Abstract
Introduction
Hyperpigmentation of skin and mucous membranes comprises a hallmark of the clinical diagnosis of Addison’s disease. However, there have been reports of patients with adrenal insufficiency from diverse causes who did not develop hyperpigmentation. The pathophysiology responsible for the absence of increased pigmentation is not clearly defined in many cases.
Case presentation
We present a patient with isolated glucocorticoid deficiency due to two novel heterozygous variants in the sphingosine-1-phosphate lyase 1 (SPGL1) gene that did not develop any hyperpigmentation.
Discussion
We elaborate on the presumed mechanism of the absence of hyperpigmentation in adrenal insufficiency due to SPGL1 deficiency and discuss the other reported cases of Addison’s disease without hyperpigmentation and the possible mechanism accounted for.
Conclusion
Absence of hyperpigmentation, a basic component of the clinical diagnosis of Addison’s disease, may lead to delay of a critical diagnosis, while causes that result in adrenal insufficiency without hyperpigmentation should explicitly be considered in pediatric cases where adrenal failure is documented by clinical symptomatology and biochemistry.
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Data availability
Genetic data of the variants have been uploaded to the LOVD database with ID number 0000410396.
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AG conceived and drafted the manuscript. AS performed the genetic analysis. AE and DC critically reviewed the manuscript.
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Giannakopoulos, A., Sertedaki, A., Efthymiadou, A. et al. Addison’s disease without hyperpigmentation in pediatrics: pointing towards specific causes. Hormones 22, 143–148 (2023). https://doi.org/10.1007/s42000-022-00415-5
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DOI: https://doi.org/10.1007/s42000-022-00415-5