Adrenal and Pituitary Flashcards
anterior pituitary is also called the ___
is derived from ____
adenohypophysis
Rathke’s pouch
non-trophic hormones produced by anterior pituitary =
GH and PRL
posterior pituitary aka ___
is an extension of ____ consisting of ___+___
neurohypophysis
neural tissue
modified glial cells
axonal processes
histology of anterior pituitary = __
acidophils =+
basophils =__+__
islands, cords of cells ; chromophobe islands
acido = somatotrophs (GH-50%) mammotrophs (PRL 20%)
baso = corticotrophs (ACTH 20%), thyrotrophs (TSH 5%) gonadotrophs (L/FSH 5%)
histology of posterior pituitary
non-myelinated axons of neurosecretory neurons
Pituitary adenoma can be associated with __ (__ syndrome)
MEN1
Wermer syndrome
3 affects of a prolactinoma
infertility
lack of libido
25% have amennorhoea
large pituitary adenoma local affects may be __+__+__
visual field defect (bitemporal hemianopia)
P atrophy of surrounding tissue
infarction => panhypopituitarism
ischaemic necrosis of pituitary that causes panhypopituitarism =
Sheehan syndrome
granulomatous disease that can cause panhypopituitarism
sarcoidosis
craniopharyngioma is derived from _____ = 1-5% of IC tumours
Rathke’s pouch remnants
4 features of craniopharyngioma =
can cause ____
slow growing often cystic may calcify most suprasellar some are in sella => panhypopituitarism
ages that get craniopharyngiomas
5-15 yos or 50-60 yos
_+__ = symptoms of craniopharyngioma
in kids may cause ___
visual disturbances and headaches
growth retardation
congenital adrenocortical hyperplasia :
pattern of inheritance =
causes _/__ of steroid enzymes => increased ___
auto recessive
lack/deficiency
androgens
nodular adrenocortical hyperplasia is ACTH dep/independent?
ACTH independent (diffuse = ACTH driven)
if adrenal cortex tumours in young then consider
Li Fraumeni Syndrome
appearance of adrenal cortex adenomas=
well circumscribed encapsulated small - 2-3cm yellow/yellow-brown (lipids) small nuclei
features of adrenal cortex carcinoma that distinguish it from adenoma
large (>20cm) haemorrhagic and necrotic frequent mitoses atypical mitoses lack of clear cells capsular/vascular invasion
primary hyperaldosteronism aka
60% associate with __
Conn’s
diffuse/nodular bilateral hyperplasia
Cushings that is ACTH dep = __/___
and leads to ___
pituitary tumour (70%) small cell lung cancer adrenal hyperplasia
Cushings that is ACTH independent can be caused by __/___
and leads to ___
adrenal adenoma (10%) or carcinoma (5%) adrenal atrophy
acute primary adrenal insufficiency caused by massive adrenal haemorrhage due to septicaemia =
Waterhouse Friederichsen
causes of acute primary adrenal insufficiency =
rapid steroid withdrawal
stress on chronic insufficiency
massive adrenal haemorrhage - newborn, anticoagulants, DIC, septicaemia
3 common causes of Addisons
AI adrenalitis
infections (tb, HIV etc.)
