Home Therapy monitoring in congenital adrenal hyperplasia by dried blood samples
Article
Licensed
Unlicensed Requires Authentication

Therapy monitoring in congenital adrenal hyperplasia by dried blood samples

  • Isabelle Wieacker , Michael Peter , Katrin Borucki , Susann Empting , Friedrich-Wilhelm Roehl and Klaus Mohnike EMAIL logo
Published/Copyright: March 7, 2015

Abstract

Careful monitoring of the therapy is crucial for patients with congenital adrenal hyperplasia (CAH) in order to prevent the effects of increased androgen production as well as life-threatening salt-wasting crisis. The key metabolite, 17α-hydroxyprogesterone (17-OHP) can be detected in serum, saliva or dried blood. In clinical practice there are challenges due to discomfort of venous blood sampling and complicated retrieval of saliva during infancy. Furthermore, the immunoassay method is limited in its specificity due to cross-reactions. In this observational study we prospectively examined over a period of 5 years, 20 patients with CAH due to 21-hydroxylase deficiency using standard immunoassays for serum samples (radioimmunoassay and enzyme immunoassay) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in dried blood spots. Bland-Altman plots show goodness of agreement between both the methods for the desirable therapeutic concentration range of 17-OHP. LC-MS/MS is characterized by a high accuracy in the therapeutic concentration range of 17-OHP <100 nmol/L (r=0.91). Dried blood samples are convenient and reliable specimen for 17-OHP measured by LC-MS/MS. This method could be used for home monitoring of hydrocortisone replacement therapy both in salt-waster and simple virilizer CAH.


Corresponding author: Klaus Mohnike, Department of Paediatrics, Otto-von-Guericke-University Magdeburg 39120, Magdeburg, Germany, E-mail:

References

1. Speiser PW, White PC. Congenital adrenal hyperplasia. N Engl J Med 2003;349:776–88.10.1056/NEJMra021561Search in Google Scholar

2. Orth DN, Kovacs WJ. Congenital adrenal hyperplasia. In: Wilson JD, Foster DW, Kronenberg HM, Larsen PR, editors. Williams textbook of endocrinology, 9th ed. Philadelphia: W. B. Saunders Company, 1998:598–605.Search in Google Scholar

3. Merke DP. Approach to the adult with congenital adrenal hyperplasia due the 21-hydroxylase deficiency. J Clin Endocrinol Metab 2008;93:653–60.10.1210/jc.2007-2417Search in Google Scholar

4. Bonfig W, Pozza SB, Schmidt H, Pagel P, Knorr D, et al. Hydrocortisone dosing during puberty in patients with classical congenital adrenal hyperplasia: an evidence-based recommendation. J Clin Endocrinol Metab 2009;94:3882–8.10.1210/jc.2009-0942Search in Google Scholar

5. Trakakis E, Basios G, Trompoukis P, Labos G, Grammatikakis I, et al. An update to 21-hydroxylase deficient congenital adrenal hyperplasia. Gynecol Endocrinol 2010;26:63–71.10.3109/09513590903015494Search in Google Scholar

6. Antal Z, Zhou P. Congenital adrenal hyperplasia: diagnosis, evaluation, and management. Pediatr Rev 2009;30:49–57.10.1542/pir.30.7.e49Search in Google Scholar

7. Hindmarsh PC. Management of the child with congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab 2009;23:193–208.10.1016/j.beem.2008.10.010Search in Google Scholar

8. New MI, Levine LS. Recent advances in 21-hydroxylase deficiency. Annu Rev Med 1984;35:649–63.10.1146/annurev.me.35.020184.003245Search in Google Scholar

9. Young MC, Robinson JA, Read GF, Riad-Fahmy D, Hughes IA. 170H-progesterone rhythms in congenital adrenal hyperplasia. Arch Dis Child 1988;63:617–23.10.1136/adc.63.6.617Search in Google Scholar

10. Sólyom J. Blood-spot 17 alpha-hydroxyprogesterone radioimmunoassay in the follow-up of congenital adrenal hyperplasia. Clin Endocrinol (Oxf) 1981;14:547–53.10.1111/j.1365-2265.1981.tb02964.xSearch in Google Scholar

11. Riordan FA, Wood PJ, Wakelin K, Betts P, Clayton BE. Bloodspot 17 alpha-hydroxyprogesterone radioimmunoassay for diagnosis of congenital adrenal hyperplasia and home monitoring of corticosteroid replacement therapy. Lancet 1984;323:708–11.10.1016/S0140-6736(84)92223-2Search in Google Scholar

