Early central blood pressure elevation in adult patients with 21-hydroxylase deficiency.

CONTEXT: Controversial data exist on cardiovascular damages in patients with congenital adrenal hyperplasia (CAH). OBJECTIVE: To assess blood pressure and early cardiovascular damages on a large cohort of adult CAH patients and control individuals. DESIGN: Case-control study. SETTING: Referral Center for Rare Disease, Pitié Salpêtrière Hospital, Paris, France. PATIENTS OR OTHER PARTICIPANTS: Fifty-eight women and 26 men with CAH diagnosed in childhood and 85 controls matched-paired for sex, age and smoking status were prospectively included. INTERVENTION: Measurement of large arteries and microcirculatory anatomical and functional indices as well as hormonal status and cardiovascular risk factors evaluation. MAIN OUTCOME MEASURE: The primary objective was to compare carotid intima-media thickness (cIMT) in CAH patients and controls. The secondary objectives were to compare blood pressure (BP), radial augmentation index (rAI), central BP, carotid-femoral pulse wave velocity (PWV), skin microcirculation indices and inflammation parameters in CAH patients and controls. RESULTS: Although PWV and cIMT were identical in patients and controls, higher rAI (64.6 ±â€Š1.7 vs. 59.9 ±â€Š1.6%, P = 0.02) and higher central SBP (101.8 ±â€Š1.5 vs. 95.1 ±â€Š1.5 mmHg, P < 0.001) were observed in CAH patients. Regarding microcirculatory indices, there was a higher functional resting capacity and a lower anatomical capillary density in CAH patients. In multivariate analysis, we found an independant association between CAH and central SBP elevation. CONCLUSION: We found an early rise in central SBP in CAH patients whereas sublinical arterial damages markers were normal. Our study suggest that vascular damages and increased cardiovascular risk could be mainly BP-driven.

Polyendocrinopathy Resulting From Pembrolizumab in a Patient With a Malignant Melanoma.

INTRODUCTION: Checkpoint inhibitors have significantly improved the prognosis of patients with advanced melanoma. These cancer immunotherapy drugs have specific endocrine autoimmune toxicity. We describe a case of an adrenal insufficiency secondary to pembrolizumab, an anti-programmed cell death-1 monoclonal antibody. Moreover, this case of polyendocrinopathy resulting from a pembrolizumab as the adrenal insufficiency occurred after a thyroiditis. PARTICIPANT: A 55-year-old female was started on pembrolizumab immunotherapy for a metastatic choroidal melanoma. Five months after initiation, she suffered from thyrotoxicosis. A thyroiditis was diagnosed by iodine-123 thyroid scintigraphy and ultrasonography. Pembrolizumab therapy was maintained. Two weeks later, without any other treatment given, she patient developed hypothyroidism and levothyroxine substitution was started. Pembrolizumab proved to be ineffective and was stopped 9 months after initiation. One month following its discontinuation, the patient was hospitalized in the intensive care unit. Severe hyponatremia (115 mmol/L) associated with hyperkalemia (5.7 mmol/L) led to the early recognition and treatment of an acute adrenal insufficiency. Positive results for adrenal cortex and 21-hydroxylase antibodies were in favor of autoimmune toxicity. CONCLUSION: This case highlights the diversity of potential endocrine toxicity of checkpoint inhibitors. Because acute adrenal crisis may be associated with substantial morbidity and mortality, physicians must be aware of these rare adverse events to allow an early diagnosis.

Influence of diagnostic criteria on the interpretation of adrenal vein sampling.

Guidelines promote the use of adrenal vein sampling (AVS) to document lateralized aldosterone hypersecretion in primary aldosteronism. However, there are large discrepancies between institutions in the criteria used to interpret its results. This study evaluates the consequences of these differences on the classification and management of patients. The results of all 537 AVS procedures performed between January 2001 and July 2010 in our institution were interpreted with 4 diagnostic criteria used in experienced institutions where AVS is performed without cosyntropin (Brisbane, Padua, Paris, and Turin) and with criteria proposed by a recent consensus statement. AVS procedures were classified as unsuccessful, lateralized, or not lateralized according to each set of criteria. Almost 5× more AVS procedures were classified as unsuccessful with the strictest criteria than with the least strict criteria (18% versus 4%, respectively). Similarly, over 2× more AVS procedures were classified as lateralized with the least stringent criteria than with the most stringent criteria (60% versus 26%, respectively). Multiple samples were available from ≥1 side for 155 AVS procedures. These procedures were classified differently by ≥2 right-left sample pairs in 12% to 20% of cases. Thus, different sets of criteria used to interpret AVS in experienced institutions translate into heterogeneous classifications and hence management decisions, for patients with primary aldosteronism. Defining the most appropriate procedures and diagnostic criteria is needed for AVS to achieve optimal performance and fully justify its status as a gold standard.