Adrenocortical function and dysfunction Flashcards
What constitutes the adrenal glands?
Adrenal cortex and medulla - 2 endocrine glands of different embryological origin that fused during development.
What is the adrenal medulla?
A modified sympathetic ganglion the secretes catecholamines - neurohormones.
What is the adrenal cortex?
A true endocrine gland; secretes steroids - classical hormones.
What are the 3 different layers to the adrenal cortex?
Zona glomerulosa, fasciculata and reticularis.
What do each of the different zones of the adrenal cortex secrete?
- Glomerulosa: aldosterone
- Fasciculata: glucocorticoids
- Reticularis: sex hormones
Where are sex hormones secreted from?
Zona reticularis and fasciculata
Which sex hormones are secreted from the adrenal cortex?
Androgens, estrogens, dehydroepiandosterone (DHEA)
Where are glucocorticoids secreted from?
Zona fasciculata and reticularis
Which glucocorticoids are secreted from the adrenal cortex?
Cortisol, stimulated by: HPAA, ACTH tropic to ZF&ZR
Where are the mineralocorticoids secreted from the adrenal cortex?
Glomerulosa only
Which mineralocorticoids are secreted from the adrenal cortex?
Aldosterone
What is aldosterone secreted stimulated by?
RAAS & plasma K+
Why do cells produce different steroids?
Because they have different enzymes
What is the precursor to corticosteroid?
Progesterone
What is the precursor to oestradiol?
Testosterone and estrone
Why can steroids have crossover effects?
Because different steroids are chemically related
What is the HPA pathway for the control of cortisol secretion?
CRH from hypothalamus stimulates anterior pituitary to release ACTH which stimulates adrenal cortex to release cortisol.
What stimulates the hypothalamus to release CRH?
Circadian rhythm and stress
Where does cortisol act? What does it do at these sites?
- Immune system (suppression)
- Liver (gluconeogenesis)
- Muscle (protein catabolism)
- Adipose tissue (lipolysis).
How is cortisol release inhibited?
By cortisol negatively feeding back to anterior pituitary and hypothalamus.
What is CRH?
Corticotropin releasing hormone
What is ACTH?
Adrenocorticotropic hormone
What does CRH mediate other than release of ACTH?
- Effects on inflammation and immune responses
- Inhibition of appetite
- Signals the onset of labour
- Appears linked to several mood disorders
- Urocortin: brain neuropeptide ↓ appetite
What is POMC?
Pro‐opiomelanocortin: a large protein that yields several bioactive peptides by proteolysis
What are some of the peptides produced by proteolysis of POMC?
- ACTH and beta‐endorphin in the anterior pituitary
- Alpha-MSH outside the pituitary
What is beta-endorphin?
Pain perception blocker
What is alpha-MSH?
Melanocyte‐stimulating hormone: ↓ food intake & ↑ skin melanin
What are the melanocortins?
- Family name for the MSH hormones and ACTH
- The effects of the peptides depend on which melanocortin receptor subtypes are stimulated
What does cortisol help the body cope with?
Long-term stress
How does cortisol protect against hypoglycaemia?
By stimulating catabolism of energy stores
What is cortisol permissive for?
For glucagon & catecholamine actions
When are the peaks and troughs of the diurnal rhythm?
- Peaks morning
- Low night
What does cortisol promote in the liver?
Gluconeogenesis
What does cortisol cause in the muscle?
Breakdown of skeletal muscle proteins - substrate for gluconeogenesis.
What effect does cortisol have on adipose tissue?
Enhances lipolysis – FA for energy
What effect does cortisol have on the immune system?
Suppresses the immune system
What effect does cortisol have on calcium?
- Causes negative calcium balance
- ↓absorption, ↑excretion, bone breakdown
What effect does cortisol have on the brain?
Influences brain function –mood, memory, learning
What are the effects of cortisol being used as a therapeutic drug?
- Suppresses the immune system
- Inhibits the inflammatory response
- Some specific uses
- Bee stings, poison ivy, and pollen allergies
- Prevents rejection of transplanted organs
What does long-term use of cortisol result in?
Inhibition of ACTH secretion and atrophy of cortisol‐secreting cells - taper doses gradually.
Is cholesterol made on demand or stored?
Made on demand.
What is the half-life of cortisol?
60-90 minutes
What factors affect the release of cortisol?
Circadian rhythm of tonic secretion; stress enhances release
Where is the receptor for cortisol located?
Intracellularly
What is the action of cortisol at the molecular level?
Initiates transcription, translation and new protein synthesis.
What are the 3 major adrenal cortex disorders resulting from hypersecretion?
- Hyperaldosteronism
- Excess Cortisol (Cushing’s syndrome)
- Excess Androgen & Estrogen (adrenogenital syndrome)
What are the 2 types of hyperaldosteronism?
