Hypothyroidism is a common disorder resulting from deficiency of thyroid hormone. Iodine deficiency is the most common cause of hypothyroidism worldwide. It can be associated with a number of symptoms including fatigue, weight gain, decreased appetite, cold intolerance, bradycardia, dry skin, hair loss, myalgia, depression, mental impairment, constipation, menstrual disturbances and impaired fertility. Myxedema coma, the most severe form of hypothyroidism, is rare.
Hypothyroidism presents with the following signs and symptoms:
The heart muscle slows down and contractility decreases therefore the cardiac output is also decreased. Bradycardia, decreased systolic and increased diastolic blood pressure, systemic hypotension and in some severe cases, pericardial effusion may occur.
Intestinal and gastric stasis, constipation and decreased appetite are common symptoms.
A complete work up includes checking of functional hormone levels of first T3 and T4 to see if the hypothyroidism is primary. Then levels of TSH and TRH are examined to determine any secondary causes. The plasma levels of Anti-TPO antibodies are also evaluated to check for Hashimoto’s .
Primary hypothyroidism can be treated by treating the cause. Nutritional deficiency can be corrected by adjusting an adequate intake of Iodine in diet . Systemic manifestations can be treated by giving Levothyroxine (LT4) between 50-75 micrograms daily for mild to moderate hypothyroidism . Effects are usually seen within 3-6 days of treatment.
Myxoedema is treated by giving a 200-250 microgram dose intravenously at first and then levelled down to about 50 microgram/day, accompanied by intravenous glucocorticoids.
Initially, there is a gradual decrease in hormone levels causing low metabolism. This results in features like lethargy, easy fatiguability, weight gain, bradycardia and hypotension. Then there is pitting edema in lower extremities, especially around the ankles, coarse brittle hair, skin pallor and dryness . A goitre may develop.
In advanced stage of this condition, the goiter may become enlarged and sometimes toxic and nodular. There may be severe hypotension and massive weight gain, slow speech and movements, hyporeflexia, myxadematous nonpitting edema, pericardial effusion, periorbital swelling and infertility.
The etiology of hypothyroidism can be broadly divided into primary, secondary and tertiary. Each category has various factors that predispose towards hypothyroidism.
This category consists of all such causes that deter the synthesis and/or secretion of thyroid hormones from the thyroid gland. It includes:
Iodine Deficiency Hypothyroidism
The most common cause of primary hypothyroidism worldwide is Iodine deficiency. Iodine is one of the basic building blocks of thyroid hormones. Required for the synthesis of T3 and T4, Iodine deficiency leads to hypertrophy and hyperplasia of the follicular cells creating a goitre.
Iodine Excess Hypothyroidism
An overload of Iodine causes a gradual inhibition of iodide organification occurring in the thyroid follicles. This effect, called the Wolff-Chiakoff effect can occur due to very high levels of Iodine in the blood caused by some radio contrast dyes, drugs like amiodarone, increased intake of seafood and seaweed, etc. the Wolff-Chiakoff effect is however, short lived due to the rapid down regulation by the sodium-iodide symporter.
Chronic Lymphocytic Hypothyroidism
This is an autoimmune condition and commonly known as Hashimoto's disease. In this disease, thyroid antigens are mistakenly taken as foreign by the immune system which then launches a full scale attack on thyroid follicles. The attacking antibodies cause a chronic immune response that leads to a build-up of a lymphocytic infiltrate and progressive damage and destruction of the gland parenchyma.
Circulating anti-thyroid peroxidase antibodies (Anti-TPO) are the hallmark of this disease.
Hashimoto's disease is the most common acquired cause of hypothyroidism in the United States as well as other countries where there is a normal intake of Iodine.
Sub acute Thyroiditis
Sub acute granulomatous thyroiditis is an uncommon, self-limiting disorder that usually affects middle aged females. It is a painful form of thyroiditis associated with viral infections leading to an increased ESR, fever and dysphagia. This disease is also known as Quatrain Disease.
Drug Induced or Iatrogenic Hypothyroidism
Many drugs are known to cause hypothyroidism if used for a prolonged period of time . The most common drugs predisposing to hypothyroidism include:
Iatrogenic causes may include the use of radioactive iodine for the treatment of Grave's disease and exposure to radiation as part of treatment of cancers such as neck neoplasms, Hodgkin's lymphoma, salivary gland tumours, etc. Patients who have undergone thyroid lobectomy, which may or may not be accompanied with isthmectomy, have a 12-30% chance of developing hypothyroidism.
After 2 months to about a year from delivery, about 10% women may develop thyroid insufficiency. This condition is usually transient and can be avoided and treated with levothyroxine but in some cases it may cause permanent hypothyroidism. Chances of developing postpartum thyroiditis is increased to about 25% in females with diabetes mellitus type I.
Secondary and Tertiary Hypothyroidism
The factors involved in this category are directly or indirectly involved in modifying the function of the thyroid gland. They include:
A deficiency in the Thyroid Stimulating Hormone secreted by the pituitary gland may cause improper functioning of the thyroid gland and decreased synthesis of T3 and T4 .
TRH Deficiency or Resistance
A deficiency in the hypothalamic Thyroid Releasing Hormone may cause none to low secretion of TSH from the pituitary gland and therefore, decreased production of thyroid hormones. TRH deficiency may arise due to an isolated mutation in the TRH gene, inherited in an autosomal recessive fashion. A defect in the TRH receptors on the pituitary, due to a mutation in the THRH gene, produces TRH resistance and it also gives the same results. TRH resistance is a very rare autosomal recessive disease.
