs	corticosteroids	levothyroxine

Effects on thyroid hormones of other drugs

Regular checks of TSH are recommended during lithium therapy because hypothyroidism can develop due to the inhibition of hormone release in the thyroid and sometimes autoimmune thyroiditis.

Effects on thyroid metabolism have been described for many other drugs. Information about an individual drug will gladly be provided on request.

Monitoring of treatment

To monitor antithyroid therapy, fT4 should be measured every 3 – 6 weeks until a euthyroid state is achieved. The half-life of fT4 is one week. After 3 months TSH should be measurable, otherwise the antithyroid therapy is most probably inadequate. During maintenance treatment, checks on TSH every 3 – 6 months are sufficient. Even if treatment is successful, pituitary function recovers only slowly and TSH secretion can remain suppressed for months.

After discontinuation of the antithyroid drug, thyroid function should initially be checked every three months, in order to detect a recurrence promptly. After one year, the interval can be extended to 6 – 12 months. Late recurrences are rare but may occur even after more than five to ten years.

If thyroid values are stable within the target range (TSH 0.4 – 2.5 mU/L) and the levothyroxine dose is unchanged, replacement can be adequately monitored by measuring TSH once to three times a year.

Following strumectomy, TSH and fT4 are checked at intervals of one to several months, e.g. after 1, 3, 6 and 12 months.

References / Links

Brent GA. Graves’ disease. New Engl J Med 2008;358:2594-605

Cooper DS. Hyperthyroidism. Lancet 2003; 362: 459–68

Dayan CM. Interpretation of thyroid function tests. Lancet 2001;357:619-24

Negro R et al. Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J Clin Endocrinol Metab 2006;91:2587-91

Pearce EN et al. Thyroiditis. N Engl J Med 2003;348:2646-55

Rajeswaran C et al. Management of amiodarone-induced thyrotoxicosis. Swiss Med Wkly 2003;133:579–85

Roberts CGT, Ladenson PW. Hypothyroidism. Lancet 2004;363:793–803

Vaidya B et al. Detection of thyroid dysfunction in early pregnancy: universal screening or targeted high-risk case finding? J Clin Endocrinol Metab 2007;92:203-7