About one out of ten patients presenting with symptoms of hypothyroidism may indeed suffer from ST. With regards to thyrotoxicosis, the share of ST patients may be even twice as high. Thus, ST is not a rare condition and should definitely be considered at the time of diagnosing thyroid disorders.

The patient's medical history may indicate recent upper respiratory infection, another viral disease or childbirth. While subacute granulomatous thyroiditis is a painful condition, subacute lymphocytic thyroiditis and subacute postpartum thyroiditis are usually painless. With regards to subacute granulomatous thyroiditis, pain may radiate to neck, jaw and ears. All types of ST may manifest with fever, swelling of the thyroid gland and consequent dysphagia. Patients don't feel well, experience fatigue and myalgia. Also, symptoms characteristic for thyrotoxicosis may be observed within the first weeks after disease onset. They are usually less severe than in patients suffering from other forms of thyroiditis or neoplasms. Thyrotoxic crises have been reported in isolated cases, but are very rare events in ST patients [8]. The following may be experienced:

• Agitation
• Insomnia
• Tachycardia
• Cardiac arrhythmia
• Hypertension
• Warm skin
• Heat intolerance
• Weight loss
• Muscle weakness
• Tremor
• Frequent defecation or diarrhea

A transient euthyroid phase of one or two weeks may be noted before symptoms of hypothyroidism manifest. Of note, the latter occurs in less than two thirds of ST patients. Lack of thyroid hormones mainly results in:

• Lethargy
• Fatigue
• Hoarseness
• Bradycardia
• Hypotension
• Dry skin
• Cold intolerance
• Weight gain
• Constipation

If spontaneous remission does not occur within two to three months, differential diagnoses should be reconsidered.

• Fever

  When fever is of unknown origin, SAT should be considered even if classic features are absent. [ncbi.nlm.nih.gov]

• Fatigue

  Other symptoms include: Tenderness when gentle pressure is applied to the thyroid gland Difficulty swallowing, hoarseness Fatigue, feeling weak Fever The inflamed thyroid gland may release too much thyroid hormone, causing symptoms of hyperthyroidism, [nlm.nih.gov]

  Both TA and subacute thyroiditis may be accompanied by fatigue, weight loss, and night sweats. We present a case of 55-year-old woman who presented with an FUO with clinical and laboratory findings suggesting TA. [ncbi.nlm.nih.gov]

  His symptoms resolved after two weeks; however, he has since developed fatigue and nervousness. The remaining review of systems is unremarkable. Medical history is negative. [mdedge.com]

  Nervousness Palpitations Sweating Tremor Weight loss Later, symptoms of too little thyroid hormone (hypothyroidism) may occur, including: Cold intolerance Constipation Fatigue Usually thyroid gland function returns to normal. [coordinatedhealth.com]

• Goiter

  We present a 25-year-old woman with amyloid goiter due to hypersensitivity vasculitis, who developed transient thyrotoxicosis resembling subacute thyroiditis. [ncbi.nlm.nih.gov]

  Thyroid function in patients with an amyloid goiter is usually normal. [edmcasereports.com]

• Transient Hypothyroidism

  She was at first thyrotoxic, then transiently hypothyroid, and finally became euthyroid. [ncbi.nlm.nih.gov]

  Patients are initially hyperthyroid, with low levels of thyroid-stimulating hormone (TSH) and elevated free thyroxine (T4); they sometimes then become transiently hypothyroid, with high TSH and low free T4. [merckmanuals.com]

• Malaise

  The most common form, subacute granulomatous, or de Quervain's, thyroiditis manifests as a sudden and painful enlargement of the thyroid gland accompanied with fever, malaise and muscle aches. [en.wikipedia.org]

  During the thyrotoxic phase, patients usually complain of fever, malaise, and goiter, which is tender in subacute granulomatous thyroiditis and painless in subacute lymphocytic thyroiditis. [amboss.com]

