Endocrinology Flashcards
What is the difference between primary and secondary disease in regards to the hypothalamus and pituitary
Primary- gland itself fails e.g thyroid, adrenal cortex, gonad
Secondary- no signal from hypothalamus or anterior pituitary
What are two types of hypothyroidism and how it impacts T3/4 and TSH levels
Primary hypothyroidism- autoimmune destruction of thyroid gland itself so T3 and T4 Fall but TSH is high (don’t measure TRH as too low in the blood) TSH is high as trying to make the gland work and there’s no negative feedback as gland isn’t able to produce T3 and T4
Secondary Hypothyroidism- pituitary tumour damaging thyrotrophs so not a problem with the gland- problem with hypothalamus or pituitary, TSH will fall and T3/4 will also fall as no TSH
What are the disorders associated with the anterior pituitary and adrenal gland
Primary Hypoadrenalism- destruction of adrenal cortex. Cortisol will fall but ACTH increases as is trying to make the gland work (Dont easure CRH but would also be high)
Secondary Hypoadrenalism- pituitary tumour damaging corticotrophs so can’t make ACTH, ACTH and cortisol low
Why is aldosterone not affected if there’s a problem with ACTH
Cortisol is regulated by ACTH but aldosterone is not as its regulated by renin angiotensin
What are the disorders associated with the anterior pituitary and the gonads
Primary hypogonadism- destruction of testes (from mumps) or ovaries (chemotherapy). Testosterone in men and oestrogen in women both fall but LH and FSH increase trying to get gonads to produce
Secondary Hypogonadism- pituitary tumour damaging gonadotrophs cant make LH or FSH so low LH FSH and oestrogen or testosterone
What are the causes of hypopituitarism
CONGENITAL- mutation of transcription factors needed for anterior pituitary development, deficient in GH and at least one other Anterior Pituitary hormone. Will have a short stature and hypoplastic (underdeveloped) anterior pituitary gland
ACQUIRED- tumours, radiation, infection, trauma, pituitary surgery, inflammatory, pituitary apoplexy (haemorrhage or infarction), peri-partum infarction (sheehans)
What is the name for loss of all anterior and posterior pituitary function
Panhypopituitarism
If there is loss of some of the anterior pituitary function and some of the posterior pituitary but not complete loss, what is the diagnosis
hypophytis
How does radiotherapy cause acquired hypopituitarism and what cells in the pituitary are most sensitive
Pituitary and hypothalamus both sensitive to radiation, can be radiotherapy to pituitary or indirect to a tumour nearby, higher the radiotherapy dose the higher the risk of HPA axis damage
GH (somatotrophins) and gonadotrophins most sensitive
Must monitor for 10 years as risk persists that long
What are the different presentations of hypopituitarism
LOW FSH/LH (secondary hypogonadism-pituitary failing) low libido, secondary amenorrhea, erectyle dysfunction, reduced pubic hair
ACTH: (secondary hypoadrenalism-pituitary failing) fatigue as cortisol about energy, (won’t affect salt loss as still have aldosterone as its under the renin angiotensin system not cortisol)
TSH: fatigue maybe weight gain
GH: reduced quality of life, short stature but only in children as adults has finished growing
PROLACTIN: can’t breastfeed
What is post-partum hypopituitarism secondary to hypotension called
Sheehans syndrome- is post partum haemorrhage
Describe Sheehan’s syndrome
In pregnancy the anterior pituitary gets larger due to the lactotrophs enlarging to prepare for breastfeeding (lactotroph hyperplasia)
Postpartum haemorrhage means that blood pressure drops massively and without fast transfusion (hypotension) thus the pituitary does not get enough blood especially due to its size so causes pituitary infarction and the pituitary stops working.
