Hypothalamic-Pituitary-Adrenal Axis Flashcards by David Houghton

What are the 3 main components that make up the Hypothalamic-pituitary-adrenal axis?

1 - hypothalamus
2 - pituitary gland
3 - adrenal gland

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The 3 main components that make up the Hypothalamic-pituitary-adrenal (HPA) axis are the hypothalamus, pituitary gland and adrenal gland. What does the hypothalamus secrete to stimulate the pituitary gland?

corticotrophin releasing hormone

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The 3 main components that make up the Hypothalamic-pituitary-adrenal (HPA) axis are the hypothalamus, pituitary gland and adrenal gland. What does the pituitary gland secrete to stimulate the adrenal gland?

adrenocorticotropic hormone

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The 3 main components that make up the Hypothalamic-pituitary-adrenal (HPA) axis are the hypothalamus, pituitary gland and adrenal gland. The anterior pituitary gland secretes adrenocorticotropic hormone to stimulate the adrenal gland. What other hormone is secreted by the hypothalamus that can also stimulate the posterior pituitary gland into releasing adrenocorticotropic hormone and further stimulate the adrenal gland?

vasopressin, also called antidiuretic hormone

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The adrenal gland is made up of 2 key parts, what are these and which is larger?

1 - adrenal cortex = aprox 80-90%

2 - adrenal medulla = aprox 10-20%

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The adrenal gland is made up of 2 key parts, the adrenal cortex and medulla. The adrenal cortex can be further divided into 3 parts. Label the image below with the names provided:

zona glomerulosa
zona reticularis
zona fasciculata

1 = zona glomerulosa (outermost layer)
2 = zona fasciculata (middle layer) 
3 = zona reticularis (innermost layer)

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The adrenal gland is made up of 2 key parts, the adrenal cortex and medulla. Embryonically, where do the adrenal cortex and medulla originate from?

cortex = mesoderm

- medulla = neural crests

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What 2 key things does the medulla secrete?

catecholamines (adrenaline and noradrenaline)

- enkephalins (involved in pain inhibition)

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What are the key cells of the adrenal medulla that synthesis and secrete - catecholamines (adrenaline and noradrenaline) and enkephalins (involved in pain inhibition)?

chromaffin cells

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The cortex is stimulated by adrenocorticotropic hormone (released by the pituitary gland), stimulating what molecule that initiates the biosynthesis of the adrenal cortes secretions. What is this molecule?

cholesterol

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The cortex is stimulated by adrenocorticotropic hormone (released by the pituitary gland), stimulating cholesterol that initiates the biosynthesis of the adrenal cortes secretions. What are the 3 main secretions of the adrenal cortex?

1 - Glucocorticoids [e.g. cortisol]
2 - Mineralocorticoids [e.g. aldosterone]
3 - Adrenal androgens [e.g. dehydroepiandrosterone [DHEA] > converts to sex hormones].

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The image below shows how the adrenal gland is stimulated and and then the enzymes and reactions that take place to synthesise and secrete:

1 - Glucocorticoids [e.g. cortisol]
2 - Mineralocorticoids [e.g. aldosterone]
3 - Adrenal androgens [e.g. dehydroepiandrosterone [DHEA] > converts to sex hormones]

Why is it important to understand these pathways?

mutations/defects in any of these enzymes can lead to pathology

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There are 3 main hormones released by the adrenal gland, namely:

1 - Glucocorticoids [e.g. cortisol]
2 - Mineralocorticoids [e.g. aldosterone]
3 - Adrenal androgens [e.g. dehydroepiandrosterone [DHEA] > converts to sex hormones]

Which of these is key in the following:

Maintenance of homeostasis during stress (haemorrhage, infection, anxiety)
Anti-inflammatory
Energy balance / metabolism (increase and maintain glucose homeostasis)
Formation of bone and cartilage
Regulation of blood pressure
Cognitive function, memory, conditioning

glucocorticoids

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In a patient with a normal circadian rhythm with sleep/wake patterns, when would the peak and drop in cortisol be present?

