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Hypothyroidism is the clinical syndrome caused by thyroid hormone deficiency, due to under-activity of the thyroid gland.

It can result from a defect arising anywhere along the hypothalamic-pituitary-thyroid axis. Primary hypothyroidism (disease of the thyroid gland) accounts for the majority of cases.

Central hypothyroidism, caused by decreased secretion of thyroid-stimulating hormones (TSH) from the anterior pituitary gland, or decreased secretion of thyrotropin-releasing hormones (TRH) from the hypothalamus, happens less often.

Causes of Hypothyroidism

The cause of hypothyroidism should be identified in every patient because it is important in the acute and long-term management of the condition. Primary hypothyroidism might be transient – requiring no therapy, or it could be caused by a medication, and resolved when the offending drug is discontinued. Causes of primary hypothyroidism include:

  • Hashimoto’s thyroiditis - The most common cause of hypothyroidism. The incidence is five to eight times more common in women than with men
  • Thyroidectomy
  • Radioactive therapy
  • External neck irradiation
  • Iodine deficiency or excess
  • Medication such as lithium, amiodarone, tyroxine kinase inhibitors, interferon alpha and interleukin 2
  • Infiltrative diseases such as hemochromatosis, sarcoidosis, tuberculosis
  • Transient hypothyroidism such as post-partum thyroiditis, subacute thyroiditis

It is important to suspect and recognise central hypothyroidism as the management differs greatly from primary hypothyroidism. Causes of central hypothyroidism include:

  • Mass lesions
  • Pituitary surgery
  • Radiation
  • Infiltrative lesions
  • Trauma
  • Infarction

Clinical Features and Diagnosis

The clinical manifestations of hypothyroidism are highly variable, depending on the age at onset, and the duration and severity of thyroid hormone deficiency. Common symptoms of thyroid hormone deficiency includes fatigue, cold intolerance, weight gain, constipation, dry skin, myalgia, and menstrual irregularities. Physical examination findings may include a goiter in primary thyroid disease, bradycardia and a delayed relaxation phase of the deep tendon reflexes.

Due to the highly variable and non-specific clinical manifestations of hypothyroidism, the diagnosis is heavily reliant on laboratory tests.

Primary hypothyroidism is characterised by a low serum free thyroxine (FT4) level, and a high serum thyroid stimulating hormone (TSH) level, whereas central hypothyroidism is characterised by a low serum FT4 level and a serum TSH level that is not appropriately elevated. More than 90% of patients with Hashimoto’s thyroiditis have elevated antibodies to thyroid peroxidase (anti-TPO) and thyroglobulin (TgAb).


Treatment of Primary Hypothyroidism

This segment will focus on the management of primary hypothyroidism.

In most patients, the treatment of hypothyroidism is life-long, unless the hypothyroidism is transient or reversible (drug-induced). The aim of treatment is to restore the euthyroid state with oral levothyroxine (LT4). It is important to know that the bioequivalence of the different brands of levothyroxine preparations differs. It is thus recommended to use the same preparation for treatment in a patient. If there is a change in preparation (e.g patient is discharged from hospital to primary care clinic), the thyroid function tests should be repeated in six weeks after changing preparations, to document that the results are still within the therapeutic target. Furthermore, the absorption and bioavailability of oral T4 is highly variable. In general, about 80% of an oral dose of LT4 is absorbed. LT4 should be taken on an empty stomach, ideally an hour before breakfast, for better absorption. It should not be taken with other medication that interferes with its absorption, such as bile acid resins, proton pump inhibitors, calcium carbonate, and ferrous sulfate.

The average replacement dose of LT4 in adults is approximately 1.6 mcg/kg body weight per day, but the range of required doses is wide, varying from 50 to ≥200 mcg/day depending on the cause of the hypothyroidism. The initial dose can be the full anticipated dose (1.6 mcg/kg/day) in young, healthy patients, but older patients should be started on a lower dose (25 to 50 mcg daily) due to the higher risk of underlying cardiovascular disease. After the initiation of LT4, thyroid function tests should be repeated every six weeks for LT4 titration until the thyroid function tests achieve the therapeutic target.

Once the proper maintenance dose is identified, a patient with stable thyroid function can be managed at the primary care setting safely in the long-term. The patient should be reviewed and thyroid function tests performed once every six months to a year.


By Dr Chew Chee Kian
Associate Consultant
Department of Endocrinology
Tan Tock Seng Hospital 

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