Presentation- tried, anorexic, weight loss, TSH/ACTH/GH deficiency, CANT lactate, secondary amenorrhea, posterior pituitary okay
in short- lactotrophs increase for breastfeeding, AP gets bigger, preganancy causes haemorrhage, AP not supplied with blood= infarction= doesnt work
What is it called when there is bleeding into the pituitary or infarction of the pituitary
Pituitary apoplexy
Describe pituitary apoplexy
Haemorrage of pituitary (fills with blood) or infarction of pituitary (not enough blood), have excruciating headache if patient has pre-existing pituitary tumours (which is normal)
Pituitary gland is much bigger in both cases, either due to blood filling or infarction will cause inflammation, this squashes the pituitary gland against optic chiasm so bitemporal hemianopia
Blood thinners can cause
Presentation- sudden severe headache, bitemporal hemianopia (optic chiasm compressed), double vision- Diplopia or CANT open eyes- ptosis (cavernous sinus problem)
What is the issue in trying to diagnose hypopituitarism and what is done instead
Lots of the hormones depend on other factors like
Cortisol is affected by time of day
T4 circulates for 5-7 days so a drop may not be detected
FSH and LH is cyclical in women
GH and ACTH is pulsatile
Instead dynamic pituitary function tests are used. This involves inducing hypoglycaemia (give insulin) which cause stress to the body and GH and ACTH release (cortisol measured for this)
TRH given to stimulate TSH
GnRH given to stimulate FSH and LH
What scan is needed to check for pituitary tumours
MRI as CT has a low resolution
How is hypopituitarism treated
Prolactin doesn’t need treatment
Growth Hormone- confirm deficiency with pituitary function test, assess the quality of life. Then do a daily injection and measure response by improvement in plasma IGF-1 and change in quality of life
Thyroid Stimulating Hormone- levothyroxine once daily, can’t use TSH to adjust dose as their TSH will stay low as it’s a pituitary problem not primary hypothyroidism, need fT4 above middle of reference range
LH/FSH-
men- replace testosterone, this doesn’t restore sperm production as this is dependent on FSH. If fertility is needed then spermatogenesis can be inducted through gonadotrophin injections (best response if it’s secondary hypogonadism after puberty). Then measure testosterone and analyse semen
women- replace oestrogen and progesterone (prog if uterus intact), if fertility required then carefully timed gonadotrophin injections
ACTH- replace cortisol , prednisolone once daily or hydrocortisone three times per day
Describe the posterior pituitary gland, its anatomy, what neurons it has and what hormones it produces
is anatomically continuous with hypothalamus
has magnocellular neurons that contain either AVP if the neurons originate in the supraoptic hypothalamic nuclei and oxytocin if they originate in the paraventricular hypothalamic nuclei
How does vasopressin work, through what receptors
vasopressin acts to stimulate water reabsorption by acting on V2 receptors in the kidneys collecting duct. (V2 is a g protein receptor so when bound, triggers adenyl cyclase, which turns ATP to cAMP which phosphorrylates protein kinase A, PKA phosphorylates aquaporins which fuse with apical/uminal membrane making it water permeable)
At high levels acts on V1 receptor to cause vasoconstriction, and stimulates ACTH release from anterior pituitary
What is osmolality
Relates to amount of particles in the blood. Is increased when there are more particles aka dehydrated, is decreased when less particles aka overhydration
What is the stimuli for vasopressin release and give examples of when these may occur
1)OSMOTIC- rise in plasma osmolality (blood that flows in) sensed by osmoreceptors in the posterior hypothalamus which stimulate magnocellular neurons (in the supraoptic hypothalamic nuclei) to secrete ADH. High osmolality means more particles in the blood so triggers ADH to absorb water from the urine to lower this, e.g. dehydration
2) NON-OSMOTIC- decrease in atrial pressure sensed by atrial stretch receptors, e.g. lots of blood/volume loss so less blood back to the atria and the lack of filling decreases the pressure, secrete ADH to build this volume back up
Describe osmotic stimulation of vasopressin release
two nuclei named the organum vasculosum (closer to pituitary) and the subfornical organ are circumventricular (sit around the 3rd ventricle) , theres no blood brain barrier so neurons can respond to changes in SYSTEMIC circulation, are highly vascularised nuclei. The neurons project to the supraoptic nucleus.
Osmotic pressure is dependent on the plasma osmolality. Plasma osmolality is in turn affected by the total body plasma volume. Following a fall in plasma volume there is an increase in the plasma sodium (Na+) concentration, and therefore the osmolarity is increased. Subsequently water exits cells, and moves down its concentration gradient into the plasma. This stimulates the osmoreceptors cells to contract/shrink, which results in increased osmoreceptor firing so more afferent signals being sent from the hypothalamus to the posterior pituitary gland to increase the release of ADH
Alternatively, if there is an increase in the total body volume then the osmolality of the plasma will reduce. In this situation, water will move down its concentration gradient from the plasma, into osmoreceptor cells, causing them to expand. As a result, afferent signals are sent from the hypothalamus to the posterior pituitary gland to decrease the release of ADH.
