endo Flashcards
complications of pituitary tumours
- press on local structures eg optic chiasm
- hypopituitism
- hyperpituitism (acromegaly, cushings, prolactinoma)
anterior pituitary hormones
FLAT PeG
GnRH > FSH* + LH* > act on gonads for germ cell development and hormone secretion
CTH > ACTH* > acts on adrenal gland to produce corticosteroids
TRH > TSH* > acts on thyroid to release T3, T4
DA > prolactin* > acts on mammary glands for milk production and breast development
endorphins
GHRH > GH* > stimulates IGF-1 production, growth
(ones with * are the ones released from anterior pituitary)
functions of cortisol
-increases insulin resistance
-suppresses immune response
-upregulates alpha 1 in arterioles to increase BP
-increases osteoclast activity (so osteoporotic)
-increased protein and carb breakdown
insulin action
biphasic release
insulin increases peripheral glucose uptake (glucose> glycogen)
1.glucose binds to GLUT2 receptors on pancreatic beta cells, stimulating insulin release
2.insulin binds to peripheral insulin receptors which activates intracellular tyrosine kinases and cascade resulting in increased GLUT4 channel expression on CSM (so increased peripheral uptake)
posterior pituitary hormones
oxytocin (paraventricular nucleus)- milk ejection and labour induction
vasopressin (ADH) (supraorbital nucleus)- recruited when decrease in BV, stress, major RAAS player
-increases APO II expression
-vasoconstricts BV
-increases aldosterone
which region of the adrenal gland releases which hormone
go find rex, make good sex
zona glomerulosa- mineralocorticoids (aldosterone)
zona fasciculata- glucocorticoids (cortisol)
zona reticularis- sex hormones (androgens)
salt, sugar, sex, deeper you go the sweeter in gets (moving inwards, controls production of salt etc)
adrenal medulla- adrenaline and noradrenaline
when is cortisol released
released with chronic stress and increasing blood sugar
Cushing’s disease/syndrome definition
hypercortisolaemia
clinical manifestation of prolonged elevated cortisol
Cushing’s syndrome- abnormal high cortisol of any cause
Cushing’s disease- high cortisol due to high ACTH from pituitary adenoma
Cushing’s epidemiology (G)
obesity, diabetes, older women
Cushing’s aetiology (G)
ACTH dependent- excessive ACTH from the pituitary gland (pituitary adenoma), or ectopic ACTH producing tumour eg small cell lung cancer, or excess ACTH administration
non ACTH dependent- excess glucocorticoid administration (iatrogenic) eg steroids eg prednisolone or adrenal adenomas
Cushing’s risk factors (G)
pituitary adenoma
adrenal adenoma
corticoid steroids
hypertension
uncontrolled diabetes
Cushing’s presentation
big in the middle, thin limbs, signs of stress
-central obesity
-round moon face
-buffalo hump (fat on back of neck)
-abdominal straie
-osteoporosis
-hypertension
-hyperglycaemia
-depression
-easy bruising and poor skin healing
-cardiac hypertrophy
-irregular periods
-erectile dysfunction
-hirsutism
Cushing’s pathophysiology (G)
negative feedback:
low blood cortisol > increased CRH from hypothalamus> ACTH from pituitary > increased cortisol from adrenal gland > negative feedback slows ACTH production when cortisol levels are sufficient
released with circadian rhythm- peaks in the mornings, least at night. With Cushing’s this rhythm is lost so unregulated CRH, ACTH, cortisol levels
Cushing’s investigations (G)
1: random plasma cortisol (midnight), if positive ACTH plasma
urinary free cortisol (24 hours)
gold:
dexamethasone overnigth test
dexamethasone is a glucocorticoid so should trigger negative feedback loop
give 1mg at 11pm and measure control, measure again at 8AM
with Cushings’s: not suppressed, >50nanomol/L
without Cushing’s: suppressed (negative feedback)
