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