What is stress
State of threatened homeostasis or dysharmony
How does the body respond to stress
Increased CV tone, ventilation
Increased glucose availability
decreased energy-consuming activities such as digestion and reproduction
Behavioural mechanisms as a response to stress
Increased;
arousal
alertness
Vigilance
What is the integrated stress response
SNS and adrenaline
CRH-ACTH-Cortisol
What hormones are stimulated under acute stress situations and which are inhibited
RAAs, ADH, GH (growth hormone), decreased thyroid hormones
Why is it important for cortisol to have an anti-inflammatory/immunosuppressive effect
IN stress-activated immune responses, cortisol protects the body against damage from potential over-activation of immune defence mechanisms
Prolonged elevated cortisol levels can lead to what
- Muscle wasting
- Hyperglycaemia
- GI ulcers (increased susceptibility)
- Impaired immune response
What disease causes glucocorticoid excess exogenous cause
Cushing’s syndrome
Can be endogenous (natural) or exogenous (causes by steroid medication)
What disease causes mineralocorticoid excess
Conn’s syndrome
What disease causes adrenal insufficiency
Addison’s disease
What are endogenous (natural causes) of Cushing’s syndrome
Primary-
-Adrenal (carcinoma, adenoma)
Secondary-
- PItuitary
- Ectopic
What are the levels of ACtH and cortisol in those with primary and secondary causes of Cushing’s
(P) Adrenal- Low ACTH, high cortisol
(S)Pituitary - high ACTH, high cortisol
(S) Ectopic- high ACTH, high cortisol
Difference between Cushing’s disease and Cushing’s syndrome
Cushing’s syndrome- umbrella term
Cushing’s disease- due to a pituitary ACTH secreting tumour
What is Cushing’s disease and what is the negative feedback loop like
Excessive production of ACTH. ACTH levels remain high as the tumour cells have impaired responsiveness to negative feedback from high cortisol levels
What causes acne, female frontal balding, female hirsutism and menstrual irregularities in Cushing’s patients
Excess production of adrenal androgens
What causes testicular atrophy, thin arms and less, muscle weakness, thin skin and purple striae (stretch marks) in Cushing’s patients
Breakdown of protein, muscle wasting, loss of collagen
What causes poor wound healing, easy bruising and infections of the skin in Cushing’s patients
Loss of collagen, immunosuppression
What other complications may arise from Cushing’s and why
Osteoporosis - altered bone metabolism
Hypertension- excess mineralocorticoid activity (sodium retention and hypokalaemia)
Diabetes- Hyperglycaemia, insulin resistance
What can excess glucocorticoids in childhood lead to
Growth retardation
How to diagnose Cushing’s
First confirm levels of high cortisol
Then look at ACTH levels to find out the cause
Then dynamic tests (Low-dose DEX test, high-dose DEX test and CRH test)
How is diurnal rhythm like in Cushing’s patient
There is a loss of diurnal rhythm of cortisol release. In a normal test, cortisol levels would be high in the morning and very low in the evening (at midnight). But in a Cushing’s patient, they remain high throughout the day
What can ACTH levels tell you about Cushing’s
Whether it is a primary or secondary cause
IN primary-low ACTH
Secondary- High ACTH
What is a low dose DEX test
Dexamethasone is a synthetic glucocorticoid
Dexamethasone suppression test:
Lack of suppression indicates hyper-autonomous secretion which confirms Cushing’s
What is a high dose DEX test and what does it tell you
There is normally suppression.
NO suppression when the cause is adrenal and an ectopic ACTH tumour
Suppression when the cause is Cushing’s disease (pituitary)
