Thyroid disorders affect 1 in 10 Australians. The thyroid is an endocrine gland, located on the anterior sides of the neck that secretes hormones involved in metabolism, protein synthesis, and controlling calcium levels in the blood. Thyroxine (T4) is the major hormone secreted by the gland. Approximately 35–40% of T4 is transformed hepatically into, the four times more potent, triiodothyronine (T3) and a good portion is converted into inactive reserve T3 (rT3). The thyroid gland uses the essential micronutrient iodine to produce T4 and T3.

Thyroid activity is controlled by the hypothalamic-pituitary-thyroid feedback (HPT) system. The hypothalamus is stimulated by exogenous factors (such as cold or stress) or endogenous factors (low thyroid hormone levels) to secrete thyrotropin-releasing hormone (TRH), which in turn stimulates the anterior pituitary to secrete thyroid-stimulating hormone (TSH). TSH regulates the secretion of T4 which is converted to T3. High thyroid hormone levels will down regulate both TRH at the hypothalamus and TSH at the pituitary. Disorders are categorised by the abnormality of function; hypothyroidism (underactive thyroid) and hyperthyroidism (overactive thyroid).

Hypothyroidism

Hypothyroidism can affect almost all body systems and is characterised by a slowing down of processes due to deficiency of thyroid hormones. Hypothyroidism features include retardation of mental, cardiovascular, gastrointestinal, and neuromuscular systems. Symptoms that appear insignificant can include; low energy, depression, slow heart rate, cold intolerance, dry skin, hair loss, and constipation. More significant symptoms are muscle fatigue, weight gain, exacerbated heart failure, myxoedema (orange peel-like skin), and goitre. More frequently hypothyroidism is subtle; however it is crucial to identify it, to avoid a chronic and progressively lethal state.

Causes of hypothyroidism are; congenital (most common), iodine deficiency, autoimmune dysfunction (Hashimoto’s disease), or anti-thyroid treatment. Hashimoto’s thyroiditis is the most common cause of goitre in hypothyroidism. Hashimoto’s disease is an autoimmune disease in which antibodies develop against thyroglobulin (binding protein for thyroid hormones) and thyroid peroxidase (enzyme involved in the production of thyroid hormones). These antibodies lead to decreased thyroid hormones and inflammation of the thyroid.

Hypothyroidism is treated using T4 replacement therapy with the aim to normalise TSH levels. Doses range from 25-200mcg depending on the patient’s response. T4 replacement is very effective and non-compliance is the main source of treatment failure. T4 should be stored in the refrigerator, or up to 14 days at room temperature. Patients who use dose administration aids (Dosette®, Webster-pak®, etc) should be informed that these packs are preferably stored in the refrigerator. Adverse effects of T4 replacement are dose related and include cardiovascular effects (angina, tachycardia and arrhythmias), muscle cramps, restlessness, flushing, excessive weight loss and osteoporosis (all the signs of hyperthyroidism).

If left untreated hypothyroidism can eventually lead to somnolence, coma, and death. The treatment of hypothyroid coma is with a slow intravenous infusion of liothyronine sodium (T3) 20mcg once or twice daily and supportive therapy (heat conservation, intubation, prevention of adrenal insufficiency if needed). This dose form is available through the Therapeutic Goods Administration Special Access Scheme (SAS) and is reserved for when the patient is in a coma.

Hyperthyroidism (Thyrotoxicosis)

Excessive thyroid hormones will likewise affect organ systems conversely to that seen in hypothyroidism. This characteristically speeds up those organ system’s activities. Signs and symptoms include irritability, rapid heart rate, excessive weight loss, heat intolerance, lid retraction and frequent bowel motions with increased appetite. Goitre, though very uncommon, may exist in hyperthyroidism. More common symptoms are subclinical and, if left untreated, patients have an increased risk of developing cardiac arrhythmias, heart failure, and osteoporosis.