Describe non-osmotic stimulation of vasopressin release and why it occurs
ADH secretion also occurs during states of hypovolemia. Baroreceptors in the left atrium, carotid artery and aortic arch detect changes in arterial blood volume.
The stretch receptors inhibit vasopressin release via the vagus nerve communicating with the hypothalamus. AVP works throught the V2 receptor to restore the circulating volume and it also causes vasoconstriction through V1 receptors
If blood pressure reduces for example due to a haemorrhage there is less stretch of atrial receptors, baroreceptors relay this to the vagus nerve, which sends afferent signals that directly stimulates the release of ADH from the posterior pituitary, less stretch= less inhibition. Conversely, in a hypervolemic state, the release of ADH will be reduced.
Vasopressin results in higher water reabosrption in the kidney via V2 receptors and vasconstriction via V1 so it is needed following a haemorrhage to increase blood volume and pressure
What is the result of dehydration
higher plasma osmolality (less water more particles)
osmoreceptors shrink and are stimulated
thirst is experienced and AVP is released
Vp acts on V2 to cause water reabsorption from renal collecting ducts. Less water in urine means less urine volume, increase in urine osmolality but decrease in plasma osmolality
what are the symptoms of diabetes mellitus and insipidus and what are the symptoms due to
polyuria
nocturia
thirst
polydispia
Diabetes mellitus- symptoms due to osmotic diuresis. the concentration of glucose exceeds the maximum re-absorption capacity of the kidney, glucose remains in the filtrate. This causes an increase in osmotic pressure causing water and potassium to move out and into the urine.
diabetes insipidus- symptoms due to a problem with arginine vasopressin
MELLITUS= GLUCOSE IN PEE
INSIPIDUS= AVP NOT WORKING
What are the types of diabetes insipidus
1) CRANIAL(central)- problem with hypothalamus and or posterior pituitary, cant make argenine vasopressin. VASOPRESSIN INSUFFICIENCY
2) NEPHROGENIC- can make ADH but the kidneys renal collecting duct is unable to respond to vasopressin. VASOPRESSIN RESISTANCE
What are the acquired and congenital causes of the two types of diabetes insipidus
CRANIAL
ACQUIRED- traumatic brain injury, pituitary tumour, pituitary syrgery, metastasis of cancers to the pituitary gland, granulomatous infliltration of pituitary stalk, autoimmune
CONGENITAL
NEPHROGENIC- much less common than cranial
ACQUIRED- drugs like lithium
CONGENITAL-rare mutation in V2 receptor, aquaporin 2 receptor
Presentation of a patient with diabetes insipidus and an explanation of why these symptoms occur
polyuria, polydipsia, polynoctuira, thirst
Urine- dilute (hypoosmolar), and large volumes (AVP is either not there or kidney resistant to it, so cantstimulate water reabsorption)
Plasma- increased concentration hyperosmolar as patient is dehydrated, increased sodium, normal glucose
WHY? argenine vasopressin problem either cranial diabetes insipidus where there is a insufficiency of vasopressin or nephrogenic where there is resistance to vasopressin, this causes impaired concentration of urine in the collecting duct- so cant concentrate urine, leads to large volumes of hypotonic urine and an increase in plasma osmolality and sodium as no water is reabsorbed. This higher osmolality stimulates osmoreceptors and causes the feeling of polydipsia aka thirst.
if the patient has access to water the circulating volume/plasma is maintained however, without water it can lead to dehydration and death
What is psychogenic polydipsia
polydipsia, polyuria, nocturia, but No problem with vasopressi. problem is that the patient drinks all the time.
