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Thyroiditis
ENDOCRINE
teristic histological feature is a diffuse lymphocytic infiltrate of B-cells and cytotoxic T-cells. Other findings include plasma cells and germinal centres, follicular destruction, colloid depletion and oxyphilic thyroid follicular epithelium.
Thyroiditis Madeline Bates Amit Allahabadia
Clinical presentation Most patients present with a painless diffuse goitre of variable consistency, ranging from rubbery to firm or very hard, depending on the cellularity and the degree of fibrosis. Rarely, patients have an acute tender thyroid swelling and the diagnosis may be confused with painful subacute thyroiditis. Palpable discrete nodules are uncommon and require fine-needle aspiration biopsy to exclude malignancy. Differentiated thyroid carcinoma and thyroid lymphoma occur more frequently in patients with Hashimoto’s thyroiditis and should be excluded in patients with sudden growth of goitre. The onset of Hashimoto’s thyroiditis is usually insidious. Initial thyroid function may be normal or mild hypothyroidism may occur. Rarely, patients may develop transient hyperthyroidism due to presence of thyroid stimulating hormone (TSH)-receptor-stimulating antibodies. Ultimately, hypothyroidism occurs in most patients and develops at an unpredictable rate. Permanent hypothyroidism is, however, not universal and some patients may revert to euthyroidism possibly due to the loss of TSH-receptorblocking antibodies.
The term ‘thyroiditis’ encompasses a group of heterogeneous disorders whose common feature is inflammation of the thyroid gland. Thyroiditis predominantly affects women. The clinical course is variable and may be acute, subacute or chronic, depending on the underlying cause. Patients may present with euthyroidism, transient hyperthyroidism or hypothyroidism, and sometimes all three thyroid states may occur during the course of the disease. Many patients ultimately develop permanent hypothyroidism.
Hashimoto’s thyroiditis Hashimoto’s thyroiditis (chronic autoimmune or lymphocytic thyroiditis) is the most common cause of thyroiditis. Most patients have a goitre, but in some the thyroid shrinks and this variant is known as atrophic thyroiditis or primary myxoedema.
Investigation Most patients (>95%) have raised serum concentrations of thyroid peroxidase (TPO) antibodies, often in very high titres (more than 1:100 000), and many have positive antithyroglobulin (Tg) antibodies. Although TSH-receptor antibodies are not routinely measured in patients with Hashimoto’s thyroiditis, sensitive assays often reveal the presence of TSH-receptor-stimulating and -blocking antibodies with concentrations varying at different times in the same patient—these may account for the variable thyroid function seen in some patients. Measurement of serum TSH concentration is the initial investigation of choice for assessing thyroid function. If a high TSH concentration is found, serum free-thyroxine (T4) concentration should be measured to assess thyroid status. A normal free-T4 concentration is consistent with subclinical hypothyroidism and a low serum free-T4 concentration is found in hypothyroidism. In patients with a suppressed TSH concentration, serum free-T4 and free-tri-iodothyronine (T3) concentrations should be measured to confirm hyperthyroidism.
Aetiology Hashimoto’s thyroiditis is an organ-specific autoimmune disorder, which is the most common cause of spontaneous hypothyroidism in iodine-rich areas. Although it can occur at any age, it usually occurs between the fifth and sixth decade. It is multifactorial in origin; an interaction of susceptibility genes and permissive constitutional and environmental factors is likely to initiate immunopathogenic mechanisms, causing disease. Association studies have shown have evidence for linkage disequilibrium with genes in the major histocompatibility complex (MHC) class II region (HLA DR3, DR4 and DR5) and with the CTLA-4 gene. Often, there is a family history of other autoimmune conditions (e.g. type I diabetes mellitus). Hashimoto’s thyroiditis also occurs more commonly in patients with Down’s and Turner’s syndromes. Environmental factors – the prevalence of disease varies with iodine intake in a population. Moreover, iodine is necessary for disease expression in experimental animals and may cause hypothyroidism in euthyroid patients with Hashimoto’s thyroiditis. Hypothyroidsm is also more likely among smokers than nonsmokers with Hashimoto’s thyroiditis. Other postulated environmental factors include infectious agents, stress and oestrogens. The mechanism for autoimmune thyroid destruction probably involves both humoral and cell-mediated immunity. The charac-
Treatment: in patients with hypothyroidism, thyroid hormone replacement with levothyroxine should be given. When patients have subclinical hypothyroidism, opinions are divided regarding the necessity and timing of thyroxine treatment. Some of the current guidelines suggest treating symptomatic patients when the serum TSH concentration is >10 mIU/l. In patients who are euthyroid, the indications for thyroid hormone treatment are less clear. Goitres which are large or cause compressive symptoms in euthyroid patients often reduce in size after thyroid hormone treatment. Long-term follow-up of euthyroid patients with Hashimoto’s thyroiditis (i.e. diffuse goitre and positive thyroid antibodies) is essential because of the risk of hypothyroidism.
