Pituitary Pathology Flashcards
Where does the pituitary gland sit in the head?
Sella turcica of the sphenoid bone
What structure sits superior to the pituitary gland?
Optic chiasm
What structures sit laterally to the pituitary gland?
Cavernous sinuses
What are the contents of the cavernous sinus?
Cranial nerves: III, IV, Va, Vb and VI
Internal carotid artery
What is the venous drainage of the pituitary gland?
Pituitary gland -> Cavernous sinus -> Petrosal sinus -> Internal Jugular Vein
What is the arterial supply to the pituitary gland?
Hypothalamic-hypophyseal portal system
How does size of pituitary change in:
-pregnancy?
-with age?
Pregnancy = doubles in size
Age = shrinks
What are the hormones produced by the anterior pituitary gland?
TSH
ACTH
FSH
LH
Prolactin
Growth hormone
What are the hormones produced by the posterior pituitary gland?
ADH
Oxytocin
What does the hypothalamus produce to stimulate the production of TSH by the anterior pituitary gland?
TRH
What does the thyroid gland produce in response to TSH?
T3
T4
What does the hypothalamus produce to stimulate the production of ACTH by the anterior pituitary gland?
CRH
What does the adrenal glands produce in response to the anterior pituitary gland producing ACTH?
Cortisol
What does the hypothalamus produce to stimulate the production of FSH and LH by the anterior pituitary gland?
GnRH
What do the testes and ovaries produce in response to the anterior pituitary gland producing FSH and LH?
Oestrogen
Testosterone
Progesterone
What does the hypothalamus produce to stimulate the production of GH by the anterior pituitary gland?
GHRH
What does the production of GH lead to the production of?
What produces this?
IGF-1
Liver produces IGF-1
What is the function of cortisol?
Increases blood glucose
Increases alertness
Increases metabolism
Inhibits immune system
Inhibits bone formation
What is the function of GH and IGF-1?
Stimulates muscle growth
Increases bone density and strength
Stimulates cell regeneration and reproduction
Stimulates growth of internal organs
What is the function of ADH?
Acts on vasopressin receptors in thhe collecting duct leading to translocation of aquaporins leading to water reabsorption
What are the 3 types of Hypopituitarism?
Partial
Complete
Panhypopituitarism
What is the definition of Hypopituitarism?
Partial or. Complete deficiency of anterior and/or posterior pituitary gland
What are some causes of Hypopituitarism?
Tumours
Infections
Infiltration
Infarction
Pituitary apoplexy
Congenital
Kallmans
Trauma
What are some infiltration pathologies that can cause hypothyroidism?
Sarcoidosis
Haemochromatosis.
What type of infarction can cause Hypopituitarism?
Sheehans syndrome
What is sheehans syndrome and how does it cause pituitary infarction causing Hypopituitarism?
Infarction to anterior pituitary following a postpartum haemorrhage/massive blood loss
In pregnancy there’s hyperplasia of lactotrophs so have a high demand for blood
Mass blood loss leads to necrosis of the anterior pituitary
What is pituitary apoplexy?
Sudden haemorrhage/infarction of the pituitary gland
How does Hypopituitarism present?
Depends on the hormones that are affected/reduced
How does a patient with Hypopituitarism leading to low GH present?
Reduced exercise tolerance
Reduced lean mass
Weight loss
Stunted growth if in children
How does a patient with Hypopituitarism leading to low FSH and LH present?
Amenorrhoea
Anovulation
Erectile dysfunction
Low libido
Impaired sexual development
How does a patient with Hypopituitarism leading to low ACTH present?
Hyperkalaemia
Hypoadrenal crisis
Fatigue
Hypoglycaemia
Hyponatraemia
How does a patient with Hypopituitarism leading to low TSH present?
Hypothyroidism presentation
How does a patient with hypothyroidism present?
Weight gain
Fatigue
Constipation
Dry skin
Fluid retention
Coarse hair
How does a patient with Hypopituitarism leading to low prolactin present?