  Definition / general Inflammation of thyroid gland that includes granulomas Rare, much less common than Hashimoto thyroiditis but most common cause of thyroid pain Painful swallowing (odynophagia), sore throat, thyroid region tenderness, fever, fatigue, malaise [pathologyoutlines.com]

  […] follicles Associated conditions medical conditions and comorbidities Prognosis patients will generally return to normal thyroid function within a year Presentation Symptoms anterior neck and jaw pain de Quer vain causes pain flu-like prodrome fever, malaise [medbullets.com]

• Hoarseness

  On 9th day of illness patient developed painful neck swelling accompanied by fever, tremors, palpitations, hoarseness of voice and odynophagia. Examination revealed acutely swollen, tender thyroid gland along with features of hyperthyroidism. [ncbi.nlm.nih.gov]

  Other symptoms include: Tenderness when gentle pressure is applied to the thyroid gland Difficulty swallowing, hoarseness Fatigue, feeling weak Fever The inflamed thyroid gland may release too much thyroid hormone, causing symptoms of hyperthyroidism, [nlm.nih.gov]

  Other symptoms include: Difficulty swallowing Fatigue Fever Hoarseness Tenderness when gentle pressure is applied to the thyroid gland ( palpation ) Weakness Symptoms of too much thyroid hormone ( hyperthyroidism ) may include: Diarrhea Heat intolerance [coordinatedhealth.com]

  Hoarseness or difficulty swallowing may also develop. Symptoms of thyroid hormone excess (hyperthyroidism) such as nervousness, rapid heart rate, and heat intolerance may be present early in the disease. [uclahealth.org]

• Sore Throat

  Our results showed that, of the 30 patients, 21 had sore throat of various degrees, and 9 had abnormal sensation of throat. [ncbi.nlm.nih.gov]

  throat; severe thyroid pain; and an enlarged damaged gland containing giant cells. [icd9data.com]

• Cough

  Coughing and swallowing tend to exacerbate the pain. The affected area is also tender. [thyroid.com.au]

  Have been tested for carpal tunnel which has come back negative, spend a good hour every morning coughing and generally not quite with it. Antibodies negative and haven't had any scans. [healthunlocked.com]

  On day +54, the patient developed a dry cough and low-grade fever. Computed tomography of the chest showed pneumonitis in both lungs. At this time, markedly high levels of CMV antigenemia were noticed ( Figure 1 ). [nature.com]

• Dysphagia

  This disease usually presents with thyroid tenderness, a low grade fever, and occasional dysphagia. The disease resolves spontaneously, usually without thyroid function abnormalities. [ncbi.nlm.nih.gov]

  Patients present with neck pain, often associated with fever and dysphagia. [icd9data.com]

• Nausea

  I had while in thyrotoxicosis: all day long panic attacks that never abated adrenaline rushes all day long tremors tacycardia (170 BPM) waking every few hours during sleep sweats frequent bowel movements, including diarrhea and cramping unrelenting nausea [elaine-moore.com]

  Somedays I dont even remember how I made it through work, my brain was foggy and I was nauseas, dizzy, emotional and had anxiety but at the same time was fatigued. I was diagnosed as "depressed " but i refused to take antideppressants. [healthboards.com]

  Regimen-related toxicities were mild; the patient complained of slight nausea and diarrhea. Bone marrow engraftment was confirmed on day +15 using karyotypic and fluorescence in situ hybridization analyses. [nature.com]

• Jaw Pain

  We present a case of FUO in a traveler returning from India whose initial complaints were that of left-sided neck pain and angle of the jaw pain, which initially suggested the diagnosis of subacute thyroiditis. [ncbi.nlm.nih.gov]

  He also reports having increasing jaw and anterior neck pain. On physical exam, his thyroid is very tender to palpation. No goiter was palpated. [medbullets.com]

