SUN-009 - Mild Hyperprolactinemia Masking Cushing Disease: A Case of Diagnostic Anchoring Bias

Introduction: Cushing disease, caused by an adrenocorticotropic hormone (ACTH)–secreting pituitary adenoma, leads to hypercortisolism and significant morbidity if unrecognized. Although classic features are well described, atypical or subtle presentations may delay diagnosis and contribute to adverse outcomes.

Objective: To demonstrate how mild hyperprolactinemia can mislead the diagnostic process and to underscore the importance of comprehensive pituitary evaluation in suspected endocrine disorders.

Case Presentation: A 26-year-old woman was referred for evaluation of persistent mild hyperprolactinemia. Body mass index was 30.3 kg/m², and vital signs were normal. Hemoglobin A1c ranged from 6.0% to 6.2%. Thyroid function, gonadotropins, and metabolic profile were within reference ranges. Prolactin levels were mildly elevated (31.8 ng/mL; repeat 33.2 ng/mL norm 4.8-25 ng/mL). Pituitary MRI demonstrated a 5 × 5 × 7 mm adenoma. Given the clinical context, further evaluation was pursued. Morning cortisol was 18.4 µg/dL with failure to suppress following low-dose dexamethasone (norm < 1.8 µg/dL) ACTH was 96 pg/mL (norm7.2-63.3 pg/mL). Twenty-four–hour urinary free cortisol was elevated at 244 µg/day (n < 220 µg/day) and confirmed ACTH-dependent hypercortisolism. The patient underwent transsphenoidal surgery. Post-surgical pathology report demonstrated strong immunohistochemical staining for ACTH. Patient had subsequent resolution of hyperprolactinemia, menstrual irregularities, and depressive symptoms.

Conclusion: This case highlights the risk of diagnostic anchoring on mild hyperprolactinemia, which may obscure underlying Cushing disease in the absence of classic features. Targeted hormonal evaluation beyond initial abnormalities is critical to avoid misdiagnosis. Early recognition of ACTH-secreting adenomas enables definitive treatment and prevents progressive metabolic and neuropsychiatric complications. Heightened clinical suspicion is essential when evaluating patients with discordant or unexplained endocrine findings

Key words: Cushing disease,pituitary adenoma, ACTH-dependent hypercortisolism, diagnostic anchoring bias

References:

(1) Endocrine Reviews, First published online November 29, 2021, bnab046 https://doi.org/10.1210/endrev/bnab046

(2) Mercedes Martinez-Gil and Kevin C J Yuen JCEM Case Reports, Volume 3, Issue 6, June 2025, luaf089 https://doi.org/10.1210/jcemcr/luaf089

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