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.
Fifteen children and adolescents (4 male) with a median age of 5.4 yr (range 1.2 -13.6 yr) were entered into a screening protocol to identify lesions of von Hippel-Lindau (VHL) disease. Fourteen had an affected first-degree relative and one had a previous VHL lesion. Screening during the period of 2000 to 2008 followed published guidelines and consisted of measurement of urinary catecholamines, adrenal and renal imaging and ophthalmological and central nervous system examinations and imaging. Screening identified 8 VHL lesions in 6 asymptomatic patients with confirmed genetic mutations. Five patients had elevated urinary noradrenaline excretion and in each case the presence of a pheochromocytoma was identified on adrenal magnetic resonance imagin scan. In one patient a left-sided tumor was identified 1 yr after a right-sided tumor had been removed. In a sixth patient a retinal capillary hemangioma and a cerebellar hemangioblastoma were identified. Patient compliance with the screening protocol was variable reflecting its time-intensive nature. A formal screening programme for this at-risk population of pediatric patients, despite being intensive, can identify VHL lesions during a pre-morbid phase and may thus have a beneficial impact on prognosis in this serious disorder.
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