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Year 2 Medicine > Hypothalamic-pituitary-adrenal axis: clinical aspects > Flashcards

Hypothalamic-pituitary-adrenal axis: clinical aspects Flashcards

1
Q

What is shown in the image?

A

Hypothalamic-pituitary axis

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2
Q

Hypothalamic-pituitary-adrenal axis

  • Releasing factors are … and to a lesser extent …
  • Trophic hormone is … (from pituitary)
  • Adrenal gland principal hormone is …
  • … feedback of cortisol at both the pituitary and hypothalamic levels
A
  • Releasing factors are CRH, AVP to a lesser extent
  • Trophic hormone is ACTH
  • Adrenal gland principal hormone is cortisol
  • negative feedback of cortisol at both the pituitary and hypothalamic levels
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3
Q

What kind of circulation does the pituitary have?

A

portal capillary circulation

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4
Q
  • Label the image (Top left, top right, bottom left, bottom right)
  • What scan is it? What plane? … weighted
A
  • top left arrow = hypothalamus
  • top right arrow = pituitary stalk
  • bottom left arrow = optic chiasm
  • bottom right arrow = pituitary gland with small adenoma (lower intensity)
  • MRI scan, coronal plane, T1 weighted
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5
Q

The adrenal cortex produces 3 different types of hormones, which are:

  1. … e.g …
  2. … e.g …
  3. … e.g …
A
  1. Glucocorticoid e.g cortisol
  2. Mineralocorticoid e.g aldosterone (regulated by renin-angiotensin-aldosterone system)
  3. Sex steroids e.g androgens
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6
Q

In the blood, 90% of cortisol is bound to cortisol binding … (CBG)

A
  • 90% is bound to cortisol binding globulin (CBG)
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7
Q

Receptors - hypothalamic-pituitary-adrenal axis

  • intracellular … and …. receptors
A
  • intracellular glucocorticoid and mineralocorticoid receptors (GR & MR)
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8
Q

Enzymes - hypothalamic-pituitary-adrenal axis

  • 11-B-hydroxy… de… (11-B-HSD)
A
  • 11-B-hydroxysteroid dehydrogenase (11-B-HSD)
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9
Q

What is shown in the image?

A

Structure of steroid hormones

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10
Q

Effects of glucocorticoids

  • maintenance of … during times of … (give examples)
  • anti-…
  • energy balance / … (increase/maintain normal …)
  • formation of … and …
  • regulation of … …
  • cognitive …, …, conditioning
A
  • maintenance of homeostasis during times of stress (give examples)
  • anti-inflammatory
  • energy balance / metabolism (increase/maintain normal glucose)
  • formation of bone and cartilage
  • regulation of blood pressure
  • cognitive function, memory, conditioning
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11
Q

Circadian rhythms

Cortisol levels:

  • rise during the …
  • peak prior to …
  • fall during …
  • low in the …
A
  • rise during the early morning
  • peak prior to awakening
  • fall during day
  • low in the evening
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12
Q

Ultradian rhythm

‘…’ of hormone release

A
  • pulsatility of hormone release
  • only when you average these do you get the circadian rhythm
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13
Q

Ultradian rhythm - rats

  • sponatenous … of varying amplitude
  • amplitude decreases in the … trough
A
  • sponatenous pulses of varying amplitude
  • amplitude decreases in the circadian trough
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14
Q

Ultradian rhythm - humans

  • Hard to distinguish the … response
A
  • Hard to distinguish the stress response
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15
Q

What is shown in the image?

A
  • Renin-angiotensin-aldosterone system
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16
Q

Circulating Androgens

  • include … and Andro… produced by the adrenal glands in both men and women
A
  • DHEAS & Androstenedione
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17
Q
  • Cortisol crosses the cell membrane and links to the … receptor
  • translocates into the … and binds there with …
  • causes gene …
A
  • Cortisol crosses the cell membrane and links to the glucocorticoid receptor
  • translocates into the nucleus and binds there with coactivators
  • causes gene transcription
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18
Q

Enzymes - hypothalamic-pituitary-axis

  • In vitro, the ‘…corticoid receptor’ has the same affinity for … and aldosterone
  • … is conferred by a ‘pre-receptor’ mechanism
  • 11-B-HSD-2 in the kidney inactivates …, enabling aldosterone to bind the … receptor
A
  • In vitro, the ‘mineralocorticoid receptor’ has the same affinity for cortisol and aldosterone
  • Specificity is conferred by a ‘pre-receptor’ mechanism
  • 11-B-HSD-2 in the kidney inactivates cortisol, enabling aldosterone to bind the MR
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19
Q

11-B-HSD enzymes

  • tissue specificity - in kidney…
  • ‘….’ of GC access to nuclear receptors
  • in liver…
  • ‘….’ of GC signal in target cells
A
  • ‘gating’ of GC access to nuclear receptors - kidney - allows aldosterone to bind
  • ‘amplification’ of GC signal in target cells - liver
20
Q

Too much cortisol

  • … syndrome
    • leading to weight …
    • central …
    • …tension
    • insulin ….
    • neuropsychiatric …
    • osteo…
A
  • Cushing’s syndrome
    • leading to weight gain
    • central obesity
    • hypertension
    • insulin resistance
    • neuropsychiatric problems
    • osteoporosis
21
Q

What syndrome is present?

