L09 - Hypothalamic-pituitary-adrenal axis: Clinical Aspects Flashcards
what does the adrenal cortex produce
what is cortisol bound to
what are the receptors
what is the enzyme involved
• Adrenal cortex hormone production GLUCOCORTICOID • CORTISOL MINERALOCORTICOID • ALDOSTERONE (renin-angiotensin-aldosterone system) SEX STEROIDS • ANDROGENS
• Binding proteins
90% cortisol bound to cortisol binding globulin (CBC)
• Receptors
— Intracellular glucocorticoid and mineralocorticoid receptors (GR
and MR)
Enzymes
1 1 -ß-hydroxysteroid dehydrogenase (11- ß-HSD)
What are the various effects of glucocorticoids
Maintenance of homeostasis during stress
— e.g. haemorrhage, infection, anxiety
Anti-inflammatory
Energy balance / metabolism
— incr / maintain normal [glucose]
Formation of bone and cartilage
Regulation of blood pressure
Cognitive function, memory, conditioning
How does circadian rhythm effect cortisol levels
• Cortisol levels: — rise during the early morning — peak just prior to awakening fall during the day — are low in the evening
tell me about ultradian rhythm
describes the pulsality of hormone release
they are spontaneous pulses of varying amplitude
the amplitude decreases in the circadian trough
it is hard to distinguish the stress response
what do the adrenal glands secrete and how does this relate to the testes
secrete DHEAS
these convert to androstenedione
this converts to test/oestro
what are the enzymes involved with glucocorticoids
what does this have the same affinity for
what is specificity conferred by?
what is the enzyme that inactivates cortisol? what does this enable?
In vitro, the ‘mineralocorticoid receptor’ (MR) has the same affinity for aldosterone and cortisol
Specificity is conferred by a ‘pre-receptor’ mechanism
11-ß-HSD-2 in the kidney inactivates cortisol, enabling aldosterone to bind the MR
How do 11-ß-HSD enzymes work
through tissue specificity
they gate GC access to nuclear receptors
they amplify GC signal in target cells
WHat happens with too much cortisol? condition
what are the big signs of it
Cushing's Syndrome — Weight gain — Central obesity ---Hypertension — Insulin resistance — Neuropsychiatric problems — Osteoporosis
CUSHING’s
what is the pathogenesis - how does it happen?
(different ways)
Excess cortisol:
— Pituitary adenoma: ACTH-secreting cells
(‘Cushing’s disease’)
— Adrenal tumour: adenoma (or carcinoma)
—‘Ectopic ACTH’: carcinoid, paraneoplastic
— Iatrogenic: steroid treatment (‘Cushingoid’)
what are the clinical features of cushings
— Central obesity with thin arms & legs
— Fat deposition over upper back (‘buffalo hump’)
— Rounded ‘moon’ face
— Thin skin with easy bruising, pigmented striae
— Hirsutism
—Hypertension
— Diabetes
— Psychiatric manifestations
— Osteoporosis
What happens with too little cortisol?
what are the main signs of this
Too little cortisol:
Addison’s disease
• The patient
— gradually falls off in general health
—becomes languid & weak
— indisposed to either bodily or mental exertion
— the body wastes
—slight pain is referred to the stomach
—there is occasionally actual vomiting
— discoloration of the skin
—at length he gradually sinks and expires
what is the pathogenesis of addison’s disease
ie what causes it
what are rare cases.
also what are other causes of hypoadrenalism
Pathoqenesis — Primary adrenal insufficiency • 'Addison's disease' • Usually autoimmune in UK • Rare causes include metastases or TB • decr in Production of all adrenocortical hormones
— Other causes of hypoadrenalism • Secondary to pituitary disease (rare) • 'Iatrogenic' — patients on high dose, long term steroid Rx, which is suddenly stopped at a time of stress
ADDISONS DISEASE
clinical features
— Malaise, weakness, anorexia, weight loss
— Increased skin pigmentation:
knuckles, palmar creases, around / inside the mouth, pressure areas, scars
— Hypotension / postural hypotension
— Hypoglycaemia
describe the two types of autoimmune polyendocrine syndromes
, Type 1 — Rare — Onset in infancy — Ar (AIRE gene) — Common phenotype: • Addison's disease • Hypoparathyroidism • Candidiasis
, Type Il — Commoner (still rare!) — Infancy to adulthood — Polygenic — Common phenotype: • Addison's disease • Tl diabetes • Autoimmue thyroid disease
What other autoimmune conditions may occur together
autoimmune polyendocrine syndromes
Type 1 diabetes — Autoimmune thyroid disease (hypo- or hyper-) • Also gestational / postpartum thyroiditis — Coeliac disease — Addison's disease — Pernicious anaemia — Alopecia — Vitiligo ---Hepatitis — Premature ovarian failure ---Myasthenia gravis
