70 - Adrenocortical Function and Dysfunction Flashcards
Relationship between adrenal cortex and medulla
Two endocrine glands of different embryological origin that fuse during development
Basic aspects of adrenal medulla
Modified sympathetic ganglion, secretes catecholamines (neurohormones)
Basic aspects of adrenal cortex
True endocrine gland. Secretes steroids (classical hormones)
Regions of adrenal cortex
1
2
3
Zona reticularis (sex hormones) Zona fasciculata (glucocorticoids) Zona glormerulosa (aldosterone)
Hormones produced by zona reticularis
Sex hormones (ndrogens, oestrogens, dehydroepiangeosterone)
Hormones produced by zona fasciculata
Glucocorticoids (cortisol)
Zones of adrenal cortex that produce hormones together
Zona reticularis and fasciculata (reticularis makes more sex hormones, fasciculata makes more glucocotricoids)
Hormones produced exclusively be zona glomerulosa
Mineralocorticoids (aldosterone)
Progenitor for aldosterone, cortisol and sex hormones
Progesterone
Active form of testosterone
Dihydro-testosterone
Two pathways to sex hormone formation
Can derive from progesterone or DHEA (dehydroepiangeosterone)
How are different steroids derived from cholesterol in the adrenal cortex?
Cells produce different steroids because they contain different enzymes
Pathway for control of cortisol secretion 1 2 3 4
1) Hypothalamus releases corticotrophin releasing hormone into portal system.
2) Anterior pituitary releases adrenocorticotrophic hormone
3) Adrenal cortex releases cortisol.
4) Cortisol negatively feeds back on ACTH and CRH release (long loop negative feedback)
Roles of cortisol 1 2 3 4 5 6 7
1) Promotes gluconeogenesis in liver
2) Causes breakdown of skeletal muscle proteins
– Substrate for gluconeogenesis
3) Enhances lipolysis – FA for energy
4) Suppresses the immune system
5) Causes negative calcium balance
– decreases absorption, increases excretion, increases bone breakdown
6) Influences brain function –mood, memory, learning
7) Adaptation to stress
Main higher brain functions involved in regulating cortisol release
Circadian rhythm and stress
Roles of CRH and ACTH, other than releasing cortisol 1 2 3 4
• CRH and ACTH have some stress‐related
functions in the immune and nervous systems
• The CRH family includes several peptides
– CRH mediates several functions
• Effects on inflammation and immune responses
• Inhibition of appetite
• Signals the onset of labor
• Appears linked to several mood disorders
– Urocortin: brain neuropeptide that decreases appetite
Roles of CRH family 1 2 3 4 5
– CRH mediates several functions
• Effects on inflammation and immune responses
• Inhibition of appetite
• Signals the onset of labor
• Appears linked to several mood disorders
– Urocortin: brain neuropeptide that decreases appetite
Roles of ACTH, other than cortisol regulation
1
2
3
• POMC (pro‐opiomelanocortin) is a large protein
thata yields several bioactive peptides by proteolysis
• ACTH and beta‐endorphin (blocks pain perception) are among the peptides produced in the anterior pituitary from POMC
• Outside the pituitary processing creates alpha‐MSH
– melanocyte‐stimulating hormone: decreasess food intake & increases skin melanin
Significance of ACTH derivation from POMC
The more the anterior pituitary is stimulated to release ACTH, more POMC needs to be cleaved to form ACTH, which will form other bioactive fragments of POMC.