Thyroid storm is however, an uncommon although serious condition that may arise from subclinical hyperthyroidism exacerbated by another acute condition (surgery, childbirth, infections, etc). In thyroid storm the metabolic abnormalities result in potential fever, cardiovascular compromise (hypertensive crisis, severe arrhythmia), and mental state changes requiring emergency intervention.

The most common causes of hyperthyroidism are Graves’ disease, thyroid adenomas, ingested T4, and other medicines high in iodine content. Graves’ disease is an autoimmune disease in which antibodies actually stimulate receptors found on the thyroid and result in goitre and over excretion of thyroid hormone. Less common is that these antibodies may actually block the receptors and result in hypothyroidism. Optical symptoms (retraction and spasm of the upper eyelid with that classic stare or frightened expression) are very common in Graves’ disease.

Drugs that can induce hyperthyroidism should be reviewed in hyperthyroid patients. These include; iodides, amiodarone, lithium, interferon-alpha, and T4 overdose.

Diagnosis of thyroid disorders

Thyroid disorders are often diagnosed incidental to investigating causes of the individual’s presenting complaint, because symptoms are often subclinical, or non-specific; therefore laboratory testing often occurs on a low index of suspicion. Blood pathology testing of serum T4, TSH (and to a lesser extent T3), thyroglobulin and antibody markers are necessary for diagnosis. The combination of results and the evidence of clinical symptoms will give an accurate indication of thyroid function.

Comparing TSH to T4 levels is usually the key to interpreting results as shown in Table 1. If the TSH level is high it can generally indicate dysfunction of the thyroid gland itself (primary hypothyroidism) and be treated as such. A low T4 level can indicate that either the thyroid is dysfunctional or the pituitary is not stimulating the thyroid. Low T4 levels should activate the HPT system, therefore if TSH levels are normal or low it could mean dysfunction of either the hypothalamus and/or pituitary (secondary hypothyroidism); so investigation, and correction, of the hypothalamus and/or pituitary should follow to avoid adrenal crisis.

Table 1. Diagnosis Matrix to Interpret Thyroid Pathology.

Pathology Result

High T4

Normal T4

Low T4

High TSH Possible adenoma and/or thyroxine resistance Early or subclinical hypothyroidism Primary Hypothyroidism
Normal TSH Possible adenoma and/or thyroxine resistance Euthyroid Possibly secondary hypothyroidism
Low TSH Hyperthyroidism Subclinical hyperthyroidism Secondary hypothyroidism

 

A high T4 level alone is not always indicative of hyperthyroidism. Because T4 is just about totally protein bound and under certain physiological conditions (pregnancy, liver disease and oestrogen administration) thyroglobulin levels are increased, moderately increasing T4 level results. Also low TSH does not necessarily indicate hyperthyroidism and may be evidence of an injured pituitary. Therefore it is ideal to show both high T4 levels and low TSH levels to diagnose hyperthyroidism. High levels of T3 can be used for confirming diagnosis if TSH levels are low and T4 is in the normal range (T3 being more potent). Refer to Table 1.

Conclusion

Thyroid function has important consequences for other disease states and dysfunction may complicate treatment regimes of these diseases. Decreased thyroid function is treated with hormone replacement to allow re-establishment of the euthyroid (healthy) state, whilst increased function is treated by means to reduce hormonal levels either pharmacologically, surgically, or through radiotherapy. Diagnosis of subclinical dysfunction is through comparison of blood hormone levels.

References:

  1. Mortimer RH. Abnormal laboratory results: Thyroid function tests. Aust Prescr 2011; 34: 12–15.
  2. Davoren P. Modern Management of Thyroid Replacement Therapy. Aust Prescr 2008; 31: 159–61.
  3. Rossi S, (Editor). Australian Medicines Handbook 2013. Adelaide: Australian Medicines Handbook Pty Ltd; 2013.
  4. Endocrinology Expert Group. Therapeutic Guidelines: Endocrinology. Version 4. Melbourne: Therapeutic Guidelines Limited; 2009.
  5. eMIMS [Internet]. St Leonards: MIMS Australia; 2013. Accessed 15 June 2013.

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