Endocrinology Flashcards
How is T3 and T4 released stimulated
- thyrotrophin releasing hormone from hypothal
- TSH anterio rpituitary
- T4, T3 thyroid
- negative feedback to hypothalamus (less TRH)
what do T3 and T4 bind to after release to be transported
thyroxine binding globulin and albumin
how do T3 and T4 become activated
- T3 is active on release
- T4 is activated peripherally by losing an iodine molecule
what are the function of thyroid hormones and what receptors do they stimulate
- increase metabolism
- via nuclear receptors
- growth and mental development
What states are thyroid binding globulin increased/reduce din
Increased:
- pregnant
- oestrogen therapy
- hepatitis
Decreased- low protein states
- nephrotic syndrome
- chronic liver disease
- acromegaly
what does primary hyper/hypothyroidism mean
- problem with the thyroid
TFT results for primary hyperthyroid
low TSH, high T4
TFT results for primary hypothyroid
hihg TSH , low T4
what does central hypo/hyperthyroid mean
issue with pituitary or hypothalamus
sx of hyperthyroid
Sweating Weight loss ****Emotional lability (irritable, psychosis) Appetite increase Tremor/tachycardia (AF) Intolerance to heat/irregular menstruation Nervousness/anxiety Goitre/GI problems (diarrhoea)
signs for hyperthyroid
- tachycardia/AF (can cause lightheadedness/syncope)
- ****- palmar erythema
- goitre
most common cause of hyperthyroidism
Grave’s
Causes of hyperthyroidism
Grave’s
toxic multinod. goitre
toxic adenoma (1x nodule)
***ectopic thyroid tissue (mets, ovarian teratoma)
***pituitary adenoma secreting TSH
exogenous-
- iodine excess
- levothyroxine excess
- *****- amiodarone, lithium
tx of hyperthyriodism
carbimazole- TFTs and sx guide dose - titrate
- ***propylthiouracil (2nd line)
- ***beta-blockers (AF)
radioiodine
thyroidectomy
what are the sx of a thyroid storm
life threatening
tachycardia, HTN anxiety/restlessness fever (>40) mental status changed D+V \+- jaundice
tx thyroid storm
- **antithyroid drug- - carbimazole OR propylthiouracil
- **beta blockers IV
- **steroids- hydrocortisone or dexamethasone - blocks T4 T3 conversion
- fluids, NG if vomiting
- bloods- TFT, cultures
- BP monitoring
- tx any infection
- paracetemol for fever
BB alternatives- diltiazem/verapamil, digoxin (AF)
causes of thyroid storm
person with thyroid disease and:
- fever, sepsis
- dehydration
- MI
- radioactive iodine
what is grave’s disease
hyperthyroidism due to circulating autoantibodies
- activate TSH receptors
- also react with orbital autoantigens
what genetic mutation is grave’s disease associated with?
what other conditions are also associated with this mutation?
HLA-DR3
vitiligo
T1DM
addisons
what populaitons is grave’s disease more commonly seen in
- females
- pregnant/post-partum
sx of Grave’s disease
hyperthyroidism- SWEATING
****- pretibial myxedema
- Goitre- smooth thyroid enlargement
eye disease
Ophthalmology
- upper eyelid retraction with lid lag,
- swelling, erythema, conjunctivitis of the eyes
- exophthalmopathy (bulging)
- diplopia
- discomfort, grittiness/tearing
what autoantibodies are seen in graves
- thyroid stimulating hormone receptor antibodies- gold standard
- thyroid perioxidase antibodies (also in Hashimoto’s)
symptoms of hypothyroid
BRADYCARDIC
Bradycardia Reflexes slow Ataxia Dry, thin hair and skin Yawning (fatigue) Cold (low temp) ****Ascites and non-pitting oedema ****Round face, obesity Depression **Immobile (proximal weakness), ileus ***Congestive HF, constipation
causes of hypothyroidism
Iodine deficiency Primary atrophic hypothyroid Hashimoto's thyroiditis thyroidectomy drug induced
what is primary atrophic thyroiditis
diffuse lymphocytic infiltration of thyroid
leads to atrophy
no goitre
no autoantibodies
tx of hypothyroidism
levothyroxine
what is autoimmune/hashimoto’s thyroiditis
- lymphocytic and plasma infiltration
- goitre
- autoantibodies
- assoc with other AI conditions and MALT lymphoma
autoantibodies found in hashimotos/autoimmune thyroiditis
*****thyroglobin antibodies
thyroid peroxidase antibodies
what is myxoedema coma, sx
- severe hypothyroid state, precedes death
- hypothermia