A
  • Cushing’s syndrome
22
Q

Cushing’s syndrome - pathogenesis

  • excess …
    • pituitary … is commonest cause (has …-secreting cells)
    • Adrenal …: adenoma or carcinoma
    • ‘ectopic ACTH’: carcinoid, paraneoplastic - rare
    • Iatrogenic: steroid treatment - may become (‘…’)
A
  • excess cortisol
    • pituitary adenomais commonest cause (hasACTH-secreting cells)
    • Adrenal tumour: adenoma or carcinoma
    • ‘ectopic ACTH’: carcinoid, paraneoplastic - rare
    • Iatrogenic: steroid treatment - may become (‘Cushingoid’)
23
Q

Cushing’s syndrome - Clinical features

  • central obesity with thin … and …
  • fat deposition over upper … known as a buffalo …
  • rounded ‘moon’ …
  • thin … with easy …, pigmented striae
  • hirsutism
    • as previously mentioned…
  • hypertension
  • diabetes
  • psychiatric manifestations
  • osteroporosis
A
  • central obesity with thin arms and legs
  • fat deposition over upper back (buffalo hump)
  • rounded ‘moon’ face
  • thin skin with easy bruising, pigmented striae
  • hirsutism
  • hypertension
  • diabetes
  • psychiatric manifestations
  • osteroporosis
24
Q

What syndrome is present?

what clinical features?

A
  • cushing’s syndrome (Adrenal carcinoma)
  • top left - buffalo hump
  • top right - thin arms, brusing
  • bottom left - striae on tummy
  • bottom right - retaining salt and water - pitting oedema - rounded moon face
25
Q

Too little cortisol: Addison’s disease

The patient:

  • Gradually falls off in general …
  • becomes languid and …
  • indisposed to either bodily or mental …
  • body …
  • slight pain is referred to …
  • occasionally actual …
  • … of skin
  • (at length gradually sinks and expires) - in those days
A
  • Gradually falls off in general health
  • becomes languid and weak
  • indisposed to either bodily or mental exertion
  • body wastes
  • slight pain is referred to stomach
  • occasionally actual vomiting
  • discolaration of skin
  • at length gradually sinks and expires
26
Q

Pathogenesis of Addison’s disease

  • Primary … insuffiency
    • usually … in the UK
    • Rare causes include … or …
    • decreased production of all … hormones
  • Other causes of hypoadrenalism
    • … to pituitary disease (Rare)
    • … - patients on high dose, long term steroid, which is suddenly stopped at a time of stress
A
  • Primary adrenal insuffiency
    • usually autoimmune in the UK
    • Rare causes include TB or metastases
    • decreased production of all adrenocortical hormones
  • Other causes of hypoadrenalism
    • secondary to pituitary disease (Rare)
    • Iatrogenic - patients on high dose, long term steroid, which is suddenly stopped at a time of stress
27
Q

Addison’s disease - Clinical features

  • malaise, …, anorexia, weight …
  • increased skin … - in areas such as …, palmar …, around/inside the …, … areas, also …
  • …/postural …
  • …glycaemia
A
  • malaise, weakness, anorexia, weight loss
  • increased skin pigmentation - knuckles, palmar creases, around/inside the mouth, pressure areas, scars
  • hypotension/postural hypotension
  • hypoglycaemia
28
Q

Autoimmune polyendocrine syndromes: Type I vs Type II

  • Type 1
    • common or rare?
    • onset is in …
    • single gene disorder?
    • Common phenotypes (3) are: …, …, …
  • Type 2
    • common or rare?
    • onset is in …
    • single gene disorder?
    • Common phenotypes (cluster of) are: …, …, …
A
  • Type 1
    • rare
    • onset is in infancy
    • Ar (AIRE gene) - single gene
    • Common phenotypes: Addison’s, hypoparathyroidism, candidiasis
  • Type 2
    • commoner
    • infancy to adulthood
    • polygenic - not single gene
    • Common phenotype: Addison’s, T1 diabetes, autoimmune thyroid disease
29
Q

Autoimmune conditions that may occur together include:

