case 9 - endocrinology Flashcards
what are adrenal hormones all derived from
cholesterol
what is DHEA
androstenedione - route for sex steroid precursors
what is the main glucocorticoid of the body
cortisol
what does over production in the glomerulosa mean
mineralocorticoid excess - Conn syndrome
what does over production in the fasiculata mean
glucocorticoid excess - Cushing syndrome
what does over production in the reticularis mean
excess sex steroid precursors +cortisol due to a tumour
what happens if there is primary underproduction
the primary: entire cortex is affected (Addison disease, TB/ HIV)
what happens if there is secondary underpriduction
Secondary; hypopituitarism; loss of ACTH I.e aldosterone secretion preserved
what happens if there is disordered production - what is the problem here with
Disordered production - problems with the enzymes
congenital adrenal hyperplasia - virtually never cancer
what is cushings syndrome
classically thought to be rare
Excessive, inappropriate endogenous cortisol secretion characterised clinically and biochemically by:
Features of glucocorticoid excess
Loss of circadian rhythm to cortisol secretion
Disruption of negative feedback loop
what are the symptom and signs of cushings syndrome
Moon face with purplish plethora
*Central obesity, buffalo hump
*Weight Gain
*Hypertension
*Depression/ psychosis
*Diabetes mellitus
*Hypogonadism
*Susceptibility to infection
*Malaise
*Osteoporosis
*Easy bruising
*Striae
*Proximal myopathy
*Poor wound healing
*Hirsuites
*Acne
Symptoms overlapping with PCOS
what can be thought of as antagonistic to insulin
cortisol - like glucagon, epinephrine and growth hormones
how does cortisol increase blood glucose levels
promotes gluconeogenesis
raises hepatic glucose output
inhibits glucose uptake by muscle and fat
what are the other effects of cortisol
lipolysis from adipose tissues
protein catabolism to release amino acids
how is glucocorticoid excess diagnosed
Loss of circadian rhythm
random cortisol is no use
Measure bedtime/nighttime serum or salivary cortisol levels
- Measure 24 hour urinary free cortisol
- If overactivity is suspected; try to suppress it
- measure cortisol after low dose of dexamethasone
- 1mg overnight or 0.5mg QID for 8 doses
- following 9am cortisol should be suppressed (less than 50nmol/L)
- Exclude pseudo-Cushing syndrome
clinical features of Cushing syndrome, which disappears when the underlying cause is resolved
Common causes alcohol, depression
Glucocorticoid excess / Cushing syndrome diagnosed
what are the two causes of Cushings syndrome
adrenal tumour. - ACTH undetectable
distinguishing between ACTH dependent causes
how do you distinguish between ACTH dependent causes
Low dose dexamethasone suppression test - diagnose Cushing Syndrome
Inferior petrosal sinus sampling
High-dose dexamethasone suppression test
localise Cushing syndrome
2mg QID (i.e 6 hourly) for 8 doses ending at midnight
Corticotrophin tumour: >50% suppression of following 9am cortical
Ectopic ACTH: <50% suppression of following 9am cortisol
For tumours - adrenalectomy
what is the medical treatment of Cushing Syndrome
untreated life expectancy <5 years
Medical
Block production of cortisol (metyrapone…ketoxonazole, mitotane)
pituitary tumours
Trans-sphenoidal hypophysectomy +/- radiotherapy
20-50% may not be permanently cured
May require bilateral adrenalectomy
ectopic ACTH
Usually palliative, surgery, DXT/chemotherapy
adrenal tumours
Adrenalectomy
what is hypoadrenalism
rare - 0.8 cases per 100,000
Primary causes
TB/AIDS
Addison disease / autoimmune (T1DM, thyroid disease, PA, vitiligo)
Lymphoma
Metastatic tumour
Intra-adrenal haemorrhage or infarction
Bilateral adrenalectomy
secondary hypoadrenalism comes from pituitary insufficiency
what are the features of hypoadrenalism
Clinical features:
Primary hypoadrenalism: lack of cortisol and aldosterone
*Non-specific
*Tiredness
*Weakness