• Urticaria

  There was one case of seronegative rheumatoid arthritis, one case of Sjögren syndrome, one case of chronic ulcerative colitis, one case of urticaria, one case of contact dermatitis, and one case of psoriasis. [academic.oup.com]

• Neck Mass

  Adults who present with a vague, slightly painful mass in the thyroid region without a fever should raise suspicion of a neoplastic lesion. Reidel's thyroiditis may mimic the presentation of a thyroid carcinoma as a rapidly growing hard neck mass. [endocrinologyadvisor.com]

  The thyroid, parathyroid, and neck masses othe than lymph nodes. In: Koss L, Melamed L, editors. Koss′ Diagnostic Cytology and its Histopathologic Basis. 5 th ed. Philadelphia, PA: Lipincott Williams and Wilkins Company; 2006. p. 1148-85. 13. [cytojournal.com]

  The rare, invasive fibrous thyroiditis (Riedel's thyroiditis) presents with a slowly enlarging anterior neck mass that is sometimes confused with a malignancy. [aafp.org]

• Headache

  Patients with TA presenting as FUO often have only headaches that may be accompanied by bilateral jaw discomfort. Endocrine causes of FUOs are rare. [ncbi.nlm.nih.gov]

  While on Methimazole for about 4 days, I had an extreme headache, pain behind my eyes, pain in my skin and bones... so I was switched to PTU for a couple of weeks. [elaine-moore.com]

Diagnosis of ST is based on anamnesis, clinical examination and laboratory analyses of blood samples. Patients may either report an upper respiratory infection some weeks before or possibly childbirth. Physical examination reveals the above described symptoms.

With regards to analysis of blood samples, serum levels of  TSH, T4 and T3 should be determined as well as inflammatory parameters. In patients suffering from hyperthyroidism, TSH levels are generally decreased to non-measurable levels while serum concentrations of T4 and T3 are elevated. Thus, these are unspecific findings merely pointing at a thyroid disorder. Only in rare cases of secondary hyperthyroidism due to TSH-producing neoplasms of the pituitary gland, TSH levels may be augmented. Elevated erythrocyte sedimentation rates and increased levels of C-reactive protein are measured in the majority of ST patients [9].

If titers of antibodies against thyroglobulin and thyroperoxidase are assessed, they are generally in their physiological ranges in patients suffering from subacute granulomatous thyroiditis. Here, slight increases have been reported but normalize after spontaneous remission. In contrast, subacute lymphocytic and postpartum thyroiditis are associated with increased titers of auto-antibodies [10]

The aforementioned laboratory test do usually not allow for differentiation between distinct forms of hyperthyroidism, although confirmed inflammation and absence of auto-antibodies may prompt a strong suspicion for ST. The radioactive iodine uptake test is most useful for confirming this disease. In ST patients, iodine uptake is very low. The thyroid gland can usually not be depicted in scintigrams.

If doubts remain after performing the radioactive iodine uptake test, a fine needle aspiration may be performed. In case of ST, the number of thyroid epithelial cells and colloid is significantly reduced. Inflammatory cells, mainly lymphocytes, may be encountered. In patients suffering from subacute granulomatous thyroiditis, multinucleated giant cells will also be present [11] [12].

• Hyperglobulinemia

  Other tests that may prove helpful diagnostically In patients with subacute thyroiditis, mild anaemia and hyperglobulinemia may be present. [endocrinologyadvisor.com]

• Hyperglobulinemia

  Other tests that may prove helpful diagnostically In patients with subacute thyroiditis, mild anaemia and hyperglobulinemia may be present. [endocrinologyadvisor.com]

• Leukocytosis

  This may cause difficulty with differential diagnosis, particularly when leukocytosis is present or the lesion is localized to the left lobe. Ultrasonography can be helpful in differentiation. [ncbi.nlm.nih.gov]

