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Hormones of the Adrenal Glands01:31

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Adrenal hormones play a pivotal role in maintaining the body's electrolyte balance and orchestrating responses to stress, showcasing the intricate functions of the adrenal cortex and medulla.
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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.
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Adrenal Gland Disorders01:27

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Adrenal gland disorders manifest when the production of adrenal hormones deviates from the norm, resulting in either excessive or insufficient concentrations.
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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.
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The adrenal or supra-renal glands, situated above the kidneys and aligned with the twelfth rib, are paired pyramid-shaped structures crucial for the body's stress response. During stress, these glands secrete hormones vital for adaptive physiological reactions.
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Stress is a multifaceted response to events perceived as challenging or threatening, highlighting physical, emotional, cognitive, and behavioral reactions. Physically, stress can lead to fatigue, sleep disruptions, and various health issues such as frequent colds, chest pains, and nausea. Emotionally, it can manifest as anxiety, depression, irritability, and anger triggered by both minor and major life events. Cognitively, it may result in difficulty in concentration, memory, and...
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Updated: Aug 8, 2025

Cortisol Measurement in Koala Phascolarctos cinereus Fur
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Cortisol: Analytical and clinical determinants.

Arturo Vega-Beyhart1, Marta Araujo-Castro2, Felicia A Hanzu3

  • 1Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Endocrinology and Nutrition, Hospital Clinic, Barcelona, Spain.

Advances in Clinical Chemistry
|March 1, 2023
PubMed
Summary

Cortisol testing in serum, urine, and saliva is complex due to biological variations and analytical challenges. Mass spectrometry offers greater accuracy than immunoassays for cortisol measurement, reducing diagnostic uncertainty.

Keywords:
Adrenal insufficiencyCortisolCushing's syndromeDexamethasone suppression testImmunoassayMass spectrometrySalivaSerumUrine free cortisol

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Area of Science:

  • Endocrinology
  • Clinical Chemistry
  • Analytical Chemistry

Background:

  • Cortisol, the primary human glucocorticoid, is synthesized in the adrenal cortex and metabolized by the liver.
  • Quantitative analysis of cortisol in serum, urine, and saliva is challenging due to circadian rhythms, stress responses, and protein-bound/free forms.
  • Cortisol is uniquely measured across serum, urine, and saliva matrices, presenting unique preanalytical and analytical hurdles.

Purpose of the Study:

  • To review the complexities of cortisol measurement across different biological matrices.
  • To compare the analytical performance of immunoassays versus mass spectrometry for cortisol determination.
  • To discuss the clinical relevance of cortisol testing in various disease states.

Main Methods:

  • Review of existing literature on cortisol analysis in serum, urine, and saliva.
  • Comparison of immunoassay and mass spectrometry techniques for cortisol quantification.
  • Discussion of preanalytical and analytical factors influencing cortisol test results.

Main Results:

  • Immunoassays, commonly used for cortisol, are prone to interference from other steroids, leading to overestimation, particularly in urine.
  • Mass spectrometry provides superior specificity and can simultaneously measure multiple steroids, enhancing diagnostic accuracy.
  • Hair cortisol analysis, though not standard, may be valuable in specific clinical scenarios.

Conclusions:

  • Accurate cortisol measurement is critical for diagnosing various endocrine disorders.
  • Mass spectrometry is recommended for precise cortisol quantification, overcoming limitations of immunoassays.
  • Further research into standardized cortisol testing protocols and interpretation is warranted.