*Nausea & vomiting
*GI disturbance
*Abdominal pain
*Weight loss
*Postural hypotension (supine and erect BP)
*Dizziness
*Fainting
*May present in circulatory failure (‘crisis’)
*Hypoglycaemia
what means primary hypoadrenalism
*Hypotensive, hyperkalaemic patient = PRIMARY HYPOADRENALISM
what is the diagnosis and treatment of hypoadrenalism
if under-activity is suspected; try to stimulate it
Short synacthen test
Give ACTH i.v./I.m. and measure cortisol 30 mins later
If less than 400nmol/L, it is inadequate
treat with hydrocortisone lifelong
10mg on waking, 5mg mid afternoon
Double in significant illness
steroid alert bracelet
Steroid card
May need mineralocorticoid replacement
Fludrocortisone
what is endocrine hypertension in the adrenal cortex due to
Conn syndrome
what is endocrine hypertension in the adrenal medulla due to
phaeocromocytoma
what is endocrine hypertension
hypertension caused by demonstrable hormone excess, which is cured upon normalising circulating levels of the homrone
these patients tend to be younger
what do these younger patients have that leads to hypertension
renal artery stenosis
coarctation of the aorta
what are the hormones that regulate blood pressure, and in excess can elevate it
angiotensin II
aldosterone
cortisol
adrenaline and noradrenaline
calcium / PTH
growth hormone
what is the body’s major mineralocorticoid
aldosterone
what does aldosterone do
promotes sodium resorption from the urine and potassium excretion
it increases blood pressure
what is aldosterone biosynthesis regulated by
the RAAS system via a negative feedback loops
serum potassium concentration
what is Conn syndrome
over production of mineralocorticoid
what does mineralocorticoid excess in the glomerulosa cause
Conn syndrome
what does mineralocorticoid excess in the fasiculata cause
Cushing syndrom
what is Conn syndrome
primary hyperaldosteronism
causes hypertension
what can you also have with Conn syndrome
hypokalaemia, weakness, lethargy
headaches due to hypertension
what are the causes of hypokalaemia
vomiting - metabolic acidosis
diarrhoea or other fluid loss
insulin therapy
diuretic use
how do spironolactone and eplernone act
aldosterone acts on the mineralocorticoid receptor in the distal convoluted tubule
spiralolactone and eplernone are MR angtaonists
what is the mechanism of liquorice
cortisol will bind to the MR and circulates in much higher concentrations
within the kidney tubule, cortisol is inactivated by cortisone by HSD11B2
this preserves the MR for aldosterone
liquorice inhibits HSD11B2
cortisol continually stimlates the MR
what are the catecholamines
adrenaline and noradrenaline q
where are noradrenaline and adrenaline stored
in the cell cytoplasm
what are these catecholamines released in response to
nervous stimuli - rapidly metabolism in the liver
where are catecholamines found
adrenal medulla
what does overactive catecholamines suggest
a tumour called phaeochromocytoma
via what receptors do catecholamines act
via alpha and beta receptor
what do catecholamies do to the brain
cause alterness, anxiety and agitiation
what do catecholamines do to the eyes
dilate the pupils
what do catecholamines do to the liver
glycogenolysis
what do catecholamines do to the lungs
bronchodilation
what do catecholamines do to the pancreas, kidney and adipose tissue
in pancreas, stimulate glucagon and insulin
in kidney, lead to renin release
in adipose, lipolysis
what are the classic triad of symptoms of phaeochromocytoma
hypertension
throbbing bilateral headaches
paliptations
what is one given for phaeochromocytoma
administration of a alpha blocker (phenoxybenzamine) and beta blocker - propranolol
what are the different types of endocrine neoplasia syndromes
*Paraganglioma/phaeochromocytoma syndromes
*MEN2 (type a: thyroid medullary carcinoma, phaeochromocytoma) (type b: as above plus musosal neuromas)
*Von Hippel Lindau syndrome
*Neurofibromatosis
