PAINFUL SUBACUTE THYROIDITIS (DE QUERVAIN'S THYROIDITIS) Sebastian A. Peter, MD Brooklyn, New York
Painful subacute thyroiditis (de Quervain's thyroiditis) usually occurs in association with systemic viral illnesses. This disorder may be manifested in various clinical forms. Primary care physicians must be aware of the clinical features of this disorder to make the correct diagnosis and treat appropriately. Three cases are reported to illustrate the different clinical manifestations of this disorder. (J Nat! Med Assoc. 1992;84:877-879.) Key words * thyroiditis * de Quervain's thyroiditis
Painful subacute thyroiditis (de Quervain's thyroiditis) is characterized by inflammatory destruction of the thyroid parenchyma with leakage of the colloid and its constituents into the circulation. The insult to the thyroid is followed by an inflammatory response, which is initially composed of polymorphonuclear leukocytes. As the disease progresses, lymphocytes, plasma cells, and histiocytes become the major components of the inflammatory response. The follicular epithelium of the thyroid disappears and is replaced by a rim of histiocytes and giant cells. Subsequently, fibrosis occurs. Finally, regeneration of follicles begins, and complete histologic recovery occurs.1 Subacute thyroiditis is a disease of adults, predominantly women, with a female:male ratio ranging between 2:1 and 6:1. The true incidence of this disease is not known because the disease may be confused clinically with other forms of thyroiditis, and many cases go unrecognized. There is evidence that subacute From the Department of Medicine, Woodhull Medical and Mental Health Center, Brooklyn, New York. Requests for reprints should be addressed to Dr Sebastian A. Peter, Dept of Medicine, Woodhull Medical and Mental Health Ctr, 760 Broadway, Brooklyn, NY 11206. JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 10
thyroiditis represents a stereotypical thyroidal inflammatory response to a variety of viruses. The disorder is usually preceded by an upper respiratory tract infection in up to 90% of cases. Fever and other systemic manifestations suggest an infectious origin but there is no leukocytosis, and complete recovery is the rule even without therapy.2'3 Elevated complement-fixing antibodies to different viruses have been demonstrated in patients with this disorder.4 Individuals with human leukocyte antigen HLA-BW35 seem to have increased susceptibility for the development of painful subacute thyroiditis.5 It has been shown that autoimmunity is not a factor in the pathogenesis of this disease.4 The following three cases are reported to illustrate the various forms of presentation of this disorder.
CASE REPORTS Case 1 A 43-year-old female presented with severe neck pain of 2 weeks duration. She had symptoms of an upper respiratory tract infection 4 weeks prior to the onset of the severe neck pain. The pain radiated to her ears and to her chest. She had frequent episodes of palpitations, profuse sweating, nervousness, and malaise. On physical examination, there was no ophthalmopathy. The thyroid gland was very tender in both lobes, which were slightly enlarged. There was no cervical adenopathy. Her pulse rate was 84/minute. The remainder of the examination was normal. Thyroid function values were as follows: thyroxine (T4) 21.2 mg/dL, triiodothyronine (T3) uptake 31% (N 25-35), and free thyroxine index 6.64 (N 1.0-4.3). A 24-hour radioactive iodine uptake was zero (N 8-35). The erythrocyte sedimentation rate was 74 mm/hour (N 0-30). A complete blood count was normal. The patient responded well to analgesic therapy, and at a 4-week follow-up visit her thyroid gland was normal, and the thyroid hormone levels returned to normal. 877
SUBACUTE THYROIDITIS
Case 2 A 35-year-old female presented with pain in the right side of her neck of 4 days duration. She had symptoms of a viral-like syndrome 2 to 3 weeks prior to the onset of pain. The patient had experienced a similar episode of pain in the left side of her neck 2 months previously. At that time, she was treated with analgesics, and the pain resolved in a few days. On physical examination, a nodule was palpated in the right lobe of the thyroid, and the gland was tender. A technetium scan done 2 weeks after the episode of pain showed a nonfunctioning (cold) nodule in the right lobe of the thyroid. Thyroid function values were as follows: T4 10.0 mg/dL (N 4.9-10.0), T3 175 mg/dL (N 99-195), and thyroidstimulating hormone (TSH) 0.1 u[U/mL (N 0.4-7). Antimicrosomal antibodies were negative. The patient responded to analgesic therapy, and after 2 months the thyroid gland was normal in size, no nodules were palpable, and there was no tenderness.
