ABSTRACT
An 84-year-old woman presented with lethargy and anorexia. Although routine biochemistry demonstrated mild hyponatraemia, moderate hyperkalaemia and severe hypocalcaemia, the patient did not demonstrate the usual symptoms of hypocalcaemia. An electrocardiogram did not demonstrate evidence of hyperkalaemia or hypocalcaemia. Repeated biochemistry confirmed hyponatraemia but that was associated with hypokalaemia and normocalcaemia. Initial management involved correction of the hyponatraemia and hypokalaemia with appropriate intravenous fluids. If serum biochemistry demonstrates hyperkalaemia in association with hypocalcaemia, pseudohyperkalaemia and pseudohypocalcaemia caused by contamination with potassium ethylenediaminetetraacetic acid should always be considered. This can be confirmed by repeating biochemistry, but ensuring the serum gel tube is drawn first when taking multiple blood samples to avoid this contamination.
Subject(s)
Diagnostic Errors , Hyperkalemia/diagnosis , Hypocalcemia/diagnosis , Aged, 80 and over , Algorithms , Blood Specimen Collection/methods , False Positive Reactions , Female , Humans , Hyperkalemia/complications , Hypocalcemia/complicationsABSTRACT
BACKGROUND: Genetic mutations and upregulation of growth factors are implicated in the pathogenesis of hyperparathyroidism. The aim of this study was to evaluate the role of Wilms' tumour suppressor gene (WT-1) and the insulin-like growth factor (IGF) axis in hyperparathyroidism. METHODS: The expression of WT-1 and IGF components was examined by immunohistochemistry, reverse transcriptase-polymerase chain reaction and western immunoblotting in a panel of parathyroid specimens from both primary and secondary hyperparathyroidism. A human parathyroid cell culture model was established to examine the parathyroid response to IGF stimulation. RESULTS: There was a significantly lower level of WT-1 expression in parathyroid tumours than in normal parathyroid glands. Most tumours expressed IGF-I and IGF-II receptors and responded to IGF stimulation. Only IGF-I was present in normal parathyroid glands, whereas IGF-II was expressed exclusively in parathyroid tumours. CONCLUSION: Abnormal expression of WT-1 and the IGF axis may play a role in the pathogenesis of hyperparathyroidism.
Subject(s)
Hyperparathyroidism/genetics , Somatomedins/genetics , WT1 Proteins/genetics , Wilms Tumor/genetics , Cells, Cultured , Female , Humans , Hyperparathyroidism/metabolism , Immunohistochemistry , Male , Mutation/genetics , Receptors, Somatomedin/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Somatomedins/metabolism , Up-Regulation , Wilms Tumor/metabolismABSTRACT
BACKGROUND: In most cell types, influx of calcium (Ca2+) induces a growth or secretory response. The opposite occurs in parathyroid (PTH), cells where there is an inverse relationship between intracellular Ca2+ concentration and PTH secretion. We have examined the effects of calcium channel and metabolism modulators on insulin-like growth factors (IGFs) in a parathyroid cell culture model. METHODS: Cell cultures were prepared from 9 patients undergoing operation for hyperparathyroidism. Following adhesion, the cells were transferred to serum-free medium and dosed with IGF I, II +/- ethyleneglycol-bis(beta-aminoethyl)-N,N,N',N'-tetraacetic acid (EGTA), nifedipine, nickel, 2-aminoethoxy-diphenylborate (2-APB), or dantrolene. Proliferation (96 hours) was assessed by measuring tritiated thymidine incorporation and PTH release (1 and 3 hours) assayed by IRMA. RESULTS: Both IGF I and II increased DNA synthesis to 162.8% +/- 10.6% (SEM) and 131.1% +/- 7.7%, respectively (P < 0.05). EGTA at 0.2 mmol (ionized Ca2+ 0.2 mmol) did not affect the response to both IGFs. EGTA at 2 mmol (ionized Ca2+ 0 mmol) reduced the DNA synthesis of IGF I and II to 29% and 26%, respectively (P < 0.05). Nifedipine and nickel (nonspecific Ca2+ channel blocker) were equally potent in negating the mitogenic effects of both IGFs. 2-APB (IP3R blocker) reduced the basal DNA synthesis to 51.3% +/- 8.4% but had no effect on either IGF. Dantrolene (ryanodine receptor blocker) negated IGF II induced mitogenisis (74.2% +/- 6.7%) and partially inhibited IGF I mitogenesis (123% +/- 6%) (P < 0.05). The rate of PTH secretion was greater after IGF II stimulation than after IGF I stimulation. CONCLUSIONS: IGFs I and II induce mitogenesis by different calcium signaling pathways. These data suggest that parathyroid cells may utilize different calcium signaling pathways to distinguish growth factors and serum calcium changes.