patient drinks more water, plasma osmolality falls, less AVP secreted, large volumes of hypotonic urine to increase plasma osmolality
How do we distinguish between diabetes insipidus and psychogenic polydipsia
water deprivation test. dont give anythig to drink and measure urine volumes, urine concentration-osmolality and plasma concentration
psychogenic polydipsia will be slight lower than normal in regards to urine osmolality and diabetes insipidus will have 0
stop the test if the patient loses more than 3% of bodyweight
plasma osmolality between the two will also be different. diabetes insipidus have a slightly higher plasma osmolality than normal and psychogenic polydipsia have a lower one than normal
Diabetes insipidus will have a high sodium (high plamsa osmolality), psychogenic polydipsia will have a low sodium
How do we distinguish between the two types of diabetes insipidus
give ddAVP/desmopressin which works like vasopressin, cranial will respond but nephrogenic wont
what is the treatment of diabetes insipidus
CRANIAL- Desmopressin which is selective for V2 receptor, it replaces vasopressin
NEPHROGENIC- rare and difficult to treat, thiazide diuretics like bendofluazide
What is SIADH, the different osmololities you would find, the causes and management
Syndrome of Inappropriate Anti Diuretic Hormone
too much ADH, reduces urine output and leads to urine retention
have high urine osmolality, low plasma osmolality as absorb too much water, dilutional hyponatraemia - less sodium due to the dilution
CAUSES-
CNS- head injury, stroke or tumour
Pulmonary disease- pneumonia or bronchiectasis
Malignancy- Lung cancer
Drug-related- SSRI’s
Idiopathic
MANAGEMENT- fluid restrict or use VAPTAN a vasopressin antagonist which binds to the V2 receptors in the kidney but is very expensive
What is the treatment for someone with primary hypothyroidism
T4 Levi-something
Increase the dose until TSH falls to normal
What is Graves’ disease, symptoms and
Autoimmune, antibodies bind to and stimulate the TSH receptor in the thyroid, causes HYPERTHYROIDISM and a smooth goitre
Symptoms : sweating, facial flushing, muscle wasting , breathlessness, exophthalmos, goitre, increased appetite with no weight gain, tachycardia, palpitation, loss of periods, pretibial myxoedema (growth of soft tissue no pitting)
In the conditions Graves, plummers and viral thyroditis what would be the difference between thyroid scans in terms of radioiodine uptake
Really dark on radioiodine scans means over activity as more is taken up
In Graves’ disease there is an enlarged goitre due to antibodies stimulating the thyroid so there will be a moderate size thyroid with uniform radioiodine uptake. Dark in scan
In plummers disease it’s a toxic nodular goitre so a small region is overactive so only one half of the thyroid will be dark and the other half light grey and usually smaller
In viral thyroditis the virus attacks the thyroid and stops it working completely so there would be no colour on the scan at all
What is plummers disease
Toxic nodules goitre, not autoimmune, a benign tumour is small and comes from thyroid cells that grow and become overactive. Will feel lumps and bumps
As it’s not autoimmune there will be no exophthalmos, no pretibial myxoedema
There will be enlargement in one side of the thyroid as it’s a nodule that overactive
What are the effects of thyroxine on the sympathetic nervous system
Sensitises beta adrenocorticotrophic to ambient(normal/resting) levels of adrenaline and noradrenaline. Means that there will be a larger response to stimuli considered normal like being nervous for an interview, it would result in palpitations, tachycardia, lid lag and tremor - WILL BE APPARENT SYMPATHETIC ACTIVATION
What is thyroid storm
Untreated hyperthyroidism
Hyperprexia- temperature over 41
Tachycardia and arrhythmia
Cardiac failure
Delirium
Hepatocellular dysfunction (stops clearing billirubin)
ANY TWO MEANS THYROID STORM
Is an emergency needs treatment
Give propanalol (beta blocker) and then give thionamides
What are the treatment options for hyperthyroidism
- Surgery
- Radioiodine
- Drugs
- thionamides the anti thyroid drugs includes propyltiouracil and carbimazole
- potassium iodide- large doses of iodine causes negative feedback which blocks TSH and thus reduces T4, only works for a short time after 10 days will make more thyroxine from the iodine (done before operation)
- beta blockers - to reduce tachycardia
Radioiodine, potassium iodide and thionamides reduce thyroid hormone synthesis whereas beta blockers are for symptoms
What are the treatments and follow up for hyperthyroidism
Thionamides like propylthiouracil and carbimazole used daily
Propranolol (a non selective beta blocker as all receptors are sensitised so all need to be blocked) for tremors as anti thyroid drugs take several weeks to have effects on tremor,anxiety and heart rate
Aim to stop anti thyroid drugs after 18 months,
How do thionamides work, what are the possible side effects
Thyroid hormone is synthesised by oxidising iodide to make iodine, this then bonds to thyroglobulin by the thyroidperoxidase enzyme and hydrogen peroxide to make thyroxine
Thionamides block thyroidperoxidase so T3/4 synthesis is decreased
Side effects- rashes and aganulocytosis (reduction of neutrophils) problem as no immunity so will tend to get streptococcus throat sores.
