Cause meno frequenti di aumento del TSH

The measurement of thyrotropin (TSH) is the most accurate way to detect thyroid disfunctions, even when they are subclinical. Among the conditions associated with TSH elevation, in addition to the most frequent autoimmune thyroiditis, there are less common situations that can be difficult to identify and can lead to misdiagnosis and inappropriate treatments. The aim of this review is to display the less frequent causes of TSH elevation, when they should be suspected and the best clinical approach to manage them. Laboratory interferences with thyroid function test, such as heterophilic antibodies and macro-TSH, are rather frequently found in clinical practice. The clinician should suspect an analytical interference when there is a considerable discrepancy between laboratory findings and clinical features. The first step to rule out a laboratory interference is repeating the test using a different assay with alternative reagents; if the suspect remains, then is often necessary to perform a second level laboratory test to confirm the interference, such as dilution test or polyethylene glycol precipitation test. Another cause of TSH elevation is resistance to TSH, a genetic disease characterized by inadequate transmission of TSH stimulatory signal into thyroid cell. More severe forms occur in patients with disrupting biallelic TSH-receptor (TSHR) mutations and follow a recessive pattern of inheritance; these ones are generally detected in the first days of life and require levothyroxine treatment. A compensating hyperthyrotropinemia is instead likely present in the carriers of monoallelic TSHR variants, these forms are frequently detected later in life and recent clinical findings show the possibility to omit treatment. Another rare cause of TSH elevation is consumptive hypothyroidism, a paraneoplastic syndrome resulting from the aberrant uncontrolled expression of deiodinase 3 that can induce a severe form of hypothyroidism by inactivating T4 and T3 in tumor tissue. This condition generally affects children with large hemangiomas but can occur also in adults with other tumor types, such as gastrointestinal stromal tumor or malignant fibrous tumor. When surgery is not an option, the management of this condition include, beyond levothyroxine, drugs aiming to reduce the deiodinase activity and the tumor extension, like steroids and beta-blockers.

La misurazione del TSH circolante rappresenta il marcatore più solido e accurato nella valutazione delle disfunzioni tiroidee, capace di rivelare anche disfunzioni tiroidee lievi o subcliniche. Per questo motivo, diverse linee guida e società scientifiche raccomandano la strategia del TSH riflesso per il depistaggio delle disfunzioni tiroidee nella popolazione. Tale raccomandazione è stata recepita largamente da diverse amministrazioni sanitarie nazionali e regionali. L’ipotiroidismo primario di origine autoimmune rappresenta la forma di disfunzione tiroidea largamente più frequente nella popolazione e si accompagna classicamente a variabili elevazioni del TSH. Questa rassegna illustra alcune delle cause meno frequenti di aumento del TSH circolante (interferenze analitiche, come il macroTSH, resistenza al TSH, ipotiroidismo da consumo, refrattarietà al trattamento sostitutivo) evidenziando quando sospettarne la presenza, come diagnosticarle e le insidie che possono rappresentare nel trattamento dei pazienti affetti.