Abstract
Objectives
Brain MRIs are considered essential in the evaluation of children diagnosed with growth hormone deficiency (GHD), but there is uncertainty about the appropriate cut-off for diagnosis of GHD and little data about the yield of significant abnormal findings in patients with peak growth hormone (GH) of 7–10 ng/mL. We aimed to assess the frequency of pathogenic MRIs and associated risk factors in relation to peak GH concentrations.
Methods
In this retrospective multicenter study, charts of patients diagnosed with GHD who subsequently had a brain MRI were reviewed. MRIs findings were categorized as normal, incidental, of uncertain significance, or pathogenic (pituitary hypoplasia, small stalk and/or ectopic posterior pituitary and tumors). Charges for brain MRIs and sedation were collected.
Results
In 499 patients, 68.1% had normal MRIs, 18.2% had incidental findings, 6.6% had uncertain findings, and 7.0% had pathogenic MRIs. Those with peak GH<3 ng/mL had the highest frequency of pathogenic MRIs (23%). Only three of 194 patients (1.5%) with peak GH 7–10 ng/mL had pathogenic MRIs, none of which altered management. Two patients (0.4%) with central hypothyroidism and peak GH<4 ng/mL had craniopharyngioma.
Conclusions
Pathogenic MRIs were uncommon in patients diagnosed with GHD except in the group with peak GH<3 ng/mL. There was a high frequency of incidental findings which often resulted in referrals to neurosurgery and repeat MRIs. Given the high cost of brain MRIs, their routine use in patients diagnosed with isolated GHD, especially patients with peak GH of 7–10 ng/mL, should be reconsidered.
Research funding: None declared.
Author contributions: PBK conceived the study. JS, PT, ANS, EK, PR, AG, SO, and PBK reviewed the medical records to collect the data. JS and AKMFR analyzed and interpreted data. JS and PBK drafted the manuscript. All authors reviewed the findings and approved of the final version of the manuscript.
Competing interests: None declared.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by all involved institutional review boards (IRB); University of Alabama at Birmingham IRB, Cook Children’s Health Care System IRB, Memorial Hermann Health System IRB, Virginia Commonwealth University IRB, Loma Linda University IRB, and Children’s National Medical Center IRB.
References
1. Rosenfeld, RG. Is growth hormone deficiency a viable diagnosis? J Clin Endocrinol Metab 1997;82:349–51.10.1210/jcem.82.2.3841Search in Google Scholar
2. Rosenfeld, RG, Albertsson-Wikland, K, Cassorla, F, Frasier, SD, Hasegawa, Y, Hintz, RL, et al.. Diagnostic controversy: the diagnosis of childhood growth hormone deficiency revisited. J Clin Endocrinol Metab 1995;80:1532–40.10.1210/jcem.80.5.7538145Search in Google Scholar
3. Ghigo, E, Bellone, J, Aimaretti, G, Bellone, S, Loche, S, Cappa, M, et al.. Reliability of provocative tests to assess growth hormone secretory status: study in 472 normally growing children. J Clin Endocrinol Metab 1996;81:3323–7.10.1210/jcem.81.9.8784091Search in Google Scholar
4. Mauras, N, Walton, P, Nicar, M, Welch, S, Rogol, AD. Growth hormone stimulation testing in both short and normal statured children: use of an immunofunctional assay. Pediatr Res 2000;48:614–8.10.1203/00006450-200011000-00010Search in Google Scholar
5. Tanaka, T, Tachibana, K, Shimatsu, A, Katsumata, N, Tsushima, T, Hizuka, N, et al.. A nationwide attempt to standardize growth hormone assays. Horm Res 2005;64(2 Suppl):6–11.10.1159/000087746Search in Google Scholar
