SUN-198 - Beyond the Textbook: A Diagnosis of Cushing Disease in an Adolescent with Weight Loss

Background
Cushing disease (CD) in adolescents is rare and classically characterized by central adiposity and progressively increasing BMI. Clinically significant weight loss during active hypercortisolism is considered highly atypical, given cortisol mediated adipogenesis and insulin resistance. Here, we describe an unusual presentation of Cushing disease in which intentional, lifestyle- driven weight loss occurred despite biochemical hypercortisolism. To our knowledge, this has not been previously reported in the literature.

Case Presentation
A 14-year-old female was evaluated for secondary amenorrhea and abnormal thyroid function tests. At presentation, her weight was 41 kg (50th percentile) with a BMI of 22 kg/m², and vital signs were notable for bradycardia (50 bpm) with normal blood pressure. Physical examination demonstrated a round face, facial and upper arm erythema, acne, facial hirsutism, and a few striae on the inner thighs. Further questioning revealed that six months prior to presentation, she had a 13 lb unintentional weight gain. In response, she adopted caloric restriction to 1000 kcal/day and engaged in high intensity exercise over two months, leading to a 10% (14 lb) weight loss.
Laboratory evaluation revealed TSH 0.4 µIU/mL, total T3 47 ng/dL, and free T4 0.9 ng/dL, Gonadotropins were suppressed (LH < 0.04 mIU/mL, FSH 0.71 mIU/mL) with low estradiol < 10 pg/mL, and total testosterone 51 ng/dL, with free testosterone 7.3 pg/mL. Screening for hypercortisolism showed an elevated late night salivary cortisol of 1.23 µg/dL. Following 1 mg dexamethasone given at midnight, the morning serum cortisol was 23.9 µg/dL, with a dexamethasone level 132 ng/dl and elevated ACTH of 126 pg/mL. MRI of the pituitary demonstrated a 12 × 7 × 9 mm pituitary adenoma and diffuse cerebral and cerebellar pseudoatrophy. Collectively, the biochemical and radiographic findings were diagnostic of Cushing disease.
The pituitary adenoma was removed via transsphenoidal surgery. A postoperative cortisol nadir was 4.5 µg/dL indicated successful adenoma resection. After normalization of cortisol, her hypogonadotropic hypogonadism, thyroid function abnormalities, and bradycardia resolved.

Conclusion
We present an unusual case of CD characterized by the absence of an elevated BMI and clinically meaningful weight loss despite active hypercortisolism, achieved through aggressive intentional lifestyle changes. This presentation underscores that a normal or declining BMI does not exclude Cushing disease and may contribute to diagnostic delay. Clinicians should consider screening for hypercortisolism when there is antecedent rapid, unexplained weight gain or characteristic cushingoid features, even if subsequent weight trends appear reassuring.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*