Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

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

The postprandial changes in glucose (a), proinsulin (b), insulin (c), free fatty acid (FFA) (d) and triglyceride (TG) (e) concentrations are shown for 180 min after the ingestion of the standardized test meal (mean ±)

<p><b>Copyright information:</b></p><p>Taken from "Gastric bypass alters the dynamics and metabolic effects of insulin and proinsulin secretion"</p><p></p><p>Diabetic Medicine 2007;24(11):1213-1220.</p><p>Published online Jan 2007</p><p>PMCID:PMC2121126.</p><p>© 2007 The Authors. Journal compilation © 2007 Diabetes UK</p> , Morbidly obese (MO) subjects; , MO subjects treated with gastric bypass (GBP) surgery; , normal weight (NW) control subjects. Glucose: a rapid increase in glucose concentration during the first 30–60 min (early phase) was observed in the GBP-treated group compared with MO subjects (30 min, < 0.001; 60 min, = 0.002) and NW control subjects (30 min, < 0.001; 60 min, = 0.015). In the late phase after ingestion (120–180 min), glucose was significantly lowered in the GBP-treated group compared with MO subjects (120 min, = 0.009; 180 min, = 0.004) and NW control subjects at 180 min ( 0.02). Proinsulin: at all postprandial time points, except at 30 min, proinsulin concentrations were higher in MO than in control subjects ( 0.030–0.008). Early-phase proinsulin concentrations were higher in the GBP-treated group compared with control subjects (30 min, = 0.002; 60 min, = 0.006), but were similar to the MO group. In the late phase, concentrations of plasma proinsulin were significantly lower in the GBP-treated group compared with the MO group (120 min, = 0.048; 180 min, = 0.009), and the GBP-treated group had similar concentrations to control subjects (120 min, = 0.307; 180 min, = 0.814). Insulin: the GBP-treated group had a rapid increase in insulin concentration at 30 min in the early phase that had decreased at 60 min (30 min, = 0.001; 60 min, = 0.026) compared with control subjects. The late-phase insulin response was significantly higher in the MO group compared with the GBP-treated group (120 and 180 min, < 0.001). Insulin concentrations during the late phase in the GBP-treated group did not differ from control subjects (120 min, = 0.072; 180 min, = 0.130). Free fatty acids: no differences were observed regarding postprandial changes between the three groups, except at 180 min, where FFA were higher in the GBP group ( 0.016). Triglycerides: no differences were observed regarding postprandial changes between the three groups, except at 180 min, where TG were higher in the MO group ( 0.001)

Establishing a valid cohort of patients with acromegaly by combining the national patient register with the Swedish pituitary register

Purpose: The aim of this study was to establish a valid national cohort of patients diagnosed with acromegaly by combining data from the general National Patient Register (NPR) and the disease-specific Swedish Pituitary Register (SPR). Methods: Patients ≥ 18 years of age at diagnosis of acromegaly reported from 1991 to 2018 who were registered in the NPR and/or SPR were included. The diagnosis of acromegaly was considered correct for patients identified in both registers or confirmed through chart review. Medical records were reviewed in two of Sweden´s six health care regions if the patient was reported only in the NPR. An algorithm for the NPR, with criteria requiring multiple diagnosis registrations and tumour and/or surgery codes, was constructed to reduce the number of patients to review in the remaining four regions. Results: A total of 1866 patients were identified. Among these, 938 were reported in both registers. After application of the algorithm and chart review, the diagnosis was confirmed for 83 of the 906 patients found only in the NPR. Among 22 patients only registered in the SPR, a review of medical records confirmed acromegaly in 13. This resulted in a total of 1034 cases with acromegaly during the study period. The incidence rate of acromegaly in Sweden 1991–2018 was calculated to 4.0/million/year in the entire population and 5.1/million/year among subjects ≥ 18 years of age. Conclusion: The combination of the SPR and NPR established a valid cohort of patients diagnosed with acromegaly and increased the estimated incidence in Sweden