peak = early morning 35-45 minutes after waking

- drop = evening

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In a patient with a normal circadian rhythm with sleep/wake patterns, cortisol peaks early morning 35-45 minutes after waking and drops in the evening. When assessing a patients adrenal function at baseline, what is an important question to ask the patient and taking into account?

profession

- shift patterns alter circadian rhythm

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What is the clinical term given to a patient with excessive cortisol levels?

cushings syndrome

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If a patient presents with elevated levels of cortisol, this is termed cushings syndrome and can be adrenocorticotropic hormone (ACTH) dependent and independent. In a patient with ACTH dependent cushings would we see raised or normal levels of ACTH?

raised levels

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If a patient presents elevated levels of cortisol, this is termed cushings syndrome and can be adrenocorticotropic hormone (ACTH) dependent and independent. In a patient with ACTH dependent cushings we would expect to see raised levels of ACTH. What are likely to be the 2 main causes of this?

1 - pituitary adenoma

2 - other cells outside of pituitary can create ACTH

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If a patient presents elevated levels of cortisol, this is termed cushings syndrome and can be adrenocorticotropic hormone (ACTH) dependent and independent. In a patient with ACTH independent cushings would we see raised or normal levels of ACTH?

low or normal levels of ACTH

- issue is not caused by pituitary gland

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If a patient presents with elevated levels of cortisol, this is termed cushings syndrome and can be adrenocorticotropic hormone (ACTH) dependent and independent. In a patient with ACTH independent cushings would we see normal or low levels of ACTH. What are the 2 main causes that may be causing this?

1 - adrenal tumour

2 - long standing steroid therapy

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If a patient presents elevated levels of cortisol, this is termed cushings syndrome and can be adrenocorticotropic hormone (ACTH) dependent and independent. Weight gain is a common clinical presentation, where does this weight tend to increase?

abdominal

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If a patient presents with elevated levels of cortisol, this is termed cushings syndrome and can be adrenocorticotropic hormone (ACTH) dependent and independent. Pigmentation can be a common symptom, but only when it is cushings syndrome that is dependent on ACTH. Why is this?

ACTH activates the pro-opiomelanocortin (POMC) pathway
ACTH binds to the melanocortin 1 receptor on the surface of dermal melanocytes

ALSO PRESENT IN BOTH PRIMARY AND SECONDARY ADRENAL INSUFFICIENCY

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When investigating a patient with suspected cushing syndrome, what would be the first 2 simple measures that can be done biochemically?

1 - midnight cortisol level measurement

2 - 24h urine cortisol measurement

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dexamethasone

- like cortisol and can lower the amount of ACTH released by the pituitary gland

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- Overnight Dexamethasone Suppression Test (ONDST) - Low Dose Dexamethasone Suppression Test (LDDST) - High Dose Dexamethasone Suppression Test (HDDST)

When investigating a patient with suspected cushing syndrome, the first 2 simple measures that can be done biochemically include cortisol measurement at midnight and then a 24h urine cortisol measurement. If these are inconclusive we can then do dynamic testing, which is where we can attempt to suppress cortisol using dexamethasone. There are 3 protocols that can be used here: - Overnight Dexamethasone Suppression Test (ONDST) - Low Dose Dexamethasone Suppression Test (LDDST) - High Dose Dexamethasone Suppression Test (HDDST) If a cortisol levels decrease in response to HDDST, what is this generally diagnostic of?

- cushings disease | - caused by pituitary tumour or ectopic ACTH release from another malignancy

- MRI

When performing adrenal imaging, a malignancy is concerning when there is what?

- when it is >6cm - heterogenous (calcification and haemorrhage within the tumour) - extending beyond the capsule (indicates cancer)

If a patient has cushing syndrome the treatment is dependent on the cause. If a patient has cushing syndrome that is independent of adrenocorticotrophin hormone (ACTH), due to steroids, what would the treatment option be?

