This paper reports the case of a 12-year-old female patient admitted for excessive weight gain surpassing her peers over a three-month period. Laboratory investigations revealed impaired glucose tolerance with insulin resistance, hypercortisolemia, and a disrupted cortisol circadian rhythm. Abdominal ultrasound showed moderate hepatic steatosis (fatty liver), and pituitary MRI suggested a small nodule in the right adenohypophysis. The patient was subsequently diagnosed with pediatric Cushing's disease following bilateral inferior petrosal sinus sampling (BIPSS). She underwent endoscopic endonasal transsphenoidal resection of the pituitary microadenoma; at the six-month follow-up, she had achieved a weight loss of 27 kg. This case report and literature review offer a valuable clinical reference for the diagnosis and management of challenging cases of adolescent Cushing's disease.