Madeline Bates is a Senior House Officer at Northern General Hospital, Sheffield, UK. Amit Allahabadia is a Consultant Endocrinologist at Northern General Hospital, Sheffield, UK.
SURGERY
303
© 2003 The Medicine Publishing Company Ltd
ENDOCRINE
Clinical presentation: patients usually have a history of a preceding systemic illness with symptoms of fever, malaise and myalgia. This is followed by intense thyroid pain radiating to the ears and jaw and tender firm enlargement of the thyroid. Symptoms of hyperthyroidism occur in about 50% of patients, but usually resolve within about 8 weeks. After euthyroidism is restored, transient hypothyroidism may occur, which is usually mild, but most patients recover completely and permanent hypothyroidism is rare. Painful subacute thyroiditis can, however, recur.
Destructive thyroiditis The term ‘destructive thyroiditis’ encompasses several conditions of different aetiology which are characterized by transient hyperthyroidism due to the release of preformed stored thyroid hormone. The most common causes of destructive thyroiditis are described below. Postpartum thyroiditis This is an autoimmune disorder which occurs in 5–10% of postpartum women in iodine-rich areas. Women with autoimmune conditions (e.g. type I diabetes) and with a family history of autoimmunity are at increased risk of developing the disease. It is most common in women with high concentrations of TPO antibodies during the first trimester of pregnancy or immediately after delivery.
Investigation: haematological investigation reveals a raised ESR and mild leukocytosis. Thyroid autoantibodies are usually absent in this condition. Thyroid function tests show a pattern of hyperthyroidism similar to postpartum thyroiditis. If the diagnosis is in doubt, it may be confirmed by a thyroid isotope scan (99mTc or 123I) which will show little or no isotope uptake.
Clinical presentation: patients present with hyperthyroidism 1 to 6 months after delivery, which lasts for up to 8 weeks. The hyperthyroid phase may be followed by a hypothyroid phase lasting between 4 and 6 months. More than 75% of women return to a euthyroid status within a year. Permanent hypothyroidism is more likely in women with a history of spontaneous abortion, multiparity and high concentrations of TPO antibodies. Women with postpartum thyroiditis have a 70% risk of developing the condition in subsequent pregnancies. Most women have a small, non-tender, firm goitre with variable symptoms and signs of hyperthyroidism. The differential diagnosis includes Graves’ disease and, in women who do not have specific signs of Graves’ disease (e.g. significant goitre, thyroid eye disease), an isotope thyroid scan can be used to confirm the diagnosis.
Treatment is aimed at symptomatic relief. NSAIDs and aspirin are effective for mild thyroid pain. In patients with more severe pain, high doses of glucocorticoids may be necessary: a typical starting dose of 40 mg of prednisolone is gradually reduced over a period of 4 to 6 weeks. Like postpartum thyroiditis, antithyroid drugs are contraindicated; beta-blockers are used instead to control symptoms of hyperthyroidism. Thyroxine is used for symptomatic patients who enter the hypothyroid phase.
Riedel’s thyroiditis (invasive fibrous thyroiditis) Riedel’s thyroiditis is very rare chronic inflammatory disorder which is characterized by proliferative invasive dense, fibrous tissue of the thyroid and surrounding tissues. The aetiology is unknown and it is not certain whether it is an autoimmune or fibrotic disorder. Middle-aged and elderly women are predominantly affected and it is often associated with other fibroproliferative disorders such as mediastinal and retroperitoneal fibrosis and sclerosing cholangitis. Histologically, thyroid tissue is replaced by cellular fibrous tissue which infiltrates through the thyroid capsule.
