HYPOTHYROIDISM: CAUSES AND TREATMENT

What is Hypothyroidism?


Hypothyroidism

Clinical features
Classic clinical features of hypothyroidism include weight gain, cold intolerance, dry skin, constipation, memory loss, lethargy/slow thought/‘slowing up’, menorrhagia, periorbital/facial oedema, loss of outer two-thirds of eye brows, deafness, chest pain and coma. Rarely seen nowadays as thyroid function tests are easy to perform and detect the disease usually at an earlier stage. Weight gain, dry skin and lethargy are frequently reported, but even in biochemically hypothyroid individuals can only confidently be ascribed to thyroid status if they reverse on treatment.


Biochemical diagnosis

• TSH with T4 in the normal range is referred to as subclinical hypothyroidism.
• TSH with 5 T4 is overt hypothyroidism. 5 T4 with TSH in the normal range may be due to pituitary failure (2° hypothyroidism) and if persistent requires pituitary function testing. See Fig. 2.14 for other patterns of thyroid function tests.

Differential diagnosis (causes)

In iodine sufficient countries, the vast majority of spontaneous hypothyroidism is due to autoimmune thyroiditis (Hashimoto’s disease if goitre present, atrophic thyroiditis if goitre absent)—antithyroid antibodies
present in 80–90% of cases. Other common causes are post-thyroidectomy, post-radioiodine therapy and side effects of amiodarone or lithium. Rarer causes include treatment with cytokines (e.g. interferons, GM-CSF, interleukin-2), vast excess iodine intake (iodine drops, water purifying tablets), congenital hypothyroidism (caused by a variety of genetic defects, should be detected by neonatal screening programme), iodine deficiency (urinary iodide excretion <45μg/day, commonest cause worldwide esp.
mountainous areas, S Germany, Greece, Paraguay—‘endemic goitre’), thyroid-blocking substances in the indigenous diet (goitrogens esp. in brassicas and cassava, e.g. in Sheffield, Spain, Bohemia, Kentucky, Virginia, Tasmania—‘endogenous goitre’ without iodine deficiency), Pendred’s syndrome (mild hypothyroidism with sensineural deafness due to Mondini cochlear defect, positive perchlorate discharge test).

Diagnostic catches
4 TSH and 5 T4 always represents hypothyroidism. If the TSH alone is 4 and the T4 is not even slightly low, a heterophile antibody interfering in the TSH assay may be present in the patient’s serum. This is especially
likely if there is no change in TSH level after thyroxine treatment but the T4 level rises (confirming compliance with tablets). For unusual patterns of thyroid function tests. Note that within the first 1–3 months (or longer) after treatment of hyperthyroidism, profound hypothyroidism may develop with a 5 T4 but the TSH may still be suppressed or only mildly raised due to the long period of TSH suppression prior to treatment.

Raised TSH alone with disproportionate symptoms of lethargy may be seen in hypoadrenalism. If suspected treat with steroids first as thyroxine may precipitate an Addisonian crisis.

Transient hypothyroidism
Transient or self-resolving hypothyroidism, often preceded by hyperthyroidism, is seen in viral thyroiditis, after pregnancy (post-partum thyroiditis) and in some individuals with autoimmune thyroiditis (positive
antithyroid antibodies). Treatment temporarily with thyroxine is only required if the patient is very symptomatic. Thyroid function should return to normal within 6 months. Hypothyroidism may also be transient in the first 6 months after radioiodine therapy.

Subclinical hypothyroidism
A raised TSH (<20mU/L) with normal T4/T3 is very common and seen in 5–10% of women and ~2% of males. It is usually due to subclinical autoimmune thyroid disease and is frequently discovered on routine testing. In randomised trials, ~20% of patients obtain psychological benefit from beginning T4 therapy, in many others it is probably truly asymptomatic. If antithyroid antibodies are detectable, the rate of progression to overt hypothyroidism is ~50% at 20 years, but higher than this with higher initial TSH levels. If the TSH alone is raised with negative antibodies (or the TSH is normal with raised antibodies alone), overt hypothyroidism develops in 25% at 20 years. A reasonable approach is a trial of thyroxine for 6 months in symptomatic patients with subclinical hypothyroidism or TSH >10mU/L, and observing the TSH level at 6–12-monthly intervals in asymptomatic patients with TSH <10mU/L.

Hypothyroidism and pregnancy
Overt hypothyroidism is associated with poor obstetric outcomes. Recent evidence suggests that subclinical hypothyroidism is associated with a slight reduction in the baby’s IQ and should be treated. Many authorities
advocate screening for hypothyroidism in all antenatal patients as early as possible in pregnancy. Patients on T4 need to increase their dose by 50 g from the first trimester of pregnancy. Maternal thyroxine can compensate for fetal thyroid failure in utero but congenital hypothyroidism must be detected at birth (screening test) to avoid mental retardation developing.

Where the mother and fetus are both hypothyroid—most commonly due to iodine deficiency—mental retardation can develop in utero (cretinisim). Note that mothers with positive antithyroid antibodies and/or subclinical hypothyroidism have a 50% chance of developing (transient) post-partum thyroiditis.


How is hypothyroidism treated?

With the exception of certain conditions, the treatment of hypothyroidism requires life-long therapy. Before synthetic levothyroxine (T4) was available, desiccated thyroid tablets were used. Desiccated thyroid was obtained from animal thyroid glands, which lacked consistency of potency from batch to batch. Presently, a pure, synthetic T4 is widely available. Therefore, there is no reason to use desiccated thyroid extract.

As described above, the most active thyroid hormone is actually T3. So why do physicians choose to treat patients with the T4 form of thyroid? T3 [liothyronine sodium (Cytomel)] is available and there are certain indications for its use. However, for the majority of patients, a form of T4 [levothyroxine sodium (Levoxyl, Synthroid)] is the preferred treatment. This is a more stable form of thyroid hormone and requires once a day dosing, whereas T3 is much shorter-acting and needs to be taken multiple times a day. In the overwhelming majority of patients, synthetic T4 is readily and steadily converted to T3 naturally in the bloodstream, and this conversion is appropriately regulated by the body's tissues.

The average dose of T4 replacement in adults is approximately 1.6 micrograms per kilogram per day. This translates into approximately 100 to 150 micrograms per day.

Children require larger doses.

In young, healthy patients, the full amount of T4 replacement hormone may be started initially.

In patients with preexisting heart disease, this method of thyroid replacement may aggravate the underlying heart condition in about 20% of cases.

In older patients without known heart disease, starting with a full dose of thyroid replacement may result in uncovering heart disease, resulting in chest pain or a heart attack. For this reason, patients with a history of heart disease or those suspected of being at high risk are started with 25 micrograms or less of replacement hormone, with a gradual increase in the dose at 6 week intervals.
Ideally, synthetic T4 replacement should be taken in the morning, 30 minutes before eating. Other medications containing iron or antacids should be avoided, because they interfere with absorption.

Therapy for hypothyroidism is monitored at approximately six week intervals until stable. During these visits, a blood sample is checked for TSH to determine if the appropriate amount of thyroid replacement is being given. The goal is to maintain the TSH within normal limits. Depending on the lab used, the absolute values may vary, but in general, a normal TSH range is between 0.5 to 5.0uIU/ml. Once stable, the TSH can be checked yearly. Over-treating hypothyroidism with excessive thyroid medication is potentially harmful and can cause problems with heart palpitations and blood pressure control and can also contribute to osteoporosis. Every effort should be made to keep the TSH within the normal range.