Both hyper- and hypothyroidism show reduced spontaneous and GHRH-stimulated GH secretion. Although impaired GHRH secretion and activity as well as reduced GH pituitary synthesis have been reported in these pathological conditions, a definitive description of the underlying pathophysiological mechanisms have not been provided yet. Ghrelin elicits a potent GH-releasing effect partially mediated by a functional somatostatin antagonism and a synergic interaction with GHRH. Moreover, the functional integrity of GHRH neurons is essential for ghrelins GH releasing effect. We aimed to investigate the GH releasing effect of ghrelin in conditions of naïve overt altered thyroid function in humans. To this aim, in 8 patients with primary autoimmune hypothyroidism (HYPO; age [mean±SEM]: 41.8±6.9yr.; BMI: 27.1±2.2 kg/m2; TSH: 16.5±5.8 mU/ml; fT3: 3.1±1.2 ng/l; fT4: 8.7±1.6 ng/l), 8 patients with thyrotoxicosis due to Basedow Disease (HYPER; age: 45.3±7.6yr; BMI: 23.5±3.0 kg/m2; TSH: 0.0±0.0 mU/l; fT3: 6.5±3.0 ng/l; fT4: 25.0±6.4 ng/l; TRAb: 47.5±7.6 U/l) and 8 control subjects (NS; age: 35.1±5.9yr.; BMI: 22.1±1.9 kg/m2) we studied the effects of the acute iv as a bolus administration at 0 of acylated ghrelin (AG; 1.0 μg/kg) and placebo (saline; 3 ml) on circulating GH levels assayed every 15′ up to 90′. The study had been approved by local Ethical Committee. In all the subjects, AG increased GH levels (P<0.01). Notably, both in HYPO (Δpeak: 30.4±6.2 μg/l; ΔAUC: 1458.7±364.0 μg/l/h) and in HYPER (Δpeak: 39.6±4.1 μg/l; ΔAUC: 1924.9±252.7 μg/l/h) the GH response to AG was lower (P<0.01) than in NS (Δpeak: 79.8±8.2 μg/l; ΔAUC: 4360.3±552.5 μg/l/h). This study shows that in presence of altered thyroid function, the GH response to ghrelin is reduced. Such an impairment could result from the above mentioned functional alterations of the GHRH/GH axis, nevertheless the existence of a specific reduced sensitivity to the GH releasing effect of ghrelin as an adjunctive mechanism of hyposomatotropism in thyroid disease is worthy being further investigated.