Failure to lactate
How does a patient with Hypopituitarism leading to low ADH present?
Polyuria
Polydipsia
What are the principles in investigating anterior pituitary gland issues?
Check levels of end gland hormones in the blood (cortisol, T3, T4, oestrogen, testosterone , IGF-1)
Then check the levels of the pituitary hormones (GH, FSH, LH, TSH, ACTH, TSH)
THEN DYNAMIC TESTING
What are the principles of dynamic testing for anterior pituitary issues?
If hormone is HIGH = SUPPRESS IT
If hormone is LOW= STIMULATE IT
What are the principles of investigating a posterior pituitary gland issue?
ADH issue
Check serum and urine osmolality, Na+
Do fluid deprivation test
What is the gold standard imagining for the pituitary gland?
MRI
What is the principle for treating pituitary issues?
Replace final hormone not the pituitary hormone
Surgical removal
What are the size classifications for pituitary tumours?
Microadeomas < 1cm
Macroadenomas > 1cm
Isoadenoma = 1cm
What is the most common type of pituitary tumour?
Adenomas:
Prolactinoma
Non functioning adenoma
Gonadotropinoma
Thyrotropinoma
How does a Prolactinoma present?
Hormone issue:
Galactorrhoea
Gonadal dysfunction:
-period irregularities
-low libido
-Erectile dysfunction
Mass effect:
-Headache
-Cranial. Nerve involvement (eye issues = optic chiasm)
-Hypopituitarism
How can the presentation of a pituitary tumour be remembered?
Mass effect of tumour (space it takes up)
Hormone specific effects
Why does a Prolactinoma cause gonadal dysfunction:
-period irregularities
-low libido
-ED
Prolactin inhibits the production of GnRH by the hypothalamus leading to low levels of FSH and LH being made
Dopamine also normally inhibits prolactin levels and vice Versa
What investigations do you do for Prolactinomas?
MRI pituitary
Prolactin levels
PRH levels
Pituitary hormone test
(FSH and LH)
Pregnancy test
U+Es
LFTs
What can cause Prolactinomas?
PCOS
Sevre hypothyroidism
Why does severe hypothyroidism cause Prolactinomas?
TRH increases leading to decreased dopamine which means levels of prolactin can increase
What visual defects are common with pituitary tumours?
Bitemporal hemianopia
What are the treatment options for Prolactinomas?
Nothing
Give Test or Oestradiol to restore gonadal function
DOPAMINE AGONISTS (BROMOCRIPTINE OR CABERGOLINE)
Transphenoidal surgery
What is acromegaly?
Too much growth hormone (growth after the age of growing)
How can acromegaly present?
Mass effect (headache, Bitemporal hemianopia)
Prorminent forehead
Sweaty skin
Large nose
Large hands and feet
Large tongue (macroglossia)
Large protruding jaw (prognathism)
Tiredness
What are some associated conditions with acromegaly?
Hypertrophic heart
HTN
Carpal tunnel syndrome (often bilateral)
Arthritis
Colorectal cancer
What investigations should be ordered if you think someone has acromegaly?
IGF-1 levels
Pituitary function test
Oral glucose tolerance test (75g glucose drink) GH and cortisol levels should reduce in a healthy individual
MRI
What should you suspect if the oral glucose tolerance test doesn’t reduce GH levels and the MRI doesn’t identify a pituitary lesion?
Might not be imaged
Ectopic production of GHRH from an ectopic source like a carcinoid tumour of the lungs or pancreas
What is the treatment for acromegaly?
Transphenoidal surgery of the pituitary adenoma = GOLD STANDARD
If caused by an ectopic carcinoid cancer surgical removal of these too
Somatostatin analogues and dopamine agonists have little proven efficacy
What is Cushing’s disease?
Excess ACTH production leading to elevated levels of cortisol/glucocorticoids in the body
What is Cushing’s syndrome?
The clinical manifestation of excessive exposure to glucocorticoids like cortisol
What are the signs a patient has Cushing’s disease or Cushing’s syndrome?
