CLINICAL- ENDOCRINE, PITUITARY Flashcards
Where are vasopressin and oxytocin produced?
In the neurosecretory neurons of the Hypothalamus
They then travel to the pituitary where they can access the circulation
What is the clinical presentation of a pituitary tumour (rare!)?
Pressure effects from the tumour: vision can be disturbed as tumour may press on the optic chiasma
Pituitary failure
Hypersecretion of one or more hormones
How do surgeons access the pituitary gland?
Through the nose
Makes it easier than going through the brain
How could you correct the visual disturbance caused by a pituitary tumour?
Correct the pressure as it’s pushing on the optic nerves and chiasm
What are non functioning pituitary tumours?
They cause problems with where they are but they don’t actually produce any hormones
The tumour grows and presses on the pituitary gland and squashes it, looses it’s function, causes problems
These account for 90% of all pituitary tumours
Treatment is surgery and we aim to protect eyesight and restore function. There isn’t a pharmacological treatment!
What are functioning pituitary tumours?
These tumours will produce hormones
Most common are prolactinomas
There is pharmacological treatment available
What is a prolactinoma? What effects does it have?
A tumour that secretes prolactin
Is has pressure effects:
Headache, loss of peripheral vision
It has hormone effects:
Women get absent periods, infertility and galactorrhoea (nipple discharge)- therefore women symptoms are quite obvious!
Men: present with erectile dysfunction
How are prolactinomas treated?
Prolactin is naturally inhibited by release of dopamine from the hypothalamus.
Dopamine receptor agonists used- dopamine released- Fall in prolactin - Tumour shrinks
How long does it take with treatment for 40% of patients with prolactinomas to be in remission if tumours disappeared and prolactin now normal?
After 3 years of treatment with dopamine receptor agonists
Dopamine agonists used to treat prolactinomas include:
Cabergoline
Bromocriptine
Quinagolide
What are our concerns with these treatments?
They all require a baseline and then annual echocardiograms (ECG) apart from quinagolide
common side effects: nausea, fatigue, mood disturbance (patients therefore advised to take at night)
What happens with dopamine agonist drugs (for prolactinomas) in pregnancy??
Cabergoline has a long half life
So bromocriptine is preferred
Usually stope treatment in pregnancy unless tumour really big
Patient presenting with: Rings not being able to fit anymore bigger fingers Underbite (bottom jaw sticks out) Bigger feet Bigger nose Headaches Diabetes What could this be?
Acromegaly
A result of a pituitary tumour- gland produces an excess of growth hormone, body excessively grows
We ask people to bring in old photographs to compare!
What does gigantism (people are giants) result from?
growth hormone secreting pituitary tumours in childhood
What is somatostatin used for?
With acromegaly (increase in GH due to pituitary tumour) the first line treatment is SuRGERY
If this doesn’t work/ there’s no cure, somatostatin and it’s analogues can control growth hormone secretion.
Somatostatin is a growth hormone inhibitory hormone with a v short half life of 2 mins so not used
Octreotide and lanreoride are analogues that are used as their half life in 2 hours
What are octoreotide and lanreotide?
Somatostatin analogues used to treat acromegaly
They’re DEPOT INJECTIONS given once a month
Only shrink tumours in 30%
What medication related to the pituitary can cause gallstones?
The somatostatin analogues octoreotide and lanreotide
Can also cause nausea and diarrhoea and glucose intolerance
What is Pegvisomont and what is it used to treat?
The only available Growth Hormone receptor antagonist
It’s actually a mutated growth hormone with polymers attached to prolong it’s half life!
With this drug we monitor IGF-1, as Pegvisomont blocks the action of GH receptor to reduce the production of IGF-1 which goes on to produce growth
Pretty successful! 90% reduction in IGF-1 so less growth!
What’s the side effect with IGF-1 reducing drug Pegvisomont?
