28- Endocrine Disorders

Question 1

describe negative feedback control of the HPT (hypothalamus-pituitary-thyroid) axis

Answer 1

hypothalamus produces TRH from parvocellular neurons in specific hypothalamic nuclei

TRH is released from axon terminals into the hypophyseal portal system - travels to the anterior pituitary gland

TRH binds to thyrotrophic cells, which released TSH proportional to TRH into systemic circulation

TRH acts on thyroid gland receptors, promoting the synthesis and release of T3 and T4

T3 is the active form, T4 is mostly produced and then converted to its active form

T3 and 4 exert negative feedback inhibition on HP as their levels rise = higher levels detected by HP receptors, decreases/ suppresses TSH and TRH release = decreases T3 and T4

HPT axis runs on negative feedback inhibition and regulation to maintain thyroid hormone levels within a physiological range

Question 2

what is Hashimoto’s disease? what type of thyroid disorder?

Answer 2

primary hypothyroidism

an autoimmune disorder where the immune system attacks toe thyroid gland = leads to inflammation and destruction of the thyroid tissue

Question 3

symptoms of Hashimoto’s?

Answer 3

weight gain
fatigue
cold intolerance

Question 4

expected TSH and thyroid level hormones for Hashimoto’s disease - why?

Answer 4

low T3 and T4
high TSH and TRH

reduced T3 and T4 due to autoimmune attack on thyroid gland, reduces negative feedback inhibition on HP, increases/ raises levels of TRH and TSH

Question 5

what is Graves’ disease? what type of thyroid disorder?

Answer 5

primary hyperthyroidism

Question 6

symptoms of Graves’ disease?

Answer 6

weight loss
heat intolerance
anxiety and tremors

Question 7

expected TSH and thyroid level hormones for Hashimoto’s disease - why?

Answer 7

high T3 and T4
low TSH and TRH

high T3 and T4 due to overstimulation of antibodies binding and activating thyroid gland receptors, increasing negative feedback inhibition on HP and decreasing TRH and TSH

Question 8

define primary thyroid disorders

Answer 8

issues with thyroid production that lie with/ caused by the thyroid gland itself

Question 9

define secondary thyroid disorders

Answer 9

dysfunction of the pituitary gland or hypothalamus, affecting TSH/TRH levels which affect stimulation of the thyroid gland for T3/T4 production

Question 10

expected TSH and thyroid level hormones for secondary hypothyroidism - why?

Answer 10

low T3 and T4
low/normal TRH and TSH

secondary issue indicated as with low T3 and 4, high TSH should be produced to compensate

Question 11

expected TSH and thyroid level hormones for secondary hyperthyroidism - why?

Answer 11

high T3 and T4
high TSH

overstimulated thyroid gland from TSH overproduction leads to overproduction of T3/T4 - indicates a secondary issue as negative feedback should lower TSH

Question 12

what is the structure of the adrenal cortex? where are the steroid hormones produced?

Answer 12

outer layer of cells is the cortex, inner layer is the medulla

three layers:
- outer = zona glomerulosa - produces mineralocorticoids like aldosterone
- middle = zona fasciculata - produces glucocorticoids like cortisol
- inner = zona reticularis - produces adrenal androgens

Question 13

how does blood supply affect adrenal steroid hormone synthesis?

Answer 13

pattern of blood supply from the outer cortical surface to inner medulla dictates pattern of synthesis of steroid hormones from their precursor cholesterol and intermediates

precursors and intermediates undergo different biochemical pathways and conversions through different adrenal zones where different synthetic enzymes are expressed

Question 14

what is Cushing’s syndrome?

Answer 14

disorder characterised by prolonged exposure to high/ excess cortisol

commonly due to iatrogenic causes - prolonged use of high-dose glucocorticoid therapy - as well as primary and secondary causes

Question 15

what is Cushing’s disease?

Answer 15

a specific form of Cushing’s syndrome = excess cortisol production caused by an anterior pituitary adenoma secreting ACTH

Question 16

what is Conn’s syndrome?

Answer 16

a condition of primary hyperaldosteronism - excess aldosterone production from dysfunction within the adrenal gland

often caused by aldosterone-producing adenomas

Question 17

how does excess aldosterone affect RAAS activation?

Answer 17

excess aldosterone stimulates the distal nephron to reabsorb Na+

increased Na+ reabsorption leads to an osmotic equivalent of water retention = expands extracellular fluid volume

increased blood volume = increased blood pressure/hypertension

Question 18

what is the effect of excess aldosterone on potassium levels?

Answer 18

excess aldosterone increases K+ secretion in distal nephron - can lead to hypokalaemia

Question 19

how is primary hyperaldosteronism diagnosed using plasma renin: aldosterone ratio?

Answer 19

adrenal gland is excessively producing aldosterone = high plasma aldosterone

high plasma aldosterone will increase blood volume and pressure = lowers RAAS signalling = low plasma renin

plasma renin: aldosterone will show low renin, high aldosterone

Question 20

what conditions can lead to secondary hyperaldosteronism?

Answer 20

renal artery stenosis = one kidney is under-perfused due to arterial blockage

Question 21

how does decreased perfusion pressure and salt delivery to the distal tubule activate RAAS in secondary hyperaldosteronism?

Answer 21

reduced perfusion pressure and salt delivery to the distal tubule activates RAAS

increased renin secretion from juxtaglomerular cells = stimulates angiotensin production = stimulates aldosterone production from the adrenal cortex

Question 22

what is the characteristic plasma renin: aldosterone ratio in secondary hyperaldosteronism?

