What question did this study set out to answer?

To characterize the genetic and biochemical mechanisms causing low total morning serum cortisol alongside normal urinary cortisol and ACTH levels in a symptomatic patient.

January 1, 2000The Journal of Clinical Endocrinology & MetabolismOpen Access

Novel Human Corticosteroid-Binding Globulin Variant with Low Cortisol-Binding Affinity1

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Authors

AEAgnès Emptoz-BonnetonUniversité Claude Bernard Lyon 1 PCPatrice CousinPfizer (France)KSKoji SeguchiWestern University

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Implication

Case investigation uncovers an Asp367Asn mutation in corticosteroid-binding globulin, indicating that preserved free cortisol maintains endocrine function despite reduced total hormone levels.

Key Points

To characterize the genetic and biochemical mechanisms causing low total morning serum cortisol alongside normal urinary cortisol and ACTH levels in a symptomatic patient.
Assessed endocrine parameters, protein-bound vs. dialyzable free cortisol fractions, and family pedigree in a 43-year-old female patient (N=1) and four living children.
Performed direct PCR sequencing of CBG-encoding exons and expressed the mutant cDNA (Asp367Asn) in Chinese hamster ovary cells for Scatchard binding analysis.
The proband was homozygous for an Asp367Asn mutation, exhibiting low serum CBG (24 mg/L vs. 44±6 mg/L) and reduced cortisol-binding affinity (Ka = 0.12 L/nmol vs. 0.82±0.29 L/nmol).
In vitro expression demonstrated that the Asn367 substitution reduced human CBG cortisol affinity approximately 4-fold (Ka = 0.15 L/nmol vs. 0.66 L/nmol for wild-type).
An elevated percentage of nonprotein-bound cortisol (8.7–9.7% vs. normal 2.9–3.9%) compensated for low total cortisol, maintaining normal circulating free cortisol levels.

Cite This Study

Emptoz-Bonneton et al. (2000) studied this question.

synapsesocial.com/papers/6a70b7965671bbf00bc2c1f4 https://doi.org/10.1210/jcem.85.1.6315

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Implication

Case investigation uncovers an Asp367Asn mutation in corticosteroid-binding globulin, indicating that preserved free cortisol maintains endocrine function despite reduced total hormone levels.

Novel Human Corticosteroid-Binding Globulin Variant with Low Cortisol-Binding Affinity1

Discussion

Member takes

Implication

Key Points

Cite This Study

Novel Human Corticosteroid-Binding Globulin Variant with Low Cortisol-Binding Affinity1

Discussion

Member takes

Implication

Key Points

Cite This Study

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