Hepatitis
What’s the main cause if Cushings on the wards?
steroid treatment!
How does cushings present?
Central obesity but thin arms and legs Bruising and thin skin Hypertension Diabetes Moon face Buffalo hump Low potassium Gastric ulcer Psychological- people go abit mad "steroid psychosis"
What’s the treatment for cushings?
Surgery
METYRAPONE given in preparation for pituitary surgery
This blocks hydrocortisone synthesis- to achieve normal cortisol
What hormone in excess causes cushings?
ACTH / cortisol
Cortisol levels are elevated by large amounts of ACTH.
If you have no cortisol, what does this cause?
Drop in blood pressure
Lowers your immune system
What mechanism are all hormones controlled by, including the pituitary, thyroid etc?
Negative feedback mechanism
METYRAPONE is given before surgery for Cushing’s/ the pituitary to get cortisol levels normal.
Why do we want normal cortisol before surgery?
To help with tissue wound healing
To reduce chance of infection before surgery
Big steroid doses suppress your immune system: this is not good before surgery so metyrapone helps get cortisol back on track so immune system is strengthened!
If the pituitary fails it’s sometimes removed in surgery. What effects can this have??
15% to patients will have major hormone defects
45% will be growth hormone deficient
So we need to replace these in the patient: the goal of replacement therapy is to mimic the normal body secretion as closely as possible
Why should hydrocortisone only be given as a replacement therapy?
It’s a short acting steroid
It only lasts 6 hours
Prednisolone can be used as a treatment in things like asthma etc
Who qualifies for growth hormone replacement?
NICE says adults with:
Stimulation test must prove Growth hormone deficiency
Low Quality of life (use AGDA score)
Must trial for 3-9 months and see an improvement in AGDA score
How do we monitor growth hormone replacement [recombinant growth hormone preparations]?
Monitor with IGF-1 (produced from growth hormone binding) Monitor symptoms (QoL AGDA score)
What’s the most common type of testosterone replacement therapy?
IM injections in bum every 3-14 weeks
Gels and tablets not very effective!
One of testosterone replacements sides effects is Polycythaemia. What is this?
An excess of red blood cells
Due to stimulated red blood cell production in the bone marrow
Can cause strokes as more Hb so blood more sticky!!
Does testosterone cause prostate cancer?
It doesn’t cause it
But there is increased risk of it so it fuels it
Side effects of testosterone (prostatism and Polycythaemia) should be monitored every 6 months
Is fludrocortisone used in pituitary failure?
No
Hydrocortisone is used to mimic cortisone levels
10mg morning, 5mg lunch, 5mg evening
Equivalent steroid doses:
What is 20mg oral hydrocortisone (the dose given to replace cortisol/ ACTH in pituatry failure) equivalent to?
5-7.5mg if prednisolone
0.75mg of Dexamethasone
These are small doses of steroids compared to other conditions,
Remember it’s a treatment dose, therefore smaller doses than usual!
This is just showing steroid equivalence because it shows how smaller amount of hydrocortisone we given as replacement therapy in pituitary failure
What are the HYDROCORTISONE sick day rules with fever (febrile illness) or a fractures limb?!!
Double the dose
What are the HYDROCORTISONE sick day rules with surgery???
IV hydrocortisone during surgery
Then double the dose
What are the HYDROCORTISONE sick day rules with gastroenteritis?
Double the dose IM hydrocortisone (as you would throw up the oral)
What are the HYDROCORTISONE sick day rules for severe shock or a long flight?
Double the dose
What are the HYDROCORTISONE sick day rules for a tooth being taken out?!!!
20mg oral hydrocortisone
What’s the roll of desmopressin (secreted from pituitary)?
Acts on kidney, allows water to be re-absorbed into blood stream
It’s given at night and to control symptoms in the day
Controls Polyuria
Check U&E’s to make sure sodium is normal!!
If we remove the pituitary gland we need to give hormone replacement therapy. Which hormones need to be replaced??
