Abstract

PurposeAnterior pituitary iron overload and volume shrinkage is common in patients with transfusion-dependent anemia and associated with growth retardation and hypogonadotropic hypogonadism. We investigated the accuracy of different MRI-based pituitary volumetric approaches and the relationship between pituitary volume and MRI-R2, particularly with respect to growth and hypogonadism.MethodsIn 43 patients with transfusion-dependent anemia (12–38 years) and 32 healthy controls (12–72 years), anterior pituitary volume was measured by a sagittal T1 GRE 3D sequence at 1.5T and analyzed by 3D semi-automated threshold volumetry (3D-volumetry). This reference method was compared with planimetric 2D-volumetry, approximate volume calculations, and pituitary height. Using a multiple SE sequence, pituitary iron as MRI-R2 was assessed by fitting proton signal intensities to echo times. Growth and hypogonadism were obtained from height percentile tables and patients’ medical charts. From body surface area and age adjusted anterior pituitary volumes of controls, Z‑scores were calculated for all subjects. Separation of controls and patients with respect to Z and pituitary R2 was performed by bivariate linear discriminant analysis.ResultsTuned 2D volumes showed highest agreement with reference 3D-volumes (bias −4.8%; 95% CI:−8.8%|−0.7%). A linear discriminant equation of Z = −17.8 + 1.45 · R2 revealed optimum threshold sensitivity and specificity of 65% and 100% for discrimination of patients from controls, respectively. Of correctly classified patients 71% and 75% showed hypogonadism and growth retardation, respectively.ConclusionAccurate assessment of anterior pituitary size requires 3D or precise 2D volumetry, with shorter analysis time for the latter. Anterior pituitary volume Z‑scores and R2 allow for the identification of patients at risk of pituitary dysfunction.

Highlights

  • Endocrine dysfunction from iron accumulation in the anterior pituitary gland is the most common cause of morbidity (> 50%) in patients with transfusion-dependent anemia (TDA), resulting in hypogonadotropic hypogonadism and growth restriction [1,2,3]

  • In TDA patients, pituitary height assessed from sagittal MR images is commonly used as a surrogate to volumetric measurements due to its simplicity and speed [5, 7,8,9,10,11]; pituitary size and shape vary considerably and assessment of pituitary size is subject to a high degree of imprecision unless true volume is measured [12]

  • Transfusion dependent anemia (TDA) patients were significantly younger, had significantly lower body surface area (BSA), pituitary height, and volume (V3D), but higher anterior pituitary R2 values compared to controls (p < 10–4)

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Summary

Introduction

Endocrine dysfunction from iron accumulation in the anterior pituitary gland is the most common cause of morbidity (> 50%) in patients with transfusion-dependent anemia (TDA), resulting in hypogonadotropic hypogonadism and growth restriction [1,2,3]. Pituitary gland size and iron deposition using MRI-R2 methods are validated markers of pituitary function [1, 4,5,6]; pituitary size can be assessed by varying metrics, and the accuracy of these methods has not been validated. R2-measurements in the anterior gland have been shown to predict preclinical and biochemical hypogonadism in TDA patients; there is paucity of data concerning the relation of pituitary volume and pituitary iron deposition [1, 13, 14]. There is limited evidence regarding the relationship of clinical manifestations of pituitary dysfunction (e.g. growth retardation) with pituitary volume and iron accumulation using MRI-R2 relaxometry [15, 16]

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