Plethoric moon shaped face
Central adiposity
Purple striae
Proximal limb muscle wasting
Enlarged upper back fat pad (buffalo hump)
Impaired skin healing
Hyperpigmentation of skin
Which type of Cushing’s will have skin hyperpigmentation and why?
Cushings disease
Cushing’s disease has increased ACTH which is what leads to increased. Prodcution of MSH
Cushing’s syndrome doesn’t have elevated ACTH
What disease Condtions can Cushings disease or syndrome cause on the body?
Oestoporosis
HTN
T2DM
Dyslipidaemia
Cardiac hypertrophy
Depression
Anxiety
What do patients with Cushing’s mostly die of and why?
PE
Due to hyper coagulability of blood
What are the causes of Cushing’s?
Cushing’s disease pituitary adenoma
Adrenal adenoma making cortisol
Paraneoplastic syndrome (small cell lung tumour releasing ACTH)
Exogenous (Prednisolone, dexamethasone)
What is the gold standard test to screen for Cushing’s syndrome?
Low dose overnight Dexamethasone suppression test
How does the low dose overnight Dexamethasone suppression test work to screen for Cushing’s syndrome?
Give dexamethasone att 11pm and it should supress the 9am cortisol levels
If not requires further testing
What further tests would be required if the low dose overnight Dexamethasone suppression test is positive for Cushing’s?
1.) Low dose 48hr dexamethasone suppression test
2.) High dose48hr Dexamethasone suppression test
What is the purpose of doing a 48hr low dose dexamethasone suppression test?
?Cushing’s syndrome
What is the purpose of doing a 48hr high dose dexamethasone suppression test?
Levels of dexamethasone will be high enough to suppress a pituitary adenoma (Cushing’s disease) leading to low suppressed levels of cortisol in the
How are adrenal adenomas and ectopic ACTH producing tumours affected by the 48hr high dexamethasone suppression test?
Unaffected
What are ACTH levels like in adrenal adenomas causing Cushing’s?
Low due to negative feedback
What are the cortisol levels following a 48hr low dose then high dose dexamethasone suppression test and the ACTH levels for CUSHINGS DISEASE/PITUITARY ADENOMA?
Low dose: cortisol HIGH
High dose: cortisol LOW/SUPPRESSED
ACTH levels: HIGH (the cause)
What are the cortisol levels following a 48hr low dose then high dose dexamethasone suppression test and the ACTH levels for an adrenal adenoma?
Low dose: HIGH
High dose: HIGH (NON SUPPRESSED)
ACTH: LOW
What are the cortisol levels following a 48hr low dose then high dose dexamethasone suppression test and the ACTH levels for an ectopic ACTH producing tumour?
Low dose: HIGH
High dose: HIGH (NOT SUPPRESSED)
ACTH: HIGH
What Investigations would be done if you suspect Cushing’s?
Low dose dexamethasone suppression test
High dose suppression test
Midnight cortisol (most sensitive, should be low here but it wont be)
Salivary cortisol
Urine cortisol
ACTH levels
FBC
U+Es
MRI pituitary
CXR (lung. Cancer)
Abdo x-ray (adrenal tumour)
Petrosal venous sampling (then PET scan if negative)
What is the treatment for Cushings disease/syndrome?
Transphenoidal surgery for pituitary adenoma
Surgical removal of ectopic ACTH tumours
Adrenal tumour removal
Bilateral Adrenalectomy (not really used)
Medications
What medications can be given for Cushing’s disease/syndrome?
Metyrapone
How does metyrapone work to treat Cushings?
Inhibits production of cortisol by the adrenal glands (inhibits CYP11B1)
Why is Adrenalectomy avoided when treating Cushing’s syndrome?
Can lead to Nelsons syndrome
Will need adrenal hormone replacement therapy
What is Nelsons syndrome?
Removing both adrenal glands leads to an anterior pituitary tumour developing that produce ACTH to try and increase cortisol levels
How does a non functioning pituitary adenoma presetn?