6. Hindmarsh, PC, Swift, PG. An assessment of growth hormone provocation tests. Arch Dis Child 1995;72:362–7.10.1136/adc.72.4.362Search in Google Scholar
7. Collett-Solberg, PF, Ambler, G, Backeljauw, PF, Bidlingmaier, M, Biller, BMK, Boguszewski, MCS, et al.. Diagnosis, genetics, and therapy of short stature in children: a growth hormone research society international perspective. Horm Res Paediatr 2019;92:1–14.10.1159/000502231Search in Google Scholar
8. Argyropoulou, M, Perignon, F, Brauner, R, Brunelle, F. Magnetic resonance imaging in the diagnosis of growth hormone deficiency. J Pediatr 1992;120:886–91.10.1016/S0022-3476(05)81955-9Search in Google Scholar
9. Kornreich, L, Horev, G, Lazar, L, Josefsberg, Z, Pertzelan, A. MR findings in hereditary isolated growth hormone deficiency. AJNR Am J Neuroradiol 1997;18:1743–7.Search in Google Scholar
10. Kornreich, L, Horev, G, Lazar, L, Schwarz, M, Sulkes, J, Pertzelan, A. MR findings in growth hormone deficiency: correlation with severity of hypopituitarism. AJNR Am J Neuroradiol 1998;19:1495–9.Search in Google Scholar
11. Bozzola, M, Adamsbaum, C, Biscaldi, I, Zecca, M, Cisternino, M, Genovese, E, et al.. Role of magnetic resonance imaging in the diagnosis and prognosis of growth hormone deficiency. Clin Endocrinol (Oxf) 1996;45:21–6.10.1111/j.1365-2265.1996.tb02055.xSearch in Google Scholar
12. Frindik, JP, Kemp, SF, Pihoker, C. Effective use of magnetic resonance imaging in the assessment of children with possible growth hormone deficiency. Endocr Pract 1996;2:8–12.10.4158/EP.2.1.8Search in Google Scholar PubMed
13. Coutant, R, Rouleau, S, Despert, F, Magontier, N, Loisel, D, Limal, JM. Growth and adult height in GH-treated children with nonacquired GH deficiency and idiopathic short stature: the influence of pituitary magnetic resonance imaging findings. J Clin Endocrinol Metab 2001;86:4649–54.10.1210/jcem.86.10.7962Search in Google Scholar PubMed
14. Maghnie, M, Triulzi, F, Larizza, D, Preti, P, Priora, C, Scotti, G, et al.. Hypothalamic-pituitary dysfunction in growth hormone-deficient patients with pituitary abnormalities. J Clin Endocrinol Metab 1991;73:79–83.10.1210/jcem-73-1-79Search in Google Scholar PubMed
15. Naderi, F, Eslami, SR, Mirak, SA, Khak, M, Amiri, J, Beyrami, B, et al.. Effect of growth hormone deficiency on brain MRI findings among children with growth restrictions. J Pediatr Endocrinol Metab 2015;28:117–23.10.1515/jpem-2013-0294Search in Google Scholar PubMed
16. Pampanini, V, Pedicelli, S, Gubinelli, J, Scire, G, Cappa, M, Boscherini, B, et al.. Brain magnetic resonance imaging as first-line investigation for growth hormone deficiency diagnosis in early childhood. Horm Res Paediatr 2015;84:323–30.10.1159/000439590Search in Google Scholar PubMed
17. Maghnie, M, Lindberg, A, Koltowska-Haggstrom, M, Ranke, MB. Magnetic resonance imaging of CNS in 15,043 children with GH deficiency in KIGS (Pfizer International Growth Database). Eur J Endocrinol 2013;168:211–7.10.1530/EJE-12-0801Search in Google Scholar PubMed
18. Di Iorgi, N, Allegri, AE, Napoli, F, Bertelli, E, Olivieri, I, Rossi, A, et al.. The use of neuroimaging for assessing disorders of pituitary development. Clin Endocrinol (Oxf) 2012;76:161–76.10.1111/j.1365-2265.2011.04238.xSearch in Google Scholar PubMed
19. Leger, J, Danner, S, Simon, D, Garel, C, Czernichow, P. Do all patients with childhood-onset growth hormone deficiency (GHD) and ectopic neurohypophysis have persistent GHD in adulthood? J Clin Endocrinol Metab 2005;90:650–6.10.1210/jc.2004-1274Search in Google Scholar PubMed