12. Minutti CZ, Lacey JM, Magera MJ, Hahn SH, McCann M, et al. Steroid profiling by tandem mass spectrometry improves the positive predictive value of newborn screening for congenital adrenal hyperplasia. J Clin Endocrinol Metab 2004;89:3687–93.10.1210/jc.2003-032235Search in Google Scholar

13. Janzen N, Peter M, Sander S, Steuerwald U, Terhardt M, et al. Newborn screening for congenital adrenal hyperplasia: additional steroid profile using liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab 2007;92:2581–9.10.1210/jc.2006-2890Search in Google Scholar

14. Bland JM, Altman DG. Measuring agreement in method comparison studies. Stat Med Res 1999;8:135–60.10.1177/096228029900800204Search in Google Scholar

15. Robinson JA, Dyas J, Hughes IA, Riad-Fahmy D. Radioimmunoassay of blood-spot 17 alpha-hydroxyprogesterone in the management of congenital adrenal hyperplasia. Ann Clin Biochem 1987;24:58–65.10.1177/000456328702400109Search in Google Scholar

16. Shimon I, Kaiserman I, Sack J. Home monitoring of 17 alpha-hydroxyprogesterone levels by filter paper blood spots in patients with 21-hydroxylase deficiency. Horm Res 1995;44:247–52.10.1159/000184636Search in Google Scholar

17. Bode HH, Rivkees SA, Cowley DM, Pardy K, Johnson S. Home monitoring of 17 hydroxyprogesterone levels in congenital adrenal hyperplasia with filter paper blood samples. J Pediatr 1999;134:185–9.10.1016/S0022-3476(99)70413-0Search in Google Scholar

18. Sarafoglou K, Himes JH, Lacey JM, Netzel BC, Singh RJ, et al. Comparison of multiple steroid concentrations in serum and dried blood spots throughout the day of patients with congenital adrenal hyperplasia. Horm Res Paediatr 2011;75:19–25.10.1159/000315910Search in Google Scholar PubMed PubMed Central

19. Shibayama Y, Higashi T, Shimada K, Kashimada K, Onishi T, et al. Liquid chromatography-tandem mass spectrometric method for determination of salivary 17alpha-hydroxyprogesterone: a noninvasive tool for evaluating efficacy of hormone replacement therapy in congenital adrenal hyperplasia. J Chromatogr B Analyt Technol Biomed Life Sci 2008;867:49–56.10.1016/j.jchromb.2008.03.009Search in Google Scholar PubMed

20. Hughes IA, Dyas J, Robinson J, Walker RF, Fahmy DR. Monitoring treatment in congenital adrenal hyperplasia. Use of serial measurements of 17-OH-progesterone in plasma, capillary blood, and saliva. Ann NY Acad Sci 1985;458:193–202.10.1111/j.1749-6632.1985.tb14604.xSearch in Google Scholar PubMed

21. Dauber A, Kellogg M, Majzoub JA. Monitoring of therapy in congenital adrenal hyperplasia. Clin Chem 2010;56:1245–51.10.1373/clinchem.2010.146035Search in Google Scholar PubMed

22. Rauh M. Steroid measurement with LC-MS/MS. Application examples in pediatrics. J Steroid Biochem Mol Biol 2010;121:520–7.10.1016/j.jsbmb.2009.12.007Search in Google Scholar PubMed

23. Hubl W, Fehér T, Rohde W, Dörner G, Taubert H, et al. Enzyme immunoassay of 17-hydroxyprogesterone in plasma, microfilter paper blood and saliva of newborns, children and patients with congenital adrenal hyperplasia. Endokrinologie 1982;79: 165–72.Search in Google Scholar

24. Pang S, Hotchkiss J, Drash AL, Levine LS, New MI. Microfilter paper method for 17 alpha-hydroxyprogesterone radioimmunoassay: its application for rapid screening for congenital adrenal hyperplasia. J Clin Endocrinol Metab 1977;45:1003–8.10.1210/jcem-45-5-1003Search in Google Scholar PubMed

25. Schwarz E, Liu A, Randall H, Haslip C, Keune F, et al. Use of steroid profiling by UPLC-MS/MS as a second tier test in newborn screening for congenital adrenal hyperplasia: the Utah experience. Pediatr Res 2009;66:230–5.10.1203/PDR.0b013e3181aa3777Search in Google Scholar PubMed

26. Rossi C, Calton L, Hammond G, Brown HA, Wallace AM, et al. Serum steroid profiling for congenital adrenal hyperplasia using liquid chromatography–tandem mass spectrometry. Clin Chim Acta 2010;411:222–8.10.1016/j.cca.2009.11.007Search in Google Scholar PubMed

