Disorders of Adrenal Function
Cushing's syndrome - clinical features, causes, investigations and
treatment
Conn's syndrome - clinical features, causes, investigations and treatmet
Hypoadrenalism (Including Addison's disease) - clinical features,
casues, investigations and treatment
Congenital adrenal hyperplasia - clinical features, causes, investigations
and treatment
The adrenal gland sits on top of the kidney and is composed of two main parts. The
cortex on the outside and the medulla in the middle.
The cortex is subdivided into three layers, from outside going in-
Zona glomerulosa – Secretes the mineralocorticoids e.g. aldosterone
Zona fasiculata – Secretes the glucocorticoids e.g. cortisol
Zona reticularis – Secretes the sex steroids e.g. testosterone
The medulla releases adrenaline and noradrenaline.
The synthesis of ….
Actions of Cortisol—
Overall glucocorticoids are essential for the response to stress!
Glucocorticoids increase plasma glucose levels through a number of ways-
-Increasing gluconeogenesis
-Decrease glucose utilisation (GLUT 4 expression inhibited)
-Increase glycogenesis
-Increase glycogen storage
Cortisol increases lipolysis, which provides energy (glyercol can be fed into
gluconeogenic pathway) (in reality, due to hyperglycemia, insulin usually takes over
this bit and so overall you get lipogenesis, which is why people with excess cortisol gain
weight)
Cortisol increases protein catabolism in muscle, which releases amino acids which can
be made available to the liver for use in gluconeogenesis (which is why people with
excess cortisol often have hyperglycemia)
Na+ and H2O retention, which maintains BP
Anti-inflammatory effects of cortisol
Increased gastric acid production – to prevent infection
, Cushing’s
Cushing’s syndrome is the clinical features of chronic exposure to excessive levels of
cortisol. The incidence is 2/1,000,000 in the population. Ratio makes incidence
significantly higher in females than males and typical age of onset is 20-40 years of age.
So as stated Cushing’s Syndrome is having excess cortisol in the blood.
Cushing’s Disease is having excess cortisol in the blood due to an ACTH secreting
pituitary tumour.
Symptoms and Signs of Cushing’s Syndrome include:
Changes in protein and fat metabolism (due to effects of high insulin and proteolysis)
-Change in body shape
-Central obesity
-Moon face
-Buffalo hump
-Thin skin, easy bruising
-Oesteoporosis (brittle bones)
-Diabetes (as cortisol promotes insulin resistance)
Changes in sex hormones (as ACTH causes release of androgens)
-Excessive hair growth
-Irregular periods
-Problems conceiving
-Impotence
Salt and water retention (due to cortisol acting on mineralocorticoid receptor)
-High blood pressure
-Fluid retention
Investigation of Cushing’s Disease
The way we investigate someone who we believe may have Cushing’s is in three stages:
-Screening -> test urinary free cortisol (we could test at midnight, when cortisol should
be at its lowest but generally we do a 24hr urinary cortisol test. This is because cortisol
rises and falls over the day) and look at diurnal rhythm (to see how it changes)
-Confirmation of the Diagnosis -> for confirmation we would do an over night
dexamethasone suppression test
-Differentiation of the Cause (-> is it true Cushing’s or pseudo or exogenous? Where in
the pituitary is it coming from? Where in body if ectopic?
Cushing's syndrome - clinical features, causes, investigations and
treatment
Conn's syndrome - clinical features, causes, investigations and treatmet
Hypoadrenalism (Including Addison's disease) - clinical features,
casues, investigations and treatment
Congenital adrenal hyperplasia - clinical features, causes, investigations
and treatment
The adrenal gland sits on top of the kidney and is composed of two main parts. The
cortex on the outside and the medulla in the middle.
The cortex is subdivided into three layers, from outside going in-
Zona glomerulosa – Secretes the mineralocorticoids e.g. aldosterone
Zona fasiculata – Secretes the glucocorticoids e.g. cortisol
Zona reticularis – Secretes the sex steroids e.g. testosterone
The medulla releases adrenaline and noradrenaline.
The synthesis of ….
Actions of Cortisol—
Overall glucocorticoids are essential for the response to stress!
Glucocorticoids increase plasma glucose levels through a number of ways-
-Increasing gluconeogenesis
-Decrease glucose utilisation (GLUT 4 expression inhibited)
-Increase glycogenesis
-Increase glycogen storage
Cortisol increases lipolysis, which provides energy (glyercol can be fed into
gluconeogenic pathway) (in reality, due to hyperglycemia, insulin usually takes over
this bit and so overall you get lipogenesis, which is why people with excess cortisol gain
weight)
Cortisol increases protein catabolism in muscle, which releases amino acids which can
be made available to the liver for use in gluconeogenesis (which is why people with
excess cortisol often have hyperglycemia)
Na+ and H2O retention, which maintains BP
Anti-inflammatory effects of cortisol
Increased gastric acid production – to prevent infection
, Cushing’s
Cushing’s syndrome is the clinical features of chronic exposure to excessive levels of
cortisol. The incidence is 2/1,000,000 in the population. Ratio makes incidence
significantly higher in females than males and typical age of onset is 20-40 years of age.
So as stated Cushing’s Syndrome is having excess cortisol in the blood.
Cushing’s Disease is having excess cortisol in the blood due to an ACTH secreting
pituitary tumour.
Symptoms and Signs of Cushing’s Syndrome include:
Changes in protein and fat metabolism (due to effects of high insulin and proteolysis)
-Change in body shape
-Central obesity
-Moon face
-Buffalo hump
-Thin skin, easy bruising
-Oesteoporosis (brittle bones)
-Diabetes (as cortisol promotes insulin resistance)
Changes in sex hormones (as ACTH causes release of androgens)
-Excessive hair growth
-Irregular periods
-Problems conceiving
-Impotence
Salt and water retention (due to cortisol acting on mineralocorticoid receptor)
-High blood pressure
-Fluid retention
Investigation of Cushing’s Disease
The way we investigate someone who we believe may have Cushing’s is in three stages:
-Screening -> test urinary free cortisol (we could test at midnight, when cortisol should
be at its lowest but generally we do a 24hr urinary cortisol test. This is because cortisol
rises and falls over the day) and look at diurnal rhythm (to see how it changes)
-Confirmation of the Diagnosis -> for confirmation we would do an over night
dexamethasone suppression test
-Differentiation of the Cause (-> is it true Cushing’s or pseudo or exogenous? Where in
the pituitary is it coming from? Where in body if ectopic?
