pathophysiology Flashcards
what is acromegaly a result of?
excess growth hormone
how common is acromegaly?
- Rare – approx. 3-4 people in every million
what is the aetiology of acromegaly?
- Most often caused by a benign pituitary tumour – can also be caused by non-endocrine tumour secreting GH
- Further divided into micro and macroadenomas (macro is most common)
- Some genetic link
are men and women affected the same with acromegaly?
yes - even split
when is acromegaly onset?
often slow and diagnosed in middle age
what are signs of acromegaly?
- Change in facial features – widening of bridge of nose, thick lips, protruding jaw and bone, macroglossia (enlarged tongue), teeth separation
- Headaches and visual disturbance – tumour
- Deeper voice
- Skin tag, excessive sweating and mild hirsutism in women (excessive growth of hair – male like patterns – usually dark and coarse)n
- Joint pain and carpal tunnel syndrome (pressure on nerve on wrist causing numbness and tingling)
- Hypertension and diabetes – extra strain
what investigations are done for acromegaly?
- Routine bloods – glucose, lipids, bone profile
- IGF-1 to exclude acromegaly if normal
- Check thyroid, prolactin, gondal and adrenal hormones – if one is abnormal you are at increased risk of others being abnormal)
- MRI to assess tumour
- CT is non endocrine tumour is suspected
- Cardiac workup – ECG, echo
- Thyroid ultrasound
what treatment is used in acromegaly?
Treatment: usually in combination
- Endoscopic trans-spinodal surgery first line with radiotherapy as an adjuvant
- Somastatin analogues eg octreside – decrease tumour size and manage symptoms
- Dopamine agonists such as bromocriptine – suppress GH hypersecretion
what is first presentation of prolactinomas?
- Usual presentation is raised prolactin – it is raised in lots of other states too ( drugs – spironolactone, NSAIDs, anti-psychotics, stress)
- Women more commonly present with irregular/ absent menstruation, galactorrhoea (milky nipple discharge unrelated to normal milk production of breast feeding), reduced libido, hirsutism
- Men have more subtle associated symptoms: erectile dysfunction, galactorrhoea, reduced beard growth, reduced libido – often presents late with osteoporosis
what symptoms do large prolactinomas tumour present as?
headaches and visual disturbances
what treatment is used in prolactinomas?
cabergoline (dopamine agonist)
what are the side effects of cabergoline?
can cause severe issues with impulse control and sleepiness
what size is a micro prolactinoma?
<1cm
what size is a macro prolactinoma?
1-4cm
what is a giant prolactinoma?
> 4cm
what condition is common following prolactinoma?
- Osteoporosis is common – around 30% lose bone density – hypogonadism and oestrogen and testosterone is required for bone mass
what does luteinising hormone do?
acts on ovaries and testes
- Adrenal gland maturation
what does LH deficiency cause in childhood?
delayed/ no puberty
what does LH deficiency do in women?
menopausal, hirsutism
what does LH deficiency do to men?
regression of sex, loss of muscle, erectile dysfunction
what does hyper LH do to a child?
early puberty, early secondary sexual characteristics
what are the complications of acromegaly?
cardiomegaly, hypotensive, T2DM – increased insulin resistance, bitemporal hemianopia (each vision field is missing outer sections on both sides), impaired glucose tolerance, colo-rectal cancer, osteoarthritis
what has an inhib effect on prolactin?
dopamine
what inhibits LH and FSH secretion?
prolactin
what is galactorrhea?
too high levels of prolactin
what can cause increase in prolactin?
- Can be caused by drugs, stress, a score over 3000 is indicative of endocrine pathology
- Common endocrine cause: pituitary adenoma
why does excess prolactin present earlier in women?
- Presents earlier in women – will stop periods, men tend to get more general symptoms – presentation comes with osteoporosis
what can hyperprolactinemia cause?
: galactorrhoea, amenorrhoea, erectile dysfunction – inhibits gonadotrophin release – infertility, hypogonadism, osteoporosis
what does adrenocorticosteroid hormone do?
ACTH: - Responsible for sex steroid production or to form cortisol
when is cortisol stimulated?
stress or during hyperglycaemia
what does cortisol do?
