16. Obesity, Cushing's and background science Flashcards
see adrenal insufficiency
What is cushings syndrome
the signs and symptoms that develop after prolonged abnormal elevation of cortisol
what is Cushing’s disease
refers to the specific conditions where a pituitary adenoma (tumour) secretes excessive ACTH
What are the common features of Cushing’s (imagine a round person in the middle with thin, weak limbs and image the effects of high levels of stress hormone)
Round "moon' face central obesity abdominal striae (red, purple) buffalo hump (fat pad on upper back) proximal limb muscle wasting
Hypertension cardiac hypertrophy hyperglycaemia (T2DM) depression insomnia
osteoporosis (protein wasting) easy bruising and poor skin healing acne Hirsutism ( women growing facial hair) hypokalaemia
what are some causes of Cushing’s syndrome
Exogenous steroids (in patients on long term high dose steroid medications)
Cushing’s Disease (a pituitary adenoma releasing excessive ACTH)
Adrenal Adenoma (a hormone secreting adrenal tumour)
Paraneoplastic Cushing’s
What is paraneoplastic Cushing’s
excess ACTH is released from a cancer (not of the pituitary) and stimulates excessive cortisol release
ACTH from somewhere other than the pituitary is called “ectopic ACTH’
what kind of cancer is the most common cause of paraneoplastic Cushing’s
small cell lung cancer
what does ACTH stand for and what is its role
Adrenocorticotropic hormone (ACTH) is a hormone produced in the anterior pituitary gland in the brain.
The function of ACTH is to regulate levels of the steroid hormone cortisol, which released from the adrenal gland.
how does the dexamethasone suppression test (DST) work
take a dose of dexamethasone (synthetic glucocorticoid steroid) at night ie 10pm and their cortisol and ACTH is measured in the morning
if the low dose dexamethasone test is normal what can be excluded
Cushings
What dose of dexamethose is used in the low dose DST and what is used in the high hose
1mg in low
8mg in high
What is the normal response for the dexamethasone test
dex suppresses the release of cortisol by effecting negative feedback of the hypothalamus and pituitary
hypothalamus responds by reducing CRH output
pituitary responds by reducing ACTH output
Lower CRH and ACTH results in low cortisol
when cortisol levels aren’t suppressed, this is abnormal and seen in Cushing’s syndrome
What does the high dose dexamethasone suppression test show in Cushing’s disease (pituitary adenoma)
at high dose the pituitary still shows some reponase to negative feedback and so if enough to suppress cortisol
low cortisol
When there is an adrenal adenoma what does the high dose dexamethasone suppression test show
cortisol production is independant from the pituitary
therefore cortisone is not surprised however ACTH will be surpassed
When there is an ectopic ACTH (eg from a small cell carcinoma) what does the high dose dex suppressio test show
neither cortisol or ACTH will be suppressed as the ACTH production is independant
What can be used as an alternative to dexamethasone suppression test to diagnose Cushing’s syndrome but won’t indicate the underlying cause
24 hour urinary free cortisol
what other tests can be used to diagnose Cushing’s depending on the cause
- FBC (raised white cells) and electrolytes (potassium may be low if aldosterone is also secreted by an adrenal adenoma)
- MRI brain for pituitary adenoma
- Chest CT for small cell lung cancer
- Abdominal CT for adrenal tumours
What is the main treatment for Cushing’s
main treatment is to remove the underlying cause (surgically remove the tumour)
- trans-sphenoidal (through the nose) removal of pituitary adenoma
- surgical removal of adrenal tumour
- surgical removal of tumour producing ectopic ACTH
- if adrenal glands are damaged then need to remove them and give life long steroids
what age does Cushing’s disease usually present in
25-45 and affects females more
What clinical features are not discriminatory for bushings
generalise obesity
oligomenorrhoea
headaches
abnormal GTT
What test can differentiate between pituitary and adrenal Cushing’s
ACTH levels
following positive initial screening for Cushing’s, what test would be performed if ACTH is raised
pituitary screening
following positive initial screening for Cushing’s, what test would be performed if aCTH is not raised
adrenal imaging
which test discriminates between a pituitary and Coptic source of excess ACTH
inferior petrosal sinus sampling
what would be the most useful first line investigation if ectopic ACTH excess was suspected
CXR
what abnormalities in the patients ions would be seen in Cushing’s in terms of sodium, potassium and bicarbonate
high sodium
low potassium
high bicarbonate
In obesity, what BMI would class someone as healthy weight overweight obesity I obesity II obesity III
healthy 18.5-24.9 overweight 25-29.9 obesity I 30-34.9 obesity II 35-39.9 obesity III 40 or more
in what ethnicities do you use lower BMI thresholds to reduce the risk of conditions such as T2DM
black African, African-caribbean and Asian (south asian and Chinese)
what are the main illnesses that are linked to obesity
T2DM fatty liver diease HTN gallstones GORD psychological and psychiatric morbidities
Under what circumstances would you consider referral to a tier 3 service for obesity
o the underlying causes of being overweight or obese need to be assessed
o the person has complex disease states or needs that cannot be managed adequately in tier 2 (for example, the additional support needs of people with learning disabilities)
o conventional treatment has been unsuccessful
o drug treatment is being considered for a person with a BMI of more than 50 kg/m2
o specialist interventions (such as a very-low-calorie diet) may be needed
o surgery is being considered.