metastases
chronic primary adrenal insufficiency aka
Addisons
signs of Addisons when >90% of adrenal glands are destroyed =
fatigue anorexia nausea and vom wt loss diarrhoea pigmentation increase K+ and decrease Na+ = hypotension hypoglycaemia
pigmentation in Addisons is caused by
ACTH having the same precursor as MSH
zona glomerulosa produces __
mineralocorticoids - aldosterone
zona fasciculatis produces ___
glucocorticoids - cortisol
zona reticularis produces ___+___
glucocorticoids and sex hormones
adrenal medulla is innervated by ___ and chrommafin cells secrete ___
pre-synaptic sympathetic fibres
catecholamines
___+___ in neuroblastoma are indicative of a poor outcome
amplification of N-myc
expression of telomerase
neuroblastoma is usually diagnosed at age ___
40% from ___ and most of the others are found ___
18months
adrenal medulla
along sympathetic chain
neuroblastoma are composed of ___ cells but can show maturation and differentiation towards ___ cells
primitive
ganglion
tumour of chromaffin cells in the adrenal medulla =
phaeochromocytoma
tumour in adrenal medulla that secretes catecholamines =
leads to secondary =
phaeochromocytoma
2ndry hypertension
detect __+___ in urine if have a phaeo
catecholamines and metabolites
90% of phaeos are associated with ___ which comes on with +++
paroxysmal hbp
stress, palpation of tumour, exercise, posture
if stain phaeo with K2Cr2O7 turns ____ as the catecholamines ____
dark brown
oxidise
nests of cells seen in phaeos
zellballen
usually phaeos metastasise to ___
skeleton
Phaeo is a feature of __ (sipple syndrome )
gene mutation =
MEN 2A
gain of function mutation in RET gene on 10q11.2
MEN2B mutation =
tumours associated =
activating point mutation in catalytic zone of encoded enzyme
phaeo
MTC, neuromas/ganglioneuromas
marfanoid habitus
tumours ass with MEN2A
phaeo in 40%
MTC in 100%
10-20% parathyroid hyperplasia
hormones from hypothalamus > ___ > stimulate the ___ pituitary
portal system
anterior
hyphothalamic hormones > ____ >stored in ___ pituitary
neuronal tracts
posterior
in synacthen test cortisol should normally rise to ___
450-500
dont give a prolonged glucagon test to __/___
epileptics or CVDs
insulin stress test =
make bg ___ the measure __+__
normal =
<2.2mmol/l
GH and cortisol
both increase so that GH >7microg/l + cortisol >500
water deprivation test - if suspect __
check + for 8hrs and then give ___ and check for 4hrs more
if urine:serum osmolarity >2 (even on random test ) = ___
Diabetes Insipidus
serum and urine osmolarities
desmopressin
normal
microadenoma = ___cm
macroadenoma =___cm
<=1cm
>1
CN at risk of compression in pituitary pathology
CN III, IV and VI
4 physiological causes of raised prolactin
Pregnancy
breast feeding
stress
sleep
5 drugs that can cause raised prolactin
D2 antagonist anti-emetics (domperidone +metoclopramide) phenothiazines TCA and SSRIs oestrogens cocaine
pathological causes of raised prolactin (3)
hypothyroidism (raised TSH => raised PRL)
stalk lesions
prolactinoma
Females with raised prolactin tend to present early/late
with ///
early amenorrhea (most common) infertility menstrual irregularity galactorrhoea
Males with raised prolactin tend to present early/late
with ///
late impotence (decreased testosterone) visual field abnormality headache anterior pituitary malfunction
investigations for suspected raised prolactin
PRL concn
MRI (prolactinoma, stalk lesion, optic chiasm)
visual fields
pituitary FTs
Rx for raised prolactin
effect on tumour size
dopamine agonists - usually cabergoline (bromocriptine / quinogolide)
tumour shrinks
route that cabergoline is given and how frequently
PO
twice a week
headache in acromegaly is caused by ___
hyperdynamic blood flow
signs and symptoms of acromegaly
thickened soft tissues spade hands macrognathia hbp HF headache sleep apnoea DM colonic polyps and cancer visual disturbances
