Article Text

A young woman with fever of unknown origin
  1. A S Kashyap,
  2. Isaac Mathew,
  3. Shekhar Kashyap
  1. Armed Forces Medical College, Pune 411 040, India

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    A 33-year-old woman presented with a 2-month history of moderate-grade fever associated with chills, headache and diminished appetite. She had lost 8 kg since the onset of illness. Clinically, she had fever (temperature 38.5° C), but the rest of the general physical and systemic examinations were normal.

    Investigations revealed an erythrocyte sedimentation rate (ESR) of 80 mm after 1 h. Routine haemogram, blood smear for malarial parasite, urine microscopic examination, urine culture, blood culture, chest X-ray and ultrasounds of abdomen and pelvis were noncontributory. Mantoux test was negative. She was initially treated empirically for malaria with chloroquine and subsequently with ciprofloxacin for enteric fever with no response. On repeated clinical examinations she was detected to have small, diffuse, nontender thyromegaly. A 131-radioiodine scan revealed markedly low uptake of tracer. Radioactive iodine uptake (RAIU) was negligible at 24 h. Serum tri-iodothyronine (T3) was 180 ng/dl (normal 60–181), serum thyroxine (T4) 10 μg/dl (normal 4.5–10.9) and thyroid-stimulating hormone (TSH) 0.4 μU/ml (normal 0.5–5.0).


    What is the diagnosis?
    Name two characteristic laboratory findings of this condition?



    Diagnosis in this case is subacute or De Quervain's thyroiditis, painless variant, presenting as fever of unknown origin.


    A high ESR and suppressed radioactive iodine uptake are characteristic laboratory findings in this condition.


    Subacute or De Quervain's thyroiditis is an uncommon but well documented cause of fever of unknown origin.1 Symptoms of thyroiditis usually follow upper respiratory tract infection. In addition to general symptoms of infection, a characteristic feature is gradual appearance of pain in the region of the thyroid gland. Pain may be referred to the lower jaw, ear or occiput. In some patients, typical features are absent and they have prolonged fever, significant weight loss and no local symptoms. The clinical course may simulate a chronic systemic infection or malignancy.2 Systemic symptoms and fever may persist for weeks or months before diagnosis is clinched. Acute onset with severe pain over the thyroid is uncommon. A few patients have symptoms of thyrotoxicosis.3 Clinical findings include exquisite tenderness and nodularity of the thyroid gland.4 Aetiologically, mumps, coxsackie virus, echovirus and adenoviruses have been implicated.5Histopathologically, the lesions are patchy in distribution. Affected follicles show infiltration with mononuclear cells and disruption of epithelium, partial or complete loss of colloid, fragmentation and duplication of the basement membrane. Colloidophagy and multinucleate giant cells surrounding colloid are characteristic features. Primary events are destruction of follicular epithelium and loss of follicular integrity.

    Preformed hormones are released leading to elevated T3, T4, suppressed TSH and clinical features of thyrotoxicosis. Low TSH is a consequence of raised thyroid. Later, serum T4and T3 levels come down, sometimes into the hypothyroid range as hormone stores are depleted, with a rise in TSH levels. T4, and T3 concentrations rise as hormone secretion resumes and TSH concentration decreases to normal. Ultimately, as the disease subsides, thyroid function returns to normal. Cytokine interleukin-6 has been implicated in thyroid destruction.

    Treatment is with aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) to control symptoms. In severe cases glucocorticoids (20–40 mg prednisolone daily) alleviate the symptoms. Steroid therapy is continued to maintain the patient in a symptom-free state. Steroids are tapered gradually once RAIU and serum T4 return to normal.6 Transient thyrotoxicosis is controlled by beta-blockers.

    Learning points

    • subacute thyroiditis is an uncommon but important cause of fever of unknown origin

    • high ESR and low RAIU are characteristic features of this condition

    • painless variant may simulate systemic or malignant disease, without signs or symptoms directly related to thyroid

    • NSAIDs and steroids are the mainstay of treatment

    • disease usually subsides within few months with complete recovery of thyroid function

    In this patient, in addition to the above investigation results, fine needle aspiration biopsy revealed subacute thyroiditis. She was treated with prednisolone 40 mg/day. She became asymptomatic after 3 weeks. Steroids were tapered off over the next 8 weeks by which time RAIU and T4 had returned to normal.

    Final diagnosis

    Subacute or De Quervain's thyroiditis.