Dr. Ron’s Research Review – April 29, 2015

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This week’s research review focuses on cobalt.

All hip implant devices with metal components used in the USA contain cobalt alloys, which may cause prosthetic hip-associated cobalt toxicity (PHACT). Signs or symptoms appeared between 3 and 72 months after arthroplasty. Hearing and cognitive impairment were the most frequently reported symptoms, occurring in at least half of the cases. Other commonly reported symptoms included paresthesias, visual impairment, headache, dysgeusia (metallic taste), dyspnea, rash or nail changes, fatigue, and weight loss. (Devlin et al., 2013)

A cross-sectional study was conducted among school children in Kerman, Iran. After the screening phase, 170 students (130 goitrous and 40 nongoitrous) were randomly selected. The serum cobalt levels were lower in goitrous subjects than in nongoitrous subjects (4.4+/-2.9 vs. 6.4+/-2.7 microg/L). The urinary iodine levels were also lower in goitrous subjects than in nongoitrous subjects (198.3+/-108.3 vs. 270.2+/-91.1 microg/L). Cobalt deficiency significantly contributed to the presence of goiter (odds ratio, 0.78; 95% CI, 0.61 to 0.99; P=0.042). Cobalt deficiency may be an important independent predicator for goiter in endemic regions, especially areas in which goiters persist despite salt iodization programs. (Sanjari et al., 2014)

A study assessed 10 adults who voluntarily ingested approximately 1.0 mg Co/day over a 3-mont period. Peak cobalt whole blood concentrations ranging between 9.4 and 117 mug/L were not associated with clinically significant changes in basic hematologic and clinical variables. (Tvermoes et al., 2014)

Dr. Ron


 

Articles

Clinical features, testing, and management of patients with suspected prosthetic hip-associated cobalt toxicity: a systematic review of cases.
            (Devlin et al., 2013) Download
Safety concerns regarding cobalt-containing metal alloy hip prosthetics (Co-HP) have resulted in product recalls, a medical device alert, and issuance of guidance for clinicians. Recently, cases of suspected prosthetic hip-associated cobalt toxicity (PHACT) from Co-HP have been reported. Although little is known about suspected PHACT, these patients may be referred to medical toxicologists for evaluation and management recommendations. We searched MEDLINE, EMBASE, and unpublished abstracts from toxicology scientific meetings for references relevant to PHACT. Authors independently screened publications for inclusion criteria: publication in English, human study population, subject(s) are symptomatic (except for isolated hip pain), and cobalt values in any matrix (blood, serum, urine, CSF, synovial fluid) available for review. Data from 10 cases are reviewed. Patients with suspected PHACT had findings consistent with cobalt toxicity, including thyroid, cardiac, and neurologic dysfunction. Signs and symptoms appeared between 3 and 72 months after arthroplasty (median 19 months). Neurologic symptoms were most common. Ancillary testing varied considerably. All patients had elevated cobalt levels in one or more matrices. Enhanced elimination was attempted in 27 % of patients. At this time, the information currently available regarding patients with suspected PHACT is inadequate to guide clinical decision making. No consensus has been reached regarding the management of Co-HP patients with systemic symptoms. Indications for chelation have not been established and require further study. Improved case definitions, improved surveillance, and controlled studies are needed to elucidate the scope of this problem and guide future investigations.

