What causes instantaneous decrease in cortisol levels?

From the Guidelines

To instantly decrease cortisol levels, etomidate is the most effective option, as it works rapidly, especially in hospitalized patients who cannot take oral medications 1. When considering instantaneous reduction in cortisol levels, the primary goal is to rapidly normalize cortisol, especially in severe cases.

• Etomidate is a viable option for rapid reduction, particularly in a hospital setting where patients may not be able to take oral medications.
• Other medications like osilodrostat and metyrapone also show promise in reducing cortisol levels, with responses typically seen within hours or days 1.
• Metyrapone, an 11β-hydroxylase inhibitor, has been shown to normalize UFC in 71% of patients, with a median dose of 2127.5 mg/d and a mean follow-up of 8.7 months 1.
• However, etomidate's rapid action makes it a preferred choice for instantaneous decrease in cortisol levels, especially in severe cases where rapid normalization is crucial 1. Key considerations include the severity of the disease, the patient's ability to take oral medications, and the potential need for combination therapy or other interventions like BLA in very severe cases 1.

From the FDA Drug Label

Metopirone is an adrenal steroid synthesis inhibitor The instantaneous decrease in cortisol levels is caused by Metyrapone, which is an adrenal steroid synthesis inhibitor 2.

• Metyrapone works by inhibiting the enzyme 11-beta-hydroxylase, which is involved in the synthesis of cortisol in the adrenal gland.
• As a result, Metyrapone decreases the production of cortisol, leading to a decrease in cortisol levels.

From the Research

Instantaneous Decrease in Cortisol Levels

• There are several factors that can cause an instantaneous decrease in cortisol levels, including:
  • Metyrapone treatment: Metyrapone is an inhibitor of 11β-hydroxylase, which can decrease cortisol secretion in patients with Cushing's syndrome 3, 4.
  • Meditation and yoga: Certain types of meditation and yoga have been shown to reduce cortisol levels, including integrative meditation 5 and Psychoneuroendocrinoimmunology-based meditation (PNEIMED) 6.
  • Yoga: Yoga has been demonstrated to reduce the parameters of stress, including cortisol levels, and may act at the level of the hypothalamus by its 'anti-stress' effects 7.

Mechanisms of Cortisol Reduction

• The mechanisms by which these factors reduce cortisol levels are not fully understood, but may involve:
  • Inhibition of 11β-hydroxylase: Metyrapone works by inhibiting the enzyme 11β-hydroxylase, which is involved in the production of cortisol 3, 4.
  • Reduction of stress: Meditation and yoga may reduce cortisol levels by reducing stress and promoting relaxation 7, 5, 6.

Effects of Cortisol Reduction

• The effects of reducing cortisol levels can include:
  • Clinical and biochemical improvement: Reduction of cortisol levels has been associated with clinical and biochemical improvement in patients with Cushing's syndrome 3, 4.
  • Body weight reduction: Normalization of urinary-free cortisol (UFC) levels has been associated with body weight reduction 4.
  • Improved mental health: Reduction of cortisol levels has been associated with improved mental health outcomes, including reduced symptoms of depression and anxiety 7, 5, 6.