- slowly reduce the steroid | - look for alternative treatment option

If a patient has cushing syndrome the treatment is dependent on the cause. If a patient has cushing syndrome that is independent of adrenocorticotrophin hormone (ACTH) or dependent to ACTH that is due to a tumour on the pituitary or adrenal gland, what would the treatment option be?

- transsphenoidal adenectomy (tumour removal from pituitary gland) - adrenalectomy (surgery to remove one or both adrenal glands) - radiotherapy

What is the major difference between primary and secondary adrenal insufficiency?

- primary = adrenal glands are damaged/affected | - secondary = likely to be pituitary gland or elsewhere damaged

What is Glucocorticoid Deficiency?

- adrenal glands do not produce certain hormones called glucocorticoids

Glucocorticoid Deficiency is where the adrenal glands do not produce certain hormones called glucocorticoids. What are the most common causes of primary and secondary adrenal insufficiency that cause low levels of glucocorticoids, called primary because it affects the adrenal glands directly?

- autoimmune (most common) - infiltrative (sarcoidosis) - infective (TB) - vascular - haemorrhage/infarction - adrenoleucodystrophy (membrane of adrenal glands is damaged) - congenital adrenal insufficiency - drugs - metastatic deposition

Glucocorticoid Deficiency is where the adrenal glands do not produce certain hormones called glucocorticoids. Primary adrenal insufficiency, called primary because it affects the adrenal glands means glucocorticoids are not secreted sufficiently. Is it only the glucocorticoid hormones that are affected?

- no - mineralocorticoids are also affected - important for treatment options

What is Addisons disease?

- chronic primary adrenal insufficiency

What is the prevalence of primary adrenal insufficiency in the UK?

- 8400

What is the most common age affected by primary adrenal insufficiency in the UK, and does this affect women or men more?

- 30-50 year olds | - women are more affected more

In primary adrenal insufficiency, what % of the adrenal cortex has to be affected/destroyed in order for symptoms to present?

- >90%

Glucocorticoid deficiency is where the adrenal glands do not produce certain hormones called glucocorticoids. Secondary adrenal insufficiency, called secondary because it does not affect the adrenal glands directly and may be from another source such as the pituitary gland or another malignancy. Are glucocorticoids the only thing that are affected?

- yes - ACTH released from pituitary is specific to glucocorticoids - mineralocorticoids are unaffected like in primary adrenal insufficiency

When investigating if a patient has glucocorticoid deficiency, what are some of the static basic biochemistry tests we need to consider?

- Cortisol measured at 9am (should peak around this time) - ACTH levels (low ACTH = pituitary source and high ACTH = adrenal source) - Na+ and K+ - pH - renin and aldosterone (mineralocortiocoid activity) - adrenal antibodies (autoimmune tests)

When investigating if a patient has glucocorticoid deficiency, what is the dynamic test that should be performed?

- patient administered tetracosactide (synthetic ACTH) - 250 nanograms administered intramuscularly at 9am - sample taken from patient at baseline, 30 and 60 minutes - normal response would be a rise in cortisol levels

When investigating if a patient has glucocorticoid deficiency, the dynamic test, detailed below, what must clinicians taken into account and control for? - patient administered tetracosactide (synthetic ACTH) - 250 nanograms administered intramuscularly at 9am - sample taken from patient at baseline, 30 and 60 minutes - normal response would be a rise in cortisol levels

- current steroid use

If a patient has gone undiagnosed or not presented with symptoms of adrenal insufficiency, they can present with adrenal crisis, which is a medical emergency of low cortisol levels. What are the 4 most common presentations of adrenal crisis?

1 - hypotension 2 - hypothermia 3 - bradykardia 4 - low Na+ and high K+

If a patient is has gone undiagnosed or not presented with symptoms of adrenal insufficiency can present with adrenal crisis, which is a medical emergency of low cortisol levels. What are the 4 initial treatment options?

- intravenous hydrocortisone - intravenous fluids - hypoglycaemia management - in primary adrenal insufficiency, mineralocorticoid and glucocorticoid are reduced. When glucocorticoid dose < 50mg/24 hr, fludrocortisone treatment should be started at 100mcg once daily)

If patients are diagnosed with adrenal insufficiency, what are the long term treatment options?

