The serotonin syndrome: initial misdiagnosis.

BACKGROUND: The selective serotonin reuptake inhibitors are major drugs used in psychiatry today. While serotonin syndrome has become more frequent in an overdose situation and when an interacting drug is given, the toxicity of SSIRs is less than that of most other psychiatric drugs. Although the characteristics of toxicity are defined, it seems that physicians are not aware of the phenomenon. OBJECTIVES: To investigate patients with serotonin syndrome who were initially misdiagnosed. METHODS: We conducted a retrospective chart review of seven patients admitted in the last 2 years with mild to severe serotonin syndrome who were initially diagnosed as having other diseases. RESULTS: Most patients (5/7) were initially diagnosed with exacerbation of their psychiatric disorder. Gastroenteritis was diagnosed in two patients. One patient was suspected of having a metastatic lesion in the brain, and severe drug overdose was diagnosed in one patient. They all recovered after withholding the culprit drugs. CONCLUSIONS: This report is an addition to the growing literature on misdiagnosis of psychiatric patients. Serotonin toxicity should be considered in patients in whom the combination of mental changes, neuromuscular abnormalities and autonomic hyperactivity are features of acute disease.

Increased urinary Na-Cl cotransporter protein in familial hyperkalaemia and hypertension.

BACKGROUND: Familial hyperkalaemia and hypertension (FHH), also termed pseudohypoaldosteronism type II, is a rare monogenic form of hypertension caused by mutations in the WNK1 or WNK4 kinases. In vitro expression of WNK4 reduces surface abundance and activity of coexpressed NaCl cotransporter (NCCT). This effect is lost in disease-producing WNK4 mutants. In two mice models of FHH, one expressing two extra copies of mutant WNK4 (Q562E) and another in which a mutant (D561A) WNK4 replaced wild-type WNK4, renal distal tubule hyperplasia with overexpression of NCCT was found. Currently no FHH human renal tissue is available to test for increased distal tubule surface abundance of NCCT. The availability of a unique large family with FHH and the Q565E WNK4 mutation enabled us to investigate this issue in an indirect manner. METHODS: Assuming that shedding of NCCT to the urine reflects its abundance in the distal tubule epithelium, we measured urinary NCCT protein in eight subjects of the FHH family and in eight unrelated controls by western blotting. RESULTS: Urinary NCCT protein was about four times higher in FHH than in controls [111.1 +/- 40.5 versus 26.1 +/- 16.4 densitometry units (P < 0.0001)]. No significant difference in urinary sodium and potassium concentrations was seen between FHH and controls. CONCLUSIONS: The increased urinary NCCT in FHH most probably reflects increased NCCT abundance in the apical membrane of distal tubule cells in patients with FHH and the WNK4 mutation and points to the pathogenetic mechanism for the clinical phenotype of FHH and the WNK4 mutation, supporting results in transgenic mice with the same mutation and in knockin mice with another mutation.