Investigation: initial thyroid function tests show biochemical hyperthyroidism (as above), but with a proportionately higher serum free-T4 than free-T3 concentration due to release of stored preformed T4 from the thyroid. High serum concentrations of TPO and/or Tg antibodies are present in more than 75% of cases. The erythrocyte sedimentation rate (ESR) is normal. A thyroid isotope scan (99mTc or 123I) will show little or no isotope uptake in postpartum thyroiditis, but diffuse increased uptake in patients with Graves’ disease.
Clinical presentation: patients present with an enlarging anterior neck mass which may extend retrosternally. The goitre may be unilateral or bilateral, is rock hard and becomes fixed to adjacent muscles, nerves, blood vessels and the trachea. Local invasion of adjacent structures by fibrous tissue may be associated with symptoms such as dyspnoea, choking, hoarseness and dysphagia. The hardness of the thyroid and invasion of adjacent tissues may raise the possibility of poorly differentiated thyroid carcinoma or lymphoma, but there is no enlargement of regional lymph nodes. Most patients are euthyroid at initial diagnosis, but become hypothyroid later when fibrous tissue replaces thyroid tissue. The diagnosis can be made only by incision biopsy. Optimal treatment is not known due to the rarity of the condition. Airway obstruction or oesopagheal compression may require surgical intervention. Glucocorticoids are of limited use, but tamoxifen has been reported to be effective in some patients, particularly when used in the early stages of disease. The effect of tamoxifen may be related to stimulation of the cytokine transforming growth factor-β, which is a potent inhibitor of growth.
Treatment: the symptoms of hyperthyroidism, if severe, can be treated with beta-blockers. Antithyroid drugs are contraindicated as there is no excess production of thyroid hormone. Symptomatic hypothyroidism is treated with thyroxine, but this should be withdrawn after 6 to 9 months to determine whether hypothyroidism is transient or permanent. Painless subacute thyroiditis This condition is similar to postpartum thyroiditis other than it does not occur after pregnancy. Painful subacute thyroiditis (de Quervain’s thyroiditis, granulomatous thyroiditis) Painful subacute thyroiditis is the most common cause of thyroid pain. It is often preceded by an upper respiratory tract infection and occurs in coincidence with outbreaks of viral diseases. No specific viral agent has, however, been identified. There is a seasonal distribution with a peak of incidence in summer and autumn.
SURGERY
304
© 2003 The Medicine Publishing Company Ltd
teristic histological feature is a diffuse lymphocytic infiltrate of B-cells and cytotoxic T-cells. Other findings include plasma cells and germinal centres, follicular destruction, colloid depletion and oxyphilic thyroid follicular epithelium.
Thyroiditis Madeline Bates Amit Allahabadia
Clinical presentation Most patients present with a painless diffuse goitre of variable consistency, ranging from rubbery to firm or very hard, depending on the cellularity and the degree of fibrosis. Rarely, patients have an acute tender thyroid swelling and the diagnosis may be confused with painful subacute thyroiditis. Palpable discrete nodules are uncommon and require fine-needle aspiration biopsy to exclude malignancy. Differentiated thyroid carcinoma and thyroid lymphoma occur more frequently in patients with Hashimoto’s thyroiditis and should be excluded in patients with sudden growth of goitre. The onset of Hashimoto’s thyroiditis is usually insidious. Initial thyroid function may be normal or mild hypothyroidism may occur. Rarely, patients may develop transient hyperthyroidism due to presence of thyroid stimulating hormone (TSH)-receptor-stimulating antibodies. Ultimately, hypothyroidism occurs in most patients and develops at an unpredictable rate. Permanent hypothyroidism is, however, not universal and some patients may revert to euthyroidism possibly due to the loss of TSH-receptorblocking antibodies.
The term ‘thyroiditis’ encompasses a group of heterogeneous disorders whose common feature is inflammation of the thyroid gland. Thyroiditis predominantly affects women. The clinical course is variable and may be acute, subacute or chronic, depending on the underlying cause. Patients may present with euthyroidism, transient hyperthyroidism or hypothyroidism, and sometimes all three thyroid states may occur during the course of the disease. Many patients ultimately develop permanent hypothyroidism.
Hashimoto’s thyroiditis Hashimoto’s thyroiditis (chronic autoimmune or lymphocytic thyroiditis) is the most common cause of thyroiditis. Most patients have a goitre, but in some the thyroid shrinks and this variant is known as atrophic thyroiditis or primary myxoedema.