- hyporeflexia
- low glucose
- bradycardia
- coma, seizures
what can cause myxoedema coma
- infection
- MI
- stroke
- Coma
management myxoedema coma
- ****- TFT, FBC, UE, cortisol, glucose, cultures
- ****- ABG
- active warming
- **- correct hypoglycaemia
- **- tx infection
- IV T3 (Liothyronine) very slowly, sometimes can give levothyroxine
what is postpartum thyroiditis
hyper/hypothyroisism within the first year following a birth
what is foetal thyrotoxicosis, what can it cause
when TSH- receptor antibodies (Graves) cross the placenta
- can cause cardiac conditions, IUGR, foetal goitre, hydrops, preterm, miscarriage
management of foetal thyrotoxicosis
- anti thyroid meds- carbimazole to mother
what is gestational thyrotoxicosis
- 1st 1/2 of pregnancy
- T4 raised, low TSH
tx of gestational thyrotoxicosis
- propanolol
- carbimazole
- surgery
mots common type of thyroid cancer
papillary- good prognosis
Paul’s Focaccia Most Awarded Loaf- papillary>follicular>medullary>anaplastic>lymphoma
-anaplastic- v bad prog
ix for ?thyroid cancer
aspirate large nodule
tx thyroid cancer
hemi/total thyroidectomy
complications of thyroidectomy
- external superior laryngeal- voice change, loss of high pitch
- recurrent laryngeal- hoarse, weak voice
- BL recurrent laryngeal- lose voice, need tracheostomy
- hypothyroidism
what are the 2 tyes of cells in the parathyroid glands
chief cells oxyphil cells (unknown use)
what do chief cells secrete
PTH
what does PTH do
released when Ca levels low
- increases serum Ca
- increased bone resorption
- increased Ca re-absorption in kidneys
- Vit D synthesis- which then acts on the gut to increase Ca absorption
- negative feedback- Ca=less PTH
causes of primary hyperparathyroidism
- solitary adenoma
- general hyperplasia
- cancer
sx hyperparathyroidism
Bones- pain, #, OP Stones Groans- abdo pain, constipation Moans- confusion, delirium, agitation, depression Thrones- polydipsia, polyuria
pancreatitis
weakness
fatigue
blood resuts in primary hyperparathyroidism
- hgih Ca
- PTH high
- reduced phosphate
what is secondary hyperparathyroidism
high PTH, but being released in an appropriate response to consistently low Ca
causes of secondary hyperparathyroidism
- low vit D
- chronic renal failure (increased Ca excretion)
- low Ca intake
- reduced intestinal Ca absorption
tx primary hyperparathyroidism
- fluids
- high Ca and vit D intake
- excise adenoma/PT glands
- conservative- cinacalcet- calcimimetic- increases PT cell sensitvity to Ca to increase -ve feedback- if surgery is unsuccessful
- consider bisphos
tx secondary hyperparathyroidsm
- correct cause
- phosphate binders
- Vit D
- cinacalcet - a calcimimetic- increases PT sensitivity to Ca
- parathyroidectomy
blood results in secondary hyperparathyroidism
low Ca
high PTH
what is tertiary hyperparathyroidism
- very LT secondary hyperparathyroidism
- hyperplasia
- inapp. PTH desensitised to Ca serum levels
blood results for tertiary hyperparathyroidism
- high Ca, very high PTH
what is primary hypoparathyroidism
failure of the glands- low PTH excretion leading to low Ca
causes of primary hypoparathyroidism
autoimmune destruction
- type 1- AIRE mutations
- Type 2- HLA D3+ and HLA D4
congenital eg diGeorge
test results for primary hypoparathyroidism
low PTH, low Ca
high or normal phosphate
sx of hypoparathyroidism
- petechiae/purpura tingling around mouth tetany muscle spasms seizures confusion cardiac arrest
tx primary hypoparathyroidism
calcium
calcitriol
synthetic PTH
What is and what causes secondary hypoparathyroidism
high calcium level
- malignancy- bony mets, vit D secretion of lymphoma, myeloma, lung, breast
- rapid burn turnover
- renal failure
- thiazides
what is pseudohypoparathyroidism
- failure of target cells to reposond to PTH
SIGNS of pseudohypoparathyroidism
- short metacarpals
- short stature
- round face
- calcified basal ganglia
test results for pseusohypoparathyroidism
- low Ca
- high PTH
- hgih phosphate
tx pseudohypoparathyroidism
Ca
what are the zones of the adrenal cortex
Glomerulosa
Fasiculata
Reticularia
what does the glomerulosa of the adrenal cortex, produce?
