17- The Adrenal Glands & Disorders

Question 1

• name the 2 parts of the adrenal gland, the 3 layers of the adrenal cortex, the hormones they each produce.
• what are steroid hormones synthesised from and give some properties if them and examples
• describe how corticosteroids exert their actions by modulating gene transcription.

Answer 1

• the cortex and medulla; cortex= 1)outermost- zona glomerulosa synthesises and relseases mineralocorticoids eg aldosterone SALT, 2)middle-zona fasiculata synthesises glucocorticoids eg cortisol SUGAR, 3)innermost before medulla- zona rericularis synthesises glucocorticoids and some androgens SEX. *these hormones are collectively known as corticosteroids**Medulla=contains chromaffin cells that produce adrenaline (80%) and NA (20%)
• synthesised from cholesterol, lipophillic, bind to receptors of nuclear family and modulate gene transcription eg glucocorticoids, mineralocorticoids, oestrogens.
• they readily diffuse across the pm, bind to glucocorticoid receptors, this binding causes dissociation of chaperone proteins, receptor-ligand complex trans locates to nucleus, dimerisation w other receptors can happen, receptors bind to glucocorticoid response elements (GREs) or TFs.

Question 2

• what is aldosterone? describe its characteristics and functions.
• describe the pathway of the RAAS system.
• define hyperaldosteronism, describe the 2 types, signs and treatment.

Answer 2

• the most abundant mineralocorticoid, synthesised and released by zona glomerulosa, steroid hormone, carried on serum albumin, main action is in DCT and collecting duct of nephron where it promotes expression of Na+/K+ pump promoting reabsorption of Na+ and excretion of K+ thereby influencing water retention and BP, large component of RAAS system.
• 1)it is activated when there is hypotension or hypovolaemia, decrease in renal perfusion drop in BP and increased symp time from baroreceptors leads to more renin release from kidneys, 2)increased renin can then cleave the angiotensinogen relseased into blood by liver into angiotensin I. Angiotensin I is then cleaved by ACE in lung endo cells into angiotensin II. 3) angiotensin II has a variety of effects, first it acts on arterioles causing vasoconstriction increasing TPR and BP. Then it increases aldosterone secretion in adrenal cortex which acts to increase Na+ and water reabsorption , finally it acts on posterior pit gland to secrete more ADH to open more aquaporin channels for more reabsorption.
• too much aldosterone produced. Primary=defect in adrenal cortex eg bilateral idiopathic adrenal hyperplasia (most common), aldosterone secreting adrenal adenoma (Conns syndrome), LOW RENIN LEVELS. Secondary=due to overactive RAAS eg renin producing tumour (rare), renal artery stenosis ( kidney senses low BP and secretes more renin) ALWAYS HIGH RENIN. signs=high BP, LV hypertrophy, stroke, high Na+, low K+ .Treat=tumour removed, spiranolactone (mineralocorticoid receptor antagonist)

Question 3

• what is cortisol and what are its actions?
• what are glucocorticoids net effects on metabolism?
• what is Cushing’s syndrome? give exogenous and endogenous causes, signs and symptoms.

Answer 3

• most abundant corticosteroid, synthesised and released by zona fasciculata in response to ACTH, steroid hormone, its carrier protein in plasma=transcortin, exerts its actions by regulating gene expression, actions=increased protein breakdown in muscle, increased lipolysis in fat, increased gluconeogenesis in liver, resistance to stress,anti inflammatory effects + mast cell degranulation therefore used in allergic reactions.
• increased glucose production, breakdown of fat and proteins, glucose sparing effect in muscles as GLUT4 is inhibited, redistributes fat around abdomen + face, increased glycogen stores.
• Cushing’s syndrome=a chronic excessive exposure to cortisol, exogenous:prescribed glucocorticoid eg steroids used to treat inflammatory diseases like IBD, eczema, asthma. should be weaned off slowly. Endogenous:rarer, Cushing’s disease (benign pituitary adenoma secreting ACTH), Adrenal Cushing’s (excess cortisol produced by adrenal tumour, ACTH suppressed ), non pituitary-adrenal tumours producing ACTH/CRH eg small cell lung cancer, v rare. Signs & symptoms=plethoric moon face, buffalo hump on back, abdominal obesity, purple striae, acute weight gain, hyperglycaemia, skinny arms and legs.