Investigation Most patients (>95%) have raised serum concentrations of thyroid peroxidase (TPO) antibodies, often in very high titres (more than 1:100 000), and many have positive antithyroglobulin (Tg) antibodies. Although TSH-receptor antibodies are not routinely measured in patients with Hashimoto’s thyroiditis, sensitive assays often reveal the presence of TSH-receptor-stimulating and -blocking antibodies with concentrations varying at different times in the same patient—these may account for the variable thyroid function seen in some patients. Measurement of serum TSH concentration is the initial investigation of choice for assessing thyroid function. If a high TSH concentration is found, serum free-thyroxine (T4) concentration should be measured to assess thyroid status. A normal free-T4 concentration is consistent with subclinical hypothyroidism and a low serum free-T4 concentration is found in hypothyroidism. In patients with a suppressed TSH concentration, serum free-T4 and free-tri-iodothyronine (T3) concentrations should be measured to confirm hyperthyroidism.
Aetiology Hashimoto’s thyroiditis is an organ-specific autoimmune disorder, which is the most common cause of spontaneous hypothyroidism in iodine-rich areas. Although it can occur at any age, it usually occurs between the fifth and sixth decade. It is multifactorial in origin; an interaction of susceptibility genes and permissive constitutional and environmental factors is likely to initiate immunopathogenic mechanisms, causing disease. Association studies have shown have evidence for linkage disequilibrium with genes in the major histocompatibility complex (MHC) class II region (HLA DR3, DR4 and DR5) and with the CTLA-4 gene. Often, there is a family history of other autoimmune conditions (e.g. type I diabetes mellitus). Hashimoto’s thyroiditis also occurs more commonly in patients with Down’s and Turner’s syndromes. Environmental factors – the prevalence of disease varies with iodine intake in a population. Moreover, iodine is necessary for disease expression in experimental animals and may cause hypothyroidism in euthyroid patients with Hashimoto’s thyroiditis. Hypothyroidsm is also more likely among smokers than nonsmokers with Hashimoto’s thyroiditis. Other postulated environmental factors include infectious agents, stress and oestrogens. The mechanism for autoimmune thyroid destruction probably involves both humoral and cell-mediated immunity. The charac-
Treatment: in patients with hypothyroidism, thyroid hormone replacement with levothyroxine should be given. When patients have subclinical hypothyroidism, opinions are divided regarding the necessity and timing of thyroxine treatment. Some of the current guidelines suggest treating symptomatic patients when the serum TSH concentration is >10 mIU/l. In patients who are euthyroid, the indications for thyroid hormone treatment are less clear. Goitres which are large or cause compressive symptoms in euthyroid patients often reduce in size after thyroid hormone treatment. Long-term follow-up of euthyroid patients with Hashimoto’s thyroiditis (i.e. diffuse goitre and positive thyroid antibodies) is essential because of the risk of hypothyroidism.
Madeline Bates is a Senior House Officer at Northern General Hospital, Sheffield, UK. Amit Allahabadia is a Consultant Endocrinologist at Northern General Hospital, Sheffield, UK.
SURGERY
303
© 2003 The Medicine Publishing Company Ltd
ENDOCRINE
Clinical presentation: patients usually have a history of a preceding systemic illness with symptoms of fever, malaise and myalgia. This is followed by intense thyroid pain radiating to the ears and jaw and tender firm enlargement of the thyroid. Symptoms of hyperthyroidism occur in about 50% of patients, but usually resolve within about 8 weeks. After euthyroidism is restored, transient hypothyroidism may occur, which is usually mild, but most patients recover completely and permanent hypothyroidism is rare. Painful subacute thyroiditis can, however, recur.
Destructive thyroiditis The term ‘destructive thyroiditis’ encompasses several conditions of different aetiology which are characterized by transient hyperthyroidism due to the release of preformed stored thyroid hormone. The most common causes of destructive thyroiditis are described below. Postpartum thyroiditis This is an autoimmune disorder which occurs in 5–10% of postpartum women in iodine-rich areas. Women with autoimmune conditions (e.g. type I diabetes) and with a family history of autoimmunity are at increased risk of developing the disease. It is most common in women with high concentrations of TPO antibodies during the first trimester of pregnancy or immediately after delivery.
Investigation: haematological investigation reveals a raised ESR and mild leukocytosis. Thyroid autoantibodies are usually absent in this condition. Thyroid function tests show a pattern of hyperthyroidism similar to postpartum thyroiditis. If the diagnosis is in doubt, it may be confirmed by a thyroid isotope scan (99mTc or 123I) which will show little or no isotope uptake.