mineralocorticoids
- aldosterone
what stimulates the glomerulosa of the adrenals
- kidneys produce renin (low BP)
- angiotensin, thats produced from liver, converted to angiotensin I
- ACEI (lungs) cnoverts angiotensin I to angiotensin II
- aldosterone production from adrenals
what does aldosterone do
- increases BP
- increases Na and H2O retention
- increases K excretion
what does the fasiculata of the adrenal cortex, produce?
- glucocorticoids
eg cortisol
what is the function of cortisol
- increase glucose in blood
- increases gluconeogenesis in liver
how is cortisol release stimulated
HPA axis
- hypothal produces corticotrop. releasing hormone
- ant pit produces adrenocorticotropic hormones
- adrenals release cortisol
what does the reticularis zone of the adrenal cortex secrete
androgens (testosterone precursors)
how is androgen release from adrenals stimulated?
HPA axis- CRH hypothal–> ACTH from ant. pituitary–> stimulation of adrenal cortex zona reticularis to prod. androgens (testosterone and others)
ACTH also stimulated cortisol release from adrenals, and to a much lesser extent , aldosterone
NB- production of testosterone does not rely on 21-hydroxylase, yet cortisol and aldosterone does (relevant in CAH)
what part of the adrenal glands are responsible for the production of catecholamines eg noradrenaline, adrenaline
medulla
when are catecholamines stimulated to be secreted
Adrenaline, norepinephrine, dopamine
Sympathetic innervation
Adrenergic receptors
- alpha (arteries)
- beta-1 (heart- increase HR, contractility)
- beta-2 (bronchioles and arteries of the skeletal muscles)
what is Cushing’s syndrome
clincial state produced by chronic glucocorticoid excess and loss of normal feedback mechanisms of HPA
What is primary Cushing’s syndrome
non-ACTH dependent:
- issues with adrenal gland
- increased release of steroid hormones without stimulation by HPA axis
blood results of primary Cushing’s syndrome
- *cortisol-secreting adenoma in the cortex of the adrenal gland**
- low ACTH (release is activated by CRH)
- high cortisol
- ACTH suppression test will not affect amount of steroid in blood, but suppresses ACTH
causes of primary Cushing’s syndrome
- adrenal adenoma/cancer
- adrenal nodular hyperplasia
what is secondary Cushing’s syndrome
increased ACTH
causing high steroid serum
causes of secondary Cushing’s syndrome
- Cushing’s disease (ACTH secreting pituitary tumour)
- Ectopic ACTH- SCC, carcinoid tumours
sx of Cushing syndrome
- increased weight (central)
- mood change (depression, psychosis, irritability)
- skin, muscle atrophy
- gonadal dysfunction (irregular menses, hirtuisism, ED)
- acne
- moon face
- bufalo bump
- easy bruising
- purple abdo striae
- OP
- HTN
- hyperglycaemia
- poor healing
sx of Cushing’s disease/pituitary tumour
- Cushing’s syndrome
- bitemporal hemianopia
- headaches
- CN III, IV, VI palsy (eye movements)
- diabetes insipidus (low ADH)- tumour pushes on post. pituitary
- temp/sleep/appetite control issues
- CSF leak through nose
what skin changes occur in very high levels of ACTH
- yellow/tanned
seen in ectopic ACTH production and addisons (increased ACTH in response to low adrenal activity)
ix for Cushing’s syndrome
- plasma cortisol (raised)
- 24hour urinary free cortisol
- midnight cortisol levels
- plasma ACTH
**- low dose dexa methasone suppression test- 1mg
Normal– dexa- hypothal CRH reduced, ACTH from pituitary reduced , cortisol level supressed
Abnormal- cortisol level not supressed
High dose dex supp (8mg)
- pit adenoma- Cort and ACTH suppressed
- Adrenal adenoma- cortisol not supressed, ACTH suppressed
- Ectopic ACTH - both not suppressed
tx of Cushing’s syndrome
- **Metyrapone- reduce cortisol prod.