  […] features of hypothyroidism References: [2] Diagnostics Thyroid function tests Thyrotoxic phase: ↑ T 3 and T 4, ↑ thyroglobulin, ↓ TSH Hypothyroid phase: ↓ T 3 and T 4, ↑ TSH Confirmatory test ↑ ESR Radioiodine uptake study : ↓ iodine uptake ( < 5% ) Leukocytosis [amboss.com]

  C 25 Patients with severe thyroid pain and systemic symptoms (e.g., high fever, leukocytosis, cervical lymphadenopathy) should undergo fine-needle aspiration to rule out infectious thyroiditis. [aafp.org]

In most cases, supportive treatment is sufficient to reduce pain and thyrotoxicosis until spontaneous remission occurs.

Non-steroidal anti-inflammatory drugs like naproxen or ibuprofen are the analgesics of choice. Often, high doses are required to alleviate pain resulting from subacute granulomatous thyroiditis. Over the course of the disease, doses of analgesics may be reduced as much as the patient's condition permits. Due to its effect on thyroid hormone protein binding, acetylsalicylic acid should be avoided. In rare cases, stronger analgesia and inhibition of inflammation are necessary for times when symptoms reach peak levels. Opioids or corticosteroids may be administered to this end.

With regards to thyrotoxicosis, anti-thyroid therapy is not effective because increased levels of T4 and T3 do not result from excess synthesis of thyroid hormones. If necessary, ipodate may be administered: This drug inhibits conversion of T4 to the more active T3. Beta sympatholytics like propranolol alleviate peripheral symptoms of thyrotoxicosis.

Hypothyroidism is usually mild and does not require any therapy. In more severe cases, thyroid hormone substitution should be considered. The latter is definitely necessary in the low share of ST patients that develop permanent hypothyroidism due to extensive tissue damage.

The disease is usually self-limiting and more than 95% of ST patients spontaneously return to euthyroid states after several weeks or months. Only severe inflammation of the thyroid gland may result in permanent tissue damage and persisting hypothyroidism.

Considerable knowledge gaps remain regarding the etiology of ST. Presumably, subacute lymphocytic thyroiditis and postpartum thyroiditis are autoimmune disorders. With regards to subacute granulomatous thyroiditis, the most widely accepted hypothesis is that viral pathogens account for this pathology. The fact that, similar to viral infections, subacute granulomatous thyroiditis incidence has been found to vary with seasons - most cases are recorded in fall - argues for this theory. Many patients do present elevated viral titers upon diagnosis of the thyroid disorder. Here, infections of the upper respiratory tract seem to play a major role, but other viral disease may also be associated with thyroiditis. In this line, distinct adenoviruses, Coxsackie virus, Epstein-Barr virus and cytomegalovirus have been proposed as possible etiologic agents. Infection or immunization with influenza virus strains may also trigger thyroiditis [2]. Further investigation is required to confirm the theory of viral etiology [3]. Also, it is not yet clear whether viral pathogens could spread to the thyroid gland or if inflammation of this endocrinologic organ may result from an immune response against such viruses.

Certain genetic patterns may render some individuals more susceptible for ST. Studies regarding the distribution of human leukocyte antigens (HLA) among ST patients and the general population ascertained a predominance of HLA-B35 in the former [4].

The annual incidence of ST has been estimated to be 5 per 100,000 individuals [5]. Neither geographical nor racial differences have been reported.

Females are affected up to four times more often than males. This applies for ST in general; due to its nature, subacute postpartum thyroiditis may only be diagnosed in women.

ST usually affects adults and most patients are older than 30 years. However, ST is not typically diagnosed in the elderly. The range is somewhat wider for subacute granulomatous thyroiditis, while subacute postpartum thyroiditis only occurs in women in fertile age. ST is very rarely diagnosed in pediatric patients [6].

As has been indicated above, ST incidence peaks in the cold times, mainly in fall.