Steroid Replacement: - steroid to mimic circadian rhythm - mineralocorticoid (if affected, namely Fluorocortisone) - education (sick day rules)

What is a hydrocortisone emergency injection kit used for?

- when adrenal crisis, vomiting or dehydrated | - main component is 3 vials of hydrocortisone phosphate (100mg/ml)

During a stress response, the body generally releases cortisol. However, if the patient is ill or has adrenal insufficiency then this can lead to adrenal crisis, a medical emergency. Illness can affect the bodies response, so it is important to be aware of the sick day rules, which are essentially rules on what to do with medication relating to adrenal glands depending on the severity of the illness. What does sick day 1 rule encompass?

- moderate/intercurrent illness (still eat ok) - infections, local anaesthesia ect.. - patients should double their normal glucocorticoids dose for 3-4 days following illness

- severe intercurrent illness (patient unable to eat and drink) - persistent vomiting, general anaesthetic, traume etc.. - hydrocortisone injection given at 100mg intravenously - infusion of hydrocortisone or intramuscular

What is Autoimmune Polyglandular Syndrome?

- autoimmune = bodies attacks itself - poly = multiple - glandular = hormone secreting organs - so autoimmune disease affecting multiple hormone secreting organs

Autoimmune Polyglandular Syndrome is an autoimmune disease affecting multiple hormone secreting organs. Does this present rapidly?

- no - presents slowly affecting any age groups - can form with a combination of multiple disease

Autoimmune Polyglandular Syndrome (APS) is an autoimmune disease affecting multiple hormone secreting organs. What are a few of the most common autoimmune disease that occur alongside APS?

- type 1 diabetes - thyroid disease (hypo- or hyper-) - addison’s disease - pernicious anaemia - alopecia - hepatitis - premature ovarian failure - myasthenia gravis

Autoimmune Polyglandular Syndrome (APS) is an autoimmune disease affecting multiple hormone secreting organs. How many different types of APS are there?

- 4

Autoimmune Polyglandular Syndrome (APS) is an autoimmune disease affecting multiple hormone secreting organs. There are 4 different types of APS, type 1, 2, 3 and 4. What are the most common forms of type 1 APS?

- chronic candidiasis (fungal infection caused by yeast) - chronic hypoparathyroidism (low parathyroid hormone secretion) - Addison's disease (at least two present)

- Addison's disease (always present) - thyroid autoimmune diseases - Type 1 diabetes mellitus

- thyroid autoimmune diseases associated with other autoimmune diseases - excluding Addison's disease and/or hypoparathyroidism)

- combination of organ‐specific autoimmune diseases not included in the previous groups

Autoimmune Polyglandular Syndrome (APS) is an autoimmune disease affecting multiple hormone secreting organs. In patients with type 1 diabetes, what important measures must be taken?

- 9am cortisol levels - weight (especially loss) - blood glucose - fatigue

Autoimmune Polyglandular Syndrome (APS) is an autoimmune disease affecting multiple hormone secreting organs. In all patients with type 1 diabetes who have GIT symptoms, what must they be screened for?

- coeliac disease

Autoimmune Polyglandular Syndrome (APS) is an autoimmune disease affecting multiple hormone secreting organs. In all patients with type 1 diabetes and/or Addisons disease must be regularly tested for what 2 things?

1 - thyroid tests | 2 - coeliac screening

When performing an endocrine history and examination, what are the main things we are looking for in appearance?

- skin - hair - weight change and distribution

When performing an endocrine history and examination, what are the 3 main things we are looking for in someones mental and physiological state?

- fatigue and lethargy - anxiety and depression - mood and affect - appetite

When performing an endocrine history and examination, what is one topic that may be uncomfortable to bring up but needs to be addressed?

- sexual activity - menstrual cycles - breast examination in males and females

Hypothalamic-Pituitary-Adrenal Axis Flashcards

(62 cards)