Case 3 A 42-year-old female, a physician, presented with a history of intermittent pain in her neck for a period of 5 months. Her first episode of pain developed 2 weeks after she had symptoms of a viral infection of the upper respiratory tract. The pain was in the left side of her neck and radiated to her left ear, and her thyroid gland was very tender. She was treated with glucocorticoids by an endocrinologist. While on steroids, she developed pain in the right lobe of the thyroid. She was treated with steroids for 3 months, and the pain and tenderness resolved. A few weeks after discontinuing steroids, she developed symptoms of an upper respiratory tract infection. One week after this episode, she developed pain and tenderness in the right lobe of her thyroid. On physical examination, there was a tender nodule in the right lobe of the thyroid. The left lobe was lobulated. There was no cervical adenopathy. The remainder of the examination was normal. A 24-hour radioactive iodine uptake of the thyroid was 1.5% (N 8-35). Thyroid functions were as follows: T4 9.3 mg/dL (N 5-11) and TSH 0.66 (N 0.4-5). Antimicrosomal antibodies were negative. She was treated with prednisone for 2 months. Since discontinuing prednisone, she has had no recurrences of neck pain.
DISCUSSION Painful subacute thyroiditis in its classic form should not be a difficult disease to diagnose. The combination of a painful, tender thyroid with an elevated erythrocyte sedimentation rate, low radioactive iodine uptake, elevated serum thyroid hormone, and thyroglobulin 878
levels is diagnostic. However, lack of awareness of this disorder has caused many errors in diagnosis, the most common error being pharyngitis.6 Needle biopsy of the thyroid showing the typical, histologic picture is confirmatory,' but this procedure is usually not necessary except in cases presenting with solitary nodules or recurrent episodes. The duration of the disease from initial insult to complete recovery is usually 6 to 8 months. The thyrotoxic phase usually lasts from 1 to 4 weeks, and for the duration of the disease, the gland is in the recovery phase. During the recovery phase, there may be a temporary period of hypothyroidism. Permanent hypothyroidism, however, is rare.2 Aspirin, nonsteroidal anti-inflammatory drugs, and glucocorticoids are the usual agents for the treatment of this disorder. Glucocorticoids are reserved for the more severe cases. However, none of these agents alter the natural course of this disease.2 The first case illustrates the classic presentation of painful subacute thyroiditis. Thyroid hormone levels during the initial painful state of the disease confirm thyrotoxicosis. The radioactive iodine uptake of less than 1% reflects the inability of the damaged thyroid follicles to concentrate iodine. The good response to a nonsteroidal, anti-inflammatory drug and the return of thyroid function to normal is customary. The second case presented with a tender solitary nodule that was non-functioning (cold) on technetium scan. The possibility of this nodule being malignant must be considered. However, the history suggestive of subacute thyroiditis occurring a few weeks previously was compelling evidence that this episode was an exacerbation of this disease. The resolution of the nodule with return to normal thyroid morphology after 2 months is not unusual.7 The third case illustrates the problem of recurrent episodes of painful subacute thyroiditis. The time course suggests that the recurrent episodes of pain were exacerbations rather than de novo episodes of subacute thyroiditis. Each new episode of a viral illness apparently caused an exacerbation of thyroiditis in a gland that had not yet fully recovered from the initial insult. Patients presenting with frequent episodes suggestive of painful subacute thyroiditis should have a needle biopsy of the thyroid to avoid diagnostic pitfalls. Amyloid, tuberculosis, and malignancy have been reported to present with such episodes.8-10 Finally, painful subacute thyroiditis, although a self-limiting disease with no mortality, can be incapacitating. Awareness of the clinical manifestations of this disease is most important in preventing diagnostic errors. JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 10
SUBACUTE THYROIDITIS
Acknowledgments The author thanks Normalee Johnson for preparing the manuscript.
system, immunoglobulins and other serum proteins. J Clin Endocrinol Metab. 1977;45:270-274. 6. Volpe R, Johnston MW. Subacute thyroiditis: a disease commonly mistaken for pharyngitis. Can Med Assoc J. 1 957;77:297-307. 7. Bartels PC, Boer RO. Subacute thyroiditis (De Quervain) presenting as a painless cold nodule. J Nucl Med. 1987;28: 1488-1490. 8. Ikenoue H, Okamura K, Kuroda T, Sato K, Yoshinari M, Fujishima M. Thyroid amyloidosis with recurrent subacute thyroiditis-like syndrome. J Clin Endocrinol Metab. 1988;67:41 45. 9. Sachs MK, Dickinson G, Amazon K. Tuberculous adenitis of the thyroid mimicking subacute thyroiditis. Am J Med. 1988;85:573-575. 10. Watts NB, Sewell CW. Carcinomatous involvement of the thyroid presenting as subacute thyroiditis. Am J Med Sci. 1 988;296:126-128.
Literature Cited 1. LiVolsi VA. Surgical pathology of the thyroid. In: Bennington JL, ed. Major Problems in Pathology. Philadelphia, Pa: WB Saunders Co; 1990:47-54. 2. Volp6 R. Subacute thyroiditis. Prog Clin Biol Res. 1981 ;74:1 15-134. 3. Greene JN. Subacute thyroiditis. Am J Med. 1971 ;51:97108. 4. Volpe R, Row VV, Ezrin C. Circulating viral and thyroid antibodies in subacute thyroiditis. J Clin Endocrinol Metab. 1967;27:1275-1281. 5. Nyulassy S, Hnilica P, Buc M, Guman M, Hirshova V, Stefanovic J. Subacute (De Quervain's) thyroiditis: association with HLA BW 35 antigen and abnormalities of the complement
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Painful subacute thyroiditis (de Quervain's thyroiditis) usually occurs in association with systemic viral illnesses. This disorder may be manifested in various clinical forms. Primary care physicians must be aware of the clinical features of this disorder to make the correct diagnosis and treat appropriately. Three cases are reported to illustrate the different clinical manifestations of this disorder. (J Nat! Med Assoc. 1992;84:877-879.) Key words * thyroiditis * de Quervain's thyroiditis
Painful subacute thyroiditis (de Quervain's thyroiditis) is characterized by inflammatory destruction of the thyroid parenchyma with leakage of the colloid and its constituents into the circulation. The insult to the thyroid is followed by an inflammatory response, which is initially composed of polymorphonuclear leukocytes. As the disease progresses, lymphocytes, plasma cells, and histiocytes become the major components of the inflammatory response. The follicular epithelium of the thyroid disappears and is replaced by a rim of histiocytes and giant cells. Subsequently, fibrosis occurs. Finally, regeneration of follicles begins, and complete histologic recovery occurs.1 Subacute thyroiditis is a disease of adults, predominantly women, with a female:male ratio ranging between 2:1 and 6:1. The true incidence of this disease is not known because the disease may be confused clinically with other forms of thyroiditis, and many cases go unrecognized. There is evidence that subacute From the Department of Medicine, Woodhull Medical and Mental Health Center, Brooklyn, New York. Requests for reprints should be addressed to Dr Sebastian A. Peter, Dept of Medicine, Woodhull Medical and Mental Health Ctr, 760 Broadway, Brooklyn, NY 11206. JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 10
thyroiditis represents a stereotypical thyroidal inflammatory response to a variety of viruses. The disorder is usually preceded by an upper respiratory tract infection in up to 90% of cases. Fever and other systemic manifestations suggest an infectious origin but there is no leukocytosis, and complete recovery is the rule even without therapy.2'3 Elevated complement-fixing antibodies to different viruses have been demonstrated in patients with this disorder.4 Individuals with human leukocyte antigen HLA-BW35 seem to have increased susceptibility for the development of painful subacute thyroiditis.5 It has been shown that autoimmunity is not a factor in the pathogenesis of this disease.4 The following three cases are reported to illustrate the various forms of presentation of this disorder.