Thyroid epithelial cells fulfill a variety of functions in thyroid hormone synthesis, storage and release: These cells synthesize thyreoglobulin and bind iodine to this protein. Subsequently, they release the resulting precursors of thyroid hormones into colloid-filled thyroid follicles that are surrounded by these same epithelial cells. Anterior pituitary gland secretion of thyroid-stimulating hormone (TSH) promotes re-uptake of hormone precursors into epithelial cells, hydrolysis and finally diffusion of thyroxine (T4) and triiodothyronine (T3) into circulation.

ST is associated with damage of thyroid epithelial cells. Loss of follicular integrity results in an uncontrolled release of stored thyroid hormone precursors, elevation of T4 and T3 serum levels and decrease of TSH release by means of negative feedback mechanisms. These pathophysiological events trigger symptoms of thyrotoxicosis, a condition that will not reverse until follicular stores are depleted or inflammation subsides. And even then, low levels of TSH and delay of tissue repair will not allow for a direct return to an euthyroid state. Instead, patients experience symptoms of hypothyroidism before complete regeneration of thyroid follicles and normalization of thyroid hormone synthesis and release [7]. This whole process may take several months.

Thyrotoxicosis and hypothyroidism both interfere with a plethora of metabolic processes throughout the body. While the former is associated with positive chronotropy, positive inotropy, possibly cardiac arrhythmia and hypertension, the opposite is the case with low levels of thyroid hormones. The overall activation of metabolism in a status of thyrotoxicosis leads to agitation, muscle weakness or tremor, heat intolerance and weight loss despite normal or increased appetite. In contrast, patients suffering from hypothyroidism show sleepiness, depression, cold intolerance and weight gain.

No preventive measures can be recommended.

In general, the medical term subacute thyroiditis (ST) refers to a self-limiting inflammation of the thyroid gland. It may be associated with symptoms of hyperthyroidism as well as hypothyroidism. Contrary to chronic thyroid disorders, this condition does neither require anti-thyroid therapy nor hormone replacement. Therefore, it is of clinical importance to differentiate ST from genetic disorders, autoimmune thyroiditis, hyperplasia, neoplasms and iodine deficiencies.

According to histopathological findings and the patient's medical history, three types of ST are distinguished:

• Subacute granulomatous thyroiditis (also referred to as de Quervain thyroiditis, in honor of the man who first described this disease)
• Subacute lymphocytic thyroiditis
• Subacute postpartum thyroiditis

Epidemiologic studies revealed a significant temporal correlation between viral infections and ST, which is why the latter is currently supposed to be triggered by viral pathogens. However, conclusive evidence is still missing. Also, the three types of ST presumably differ in etiology, but little details are known to this end.

Thyroid inflammation is associated with cellular damage and thus, precursors of thyroid hormones stored in thyroid follicles may be released. During this stage of ST, patients may present with thyrotoxicosis. It must be emphasized that elevated serum levels of thyroid hormones do not originate from an excess production or from disturbances of the regulatory mechanisms, but from uncontrolled release of stored quantities of thyroid hormones.

All types of ST may induce fever, but pain is typically only ascribed to the granulomatous form. Thyroid swelling may be noted. Fever, pain and thyrotoxicosis generally reach peak levels within one week after symptom onset [1]. However, the condition may remain more or less unchanged for several more weeks.

Inflammation subsides spontaneously after one to three months. However, depletion of hormone stores and tissue damage impair release of "old" thyroid hormones as well as synthesis of "new" ones. Therefore, patients may now show signs of mild to moderate hypothyroidism and this stage of the disease may last another two months. Follicles regenerate and hormone levels usually normalize without specific treatments.

Subacute thyroiditis (ST) is a transient inflammatory disease of the thyroid gland. Three types of subacute thyroiditis are distinguished:

• Subacute granulomatous thyroiditis (also referred to as de Quervain thyroiditis, in honor of the man who first described this disease)
• Subacute lymphocytic thyroiditis
• Subacute postpartum thyroiditis

While the terms granulomatous and lymphocytic refer to histopathological findings, the latter may only be diagnosed in women who gave childbirth in recent months.