How does potassium iodide work
Directly inhibits thyroglobulin with some effect on thyroperoxidase
Causes the
Wolff-Chaikoff effect is an autoregulatory phenomenon, whereby a large amount of ingested iodine acutely inhibits thyroid hormone synthesis within the follicular cells, irrespective of the serum level of thyroid-stimulating hormone (TSH)
Symptoms reduce within 1-2 days
Vascularity and size of gland reduce within 10-14 days
What are the risks of thyroid surgery
Risk of voice change due to recurrent laryngeal nerve
Risk of losing parathyroid glands- can become hypocalcaemic
Scar
Anaesthetic
How does the radioiodine treatment work
Swallow a capsule
Can’t use when pregnant and bead to avoid children and pregnant mums for a few days
What is the condition where a virus attack the thyroid, what are the symptoms and what’s the treatment
Viral thyroditis
Virus attacks the thyroid gland causing pain and tenderness, causes thyroid gland to stop making thyroxine and makes viruses instead so no iodine uptake if tested, instead will release all thyroxine, eventually will become hypothyroid as cant produce thyroid hormone and has exhausted its stores .
Painful dysphasia, hyperthyroidism, prexia and thyroid inflammation, tender pretracheal lymph nodes, pain radiating to ear, neck painful, free T4 rises as thyroxine stores are released, TSH drops, no new thyroxine
fT4 drops after a month (hyperthyroid for a month) then become hypothyroid
Treatment- none as will resolve by itself in two months
How are pituitary tumours classified
Microadenoma or macroadenoma
Sellar or suprasellar
Compress optic chiasm or not
Invade cavernous sinus or not
Excess secretion of a specific pituitary neurone or no excess e.g prolactinoma or non functioning adenoma
Benign or malignant , pituitary adenomas can have benign histology but display malignant behaviour
Describe the pituitary tumours and which ‘troph’ cells they come from in the anterior pituitary
Acromegaly - somatotrophic cells
Prolactinoma- lactotrophs
TSHoma- thyrotrophs
Gonadotrophinoma- gonadotrophs
Cushings/ corticotrophadenoma- corticotrophs
Describe the cells in the anterior pituitary and the hormones they produce
Somatotroph- produce growth hormone/somatotrophin
Lactotrophs- Prolactin
Gonadotrophs- LH and FSH
Thyrotrophs- TSH
Corticotrophs- ACTH
How are pituitary tumours classified
Radiological- Microadenoma is less than 1cm, macroadenoma if over. can be sellar or suprasellar. whether it compresses the optic chiasm or invades the cavernous sinus.
Can be a hormone secreting tumour or a non functioning one.
Ki-67 index used to see how many cells are dividing.
even if have a benign histology can have malignant behaviour.
How does prolactin affect the hypothalamic pituitary axis
Prolactin binds to prolactin receptors on kisspeptin neurones in the hypothalamus inhibiting the release of kisspeptin. Kisspeptin stimulates the release of GnRH, so without this GnRH decreases which stops the anterior pituitary gonadotrophs releasing LH, FSH and thus Testosterone and Oestrogen
How does hyperprolactinaemia/a prolactinoma affect a patient
GnRH needs to be pulsatile to for puberty, GnRH is also needed to stimulate release of LH and FSH. Too much prolactin inhibits this.
Thus high prolactin will cause oligo-amenorrhea, low libido, erectile dysfunction, galactorrhoea, sub/infertility (infertility if happens before puberty) or osteoporosis
What are some causes of elevated prolactin
pregnancy
stress- venepuncture, exercise, seizures
primary hypothyroidism - problem with thyroid so get high TRH which also stimulates lactotrophs to release prolactin
polycystic ovarian syndrome
chronic renal failure- reduces the clearance and brakdown of prolactin
Antipsychotics, SSRI, high doses of oestrogen, opiates
If serum prolactin in a patient is elevated, what should you do next
Pituitary MRI
if a prolactinoma is confirmed, how would you treat it?
