We report here five new patients with McCune-Albright syndrome and acromegaly. In the five patients studied (three males and two females aged 18-42 years), acromegaly began before the age of 20 years and was recognized after the diagnosis of fibrous dysplasia, which was polyostotic in three cases and monostotic in two. Bone fibrous dysplasia always involved the base of the skull and in four patients prevented surgical removal of the pituitary adenoma, which was visualized easily by magnetic resonance imaging. Serum growth hormone (GH) levels ranged between 20 and 48 micrograms/l and were not suppressed by an oral glucose load. Thyrotropin-releasing hormone administration produced a paradoxical increase in serum GH levels in all the patients. Four of the five patients had hyperprolactinemia (43-670 micrograms/l). In the sole patient who could be operated on, a typical adenoma with positive immunostaining for GH was incompletely removed and postoperative radiation therapy failed to cure the acromegaly. In two patients, medical therapy with bromocriptine and/or octreotide was partially or totally ineffective whatever the dose (up to 1.5 mg per day) and duration (2-4 years) of octreotide treatment.

Complete analysis of the CYP21 gene was performed in 56 unrelated French women with symptomatic nonclassical congenital adrenal hyperplasia. The mutational spectrum and the phenotype-genotype correlation were examined. The overall predominant mutation was V281L, which was present on 51% of alleles and in 80% of women. Three novel mutations were found: L317M, R435C, and a 5'-end gene conversion. Sixty-three percent of the women were carrying a severe mutation of the CYP21 gene, and hence risk giving birth to children with a classical form of the disease. In such cases, screening for heterozygosity in the partner is crucial. Potential genotype/phenotype correlations were examined by classifying the patients into three groups according to the CYP21 allelic combinations: A (mild/mild), B (mild/severe), and C (severe/severe). Primary amenorrhea was more frequent, and mean basal and stimulated 17-hydroxyprogesterone levels were higher in compound heterozygotes for mild and severe mutations (group B) compared with women with two mild mutations (group A), but there was a considerable overlap for individual values. Surprisingly, in two women, a severe mutation was found on both alleles (group C). Therefore, the phenotype cannot be accurately predicted from the genotype. Variability in phenotypic expression may be conditioned by mechanisms other than genetic heterogeneity at the CYP21 locus.

Activating mutations of G proteins, which are membrane signal transducers, have been associated recently with the development of various endocrine neoplasms. Mutations of two highly conserved codons, Arg201 and Gln227, in the alpha-subunit of the Gs protein, the adenylyl cyclase-stimulating protein, were first described in growth hormone-producing pituitary tumours. They resulted in constitutive activation of the alpha s-subunit by decreasing intrinsic GTPase activity. A similar mutation, affecting codon Arg179 (exon 5) in the alpha-subunit of the Gi2 protein, the adenylyl cyclase-inhibiting protein, has been described by a single group in ovarian and adrenocortical tumours. We evaluated the frequency of activating mutations in the alpha-subunit of the Gi2 protein in 18 human adrenocortical tumours. We screened exons 5 (codon Arg179) and 6 (codon gln205) for mutations by denaturing gradient gel electrophoresis analysis of leucocyte and tumoural DNA. No abnormal migration pattern was found in either exon. The absence of mutation in exon 5, which includes the Arg179 codon, was confirmed in all tumoural DNA by direct sequencing. In conclusion, we did not find any oncogenic mutations in the GTPase domain of the alpha-subunit of the Gi2 protein in adrenocortical tumours. Thus, the previously oncogenic gip2 mutations do not appear to be determinant for adrenocortical tumourigenesis.

