What are the causes of thyroid atrophy?

Causes of Thyroid Atrophy

Thyroid atrophy is primarily caused by autoimmune destruction of the thyroid gland, specifically through atrophic autoimmune thyroiditis (also called primary myxedema), which represents the end-stage of chronic autoimmune thyroid disease where cytotoxic antibodies and cellular immune mechanisms progressively destroy thyroid tissue without goiter formation. 1

Primary Autoimmune Mechanism

• Atrophic autoimmune thyroiditis (AAT) is characterized by antibody-dependent cell-mediated cytotoxicity that directly destroys thyroid follicular cells, leading to progressive gland shrinkage 1
• Cytotoxic antibody activity is significantly higher in atrophic disease (80% of patients) compared to goitrous autoimmune thyroiditis (39% of patients), with median specific lysis of 30% versus 16.9% respectively 1
• The atrophic form occurs when cytotoxic immune mechanisms predominate over inflammatory hyperplasia, resulting in thyroid volume reduction to approximately 6 ml (median) compared to 36 ml in goitrous variants 1

Distinguishing Atrophic from Goitrous Autoimmune Thyroiditis

• AAT and Hashimoto's thyroiditis may represent different pathogenic entities rather than variants of the same disease, as conventional thyroid autoantibodies (TPO, thyroglobulin) cannot distinguish between them serologically 1
• The key differentiator is the presence and intensity of cytotoxic antibodies—these humoral and cellular cytotoxic events specifically induce gland atrophy 1
• Patients with AAT have no thyroid enlargement and may remain clinically euthyroid despite the presence of antithyroid antibodies and lymphoplasmocytic infiltration 2

Clinical Presentation and Epidemiology

• AAT affects 5-15% of the general population and is especially prevalent in elderly women 2
• The atrophic phenotype often presents with delayed diagnosis because the absence of goiter means patients lack the obvious physical finding that prompts thyroid evaluation 3
• In pediatric cases, AAT can present with severe growth impairment and pituitary hyperplasia due to prolonged undiagnosed hypothyroidism, with 75% of affected children showing complete height growth arrest 3

Laboratory and Imaging Findings

• Circulating thyroid hormones may remain in the normal range initially, but peak TSH response to TRH and basal TSH values are elevated in two-thirds of AAT cases 2
• Thyroid ultrasound shows a frankly atrophic or normal-sized gland without goiter, distinguishing it from the enlarged gland seen in Hashimoto's thyroiditis 3
• The presence of antithyroid antibodies (particularly cytotoxic antibodies) correlates with thyroid lymphoplasmocytic infiltration even in the absence of clinical hypothyroidism 2

Progression and Natural History

• Development of overt hypothyroidism in AAT patients is common, making preventive thyroid replacement therapy indicated in patients with elevated basal TSH levels 2
• The atrophic process represents end-stage autoimmune thyroid destruction where the gland has been progressively replaced by fibrous tissue and lymphocytic infiltrate 1
• There is familial aggregation of AAT and frequent association with other autoimmune diseases, suggesting shared genetic susceptibility 2

Critical Diagnostic Pitfall

• Do not assume normal thyroid function based on the absence of goiter—AAT can cause severe hypothyroidism and growth failure in children despite a non-palpable thyroid gland 3
• In patients presenting with growth impairment, hypothyroidism should always be excluded even in the absence of clear clinical signs of dysthyroidism or thyroid enlargement 3
• The atrophic phenotype may be specifically correlated with severe clinical presentations including pituitary hyperplasia secondary to prolonged TSH elevation 3