Cushing’s management (G)
stop taking steroids
-Cushing’s disease: transspheinoidal resection to remove pituitary adenoma
-if adrenal- adrenalectomy
-ectopic ACTH- remove neoplasm
Cushing’s complications (G)
osteoporosis, type 2 diabetes,
Cushing’s prognosis
untreated- 50% mortality in 5 years
treated is good prognosis
Acromegaly definition (G)
excess secretion of growth hormone from a pituitary tumour or hyperplasia results in bone and soft tissue overgrowth
acromegaly in adults
gigantism in children (before epiphyseal plates fuse)
acromegaly epidemiology (G)
2-13/100000
effects men and women equally
median age of diagnosis: 50s
acromegaly aetiology (G)
Unregulated GH secretion due to anterior pituitary adenoma
rarely ectopic GH from non-endocrine tumour eg lung
acromegaly risk factors (G)
MEN-1
(multiple endocrine neoplasia)
Acromegaly pathophysiology (G)
GHRH (released from hypothalamus) > excessive GH (anterior pituitary) > excessive production of IGF-1 (insulin growth factor 1)
IGF-1 stimulates growth of bone and muscle, increased protein synthesis, lipolysis
acromegaly presentation (G)
-box jaw
-coarse facial features
-spade like hands and feet
-increase in shoe size
-interdental separation
-macroglossia
-snoring
-deep voice
-obstructive sleep apnoea
-sweating
-arthritis
-back pain
-arthralgia
-carpal tunnel
tumour related symptoms:
-visual disturbances (bitemporal hemianopia)
-headaches
Acromegaly investigations (G)
1st:
serum IGF-1 (raised)
random serum GH (raised, not diagnostic as fluctuates with circadian rhythm)
gold:
oral glucose tolerance test
(failure of glucose to suppress GH)
other:
MRI pituitary
acromegaly management (G)
1st:
transsphenoidal removal of pituitary tumour
medication:
2nd: somatostatin analogue to block GH release eg octreotide
3rd: dopamine agonist to block GH release eg carbergoline
4th: growth hormone receptor antagonist: pegvisomant
radiotherapy
acromegaly monitoring and prognosis (G)
-lifelong monitoring of IGF-1 and GH
-prognosis good with surgery
acromegaly DD (G)
pseudo-acromegaly
Acromegaly complications (G)
T2DM, sleep apnoea
prolactinoma definition (G)
benign lactotroph adenoma releases excess prolactin, resulting in hyperprolactinaemia
prolactinoma epidemiology (G)
more women than men, child bearing years, 20-40, presents earlier in women than men
prolactinoma aetiology (G)
prolactin is released from the anterior pituitary and is inhibited by dopamine from the hypothalamus
excess prolactin:
pituitary adenoma, other non-functioning tumour compressing the infundibulum
lack of dopamine:
reduced dopamine levels, drug induced: dopamine antagonist or antipsychotics
Prolactinoma risk factors (G)
women 20-50, pregnant, oestrogen therapy
men 30-60
prolactinoma presentation
infertility
loss of libido
tumour: visual disturbances, headaches
women:
amenorrhea/ oligomenorrhea
galactorhhea
men:
gynecomastia
hypogonadiam
osteoporosis
erectile dysfunction
prolactinoma pathophysiology (G)
increased prolactin inhibits GnRH
decreased GnRH > decreased LH + FSH > decreased oestrogen/ progesterone in women, less testosterone in men
prolactin stimulates mammary glands > galactorrhoea
can be micro <10mm or macro
prolactinoma investigations (G)
1st/gold:
basal serum prolactin (elevated)
other:
pituitary MRI, CT head
prolactinoma management
dopamine agonist:
1.carbergoline,
2.bromocriptine
transsphenoidal removal of tumour
hormone replacement therapy
radiotherapy
prolactinoma complications (G)
infertility
sight loss
raised ICP
prolactinoma DD (G)
drug induced hyperproclactinaemia
primary hypothyroidism
renal insufficiency
pregnancy
PCOS
Adrenal insufficiency/ Addison’s disease definition (G)