CASE REPORTS Case 1 A 43-year-old female presented with severe neck pain of 2 weeks duration. She had symptoms of an upper respiratory tract infection 4 weeks prior to the onset of the severe neck pain. The pain radiated to her ears and to her chest. She had frequent episodes of palpitations, profuse sweating, nervousness, and malaise. On physical examination, there was no ophthalmopathy. The thyroid gland was very tender in both lobes, which were slightly enlarged. There was no cervical adenopathy. Her pulse rate was 84/minute. The remainder of the examination was normal. Thyroid function values were as follows: thyroxine (T4) 21.2 mg/dL, triiodothyronine (T3) uptake 31% (N 25-35), and free thyroxine index 6.64 (N 1.0-4.3). A 24-hour radioactive iodine uptake was zero (N 8-35). The erythrocyte sedimentation rate was 74 mm/hour (N 0-30). A complete blood count was normal. The patient responded well to analgesic therapy, and at a 4-week follow-up visit her thyroid gland was normal, and the thyroid hormone levels returned to normal. 877
SUBACUTE THYROIDITIS
Case 2 A 35-year-old female presented with pain in the right side of her neck of 4 days duration. She had symptoms of a viral-like syndrome 2 to 3 weeks prior to the onset of pain. The patient had experienced a similar episode of pain in the left side of her neck 2 months previously. At that time, she was treated with analgesics, and the pain resolved in a few days. On physical examination, a nodule was palpated in the right lobe of the thyroid, and the gland was tender. A technetium scan done 2 weeks after the episode of pain showed a nonfunctioning (cold) nodule in the right lobe of the thyroid. Thyroid function values were as follows: T4 10.0 mg/dL (N 4.9-10.0), T3 175 mg/dL (N 99-195), and thyroidstimulating hormone (TSH) 0.1 u[U/mL (N 0.4-7). Antimicrosomal antibodies were negative. The patient responded to analgesic therapy, and after 2 months the thyroid gland was normal in size, no nodules were palpable, and there was no tenderness.
Case 3 A 42-year-old female, a physician, presented with a history of intermittent pain in her neck for a period of 5 months. Her first episode of pain developed 2 weeks after she had symptoms of a viral infection of the upper respiratory tract. The pain was in the left side of her neck and radiated to her left ear, and her thyroid gland was very tender. She was treated with glucocorticoids by an endocrinologist. While on steroids, she developed pain in the right lobe of the thyroid. She was treated with steroids for 3 months, and the pain and tenderness resolved. A few weeks after discontinuing steroids, she developed symptoms of an upper respiratory tract infection. One week after this episode, she developed pain and tenderness in the right lobe of her thyroid. On physical examination, there was a tender nodule in the right lobe of the thyroid. The left lobe was lobulated. There was no cervical adenopathy. The remainder of the examination was normal. A 24-hour radioactive iodine uptake of the thyroid was 1.5% (N 8-35). Thyroid functions were as follows: T4 9.3 mg/dL (N 5-11) and TSH 0.66 (N 0.4-5). Antimicrosomal antibodies were negative. She was treated with prednisone for 2 months. Since discontinuing prednisone, she has had no recurrences of neck pain.