Answer 22

high plasma renin, high aldosterone

excess aldosterone production is secondary to increased RAAS activity - caused by under perfusion of kidney from renal artery stenosis rather than dysfunction within the adrenal gland

high renin causes the high aldosterone, high renin levels continue from the arterial blockage & under perfusion

Question 23

compare the plasma renin: aldosterone levels of primary vs secondary hyperaldosteronism

Answer 23

primary - high aldosterone, low renin

secondary - high aldosterone, high renin

Question 24

what is hypocortisolism?

Answer 24

a condition of adrenal insufficiency resulting in low cortisol

Question 25

what is Addison’s disease?

Answer 25

a progressive condition of primary adrenal insufficiency, characterised by lack of cortisol and aldosterone from the adrenal glands

Question 26

distinguish primary and secondary adrenal insufficiency

Answer 26

primary adrenal insufficiency - Addison’s disease:
- insufficient production of cortisol and aldosterone from autoimmune destruction of the adrenal cortex, leads to adrenal failure
- low cortisol and aldosterone

secondary adrenal insufficiency:
- pituitary or hypothalamic disease leading to insufficient cortisol production
- adrenal gland is still functional = low cortisol
- aldosterone/ mineralocorticoid production is regulated by RAAS

Question 27

symptoms commonly associated with Addison’s disease (4)

Answer 27

anorexia
fatigue, weakness
GI symptoms - constipation, diarrhoea, abdominal pain
hyperpigmentation

Question 28

diagnostic signs observed in Addison’s disease (5)

Answer 28

hypotension
low/normal plasma Na+
normal/high plasma K+
high ACTH
high plasma renin

Question 29

how is Addison’s disease diagnosed?

Answer 29

hallmarked by high ACTH and low cortisol

dynamic tests - e.g. ACTH stimulation/ syancthen test - used to assess the adrenal glands’ ability to produce cortisol in response to ACTH

Question 30

describe activation of the RAAS system

Answer 30

RAAS is activated by factors interpreted as a fall in blood volume:
- reduced renal perfusion pressure = interpreted as a fall in blood pressure from decreased blood volume
- increased sympathetic activity = vasoconstriction decreases blood pressure

fall in blood volume = reduced renal perfusion pressure = decreased fluid delivery & filtration in the DCT

reduced salt delivery is detected by macula densa cells, which send signals to juxtaglomerular cells to release renin into blood

renin enzymatically cleaves angiotensinogen produced by the liver into angiotensin I, and angiotensin I is cleaved by ACE enzyme into angiotensin II in the lungs

angiotensin II is an active hormone, acts to increase blood volume by:
- stimulating thirst, acting on brain receptors
- increases vasoconstriction
- stimulates aldosterone release from adrenal cortex

aldosterone release is also stimulated by high plasma K+ conc - its release acts to:
- decrease plasma K+ by increasing renal K+ excretion
- increases Na+ reabsorption = increases water retention = expands extracellular fluid volume and increases blood volume and pressure

Question 31

what does the RAAS system aim to do?

Answer 31

detects factors associated with a fall in blood pressure and volume - e.g. reduced renal perfusion pressure, increased sympathetic activity - and aims to increase blood volume and pressure through affecting reabsorption through kidney tubules

namely affects Na+ reabsorption, which induces water retention/ reabsorption to expand extrac. fluid volume

Question 32

list three main functions of cortisol

Answer 32

immunosuppressant
maintaining cardiovascular health - blood pressure
metabolic effects - preserves plasma glucose

Question 33

what is cortisol’s immunological function?

Answer 33

acts as an immunosuppressant

cortisol drugs are used in immunosuppressive therapy

Question 34

how does cortisol contribute to cardiovascular health?

Answer 34

helps maintain normal blood pressure

lack of cortisol = inappropriate vasodilation

excess cortisol = hypertension

Question 35

what are the metabolic effects of cortisol, particularly in terms of preserving plasma glucose?

Answer 35

cortisol ensures there is enough glucose for the brain by preserving plasma glucose levels, especially during stressful times.

• promotes insulin resistance in skeletal muscle
• stimulates lipolysis
• enhances gluconeogenesis in the liver.

Question 36

what are the consequences of high cortisol levels in the absence of physiological stress?

Answer 36

• insulin resistance in muscles can lead to hypoglycaemia
• increased gluconeogenesis contributes to high blood glucose, which stimulates insulin release
• insulin promotes lipogenesis = results in increased central adiposity and thinning of the extremities - traits of Cushing’s disease

Question 37

what hormones control the adrenal cortex in the HPA axis?

Answer 37

hypothalamus releases CRH - travels through portal vein to pituitary gland

anterior pituitary gland releases ACTH into systemic circulation - binds to adrenal cortex receptors

adrenal cortex produces and releases cortisol

Question 38

how does cortisol exert negative feedback regulation in the HPA axis?

Answer 38

cortisol levels rise = bind to cortisol receptors in the hypothalamus and anterior pituitary, inhibits the release of CRH and ACTH

this provides negative feedback regulation of the HPA axis = maintains cortisol levels within a set point controlled at the hypothalamic level

Question 39

why is it challenging to measure plasma cortisol levels accurately?

Answer 39

cortisol levels fluctuate throughout the day due to pulsatile release of hypothalamic hormones and circadian rhythms

• peaks in the morning
• fluctuates during the day
• lowest at midnight

hard to establish a single reference range for cortisol measurement

Question 40

how does cortisol secretion affect vasopressin (ADH) secretion?

Answer 40

cortisol exerts negative feedback on ADH secretion, doesn’t outright shut down ADH

high cortisol levels reduce ADH secretion; more ADH is secreted in the absence of cortisol