2 best Investigations for suspected acromegaly
IGF-1 blood test (increased)
OGTT - and check GH response normal = <0.4microg/l
first line treatment for acromegaly
transspenoidal Sx
drug treatment for acromegaly if tumour is unresectable
somatostatin analogues - octreotide / lanreotide
D2 agonists - cabergoline
GH receptor antagonists - pegvisomant (last line)
D2 agonists are better for the treatment of acromegaly if there is also ___
co-secretion of PRL
can use SSAs pre op for acromegaly because it __/___
relieves headache in 1hr
gives a better outcome
side effects of SSAs used for Rx of acromegaly
flatulence, diarrhoea (long term)
gallstones (decreased GB contractions)
___ = drug that can reduce the size of acromegalic pituitary tumour
SSAs - octreotide
re-expands 6wks after stop the drug
cancer surveillance for acromegalic patients = __+__
colon and tubulo-villous adenoma - every 3 yrs
excess cortisol in Cushings causes __ loss, altered __+__ metabolism, __ and central ___
protein loss
lipid and carb
DM
obesity
proximal myopathy, thin skin, frontal balding (F), chemosis and osteoporosis are characteristics of __
Cushing’s
chemosis =
conjunctival oedema
best screening test for Cushing’s =
normal and abnormal limits =
overnight 1mg dexamethasone suppression test
normal = <50nmol/l
abnormal =>100
2 screening test for Cushing’s =
overnight 1mg dexamethasone suppression test
urine free cortisol (24hr urine collection)
definitive diagnostic test for Cushing’s =
normal =
low dose dexamethasone suppression test
2mg/day for 2 days
normal = <50nmol/l 6 hrs after last dose
Cushing’s disease is due to a __
pituitary cause
ACTH test results for pituitary, adrenal and ectopic causes of Cushing’s
pit = <300 adrenal = <1 ectopic = >300
high dose DST result in pituitary, adrenal and ectopic causes of Cushing’s
pit = suppress by 50%
adrenal and ectopic = nil
treatment for pituitary cushings
hypophysectomy (maybe + external radio.)
OR bilateral adrenalectomy
treatment for adrenal causes of Cushings
adrenalectomy
drug treatment for Cushings if Sx fails
metyrapone, ketoconazole, pasireotide (SSA)
if get normal pituitary hormone levels with low peripheral hormones= _____ = __
inappropriately normal
hypopituitarism
treatment of hypopituitarism =
replacement hormones - give hydrocortisone and then thyroxine then the others
testosterone replacements IM = ___, PO = ___
IM = nebido every 10-14wks PO = restandol (if very mild hypo-testosterone)
DIDMOAD aka __
stands for ___
pattern of inheritance =
Wolfram Syndrome
Diabetes insipidus, Diabetes mellitus, opti atrophy, deaf
auto recessive
test to diagnose DI
water deprivation test
treatments for DI =
desmospray (nasal)
desmopressin PO/IM
if a Glucocorticoid receptor dimer is allowed to bind to GRE then steroid causes ___
activation of the gene
if nGRE only allows a GR monomer to bind then steroid causes ___
gene repression
steroid effect depends on __ not on __
gene sequence
not on the steroid used/the type of receptor
steroids also activate the ___ which leads to the adverse effects __+__
mineralocorticoid receptor
thin skin and poor wound healing
if co-administer a ___ with steroids then can inhibit __+__ as it saturates the __
mineralocorticoid
inhibit skin atrophy and increase wound healing
Mineralocorticoid receptor
GR activation in the __ of the brain can lead to ___
amygdala
alcohol craving
Is licensed for acute Cushing’ crisis as it binds to GR and blocks =
mifepristone (morning after pill)
sign of high androgen levels in CAH for F and M
F = ambiguous genitalia M = precocious puberty
adrenal cortex layers outer to inner =
GFR
glomerulosa
fasciculata
reticularis
zona glomerulosa is regulated by
ATII and extracellular K+
zona fasciculata is regulated by
ACTH
zona reticulatis is regulated by
ACTH and others
RAS is activated by ___ and it causes __+___
decreased bp vasoconstriction (ATII) salt retention (aldosterone)