- Causing insulin resistance, central adiposity, raised cholesterol, muscle catabolism, reduced bone density, Na retention, K+ loss, emotional changes, growth – important but also inhibs excessive growth, anti-inflam effects
what are features of Cushing’s?
- Features: moon face, fat pad on back of neck, central adiposity, thinning of skin, distal limb wasting, stretch marks, acne, T2DM, vertigo, bruising
- Women: hirsutism
what is the aetiology of cushings syndrome?
ectopic ACTH, adrenal adenomas
what is the aetiology of cushings disease?
iatrogenic (long term steroids)
what can cause pseudo cushings?
obesity, alcohol, depression
how do you confirm cushings?
- Confirm diagnosis – 24hr urinary cortisol and overnight dex suppression test
how do you manage cushings?
depends on cause – trans-sphenoidal surgery B/L adrenalectomy
what is addison’s?
Too low cortisol: addisons – adrenal deficiency
what are features of addisons?
- Features: weight loss, hypotension, skin change, hypoglycaemia, loss in sex hormones – loss of body and pubic hair, loss in libido/ amenorrhoea, muscle wasting and limbs
what signs indicate addison’s?
: hypotension, hyperkalaemia, hyponatremia – not reabsorbed, hypoglycaemia, weight loss and high plasma – renin
why is there an increase in skin pigmentation in addisons?
more Melatonin secreting hormone
what is an addisonian crisis? - what symptoms
adrenal crisis
- Profound fatigue
- Dehydration
what signs are seen in addisonian crisis?
- Vascular collapse (hypotensive)
- Renal shut down
- Decrease in serum Na
- Increase in serum K
what might be the first presentation of addisons?
addisonian crisis
what can be the aetiology of addisons - adrenal insufficiency?
- Addisons: autoimmune, TB, HIV, metastasis (anything that stretches adrenal system), lymphoma, haemorrhage
why can chronic steroid use cause adrenal insufficiency?
: chronic steroid use (body switches off cortisol production – needs to be stepped down or it will cause an Addisonian crisis),
what investigations are needed within adrenal insufficiencies?
- Hyponatraemia and hyperkalaemia
- Hypoglycaemia
- ACTH level, renin- aldosterone levels
- 21 hydroxylase adrenal autoantibodies
how do you manage adrenal insufficiencies?
- Hydrocortisone (IV STAT in crisis), oral glucocorticoid
- Fludocortisone (mineralcorticoid)
what is pheochromocytoma?
tumour of adrenal glands that secretes unregulated excessive amounts of catecholamines – adrenaline
why does the symptoms of pheochromocytoma in episodes?
adrenaline secreted in bursts
is phaechromacytoma a genetic disorder?
- Phaeochromocytoma – more common in certain genetic disorders – MEN2, neurofibromatosis type 1, von hippel-lindau disease
how does phaeochromocytoma present?
- Presentation: tachycardia, palpitations, SVT, sweaty, tremor, flushed, GI disturbances, HTN – signs of fight response
what is the 10% pattern to phaeochromocytoma?
- 10% pattern to tumours – 10% bilateral, 10% cancerous, 10% outside adrenal gland
what is vitiligo?
Vitiligo – skin condition
- Large patches (nearly whole hand of hyper pigmentation)
what is hypopituitarism?
reduced production of all pituitary hormones
what is - Panhypopituitarism
reduction in all anterior pituitary hormones
what causes hypopituitism?
disease of hypothalamus-stalk and pituitary
name some causes of disease of hypothalamus-stalk and pituitary
- Irradiation, surgery, pituitary tumour, ischaemia or bleed, infiltration (amyloidosis, haemochromatosis) infection – TB, meningitis
- Specific causes: kallman syndrome, craniopharyngioma, apoplexy (pituitary haemorrhage or infarct). Sheehans syndrome – apoplexy (unconscious from haemorrhage) due to ischaemia from maternal haemorrhage
what clinical signs would indicate hypopituitism?
reduced LH, FSH, testosterone, TSH, T4/T3, prolactin may be raised
