Translational Neuroendocrinology

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Microstructure alterations in the Hypothalamus in cranially radiated Childhood Leukemia survivors but not in Craniopharyngioma patients unaffected by hypothalamic damage

Follin C1, Fjalldal S1, Svärd D2,3, van Westen D2,3, Gabery S4, Petersén Å4, Lätt J3, Rylander L5 and Erfurth EM1.

1. Department of Endocrinology, Skåne University Hospital, Lund, Sweden.
2. Clinical Sciences Lund, Diagnostic Radiology, Lund University, Lund, Sweden.
3. Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden.
4. Translational Neuroendocrine Research Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
5. Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.

Clinical Endocrinology. 87(4): 359-366 (2017)

Abstract

Metabolic complications are frequent in childhood leukemia (ALL) survivors treated with cranial radiotherapy (CRT). These complications are potentially mediated by damage to the hypothalamus (HT), as childhood onset (CO) craniopharyngioma (CP) survivors without HT involvement are spared overt obesity. Diffusion tensor imaging (DTI) shows brain tissue microstructure alterations, by fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). We used DTI to determine the integrity of the microstructure of the HT in ALL survivors.

Design:
Case-control study.

Patients:
Three groups were included: i) 27 CRT treated ALL survivors on hormone supplementation, ii) 17 CO-CP survivors on hormone supplementation but without HT involvement, and iii) 27 matched controls.

Measurements:
DTI parameters of the HT were measured and body composition.

Results:
Microstructural alterations in the HT were more severe in ALL survivors with a BMI ≥ 25 than with BMI < 25. Compared to controls, ALL survivors had reduced FA (P=0.04), increased MD (P<0.001), AD (P<0.001), and RD (P<0.001) in the right and left HT. In the right HT ALL survivors with a BMI ≥ 25 showed elevated MD (P=0.03) and AD (P=0.02) compared to ALL survivors with BMI < 25. In contrast, DTI parameters did not differ between CP survivors and controls.

Conclusions:
Long-term follow up after CRT for ALL DTI measures were affected in the HT despite complete hormone replacement. The present data suggest that ALL survivors have demyelination and axonal loss in the HT.

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