Causes

Little is known about the causes of ST. Patients suffering from subacute granulomatous thyroiditis often report a recent upper respiratory infection, which is why the current hypothesis regarding this condition is that it is somehow triggered by viral pathogens. In contrast, subacute lymphocytic thyroiditis and postpartum thyroiditis are autoimmune diseases, i.e., an immune response directed against endogenous tissues causes thyroid inflammation.

Symptoms

All types of ST are associated with malaise, fever and swelling of the thyroid gland. Only subacute granulomatous thyroiditis is painful. Within days after symptom onset, patients may experience the consequences of increased levels of thyroid hormones. This condition is called thyrotoxicosis and manifests as agitation, sleeping disturbances, warm skin, heat intolerance, weight loss, muscle weakness and trembling. During later stages of the diseases, hypothyroidism may be observed. Lethargy, fatigue, dry skin, cold intolerance and weight gain are typical for the latter.

Diagnosis

The patient's medical history, clinical examination and laboratory analyses of blood samples usually prompt a strong suspicion for ST. An radioactive iodine uptake test evaluates thyroid function and is most widely applied to confirm this diagnosis. In some cases, small tissue samples may be obtained with a fine needle to be subsequently analyzed histopathologically.

Treatment

Supportive treatment is provided to relieve pain in case of subacute granulomatous thyroiditis. Here, non-steroidal anti-inflammatory drugs like naproxen or ibuprofen are the compounds of choice. Peripheral symptoms of thyrotoxicosis and possibly hypothyroidism are usually mild, but may be treated with beta-blockers or thyroid hormones, respectively, if necessity arises.

1. Nishihara E, Ohye H, Amino N, et al. Clinical characteristics of 852 patients with subacute thyroiditis before treatment. Intern Med. 2008; 47(8):725-729.
2. Cunha BA, Berbari N. Subacute thyroiditis (de Quervain's) due to influenza A: presenting as fever of unknown origin (FUO). Heart Lung. 2013; 42(1):77-78.
3. Desailloud R, Hober D. Viruses and thyroiditis: an update. Virol J. 2009; 6:5.
4. Kramer AB, Roozendaal C, Dullaart RP. Familial occurrence of subacute thyroiditis associated with human leukocyte antigen-B35. Thyroid. 2004; 14(7):544-547.
5. Fatourechi V, Aniszewski JP, Fatourechi GZ, Atkinson EJ, Jacobsen SJ. Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota, study. J Clin Endocrinol Metab. 2003; 88(5):2100-2105.
6. Ogawa E, Katsushima Y, Fujiwara I, Iinuma K. Subacute thyroiditis in children: patient report and review of the literature. J Pediatr Endocrinol Metab. 2003; 16(6):897-900.
7. Hennessey JV. Subacute Thyroiditis. In: De Groot LJ, Beck-Peccoz P, Chrousos G, et al., eds. South Dartmouth (MA): MDText.com, Inc.; 2000.
8. Sherman SI, Ladenson PW. Subacute thyroiditis causing thyroid storm. Thyroid. 2007; 17(3):283.
9. Pearce EN, Bogazzi F, Martino E, et al. The prevalence of elevated serum C-reactive protein levels in inflammatory and noninflammatory thyroid disease. Thyroid. 2003; 13(7):643-648.
10. De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012; 97(8):2543-2565.
11. Shabb NS, Salti I. Subacute thyroiditis: fine-needle aspiration cytology of 14 cases presenting with thyroid nodules. Diagn Cytopathol. 2006; 34(1):18-23.
12. Chang TC, Lai SM, Wen CY, Hsiao YL. Three-dimensional cytomorphology in fine needle aspiration biopsy of subacute thyroiditis. Acta Cytol. 2004; 48(2):155-160.