A Case of Renal Osteodystrophy with Unexpected Serum Intact Parathyroid Hormone Concentrations

Abstract

CASEA 64-year-old female with long-standing end-stage renal disease (ESRD), 3 status post 2 failed renal transplants, was evaluated for management of renal osteodystrophy with particular concern for adynamic bone disease (ABD). ABD was suspected because of low normal serum intact parathyroid hormone (PTH) concentrations (range 2.5-54 ng/L, reference range 10 -65 ng/L), intermittently increased serum calcium concentrations (range 88 -107 mg/L, reference range 84 -105 mg/L), and severe osteoporosis. However, her mildly increased serum alkaline phosphatase activities (range 149 -196 U/L, reference range 30 -120 U/L) were inconsistent with the low bone turnover observed in ABD. This discrepant clinical profile prompted investigation into the PTH assay used at our institution. Simultaneous samples were analyzed for intact PTH on our Roche Elecsys 2010 immunoassay analyzer and at a reference laboratory (Quest Diagnostics) on the Siemens Immulite 2000 immunoassay analyzer. Discrepant values of 48 and 786 ng/L were obtained, respectively. DISCUSSIONParathyroid hormone functions to maintain serum calcium concentrations within a tight physiologic range. Patients with chronic renal failure develop secondary hyperparathyroidism owing to decreased renal production of 1,25-dihydroxyvitamin D and hyperphosphatemia, both of which result in hypocalcemia. These derangements in mineral metabolism stimulate PTH production to raise serum calcium and promote phosphorus excretion. Increased serum PTH leads to excessive bone resorption through stimulation of osteoblasts and osteoclasts. The combination of secondary hyperparathyroidism and mineralization defects (osteomalacia) represents the most common form of renal osteodystrophy (ROD). In contrast, a subtype of ROD known as adynamic bone disease can be observed in the setting of prolonged peritoneal or hemodialysis, oversuppression of PTH with calcitriol or calciumbased phosphate binders, or the use of bisphosphonates for osteoporosis treatment (1 ). ABD is characterized by marked suppression of bone remodeling that leads to fracture. Common biochemical hallmarks of ABD include hypercalcemia, low or inappropriately normal PTH concentrations, and reduced markers of bone turnover (e.g., alkaline phosphatase) (2 ).In this case, the increased intact PTH result from the reference laboratory (786 ng/L) was more consistent with the patient's clinical picture, suggesting that the 48 ng/L value obtained in our clinical laboratory was falsely low. The magnitude of the difference between the 2 results suggested an assay interference as opposed to method differences or specificities (3 ), and therefore the following studies were performed. Dilution studies confirmed the presence of a negative interference, since PTH concentrations were higher in the diluted samples than in the undiluted sample (undiluted, 48 ng/L; diluted 1:20, 567 ng/L). Treatment with heterophilic blocking reagent (Scantibodies Laboratory) had no effect (intact PTH posttreatment 68 ng/L), suggesting that heterophile antibodies...

False biochemical diagnosis of hyperthyroidism in streptavidin-biotin-based immunoassays: the problem of biotin intake and related interferences

“…In a case of end-stage renal failure, the PTH erroneous result remained and lasted up to 15 days after withdrawal of a treatment with 10 mg biotin [5].…”

“…Measurement of serum free biotin concentration was performed in one case, using a microbial growth assay: the free biotin was assayed in a patient receiving 10 mg biotin, suffering from end-stage renal disease [5]. The free biotin concentration measured was 4.8 µg/L, i.e.…”

“…This may seem surprising as, according to the reagent notice, no artifact should occur up to 205 nmol/L of serum biotin concentration (see Table 2, Roche PTH assay). This might be related to metabolites (such as bisnorbiotin, biotin sulfoxide [10]) and/ or in vivo biotinylated compounds, that may also participate in the artifact [5]. As a matter of fact, it is known that biotin derivatives may bind to avidin, although less tightly [10].…”

“…As a matter of fact, it is known that biotin derivatives may bind to avidin, although less tightly [10]. Therefore assay of serum free biotin may not be a contributing element to evaluate the extent of an error [5]. For the same reason, in vitro spiking experiments with free biotin might fail to reproduce the magnitude of the artifact observed in patients treated with biotin.…”

“…This is related to the two different assay formats in use in immunoassays, in which inhibition of immune complexes separation, whatever the cause, will lead to opposite erroneous results. This opposite impact may mimic an endogenous endocrine pathological condition, and lead to a seemingly consistent biochemical diagnosis of hyperthyroidism [1][2][3], as well as vitamin D intoxication [4], or parathyroid hormone (PTH) suppression [5]. Some new therapeutic protocols involving high doses of biotin (300 mg) in neurology have very recently attracted our attention to this problem [1][2][3]6].…”