In Focus
Vitamin D testing should not be done by routine screening but should be used only in people with clear signs of deficiency, or who are at risk for deficiency, for whom treatment is likely to be of benefit, according to a position statement from the Royal College of Pathologists of Australasia. The statement recommends that vitamin D should be measured as 25-hydroxyvitamin D (25OH-D) and argues that an assay that measures only 25OH-D3 is sufficient for use in Australia and New Zealand. Patients should be monitored by the same laboratory after treatment because vitamin D assays vary. After reviewing available scientific literature, a working party from the College advised against routine screening for vitamin D deficiency in adults (including pregnant women), healthy infants, and children. “As the main source of vitamin D is UVB sunlight exposure, vitamin D levels are correlated with time spent outdoors, exercise, and other aspects of a healthy
lifestyle including bodyweight”, says Professor Yee Khong, President of the College. The working group believes that testing healthy individuals would identify a substantial subgroup of patients with low 25OH-D concentrations, who would then be given treatment and repeat testing, without evidence that they would benefit from vitamin D supplementation. Khong warns, “The quality of evidence for health benefits of an adequate vitamin D status is highly variable and trials to improve this evidence are underway”. William Fraser (University of East Anglia, Norwich, UK), believes that the statement is useful, but he cautions that it is based on the situation in Australia and New Zealand. “Some of the broad statements made would not be applicable in other countries throughout the world. The recent guideline published by the National Osteoporosis Society is much more applicable in the UK and other
countries where vitamin D2 is present in the food chain, is freely available as a supplement, or is used as a prescribed medication.” The Australasian group suggests that the target concentration for serum 25OH-D should be greater than 50 nmol/L at the end of winter. Serum 25OH-D concentrations should be retested no earlier than 3 months after commencement of supplementation with vitamin D. Once a desirable target has been achieved, no further testing is needed unless risk factors change. Fraser questions the recommendation to measure only 25OH-D3 when the statement notes that D2 supplementation could be being used by some individuals tested. “It is a relatively short time since Australia moved from prescribing D2 supplementation to D3 supplementation, and I am left wondering if D2 is totally absent from the food and supplement chain.”
Nick Dolding
Targeted vitamin D testing recommended in Australasia
Published Online June 13, 2013 http://dx.doi.org/10.1016/ S2213-8587(13)70037-8 For the position statement from the Royal College of Pathologists of Australasia see http://www.rcpa.edu.au/static/ file/Asset%20library/public%20 documents/Policy%20Manual/ Position%20Statements/ Use%20and%20 Interpretation%20of%20 Vitamin%20D%20Testing.pdf For the National Osteoporosis Society vitamin D guidelines see http://www.nos.org.uk/ document.doc?id=1352
Susan Mayor
MKRN3 and central precocious puberty New research shows that mutations in MKRN3 can lead to central precocious puberty. Ana Paula Abreu and colleagues used wholeexome sequencing to analyse genes from 40 members (32 with central precocious puberty and eight with normal timing of puberty) of 15 families. They identified four novel heterozygous mutations (frameshift and missense) in MKRN3 in five of the 15 families. Suzy Bianco (University of Miami, Miami, FL, USA) says that the findings are exciting because MKRN3 has not been linked to reproductive disorders before. She believes that the finding that the mutations were present equally in both sexes is particularly important. “The unexpected lack of sexual dimorphism in the incidence of
central precocious puberty associated with MKRN3 mutations is an especially important detail. After eliminating those with mutations in MKRN3, familial central precocious puberty exclusively affected girls, which points to an extreme sexual dimorphism of this disorder when MKRN3 mutations are not involved.” Lourdes Ibáñez (Hospital Sant Joan de Déu, Barcelona, Spain) is cautious about the results: “The investigators recommend screening for MKRN3 mutations in sporadic cases of central precocious puberty to add information on the role of this gene in pubertal timing. This recommendation may be helpful provided that the screening is performed in homogeneous populations that are prospectively followed up until completion of
www.thelancet.com/diabetes-endocrinology August 2013
puberty. Ideally, this endeavour should also take into account environmental factors that potentially modify the timing of puberty. However, screening for MKRN3 mutations for diagnostic purposes in clinical practice does not seem advisable.” Other genes might also have a role in the onset of precocious puberty. Maurizio Genuardi (University of Florence, Florence, Italy) explains why: “Despite the frequent inactivation of MKRN3 in patients with Prader-Willi syndrome, premature puberty occurs only occasionally. Hence, it seems that inactivation of other genes in the Prader-Willi syndrome critical region prevents the appearance of precocious puberty in Prader-Willi syndrome.”
