Partial Lipodystrophy Mimicking Cushing’s Syndrome: Clinical and Metabolic Insights from a Multicenter Study
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ID: 323809
2026
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Abstract
CONTEXT: Partial lipodystrophies (PLD) can closely mimic the clinical presentation of Cushing's syndrome (CS). Simplified risk scores have been developed to estimate the clinical probability of CS. However, their ability to discriminate CS from overlapping conditions such as PLD remains unclear. Moreover, reduced leptin action in lipodystrophy may influence the hypothalamic-pituitary-adrenal (HPA) axis, although human data are limited. OBJECTIVES: To compare clinical and metabolic features of PLD and CS, evaluate the discriminatory ability of clinical risk scores for CS, and explore leptin-HPA axis interactions in PLD. METHODS: Retrospective multicenter study including 61 patients with PLD and 56 patients with CS. Clinical and laboratory data were retrieved from medical records. Two clinical risk score for CS were calculated, and PLD and CS features were compared. RESULTS: Most PLD patients showed at least one feature suggestive of hypercortisolism. Facial fullness, facial plethora, dorsocervical fat pad, and hirsutism (p < 0.001, p = 0.049, p < 0.001, and p < 0.001 respectively) were more frequent in PLD, while proximal muscle atrophy and osteoporosis (p < 0.001 and p = 0.010) were more common in CS. Higher rates of diabetes and hypertriglyceridemia were also observed in PLD (p < 0.001). PLD patients achieved similar or even higher clinical CS score values than CS patients. In multivariable regression analysis, proximal muscle atrophy and osteoporosis were associated with CS (p < 0.04), whereas diabetes and hypertriglyceridemia were associated with PLD (both p < 0.001). No correlation was found between leptin levels and glucocorticoid-related hormonal parameters. CONCLUSIONS: PLD patients often exhibit cushingoid features, limiting the specificity of simplified clinical risk scores for CS. Increased awareness of lipodystrophy phenotypes and their distinguishing features is essential to reduce misdiagnosis.
| Reference Key |
openalex_W7172506778
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| Authors | Stella Pigni, Carolina Cecchetti, Marina Caputo, Laura Rotolo, Maria Francesca Birtolo, Caterina Pelosini, Mara Giordano, Gherardo Mazziotti, Andrea Lania, Alessandra Gambineri, Flavia Prodam |
| Journal | the journal of clinical endocrinology & metabolism |
| Year | 2026 |
| DOI |
10.1210/clinem/dgag314
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| URL | |
| Keywords | Keywords not found |
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