- **Ketoconazole - reduce cortisol prod.
Adrenal adenoma/carcinoma (primary):
- adrenalectomy
Paraneoplastic/Cushing’s disease (secondary)
- surgery - removal of tumour
- RT
Iatrogenic
- stop steroids
What is Addison’s
Primary adrenal Insufficiency
No negaive feedback to pituitary or hypothal (high ACTH levels, low cortisol/aldotserone/androgens)
sx of addison’s
- GI- abdo pain/diarrhoea/constipation
- weakness, fatigue
- weight loss
- hyperpigmentation of skin (golden)/vitiligo- high ACTH released from ant. pituitary
- depression, psychosis, low self esteem
- hyponatraemia- N+V, headache, fatigue, weakness/cramps/spasms, confusion, seizures, coma
- hyperkalaemia- abdo pain, diarrhoea, palpitations, weakness, paraesthesia, N+V
- hypercalcaemia- stones, moans, groans, thrones, polyuria/polydipsia
causes of Addisons’
primary
- destruction of adrenals
- autoimmune
- **- infective (TB, CMV, HIV)
- adrenal haemorrhage
- malignancy
- **Secondary
- LT steroid use supresses pituitary ACTH production, so adrenals underproduce steroids
ix for ?addison’s
- low Na and high K- low mineralocorticoids (aldosterone)
- low glucose (low cortisol)
-uraemia, hyperCa, eosinophilia, anaemia
- ACTH response test- cortisol response to ACTH measured- no response in primary/LT secondary
- ACTH- high in primary addison’s , low in secondary causes
- 21-hydroxylase autoantibodies for autoimmune (primary) cause
tx addisons
- stop exogenous corticosteroid slowly if possible
- hydocortisone (cortisol and mineralocorticoid action)
+- fludrocortisone (mineralocorticoid, replaces aldosterone)
what is primary hyperaldosternoism
Conn’s
excess production of aldosterone, independent of RAAS
Cause:
- adrenal adenomas
- adrenal hyperplasia
what is seondary hyperaldosteronism
ecxess aldosterone due to hgih levels of renin
ix for primary hyperaldosteronism (Conn’s)
- aldosterone-to-renin ratio- high (ald high, renin levels low)- GOLD STANDARD
- UEs- low K, high HCO3, high Na
- CT abdo- adenoma
what is Conn’s syndrome
- primary hyperaldosteronism
Causes:
- solitary aldosterone producing adrenal adenoma
- adrenal gland hyperplasia
- adrenal cancer
- familial
causes of secondary hyperaldosteronism
***Due to excessive RAAS activation**** renal artery stenosis accelerated HTN diuretics cong HF hepatic failure
what is Batter’s syndrome
- loss of Na and Cl in loop of henle (defect channels)
- sodium loss means volume depletion
- increased renin
sx of hyperaldosteronism
asx
Hypernatraemia:
- weakness
- polydipsia, thirst
- confusion
hypokalaemia:
- paraesthsia
- cramps, weakness, paralysis
- polyuria
- polydipsia
- HTN
tx of hyperaldosteronism
- Conn’s- removal of adenoma
- aldosterone antag- spironolactone, eplerenone
- *- dexamethasone (supresses aldosterone)
where is prolactin produced
anterior pituitary
what inhibits prolactin secretion
dopamine form hypothal