Melanocortins
1
2
– Family name for the MSH hormones and ACTH
– The effects of the peptides depend on which
melanocortin receptor subtypes are stimulated
Broad roles of cortisol 1 2 3 4
• Essential for life
• Helps body cope with long‐term stress
• Protects against hypoglycemia by stimulating
catabolism of energy stores
• Permissive for glucagon & catecholamine
actions
Diurnal rhythm of cortisol
Peaks in the morning, lowest at night
Therapeutic roles of cortisol 1 2 3 4
• Suppresses the immune system
• Inhibits the inflammatory response
• Some specific uses
– Bee stings, poison ivy, and pollen allergies
– Prevents rejection of transplanted organs
• Long‐term use results in inhibition of ACTH
secretion and atrophy of cortisol‐secreting cells
– Taper doses gradually when stopping cortisol therapy
Half life of cortisol
60 - 90 minutes
Hypersecretion disorders of the adrenal cortex
1
2
3
1) Hyperaldosteronism
2) Cushing’s syndrome
3) Adrenogenital syndrome (excess androgens and oestrogen)
Hyperaldosteronism effects
1
2
3
– Primary hyperaldosteronism (Conn’s syndrome)
– Secondary hyperaldosteronism (RAS)
• Both cause hypernatremia, hypokalemia, hypertension
Cushing's syndrome effects 1 2 3 4
– Primary adrenal cortex tumors that autonomously secretes cortisol
– Secondary pituitary tumor that autonomously secretes ACTH (Cushing’s disease)
– Hyperstimulation (CRH, ACTH)
– Iatrogenic (physician-caused) hypercortisolism – treat with cortisol therapy
• All cause glucose excess, protein shortage, abnormal fat distribution
Androgenital syndrome effects 1 2 3 4
Excess androgens and oestrogen
– Lack enzyme in cortisol steroidogenic pathway
– Inappropriate masculinisation in all but adult males
– Treat with glucorticoids
– Repairs glucorticoid deficit and inhibits ACTH (reducing steroid secretion)
Symptoms of Cushing's syndromes 1 2 3 a, b 4 a 5 6
– Excess gluconeogenesis causes hyperglycemia mimics diabetes
– Muscle protein breakdown, lipolysis causes wasting
– Paradoxical fat deposits in trunk & face due to increased appetite
a) Thin arms & legs, trunk obesity, “moon face”
b) Stretched skin due to fat depots causes reddish purple striae
– Mineralocortocoid action of excess glucocorticoid (because of similar structure)
a) Salt & water retention, “moon face”, weakness, hypertension
– Osteoporosis
– Mood elevation then depression, difficult
learning & memory
Hormone profile of secondary Cushing’s from hypothalamic hypersecretion
High CRH
High ACTH
High cortisol
Hormone profile of secondary Cushing’s from anteroir pituitary hypersecretion
Low CRH
High ACTH
High cortisol
Hormone profile of primary Cushing’s
Low CRH
Low ACTH
High cortisol
Most common primary adrenal cortex disorder of hyposecretion
Addison’s disease
Addison's disaese 1 2 3 a, b 4 a
Primary adrenal insufficiency Addison’s Disease
– Autoimmune destruction of adrenal cortex
– Hyposecretion of all adrenal steroid hormones
– Decreased Aldosterone
a) K+ retention → Cardiac arrhythmias
b) Na+ depletion → hypotension
– Decreased Cortisol
a) Decreased stress response & hypoglycaemia
Are hypersecreting or hyposecreting adrenal cortex defects more common?
Hypersecreting are more common
Adrenal cortex hyposecreting defects
1
2
1) Addison’s disease
2) Adrenal steroid enzyme defects
Effect of adrenal steroid enzyme defects
Lack of cortisol & aldersterone causes increased androgens & adrenogenital syndrome
Catecholamines produced in adrenal medulla
1
2
3
1) Epinephrine (only made in adrenal medulla)
2) Norepinephrine
3) Dopamine
Chromaffin cells
Modified postganglionic sympathetic neurons that release epinephrine.
Synapsed onto by preganglionic sympathetic neurons from the spinal cord.
Adrenomedullary hormone effects 1 2 3 4
• Fight‐or‐flight responses – Increased cardiac rate and contractility, increased TPR, increased BP • Metabolic effects – Increased glucose & FFA, increased BMR • Central Effects – Increased arousal & alertness • Stress Responses – Physical – Psychological
Hyposecretion disorders of the adrenal medulla
None recognised
Hypersecretion disorders of adrenal medulla 1 2 3 4
– Pheochromocytomas (tumor)
– Rare
– Potentially deadly (hypertension)
– Treatment: removal
