Hypothyroidism

Hypothyroidism or underactive thyroid function, occurs when the thyroid gland fails to produce sufficient amounts of the thyroid hormones T4 and T3. Four common causes of hypothyroidism are:

1. Hashimoto’s thyroiditis, an autoimmune disease that results in inflammation of the thyroid gland. This condition is more common in women than in men and often runs in families.
2. Treatment of Graves’ hyperthyroidism or toxic multinodular goiter with radioactive iodine.
3. Congenital hypothyroidism (in individuals born without a thyroid gland or a poorly functioning one); and
4. Surgical removal of the thyroid gland as a treatment for thyroid cancer or hyperthyroidism.

Rarely, hypothyroidism can occur secondary to disorders of the pituitary gland or the hypothalamus. This is because normal function of the thyroid gland depends on carefully regulated secretion of thyroid stimulating hormone (TSH) from the pituitary gland and thyrotopin releasing hormone (TRH) from the hypothalamus. These two glands, located in the brain, act as “master glands” which control the functioning of the thyroid gland. Another important, but “transient” form of hypothyroidism occurs with postpartum thyroiditis or subacute thyroiditis. Postpartum thyroiditis is inflammation of the thyroid gland which occurs immediately after delivery. Subacute thyroiditis is painful inflammation of the thyroid gland usually associated with a sore throat and/or fever. Although hypothyroidism associated with these conditions is transient and self-resolving, in some cases, it stays long term.

Clinical Features

Hypothyroidism affects approximately 5 individuals in 100³, its prevalence increasing with age. The signs and symptoms occur because there is a deficiency of thyroid hormone secretion and all metabolic processes in the body “slow down”. As a result, the patient can have poor appetite; intolerance to cold; dry, coarse skin; brittle hair; fatigue; constipation; muscle weakness; and poor memory retention. Sometimes the voice becomes croaky and hoarse. Examination may reveal dry, scaly, cold, pale skin; a thickening of the skin and underlying tissues (called myxedema); very slow reflexes; and a slow heart rate. The thyroid gland can be normal in size, increased (goiter), or non palpable.

Diagnosis

Your physician may confirm the diagnosis of hypothyroidism by testing TSH levels in your blood. If the TSH levels are elevated, you might also be tested for “free” thyroid hormones (called “free t4”) in the blood. Current guidelines from a combined task force¹ of American Association of Clinical Endocrinologists (AACE) and American Thyroid Association (ATA) have not recommended use of the other free thyroid hormones, free t3 or T3, for the diagnosis of hypothyroidism. Measurement of total triiodothyronine (T3) or Free T3 should not be used to diagnose hypothyroidism. In some cases, where goiter is felt upon palpation, a thyroid ultrasound can be ordered by your physician to evaluate for any nodules (lumps) in the enlarged thyroid gland. In most cases of hypothyroidism, TSH levels are elevated while free t4 levels are low. In some cases, only the TSH level is elevated while free t4 is in the normal range. In this condition, referred to as “subclinical hypothyroidism”, the thyroid gland is not functioning fully so it requires more than normal amounts of TSH secreted from the pituitary gland to function normally. While most cases of hypothyroidism require treatment with replacement of thyroid hormones, not all cases of subclinical hypothyroidism require treatment with medication. Your physician will make the decision based upon your symptoms and your clinical profile.

Treatment

Treatment of hypothyroidism is usually simple, in the form of a tablet of thyroid hormones taken once a day. This hormone pill usually contains T4 hormones and is to be taken on an empty stomach preferably in the morning separately from other medications. This is important so that other medications do not interfere in T4 absorption from the gut. With this replacement of T4 hormones externally, T4 hormones in the blood are restored to the required levels. Once the blood T4 levels are replenished and “sensed” by the hypothalamo-pituitary gland system in the brain, the elevated TSH levels automatically come down to the normal range. Your physician might ask you to follow up at regular intervals to check the levels of TSH and T4 hormones in your blood to ensure you are on the right dose of hormone pill to normalize the TSH and T4 levels. Please note that the hormone pill is not correcting the inflammation or disorder in your thyroid gland; it is just a way to ensure the thyroid hormone levels in your blood are in the normal range. In most cases, this means that you must take the daily pill for the rest of your life unless the primary thyroid pathology corrects itself.

Controversies in treatment of hypothyroidism

The standard and most common way of treating hypothyroidism is using a synthetic form of thyroid hormone, L-thyroxine or T4. However, some studies such as one published in 2009², have shown that combination therapy with T4 and T3 hormones can result in better relief of symptoms of hypothyroidism than just T4 monotherapy. This combination therapy is widely available as desiccated thyroid or by taking separate pills of synthetic T4 and T3 hormones together. Desiccated thyroid is thyroid extract derived directly from the processing of the thyroid gland of animals of porcine or bovine origin. Although desiccated thyroid contains “natural” forms of both T4 and T3 hormones, the content of these hormones and the ratio of T4 and T3 may vary depending upon the product brand and the animal origin. The AACE and ATA guidelines acknowledge that some patients prefer, and some patient subgroups may benefit from, a combination of T4 and T3 therapy, as shown in some studies, however they do not support general use of T4 and T3 combination therapy for treatment of hypothyroidism. When to see an endocrinologist (hormone specialist)? Treatment of hypothyroidism can be initiated and monitored by your family physician. However, in certain patients and conditions, treatment under an endocrinologist’s care might be required. This includes an extensive list of conditions not limited to: pregnant females or women planning to get pregnant or with history of infertility and miscarriages; complicated cases where hypothyroidism is associated with goiter, thyroid nodules, pituitary dysfunction, cardiac disease, or use of medications causing hypothyroidism; or situations in which your family physician feels there is need to see an endocrinologist.

Neonatal Hypothyroidism

Newborn babies are tested using a “heelpad blood-spot test”. Neonatal hypothyroidism is caused, in most cases, by the absence or underdevelopment of the thyroid gland. In other cases, proteins necessary for the production of thyroid hormones are not functioning properly. Thyroid hormones are essential for brain development and growth. During pregnancy, maternal thyroid hormones cross the placenta and provide for some of the foetal needs. Newborn infants with hypothyroidism that are not treated develop cretinism characterized by severe body and mental defects. These include mental retardation, poor vision, thick dry skin, protrudent tongue, muscle weakness, severe lethargy and tiredness. If diagnosed and treated soon after birth, growth and mental development can proceed relatively normally. Much of the research work in making an early diagnosis of Neonatal Hypothyroidism was carried out in Canada by Dr. J.H. Dussault at Laval University in Quebec City.

¹ Garber et al., Endocrine Practice, 2012 Nov-Dec; 18(6): 988-1028
² Nygaard et al., European Journal of Endocrinology (2009); 161(6): 895-902
³ ATA Clinical Thyroidology for the Public, Volume 16 Issue 8

Updated in 2014 by Prakash Chandra, MD MS D. ABIM. Original written by Irving B. Rosen, MD FRCS(C) and Paul B. Walfish CM MD FRCP(C) FACP FRSM. Revised in 2010 by Hortensia Mircescu, MD FRCPC.

Important notice – The information contained within is for general information only and consequently cannot be considered as medical advice to any person. For individual treatment or diagnosis consult your health care professional.