contraversies in totalvitamindassay
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Transcript of contraversies in totalvitamindassay
Controversies in total vitamin D assay
ByDr salwa .E. Al-Ansari
Clinical Biochemistry departmentj.a. armed forces hospital
Ministry of defenseKuwait.
vitamin D Fat soluble vitaminMajor two forms :1. D3 - 25 (OH) D3 (liver)- 1,25 (OH) D3 (kidney) , active form - 1.25(OH) T1/2 < 25 (OH)
2. D2 synthesized in plants.
Vitamin D roles1. Bone health Osteoporosis Rickets Muscle weakness
2. Protective role (New!) Cancers CVD Renal diseases Autoimmune DM MS
Sources:
1. Diet:- D2 Plant- D3 Animal
2. Sun :e.g. : In Boston, from April to October at 12 PM EST an individual with type III skin, with 25.5% of the body surface area exposed, would need to spend 3 to 8 minutes in the sun to synthesize 400 IU of vitamin D.
Frank Vt.D deficiencySerum levels < 10 ng/ml or 25 nmol/l
Vt.D insufficiency Serum levels 10-30 ng/ml or < 25-75 nmol/l
Previous laws
WHO Below 10 ng /ml : deficiency Below 20 ng /ml : insufficiency
Research:Depending on the range : 30 -76 ng/ml ↑ prevalence of vt.D insufficiency
New Laws
2007 International workshop on vt.D : min. range 20 ng/ml.
2010 International osteoporosis federation :< 30 ng /ml insufficiency.
Endocrine society: vt.D deficiency < 50 nmol/l .
US institute of medicine normal range ≥ 50 nmol/l
Reference Laboratories raised lower boundaries. 75-250 nmol/l.
Certain studies ; 30 ng / ml optimum : below↑ PTH : active Ca resorption.
Criticism:
PTH & vt. D not curve linear .
PTH variation when vt. D 20-30 ng / ml
No absolute threshold level.
One study (old women): risk of hip fracture not ↑ by high dose vt.D
Switzerland study: women vt.D <20 ng/ ml not related to ↑ risk fracture (5 years follow up).
No large randomized controlled trials : vt D supplements → ↓ chronic diseases other than osteoporosis.
Storage & re-entry into circulation is poorly understood.
Optimum dosage of vt.D :↑100IU → ↑ 3 nmol/l
Observational studies:↑vt.D levels < 150 nmol/l associated with pancreatic cancer.
Vt.D supplements studies : protective role depends on dose and stage of life to be given .
Vitamin D assayMost assays for 25(OH)D cannot differentiate the two distinct forms, 25(OH) D2 from 25(OH) D3, so the abbreviation 25(OH)D is used.
Types of assays:HPLC-Chromatography RIAImmunoassay
Main Issue:
Reference laboratories ↑ demands for test by 50 % in 2009 than 2008 ???
Problems:
- Laboratories raised lower boundaries.
- Several assay : accuracy & precision problems.
-[vt. D] changes / seasons, exposure, to sun light & dietary intake
-Vt. D molecule lipophilic in nature →↑Matrix factors effect → ↓ validity of the assay.
J . A. Armed Forces Hospital
2006-2007 : Cobas 25(OH) vit.D assay
Most samples Low results
lowest levels : 0 ng/ml
Unstable readings for patients on tablets.
Good results ~ 100 ng/ml for patients on injections.
New generation of the assay : total Vt.D
Total vitamin D results from randomly selected 243 patients attending J.A. armed forces hospital using method LIAISON, diaSorin.
We compared vt.D assay for samples at our hospital (LIAISON, diaSorin: chemiluminescent immunoassay technology) and ROCHE, COBAS 6000 from Ministry of Health hospital).
Both instruments are using chemileuscence technology.
We studied the link between total vt. D, serum calcium, parathyroid hormone, glucose and hba1c
A 39 healthy volunteers to establish laboratory reference range.
Patients' age 26-50 years old. Samples withdrawn in foil covered plain tube. Results analyzed using SPSS .
Results:Vt.D nmol/l
Calcium mmol/l
PTH pmol/l
glucose mmol/l
Hba1c %
median 22.3 2.3 26.4 5.4 7.1
25 % I.Q.R 19.03 2.2 17.8 5 6.2
75% I.Q.R 58.1 2.4 60.8 6.5 9.1
Calculated volunteers reference range (26.7- 90 nmol/l).
No relation was found between vt.D & ca (P = 0.9), PTH (P = 0.4), Glucose (P = 0.6) or hba1c (P = 0.2) Spearman’s correlation.
ConclusionMeasurement of total vt.D provides crude assessment of its status but may give inaccurate indication of its biological activity.
Most people have Vt.D levels < 75 nmol/l as consequence of sedentary and largely indoor life style.
Notes
Although it may be tempting to recommend intentional sun exposure based on our findings, it is difficult, if not impossible to titrate one’s exposure. There are well-known detrimental side effects of ultraviolet irradiation. Therefore, oral supplementation remains the safest way for increasing vitamin D status.
( J Am Acad Dermatol 2010;62:929.e1-e9.)
Low vitamin D levels
Dark Skin Obese Poor Dietary intake Malabsorbtion Poor Exposure to sunlight Drugs… Phynetoin, steroids
Clues:
Cancer risk reduced by vitamin D and sunbathing.
Multiple sclerosis linked to long winters.
Sunshine vitamin prevents early diabetes.
Heart disease epidemic in sun-starved Britons.
Vt.D dose
Adults over 50 years of age who are at moderate
risk for vitamin D deficiency. Supplementation
with at least 20–25 μg (800–1000 IU) of vitamin
D3 daily is recommended. To achieve optimal
vitamin D status (> 75 nmol/L), many individuals
may require supplementation at greater than 25
μg (1000 IU) daily
Treatment of severe deficiency (rickets or
osteomalacia) requires higher doses, e.g.,
1250 μg (50 000 IU) daily for two to four
weeks, then weekly or biweekly, with
monitoring of serum 25-hydroxyvitamin D at
one and three months.