Unusual causes of hyperthyrotropinemia and differential diagnosis of primary hypothyroidism: a revised diagnostic flowchart

Abstract

The clinical consequences of primary hypothyroidism include cardiovascular morbidity, increased mortality, and poor quality of life; therefore guidelines endorsed by several Scientific Societies recommend measuring circulating thyroid-stimulating hormone (TSH) in patients at risk. The assessment of serum TSH levels i s also deemed to be the most robust and accurate biomarker during the management of rep lacement therapy in patients with a previous diagnosis of primary hypothyroidism . In line with a reflex TSH laboratory strategy, free thyroxine is measured only if the TSH falls outside specific cutoffs, in order to streamline investigations and save unjustifi ed costs. This serum TSH-based approach to both diagnosis and monitoring has been widely accepted by several national and local health services; nevertheless, false-negative or -positive testing may occur, leading to inappropriate management or treatment. This r eview aims to describe several infrequent causes of increased circulating TSH, includi ng analytical interferences, resistance to TSH, consumptive hypothyroidism, and refractoriness to levothyroxine replacement treatment. We propose a clinical flowchart to aid co rrect recognition of these various conditions, which represent important potential pitfalls in the diagnosis and treatment of primary hypothyroidism.

Keywords

• tsh
• hypothyroidism
• deiodinases
• assay artifacts
• malabsorption
• resistance to tsh
• consumptive hypothyroidism
• macro-tsh