  • Type . ….
  • autoimmune … disease (hypo or hyper)
    • also gestational / post-partum …
  • … disease
  • … disease
  • … anaemia
  • Alo…
  • Vitiligo
  • Hepatitis
  • Premature … failure
  • … gravis
A
  • Type 1 diabetes
  • Autoimmune thyroid disease (hypo or hyper)
    • also gestational / post-partum thyroiditis
  • Coeliac disease
  • Addison’s disease
  • Pernicious anaemia
  • Alopecia
  • Vitiligo
  • Hepatitis
  • Premature ovarian failure
  • Myasthenia gravis
30
Q

Clinical implications of autoimmune polyendocrine syndromes:

  • … index of suspicion for additional autoimmune endocrine disorders
    • T1 Diabetes with fatigue, weight loss and hypoglycaemia - screen for … disease
    • T1 diabetes with non-specific GI symptoms/diarrhoea - screen for … disease
  • Consider screening in patients with T1 DM and/or Addison’s disease
    • … screen
    • … function tests (especially in pregancy/post-partum)
A
  • high index of suspicion for additional autoimmune endocrine disorders
    • T1 Diabetes with fatigue, weight loss and hypoglycaemia - screen for addison’s disease
    • T1 diabetes with non-specific GI symptoms/diarrhoea - screen for coeliac disease
  • Consider screening in patients with T1 DM and/or Addison’s disease
    • Coeliac screen
    • Thyroid function tests (especially in pregancy/post-partum)
31
Q

Assessment of the hypothalamic-pituitary-adrenal axis

  • Basal tests
    • … (cortisol, ACTH)
    • … (cortisol)
    • … (cortisol)
  • Dynamic tests (… or …)
A
  • Basal tests
    • blood (cortisol, ACTH)
    • urine (cortisol)
    • saliva (cortisol)
  • Dynamic tests (stimulated or suppressed)
32
Q

Assessment of the hypothalamic-pituitary-adrenal axis

  • Basal tests
    • blood (cortisol, ACTH) - important to remember … rhythm and … rhythm, also … response
    • urine (cortisol) - area under curve by using a … collection
    • saliva (cortisol) - … is important - but no stress - proportionate
  • Dynamic tests
    • stimulated - e.g. …, … or stress using … to make them …
    • suppressed - … - a synthetic glucocorticoid
A
  • Basal tests
    • blood (cortisol, ACTH) - important to remember circadian rhythm and ultradianrhythm, alsostress response
    • urine (cortisol) - area under curve by using a 24 hour collection
    • saliva (cortisol) - timing is important - but no stress - proportionate
  • Dynamic tests
    • stimulated - e.g. ACTH,CRH, or stress using insulin to make them hypoglycaemic
    • suppressed - dexamethasone - a synthetic glucocorticoid
33
Q

What is shown here?

A

Assessment of the hypothalamic-pituitary-adrenal axis

34
Q

Too much cortisol? - tests would include:

  • 24 hour urinary free cortisol - measure the …
  • midnight cortisol (blood/saliva) - shows a ‘…’
  • 9 am … (with paired cortisol) - pituitary/adrenal/ectopic? - negative feedback at pituitary
  • … suppression - assessing sensitivity to GC … feedback at pituitary
A
  • 24 hour urinary free cortisol - measure the area under curve
  • midnight cortisol (blood/saliva) - trough
  • 9 am ACTH (with paired cortisol) - pituitary/adrenal/ectopic? - negative feedback at pituitary
  • dexamethasone suppression - sensitivity to GC negative feedback at pituitary (normally would get complete suppression of cortisol production with dexamethasone, not in patient with cushing’s syndrome)
35
Q

Dexamethasone suppression

  • sensitivity to GC negative feedback at pituitary
  • what would you expect in healthy individual?
A
  • normally would get complete suppression of cortisol production with dexamethasone, but not in a patient with cushing’s syndrome
36
Q
  • Pituitary cause of Cushing’s syndrome - expect ACTH to be … and cortisol to be …
  • Adrenal cause of Cushing’s syndrome - expect ACTH to be … and cortisol to be …
  • Ectopic cause of Cushing’s syndrome (lung cancer or carcinoma making ACTH) - expect ACTH to be … and cortisol to be …
A
  • Pituitary cause of Cushing’s syndrome - expect ACTH to be high and cortisol to be high
  • Adrenal cause of Cushing’s syndrome - expect ACTH to be low and cortisol to be high
  • Ectopic cause of Cushing’s syndrome - expect ACTH to be high and cortisol to be high
37
Q
A
38
Q

Too little cortisol? - tests would include:

  • 9 am cortisol - looking for a …
  • SynACTHen test - … response to ACTH - trophic effect on ACTH on adrenals
  • … tolerance test to measure the response to … stress - but this can be dangerous
  • U & E (… sodium, … potassium in Addison’s disease)
    • this is due to a … deficiency
    • can measure … (expecing to be high) & … (expecting to be low) concentrations - due to negative feedback
  • decreased … levels
A
  • 9 am cortisol - looking for a peak
  • SynACTHen test - adrenal response to ACTH - trophic effect on ACTH on adrenals
  • Insulin tolerance test to measure the response to hypoglycaemic stress - but this can be dangerous
  • U & E (decreased sodium, increased potassium in Addison’s disease)
    • this is due to a mineralocorticoid deficiency
    • can measure renin & aldosterone concentrations
  • decreased glucose levels
39
Q

Two golden rules - clinical aspects of hypothalamic-pituitary-adrenal axis

  1. Never start investigating a patient for an endocrine condition unless their symptoms and signs suggest they have it due to …
  2. Never image any endocrine gland until you have established the diagnosis biochemically! - risk of …
A
  1. Never start investigating a patient for an endocrine condition unless their symptoms and signs suggest they have it - due to risk of false positive results
  2. Never image any endocrine gland until you have established the diagnosis biochemically! - risk of discovering‘incidentalomas’
40
Q

Imaging - for Cushing’s syndrome/Addison’s disease

  • Once you have confirmed a patient has Cushing’s syndrome, consider … (3 things)
  • Patients with Addison’s disease - do they need imaging? When may they need it?
A
  • Once you have confirmed a patient has Cushing’s syndrome, consider 1) CXR 2) MRI pituitary 3) CT adrenals
  • Patients with Addison’s disease - do they need imaging? When may they need it?
    • Usuaully rare - unless concerned that they may have TB or metastatic cancer
41
Q

Management of Cushing’s syndrome

  • largely …
    • adrenal cause = …
    • pituitary cause = … ….
  • pituitary … as may be hard to cure surgically
A
  • largely …
    • adrenal cause = adrenalectomy
    • pituitary cause = transphenoidal adenectomy
  • pituitary radiotherapy - may be hard to cure with surgery alone
42
Q

Management of Addison’s disease

  • … hormone replacement therapy (glucocorticoid) - usually this is …, but occassionally use …
  • Patients with … adrenal insufficiency also need mineralcorticoid replacement therapy (…)
  • patients with … adrenal insuffiency will often be taking other hormone replacement therapy so do not need this
A
  • Steroid hormone replacement therapy (glucocorticoid) - usually this is hydrocortisone, but occassionally use prednisolone
  • Patients with primary adrenal insufficiency also need mineralcorticoid replacement therapy (fludrocortisone)
  • patients with secondary adrenal insuffiency will often be taking other hormone replacement therapy so do not need this
43
Q

Managing treatment of Addison’s disease in certain circumstances

  • dose of glucocorticoids needs to be increased to cover ‘….’ such as intercurrent …
  • …/…-… period - recommendations depend on the procedure
  • Patients will require IV/IM … if unable to take tablets due to … or ‘… .. …’
A
  • dose of glucocorticoids needs to be increased to cover ‘stresses’ such as intercurrent illness (like the flu)
  • operations/post-op period - recommendations depend on the procedure
  • Patients will require IV/IM steroids if unable to take tablets due to vomiting or ‘nil by mouth’
44
Q

Patients taking steroids for other reasons:

  • patients may be treated with long-term high dose steroids for many reasons (glucocorticoids - usually …)
  • usually the steroids are being used for what effects?
  • Conditions include severe …/COPD, temporal … / polymyalgia … - these patients may look ‘…’ especially those with COPD
A
  • patients may be treated with long-term high dose steroids for many reasons (glucocorticoids - usually prednisolone)
  • usually the steroids are being used for what effects? - Anti-inflammatory
  • Conditions include severe asthma/COPD, temporal arteritis/ polymyalgia rheumatica - these patients may look ‘Cushingoid’ especially those with COPD
45
Q

Patients taking steroids

  • the endogenous … function of patients on long-term high dose steroid therapy may be suppressed:
    • they may not mount an adequate ‘…’ response
    • their steroid treatment should not be stopped …
    • if they need a major …, they require increased steroid cover as described
    • they should be given a ‘steroid … card’ to remind them (& their doctors) about this
A
  • the endogenous adrenal function of patients on long-term high dose steroid therapy may be suppressed:
    • they may not mount an adequate ‘stress’ response
    • their steroid treatment should not be stopped suddenly
    • if they need a major procedure/an operation, they require increased steroid cover as described
    • they should be given a ‘steroid treatment card’ to remind them (& their doctors) about this

Year 2 Medicine (162 decks)

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