Clinical presentation: patients present with hyperthyroidism 1 to 6 months after delivery, which lasts for up to 8 weeks. The hyperthyroid phase may be followed by a hypothyroid phase lasting between 4 and 6 months. More than 75% of women return to a euthyroid status within a year. Permanent hypothyroidism is more likely in women with a history of spontaneous abortion, multiparity and high concentrations of TPO antibodies. Women with postpartum thyroiditis have a 70% risk of developing the condition in subsequent pregnancies. Most women have a small, non-tender, firm goitre with variable symptoms and signs of hyperthyroidism. The differential diagnosis includes Graves’ disease and, in women who do not have specific signs of Graves’ disease (e.g. significant goitre, thyroid eye disease), an isotope thyroid scan can be used to confirm the diagnosis.
Treatment is aimed at symptomatic relief. NSAIDs and aspirin are effective for mild thyroid pain. In patients with more severe pain, high doses of glucocorticoids may be necessary: a typical starting dose of 40 mg of prednisolone is gradually reduced over a period of 4 to 6 weeks. Like postpartum thyroiditis, antithyroid drugs are contraindicated; beta-blockers are used instead to control symptoms of hyperthyroidism. Thyroxine is used for symptomatic patients who enter the hypothyroid phase.
Riedel’s thyroiditis (invasive fibrous thyroiditis) Riedel’s thyroiditis is very rare chronic inflammatory disorder which is characterized by proliferative invasive dense, fibrous tissue of the thyroid and surrounding tissues. The aetiology is unknown and it is not certain whether it is an autoimmune or fibrotic disorder. Middle-aged and elderly women are predominantly affected and it is often associated with other fibroproliferative disorders such as mediastinal and retroperitoneal fibrosis and sclerosing cholangitis. Histologically, thyroid tissue is replaced by cellular fibrous tissue which infiltrates through the thyroid capsule.
Investigation: initial thyroid function tests show biochemical hyperthyroidism (as above), but with a proportionately higher serum free-T4 than free-T3 concentration due to release of stored preformed T4 from the thyroid. High serum concentrations of TPO and/or Tg antibodies are present in more than 75% of cases. The erythrocyte sedimentation rate (ESR) is normal. A thyroid isotope scan (99mTc or 123I) will show little or no isotope uptake in postpartum thyroiditis, but diffuse increased uptake in patients with Graves’ disease.
Clinical presentation: patients present with an enlarging anterior neck mass which may extend retrosternally. The goitre may be unilateral or bilateral, is rock hard and becomes fixed to adjacent muscles, nerves, blood vessels and the trachea. Local invasion of adjacent structures by fibrous tissue may be associated with symptoms such as dyspnoea, choking, hoarseness and dysphagia. The hardness of the thyroid and invasion of adjacent tissues may raise the possibility of poorly differentiated thyroid carcinoma or lymphoma, but there is no enlargement of regional lymph nodes. Most patients are euthyroid at initial diagnosis, but become hypothyroid later when fibrous tissue replaces thyroid tissue. The diagnosis can be made only by incision biopsy. Optimal treatment is not known due to the rarity of the condition. Airway obstruction or oesopagheal compression may require surgical intervention. Glucocorticoids are of limited use, but tamoxifen has been reported to be effective in some patients, particularly when used in the early stages of disease. The effect of tamoxifen may be related to stimulation of the cytokine transforming growth factor-β, which is a potent inhibitor of growth.
Treatment: the symptoms of hyperthyroidism, if severe, can be treated with beta-blockers. Antithyroid drugs are contraindicated as there is no excess production of thyroid hormone. Symptomatic hypothyroidism is treated with thyroxine, but this should be withdrawn after 6 to 9 months to determine whether hypothyroidism is transient or permanent. Painless subacute thyroiditis This condition is similar to postpartum thyroiditis other than it does not occur after pregnancy. Painful subacute thyroiditis (de Quervain’s thyroiditis, granulomatous thyroiditis) Painful subacute thyroiditis is the most common cause of thyroid pain. It is often preceded by an upper respiratory tract infection and occurs in coincidence with outbreaks of viral diseases. No specific viral agent has, however, been identified. There is a seasonal distribution with a peak of incidence in summer and autumn.
SURGERY
304
© 2003 The Medicine Publishing Company Ltd