Published Online June 13, 2013 http://dx.doi.org/10.1016/ S2213-8587(13)70041-X For Ana Paula Abreu and colleagues’ report see N Engl J Med 2013; published online June 5. DOI:10.1056/ NEJMoa1302160
Farhat Yaqub s15
Vitamin D testing should not be done by routine screening but should be used only in people with clear signs of deficiency, or who are at risk for deficiency, for whom treatment is likely to be of benefit, according to a position statement from the Royal College of Pathologists of Australasia. The statement recommends that vitamin D should be measured as 25-hydroxyvitamin D (25OH-D) and argues that an assay that measures only 25OH-D3 is sufficient for use in Australia and New Zealand. Patients should be monitored by the same laboratory after treatment because vitamin D assays vary. After reviewing available scientific literature, a working party from the College advised against routine screening for vitamin D deficiency in adults (including pregnant women), healthy infants, and children. “As the main source of vitamin D is UVB sunlight exposure, vitamin D levels are correlated with time spent outdoors, exercise, and other aspects of a healthy
lifestyle including bodyweight”, says Professor Yee Khong, President of the College. The working group believes that testing healthy individuals would identify a substantial subgroup of patients with low 25OH-D concentrations, who would then be given treatment and repeat testing, without evidence that they would benefit from vitamin D supplementation. Khong warns, “The quality of evidence for health benefits of an adequate vitamin D status is highly variable and trials to improve this evidence are underway”. William Fraser (University of East Anglia, Norwich, UK), believes that the statement is useful, but he cautions that it is based on the situation in Australia and New Zealand. “Some of the broad statements made would not be applicable in other countries throughout the world. The recent guideline published by the National Osteoporosis Society is much more applicable in the UK and other
countries where vitamin D2 is present in the food chain, is freely available as a supplement, or is used as a prescribed medication.” The Australasian group suggests that the target concentration for serum 25OH-D should be greater than 50 nmol/L at the end of winter. Serum 25OH-D concentrations should be retested no earlier than 3 months after commencement of supplementation with vitamin D. Once a desirable target has been achieved, no further testing is needed unless risk factors change. Fraser questions the recommendation to measure only 25OH-D3 when the statement notes that D2 supplementation could be being used by some individuals tested. “It is a relatively short time since Australia moved from prescribing D2 supplementation to D3 supplementation, and I am left wondering if D2 is totally absent from the food and supplement chain.”
Nick Dolding
Targeted vitamin D testing recommended in Australasia
Published Online June 13, 2013 http://dx.doi.org/10.1016/ S2213-8587(13)70037-8 For the position statement from the Royal College of Pathologists of Australasia see http://www.rcpa.edu.au/static/ file/Asset%20library/public%20 documents/Policy%20Manual/ Position%20Statements/ Use%20and%20 Interpretation%20of%20 Vitamin%20D%20Testing.pdf For the National Osteoporosis Society vitamin D guidelines see http://www.nos.org.uk/ document.doc?id=1352
Susan Mayor
MKRN3 and central precocious puberty New research shows that mutations in MKRN3 can lead to central precocious puberty. Ana Paula Abreu and colleagues used wholeexome sequencing to analyse genes from 40 members (32 with central precocious puberty and eight with normal timing of puberty) of 15 families. They identified four novel heterozygous mutations (frameshift and missense) in MKRN3 in five of the 15 families. Suzy Bianco (University of Miami, Miami, FL, USA) says that the findings are exciting because MKRN3 has not been linked to reproductive disorders before. She believes that the finding that the mutations were present equally in both sexes is particularly important. “The unexpected lack of sexual dimorphism in the incidence of
central precocious puberty associated with MKRN3 mutations is an especially important detail. After eliminating those with mutations in MKRN3, familial central precocious puberty exclusively affected girls, which points to an extreme sexual dimorphism of this disorder when MKRN3 mutations are not involved.” Lourdes Ibáñez (Hospital Sant Joan de Déu, Barcelona, Spain) is cautious about the results: “The investigators recommend screening for MKRN3 mutations in sporadic cases of central precocious puberty to add information on the role of this gene in pubertal timing. This recommendation may be helpful provided that the screening is performed in homogeneous populations that are prospectively followed up until completion of
www.thelancet.com/diabetes-endocrinology August 2013
puberty. Ideally, this endeavour should also take into account environmental factors that potentially modify the timing of puberty. However, screening for MKRN3 mutations for diagnostic purposes in clinical practice does not seem advisable.” Other genes might also have a role in the onset of precocious puberty. Maurizio Genuardi (University of Florence, Florence, Italy) explains why: “Despite the frequent inactivation of MKRN3 in patients with Prader-Willi syndrome, premature puberty occurs only occasionally. Hence, it seems that inactivation of other genes in the Prader-Willi syndrome critical region prevents the appearance of precocious puberty in Prader-Willi syndrome.”
Published Online June 13, 2013 http://dx.doi.org/10.1016/ S2213-8587(13)70041-X For Ana Paula Abreu and colleagues’ report see N Engl J Med 2013; published online June 5. DOI:10.1056/ NEJMoa1302160
Farhat Yaqub s15
