endocrine Flashcards
what is the action of insulin
Secreted post pranidal to increase glucose uptake into cells and replenish glycogen storage
inhibits Glucagon gluconeogenisis and ketogenisis
uptake of potasium into cells
what is the action of glucagon
secreted during fasting causes glycogenolysis and for muscles and cells to take up less glucose and use FFA. promotes gluconeogenisis and ketoacidosis in prolonged fasting
where does ketogenisis occur
in the mitrochondria of the liver cells
what is diabetes mellitus
chronic state of hyperglycemia due to inadequate insulin secretion or resistance to insulin or both
Type 1 Diabetes mellitus
cause and prevalence and associations
autoimmune disorder (has auto-antibodies) causing destruction of Beta cells usually presents under 30 most common 5-15 YO lean
associated with other autoimmune like pernicious anaemia or thyroid disease
eventually fully stops producing insulin and causes ketogenisis
genetic susceptibility associations HLA DR3 DQ4 +DR4 DQ8
more environmental factors
10 % of diabetics are type 1
Type 2 diabetes mellitus
cause and prevalence and pathophysiology
mainly resistance to insulin but also inadequate insulin secretions.
in older patients and more obese.
continues to produce insulin.
more genetic factors
initally starts of producing more deficent insulin from reduced cell mass but them glucotoxicity causes B cell depletion and they produce less insulin
associated with hypertension and other cardiovascular risk factors
2-3% of UK are diabetic
Primary and secondary causes of DM
primary Type 1 or 2
Secondary- Cushings acromegaly and prolonged glucocorticoid use, since these hormones act similar to glucagon
CF and pancreatitis
B blockers
acanthosis nigricans- sign of insulin resistance due to receptor abnormality
risk factors for T2DM
age
obesity
family history
ethnicity
symptoms of DM
main specific:
polyuria,
polydipsia and dehydration
weight loss
other: lack of energy
visual disturbances
itchy genitalia
signs of DM
weight loss dehydration acanthosis nigricans - severe resistance genetic receptor abnormality retinopathy keton smell-type 1
diagnoses of DM and investigations
fasting plasma glucuose, random plasma glucose HBA1C normal glucose <7.8mmol/L normal fasting<7 diabetic glucose >11.1 diabetic fasting >7 HBA1C> 48mmol/L or 6.5%
Conservative treatment for DM2 or prediabetes
Improve vascular control:control hypertension
statins
improve diet low on sugar and high in carbs moderate on protein
stop smoking and lose weight
educate on dangers of hypoglycemia and alcohol and on risks of complication like retinopathy or diabetic foot
pharmacological treatment for Type 2 DM
start on metformin
if uncontrolled, HBA1C>7%, progress to insulin or sulphonlyurea or gliatazone
most eventually need insulin
mode of action of metfromin
CI
advantages
increases insulin sensitivity and inhibits gluconeogenisis
CI in renal disease
doesn’t produce insulin so no hypoglycemic risk
Sulphonlyreate mode of action
stimulates insulin secretion
mode of action of gliatazone
reduces insulin resistance
Pharmacological treatment on Type 1 DM
start on Insulin
Complications of insulin therapy
lipohypertrophy due to reoccuring injections
Insulin resistance
weight gain- insulin makes you hungry
Major and commonest side effect - Hypoglycemia
What is the presentation of hypoglycemia
which are warning signs
Sweating/cold sweats tremor pounding heartbeat pallor Irritability/agitated clumsy behaviour
loss of consciousness and coma
convulsions
Hemiparesis that returns on euglycemia
hypoglycemia makes u STUPPID d for diabled
how to treat hypoglycemia mild and severe
mild= sugary drinks
severe= Iv glucose
IM glucagon
presentation of ketoacidosis
confusion
think just had acid- nausea vomiting and abdominal pain
plus tachypnoea to produce alkalosis to normalise PH
can lead to circulatory failure and death
diagnosis of Diabetic ketoacidosis
blood test= ketoacidotic and hyperglycemic both ketones and glucose elevated
Treatment of Diabetic ketoacidosis
IV saline to restore fluid loss
insulin to stop producing Ketones
complications of DM
Nephropathy due to renal ischaemia causing afferent to dilate and chronic increased GFR= albuminurea
Retinopathy due to lesions in macula
