What are the causes of subclinical hypothyroidism?

Causes of Subclinical Hypothyroidism

Subclinical hypothyroidism is most commonly caused by autoimmune (Hashimoto's) thyroiditis in iodine-sufficient areas, with other important causes including previous thyroid treatment, iodine deficiency, and inadequate thyroid hormone replacement. 1, 2

Primary Autoimmune Causes

• Hashimoto's thyroiditis (chronic autoimmune thyroiditis) is the leading cause in industrialized nations, characterized by lymphocytic infiltration and elevated antibodies against thyroid peroxidase (TPO) and thyroglobulin 3, 1
• The presence of positive TPO antibodies significantly increases the risk of progression from subclinical to overt hypothyroidism (2-5% annually), making this a critical prognostic marker 3, 1, 2

Iatrogenic and Treatment-Related Causes

• Previous treatment for hyperthyroidism (radioactive iodine therapy, thyroidectomy, or antithyroid medications) commonly results in subsequent hypothyroidism 3, 1
• Inadequate thyroid medication dosing affects approximately 20% of patients already taking thyroid hormone, representing a major preventable cause 3, 1
• Previous head and neck radiation therapy for cancer damages thyroid tissue and leads to hypothyroidism 3, 1

Nutritional and Environmental Causes

• Iodine deficiency remains the most common cause worldwide, though less prevalent in industrialized nations with iodine supplementation 3, 1
• Certain medications, particularly amiodarone (an iodine-containing antiarrhythmic), can cause TSH elevation through high iodine content and direct thyroid effects 1

Associated Medical Conditions

• Type 1 diabetes mellitus is associated with increased risk due to shared autoimmune mechanisms, requiring regular thyroid monitoring in these patients 3, 1
• Subacute thyroiditis can cause transient elevations in TSH during the recovery phase 1
• Untreated primary adrenal insufficiency may present with elevated TSH 1

Demographic Risk Factors

While not direct "causes," these factors substantially increase likelihood:

• Advanced age: Up to 20% of women over 60 years have subclinical hypothyroidism, though age-related TSH elevation may represent physiological changes rather than true disease 3, 1, 2
• Female sex: Women have significantly higher prevalence than men across all age groups 3, 1
• Family history of thyroid disease indicates genetic predisposition 3, 1
• Race: Prevalence in Black individuals is approximately one-third that of white individuals 3, 1

Important Clinical Pitfalls

• Approximately 5% of elevated TSH levels normalize spontaneously within one year, and up to 40% may resolve without treatment, emphasizing the need for confirmatory testing before initiating therapy 3, 4
• Heterophilic antibodies can cause falsely elevated TSH in some laboratory assays, requiring alternative testing methods if clinical suspicion is low 1
• Age-related TSH elevation in elderly patients (>70-85 years) may not represent true pathology, as the normal reference range shifts upward with aging 1, 2
• Recent adjustments in levothyroxine dosage or recovery from severe illness can cause transient TSH elevations 1