Soule Steven, Florkowski Chris, Potter Howard, Pattison David, Swan Martin, Hunt Penny, George Peter
Department of Endocrinology, Canterbury Health Laboratories, University of Otago Christchurch School of Medicine and Hospital, Christchurch, New Zealand.
Ann Clin Biochem. 2008 Sep;45(Pt 5):520-3. doi: 10.1258/acb.2007.007211.
A 20-year-old fit male soldier presented on two separate occasions 16 months apart with severe, symptomatic hyponatraemia and a clinical and biochemical picture consistent with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In the intervening period, repeated plasma sodium values were in the reference range. Intensive investigation failed to reveal a cause for SIADH that was initially considered idiopathic. The description of a family comprising several adults with intermittent or water load induced-hyponatraemia associated with an activating mutation in the arginine vasopressin (AVP) receptor type 2 (AVPR2) raised the question of whether our patient could have a similar 'nephrogenic syndrome of inappropriate antidiuresis'. Mutational screening of AVPR2 in our patient revealed a single missense mutation (R137C) in the second intracellular loop, which has been associated with constitutive activation of the AVPR2. In conclusion, adults with intermittent, severe hyponatraemia may have a constitutively activating mutation in the AVPR2 with resultant nephrogenic syndrome of inappropriate antidiuresis. Patients with idiopathic SIADH, particularly those with unmeasurable circulating AVP concentrations, should be considered for mutational screening of AVPR2.
一名20岁身体健康的男性士兵在相隔16个月的两次就诊时,均出现严重的有症状低钠血症,临床和生化表现符合抗利尿激素分泌不当综合征(SIADH)。在这期间,多次血浆钠值处于参考范围内。深入检查未能发现最初被认为是特发性的SIADH病因。一个包含几名成年人的家庭,他们有间歇性或水负荷诱导的低钠血症,且与2型精氨酸血管加压素(AVP)受体(AVPR2)的激活突变有关,这引发了一个问题,即我们的患者是否可能患有类似的“肾源性抗利尿不当综合征”。对我们患者的AVPR2进行突变筛查发现,在第二个细胞内环中有一个单一的错义突变(R137C),该突变与AVPR2的组成性激活有关。总之,患有间歇性严重低钠血症的成年人可能在AVPR2中有组成性激活突变,从而导致肾源性抗利尿不当综合征。对于特发性SIADH患者,尤其是那些循环中AVP浓度无法测量的患者,应考虑对AVPR2进行突变筛查。