Neuropathy due to lesions in vaso nervorium causing visual blurring and distal parasthesia plus sensory loss which leads to diabetic foot. ischaemic and ulceration
15% get diabetic foot
DM causing increased risk of atherosclerosis= increased risk of stroke, MI or Peripheral vascular disease
symptoms of acromegaly
arthagia excessive sweating sleep apnoea headache very common acroparasthesia back ache
signs of acromegaly
acral enlargement
growth of soft tissue ( ears nose tongue)
thickening of skin
change of appearance
hypogonadism + galactorrhea +amenorrhea pituitary linked with headache
visual disturbances
DM
sleep apnoa arthritis hypertension
proximal weakness + carpul tunnel syndrome
associations of acromegaly
Hypertension other pituitary disease diabetes, insulin resistance due to IGF1 arthritis Sleep apnoea
causes of acromegaly
99% due to pituitary adenoma
can be due to MEN- hyperplasia
Investigations and diagnoses of acromegaly
measure GH-pulsate so not always accurate IGF1- not pulsate Glucose tolerence test look at old photos pituitary MRI + visual field exam
Treatment of acromegaly
Transshenoidal pitutary resection
or radiotherapy +somatostain analogues
or dopamine agonist (added benefit of shrinking tumour) or growth hormone antagonist
HyperProlactinemia causes
functional pituitary adenoma secreting prolactin 95%
other
hypothyroidism
adenoma pressing on pituitary stalk causing disinhibition
ectopic prolactin secreting tumour or PCOS
due to drugs- dopamine antagonist in schizophrenia
presentation of hyperprolactinemia
Galactorrhea
amenorrhea
male infertility and hypogonadism
hirsutism
other: erectile dysfunction loss of libido failure to thrive in children
Visual disturbances due to pituitary tumour
Hyperprolactinoma prevalence
commonest pituitary hormone disturbance 0.1%
Investigations of hyperprolactinoma
serum prolactin
MRI pituitary
Visual field examination
Thyroid function test
management of prolactinoma
surgery is difficult but an option
1st line= dopamine agonist- cabergoline or bromocriptine
radiotherapy
hyperthyroidism symptoms
heat intolerance sweating weight loss tachycardia and palpitations hypertension diarrhea insomnia anxiety amenorrhea
causes of hyperthyroidism
graves disease, commonest
toxic multinodular goitre - due to iodine deficency
iodine excess, usually iatrogenic
adenoma- TSH also high
ectopic thryoid tissue, lung or ovaries
amioderone induced thyrotoxicosis
graves investigations
TSH low, T3 T4 high and thyroid antibodies.
TSH receptor antibodies (LATS,TRAb) +VE
glucose = high
LFT FBC
Radioiodine uptake test: localise thyroid
Graves signs
exophthalmos
pretibial myexodema
goitre
hyperthyroidism signs
Goitre Irregular pulse warm skin thin hair fine tremor lid lag palmar erythema tachycardia and hypertension
Graves disease what is it pathophysiology and causes
autoimmune disease producing TRAb.
this stimulation of thyroid causes hyperplasia and hypertrophy- goitre
also stimulates glycosaminoglycans production around eye causing exophthalmos
glycosaminoglycans can also cause pretibial Myxoedema
associated with other autoimmune diseases like pernicious anaemia, type 1, Addison, rheumatoid
Pharmacological treatment of graves disease
Propranolol -B Blocker- symptomatic treatment
Carbimazole -antithyroid - prevents T3/T4 synthesise
Surgical treatment of graves disease
radioiodine therapy
thyroidectomy
Graves disease onset, triggers and prevalence
Childbirth, Stress
more common in women 20-40
affects 2-5% of all women
complications of hyperthyroidism
thyroid storm. Pyrexia, arrhythmia hypovolemia potentially fatal heart failure DM osteoporosis angina Af infertility Blindness due to ophthalmopathy -graves
exophthalmos risk factors investigation an treatment
smoking
CT or MRI
Steroids (methotrexate) and surgery
hypothyroidism and prevalence
underactivity of the thyroid
1% prevalence 9% lifetime risk in women
10F=M
complications of undiagnosed hypothyroidism
HF and dementia
causes of hypothyroidism
Hashimoto’s thyroiditis -commonest cause
Primary atrophic hypoparathyroidism
Iodine deficiency in diet or iodine excess in drugs
drug induced by amiodarone antithyroid or iodine
post thyroidectomy or radioiodine therapy
Tumour causing hypopituitary
Hashimotos thyroiditis pathophysiology
Autoimmune disease causing atrophy and regeneration= causes goitre.