DISCUSSION Painful subacute thyroiditis in its classic form should not be a difficult disease to diagnose. The combination of a painful, tender thyroid with an elevated erythrocyte sedimentation rate, low radioactive iodine uptake, elevated serum thyroid hormone, and thyroglobulin 878
levels is diagnostic. However, lack of awareness of this disorder has caused many errors in diagnosis, the most common error being pharyngitis.6 Needle biopsy of the thyroid showing the typical, histologic picture is confirmatory,' but this procedure is usually not necessary except in cases presenting with solitary nodules or recurrent episodes. The duration of the disease from initial insult to complete recovery is usually 6 to 8 months. The thyrotoxic phase usually lasts from 1 to 4 weeks, and for the duration of the disease, the gland is in the recovery phase. During the recovery phase, there may be a temporary period of hypothyroidism. Permanent hypothyroidism, however, is rare.2 Aspirin, nonsteroidal anti-inflammatory drugs, and glucocorticoids are the usual agents for the treatment of this disorder. Glucocorticoids are reserved for the more severe cases. However, none of these agents alter the natural course of this disease.2 The first case illustrates the classic presentation of painful subacute thyroiditis. Thyroid hormone levels during the initial painful state of the disease confirm thyrotoxicosis. The radioactive iodine uptake of less than 1% reflects the inability of the damaged thyroid follicles to concentrate iodine. The good response to a nonsteroidal, anti-inflammatory drug and the return of thyroid function to normal is customary. The second case presented with a tender solitary nodule that was non-functioning (cold) on technetium scan. The possibility of this nodule being malignant must be considered. However, the history suggestive of subacute thyroiditis occurring a few weeks previously was compelling evidence that this episode was an exacerbation of this disease. The resolution of the nodule with return to normal thyroid morphology after 2 months is not unusual.7 The third case illustrates the problem of recurrent episodes of painful subacute thyroiditis. The time course suggests that the recurrent episodes of pain were exacerbations rather than de novo episodes of subacute thyroiditis. Each new episode of a viral illness apparently caused an exacerbation of thyroiditis in a gland that had not yet fully recovered from the initial insult. Patients presenting with frequent episodes suggestive of painful subacute thyroiditis should have a needle biopsy of the thyroid to avoid diagnostic pitfalls. Amyloid, tuberculosis, and malignancy have been reported to present with such episodes.8-10 Finally, painful subacute thyroiditis, although a self-limiting disease with no mortality, can be incapacitating. Awareness of the clinical manifestations of this disease is most important in preventing diagnostic errors. JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 10
SUBACUTE THYROIDITIS
Acknowledgments The author thanks Normalee Johnson for preparing the manuscript.
system, immunoglobulins and other serum proteins. J Clin Endocrinol Metab. 1977;45:270-274. 6. Volpe R, Johnston MW. Subacute thyroiditis: a disease commonly mistaken for pharyngitis. Can Med Assoc J. 1 957;77:297-307. 7. Bartels PC, Boer RO. Subacute thyroiditis (De Quervain) presenting as a painless cold nodule. J Nucl Med. 1987;28: 1488-1490. 8. Ikenoue H, Okamura K, Kuroda T, Sato K, Yoshinari M, Fujishima M. Thyroid amyloidosis with recurrent subacute thyroiditis-like syndrome. J Clin Endocrinol Metab. 1988;67:41 45. 9. Sachs MK, Dickinson G, Amazon K. Tuberculous adenitis of the thyroid mimicking subacute thyroiditis. Am J Med. 1988;85:573-575. 10. Watts NB, Sewell CW. Carcinomatous involvement of the thyroid presenting as subacute thyroiditis. Am J Med Sci. 1 988;296:126-128.
Literature Cited 1. LiVolsi VA. Surgical pathology of the thyroid. In: Bennington JL, ed. Major Problems in Pathology. Philadelphia, Pa: WB Saunders Co; 1990:47-54. 2. Volp6 R. Subacute thyroiditis. Prog Clin Biol Res. 1981 ;74:1 15-134. 3. Greene JN. Subacute thyroiditis. Am J Med. 1971 ;51:97108. 4. Volpe R, Row VV, Ezrin C. Circulating viral and thyroid antibodies in subacute thyroiditis. J Clin Endocrinol Metab. 1967;27:1275-1281. 5. Nyulassy S, Hnilica P, Buc M, Guman M, Hirshova V, Stefanovic J. Subacute (De Quervain's) thyroiditis: association with HLA BW 35 antigen and abnormalities of the complement
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