The Association between Cobalt Deficiency and Endemic Goiter in School-Aged Children.
            (Sanjari et al., 2014) Download
BACKGROUND: In Iran, an iodine deficiency control program was initiated in 1989 by iodizing salt. Despite this program, goiters have remained an endemic condition in most parts of Iran. Thus, it is possible that other factors aside from iodine deficiency may contribute to endemic goiter. The aim of this study was to investigate the association between cobalt deficiency and endemic goiter in a region of Iran with a high prevalence of goiter. METHODS: A cross-sectional study was conducted among school children aged 9 to 11 years in the city of Kerman, Iran. In the first phase of the study, a multistage, proportional-to-size, cluster sampling method was used to screen 5,380 out of 29,787 students. After the screening phase, 170 students (130 goitrous and 40 nongoitrous) were randomly selected, and serum and urine specimens were obtained. We measured thyroid function, serum cobalt level, and urinary iodine excretion. Univariate and multiple logistic regression analyses were performed. RESULTS: The prevalence of grade 2 goiters was 34.8% (95% confidence interval [CI], 31.5 to 42.5), with both sexes being equally affected. The weight and body mass index of goitrous subjects was significantly lower (P<0.001) than those of nongoitrous subjects. The serum cobalt levels were lower in goitrous subjects than in nongoitrous subjects (4.4+/-2.9 microg/L vs. 6.4+/-2.7 microg/L). The urinary iodine levels were also lower in goitrous subjects than in nongoitrous subjects (198.3+/-108.3 microg/L vs. 270.2+/-91.1 microg/L). Multiple regression analysis showed that only cobalt deficiency, not iodine deficiency, significantly contributed to the presence of goiter (odds ratio, 0.78; 95% CI, 0.61 to 0.99; P=0.042). CONCLUSION: Cobalt deficiency may be an important independent predicator for goiter in endemic regions, especially areas in which goiters persist despite salt iodization programs.

Effects and blood concentrations of cobalt after ingestion of 1 mg/d by human volunteers for 90 d.
            (Tvermoes et al., 2014) Download
BACKGROUND: Over-the-counter cobalt supplements are available for sale in the United States, but little is known regarding their clinical effects and biokinetic distribution with long-term use. OBJECTIVE: We assessed blood kinetics, biochemical responses, and clinical effects in 5 adult men and 5 adult women who voluntarily ingested approximately 1.0 mg Co/d (0.080-0.19 mg Co . kg(-)(1) . d(-)(1)) of a commercially available cobalt supplement over a 3-mo period. DESIGN: Volunteers were instructed to take the cobalt dietary supplement in the morning according to the manufacturer's label. Blood samples were collected and analyzed for a number of biochemical variables before, during, and after dosing. Hearing, vision, cardiac, and neurologic functions were also assessed in volunteers before, during, and after dosing. RESULTS: After approximately 90 d of dosing, mean cobalt blood concentrations were lower in men than in women. Mean cobalt whole blood and serum concentrations in men were 20 mug/L (range: 12-33 mug/L) and 25 mug/L (range: 15-46 mug/L), respectively. In women, mean cobalt whole blood and serum concentrations were 53 mug/L (range: 6-117 mug/L) and 71 mug/L (range: 9-149 mug/L), respectively. Estimated red blood cell (RBC) cobalt concentrations suggested that cobalt was sequestered in RBCs during their 120-d life span, which resulted in a slower whole blood clearance compared with serum. The renal clearance of cobalt increased with the serum concentration and was, on average, lower in women (3.5 +/- 1.3 mL/min) than in men (5.5 +/- 1.9 mL/min). Sex-specific differences were observed in cobalt absorption and excretion. There were no clinically significant changes in biochemical, hematologic, and clinical variables assessed in this study. CONCLUSION: Peak cobalt whole blood concentrations ranging between 9.4 and 117 mug/L were not associated with clinically significant changes in basic hematologic and clinical variables.

 

References

Devlin, JJ, et al. (2013), ‘Clinical features, testing, and management of patients with suspected prosthetic hip-associated cobalt toxicity: a systematic review of cases.’, J Med Toxicol, 9 (4), 405-15. PubMedID: 24222555
Sanjari, M, A Gholamhoseinian, and A Nakhaee (2014), ‘The Association between Cobalt Deficiency and Endemic Goiter in School-Aged Children.’, Endocrinol Metab (Seoul), 29 (3), 307-11. PubMedID: 25309789
Tvermoes, BE, et al. (2014), ‘Effects and blood concentrations of cobalt after ingestion of 1 mg/d by human volunteers for 90 d.’, Am J Clin Nutr, 99 (3), 632-46. PubMedID: 24500148