Dopamine receptor agonist - cabergoline
is safe in pregnancy and dosage relates to how big the prolactinoma is
How does cabergoline work ?
Lactotrophs in the anterior pitutary have D2 dopamine receptors, Dopamine binds to the D2 receptor and inhibits the secretion of prolactin. Cabergoline is a dopamine receptor agonist so will bind to the D2 receptor and also inhibit prolactin secretion
Pituitary tumours that secrete excess GH cause what conditions
Gigantism (in children)
Acromegaly (in adults)
How does acromegaly present
Slow presentation
Sweatiness
Headache
Coarsening of facial features- Macroglossia and a prominent nose, a large jaw
increased hand and feet size
anoring and obstructive sleep apnoea
hypertension
Impaired glucose tolerance- diabetes mellitus
What is the mechanism of growth hormone
Anterior pituitary when stimulated secretes growth hormone (somatotrophin) which acts on body tissues to cause growth and development.
At the same time GH also acts on the liver to secrete Insulin-like Growth Factor (somatomedin) to act on IGF-1 receptors on body tissues to increase growth and development. IGF-2 is predominantly in children.
How is acromegaly diagnosed
Since GH is pulsatile, cant easily measure it so:
- Elevated serum IGF-1
- Rise of GH when given an oral glucose load, normal peoples GH will lower
Ho is acromegaly treated
Surgical because acromegaly increases cardiovascular risk
trans-sphenoidal pituitary surgery.
Prior to surgery somatostatin analogues such as octreotide or dopamine agonists like cabergoline (pituitary tumours usually have D2 receptors) can be used to shrink the tumour.
Radiotherapy not recommended as will lose all pituitary tumours.
A patient has:
red cheeks
high blood pressure
proximal myopathy (muscle weakness)
Purple striae
Easy bruising
Moon face
Buffalo hump
fat deposition on abdomen
amenorrhea/hirtuism in women and erectile dysfunction in men
What is the condition?
Cushings disease
What is cushings syndrome and what are the causes
Excess of cortisol or other glucocorticoid
Causes are ACTH dependent like : pituitary/corticotroph adenoma which is Cushings disease , ectopic ACTH, adrenal adenoma or carcinoma
What is cushings disease and what are the causes
Excess of cortisol or other glucocorticoid
Causes can be ACTH dependent: pituitary/corticotroph adenoma which is Cushings disease
Or ACTh independent : ectopic ACTH- lung cancer can cause, adrenal adenoma or carcinoma or taking too many steroids
What is the difference between Cushings syndrome and Cushings disease?
syndrome= excess cortisol
disease= a corticotropph adenoma/ pituitary tumour that secretes ACTH
How is Cushings disease diagnosed/investigated
24 hour urine test which measures free cortisol secretion
Cortisol has a diurnal rhythm, in Cushings cortisol remains high throughout the day (elevation of late night cortisol)
Or, the patient is given oral dexamethasone an exogenous glucocorticoid, if there is increase cortisol after then there must be a corticotroph adenoma because giving a glucocorticoid should switch off cortisol. If cortisol not 0 by end of test then have.
Is Cushings disease ACTH independent or dependent
Dependent, so should measure ACTH once find that there is high levels of cortisol, then a pituitary MRI
How would a non functioning pituitary adenoma present and how would it be treated
Bitemporal hemianopia - visual disturbance
Serum prolactin may be raised since dopamine cant travel down the pituitary stalk
can preset with hypopituitarism
trans-sphenoidal surgery needed
Describe the hypothalamo pituitary axis
Hypothalamus and anterior pituitary both recognises low thyroid hormones (low T4 and T3), low adrenal hormone levels (cortisol) and sex hormone levels and there is negative feedback- increasing stimulation.
GRH/TRH/CRH/GnRH is therefore secreted from the hypothalamic paraventricular nucleus to the thyrotrophs/corticotrophs/gonadotrophs in the pituitary.
The anterior pituitary thus secretes GH/TSH/ACTH/LH/FSH.