presence of TPOAb
TgAb
Primary atrophic Hypothyroidism pathophysiology
autoimmune disease- has TPOAb and TgAb
causes atrophy, fibrosis and no goitre
does amioderone cause hypo or hyperthyroidism
it causes both. anti arrhythmia drug that contains a lot of iodine
Investigations in hypothyroidism
Thyroid function Test
TSH low, if TSH high then think of pituitary adenoma
T4 low. if T3 is also low could be sick euthyroidism
FBC-anaemia
management of hypothyroidism
replacement therapy- levothyroxine, T4
monitoring and altering levels
what are the actions of PTH
on renal= increases Ca reabsorption and decreases Po4- reabsorption. also increases the synthesis of calcitriol
on bone= increases resorption of Ca and PO4-
on GI= Increased calcitriol= increased uptake of Ca
what are the causes of secondary hyperparathyroidism
and what does it cause
Vitamin D deficency causes reduced Ca and as a result increased PTH (appropriate response)
PO4- is decreased
what is the treatment for secondary hyperparathyroidism
vitamin D to correct the cause
or Cinacalcet- which is anti PTH
what is the presentation of hypocalcemia
ECG long QT and wide QRS
paresthesia and muscle spasm (of hands or feet or larynx causing SOB)
seizures and basal ganglia calcification
signs: Chvostek sign (facial tap causes spasm)
Trousseau sign (blood pressure cuff causes spasm)
causes of hypocalcemia
Vit D deficiency (secondary Hyperparathyroidism)
hypoparathyroidism Primary or secondary (post surgery, Commonest)
PseudoHypoparathyroidism
signs of vit D deficency
Hypocalcemia signs plus causes pseudofractures due to osteomalicia
causes of hypoparathyroidism
Primary-Autoimmune genetic or congenital di george syndrome
secondary- post surgery or radiotherapy
magnesium deficiency since Mg required for PTH to leave the parathyroid
Ca PTH and PO4- in hypoparathyroidism and pathophysiology
low PTH
causes Low Ca and high PO4-
Pseudohypoparathyroidism causes Ca PTH and PO4- and pathphysiology
genetic disease causing resistance to PTH
PTH high Ca low PO4- High
Pseudohypoparathyroidism presentation
Hypocalcemia short stature fat round face learning difficulties short 4th metacarpal other hormone resistances
Treatment for all types of hypoparathyroidism
Ca supplements + calcitriol
what is cinacalcet
cabergoline
carbimazole
carbamazepine
anti PTH
AntiHyperprolactinoma, dopamine agonist
anti thyroid
anti seizure
hypercalcemia presentation
excess calcium increases osmolality causes polyuria and dehydration- weight loss
renal stones attempting to clear Ca
gut staisis leading to nausea and constipation
parasthesia
muscle cramp
short QT
causes of hypercalcemia
commonest are malignancy of bone and hyperparathyroidism
what are hypercalemia malignancies
Myloma and bone metastasis
cause excess resorption of bone leading to increased CA
PTHrP, some tumours like lung or renal secret PTHrP which is similar to PTH in effect but isnt picked up in PTH tests
Granuloma diseases like TB sarcoid Lymphoma release calcitriol which increases Ca absorbtion
presentation of primary hyperparathyroidism
bones moans stones and groans
osteoporosis, osteitis fibrosia cystica, punched out holes in skull
moand abdominal pain or renal colic pain due to increased Ca stone
groans=confusion
and hypertension
causes of primary hyperparathyroidism
commonest is single adenoma
MEN especially in younger people
investigations for primary hyperparathyroidism
Ca increased PTH increased (inapproriate) PO4- Decreased
DEXA scan
xray looks for bone changes ostiets fibrosa cytics
Treatment for primary hyperparathyroidism
surgically remove adenoma
increase fluid intake
reduce diatary calcium and vit D
Cincalcet to reduce PTH
tertiary hyperparathyroidism causes
chronic renal disorder. no Vit D production= no absorption of Ca= increased PTH chronically.