Question 4

• what is Addison’s disease?
• give its signs and symptoms & explain why hyperpigmentation can happen.
• what is an Addisonian crisis, what are its causes, symptoms and treatment.

Answer 4

• a chronic adrenal insufficiency, main cause was TB but now more autoimmune, infection,affects women more.
• signs and symptoms=postural hypotension, lethargy, weight loss, anorexia, increased skin pigmentation (decreased cortisol means a negative feedback on anterior pituitary reduced, more POMC (precursor) needed to make ACTH & MSH (melanocyte stimulating hormone, When MSH is increased, more melanocytes are made thus causing hyperpigmentation)
• a life threatening emergency due to adrenal insufficiency, caused by:severe stress, lack of salt, infection, trauma, cold, abrupt steroid removal. Symptoms=nausea, vomiting, pyrexia, hypotension. Treat=fluid replacement, cortisol IV (lifelong replacement)

Question 5

• what are androgens?what are they secreted as and what do they do in males and females?
• how can the adrenal medulla be described in terms of its function? what do chromaffin cells act as?
• using QISS QIQ give the adrenergic receptors and their pathways and functions
• give the hormonal actions of adrenaline
• what is phaeochromocytoma? Give its characteristics. What is it caused by?
• what’s a paraganglioma? Cause?

Answer 5

• made in the innermost layer of the adrenal cortex (zona reticularis), secretes DHEA, partially regulated by ACTH & CRH, in males=DHEA converted to testosterone in testes but after puberty insignificant as testes make it themselves, in females=promote libido, converted to oestrogens, only source after menopause.
• adrenal medulla known as a modified sympathetic ganglion of ANS, chromaffin cells lack an axon but act the same to release hormones into blood.
• Q=Alpha 1, stimulates phospholipase C to DAG & IP3, PKC and Ca2+ release via IP3 receptor to target proteins. I= alpha2, inhibits adenylyl cyclase, converts ATP to cAMP, protein kinase A, then target proteins *see LMSRS pic**
• adrenaline involved in fight or flight, B1 adrenoceptor increases HR + contractility, B2 adrenoceptor causes bronchodilation, alpha1= vasoconstriction , B2 vasodilation.
• a chromaffin cell tumour that stains dark with chromium salts. Signs-severe hypertension bc of too much adrenaline,headaches, palpitations, damage to BVs.
• cause=genetic
• paraganglioma=extra adrenal tumour w chromaffin tissue origin, rare, also genetic.

Question 6

• how does adrenal cortex disease present? Split them into 3 categories. Give biochemical assessments to confirm disease.
• how does adrenal medulla disease present (adrenaline & NA)? Give biochemical assessments to confirm disease.
• how can you image to assess an adrenal disease?

Answer 6

• 1)adrenal hormone deficiency=lack of cortisol causes tiredness, weakness, lack of mineralocorticoid causes dizziness, lack of androgen causes low libido. 2) adrenal hormone excess=high cortisol causes weight gain, high mineralocorticoid causes high BP and low K+, high androgen causes increased male features in women.3)ACTH excess from pituitary causes skin pigmentation eg in Addison’s. Biochemical assessments=suspected deficiency:test basal cortisol at 09:00 when it’s at its highest, stimulation test. Suspected excess: see a high BP, low K+, 24hr urine cortisol high.
• excess adrenaline and NA causes sweating, acute episodes, high or low BP, palpitations. Biochemical assessments=24hr urine catecholamines (adrenaline & NA).
• imaging=CT scan, MRI, PET scans to fund tumour