Regulation of cortisol secretion in humans: relation to vasopressin action at the adrenals in macronodular and micronodular adrenocortical tumours; and well-being in Addison’s Disease.
type: CreativeWork
description: The hypothalamic-pituitary-adrenal (HPA) axis exhibits tight physiological regulation on a circadian and ultradian basis in humans. Key central regulators include the peptides corticotrophin-releasing hormone (CRH) and arginine vasopressin (VP), acting at the pituitary, and at peripheral structures relevant to the HPA axis and other components of the stress system. Altered regulation has many causes, frequently related to tumorigenesis, and can lead to disease due to an excess of the HPA axis end-organ hormone cortisol, as in Cushing’s syndrome (CS), or cortisol deficiency, as in Addison’s disease. More subtle alterations of HPA axis function have been associated with many diseases. It may be that a lack of normal circadian and ultradian regulation leads to altered well-being. Studies of three families with the rare cause of cortisol excess, ACTH-independent macronodular adrenal hyperplasia (AIMAH) revealed that adrenal function could be directly stimulated by an aberrant response to exogenous vasopressin (VP; VPs-AIMAH). In addition, it appeared possible to define subtle forms of adrenal dysregulation or early tumour formation, short of clinical CS, thereby expanding the range of phenotypic expression of this disorder for the first time, and further highlighting the familial nature of VPs-AIMAH. Studies of germline DNA, as well as expression of genes potentially relevant to the VP response in adrenal tumours, did not reveal any abnormality to explain heritable VPs-AIMAH. A SNPbased linkage study in the largest (seven affected) family revealed a single potential locus (LOD score 1.83) leading to sequencing of a number of positional candidates. Further studies have included gene expression studies of the familial AIMAH tumours, the most extensive of these studies internationally, in vivo stimulation studies of adrenal steroid intermediates, and finally whole exome capture and next-generation sequencing, all of which has led to increased knowledge in the AIMAH field, …
abstract: The hypothalamic-pituitary-adrenal (HPA) axis exhibits tight physiological regulation on a circadian and ultradian basis in humans. Key central regulators include the peptides corticotrophin-releasing hormone (CRH) and arginine vasopressin (VP), acting at the pituitary, and at peripheral structures relevant to the HPA axis and other components of the stress system. Altered regulation has many causes, frequently related to tumorigenesis, and can lead to disease due to an excess of the HPA axis end-organ hormone cortisol, as in Cushing’s syndrome (CS), or cortisol deficiency, as in Addison’s disease. More subtle alterations of HPA axis function have been associated with many diseases. It may be that a lack of normal circadian and ultradian regulation leads to altered well-being. Studies of three families with the rare cause of cortisol excess, ACTH-independent macronodular adrenal hyperplasia (AIMAH) revealed that adrenal function could be directly stimulated by an aberrant response to exogenous vasopressin (VP; VPs-AIMAH). In addition, it appeared possible to define subtle forms of adrenal dysregulation or early tumour formation, short of clinical CS, thereby expanding the range of phenotypic expression of this disorder for the first time, and further highlighting the familial nature of VPs-AIMAH. Studies of germline DNA, as well as expression of genes potentially relevant to the VP response in adrenal tumours, did not reveal any abnormality to explain heritable VPs-AIMAH. A SNPbased linkage study in the largest (seven affected) family revealed a single potential locus (LOD score 1.83) leading to sequencing of a number of positional candidates. Further studies have included gene expression studies of the familial AIMAH tumours, the most extensive of these studies internationally, in vivo stimulation studies of adrenal steroid intermediates, and finally whole exome capture and next-generation sequencing, all of which has led to increased knowledge in the AIMAH field, …
author: Gagliardi, Lucia
keywords: Cushing's; AIMAH; Addison's; vasopressin
date published: 2011
date modified: 2026-07-24T00:50:50Z
provider: University of Adelaide
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Adelaide

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property ID: Handle
value: http://hdl.handle.net/2440/78635