Hypothyroidism is a common endocrine condition which affects approximately one to two percent of the UK population, increasing to five percent in people over 60 and more than ten percent in adults over 80.
The most common cause of hypothyroidism is iodine deficiency due to low dietary intake. Iodine is an essential mineral for the production of the thyroid hormones triiodothyronine and tetraiodothyronine, known as T3 and T4 respectively. However, in countries with sufficient dietary iodine intake, such as the UK where foods are fortified, aetiology of hypothyroidism differs and the disorder is categorised as primary, secondary, tertiary or peripheral, dependant on the origin of dysfunction.
In the UK, 99 percent of cases are classed as primary hypothyroidism, which is attributable to dysfunction from within the thyroid gland itself, with 95 percent of these due to autoimmune mediated destruction of thyroid follicle cells, the chief site of thyroid hormone production. In clinical practice primary hypothyroidism is further subcategorised into ‘overt’ and ‘subclinical’ (see below).
The other classifications of hypothyroidism account for only 1 percent of cases combined. Both secondary and tertiary hypothyroidism arise due to impaired stimulation of the thyroid gland from either the anterior pituitary or hypothalamus respectively. Peripheral hypothyroidism occurs from either tissue resistance to thyroid hormone or increased rates of deactivation of circulating free thyroid hormone.
Symptoms
Regardless of aetiology, symptoms of hypothyroidism will be similar, with some additional signs seen in secondary and tertiary indicating central involvement, such as headache or symptoms of other hormone deficiency:
General
- Fatigue
- Hoarse voice
Cardiac
- Bradycardia
- Diastolic hypertension
- Pericardial effusion
Gastrointestinal
- Weight gain
- Decreased appetite
- Abdominal distension
- Constipation
Neuromuscular
- Sensitivity to cold
- Depression
- Impaired cognition or ‘brain fog’
- Peripheral neuropathy
- Muscle weakness or pain
Reproductive
- Irregular menstrual cycle and menorrhagia
- Infertility or subfertility
Skin and appearance
- Dry flaking thickened skin
- Goitre
- Reduced sweating
- Yellow complexion
- Facial swelling, particularly of the eye lids
- Brittle nails
- Coarse hair
- Hair loss, particularly of the eyebrows
Diagnosis
Diagnosis of hypothyroidism is relatively simple, based on assessment of presenting symptoms and confirmed through biochemical testing of thyroid function with thyroid stimulating hormone (TSH) levels and free serum T4 (FT4) levels (peripheral hypothyroidism requires more complex investigation.
Treatment
Treatment aims to replace depleted T4 through supplementation. Efficacy is measured through monitoring of TSH in primary cases, and in secondary and tertiary cases where TSH level is unrelated to T4 production due to impaired feedback mechanisms, FT4 is monitored.
Levothyroxine, a synthetic T4, remains the first line treatment for hypothyroidism, with a starting dose of 1.6microgram/kg daily rounded to the nearest 25 micrograms. However, patients over the age of 65 or with pre-existing cardiovascular disease may be started on 25-50 microgram daily and then titrated up to effect to avoid risks associated with over treatment. Contraindications for levothyroxine include previous hypersensitivity, hyperthyroidism and uncontrolled adrenal insufficiency, due to risks of exacerbation.
Levothyroxine is a prohormone activated through hepatic metabolism and is therefore subject to effect from drugs that alter liver enzyme function such as phenytoin, carbamazepine and rifampicin.
Often, patients who fail to sufficiently respond to levothyroxine struggle with concordance or reduced absorption linked with an unrecognised interaction. Absorption of levothyroxine is diminished by ferrous sulphate, calcium supplements and cholestyramine, as well as food intake which can reduce absorption by up to 80 percent.
Second line therapy of liothyronine, a synthetic form of T3, is available in rare cases where levothyroxine is truly intolerable. Liothyronine acts faster and is five times more potent but due to lack of evidence of superiority over levothyroxine and greater cost associated, specialist endocrinologist assessment is required before initiation. Despite debates, combining these therapies is not recommended due to sparce evidence regarding efficacy.
Supporting the management of hypothyroidism
Although commonly encountered, hypothyroidism is not to be overlooked or forgotten. Pharmacists have a major role to play in supporting the management of hypothyroidism, through effective counselling on the importance of concordance, advising on drug interactions and providing direct care in thyroid clinics.
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Competing interest statement:
The author declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
