Segmental MRI pituitary and hypothalamus volumes post Fontan: An analysis of the Australian and New Zealand Fontan registry

Waverley Gee; Joseph Yuan-Mou Yang; Tom Gentles; Sonja Bastin; Ajay J Iyengar; Jian Chen; Dug Yeo Han; Rachael Cordina; Charlotte Verrall; Craig Jefferies; Australian and New Zealand Fontan Registry

doi:10.1016/j.ijcchd.2024.100549

Segmental MRI pituitary and hypothalamus volumes post Fontan: An analysis of the Australian and New Zealand Fontan registry

Int J Cardiol Congenit Heart Dis. 2024 Oct 22:18:100549. doi: 10.1016/j.ijcchd.2024.100549. eCollection 2024 Dec.

Authors

Waverley Gee^{1

2}, Joseph Yuan-Mou Yang^{3

4

5

6}, Tom Gentles^{7

8

2}, Sonja Bastin^{1

2}, Ajay J Iyengar^{7

9

2}, Jian Chen^{10

6}, Dug Yeo Han^{11

2}, Rachael Cordina^{12

13

14}, Charlotte Verrall^{12

13

14}, Craig Jefferies^{15

16

2}; Australian and New Zealand Fontan Registry

Affiliations

¹ Department of Paediatric Radiology, Starship Child Health, Te Toka Tumai Auckland Te Whatu Ora, Auckland, New Zealand.
² Starship Children's Hospital, 2 Park Road, Grafton, Auckland, 1023, New Zealand.
³ Neuroscience Advanced Clinical Imaging Service (NACIS), Department of Neurosurgery, Royal Children's Hospital, Parkville, Melbourne, Australia.
⁴ Neuroscience Research, Murdoch Children's Research Institute, Parkville, Melbourne, Australia.
⁵ Department of Paediatrics, University of Melbourne, Parkville, Melbourne, Australia.
⁶ Royal Children's Hospital, 50 Flemington Rd, Parkville, VIC 3052, Australia.
⁷ Paediatric and Congenital Cardiology Service, Starship Child Health, Te Toka Tumai Auckland Te Whatu Ora, Auckland, New Zealand.
⁸ Department of Paediatrics, Child and Youth Health, University of Auckland, Auckland, New Zealand.
⁹ Department of Surgery, University of Auckland, Auckland, New Zealand.
¹⁰ Developmental Imaging, Murdoch Children's Research Institute, Parkville, Melbourne, Australia.
¹¹ Starship Research and Innovation Office, Starship Child Health, Te Toka Tumai Auckland Te Whatu Ora, Auckland, New Zealand.
¹² Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
¹³ Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
¹⁴ Royal Prince Alfred Hospital, 50 Missenden Rd, Camperdown, NSW, 2050, Australia.
¹⁵ Paediatric Diabetes and Endocrine Service, Starship Child Health, Te Toka Tumai Auckland Te Whatu Ora, Auckland, New Zealand.
¹⁶ Liggins Institute and Department of Paediatrics, University of Auckland, Auckland, New Zealand.

Abstract

Objective: Short stature, central hypothyroidism and infertility are common in those with a Fontan circulation. Given that the Fontan circulation often results in hepatic portal venous congestion, we hypothesize that the hypothalamic-pituitary portal circulation is also affected, contributing to subsequent hypothalamic-pituitary axis dysfunction.

Methods: MRI data from the Australian and New Zealand Fontan Registry (86 cases) was compared to 86 age- and sex-matched normal published controls. Total pituitary volumes (both anterior and posterior glands) were measured using a manual tracing segmentation method, and hypothalamic (and subunit) volumes using an automated segmentation tool. Measured gland volume was normalized to total brain volumes. A generalized linear model was used for statistical analysis.

Results: Normalized total pituitary volumes (nTPV) were increased in Fontan patients compared to controls (p < 0.0001), due to an increase in anterior pituitary volumes (nAPV) (p < 0.0001), with no difference in normalized posterior pituitary volumes (p = 0.7). Furthermore, normalized anterior and tubular hypothalamic subunit groups) were increased in Fontan patients compared to the controls (p < 0.01 and p < 0.0001, respectively).The time between Fontan and MRI was positively related to nTPV, nAPV and bilateral hypothalamic volumes. nTPV increased with age, and the increase in nAPV was greater in Fontan patients.

Conclusions: Segmental MRI Pituitary and Hypothalamus volumes post Fontan are increased and are related to the time since Fontan procedure. These findings are consistent with venous congestion of the anterior hypothalamic-pituitary portal venous system and may explain the high frequency of endocrine dysfunction in this patient group.

Keywords: Endocrine dysfunction; Fontan circulation; Hypothalamic-pituitary axis; Hypothyroidism; Infertility; Magnetic resonance imaging; Portal venous; Segmentation; Short stature; Venous congestion.