- Primary hyperaldosteronism (Conn’s syndrome)
- Secondary hyperaldosteronism (RAS)
What do the 2 types of hyperaldosteronism cause?
Cause hypernatremia, hypokalaemia, hypertension
What are the different causes of excess cortisol (Cushing’s syndrome)?
- Primary adrenal cortex tumors that autonomously secretes cortisol
- Secondary pituitary tumor that autonomously secretes ACTH (Cushing’s disease)
- Hyperstimulation (CRH, ACTH)
- Iatrogenic (physcian caused) hypercortisolism – treat with cortisol therapy
What does excess cortisol (Cushing’s syndrome) cause?
Glucose excess, protein shortage, abnormal fat distribution
What causes excess Androgen & Estrogen (adrenogenital syndrome)?
- Lack enzyme in cortisol steroidogenic pathway
- Inappropriate masculinisation in all but adult males
How is excess Androgen & Estrogen (adrenogenital syndrome) treated?
With glucorticoids - repairs glucorticoid deficit and inhibits ACTH (reducing steroid secretion)
What are the signs and symptoms of Cushing’s syndrome (hypercortisolism)?
- Excess gluconeogenesis causes hyperglycemia; mimics diabetes
- Muscle protein breakdown, lipolysis causes wasting
- Paradoxical fat deposits in trunk & face due to ↑appetite
- Thin arms & legs, trunk obesity, “moon face”
- Stretched skin due to fat depots causes reddish purple striae
- Mineralocortocoid action of excess glucocorticoid
- Salt & water retention, “moon face”, weakness, hypertension
- Osteoporosis
- Mood elevation then depression, difficult learning & memory
What is the primary pathology that can lead to hypercortisolism (Cushing’s syndrome)?
Primary secretion due to problem with adrenal cortex: CRH and ACTH low (due to cortisol inhibitory feedback) Cortisol levels high.
What are the secondary pathologies that can lead to hypercortisolism (Cushing’s syndrome)?
- Secondary secretion due to hypothalamic or pituitary problem.
- Hypothalamic: high CRH, ACTH and cortisol.
- Pituitary: low CRH, high ACTH and cortisol.
What is cortisol hyposecretion due to?
Adrenocortical insufficiency
What is Addison’s disease?
Primary adrenal insufficiency - autoimmune destruction of adrenal cortex.
What happens in Addison’s disease?
- Autoimmune destruction of adrenal cortex
- Hyposecretion of all adrenal steroid hormones
- ↓Aldosterone
- K+ retention → Cardiac arrhythmias
- Na+ depletion → hypotension
- ↓Cortisol
- ↓stress response & hypoglycaemia
What hereditary problems can cause cortisol hyposecretion?
Adrenal steroid enzyme defects - lack of cortisol & aldosterone causes ↑ androgens & adrenogenital syndrome
What happens in secondary cortisol hyposecretion?
- Deficient cortisol only:
- Abnormal hypothalamus or pituitary
- ↓ACTH & ↓cortisol only (normal aldosterone)
What is the embryological origin of the adrenal medulla?
Modified part of SNS
What happens in the adrenal medulla?
Modified postganglionic sympathetic neurons (chromaffin cells) secrete neurohormones (catecholamines).
What are the 3 catecholamines?
- Adrenaline (only made in adrenal medulla)
- Noradrenaline
- Dopamine
What are secretions from the adrenal medulla stimulated by?
Preganglionic sympathetic neurons.
What is the precursor to dopamine?
DOPA
What converts tyrosine to DOPA?
Tyrosine hydroxylase
What converts DOPA to dopamine?
Amino acid decarboxylase
What converts dopamine to noradrenaline?
Dopamine-beta-hydroxylase
What converts noradrenaline into adrenaline?
PNMT
Where is PNMT found outside of the CNS?
In the adrenal medulla
What are the adrenomedullary hormone actions on flight-or-fight responses?
↑cardiac rate and contractility, ↑TPR, ↑BP
What are the adrenomedullary hormone actions on metabolic effects?
↑glucose & FFA, ↑BMR
What are the adrenomedullary hormone actions on central effects?
↑arousal & alertness
What are the adrenomedullary hormone actions on stress responses?
- Physical
- Psychological
Have there been any recognised hyposecretion disorders of the adrenal medulla?
No
What is adrenomedullary hypersecretion disorder?
- Pheochromocytomas (tumor)
- Rare
- Potentially deadly (hypertension)
- Treatment: removal
What role does stress play in cortisol secretion?
- Nonspecific stimuli (“stressors”) disrupt homeostasis
- Two types of stress elicit two responses
- Acute stress results in the fight‐or‐flight reaction
- Chronic stress elevates cortisol levels, which suppresses immune responses
What is the MoA of stress on the hypothalamus?
See image.