what is the criteria for bariatric surgery
o They have a BMI of 40 kg/m2 or more, or between 35 kg/m2 and 40 kg/m2 and other significant disease (for example, type 2 diabetes or high blood pressure) that could be improved if they lost weight.
o All appropriate non-surgical measures have been tried but the person has not achieved or maintained adequate, clinically beneficial weight loss.
o The person has been receiving or will receive intensive management in a tier 3 service[10].
o The person is generally fit for anaesthesia and surgery.
o The person commits to the need for long-term follow-up.
if orlistat does cause at least a ___% body weight loss within 12 weeks of starting, then the treatment must be stopped
5%
In an adrenal crisis how will the patient present
hypotensive and hyponatraemia
what would the treatment of an adrenal crisis be
o Needs a random serum cortisol and plasma ACTH
o TREAT with high dose, replacement hydrocortisone – 100mg IV every 6 hours
o IV saline- 2/3 L first hour, then 3-4 L per day
What important structure is situated immediately anteriorly to the pituitary gland and what can. allege pituitary tumour cause
optic chiasm
bitemporal hemianopia
Explain the HPA axis
hypothalamus releases corticotrophin-releasing hormone (CRH) which acts on the pituitary gland to cause adrenocorticotropic hormone (ACTH) to be released and acts of the adrenal glands to make them release cortisol
where are the adrenal glands located and what is their role
over the medical aspects of the upper poles of each kidney
role is to secrete steroid and catecholamine hormones
arterial supply is via 3 main arteries;
Where does the anterior supra-renal artery arise from
inferior phrenic artery
arterial supply is via 3 main arteries;
where does the middle supra-renal artery arise from
directly from the abdominal aorta
arterial supply is via 3 main arteries;
where doe the inferior suprarenal artery arise from
renal artery
what is the venous drainage of the adrenal gland
suprarenal veins
left suprarenal vein drains into the left renal vein
right suprarenal vein drains into the inferior vena cava
what is the issue with the adrenal glands having a rich blood supply
accounts for frequent metastasis of malignancies such as lung cancer, to the adrenal glands
Name the 4 main regions of the adrenal gland from most superficial to deep
Zona Glomerulosa
Zona Fasiculata
Zona Reticularis
medulla
which region of the adrenal gland produces minteralcorticoids and give an example of one Zona Glomerulosa Zona Fasiculata Zona Reticularis medulla
zona glomerulosa
aldosterone
which disease affects the Zona Glomerulosa and the production of aldosterone
Conns
Excess aldosterone results in electrolyte imbalances and hypertension
which regions of the adrenal gland produces glucocorticoids and give an example Zona Glomerulosa Zona Fasiculata Zona Reticularis medulla
Zona Fasiculata
cortisol
which disease affects the Zona fasculata and affects. glucocorticoid hormone release
Cushing’s syndrome
Adrenal tumour resulting in excess glucocorticoid secretion
which region of the adrenal gland produces androgen precursors and give some examples Zona Glomerulosa Zona Fasiculata Zona Reticularis medulla
zona rectularis
DHEA & androstenedione (converted to testosterone or oestrogen by gonads)
what disease Resulting in lack of mineralocorticoids and glucocorticoids and excess of testosterone and its derivatives
congenital adrenal hyperplasia
which region of the adrenal gland produces catecholamines and give some examples Zona Glomerulosa Zona Fasiculata Zona Reticularis medulla
medulla
Adrenaline and noradrenaline
which disease is a neuroendocrine tumour of the medulla and results in excess secretion of adrenaline
Phaeochromocytoma
The drug metyrapone is a glucocorticoid synthesis inhibitor which inhibits 11 beta-hydrolase, therefore inhibiting synthesis of what hormone
cortisol
what are hte long term side effects of steroid therapy
o HTN o Diabetes mellitus o Fatty liver o Susceptibility to infection o Osteoporosis o Avascular necrosis of bone o Skin sepsis o Electrolyte disturbance; hypokalaemia, metabolic alkalosis
what is important to consider if someone is on long term steroids
if they become sick they will need a higher dose of treatment and if they are having surgery then they need steroid cover if they are on a dose of 10mg or more of something like prednisolone
What patients should receive steroid cover for surgery
o Patients on corticosteroids at a dose of 10 mg or more of prednisolone (or equivalent) daily (equivalent to betamethasone 1.6 mg, dexamethasone 1.6 mg, hydrocortisone 40 mg, methylprednisolone 8 mg daily).
o Patients who have received corticosteroids 10 mg daily within the three months preceding surgery.
o Patients on high-dose inhaled corticosteroids (for example, beclomethasone 1.5 mg a day).