Sheehan syndrome, a postpartum complication in which pituitary cells are infarcted due to increased blood loss during delivery may lead to decreased production of TSH and therefore, T3 and T4.
Pituitary and Hypothalamic Tumours
Tumours in or around these two glands may impinge on and suppress the function of hormone secreting cells causing hypothyroidism.
Congenital Non-Goiterous Hypothyroidism Type 4
This autosomal recessive disease results in low TSH levels which remain low despite injecting TRH . It is caused by a mutation in the TSHB gene.
Drugs and Radiation
Continuous use of some drugs like prednisone and dopamine as well as exposure to direct radiation may damage the hypothalamic-pituitary axis causing hypothyroidism, among other systemic manifestations.
Hypothyroidism occurs worldwide.
It is more common in females, the female-to-male ratio being 10:1
It is more prevalent in Caucasians than in Hispanics or Blacks.
Hypothyroidism affects people of all ages. Primary hypothyroidism can occur at any age but a higher prevalence is found in patient over 65 years.
Under normal conditions the thyroid gland releases around 100-125 nmol of T4 daily of which most is converted in the peripheral tissues into T3, the active form of the hormone. This conversion from prohormone to active hormone is due to 5' deiodination.
The active hormone, T3 now circulates in the blood and acts on various receptors causing a wide range of systemic and metabolic effects.
Due to an infection, glandular loss, autoimmune attack or iodine deficiency, or due to any other cause mentioned above, the synthesis of T4 is impaired. Decreased production and secretion of T4 leads to decreased levels of T3 in blood which is unable to act on all its receptors, producing systemic manifestations.
Effects of hypothyroidism include decreased heart contractility and cardiac output, increased insulin resistance, increased cholesterol levels particularly those of LDL. Effects in the gastrointestinal tract include achloroydia, decreased metabolic rate leading to gastric stasis, prolonged intestinal transit time and weight gain. Menstrual disturbances and infertility are common.
Hypothyroidism can be prevented by taking adequate Iodine in diet and avoiding consanguineous marriages (in case of congenital hypothyroidism).
Hypothyroidism is a very common endocrine disorder in which the thyroid gland does not function properly. This results in a decreased production of the thyroid hormone which causes systemic defects and characteristic symptoms.
Hypothyroidism can be primary or secondary. Primary hypothyroidism is due to a defect in the thyroid gland itself causing decreased synthesis and secretion of thyroid hormones T3 and T4. This primary defect can be caused either by a deficiency in one or more of the building products of the hormones, most common of which is iodine, or it could arise from an infection in the gland's parenchyma.
Another factor which also happens to be one of the most common one is autoimmune where autoantibodies attack the thyroid gland and greatly disturb its functioning . Whatever the underlying cause may be, the defect is clearly centred on the gland itself.
In the case of secondary or central hypothyroidism, the defect lies in an organ other than the thyroid gland. In this instance, the pituitary gland could be responsible as it could be releasing decreased levels of TSH or the hypothalamus may be at fault, for secreting low levels of TRH (the latter is sometimes categorised as tertiary hypothyroidism).
Whatever the cause may be, the resultant decrease of T3 and T4 hormones causes widespread effects.
Hypothyroidism is a disorder in which there is decreased or inadequate functioning of the thyroid gland leading to widespread effects.
The most common ones include decreased appetite, weight gain, and lethargy, swelling in the neck called goitre, decreased blood pressure, constipation, muscle pain and ankle swelling and menstrual abnormalities in females.
The most common worldwide form of hypothyroidism can be prevented by taking adequate Iodine in diet .
Hormone replacement therapy successfully treats this disease.
1. Wolter P, Dumez H, Schöffski P. Sunitinib and hypothyroidism. N Engl J Med. Apr 12 2007;356(15):1580; author reply 1580
2. Cetani F, Barbesino G, Borsari S, Pardi E, Cianferotti L, Pinchera A, et al. A novel mutation of the autoimmune regulator gene in an Italian kindred with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, acting in a dominant fashion and strongly cosegregating with hypothyroid autoimmune thyroiditis. J Clin Endocrinol Metab. Oct 2001;86(10):4747-52.
3. Doeker BM, Pfäffle RW, Pohlenz J, Andler W. Congenital central hypothyroidism due to a homozygous mutation in the thyrotropin beta-subunit gene follows an autosomal recessive inheritance. J Clin Endocrinol Metab. May 1998;83(5):1762-5.
4. Sawin CT, Castelli WP, Hershman JM, McNamara P, Bacharach P. The aging thyroid. Thyroid deficiency in the Framingham Study. Arch Intern Med. Aug 1985;145(8):1386-8.
5. Clinical guideline, part 1. Screening for thyroid disease. American College of Physicians. Ann Intern Med. Jul 15 1998;129(2):141-3.
6. Baskin HJ, Cobin RH, Duick DS, Gharib H, Guttler RB, Kaplan MM, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract. Nov-Dec 2002;8(6):457-69.
7. Gullo D, latina A, Frasca F, Moli RL, Pellegriti G, et al. Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients. PLoS One 2011;6(8):e22552. Epub 2011 Aug 1.
8. Abalovich M, Vazquez A, Alcaraz G, et al. Adequate levothyroxine doses for the treatment of hypothyroidism newly discovered during pregnancy. Thyroid. Nov 2013;23(11):1479-83.
9. Rosário PW, Bessa B, Valadão MM, Purisch S. Natural history of mild subclinical hypothyroidism: prognostic value of ultrasound. Thyroid. Jan 2009;19(1):9-12.
10. Wartofsky L. Myxedema coma. Endocrinol Metab Clin North Am. Dec 2006;35(4):687-98, vii-viii.