20. Zenaty, D, Garel, C, Limoni, C, Czernichow, P, Leger, J. Presence of magnetic resonance imaging abnormalities of the hypothalamic-pituitary axis is a significant determinant of the first 3 years growth response to human growth hormone treatment in prepubertal children with nonacquired growth hormone deficiency. Clin Endocrinol (Oxf) 2003;58:647–52.10.1046/j.1365-2265.2003.01768.xSearch in Google Scholar
21. Kara, O, Esen, I, Tepe, D, Gulleroglu, NB, Tayfun, M. Relevance of pituitary gland magnetic resonance imaging results with clinical and laboratory findings in growth hormone deficiency. Med Sci Monit 2018;24:9473–8.10.12659/MSM.911977Search in Google Scholar PubMed PubMed Central
22. Guzzetti, C, Ibba, A, Pilia, S, Beltrami, N, Di Iorgi, N, Rollo, A, et al.. Cut-off limits of the peak GH response to stimulation tests for the diagnosis of GH deficiency in children and adolescents: study in patients with organic GHD. Eur J Endocrinol 2016;175:41–7.10.1530/EJE-16-0105Search in Google Scholar PubMed
23. Alba, P, Tsai, S, Mitre, N. The severity of growth hormone deficiency does not predict the presence or absence of brain magnetic resonance imaging abnormalities – a retrospective review. Eur Endocrinol 2020;16:60–4.10.17925/EE.2020.16.1.60Search in Google Scholar PubMed PubMed Central
24. Oren, A, Singer, D, Rachmiel, M, Hamiel, U, Shiran, S, Gruber, N, et al.. Questioning the value of brain magnetic resonance imaging in the evaluation of children with isolated growth hormone deficiency. Horm Res Paediatr 2020;93:245–50.10.1159/000509366Search in Google Scholar PubMed
25. Ribeiro de Oliveira Longo Schweizer, J, Ribeiro-Oliveira, AJr., Bidlingmaier, M. Growth hormone: isoforms, clinical aspects and assays interference. Clin Diabetes Endocrinol 2018;4:18.10.1186/s40842-018-0068-1Search in Google Scholar PubMed PubMed Central
26. Shareef, M, Nasrallah, MP, AlArab, N, Atweh, LA, Zadeh, C, Hourani, R. Pituitary incidentalomas in paediatric population: incidence and characteristics. Clin Endocrinol (Oxf) 2020 Oct 23. https://doi.org/10.1111/cen.14353 [Epub ahead of print].Search in Google Scholar
27. Thaker, VV, Lage, AE, Kumari, G, Silvera, VM, Cohen, LE. Clinical course of nonfunctional pituitary microadenoma in children: a single-center experience. J Clin Endocrinol Metab 2019;104:5906–12.10.1210/jc.2019-01252Search in Google Scholar PubMed PubMed Central
28. Kessler, M, Tenner, M, Frey, M, Noto, R. Pituitary volume in children with growth hormone deficiency, idiopathic short stature and controls. J Pediatr Endocrinol Metab 2016;29:1195–200.10.1515/jpem-2015-0404Search in Google Scholar PubMed
29. Backeljauw, PF, Dattani, MT, Cohen, P, Rosenfeld, RG. Disorders of growth hormone/insulin-like growth factor secretion and action. In: Sperling, M, editor. Pediatric endocrinology. Philadelphia, PA: Elsevier/Saunders; 2014.10.1016/B978-1-4557-4858-7.00019-6Search in Google Scholar
30. Almaghraby, A, Jaju, A, Ryan, ME, Rychlik, K, Habiby, RL, Brickman, W. Is there a need to use gadolinium contrast for pituitary MRI in the evaluation of pediatric short stature and growth hormone deficiency? J Endocr Soc 2020;4(1 Suppl):SAT-LB19.10.1210/jendso/bvaa046.2114Search in Google Scholar
31. FDA Drug Safety Communication. FDA warns that gadolinium-based contrast agents (GBCAs) are retained in the body; requires new class warnings; 2018. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-gadolinium-based-contrast-agents-gbcas-are-retained-body.Search in Google Scholar
© 2021 Walter de Gruyter GmbH, Berlin/Boston