All secreted from the anterior pituitary:
Growth hormone (especially in children as they’re growing!!)
Oestrogen and testosterone (LH and FSH)
Thyroxine
Cortisol (ACTH)
Secreted from the posterior pituitary:
Desmopressin
What are the SIGNS of Hypothyroid disease?
Facial swelling Hair loss Dry skin Reduced heart rate Husky voice!! Hypothermia
What are the SIGNS of hyperthyroidism?
Tremor Warm skin Agitation Goitre (swollen gland, Lump in neck-Gdad Brian!) Exophthalmos (bulging of the eyes) Atrial fibrillation
What can cause drug induced thyroid disease?
Amiodarone
Lithium
What would you expect the thyroid function tests to look like in hypothyroidism?
Low T4
Low T3
High TSH
Secondary hypothyroidism: TSH low
What abnormal tests would you expect with hyperthyroidism?
High T3
High T4
Low TSH
Hyperthyroidism leads on to thyrotoxicosis (excessive amount of thyroid hormones in blood). What is a common cause of this?
Graves’ disease (immune system attacks the thyroid gland leading to hyperthyroidism)
Also Amiodarone induced!
What are the SYMPTOMS of hypothyroidism?
Patients will feel: Constipated Put on weight (we know this with underactive thyroids!) Depression Menorrhagia (heavy P) Psychosis Hearing loss
What are the SYMPTOMS of hyperthyroidism?
Palpitations Diarrhoea Weight loss Sweating Heat intolerance Hunger and thirst Anorexia
How do we MONITOR patients with thyroid diseases?
Their levels of: TSH T4 T3 Also monitor symptoms
How is it thought that Amiodarone causes drug induced thyroid disease?
It contains 40% iodine
It inhibits the conversion of T4 to T3, and can also inhibit the thyroid glands function so this leads to Hypothyroidism
It can cause an inflammatory process leading to increased release of thyroid hormones, leads to Hyperthyroidism
Who should get thyroid screening??
Patients who take amiodarone or lithium Patients who have diabetes Patients with Atrial Fibrillation Patients with hyperlipidaemia Down's syndrome, turners syndrome, Addison's
What’s the link between thyroid and heart disease??
Thyroid dysfunction can lead to changes in:
Cardiac output
contractility
Blood pressure
The cardiovascular abnormalities usually resolve with restored thyroid function!!!
Adrenal gland dysfunction often caused 2 conditions. What are these?
Cushing’s syndrome
Addison’s disease
What do the adrenal glands secrete?
Our natural Steroids:
Mineralcorticoids
Glucocorticoids (cortisol)
Gonadocorticoids
Cells in the adrenal cortex make hormones: cortisol, aldosterone, androgens
Also epinephrine (adrenaline) and norepinephrine (noradrenaline)
What’s the difference between Cushing’s syndrome and Cushing’s disease?
Cushing’s syndrome: hormone disorder caused by high levels of cortisol in the blood. Can be caused by steroid drugs or tumor producing ACTH.
Cushings disease: one specific cause of the syndrome; pituitary tumour producing large amounts of ACTH: in turn elevates cortisol. It’s the most common cause of Cushing’s syndrome apart from those caused by steroids.
What’s the most common cause of Cushing’s syndrome ?
Most commonly drug induced- high doses of steroids (glucocorticoids): result in excess cortisol!
Or less commonly caused by tumours in the pituitary or adrenal glands that produce cortisol or ACTH
What do we lack in Addison’s?
Lack of cortico and mineralo corticoids
Addison’s involves the slow progressive loss of cortisol and aldosterone
Most commonly caused by auto-immune diseases where antibodies attack the adrenal glands
What are the common signs and symptoms of Addison’s? Think of the algorithm!!