27. Janzen N, Sander S, Terhardt M, Steuerwald U, Peter M, et al. Rapid steroid hormone quantification for congenital adrenal hyperplasia (CAH) in dried blood spots using UPLC liquid chromatography-tandem mass spectrometry. Steroids 2011;76:1437–42.10.1016/j.steroids.2011.07.013Search in Google Scholar PubMed

Received: 2014-7-16
Accepted: 2015-1-29
Published Online: 2015-3-7
Published in Print: 2015-7-1

©2015 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Thyroid
  3. Thyroid disorders revisited
  4. Genetic analysis of the paired box transcription factor (PAX8) gene in a cohort of Polish patients with primary congenital hypothyroidism and dysgenetic thyroid glands
  5. Prognostic factors in pediatric differentiated thyroid cancer patients with pulmonary metastases
  6. Reclassification of cytologically atypical thyroid nodules based on radiologic features in pediatric patients
  7. Evaluation of inflammatory and oxidative biomarkers in children with well-controlled congenital hypothyroidism
  8. Investigation of autoimmune diseases accompanying Hashimoto’s thyroiditis in children and adolescents and evaluation of cardiac signs
  9. Neonatal thyroid storm accompanied with severe anaemia
  10. Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion
  11. Subclinical hypothyroidism as a rare cofactor in chronic kidney disease (CKD) – related anemia
  12. Cytometric analysis of perforin expression in NK cells, CD8+, and CD4+ lymphocytes in children with autoimmune Hashimoto’s thyroiditis – a preliminary study
  13. Papillary thyroid cancer and autoimmune polyglandular syndrome
  14. Review article
  15. Should radioiodine be the first-line treatment for paediatric Graves’ disease?
  16. Image in pediatric endrocrinology
  17. Diffusion-weighted magnetic resonance imaging in a case of severe classic maple syrup urine disease
  18. Original articles
  19. Novel mutations of DAX1 (NR0B1) in two Chinese families with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism
  20. Rickets and vitamin D deficiency in Alaska native children
  21. Persistent elevation of fibroblast growth factor 23 concentrations in healthy appropriate-for-gestational-age preterm infants
  22. Parents’ experiences of having a baby with ambiguous genitalia
  23. Effect of GnRHa 3.75 mg subcutaneously every 6 weeks on adult height in girls with idiopathic central precocious puberty
  24. Congenital adrenal hyperplasia in children – a survey on the current practice in the UK
  25. Randomized clinical trial evaluating metformin versus oral contraceptive pills in the treatment of adolescents with polycystic ovarian syndrome
  26. Influence of the body weight on the onset and progression of puberty in boys
  27. Therapy monitoring in congenital adrenal hyperplasia by dried blood samples
  28. Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene
  29. Sulfonylurea in the treatment of neonatal diabetes mellitus children with heterogeneous genetic backgrounds
  30. Monitoring gonadotropin-releasing hormone analogue (GnRHa) treatment in girls with central precocious puberty: a comparison of four methods
  31. Dietary intake, body composition, and physical activity among young patients with type 1 diabetes mellitus
  32. Metabolic syndrome in obese children and adolescents in Serbia: prevalence and risk factors
  33. Progressive osseous heteroplasia, as an isolated entity or overlapping with Albright hereditary osteodystrophy
  34. Patient reports
  35. 17α-Hydroylase/17,20-lyase deficiency related to P.Y27*(c.81C>A) mutation in CYP17A1 gene
  36. A patient developing anaphylaxis and sensitivity to two different GnRH analogues and a review of literature
  37. Idiopathic short stature due to novel heterozygous mutation of the aggrecan gene
  38. Triple A syndrome with a novel indel mutation in the AAAS gene and delayed puberty
  39. Case report: long-term follow-up of a 45,X male with SHOX haploinsufficiency
  40. Antenatal Bartter syndrome presenting as hyperparathyroidism with hypercalcemia and hypercalciuria: a case report and review
  41. Successful use of continuous subcutaneous hydrocortisone infusion after bilateral adrenalectomy secondary to bilateral pheochromocytoma
  42. Donohue syndrome: a new case with a new complication
  43. Euprolactinemic galactorrhea secondary to domperidone treatment
  44. 17βHSD-3 enzyme deficiency due to novel mutations in the HSD17B3 gene diagnosed in a neonate
  45. Two different patterns of mini-puberty in two 46,XY newborns with 17β-hydroxysteroid dehydrogenase type 3 deficiency
  46. Short communication
  47. Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1
Downloaded on 28.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jpem-2014-0303/html?lang=en
Scroll to top button