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We enjoyed this thought-provoking article regarding the importance of
early recognition and investigation for acromegaly [1]. We wish to
highlight potential pitfalls in the biochemical screening for this
condition. It is stated that "Random growth hormone levels below 0.4 ug/l,
and normal IGF-1 values matched for age and gender effectively exclude the
diagnosis" [1].
Growth hormone is secreted in a pulsatile manner with serum
concentrations varying between 10 to 40-fold in healthy individuals during
the day [2]. Growth hormone is a heterogenous molecule being present in
the serum in monomeric, dimeric and oligomeric forms, which contributes to
a significant analytical variability due to variable detection of these
forms by routine immunoassay measurement. Indeed, as judged by external
quality assurance data there is a 60% difference in growth hormone
concentrations between laboratories depending on the analytical method
used [3,4].
The cut-off concentration of random growth hormone of <0.4 ug/l
was determined by a consensus group [5] but has attracted a lot of
criticism [6,7]. Due to the analytical variability and lack of assay
standardisation of growth hormone assays a cut-off value of 0.4 ug/l could
be potentially misleading[7,8]. Many methods can not even reliably measure
concentrations of 0.4 ug/l which have lead to the recommendation of assay
specific cut points [4].
In addition, this is a relatively costly test (12 pounds per test at
our laboratory) and together with its very limited diagnostic utility, we
agree with others in not recommending the use of a random growth hormone
test to screen for acromegaly.
Claire L Meek, Ben Jones, Adie Viljoen.
Corresponding author: Dr Claire Meek, claire.meek@nhs.net
2: Klerman EB, Adler GK, Jin M, Maliszewski AM, Brown EN. A
statistical model of diurnal variation in human growth hormone. Am J
Physiol Endocrinol Metab 2003; 285: E1118-E1126.
2: Wood P. Growth hormone: its measurement and the need for
standardisation. Ann Clin Biochem 2001; 38: 471-482.
3: Markkanen H, Pekkarinen T, Valimaki M.J, Alfthan H, Kauppinen-
Makelin R, Sane T, Stenman U. Effect of Sex and Assay Method on Serum
Concentrations of Growth Hormone in Patients with Acromegaly and in
Healthy Controls. Clinical Chemistry 2006; 52:3; 468-473.
4: Giustina A, Barkan A, Casanueva FF, Cavagnini F, Frohman L, Ho K,
et al. Criteria for cure of acromegaly: a consensus statement. J Clin
Endocrinol Metab 2000;85:526-9.
5: Trainer P. J. Acromegaly--Consensus, What Consensus? J. Clin.
Endocrinol. Metab. 2002; 87: 3534-3536.
6: Wieringa GE & Trainer PJ. Commentary: harmonizing growth
hormone measurements: learning lessons for the future. Journal of Clinical
Endocrinology and Metabolism 2007; 92:2874-2875.
7: Bidlingmaier M. Problems with GH assays and strategies toward
standardization. Eur J Endocrinol. 2008; 159 Suppl 1:S41-4
Competing interests:
Dr Viljoen and Dr Meek have had contact with organisations relevant to the treatment of hypercholesterolaemia and diabetes mellitus, including AstraZeneca, Novo Nordisk, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, Bristol-Myers Squibb, Merck-Sharp & Dohme, Sanofi-Aventis and Takeda pharmaceuticals.Dr Jones has no conflict of interest to declare.
Pitfalls in Biochemical Screening for Acromegaly
We enjoyed this thought-provoking article regarding the importance of
early recognition and investigation for acromegaly [1]. We wish to
highlight potential pitfalls in the biochemical screening for this
condition. It is stated that "Random growth hormone levels below 0.4 ug/l,
and normal IGF-1 values matched for age and gender effectively exclude the
diagnosis" [1].
Growth hormone is secreted in a pulsatile manner with serum
concentrations varying between 10 to 40-fold in healthy individuals during
the day [2]. Growth hormone is a heterogenous molecule being present in
the serum in monomeric, dimeric and oligomeric forms, which contributes to
a significant analytical variability due to variable detection of these
forms by routine immunoassay measurement. Indeed, as judged by external
quality assurance data there is a 60% difference in growth hormone
concentrations between laboratories depending on the analytical method
used [3,4].
The cut-off concentration of random growth hormone of <0.4 ug/l
was determined by a consensus group [5] but has attracted a lot of
criticism [6,7]. Due to the analytical variability and lack of assay
standardisation of growth hormone assays a cut-off value of 0.4 ug/l could
be potentially misleading[7,8]. Many methods can not even reliably measure
concentrations of 0.4 ug/l which have lead to the recommendation of assay
specific cut points [4].
In addition, this is a relatively costly test (12 pounds per test at
our laboratory) and together with its very limited diagnostic utility, we
agree with others in not recommending the use of a random growth hormone
test to screen for acromegaly.
Claire L Meek, Ben Jones, Adie Viljoen.
Corresponding author: Dr Claire Meek, claire.meek@nhs.net
References
1: Reddy R, Hope S, Wass J. Easily Missed? Acromegaly. BMJ 2010; 341:
c4189.
2: Klerman EB, Adler GK, Jin M, Maliszewski AM, Brown EN. A
statistical model of diurnal variation in human growth hormone. Am J
Physiol Endocrinol Metab 2003; 285: E1118-E1126.
2: Wood P. Growth hormone: its measurement and the need for
standardisation. Ann Clin Biochem 2001; 38: 471-482.
3: Markkanen H, Pekkarinen T, Valimaki M.J, Alfthan H, Kauppinen-
Makelin R, Sane T, Stenman U. Effect of Sex and Assay Method on Serum
Concentrations of Growth Hormone in Patients with Acromegaly and in
Healthy Controls. Clinical Chemistry 2006; 52:3; 468-473.
4: Giustina A, Barkan A, Casanueva FF, Cavagnini F, Frohman L, Ho K,
et al. Criteria for cure of acromegaly: a consensus statement. J Clin
Endocrinol Metab 2000;85:526-9.
5: Trainer P. J. Acromegaly--Consensus, What Consensus? J. Clin.
Endocrinol. Metab. 2002; 87: 3534-3536.
6: Wieringa GE & Trainer PJ. Commentary: harmonizing growth
hormone measurements: learning lessons for the future. Journal of Clinical
Endocrinology and Metabolism 2007; 92:2874-2875.
7: Bidlingmaier M. Problems with GH assays and strategies toward
standardization. Eur J Endocrinol. 2008; 159 Suppl 1:S41-4
Competing interests: Dr Viljoen and Dr Meek have had contact with organisations relevant to the treatment of hypercholesterolaemia and diabetes mellitus, including AstraZeneca, Novo Nordisk, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, Bristol-Myers Squibb, Merck-Sharp & Dohme, Sanofi-Aventis and Takeda pharmaceuticals.Dr Jones has no conflict of interest to declare.