6 - ENDOCRINE DISORDERS: THE ADRENAL GLAND Flashcards
CRH
Corticotropin Releasing Hormone
ACTH
AdrenoCortico Tropic Hormone
Adrenal cortex layers
- zona glomerulosa
- zona fasciculata
- zona reticularis
zona glomerulosa
secreting aldosterone, control of renin from kidney.
Na rabsorption.
Production of mineralcorticoids
zona fasciculata
glucocorticoid secretion - cortisol
zona reticularis
secretion of sex hormones - androgen.
Precursor for testosterone and oestrogen.
Produces DHEA (precursor to androgens)
adrenal cortex
all hormones synthesised from cholesterol.
Has lots of LDL receptors to combine cholesterol and can act as store to synthesise hormones rapidly.
ALDOSTERONE
- Regulates Na and K homeostasis
- Secreted in response to low blood pressure/volume
- Promotes Na reabsorption and K+ excretion in the kidney
Cortisol
- Raises blood glucose
- Increases lipid and protein breakdown
- Resistance to stress
- Immune response depression
- Bound by cortisol binding protein in the blood
- Highest levels 8am, lowest midnight.
DHEA
produced from zona reticularis
- precursor to androgens, tested for adrenal gland function
ANDROGENS
made from Dehydroepiandrosterone (DHEA)
Converted to testosterone in circulation, converted to oestrogen in ovaries if female
Secondary sexual characteristics
Prepubertal growth spurt
THE ADRENAL MEDULLA
• Produces adrenaline, noradrenaline (CATECHOLAMINES) from chromaffin cells in response to nervous stimulation.
• Fight/flight response
Not under control of ACTH from anterior pituitary.
Catecholamines (epinephrine and norepinephrine)
Line blood vessels, increase heart rate, force and pressure, increase glucose levels.
COMT (catechol-o-methyltransferase)
enzyme that breaks down catecholamines and Metabolises into metanephrine and normethanephrine.
- broken down products seen in urine
- assess quantity of adrenaline
- cannot measure adrenaline as broken down too quick
Assess Adrenal function
Competitive ELISA - cortisol, aldosterone, DHEA, metanephrine
OR
2-site ELISA - plasma ACTH
Competitive ELISA (cortisol, aldosterone, DHEA, metanephrine)
- Antibody attached to well (specific for hormone X)
- Patient’s serum added PLUS HRP labelled hormone X
- TMB subsrate added
- Yellow Colour development
- This e.g. = low patient hormone X as few binding sites filled, high colour absorbance
2-site ELISA
Measure plasma ACTH
- Antibody to ACTH in well.
- Serum added.
- C-terminal of ACTH binds to antibody in well.
- Antibody added to bind to N-terminal, linked to HRP enzyme.
- TMB substrate added, yellow colour change.
- High absorbance = more colour change. Directly proportional.
Dexamethasone (glucocorticoid) suppression test
Looks like cortisol to body. Tests if cortisol production is regulated by negative feedback.
- dexamethasone inhibits ACTH release in healthy people, -ve feedback.
- If no decrease in cortisol, ACTH and CRH is still being released.
Pituitary tumour or ectopic ACTH source. Produced from tumour instead of anterior pituitary.
Stress hormone pathway
Corticotropin-releasing hormone (hypothalamus),
Adrenocorticotropic hormone (ACTH) (anterior pituitary),
cortisol (adrenal gland).
Synacthen test
Tests if adrenal gland responds to ACTH.
- give patient IV synacthen, looks like ACTH
- should stimulate cortisol production in adrenal gland.
- measure cortisol, if no rise then suspect adrenal insufficiency.
Adrenal cortical insufficiency
not producing enough hormones, aldosterone.
Addison’s disease
destruction of both adrenal glands by autoimmune disease or infection.
Adrenal cortical insufficiency symptoms
muscle weakness, tiredness, skin pigmentation, vomiting, sweating, hypotension, low blood Na.
High K causes cardia arythmias.
High ACTH to increase cortisol levels.
Precursor to ACTH causes pigmented skin.
DIAGNOSTIC FINDINGS OF ADRENAL CORTICAL INSUFFICIENCY
Plasma ACTH higher than normal range Plasma cortisol less than normal range Synacthen test (ACTH analogue) – little, if any, increase in cortisol
If aldosterone production is decreased too:
Hyponatraemia (serum sodium low)
Hyperkalaemia (serum potassium high)
Uraemia – high levels of urea in blood (dehydrated)
HYPERADRENALISM
excess cortical hormone secretione.g. Cushing’s syndrome
Hyperadrenalism (Cushing’s syndrome) symptoms
muscle weakness, hypertension (cortisol stimulates mineralcorticoid leading to aldosterone effects), hirsutism (unwanted hair), central obesity, osteoporosis.
Conn’s Syndrome (hyperaldosteronism)
Aldosterone in response to low blood pressure, cause water retention by reabsorption of Na.
symptoms:
- Hypertension
- Hypokalemia
- metabolic alkalosis
- decreased renin secretion
SOME CAUSES OF HYPERADRENALISM
- Adrenal cortical hyperplasia
- Adrenal cortical adenoma
- Adrenal cortical carcinoma
Adrenal cortical hyperplasia
Increase in cell number
Increased ACTH stimulation, maybe tumour in pituitary gland.
Diagnosis = dexamethasone suppression test shows raised cortisol with no negative feedback
Adrenal cortical adenoma
• May secrete excess cortisol (Cushing’s) or aldosterone (Conn’s) • Yellow cut surface- stored cholesterol • Diagnosis: ACTH not detectable • If cortisol-secreting: - Cortisol increase • If aldosterone-secreting - Plasma aldosterone high - Serum Na high - Serum K low - Urine K high
Adrenal cortical carcinoma
• Yellow/white tumour • Often secrete cortisol - Cushing’s • Often secrete androgens - hirsutism • Diagnosis: - Cortisol increase - DHEA increase
PHEOCHROMOCYTOMA – ADRENAL MEDULLA TUMOUR
• Symptoms: sweating, headaches, palpitations, hypertension…
• Diagnosis:
- Increase in adrenaline/noradrenaline breakdown products (metanephrine and normetanephrine)
