Cushings syndrome Flashcards
Definition
A disorder that occurs when your body makes too much of the hormone cortisol over a long period of time
Aetiology
Most cases occur from the administration of synthetic steroids or ACTH (adrenocorticotrophic hormone), for the treatment of certain medical conditions. e.g: asthma
Spontaneous cushings is rare- pituitary tumours account for 65% of all spontaneous cushings
the cases can be split into ACTH-dependant and non-ACTH dependant cases:
– ACTH dependant:
—- pituitary dependant (Pituitary adenoma, Cushings disease)
—- ectopic ACTH producing tumours (small cell lung cancer, carcinoid tumours)
—- ACTH administration
– Non-ACTH-dependent causes:
—- Adrenal adenomas
—- adrenal carcinomas
—- glucocorticoid administration
Others:
– alcohol induced pseudo-Cushings syndrome
Differentiating cushings syndrome from cushings disease
Cushings syndrome:
– term which refers to the abnormalities resulting from a chronic excess of glucocorticoids whatever the cause
Cushings disease:
– specifically refers to excess glucocorticoids resulting from inappropriate ACTH secretion from the pituitary
Pathophysiology
Cortisol pathway:
– hypothalamus produces CRH (cortisol releasing hormone), this stimulates the anterior pituitary leading to the production of ACTH.
– ACTH bings to the receptors of the adrenal cortex, meaning there will be production of ACTH.
– if these cushings syndrome, there is hyper stimulating of the adrenal gland to produce more cortisol
Cushings causing the central fat distribution:
– increased cortisol will stimulate a process called lipolysis (by breaking down triglycerides and turning them into FFA and glycerol)
– it also stimulates fat redistribution
This is due to lipolysis occurring in the peripheries and then the fat will be redistributed centrally
– this leading to a moon face, buffalo hump and significant abdominal obesity
Symptoms of skin and muscle:
– Cortisol will bind onto multiple different types of cells like muscle, connective tissue and bone
– it will break down proteins and initiate proteolysis.
– it will also inhibit collagen synthesis
Leading to:
– muscle atrophy (most commonly proximal muscles, proximal myopathy)
– bone weakness, leading to an increased risk of osteoporosis
– collagen by part in dermis, leads to thin skin (leading to striae, also poor wound healing along with decreased immune system).
Causing hypertension:
– increased cortisol– increases activity of the sympathetic nervous system, meaning an increased release norepinephrine.
– also increased beta receptors from the heart, norepinephrine will bind to them increasing CO leading to increased BP
Causing problems with the immune system (poor wound healing, more susceptible to illness):
– reduced neutrophil marination, inhibits T cell proliferation and inhibits antibody production from the plasma cells
—- meaning it cant fight off disease as well
Causing the complication of DM:
– increased cortisol acts on the liver, increasing gluconeogenesis, there will be an increased glucose in the blood
– meaning the pancreas will release insulin, increased cortisol also inhibits insulin to some extent
– causing hyperglycaemia increasing the chances of DM
—- known as the DIABETOGENIC AFFECT OF CORTISOL
Clinical presentation
Pts are obese with fat distribution centrally, affecting the trunk and abdomen creating a buffalo hump in the neck
Symptoms that differentiate this from just normal obesity:
Plethoric complexion with a moon face
Skin is thin and bruises easily and there are purple striae on the abdomen, breasts and thighs
– acne
– poor healing cuts
– depression
– psychosis
Proximal myopathy
hypertension
musculoskeletal problems like osteoporosis
ACTH dependant causes will see:
– pigmentation occurring
Signs and symptoms women may experience:
– thicker or more visible body and facial hair
– irregular or absent periods not related to the menopause
Men may experience:
– decreased libido
– erectile dysfunction
– decreased fertility
Untreated cushings can lead to:
– diabetes mellitus
