28- Endocrine Disorders Flashcards

conn's syndrome is still here, and the thyroid disorders

1
Q

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

A

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

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2
Q

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

A

primary hypothyroidism

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

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3
Q

symptoms of Hashimoto’s?

A

weight gain
fatigue
cold intolerance

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4
Q

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

A

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

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5
Q

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

A

primary hyperthyroidism

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6
Q

symptoms of Graves’ disease?

A

weight loss
heat intolerance
anxiety and tremors

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7
Q

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

A

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

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8
Q

define primary thyroid disorders

A

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

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9
Q

define secondary thyroid disorders

A

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

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10
Q

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

A

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 but isn’t (issue with HP)

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11
Q

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

A

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

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12
Q

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

A

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

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13
Q

how does blood supply affect adrenal steroid hormone synthesis?

A

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

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14
Q

what is Cushing’s syndrome?

A

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

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15
Q

what is Cushing’s disease?

A

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

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16
Q

what is Conn’s syndrome?

A

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

often caused by aldosterone-producing adenomas

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17
Q

how does excess aldosterone affect RAAS activation?

A

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

18
Q

what is the effect of excess aldosterone on potassium levels?

A

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

19
Q

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

A

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

20
Q

what conditions can lead to secondary hyperaldosteronism?

A

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

21
Q

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

A

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

22
Q

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

A

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

23
Q

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

A

primary - high aldosterone, low renin

secondary - high aldosterone, high renin

24
Q

what is hypocortisolism?

A

a condition of adrenal insufficiency resulting in low cortisol

25
Q

what is Addison’s disease?

A

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

26
Q

distinguish primary and secondary adrenal insufficiency

A

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

27
Q

symptoms commonly associated with Addison’s disease (4)

A

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

28
Q

diagnostic signs observed in Addison’s disease (5)

A

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

29
Q

how is Addison’s disease diagnosed?

A

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

30
Q

describe activation of the RAAS system

A

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

31
Q

what does the RAAS system aim to do?

A

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

32
Q

list three main functions of cortisol

A

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

33
Q

what is cortisol’s immunological function?

A

acts as an immunosuppressant

cortisol drugs are used in immunosuppressive therapy

34
Q

how does cortisol contribute to cardiovascular health?

A

helps maintain normal blood pressure

lack of cortisol = inappropriate vasodilation

excess cortisol = hypertension

35
Q

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

A

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.
36
Q

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

A
  • 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
37
Q

what hormones control the adrenal cortex in the HPA axis?

A

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

38
Q

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

A

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

39
Q

why is it challenging to measure plasma cortisol levels accurately?

A

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

40
Q

how does cortisol secretion affect vasopressin (ADH) secretion?

A

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