First case report of an adrenocortical carcinoma caused by a BRCA2 mutation.

BACKGROUND: Adrenocortical carcinoma (ACC) may rarely be a component of inherited cancer syndromes such as Li-Fraumeni syndrome and Beckwith-Wiedemann syndrome. ACC caused by a BRCA2 mutation has never been reported. METHODS: Nucleotide sequencing of BRCA2 in lymphocyte and tumoral DNA of a 50-year-old male who presented with an androgen-secreting ACC and a strong family history of breast, ovarian, and pancreatic cancers. RESULTS: A germline BRCA2 2 bp heterozygous deletion at nucleotide 8765 (8765delAG) leading to a frameshift mutation (p.Glu2846GlyfsX23) was detected. Only the BRCA2 deleted allele was retained in the ACC tumoral DNA compared with the control DNA supporting a loss of heterozygosity in the tumor. CONCLUSION: This is the first reported case of a patient with ACC associated with a BRCA2 germline mutation. Loss of heterozygosity in ACC DNA suggests a causal link with the BRCA2 8765delAG mutation.

2012 update in the treatment of prolactinomas.

New information has been provided over the last years regarding treatment of prolactinomas and will be reviewed in this update. Medical treatment with a dopamine agonist (DA) remains the cornerstone of therapy and cabergoline is the first choice, due to its high efficacy and good tolerability profile. Prolonged remission after discontinuation of DA may be observed if treatment has been given for at least two years, normal prolactin has been obtained with a low dose and tumoral diameter has been reduced by at least 50%. Although the risk of restrictive cardiac valve disease is low at the standard doses of cabergoline used for the treatment of hyperprolactinaemia, long-term echocardiographic surveillance is however indicated, in particular in resistant patients who need higher doses of cabergoline (2.0 mg/week or more). Neurosurgical treatment of prolactinomas is less effective than medical therapy and recurrence of hyperprolactinaemia is frequent. Besides classical indications such as drug intolerance, resistance or acute complications, new indications have emerged such as young patients with a high likelihood of complete tumour resection and who do not wish to take prolonged medical treatment, or patients who require high doses of cabergoline, in whom surgical debulking may significantly improve postoperative hormonal control. Finally, recent data indicate that cabergoline is safe for the developing foetus and for the mother, and therefore should not be preventively withdrawn in a young woman wishing to become pregnant.

Outcomes of transsphenoidal surgery in prolactinomas: improvement of hormonal control in dopamine agonist-resistant patients.

CONTEXT: Few studies have recently re-examined the efficacy of neurosurgery in prolactinoma patients operated for various indications. OBJECTIVE: To analyze outcomes of patients with a prolactinoma treated by transsphenoidal surgery, to identify factors associated with remission and relapse, and to evaluate if surgical debulking allows for better hormonal control in patients with preoperative resistance to dopamine agonists (DAs). PATIENTS AND METHODS: This was a retrospective review of patients with a benign prolactinoma followed preoperatively and postoperatively in our department and treated by transsphenoidal surgery (n=63; 45 women; mean age: 31 ± 14 years). RESULTS: Postoperative remission was obtained in 63% of microprolactinomas, 60% of noninvasive macroprolactinomas, and none of the invasive macroprolactinomas. Better remission rate was independently predicted by lower diagnostic prolactin (PRL) levels and by the lack of abnormal postoperative residual tissue (P<0.05). A recurrence of hyperprolactinemia was observed in 34% of patients after a median follow-up period of 36 (7-164) months. In patients with preoperative DA resistance treated again after surgery, there was a significant reduction in PRL levels postoperatively (26 (6-687) ng/ml) vs preoperatively (70 (22-1514) ng/ml; P<0.01) under a lower DA dose, and about half of the patients had PRL normalization. CONCLUSIONS: Recurrence of hyperprolactinemia is observed in one-third of prolactinoma patients after surgical remission and may occur as late as 13 years after surgery. Resistance to DA can be considered as a good surgical indication, as partial tumor resection allows for better hormonal control with a lower dose of DAs.

Identifying metabolically healthy but obese individuals in sedentary postmenopausal women.

The purpose of this study was to compare different methods to identify metabolically healthy but obese (MHO) individuals in a cohort of obese postmenopausal women. We examined the anthropometric and metabolic characteristics of 113 obese (age: 57.3 +/- 4.8 years; BMI: 34.2 +/- 2.7 kg/m(2)), sedentary postmenopausal women. The following methods were used to identify MHO subjects: the hyperinsulinemic-euglycemic clamp (MHO: upper quartile of glucose disposal rates); the Matsuda index (MHO: upper quartile of the Matsuda index); the homeostasis model assessment (HOMA) index (MHO: lower quartile of the HOMA index); having 0-1 cardiometabolic abnormalities (systolic/diastolic blood pressure > or =130/85 mm Hg, triglycerides (TG) > or =1.7 mmol/l, glucose > or =5.6 mmol/l, HOMA >5.13, high-sensitive C-reactive protein (hsCRP) >0.1 mg/l, high-density lipoprotein-cholesterol (HDL-C) <1.3 mmol/l); and meeting four out of five metabolic factors (HOMA < or =2.7, TG < or =1.7 mmol/l, HDL-C > or =1.3 mmol/l, low-density lipoprotein-cholesterol < or =2.6 mmol/l, hsCRP < or =3.0 mg/l). Thereafter, we measured insulin sensitivity, body composition (dual-energy X-ray absorptiometry), body fat distribution (computed tomography scan), energy expenditure, plasma lipids, inflammation markers, resting blood pressure, and cardiorespiratory fitness. We found significant differences in body composition (i.e., peripheral fat mass, central lean body mass (LBM)) and metabolic risk factors (i.e., HDL-C, hsCRP) between MHO and at risk individuals using the different methods to identify both groups. In addition, significant differences between MHO subjects using the different methods to identify MHO individuals were observed such as age, TG/HDL, hsCRP, and fasting insulin. However, independently of the methods used, we noted some recurrent characteristics that identify MHO subjects such as TG, apolipoprotein B, and ferritin. In conclusion, the present study shows variations in body composition and metabolic profile based on the methods studied to define the MHO phenotype. Therefore, an expert consensus may be needed to standardize the identification of MHO individuals.