Endocrinology · Thyroid Disorders
The facts most likely to be tested
Hashimoto thyroiditis is the most common cause of hypothyroidism in iodine-sufficient regions and is characterized by autoimmune destruction of the thyroid gland.
The hallmark serologic finding is the presence of anti-thyroid peroxidase (anti-TPO) antibodies and anti-thyroglobulin antibodies.
Histopathologic examination reveals lymphocytic infiltration with formation of germinal centers and Hürthle cells.
Patients frequently present with a painless, diffuse goiter and clinical signs of hypometabolism such as fatigue, weight gain, and cold intolerance.
Hashimoto thyroiditis is strongly associated with HLA-DR3 and HLA-DR5 genetic predispositions.
There is a significantly increased risk of developing thyroid lymphoma, specifically non-Hodgkin B-cell lymphoma, in patients with long-standing disease.
The standard of care for management is lifelong levothyroxine replacement therapy, with dosage titrated to normalize thyroid-stimulating hormone (TSH) levels.
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A 42-year-old woman presents to the clinic complaining of persistent fatigue, a 10-lb weight gain, and increased sensitivity to cold over the past six months. Physical examination reveals a diffuse, firm, non-tender goiter and delayed relaxation of deep tendon reflexes. Laboratory studies demonstrate an elevated TSH and low free T4. Serum analysis is positive for anti-thyroid peroxidase antibodies.
What is the most likely diagnosis?
Hashimoto thyroiditis
The patient's presentation of primary hypothyroidism combined with a diffuse goiter and positive anti-TPO antibodies is pathognomonic for Hashimoto thyroiditis, as described in bets 1, 2, and 4.
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Etiology / Epidemiology
Most common cause of hypothyroidism in the US; autoimmune destruction of the thyroid gland. Strong female predominance (10:1) and genetic predisposition.
Clinical Manifestations
Painless, diffuse goiter with symptoms of hypothyroidism. Myxedema and bradycardia are classic findings.
Diagnosis
Anti-thyroid peroxidase (TPO) antibodies are the diagnostic hallmark. Elevated TSH with low free T4 confirms primary hypothyroidism.
Treatment
Levothyroxine is the standard of care. Avoid over-replacement to prevent iatrogenic hyperthyroidism and atrial fibrillation.
Prognosis
Lifelong replacement required. Increased risk of thyroid lymphoma (non-Hodgkin) in long-standing cases.
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Epidemiology & Etiology
Hashimoto is the leading cause of hypothyroidism in iodine-sufficient regions. It is an autoimmune disorder often associated with other conditions like Type 1 Diabetes or Addison disease. Peak incidence occurs between 30-50 years of age.
Pertinent Anatomy
The thyroid gland undergoes progressive lymphocytic infiltration and fibrosis. The resulting goiter is typically firm, rubbery, and non-tender on palpation.
Pathophysiology
T-cell mediated immunity leads to the destruction of thyroid follicular cells. The presence of anti-TPO and anti-thyroglobulin antibodies serves as a marker of immune-mediated damage. Initial transient hyperthyroidism (Hashitoxicosis) may occur due to the release of preformed hormone during follicular rupture.
Clinical Manifestations
Patients present with fatigue, weight gain, cold intolerance, and dry skin. Physical exam reveals a diffuse, firm goiter. Red flags include rapid enlargement or compressive symptoms (dysphagia, hoarseness), which raise suspicion for thyroid lymphoma.
Diagnosis
The Anti-TPO antibody test is the most sensitive diagnostic marker. Serum TSH is the most sensitive screening test for thyroid function; a TSH > 4.0 mIU/L with low free T4 confirms the diagnosis. Ultrasound is reserved for evaluating suspicious nodules or asymmetry.
Treatment
Levothyroxine is the first-line therapy, dosed based on weight (typically 1.6 mcg/kg/day). Contraindications include untreated adrenal insufficiency. TSH levels should be rechecked 6-8 weeks after initiation or dose adjustment to ensure the patient is euthyroid.
Prognosis
Most patients require lifelong hormone replacement. Patients are at a significantly increased risk for non-Hodgkin lymphoma of the thyroid. Annual monitoring of TSH is required to prevent iatrogenic thyrotoxicosis.
Differential Diagnosis
Subacute thyroiditis: painful, tender thyroid gland
Postpartum thyroiditis: occurs within 1 year of delivery
Iodine deficiency: endemic goiter in non-autoimmune settings
Riedel thyroiditis: 'rock-hard' thyroid with fibrosis
Thyroid cancer: usually presents as a discrete, cold nodule