long term increase causes parathyroid autonomy and hypertrophy leading to chronically activate causing increased PTH secretion- increased Ca and PO4-
causes of Hyperkalemia
insulin deficency hyperosmolality cell lysis B Blockers iatrigenic due to excess fluid hypoaldersetone- adrenal insufficiency- addisons ACEi ARB acute kidney injury
what does hyperkalemia cause
weakness,
flaccid paralysis
arrhythmia
cardiac arrest
Diagnosing hyperkalemia
increased serum K
ECG- peaked T wave
Short QT
think repolarisation is fast and hard
ST depression
treatment of hyperkalemia
calcium, stabilises myocytes
insulin, glucose B agonist and bicarbonate as these shift K into cell `
functions of cortisol
Gluconeogenis fat deposition protein breakdown increase glycogen store retain sodium, loss potassium water clearance
cushing syndrome
symptom causing over production of cortisol
causes of cushing syndrome
commonest cause is iatrogenic - oral steroid excess cause
commonest endogenous cause is cushings disease
other is adrenal carcinoma
ectopic ACTH secreting tumour
symptoms of cushings syndrome
weight gain erectile dysfunction gonadal dysfunction amenorrea hirtusim mood changes (psychiatric changes) Easily bruising and purpura Fractures
signs of cushing syndrome
central obesity buffalo hump moon face supraclavicular fat facial plethora Purpura increased BP due to sodium retention
Investigations of cushings disease
serum glucose = increased
Diagnosis of cushing’s (hypercortisol) do just one of these:
dexamethasone suppression test= cortisol not suppressed
Cortisol salivary test or 24 hour urinary cortisol
Further Investigating of cause
test serum ACTH= if high then investigate as cushings MRI pituitary
if ACTH=low then investigate adrenal CT
Treatment of cushing syndrome
if iatrogenic= stop steroids
if cushing’s disease= transsphenoidal surgery
any other carcinoma= surgery
before surgery reduce cortisol with metyrapone or ketoconazole
after surgery replace cortisol with hydrocortisone
what is addisons disease
adrenal insufficiency or primary hypoaldosteronism
autoimmune disease destroying adrenal cortex causing shortage of mineralocorticoids and glucocorticoids
Presentation of addisons disease
hypotension/postural hypotension, hypovolemia hyponatremic hyperkalemic
weight loss anorexia confusion diarrhoea constipation and vomiting
dehydration
largest sign is dull grey pigmentation, buccal pigmentation palmar pigmentation
what causes pigmentation in addisons disease
due to low cortisol causing excess ACTH. ACTH is assosiated with MSH which causes pigmentation
what is adrenal insufficency crisis and how is it treated
Hypovelemia hypotension
treat with IV saline and IM hydrocortisone
Investigations for addisons disease
electrolytes= low Na high K
serum cortisol= low between 0800 and 0900
ACTH stimulation test= cortisol still low
serum renin and aldosterone = high renin and low aldosterone
adrenal antibodies
glucose test= low
management for addisons
replacement glucocorticoids - hydrocortisone, prednisolone replacement mineralocorticoids- fludrocortisone general=carry steroid card plus keep supple in case run out
prevalnce and of secondary hypertension
10% of all hypertension. more common in younger people and those not responding to antihypertensives
causes of secondary hypertension
renal artery stenosis
hyperaldosteronism
CKD
what is primary hyperaldesteronism
Conn’s syndrome, adrenal adenoma secreting aldesterone
presentation of conns syndrome
hypertension
hypernatremia
hypokalemia
also muscle weakness. tetany and nocturia
Investigations of Conn’s syndrome
renin : aldosterone ratio serum aldosterone: high serum renin low Na high K low to identify cause carry out adrenal CT or MRI
causes of secondary hyperaldesteronism
renal stenosis
treatment for hyperaldosteronism
removal of adrenal adenoma
pre control using CCB for BP
or aldosterone antagonist like spironolactone or amiloride
Hypothyroidism signs
Bradycardic Reflexes relax slowly Ataxia yawning - fatigue Cold ascites/oedema round face/weight gain defeated demeanour CCF Ileus
Goitre
Hypothyroidism symptoms
Tired Sleepy lethargy cold weight gain constipation menorrhea memory loss (progress to dementia) CCF
