Abstract Disclosure: E.B. Geer: Consulting Fee; Self; Amryt. Research Investigator; Self; Ionis, Amryt. W. Huang: Consulting Fee; Self; Amryt. Speaker; Self; Amryt. M.B. Gordon: Consulting Fee; Self; Recordati, Novo Nordisk. Research Investigator; Self; Amryt, Crinetics, Recordati, Novo Nordisk. K.C. Yuen: Consulting Fee; Self; Novo Nordisk, Ipsen, Amryt, Crinetics, Recordati, Xeris. Speaker; Self; Recordati. S.E. Lubitz: None. R. Salvatori: Consulting Fee; Self; Novo Nordisk, Camurus, Recordati, Ipsen. M. Fleseriu: Consulting Fee; Self; Amryt, Camurus, Debiopharm, Ipsen, Recordati, Pfizer, Inc. Research Investigator; Self; Amryt, Crinetics, Ionis. A.G. Ioachimescu: Consulting Fee; Self; Amryt, Recordati, Camurus. E.A. Christofides: Advisory Board Member; Self; Amryt. Speaker; Self; Amryt. J. Sisco: None. S.D. Mathias: Employee; Self; Health Outcomes Solutions. Other; Self; Amryt. J.A. Crompton: Employee; Self; Amryt. M.E. Molitch: Consulting Fee; Self; Amryt, Takeda, Sention, Janssen Research & Development Company. BACKGROUND: The Management of Acromegaly (MACRO) registry is a prospective, observational cohort study of patients with active acromegaly on medical therapy or eligible for medical therapy that includes paired data from patients and their physicians allowing for comparison of symptom-related data. METHODS: Patients and physicians completed questionnaires at enrollment and then every 3 months for up to 3 years. Information collected included demographic, disease activity, and treatment information, including ratings of symptom and biochemical control, and patient-reported outcomes (PROs) (AcroQOL, Acro-TSQ, and WPAI). Descriptive, concordance and correlation statistics were calculated. RESULTS: Data from 199 patients were available (54% female; mean age = 52; mean time since diagnosis = 10 years). IGF-I data was available in 191/199 (96%) patients of which 147/191 (77%) patients were biochemically controlled (defined as a baseline IGF-I level ≤ 1x ULN). Symptoms in biochemically controlled patients at enrollment were as follows: joint pain (54%), fatigue (52%), memory problems (42%), sleep apnea (39%), swelling (31%), headaches (25%), sweating (22%), and visual changes (20%). In the biochemically controlled group, 107/147 (73%) patients and 106/147 (72%) physicians reported symptoms as well-controlled. Conversely, concordance within individual patients between their physician’s and their own rating of symptom control was low (kappa = 0.272; p<0.001). Memory problems, fatigue, and joint pain were the most frequent symptoms reported at baseline by biochemically controlled patients that were not reported by their matched physician (33, 25 and 18% of patients, respectively). In the 45 biochemically controlled patients that rated any of their symptoms as severe, physicians who also reported the symptom provided the same rating of severity in only 5 (11%) cases. In the remaining cases rated as severe by patients, 26 (58%) and 14 (31%) were rated by their physician as mild or moderate. Well-controlled symptoms as reported by patients were associated with significantly higher (better) AcroQOL scores across all scales and 5 of the 6 Acro-TSQ domains (p < 0.001 except injection site interference) and less impairment on 3 of 4 WPAI scales (p < 0.001 except absenteeism). CONCLUSIONS: Symptoms persist in acromegaly patients despite achieving biochemical control. Adequate symptom control and physician-patient agreement on the extent of symptom control continues to be underrecognized and constitutes an unmet need in acromegaly patients despite its association with better patient-reported outcomes. Presentation: Saturday, June 17, 2023