Insufficient production of steroids (mainly cortisol (glucocorticoid), aldosterone (mineralocorticoid) from the adrenal gland. Steroids are essential to life so can be fatal
primary- Addison’s disease. Due to autoimmune destruction of the adrenal gland
secondary- pathology of the pituitary gland results in inadequate ACTH stimulating the adrenal gland
tertiary- pathology of the hypothalamus results in inadequate CRH release
CRH> ACTH> cortisol and aldosterone
Adrenal insufficiency/ Addison’s disease epidemiology (G)
more women than men
mostly autoimmune
30-50
Adrenal insufficiency/ Addison’s disease aetiology (G)
- -developed world: autoimmune destruction of adrenal antibodies (21-alpha-hydroxylase) results in destruction of adrenal gland
-developing world: TB
-adrenal metastases eg liver, lung, breast
-adrenal haemorrhage (AKA waterhouse-Friderichsen syndrome commonly caused by meningococcol menigitis)
-antiphospholipid syndrome - pituitary insufficiency due to long term steroid (iatrogenic) use or pituitary adenoma
- hypothalamus insufficiency due to long term steroid use or radiotherapy
Adrenal insufficiency/ Addison’s disease risk factors (G)
female
adrenal haemorrhage
adrenocortical antibodies
other autoimmune conditions
Adrenal insufficiency/ Addison’s disease pathophysiology
- autoimmune destruction of adrenal antibodies (21-alpha-hydroxylase), destruction of adrenal gland so less cortisol/aldosterone production. This results in excess ACTH as lack of negative feedback. Rising ACTH acts on melanocytes to produce melanin resulting in hyperpigmentation
- Pituitary/ hypothalamus insufficiency causes HPA axis suppression, causing decreased ACTH so no hyperpigmentation
Adrenal insufficiency/ Addison’s disease presentation (G)
remember 4Ts- tanned, tired, tearful, thin
-hyperpigmentation (tanned, bronzed, in palmar creases especially)
-vitiligo
-weight loss/ anorexia
-tearful/ depressed
-loss of axillary/ pubic hair in women
-tired
-N+V
-weakness
-abdominal cramps
-postural hypotension
-hypoglycaemia
-headaches
Adrenal insufficiency/ Addison’s disease investigations
1:
serum electrolytes (Na+ low, K+ high, due to low aldosterone, high glucose)
morning serum cortisol (low)
plasma ACTH (1-high, 2-low)
gold:
ACTH stimulation Short Synacthen test (to test adrenal reserve)
-measure basal cortisol at 9am (highest here, if low, major problem)
-administer synacthen
-measure cortisol 30 and 60 mins after
failure for ACTH to stimulate rise in cortisol (less than double baseline) shows primary adrenal insufficiency <500nmol/l. If over 580 can rule out addisons
other:
renin: aldosterone (renin high in addisons, aldosterone low)
FBC (anaemia)
Adrenal insufficiency/ Addison’s disease DD (G)
1/2/3 adrenal insufficiency,
adrenal suppression due to glucocorticoid drugs,
hyperthyroidism
Adrenal insufficiency/ Addison’s disease management (G)
1:
hydrocortisone (glucocorticoid to replace cortisol)
fludrocortisone (mineralocorticoid to replace aldosterone)
-will correct Na K+ and postural hypotension
double steroid use in illness/ trauma/ infection/ stress as cortisol needed in stress respone
patients given steroid card and emergency ID to alert emergency services as dependent on steroids for life
secondary: long term steroids weaned off, treat cause
Adrenal insufficiency/ Addison’s disease red flags (G)
trauma
infection
dehydration
ending steroid treatment
Adrenal insufficiency/ Addison’s disease complications (G)
Addisonian/ adrenal crisis:
-severe adrenal insufficiency (esp cortisol),
-presents with shock, reduced consciousness, hypotension, hypoglycaemia, hyponatraemia, hypokalaemia,
-management: immediate IV hydrocortisone, IV fluid resus, correct hypoglycaemia with dextrose
- shock, coma, death if not treated
