Clinical, Laboratory, and Imaging Features Associated with Arginine Vasopressin Deficiency (Central Diabetes Insipidus) in Erdheim–Chester Disease (ECD)

TL;DR

This study explores how arginine vasopressin deficiency in Erdheim–Chester disease is linked to younger age, hormonal issues, and BRAF mutations, offering insights for better patient care.

Contribution

The study identifies AVP-D in ECD as associated with BRAF V600E mutations and specific hormonal and imaging features, suggesting a need for comprehensive assessments.

Findings

Subjects with AVP-D were younger and had more central endocrine deficiencies and pituitary imaging abnormalities.

AVP-D was associated with a higher burden of BRAF V600E pathogenic variants.

Absent posterior pituitary bright spots and abnormal pituitary imaging were linked to AVP-D.

Abstract

Arginine vasopressin deficiency (AVP-D, previously known as central diabetes insipidus) is among the most common initial presentations of ECD, implying that a deeper understanding of AVP-D-related factors may help improve outcomes. We performed a cross-sectional analysis of clinical, molecular and imaging features associated with AVP-D in ECD. Subjects with AVP-D were younger, and had more central endocrine deficiencies and pituitary imaging abnormalities. Importantly, AVP-D was associated with a higher burden of BRAF V600E pathogenic variants, which is also a therapeutic target. Together, our findings provide insights for triaging the care of AVP-D in ECD, suggesting that subjects with AVP-D may benefit from a comprehensive hormonal, molecular, and radiological assessment.

Purpose: Erdheim–Chester disease (ECD) is an L Group Langerhans histiocytosis associated with pathogenic variants within the MAPK pathways, most commonly the BRAF gene. We analyzed prevalence, genetic, biochemical, and pituitary imaging features associated with arginine vasopressin deficiency (AVP-D), one of the most common endocrinopathies in ECD. Methods: A cross-sectional descriptive study of 61 subjects with ECD was conducted at a clinical research center from January 2011 to December 2018, with molecular genetics, baseline biochemical and pituitary endocrine function studies, and dedicated pituitary MRI (or CT) studies. AVP-D and anterior pituitary endocrinopathies (hypothyroidism, hypogonadism, adrenal insufficiency and panhypopituitarism) were assessed. Students’ t-tests, nonparametric tests, Fisher’s exact tests, and logistic regression were employed for analysis. Results: In total, 22 out of 61 subjects (36%; 19 males and 3 females) had AVP-D; 18 subjects with AVP-D were in active treatment with desmopressin. Those with versus without AVP-D were younger [mean (±SD): 50.00 (±10.45) vs. 56.72 (±10.45) years], had higher prevalence of BRAF V600E pathogenic variants [68% vs. 43%], lower IGF-1 [mean (±SD): 137.05 (±67.97) vs. 175.92 (±61.89) ng/mL], lower urine osmolality [416.00 (250.00–690.00) vs. 644.50 (538.75–757.75)) mOsm/kg], and a higher burden of central hypogonadism [81.82% vs. 36.00%], central hypothyroidism [23% vs. 2.5%], panhypopituitarism [41% vs. 0%], anterior pituitary endocrine deficits, absent posterior pituitary bright spots [63.64% vs. 20.51%], and abnormal pituitary imaging. In adjusted models, [OR (95%CI)] BRAF V600E mutation [7.38 (1.84–39.01)], central hypogonadism [6.193 (1.44–34.80)], primary hypothyroidism [13.89 (1.401–406.5)], absent posterior pituitary bright spot [12.84 (3.275–65.04)], and abnormal pituitary imaging [10.60 (2.844–48.29)] were associated with higher odds of having AVP-D. Conclusions: AVP-D is common in ECD and accompanied by a higher burden of pituitary endocrinopathies, BRAF V600E pathogenic variants, abnormal pituitary imaging, and absent posterior pituitary bright spots.

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