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.

CJ has a Health Research Council of New Zealand Clinical Practitioner Research Fellowship, Grant/Award Number: 20-026. JYMY received positional funding from the Royal Childrens Hospital Foundation (RCHF 2022-1402).

CJ has a Health Research Council of New Zealand Clinical Practitioner Research Fellowship, Grant/Award Number: 20-026. JYMY received positional funding from the Royal Childrens Hospital Foundation (RCHF 2022-1402). This study did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sectors.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Existing data were used from the Australia and New Zealand Fontan Registry; participants were recruited as part of an older study. Ethics approval was obtained at each recruitment site (Human Research Ethics Committee for Royal Children's Hospital Melbourne, Human Research Ethics Committee for the Sydney Children's Hospital Network (Royal Prince Alfred Hospital, The Children's Hospital at Westmead). Auckland District Health Board Locality Authorisation for Starship Children's Hospital.

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