A always tired D dizzy when standing D drop in blood pressure on standing I inexplicable weight loss S skin colour changes O only eating sparingly/ anorexia N no strength in hand grip or limbs (weakness!) S sick or nauseous
Also: Low sodium, high potassium
What can happen in Acute Addison’s disease?
Shock!
No fight or flight system in place due to deterioration of the adrenal gland so insufficient production of hormones such as glucocorticoids (such as Cortisol, needed to help the body respond to stress)
Addison’s can result in insufficient levels of mineralcorticoids. How do we replace these?
Using Fludrocortisone
Addison’s can result in insufficient levels of glucocorticoids (such as cortisol) how do we replace these?
Use hydrocortisone
Why? Because it can be biochemically monitored
How could Cushing’s be linked to asthma?
In asthma, oral corticosteroids can be prescribed if the other steps of the treatment pathway haven’t worked.
These patients can therefore be predisposed to cushings
Should be weaned off high steroid doses but can be difficult if patients keep having bad attacks of asthma.
Why is diabetes a symptom of cushings??
Cortisol helps to balance insulin in regulating blood sugar levels
Hyperglycaemia is related to corticosteroids use.
Ideally to treat this we want to take the person off the steroid, Sometimes this isn’t possible so we would probably consider using Metformin or the thizolidinediones such as rosiglitazone or pioglitazone.
The treatment of glucocorticoid induced diabetes usually resembles the treatment of type 2 diabetes, the prognosis of this diabetes is usually good as it’s well treatable
What is CORTISOL important for?
Regulating blood pressure
Regulating the immune system
Responding to stress
Helping to balance insulin in regulating blood sugar level
What two parts of the brain is the release of cortisol regulated by?
The hypothalamus and the pituitary
What is Aldosterone important for?
Maintaining the balance of salt and water in the body, helping to control blood pressure
Where is the pituitary gland located? (Hint: same place as hypothalamus!)
The brain/ behind the lower skull
Impaired function of the adrenal glands can lead to increased or decreased production of adrenal hormones. Cushing’s and Addison’s disease are both to do with abnormal adrenal function.
What is the key difference between Addison’s and Cushing’s?
Cushings is to do with levels of cortisol remaining high over an extended period of time.
Addison’s is to do with hormone deficiency (so the opposite): glucocorticoid (incl. cortisol) and mineralocorticoids are deficient
What tests and observations may help to detect Addison’s as it is commonly misdiagnosed??
BP: low: 90/60
Low sodium; 130 (normal range is 135-145)
High potassium; 5.7 (normal range is 3.5-5.5)
Patients can look ‘tanned’: hyper pigmentation
What mechanism is used to regulate the levels of glucocorticoids such as cortisol?
A negative feedback loop
Hypothalamus secretes CRH,
which causes the pituitary gland to release ACTH,
which causes the adrenal cortex to release cortisol,
high levels of cortisol are then detected by the hypothalamus and pituitary
so they no longer stimulate the adrenal cortex!!
What is hyperpigmentation a characteristic of?
Characteristic feature of Addison’s
It’s caused by increasing levels of ACTH as this causes darkening of the skin
Salt loss is a common symptom of Addison’s
We know that we see low sodium levels with this disease
Loss of salt leads to patients having salt cravings
What two drugs are used to treat Addison’s disease??
Hydrocortisone
Fludrocortisone
What’s the test called we use to diagnose Addison’s??
Short Synacthen test
We inject tetracosactide (a chemical copy of ACTH, ACTH usually stimulates the adrenal gland to produce cortisol, so if the glands are working this chemical should do the same)
If inadequate serum cortisol response is shown we refer them for a Plasma Adrenocorticotropic hormone test, if raised it confirms Addison’s
What’s the risk with adults taking hydrocortisone doses of 25mg or higher for Addison’s and what should we monitor?
Osteoporosis, there’s decreased bone mineral density
Clinical risk factor of fracture!!
