What are the causes of suppressed Thyroid-Stimulating Hormone (TSH) levels?

Causes of Suppressed TSH Levels

Suppressed TSH levels (typically <0.1-0.4 mIU/L) indicate either primary hyperthyroidism from thyroid overproduction, destructive thyroiditis with passive hormone release, exogenous thyroid hormone excess, or rarely, central causes—with Graves' disease accounting for 70% of cases, followed by toxic nodular disease (16%), thyroiditis (3%), and medications (9%). 1

Primary Hyperthyroidism (Increased Thyroid Hormone Production)

Graves' Disease

• Graves' disease causes 70% of all hyperthyroidism cases and 95% during pregnancy, characterized by diffuse thyroid enlargement, elevated free T4/T3, and suppressed TSH. 2, 1
• Distinctive features include ophthalmopathy (eyelid lag or retraction) and pretibial myxedema, with diagnosis confirmed by positive TSH-receptor antibodies. 2
• The condition results from autoimmune stimulation of TSH receptors, causing unregulated thyroid hormone synthesis. 1

Toxic Nodular Goiter

• Toxic multinodular goiter and toxic adenoma together account for 16% of hyperthyroidism cases, typically occurring in older patients. 1
• These autonomous nodules produce thyroid hormone independent of TSH regulation, leading to suppressed TSH with elevated thyroid hormones. 3, 4
• Diagnosis is confirmed by thyroid scintigraphy showing focal areas of increased uptake with suppression of surrounding tissue. 4

Destructive Thyroiditis (Passive Hormone Release)

Painless (Silent) Thyroiditis

• Painless thyroiditis causes 3% of hyperthyroidism cases through passive release of preformed thyroid hormones from inflamed thyroid tissue, not increased synthesis. 3, 1
• The clinical presentation mimics other causes of hyperthyroidism with suppressed TSH and elevated thyroid hormones, but the condition is typically mild and transient. 3, 4
• This destructive process requires only symptomatic management or glucocorticoid therapy in severe cases, as the thyrotoxicosis resolves spontaneously. 4

Subacute Granulomatous Thyroiditis

• Subacute thyroiditis accounts for 3% of hyperthyroidism cases, typically viral in origin, causing painful thyroid inflammation with passive hormone release. 1
• The condition is self-limited, with TSH suppression lasting weeks to months before spontaneous resolution. 1

Medication-Induced TSH Suppression

Exogenous Thyroid Hormone

• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, creating iatrogenic subclinical or overt hyperthyroidism. 5
• Intentional TSH suppression occurs in thyroid cancer patients, where target TSH levels range from 0.1-0.5 mIU/L for intermediate-risk disease to <0.1 mIU/L for structural incomplete response. 5, 6
• Overtreatment increases risks for atrial fibrillation (especially in patients ≥45 years), osteoporosis, fractures, and cardiovascular mortality. 5

Other Medications

• Amiodarone causes TSH suppression in 9% of hyperthyroidism cases through its high iodine content and direct thyroid tissue effects. 7, 1
• Tyrosine kinase inhibitors and immune checkpoint inhibitors cause drug-induced thyroid dysfunction with TSH suppression in 5-20% of treated patients. 1, 4

Central (Secondary) Hyperthyroidism

TSH-Producing Pituitary Tumors

• TSH-secreting pituitary adenomas (TSHomas) cause central hyperthyroidism with the paradoxical combination of elevated or inappropriately normal TSH alongside elevated free T4 and T3. 8
• These rare tumors result from monoclonal expansion of neoplastic thyrotropes, causing primary TSH overproduction with subsequent thyroid enlargement. 8
• Diagnosis requires measuring serum alpha-subunit, TRH stimulation testing, and pituitary MRI to differentiate from primary hyperthyroidism. 8

Pituitary Resistance to Thyroid Hormone

• The syndrome of pituitary resistance to thyroid hormone (PRTH) causes central hyperthyroidism through inherited mutations in the thyroid hormone receptor beta gene. 8
• The pituitary remains resistant to feedback inhibition while peripheral tissues respond normally, causing patients to experience thyrotoxic symptoms despite nonsuppressed TSH. 8

Critical Diagnostic Approach

Initial Confirmation

• When TSH is suppressed, measure free T4 and total or free T3 to distinguish overt hyperthyroidism (elevated hormones) from subclinical hyperthyroidism (normal hormones). 4
• Overt hyperthyroidism shows suppressed TSH with elevated free T4 and/or T3, while subclinical hyperthyroidism shows suppressed TSH (0.1-0.45 mIU/L) with normal thyroid hormones. 1, 4

Determining the Underlying Cause

• Measure TSH-receptor antibodies to identify Graves' disease, which are positive in autoimmune hyperthyroidism. 4
• Perform thyroid scintigraphy if antibodies are negative to differentiate toxic nodular disease (increased uptake) from thyroiditis (decreased uptake). 4
• Check medication history for exogenous thyroid hormone, amiodarone, or immunotherapy agents. 1

Common Pitfalls to Avoid

• Never assume a single suppressed TSH indicates true hyperthyroidism—confirm with repeat testing and free T4/T3 measurement, as transient suppression occurs with acute illness, recovery from thyroiditis, or assay interference. 5, 7
• Failing to distinguish between hyperthyroidism (increased synthesis) and thyroiditis (passive release) leads to inappropriate treatment with antithyroid drugs when only symptomatic management is needed. 3, 4
• In patients on levothyroxine, always determine whether TSH suppression is intentional (thyroid cancer requiring suppression) or iatrogenic (overtreatment of hypothyroidism), as management differs completely. 5, 6
• Missing central hyperthyroidism by not checking free T4 when TSH is inappropriately normal or elevated despite clinical thyrotoxicosis. 8