Transition of young adults with endocrine and metabolic diseases: the 'TRANSEND' cohort.

OBJECTIVE: The transition from paediatric to adult medicine involves risks of poor patient outcomes and of significant losses of patients to follow up. The research aimed to analyse the implementation in an initial cohort of patients of a new programme of transition to adult care based on a case management approach. DESIGN: A longitudinal study of the case management approach to transition, initiated in a university hospital in France in September 2016. METHODS: Patients with the endocrine or metabolic disease diagnosed during childhood and transferred to adult care were included. The transition programme includes three steps based on case management: liaising with paediatric services, personalising care pathways, and liaising with structures outside the hospital (general practitioners, agencies in the educational and social sector). RESULTS: The cohort included 500 patients, with malignant brain tumour (n = 56 (11%)), obesity (n = 55 (11%)), type 1 diabetes (n = 54 (11%)), or other disease (n = 335 (67%)). Their median age at transfer was 19, and the sex ratio was 0.5. At median 21 months of follow-up, 439 (88%) had a regular follow-up in or outside the hospital, 47 (9%) had irregular follow-up (absence at the last appointment or no appointment scheduled within the time recommended), 4 had stopped care on doctor's advice, 4 had died, 3 had moved, and 3 had refused care. The programme involved 9615 case management actions; 7% of patients required more than 50 actions. Patients requiring most support were usually those affected by a rare genetic form of obesity. CONCLUSIONS: Case managers successfully addressed the complex needs of patients. Over time, the cohort will provide unprecedented long-term outcome results for patients with various conditions who experienced this form of transition.

Liver adenomatosis in patients with hepatocyte nuclear factor-1 alpha maturity onset diabetes of the young (HNF1A-MODY): Clinical, radiological and pathological characteristics in a French series.

BACKGROUND: Liver adenomatosis (LA) is a rare disease resulting from biallelic inactivation of the hepatocyte nuclear factor-1 alpha (HNF1A) gene, which induces the proliferation of adenoma cells in liver parenchyma. Liver adenomatosis has only been documented in case reports from patients carrying a HNF1A germline mutation. We have evaluated the frequency of LA among a large cohort of patients with HNF1A-maturity onset diabetes of the young (MODY), previously termed "MODY3," and herein describe its clinical, radiological, and pathological characteristics. METHODS: In all, 137 HNF1A-MODY subjects from 74 families were screened by liver ultrasonography in 13 centers, and 15 additional cases of LA were later included in the series. Liver adenomatosis was confirmed by liver computed tomography, magnetic resonance imaging (MRI), and/or histopathology. RESULTS: Among 137 carriers of an HNF1A mutation, 9 patients (6.5%) from seven families were diagnosed with LA. Diabetes mellitus was present in 87.5% of patients with LA. In 25% of patients, LA was diagnosed due to intra-abdominal or intratumoral bleeding. Liver biochemistry was near normal in all patients. Liver imaging showed adenomas of various sizes and numbers. On MRI, most nodules had the radiological characteristics of steatotic adenomas. Histopathological confirmation of LA was available in 13 cases, and these adenomas were mostly steatotic. Surgery was initially performed in 37.5% of patients, and liver disease progression was observed in 30%. No disease progression was observed in 14 pregnancies. CONCLUSIONS: The frequency of LA in a cohort of screened HNF1A-MODY patients and the high incidence of LA progression and/or hemorrhage warrants systematic screening for liver adenomatosis in HNF1A-MODY families.

Insulin Pump Combined with Flash Glucose Monitoring: A Therapeutic Option to Improve Glycemic Control in Severely Nonadherent Patients with Type 1 Diabetes.

Some patients with type 1 diabetes (T1D) are severely noncompliant; they rarely perform self-blood glucose measures and miss insulin injections. Their HbA1c is far above the target rate. Current guidelines do not recommend starting treatment with an insulin pump (continuous subcutaneous insulin infusion [CSII]) for these persons. The aim of this study was to determine whether a CSII associated with a flash glucose monitoring (FGM) device could reduce HbA1c without increasing the risk of acute events, diabetic ketoacidosis (DKA) and severe hypoglycemia (SH), in these patients. We conducted a 6-month nonrandomized, pilot prospective study. Patients with T1D on multiple daily injections who performed less than two self-blood glucose tests/day and had an HbA1c >9% were equipped with CSII and an FGM device. The primary composite endpoint was defined by a change in HbA1c ≥1% without any episode of DKA or SH during 6 months. Change in mean HbA1c, weight, treatment satisfaction, frequency of minor hypoglycemia, and ketoacidosis were secondary endpoints. Nineteen adults were included. Median (Q1-Q3) HbA1c at baseline was 10.8 (10.3-13.0), 14 participants did not perform any self-monitoring and 5 performed maximum two tests daily. Twelve participants (63%) (95% confidence interval 41%-81%) met the primary composite endpoint. Seventeen patients completed the study. HbA1c decreased by 2% (1.0-3.3) (P < 0.001), and satisfaction with treatment significantly improved. Three participants experienced SH and one a DKA, versus, respectively, five and eight in the year preceding the study. Participants scanned the sensor 4 (3-6) times per day and injected 3 (2.7-4.1) boluses per day. Weight increased significantly. An association of an insulin pump with an FGM device can be an effective and safe therapeutic option in severely nonadherent and noncompliant patients with high HbA1c.

Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study.

CONTEXT: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. OBJECTIVE: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. DESIGN: This study was an international, multicenter, retrospective case collection/database analysis. SETTING: The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. PATIENTS: Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. RESULTS: The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. CONCLUSIONS: AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility.