Purpose: There are few studies on the glucose metabolic characteristics of the extra-hypothalamic cortex in the hypothalamic hamartomas (HH). A comprehensive understanding of pathogenic progression of the disease is required from the perspective of cortical metabolism; therefore, we aimed to characterize metabolic characteristics of extra-hypothalamic in HH patients. Methods: We investigated the metabolic characteristics of 16 HH patients, all of whom underwent epilepsy evaluation at Xuan Wu Hospital between 2017 and 2019. The lateralization and cortical distribution pattern of hypometabolism was assessed and related to HH mass neuroanatomy on magnetic resonance imaging (MRI) as well as scalp-electroencephalogram (scalp-EEG) abnormalities. Furthermore, asymmetry measurements of region of interest (ROI) in the temporal cortex (hippocampal formation, amygdala, and lateral temporal neocortex) were quantitatively assessed based on the normalized average positron emission tomography (PET) voxel values. The surgery prognosis was assessed using the International League Against Epilepsy (ILAE) classification system. Results: The lateralization of hypometabolism in global visual ratings was consistent with the HH mass lateralization seen on MRI. Cortical hypometabolism showed three patterns depending whether the HH mass involved mammillary bodies, middle hypothalamus nucleus, or both. The three patterns were hypometabolism of the mesial temporal cortex with symptom of mesial temporal epilepsy (3/16, pattern I), lateral temporal, and extratemporal (frontal or parietal) cortex with symptom of neocortex temporal or frontal epilepsy (5/16, pattern II), and mesial and lateral temporal cortex and extratemporal (frontal or parietal) cortex with varied symptoms (8/16, pattern III), respectively. A significant difference in PET voxel values was found between bilateral hippocampal formation (P = 0.001) and lateral temporal neocortex in the third group (P = 0.005). We suggest that the hypometabolic characteristics of the extra-hypothalamic cortex in HH patients have three patterns. The final cortical hypometabolic pattern depends on the neuroanatomic location of the HH mass and was consistent with the main involved cortex of the interictal and ictal discharges. The third hypometabolic pattern with the most extensive cortical hypometabolism has a poorer prognosis. Copyright © 2021 Yang, Wei, Meng, An, Fan, Wang, Wang, Ren, Shan and Zhao.