Identify the possibility of hypothyroidism when the patient's symptoms include fatigue, constipation, feeling cold, impaired memory and slow heart rate.
The disease is common and its symptoms may be vague.
Diagnosis of hypothyroidism and treatment of hypothyroidism originating in the thyroid gland (primary hypothyroidism) are tasks of the primary health care.
Hypothyroidism is easy to confirm or exclude by determining TSH and free T4 (FT4) concentrations.
Check readily whether the thyroid gland functions normally by determining TSH and FT4 concentrations before possible pregnancy and after pregnancy.
Remember also that hypothyroidism can be the cause of high serum cholesterol or creatine kinase (CK) concentrations.
In replacement therapy, a young or middle-aged patient usually feels best if TSH concentration is about 1-2 mU/l and FT4 concentration is close to the upper limit of the reference range.
Elderly patients with e.g. angina pectoris or arrhythmias often are more susceptible to the effects of thyroxine. In them, the maintenance dose remains slightly lower and TSH concentration respectively a little higher.
Ultrasonography has no role in the investigation of hypothyroidism (unless it is indicated by the findings on palpation).
Thyroxine should not be used for the treatment of e.g. depression, low energy level or overweight in a person who is biochemically euthyroid.
Causes of hypothyroidism
Permanent hypothyroidism
Primary hypothyroidism (95% of patients)
Autoimmune thyroiditis Chronic Autoimmune Thyroiditis is the most common cause (serum TPO antibody concentration increased).
Other causes: thyroid surgery, radio-iodine therapy
Deficiency or lacking effect of TSH (central hypothyroidism; 5% of patients)
Hypothyroid phase associated with postpartum thyroiditis, usually about (2-)4-8 months from delivery. The disease typically begins with transient thyrotoxicosis, see Chronic Autoimmune Thyroiditis.
A number of drugs affect thyroid function (may cause hypo- or hyperthyroidism), e.g lithium, amiodarone.
Symptoms
The symptoms and their severity vary in different individuals.
In deep hypothyroidism the systemic symptoms include lack of initiative, fatigue, depressive mood, memory problems, slow motor functions and speech, feeling cold, constipation, weight gain and slow heart rate. The skin is dry, rough, cold or pale. Hair may become rough, and there is hair loss. The symptoms may also include muscle weakness, ache and stiffness.
The menstrual cycle may be disturbed.
In the elderly the clinical picture is often atypical with slowing and depression that may simulate dementia.
In young women the first symptom may be amenorrhoea or infertility and/or hyperprolactinaemia.
The thyroid gland is palpated (size, concistency).
Laboratory tests
Serum TSH and FT4 are the primary investigations.
Slightly increased TSH concentration may also be associated with the patient's current medication.
Free T3 (FT3) assay is of no benefit.
In primary hypothyroidism, TSH concentration is above reference range and FT4 is below it.
In subclinical hypothyroidism, FT4 concentration is within reference range but TSH concentration is permanently increased. The patient usually has only mild symptoms or is symptomless. The permanent nature of the change has to be confirmed by repeating the TSH assay after 6-8 weeks. Serum TPO antibody concentration is determined at the same time.
In central hypothyroidism, TSH concentration is within reference range or slightly decreased and FT4 is below reference range. These patients are referred to specialized care for assessment.
The patient may also have a more extensive hypofunction of the pituitary gland.
Thyroxine substitution is always indicated if serum TSH concentration is increased and FT4 concentration is decreased.
In subclinical hypothyroidism, therapy is started if TSH concentration is over 10 or if the patient is pregnant. If serum TSH concentration is permanently but only slightly increased (> 3.6-4 mU/l), following factors support the initiation of therapy: symptoms suggesting hypothyroidism, young age, pregnancy, increased concentration of TPO antibodies, goitre and hypercholesterolaemia.
In mild subclinical hypothyroidism, treatment decisions are made individually. Before starting the possible thyroxine substitution, a repeat TSH measurement should be performed. According to current recommendations, subclinical hypothyroidism (TSH < 10 mU/l, FT4 within reference range) should not be treated in very old persons.
Before starting permanent thyroxine substitution, it is often advisable to carry out a therapeutic trial of 3-6 months.
In young patients the initial dose of thyroxine is 50-100 µg/day. If the patient has been hypothyroid for a long time, the dose is gradually increased by 25 µg every 2 weeks until the dose 100 µg/day is reached.
The maintenance dose correlates with the patient's body weight. The usual maintenance dose is approximately 100-200 µg/day. In subclinical hypothyroidism, a lower maintenance dose is usually required.
TSH is checked at the earliest 4 weeks from the latest dose increase. On that occasion, the maintenance dose is adjusted to a suitable level. The patient often feels well if TSH concentration is 1-2 mU/l and FT4 is within the upper third of the reference range.
In the elderly and in patients with ischaemic heart disease the initial dose is 25 µg/day. The dose is gradually increased at 3 to 4 week intervals.
In patients who are elderly or who have a cardiac disease, the maintenance dose is often left lower than usual, in which case TSH concentration is close to the upper limit of the reference range.
After a change in the dose of thyroxine, serum FT4 and TSH are determined after 4 weeks at the earliest because the concentration of TSH changes slowly. When the maintenance dose has been established, TSH is determined every 1 to 2 years, e.g. in conjunction with prescription renewal. In full substitution, the dose usually remains stable.
In controversial cases (e.g. in possibly transient hypothyroidism) serum TSH should be determined 6 weeks after discontinuation of treatment. If serum TSH rises above the reference range permanent thyroxine substitution is indicated.
Thyroxine is taken in the morning as a single dose on an empty stomach.
Certain drugs, especially iron and calcium medications, disturb the absorption of thyroxine; such medications should not be taken until at least 4 hours after the intake of thyroxine.
Oestrogen replacement therapy has the same effect as pregnancy: need for thyroxine increases with up to one third.
It is good to ensure that the serum TSH concentration in a woman on thyroxine substitution is < 2.5 mU/l already when she is trying to become pregnant.
Thyroxine requirement is increased by 25-50 µg during pregnancy. The dose is increased by 25 µg as soon as the pregnancy is detected, or according to TSH concentration so that during pregnancy TSH remains below 2.5 mU/l in the first and below (2.5-)3 mU/l in the second and third trimester.
Sufficient supply of thyroxine is important also for the foetus, particularly in early pregnancy.
After pregnancy, the previous maintenance dose is reinstated.
In the rare central hypothyroidism, TSH does not work as a follow-up parameter during pregnancy either.
References
Pearce SH, Brabant G, Duntas LH ym. 2013 ETA Guideline: Management of Subclinical Hypothyroidism. Eur Thyroid J 2013;2(4):215-28. [PubMed]