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Aspects of pituitary morphology and function in children

Borghammar, Camilla LU orcid (2025) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Background: Evidence-based guidelines for assessing pituitary function in children remain limited. Improved understanding of paediatric pituitary diseases may improve clinical management and patient counselling.
Aim: This thesis aimed to evaluate diagnostic aspects of paediatric pituitary diseases, focusing on radiological follow-up of pituitary microadenomas and cysts, pituitary refractoriness to growth hormone (GH) secretion, and plasma cortisol and GH levels during stimulation tests.
Methods: Studies I–III were retrospective reviews of medical records. Study I included 74 children with a non-functioning pituitary microadenoma or cyst <10 mm on magnetic resonance imaging (MRI). Study II assessed GH levels in 257 children with... (More)
Background: Evidence-based guidelines for assessing pituitary function in children remain limited. Improved understanding of paediatric pituitary diseases may improve clinical management and patient counselling.
Aim: This thesis aimed to evaluate diagnostic aspects of paediatric pituitary diseases, focusing on radiological follow-up of pituitary microadenomas and cysts, pituitary refractoriness to growth hormone (GH) secretion, and plasma cortisol and GH levels during stimulation tests.
Methods: Studies I–III were retrospective reviews of medical records. Study I included 74 children with a non-functioning pituitary microadenoma or cyst <10 mm on magnetic resonance imaging (MRI). Study II assessed GH levels in 257 children with short stature using a short spontaneous nocturnal profile (SSNP) and an arginine insulin tolerance test (AITT). Study III evaluated cortisol levels in 171 short-statured children using a glucagon stimulation test (GST). Study IV was a prospective study of adrenal function in 26 children treated with high-dose dexamethasone for acute lymphoblastic leukaemia (ALL), assessed with extended glucocorticoid analysis and low-dose ACTH tests two days and two weeks post treatment.
Results: Study I revealed that no microadenoma or cyst increased significantly in size during follow-up in children without hormonal abnormalities. In Study II, 21.9% of the children had a GH peak below the cut-off (≥7 mikrog/L) in the AITT, despite a normal GH peak during SSNP. In Study III, peak cortisol during the GST negatively correlated with age (rs = -0.26, p <0.001). Females had higher peak cortisol than males (667.5 nmol/L vs. 602 nmol/L, p = 0.005), a finding that remained after adjustment for age (β (95% confidence interval) 65.3 (15.9–114.6), p = 0.01). In Study IV, peak cortisol during low-dose ACTH testing correlated with cortisol/cortisone ratio (rs = 0.39, p = 0.0497) and increased significantly in the second test among children who exceeded the cortisol cut-off (≥450 nmol/L) in both tests (p = 0.018).
Conclusion: The likelihood of size progression in non-functioning pituitary microadenomas or cystic lesions appears small. Moreover, in GH stimulation tests, pituitary refractoriness to GH production after a prior spontaneous peak should be considered. Concerning plasma cortisol evaluation, sex- and age-specific reference intervals may be necessary. Further research is needed to determine cortisol cut-offs and the role of the cortisol/cortisone ratio in evaluating adrenal function in children.
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author
supervisor
opponent
  • Professor Nilsson, Ola, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
organization
publishing date
type
Thesis
publication status
published
subject
keywords
pituitary microadenoma, pituitary cyst, MRI follow-up, growth hormone refractoriness, childhood cortisol levels, cortisol/cortisone ratio, spontaneous nocturnal GH profile, insulin arginine tolerance test, glucagon stimulation test, low-dose ACTH test
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2025:144
pages
97 pages
publisher
Lund University, Faculty of Medicine
defense location
Belfragesalen, BMC D15, Klinikgatan 32 i Lund
defense date
2025-12-19 09:00:00
ISSN
1652-8220
ISBN
978-91-8021-796-5
language
English
LU publication?
yes
id
dcf76167-cdc7-4ecf-8bae-6ab5f46945bb
date added to LUP
2025-10-07 11:34:11
date last changed
2025-11-12 03:35:37
@phdthesis{dcf76167-cdc7-4ecf-8bae-6ab5f46945bb,
  abstract     = {{Background: Evidence-based guidelines for assessing pituitary function in children remain limited. Improved understanding of paediatric pituitary diseases may improve clinical management and patient counselling.<br/>Aim: This thesis aimed to evaluate diagnostic aspects of paediatric pituitary diseases, focusing on radiological follow-up of pituitary microadenomas and cysts, pituitary refractoriness to growth hormone (GH) secretion, and plasma cortisol and GH levels during stimulation tests.<br/>Methods: Studies I–III were retrospective reviews of medical records. Study I included 74 children with a non-functioning pituitary microadenoma or cyst &lt;10 mm on magnetic resonance imaging (MRI). Study II assessed GH levels in 257 children with short stature using a short spontaneous nocturnal profile (SSNP) and an arginine insulin tolerance test (AITT). Study III evaluated cortisol levels in 171 short-statured children using a glucagon stimulation test (GST). Study IV was a prospective study of adrenal function in 26 children treated with high-dose dexamethasone for acute lymphoblastic leukaemia (ALL), assessed with extended glucocorticoid analysis and low-dose ACTH tests two days and two weeks post treatment.<br/>Results: Study I revealed that no microadenoma or cyst increased significantly in size during follow-up in children without hormonal abnormalities. In Study II, 21.9% of the children had a GH peak below the cut-off (≥7 mikrog/L) in the AITT, despite a normal GH peak during SSNP. In Study III, peak cortisol during the GST negatively correlated with age (rs = -0.26, p &lt;0.001). Females had higher peak cortisol than males (667.5 nmol/L vs. 602 nmol/L, p = 0.005), a finding that remained after adjustment for age (β (95% confidence interval) 65.3 (15.9–114.6), p = 0.01). In Study IV, peak cortisol during low-dose ACTH testing correlated with cortisol/cortisone ratio (rs = 0.39, p = 0.0497) and increased significantly in the second test among children who exceeded the cortisol cut-off (≥450 nmol/L) in both tests (p = 0.018).<br/>Conclusion: The likelihood of size progression in non-functioning pituitary microadenomas or cystic lesions appears small. Moreover, in GH stimulation tests, pituitary refractoriness to GH production after a prior spontaneous peak should be considered. Concerning plasma cortisol evaluation, sex- and age-specific reference intervals may be necessary. Further research is needed to determine cortisol cut-offs and the role of the cortisol/cortisone ratio in evaluating adrenal function in children.<br/>}},
  author       = {{Borghammar, Camilla}},
  isbn         = {{978-91-8021-796-5}},
  issn         = {{1652-8220}},
  keywords     = {{pituitary microadenoma; pituitary cyst; MRI follow-up; growth hormone refractoriness; childhood cortisol levels; cortisol/cortisone ratio; spontaneous nocturnal GH profile; insulin arginine tolerance test; glucagon stimulation test; low-dose ACTH test}},
  language     = {{eng}},
  number       = {{2025:144}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Aspects of pituitary morphology and function in children}},
  url          = {{https://lup.lub.lu.se/search/files/232709613/Avhandling_Camilla_B_LUCRIS.pdf}},
  year         = {{2025}},
}