Ten year major fracture risk should be monitored and managed
Calcium and Vitamin D intake should be optimised in these patients, along with stopping smoking and limiting alcohol intake
Most adults can be successfully treated on doses of 15-20mg daily
When may Calcium and vitamin D be prescribed in endocrine patients?
With Addison’s patients taking corticosteroids, there’s deemed to be a risk of osteoporosis
These should be prescribed to optimise their levels and make their bones less likely to break
They are also advised to do weight baring excersise to strengthen bones, stop smoking and limit their alcohol intake
When you are ill with a fever and have Addison’s, what do you need to do to your dose of hydrocortisone?
What if the fever goes above 39 degrees?
Fever (over 37.5) DOUBLE your dose of hydrocortisone
Over 39: Triple your dose of hydrocortisone
What happens if you have a serious injury and have Addison’s?
You need to take 20mg of hydrocortisone immediately on top of your normal daily dose. Probably best to use an emergency injection of hydrocortisone or can take it orally, Addison’s patients are issues with emergency kitts
For any illness or injury or operation in a patient with Addison’s, they will need extra hydrocortisone. Why is this?
Because usually when the patient is ill they require extra cortisol to help them get better with things causing stress, but in Addison’s the levels of cortisol are low so we have to give more hydrocortisone to replace this, otherwise they will use all their low levels of cortisol and run the risk of going into adrenal shock!!
What happens if you vomit and you have Addison’s??
Vomit once: take 20mg hydrocortisone immediately
Vomit twice: use emergency injection of hydrocortisone (patients are usually issued with 3-5 vials of injectable hydrocortisone as an emergency kit for IM injection)
Why is it so important for people to let doctors, dentists etc know that they have Addison’s?
Because they will need extra doses of hydrocortisone to deal with the stress!!
Other than being ill or injured, what other situations do Addison’s patients need to think about with regards to their hydrocortisone doses??
Going on holiday- make sure they have supplies plus emergency injections with them
Doing strenuous Exercise: take extra hydrocortisone and fluids or avoid dehydration
People working shifts: normally hydrocortisone doses are shaped around a normal routine so check with doctor what to do.
What are the symptoms of adrenal crisis??
Vomiting Abdominal pain Myalgia Joint pains Severe hypotension Hypovolemic shock (severe blood and fluid loss)
Need to use your emergency hydrocortisone injection kit!!!
How can a pharmacist get involved with helping patients with Addison’s?
Advising on timing of doses:
Steroid doses should be taken in morning and at lunch time.
Doubling doses if patients are unwell and advise on sick day rules.
Managing adrenal crisis
Can advise patients to have Flu vaccinations to avoid getting ill
What should Addison’s patients requiring antibiotic treatment for infection be told to do with their hydrocortisone??
Double their normal dose
We know that acromegaly is over production of growth hormone in adults, and if this happens in children it is gigantism.
What is hypo-pituitarism??
A deficiency in growth hormone.
Leads to dwarfism
We can give these patients Somatropin (growth hormone) - DO NOT GET MIXED UP WITH SOMASTATIN USED FOR AGROMEGALY!!!
One of the hormones produced in the hypothalamus but then is released into the circulation via the pituitary is vasopressin (ADH).
In hypo-pituitarism, what does a lack of ADH release cause??
Diabetes insipidus (rare condition, produce large amount of dilute urine and feel thirsty)
This is because ADH (vasopressin) is antidiuretic hormone, which is in charge of controlling water content in the body.
If there is a lack of production of this, body’s water regulation out of control: diabetes insipidus
What does the management of acute adrenal crisis involve??
I.e. Somebody has gone into shock as cortisol/ aldosterone levels are so low
Dial 999- it’s an emergency
Use parenteral hydrocortisone
Administer IV fluids
What is the most common cause of destruction of the adrenal gland in Addison's? TB Autoimmune: immune system attacks it Steroid induced Diabetes
Autoimmune!
TB can also cause it be not very common
Other 2: not true