GH acts on tissues
TSH acts on the thyroid to secrete T3 and T4
ACTH acts on the adrenal glands zona fasciculata to secrete the glucocorticoid cortisol
LH/FSH acts on the sex glands to make testosterone or oestrogen
What is Graves disease and how would it present
An autoimmune condition, antibodies made bind to and stimulate the TSH receptor in the thyroid, this causes the thyroid to enlarge making a smooth goitre and results in hyperthyroidism.
Symptoms: facial flushing, goitre, tachycardic, palpatations, increased appetite but loose weight, shortness of breath (these symptoms happen because patient is sensitised to beta adrenergic receptors so adrenaline is much higher). The antibodies may also bind to other areas causing exophthalamos, pretibial myxoedema (non-pitting swelling on shins due to soft tissue growth),
If radioactive iodine was given to patients with Graves disease, Plummers and Viral Thyroiditis how would the thyroid scans differ
Graves disease: uniform radioiodine uptake
Plummers disease: uptake of iodine on one side- one hot nodule
Viral Thyroiditis: wont see thyroid on scan
What is plummers disease, and how would it present
A toxic nodular goitre- a small benign adenoma that s overactive making too much thyroxine, is not autoimmune.
Will see enlargement on one side of goitre
How does thyroxine affect the sympathetic nervous system
Sensitises beta adrenoceptors to normal/ambient adrenaline and noradrenaline levels which causes sympathetic activation.
This means there is an exaggerated reaction of tachycardia, hand tremor and lid lag to normal stimuli
Describe symptoms of Hyperthyroidism and name three diseases it causes
Graves Disease, Plummers Disease, Viral Thyroiditis
Weight loss despite increased appetite
breathlessness
palpatations, tachy, sweat
heat intolerance
diarrhoea
lid lag
What is a thyroid storm and how is it classified
Hyperthyroidism
Medical emergency
Any two of the following:
Hyperpyrexia- temp over 41
Tachycardia HR is high
Cardiac failure
Delirium
Jaundice as hepatocytes dysfunction
How is hyperthyroidism treated
Thionamides- Propylthiouracil and carbimazole: inhibit thyroid peroxidase which stops thyroglobulin being oxidised and stops T3/4 being made
Potassium Iodide - large amounts of iodine negatively feedback on pituitary by directly blocking thyroglobulin by stopping iodination, it also inhibits H2O2 generation so TPO cant react with it- Wolff-Chaikoff effect
Non-selective B-blockers- such as propranolol reduces tremor and tachycardia, Needed since anti-thyroid drugs take so long to work, needs to be non-selective as all receptors are sensitised due to high thyroxine
Aim to end anti-thyroid drug after 1.5 yrs
How is thyroid hormone synthesised
ANterior pituitary secretes TSH (thyrotrophin) which binds to the TSH-R on the basolateral membrane of follicular cells
When TSH binds to its receptors three things happen:
- Sodium-iodide transporter on basolateral membrane is activated, sodium and iodide is thus transported into follicular cells. The iodide moves further into the colloid where it undergoes iodination to make iodine
- Thyroglobulin a prohormone is made and transported into the follicular cells colloid
- TPO (thyroperoxidase) enzyme is activated, moves into colloid. TPO + H2O2 catalyse the reactions of Iodine and tyrosine residues in thyroglobulin. When TPO iodinates thyroglobulin it makes 3-monoiodotyrosine and 3,5 diiodotyrosine
these combine to make T3 which is 3,5,3 triiodothyronine or T4 3,5,3,5, tetraiodothyronine
What are the side effects of thionamides
Agranulocytosis- reduction in neutrophils, may get streptococcus and a sore throat since immune system is weak
rashes
Why is surgery not the best option in hyperthyroidism
Could have a thyroidectomy
Can damage recurrent laryngeal nerve which may cause a voice change
May lose parathyroid gland and become hypocalcaemic
Scars
How is radioiodine used and if taken what do they need to be careful of
For scans only
Shouldnt use in pregnancy
Need to avoid children and pregnant women
What is Viral thyroiditis (de Quervain’s) and how will it present
A virus attacks the thyroid gland and causes pain and tenderness, thyroid stops working and makes viruses instead, this means no iodine uptake so thyroid wont show on a scan
Painful dysphagia
Painful neck for a month
Hyperthryoidism (high T4, low TSH) : as causes all thyroxine that is stored in colloid will be released, after four weeks will be hypothyroid until the follicular cells regenerate
Pyrexia
Thyroid inflammation
What is postpartum thyroiditis
same as viral thyroiditis but no pain, happens after pregnancy
Which hormones increase and decrease serum calcium and how
INCREASE:
Vitamin D
Parathyroid Hormone (PTH)
regulate calcium and phosphate homeostasis via actions on kidney, bone and gut
DECREASE:
Calcitonin
Describe Vitamin D metabolism
UVB stimulates skin cells to make Vitamin D3 (cholecalciferol), or Vitamin D2 (ergocalciferol) is taken from the diet.