Just mass effects
Headache
Optic chiasm involvement (Bitemporal hemianopia)
Apoplexy
How do you investigate a non functioning pituitary adenoma?
MRI pituitary
Pituitary function tests
How do you treat a non functioning pituitary adenoma?
Non if microademona <1cm
Surgical (Transphenoidal) if macroadeoma or radiotherapy
How does a gonadotropinoma present?
Mass effect (headache, Bitemporal hemianopia)
Rarely macroorchidism
How do you investigate a gonadotropinoma?
MRI
Pituitary function test
How does a thryotropinoma present?
Hyperthyroidism:
-agitation
-sweaty
-weight loss
-diarrhoea
Mass effects
What investigations are done if you think a patient has a thryotropinoma?
Free T3, T4, TSH
MRI
Pituitary function tests
How do you treat a thryotropinoma?
Surgical removal (Transphenoidal)
How does a pituitary carcinoma present?
VERY RARE
Mainly mass effect (Headache, bilateral temporal hemianopia)
What investigations are done for pituitary carcinoma?
MRI
Pituitary function
How is a pituitary carcinoma treated?
Surgery if possible
Extremely poor prognosis
What is the main issue with the posterior pituitary that can occur?
Lack of ADH production / Diabetes Insipidus
What are the 2 types of diabetes Insipidus?
Cranial diabetes Insipidus
Nephrogenic diabetes Insipidus
What is cranial diabetes Insipidus?
Posterior pituitary doesn’t produce sufficient ADH
What is Nephrogenic diabetes Insipidus?
When the kidneys (collecting ducts) dont respond to ADH but the posterior pituitary produces sufficient ADH
What can cause cranial diabetes Insipidus?
Brain tumours
Brain injury
Brain surgery
Brain infections (meningitis, encephalitis)
Genetic mutation
Vasculitis
Infiltration
What can cause Nephrogenic diabetes Insipidus?
Medications
Genetic mutations in ADH receptor gene
Hypercalcaemia
Hypokalaemia
CKD (PKD)
What is the presentation for diabetes Insipidus?
Polyuria
Polydipsia
Dehydration
Postural hypotension
What is the volume of urine to classify Polyuria for diabetes Insipidus?
3L or more in 24hrs
What investigations would you do if you suspect diabetes Insipidus?
Urine output (>3L)
Urine Osmolality should be low (DILUTE < 300mOsm/kg)
Serum Osmolality high
WATER DEPRIVATION TEST
MRI Pituitary
What would expect the urine Osmolality and serum osmolality to be like in diabetes Insipidus?
Urine osmolality = low because it’s dilute
Serum osmolality = high or normal due to lack of fluid
What is the process of the water deprivation test?
Patient doesn’t drink water 8hrs before test
Desmopressin then given and the urine osmolality is then measured
Following a water deprivation test, What will the urine osmolality be for a patient with primary Polydipsia (drinks too much water)?
Serum osmolality will be measured high due to urine being concentrated from the ADH production
Following a water deprivation test, What will the urine osmolality be for a patient with primary Cranial Diabetes Insipidus?
Urine osmolality will be low indicating pathology (dilute when shouldn’t be)
After giving desmopressin the urine osmolality becomes high since the kidneys can respond to the exogenous ADH/desmopressin
Following a water deprivation test, What will the urine osmolality be for a patient with primary Nephrogenic Diabetes Insipidus?
Urine osmolality will be low indicating pathology (dilute when shouldn’t be)
After giving desmopressin the urine osmolality stays low since the kidneys are unable to respond to the exogenous ADH/desmopressin
What electrolyte changes can happen with diabetes Insipidus?
Hypernatraemia.
How is cranial diabetes Insipidus managed?
Desmopressin
Sodium levels need monitoring since Desmopressin might be too effective causing dilutional hyponatraemia
How is Nephrogenic diabetes Insipidus managed?
Thiazides
Indomethacin (an NSAID)
High dose desmopressin
Lots of water
