Central hyperthyroidism, elevation in T3 and T4 concentration with an unsuppressed TSH can be seen in TSH-secreting pituitary adenomas (TSH-oma), thyroid hormone resistance (RTH) and heterophile antibody interference. We present a case of 35-year-old male with central hyperthyroidism and large pituitary macroadenoma measuring 24.7 × 18.8 × 26.7 mm initially suggestive of TSH-oma. However, subtle clinical features including childhood hearing impairment and speech delay, along with biochemical testing with borderline alpha subunit level of 0.7 U/L (< 0.7 U/L), SHBG of 19 nmol/L (10-50 nmol/L) prompted further dynamic testing with TRH stimulation test. The TRH stimulation showed a six-fold increase TSH consistent with receptor resistance and confirmatory genetic testing was done which showed an autosomal dominant heterozygous missense mutation in the THRB gene (Val458Ala) and therefore avoided unnecessary pituitary surgery. Adults with THRβ resistance develop a unique metabolic profile due to heterogeneous tissue sensitivity to thyroid hormone. Tissues expressing predominantly WT THRα, such as bone, vascular smooth muscle, and skeletal muscle, are exposed to a relative state of thyrotoxicosis. Over time, this can increase the risk of developing osteoporosis, systolic hypertension, and sarcopenia. In contrast, tissues predominantly expressing mutant THRβ, particularly the liver, exhibit a hypothyroid state despite elevated circulating thyroid hormone which causes dyslipidaemia and risk of fatty liver disease. Retrospective cohort studies of individuals with heterozygous THRβ mutations reported an increased incidence of earlier-onset major adverse cardiovascular events, occurring on average 11 years earlier. The challenge in this case is he may need to undergo pituitary surgery at some stage if the macroadenoma were to further grow and threaten his vision, post operative hormone replacement will be challenge as TSH and free T4 are unreliable markers of treatment adequacy in this patient cohort.