The incidental pituitary hypermetabolism on 18F-FDG PET/CT should be further evaluated for discriminating between pathologic and physiologic uptake, but a recent study suggests that pituitary hypermetabolism is common in patients with differentiated thyroid carcinoma (DTC) undergoing thyroid hormone withdrawal (THW). The aim of this retrospective study was to compare pituitary metabolism in patients with DTC undergoing 18F-FDG PET/CT under THW versus recombinant human thyroid-stimulating hormone (rhTSH) stimulation. We confirmed a higher pituitary SUVmax and SUVratio with a higher prevalence of pituitary hypermetabolism in the THW group compared to the rhTSH group. A positive correlation between serum TSH levels and pituitary SUVmax was observed only in the THW group. The present findings support the hypothesis that pituitary hypermetabolism on 18F-FDG PET/CT in patients with DTC undergoing THW is a common physiological response to hypothyroidism. Awareness of this physiological hypermetabolism is important to avoid potential pitfalls in image interpretation that could trigger unnecessary investigations.