These go to the liver where 25-hydroxylase hydroxylates vitamin D into 25(OH)cholecalciferol which is an inactive form of Vitamin . It then moves to the kidney and is hydroxylated a second time by 1-alpha-hydroxylase to the active 1,25(OH)2 cholecalciferol (same as calcitriol).
After making certain amounts of calcitriol theres negative feedback to stop 1-alpha-hydroxylase, which stops more active vitamin D being formed
How does calcitriol/active vitamin D work
Promotes Ca2+ reabsorption from the bone
Stimulates Ca2+ and PO4^3- absorption from gut
Stimulates Ca2+ and PO4^3 reabsorption in kidney, so less in urine
Where is parathyroid hormone secreted from and how does it work
Chief cells in parathyroid glands detect change in serum calcium through the G-protein coupled calcium receptor. PTH secretion is inversely proportional to serum calcium (more calcium binding to parathyroid cells, the less PTH made, less calcium binding the more PTH) so when calcium is low, it secretes pre-pro-PTH a large protein precursor and cleaved to PTH.
What are the actions of PTH
Promotes Ca2+ reabsorption from the bone
Stimulates Ca2+ reabsorption and PO4^3 excretion in kidney.
Increases 1-alpha-hydroxylase activity of kidney which increases 1,25(OH)2cholecalciferol aka calcitriol synthesis. And active vitamin D works on the gut to increase Ca2+ and PO4^3- absorption
How does PTH and calcitriol affect the bone, whats the difference?
PTH binds to PTH receptor on osteoblasts, stimulates them to release osteoclast activating factors like RANKL to become osteoblast and results in bone reabsorption. Results in phosphate excretion
Calcitriol does the same, if serum calcium is low then calcitriol increases reabsorption from bone as well as promoting osteoblast formation. results in phosphate absorption
How is PTH regulated
Fall in plasma Ca2+ is sensed by receptors on parathyroidgland and stimulates an increase in PTH.
PTH works on bone stimulating osteoclast formation, works on kidney to increase calcium reabsorption, works indirectly on gut by increasing 1-alpha-hydroxylase activity of kidney which increases 1,25(OH)2cholecalciferol which increases calcium absorption from the gut.
As calcium is restored to normal, it negatively feedsback on the thyroid gland to switch PTH off
What is calcitonin and how does it affect calcium
Parafollicular cells of thyroid secrete calcitonin which decreases osteoclast activity, increases kidney Ca2+ excretion and results in lower plasma Ca2+
What does FGF23 regulate and how?
FGF23 reduces phosphate in two ways
1) inhibits the sodium/phosphate co transporter in the proximal convoluted tubule , this means phosphate and sodium can’t be reabsorbed so more is excreted
2) inhibits calcitriol (1,25(OH)2D3), active Vitamin D Causes PO4^3- absorption from the gut, by blocking it then less is absorbed.
What are the symptoms of hypocalcaemia
Calcium sensitises excitable tissues so get muscle cramps, tetany, tingling
Paraesthesia of hands mouth feet and lips
Convulsions
Arrhythmias
Tetany- involuntary contractions
Signs:
Chvosteks’ sign- facial paresthesia
Trousseau’s sign- carpopedal spasm
What are the causes of hypocalcaemia
Low PTH level/hypoparathyroidism: can be from autoimmunity,surgical, magnesium deficiency, congenital
Low Vitamin D levels: poor diet/malabsorption, lack of UV, renal failure (cant make 1-alpha hydroxylase)
what are the symptoms of hypercalcaemia
Stones- Nephrocalcinosis which can lead to renal colic
GI effects- anorexia, dyspepsia, constipation, pancreatitis
CNS effects- fatigue, depression, impaired concentration, coma is very low
