Endocrine Abstracts

Introduction: Resistance to thyroid Hormones (RTH) is a syndrome characterized by reduced tissue responsiveness to thyroid hormones (TH).

This results to constantly elevated levels of TSH despite high levels of free T3 (FT3) and free T4 (FT4).

RTH is due to mutations of the gene encoding the b-isoform of the receptor of TH (THR-b gene), inherited in the autosomal dominant manner.

Clinical expression of RTH varies reflecting different levels of tissue resistance to TH, different mutations and genetic heterogeneity of factors affecting TH action.

Most patients are asymptomatic. Few present with hypo- or hyperthyroidism. Coexistence of both hypo- and hyperthyroidism symptoms in the same patients is not rare. Goiter is quite common.

Case report: We describe two patients with RTH; a 36-year old female (1st patient) and a 58-year old male (2nd patient).

Both patients had undergone total thyroidectomy for multinodular goiter.

After thyroidectomy, increasing doses of levothyroxine were not enough to lower TSH down to normal, whereas FT3 and FT4 levels were elevated.

Negative pituitary MRI and normal TSH response to TRH stimulation excluded thyrotropinoma (TSH-secreting adenoma) in both patients.

Genetic analysis revealed RTH.

In the first patient analysis of the exon 10 (chromosome 3) showed a C insertion in codon 448, that lengthens the polypeptide chain by two aminoacids.

In the second patient there was a heterozygous replacement of C to T in codon 383 resulting to a change from arginine to cytosine.

In both cases further increase in levothyroxine dose reduced TSH levels to slightly above normal.

Conclusion: Elevated FT3 and FT4 levels without suppression of TSH should raise suspicion of RTH.

Pituitary MRI and TRH stimulation test are necessary to exclude thyrotropinoma. RTH is confirmed by genetic analysis.

In many patients RTH is ‘unmasked’ after thyroidectomy, because post-thyroidectomy hypothyroidism is difficult to treat

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector