Related Experiment Video
Updated: Jun 26, 2026
07:08
Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
Increased hypothalamic-pituitary-adrenal axis activity in Huntington's disease
N Ahmad Aziz1, Hanno Pijl, Marijke Frölich
1Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. N.A.Aziz@lumc.nl
The Journal of Clinical Endocrinology and Metabolism
|January 29, 2009
Summary
Huntington's disease patients show higher cortisol levels and secretion rates, indicating early hypothalamic-pituitary-adrenal axis hyperactivity. This dysfunction correlates with disease severity and may contribute to HD symptoms.
Area of Science:
- Neuroendocrinology
- Neurodegenerative Diseases
Background:
- Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder with motor, cognitive, and behavioral symptoms.
- Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is implicated in HD, but its diurnal cortisol patterns remain unstudied.
Purpose of the Study:
- To analyze HPA axis function in early-stage Huntington's disease patients.
- To correlate cortisol secretion dynamics with clinical signs and symptoms of HD.
Main Methods:
- Studied 24-hour cortisol secretion in 8 early-stage, medication-free HD patients and 8 controls.
- Measured cortisol every 10 minutes.
- Applied multiparameter autodeconvolution and cosinor regression for secretion rate and diurnal variation analysis.
Main Results:
- HD patients exhibited significantly higher total cortisol secretion rates and diurnal profile amplitude compared to controls.
- Cortisol levels were elevated in HD patients during morning and early afternoon.
- Mean 24-hour cortisol levels correlated with motor scores, functional capacity, and BMI in HD patients.
Conclusions:
- HPA axis hyperactivity is an early feature of Huntington's disease.
- This hyperactivity likely stems from disturbed central glucocorticoid feedback due to hypothalamic pathology.
- HPA axis dysfunction may contribute to the clinical manifestations of HD.
More Related Videos
Related Concept Videos
01:37Hypothalamic-Pituitary Axis
The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
01:19Cushing Syndrome II: Pathophysiology
Cortisol production is normally governed by the hypothalamic–pituitary–adrenal (HPA) axis, which maintains hormonal balance through tightly regulated feedback mechanisms. Disruption of this regulatory system is central to the development of Cushing syndrome, whether the excess cortisol originates from external medications or internal pathology. Persistent cortisol elevation alters metabolism, immune function, and endocrine signaling, producing the characteristic clinical features of the...
01:21Huntington Disease l: Introduction
Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...
01:26Cushing Syndrome I: Introduction
Cushing syndrome refers to the collection of clinical manifestations that arise when tissues are exposed to excessive amounts of cortisol or cortisol-like medications over an extended period. Cortisol, a glucocorticoid produced by the adrenal cortex, regulates metabolism, immune responses, and the body’s adaptation to stress. When its concentration remains chronically elevated, these physiological pathways become dysregulated, resulting in the characteristic features of the syndrome.Exogenous...
01:27Adrenal Gland Disorders
Adrenal gland disorders manifest when the production of adrenal hormones deviates from the norm, resulting in either excessive or insufficient concentrations.
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
01:24Physiological Foundation of Stress
Stress triggers a coordinated physiological response involving the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. This dual activation ensures that the body is prepared for both immediate and prolonged stress management. The process begins with the perception of a stressor. This initial phase activates the SNS, leading to the rapid release of adrenaline (epinephrine) from the adrenal glands.
Role of the Sympathetic Nervous System
Adrenaline triggers the...
Role of the Sympathetic Nervous System
Adrenaline triggers the...