AimsTo identify simple insulin regimens for people with Type 2 diabetes mellitus that can be accepted and implemented earlier in primary and specialist care, taking into consideration each individual's needs and capabilities.MethodsUsing randomized clinical trials identified by a search of the PubMed database, as well as systematic reviews, meta‐analyses and proof‐of‐concept studies, this review addresses topics of interest related to the progressive intensification of a basal insulin regimen to a basal‐plus regimen (one basal insulin injection plus stepwise addition of one to three preprandial short‐acting insulin injections/day) vs a basal‐bolus regimen (basal insulin plus three short‐acting insulin injections per day) in people with Type 2 diabetes. The review explores approaches that can be used to define the meal for first prandial injection with basal‐plus regimens, differences among insulin titration algorithms, and the importance of self‐motivation and autonomy in achieving optimum glycaemic control.ResultsA basal‐plus regimen can provide glycaemic control equivalent to that obtained with a full basal‐bolus regimen, with fewer injections of prandial insulin. The first critical step is to optimize basal insulin dosing to reach a fasting glucose concentration of ~6.7 mmol/l; this allows ~40% of patients with baseline HbA1c >75 mmol/mol (9%) to be controlled with only one basal insulin injection per day.ConclusionsCompared with a basal‐bolus regimen, a basal‐plus insulin regimen is as effective but more practical, and has the best chance of acceptance and success in the real world.

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Aims: The primary objective of the TROPHIES observational study is to estimate the duration of treatment on dulaglutide or liraglutide without a significant treatment change by 24 months in patients with type 2 diabetes (T2D) initiating their first injectable treatment with these glucagon-like peptide-1 receptor agonists (GLP-1 RAs). This manuscript presents 12-month interim data. Materials and Methods: TROPHIES is a prospective, non-comparative, observational study of patients with T2D in Europe, naïve to injectable antihyperglycaemic treatments and initiating dulaglutide or liraglutide. Data on clinical characteristics, GLP-1 RA persistence and treatment patterns of glucose-lowering medication were collected at initiation of first injectable therapy and by 12 months. Results: By 12 months, 1014 dulaglutide and 991 liraglutide patients were eligible across France, Germany and Italy. Both cohorts presented a high probability [95% confidence interval (CI)] of GLP-1 RA persistence [dulaglutide, 0.88 (0.86 to 0.90); liraglutide, 0.83 (0.80 to 0.85)] and reduction in mean glycated haemoglobin percentage (95% CI) from baseline [dulaglutide, À1.18 (À1.27 to À1.08); liraglutide, À1.15 (À1.26 to À1.05)] with 48.2% of dulaglutide and 41.2% of liraglutide patients reaching their individualized glycated haemoglobin percentage target set by the physician at baseline. Mean weight (95% CI) change from baseline was À3.2 kg (À3.6 to À2.8) for dulaglutide and À3.4 kg (À3.9 to À3.0) for liraglutide. Slight changes in concomitant medications were observed compared with baseline. * Joint first author because of equal contributions.

Introduction:The REWIND study demonstrated a cardiovascular (CV) benefit of dulaglutide treatment in patients with type 2 diabetes (T2D) with or without established cardiovascular disease (CVD). The current study aims to describe similarities and differences between characteristics of patients with T2D in France and the REWIND population. Methods: A retrospective, observational study was conducted in France using primary care IQVIA electronic medical records. Patients aged C 18 years with at least one clinical visit and/or glucose-lowering agent prescription in 2019 were identified. The percentages of patients aged C 50 years with established CVD, aged C 55 years with subclinical CVD or aged C 60 years with multiple CV risk factors based on REWIND definitions were calculated. Results: A total of 63,927 patients with T2D were included. Mean age was 67 years, 93% were aged C 50 years and 58% were male. The median time since T2D diagnosis was 5.6 years, mean glycated hemoglobin was 7.1% and mean body mass index was 30.4 kg/m 2 . Of the patients included in the current study, 59.4% fulfilled REWIND CV criteria; 12.4% of patients were C 50 years old with established CVD; 9.7% of patients were aged C 55 years with subclinical vascular disease and 44.7% were aged C 60 years with C 2 CV risk factors. Conclusion: Almost 60% of this primary care French cohort with T2D fulfilled key REWIND CV criteria, with a lower percentage of patients having established CVD than REWIND participants.

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