Context
Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs).
Objective
To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients.
Design
12-year prospective, observational study.
Participants & Setting
We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases.
Interventions & Outcome
AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310).
Results
Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650).
Conclusions
Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course.
IntroductionWe report week-52 results from an open-label extension that assessed the effi cacy and safety of adalimumab (ADA) in anti-TNF-naïve patients with moderately to severely active ulcerative colitis (UC). Methods Patients were adults with UC (Mayo scores ≥6 points and endoscopic subscores ≥2 points) despite treatment with corticosteroids and/or immunosuppressants. After an 8-week, randomised, placebo-controlled period, patients could enter an open-label extension to receive ADA 40 mg every other week (eow) as maintenance therapy through week 52. Data were analyzed with non-responder imputation (NRI); missing scores and values after adjustment to weekly dosing (for fl ares/nonresponse) were imputed as treatment failures. Modifi ed NRI (mNRI) analyses (post-hoc), which did not count patients who dose escalated as failures, and as-observed analyses were also performed. Results Of 390 patients in the primary analysis population, 360 received open-label ADA eow and 117 had their dosages increased to weekly ADA. Mean/median changes in Mayo (0-12) and partial Mayo (0-9) scores from baseline to week 52 (observed values, N=274) were -5.0/-5.0 and -3.7/-4.0, respectively (all p<0.001). The table 1 summarises rates of clinical remission and other secondary end points at week 52. Remission rates at week 52 were 25.6% (NRI) and 29.5% (mNRI). No deaths or cases of tuberculosis were reported.Conclusion Treatment with open-label ADA 40-mg eow/ weekly generally maintained clinical remission and other efficacy end points in patients with moderately to severely active UC. The safety profi le in UC was consistent with the known safety profi le of ADA.
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