Abstract
Familial Glucocorticoid deficiency (FGD), in which the adrenal cortex fails to produce glucocorticoids, was first shown to be caused by defects in the receptor for ACTH (MC2R) or its accessory protein (MRAP). Certain mutations in the steroidogenic acute regulatory protein (STAR) can also masquerade as FGD. Recently mutations in mini chromosome maintenance-deficient 4 homologue (MCM4) and nicotinamide nucleotide transhydrogenase (NNT), genes involved in DNA replication and antioxidant defence respectively, have been recognised in FGD cohorts. These latest findings expand the spectrum of pathogenetic mechanisms causing adrenal disease and imply that the adrenal may be hypersensitive to replicative and oxidative stresses. Over time patients with MCM4 or NNT mutations may develop other organ pathologies related to their impaired gene functions and will therefore need careful monitoring.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adrenal Gland Diseases / genetics*
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Adrenal Glands / metabolism*
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Adrenal Insufficiency / genetics*
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Adrenal Insufficiency / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cholesterol Side-Chain Cleavage Enzyme / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Glucocorticoids / biosynthesis*
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Humans
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Minichromosome Maintenance Complex Component 4
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / metabolism
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NADP Transhydrogenase, AB-Specific / genetics
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NADP Transhydrogenase, AB-Specific / metabolism
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Receptor, Melanocortin, Type 2 / genetics
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Receptor, Melanocortin, Type 2 / metabolism
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Steroid Metabolism, Inborn Errors / genetics*
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Steroid Metabolism, Inborn Errors / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Cell Cycle Proteins
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DNA-Binding Proteins
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Glucocorticoids
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MRAP protein, human
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MRAP2 protein, human
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Membrane Proteins
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Mitochondrial Proteins
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Nuclear Proteins
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Phosphoproteins
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Receptor, Melanocortin, Type 2
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steroidogenic acute regulatory protein
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Cholesterol Side-Chain Cleavage Enzyme
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NADP Transhydrogenase, AB-Specific
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NNT protein, human
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MCM4 protein, human
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Minichromosome Maintenance Complex Component 4
Supplementary concepts
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Familial Glucocorticoid Deficiency 1