Hyperthyroxinemia with a non-suppressed TSH: how to confidently reach a diagnosis in this clinical conundrum

Abstract

Disorders of thyroid function are among the commonest referrals to endocrinology. While interpretation of thyroid function testing is usually straightforward, accurate interpretation becomes significantly more challenging when the parameters do not behave as would be expected in normal negative feedback. In such cases, uncertainty regarding further investigation and management arises. An important abnormal pattern encountered in clinical practice is that of high normal or raised free thyroxine (fT4) with inappropriately non-suppressed or elevated thyroid-stimulating hormone (TSH). In this short review using two clinical vignettes, we examine the diagnostic approach in such cases. A diagnostic algorithm is proposed to ensure that a definitive diagnosis is reached in these challenging cases.

Elevated Thyroxine Concentration and Lithium Intoxication—An Analysis Based on the LiSIE Retrospective Cohort Study

“…Thyroxine concentrations higher than expected without TSH suppression (euthyroid hyperthyroxaenemia) can occur in a variety of somatic conditions [ 21 ]. Several pharmacological substances can also increase thyroxine concentrations [ 22 ]. Acute psychiatric disorders have also been linked to elevated thyroxine concentrations for reasons yet to be understood [ 11 , 23 ].…”

Refractory Hypothyroidism: Unraveling the Complexities of Diagnosis and Management

“…When encountering elevated thyroid hormones along with inappropriately non-suppressed or elevated TSH levels, and after excluding assay interferences, THR and TSH-oma must be considered. 83 It is recommended to measure the serum glycoprotein alpha subunit, elevated in 70% of TSH-oma cases, and the thyrotropin-releasing hormone-stimulated TSH level, indicating a low or absent TSH response in TSHoma. Additionally, performing a T3 suppression test, revealing no TSH suppression in TSH-oma, and conducting DNA sequencing to identify the most prevalent mutations occurring in the thyroid hormone receptor b genes, is advisable.…”

“…Additionally, performing a T3 suppression test, revealing no TSH suppression in TSH-oma, and conducting DNA sequencing to identify the most prevalent mutations occurring in the thyroid hormone receptor b genes, is advisable. 83,84 In the diagnostic evaluation of TSH-omas, conducting a pituitary magnetic resonance imaging is recommended. 69,71,85,86 The assessment of family members for symptoms associated with type B THR holds significant importance.…”