excess cortisol causes osteoporosis because
increases osteoclastic activity
decreases serum Ca2+
cortisol ___ lipolysis and cause fat to be deposited __
increases
centrally
effect of cortisol on proteolysis
increases it
cortisol ___ capillary dilatation and permeability
decreases
cortisol ___ CO, bp, renal blood flow and GFR
increases
Ix for diagnosis of Addisons (5)
biochem (Na + bg low, K+ high) short synACTHen raised ACTH in blood raised renin and low aldosterone levels adrenal autoIgs
Rx for addison crisis
DON’T delay treatment
hydrocortisone IV immediately
later = fludrocortisone
Rx that replaces aldosterone
fludrocortisone
sick day rules for Rx of Addisons
x2 dose if sick
if vomit - retake
if cant keep anything down = IM and go to hospital within 6-8hrs
2ndry adrenal insufficiency has same features as primary but __+___
no pigmentation (ACTH low) and aldosterone production is intact
Rx in secondary adrenal insufficiency
just hydrocortisone
no need for fludrocortisone
results of long ACTH test in 2ndry adrenal insufficiency -
long gradual rise = due to adrenal atrophy
purple striae =
Cushings
gradual withdrawal of steroid therapy is over ___
4-6wks
Conns (primary hyperaldosteronism) features =__+__
increases number and activity of _____
can lead to __+__
hbp and hypokalaemia
Na+ reabsorption channels
LV hypertrophy and atheroma
commonest cause of primary hyperaldosteronism (usually older patients) =
bilateral adrenal hyperplasia
cause of primary hyperaldosteronism (usually in young patients)
Conn’s - adrenal adenoma
genetic mutations in ___ can cause primary hyperaldosteronism
K+ channels
to confirm hyperaldosteronism Ix = __
if it is increased then test to confirm primary hyperaldosteronism =
plasma aldosterone:renin, plasma K+
saline suppression test (fail to suppress by >50% with 2L = PA)
3 Ix to confirm the subtype of primary hyperaldosteronism
adrenal CT
adrenal vein sampling (confirms adenoma)
11C metomidate PET-CT
if adrenal adenoma is cause of primary hyperaldosteronism Rx =
unilateral laparoscopic adrenalectomy
if bilateral adrenal hyperplasia is cause of primary hyperaldosteronism Rx =
MR antagonists (spironolactone)
classical CAH = __+__
non-classical = __
salt wasting + virilising
hyperandrogenaemia
diagnosis of CAH is dependent on __+__ (Ix)
basal/stimulated 17-OH progesterone concn (increased)
gene analysis
____ is the stage before 21alpha hydroxylase - a precursor for __>testosterone
17-OH progesterone
androstenedione
Rx for CAH in paeds =
gluco (+maybe mineralo) corticoid replacement
Sx
Rx for CAH in adults -
control androgen excess
restore fertility
avoid overreplacing steroids
__>L-DOPA>___>NA>___
tyrosine
dopamine
adrenaline
biochemistry of phaeo =
hyperglycaemic maybe decreased K+ increased Hb mild hyperCa2+ lactic acidosis
Ix to confirm catecholamine excess in phaeo/paragangliomas
2x24hr urine fo catecholamines/metanephrins
plasma levels of catecholamines
3 diagnostic Ix for phaeo/paraganglioma=
MRI
MIBG (meta-iodidbenzylguanidine)
PET (-ve in slow growing/benign)
drugs for phaeo/paraganglioma
alpha blocker (phenoxybenzamine 1st line - others = prazosin/doxazosin) followed by beta blocker (propanolol/metoprolol)
malignant phaeos and extraadrenal paragangliomas are less efficient at catecholamine synth and so instead ___ increase
precursor levels eg. dopamine
ectopic causes of cushings commonly originate in ++_
thymus
lungs
pancreas
if low dose dex suppression test confirm Cushings then next Ix= ___ to determine if pituitary, adrenal or ectopic
high dose dexamethasone suppression test (2mg/6hrs for 2 days)
adrenaline acts on ___ receptors in the heart
___ in the vessels
__ in muscles
__ in islet beta cells
beta1 heart
alpha 1 vessels
beta2
beta2
paragangliomas commonly occur here
aortic bifurcation
pigmentation in addisons is especially noticable in __+__
buccal mucosa
palmar creases
