S9) The Adrenal Glands & Disorders Flashcards
Describe the macroscopic and microscopic structure of the adrenal glands
What are the three areas in the adrenal cortex?
- Zona glomerulosa
- Zona fasiculata
- Zona reticularis
Identify and describe the hormones in the different regions of the adrenal cortex
Steroid hormones are lipid soluble.
Describe their formation and function
- Formation: synthesised from cholesterol in adrenal glands and gonads
- Function: bind to receptors of the nuclear receptor family to modulate gene transcription
Provide five examples of steroid hormones
- Glucocorticoids
- Mineralocorticoids
- Androgens
- Oestrogens
- Progestins
Corticosteroids exert their actions by regulating gene transcription.
In six steps, outline this process
⇒ Corticosteroids readily diffuse across plasma membrane
⇒ Bind to glucocorticoid receptors
⇒ Binding dissociates chaperone proteins
⇒ Receptor-ligand complex translocates to nucleus
⇒ Dimerisation with other receptors can occur
⇒ Receptors bind to GREs / other transcription factors
Aldosterone is the most abundant mineralocorticoid.
Describe its function and transport
- Transport: carrier protein (mainly serum albumin or transcortin)
- Function: central role in regulation of plasma Na+, K+ and arterial blood pressure
Aldosterone is a central component of renin-angiotensin-aldosterone system.
In light of this, explain its specific actions
- Promotes expression of Na+/K+ pump increasing reabsorption in distal tubules and collecting ducts of nephron
- This influences water retention, blood volume & therefore blood pressure
Outline all the cellular and hormonal mechanisms involved in RAAS
What is hyperaldosteronism?
Hyperaldosteronism is a physiological state/condition wherein there is an excessive production of aldosterone
Distinguish between the two forms of hyperaldosteronism
- Primary – defect in adrenal cortex (high aldosterone:renin ratio)
- Secondary – over-activation of RAAS (low aldosterone:renin ratio)
Identify two causes of primary hyperaldosteronism
- Bilateral idiopathic adrenal hyperplasia (most common)
- Aldosterone-secreting adrenal adenoma (Conn’s syndrome)
Identify two causes of secondary hyperaldosteronism
- Renin producing tumour e.g. juxtaglomerular tumour (rare)
- Renal artery stenosis
Identify 5 clinical signs of hyperaldosteronism
- High blood pressure
- Left ventricular hypertrophy
- Stroke
- Hypernatraemia
- Hypokalaemia
The treatment for hyperaldosteronism depends on its form.
Describe the possible options
- Aldosterone-producing adenomas removed by surgery
- Spironolactone (mineralocorticoid receptor antagonist)
Cortisol is the most abundant corticosteroid & accounts for ~95% of glucocorticoid activity.
Describe its formation and transport
- Formation: synthesised and released by zona fasiculata in response to ACTH
- Transport: carrier protein in plasma (transcortin)
Cortisol is the most abundant corticosteroid & accounts for ~95% of glucocorticoid activity.
Describe its function and regulation
- Function: cortisol receptor exerts its actions by regulating gene transcription
- Regulation: negative feedback to hypothalamus inhibits CRH & ACTH release
Cortisol can act in 6 different ways.
Identify these
- Increased proteolysis in muscle
- Increased lipolysis in fat
- Increased gluconeogenesis in liver
- Resistance to stress
- Anti-inflammatory effects
- Depression of immune response
Cortisol is useful medication for allergic reactions
Describe its anti-inflammatory effects
- Inhibits macrophage activity
- Mast cell degranulation
Explain the resistance of cortisol to stress
- Increased supply of glucose
- Raise BP by making vessels more sensitive to vasoconstrictors
Identify one use of cortisol due to its ability to depress the immune response
Cortisol is prescribed to organ transplant patients
Outline the HPA axis
Explain how the glucocorticoid actions on metabolism lead to the following:
- Increased glucose production
- Breakdown of protein
- Redistribution of fat
What is Cushing’s syndrome?
- Cushing’s Syndrome is a clinical condition arising due to chronic excessive exposure to cortisol
- It leads to the re-distribution of fat especially in abdomen, supraclavicular fat pads, dorso-cervical fat pad, (buffalo hump), & on face (moon face)
Describe the aetiology of Cushing’s syndrome in terms of its endogenous and exogenous causes
Identify some signs and symptoms of Cushing’s syndrome
- Plethoric moon-shaped face
- Buffalo hump
- Abdominal obesity
- Purple striae
- Acute weight gain
- Hyperglycaemia
- Hypertension
Identify two examples of steroid drugs
- Prednisolone
- Dexamethasone
Steroid drugs have anti-inflammatory & immunomodulatory effects, thus are used to treat inflammatory disorders.
Provide some examples of these conditions
- Asthma
- Inflammatory bowel disease
- Rheumatoid arthritis
- Other auto-immune conditions
Describe the possible side effects due to steroid drugs
Side-effects are the same as the effects of higher levels of cortisol, plus can also have mineralocorticoid effects
How might one stop steroid drug usage?
Steroid dosage should be reduced gradually and not stopped suddenly
What is Addison’s disease?
- Addison’s disease is a clinical condition due to chronic adrenal insufficiency, commonly due to the destructive atrophy from autoimmune response
- Affects more women than men and the exact reason for autoimmunity is unknown
Identify some rare causes of Addison’s disease
- Fungal infection
- Adrenal cancer
- Adrenal haemorrhage e.g. following trauma
Identify some signs and symptoms of Addison’s disease
- Postural hypotension
- Lethargy
- Weight loss
- Anorexia
- Increased skin pigmentation
- Hypoglycaemia
What is the reason for the hyperpigmentation presenting in Addison’s disease?
- Increased melanin synthesis due to increased MSH & increased POMC
- ACTH can also directly activate melanocortin receptors on melanocytes
What is Addisonian Crisis?
- Addisonian Crisis is a life threatening emergency due to adrenal insufficiency
- It is often precipitated by severe stress, salt depravation, infection, trauma or abrupt steroid drug withdrawal
How does Addisonian Crisis present?
- Nausea
- Vomiting
- Pyrexia
- Hypotension
- Vascular collapse
What is the treatment for Addisonian Crisis?
- Fluid replacement
- Cortisol
Identify the two types of androgens
- Dehydroepiandrosterone (DHEA)
- Androstenedione
Describe the role of androgens in males and females respectively
- Male – DHEA converted to testosterone in testes (insignificant after puberty)
- Female – adrenal androgens promote libido and are converted to oestrogens by other tissues (only source of oestrogens after menopause)
Describe the role of androgens in both sexes
Promote axillary and pubic hair growth
The adrenal medulla is a modified sympathetic ganglion of autonomic nervous system.
Describe the role of is chromaffin cells
Chromaffin cells in adrenal medulla lack axons but act as postganglionic nerve fibres that release hormones into blood – adrenaline (~80%), noradrenaline (~20%)
Explain why adrenaline is the dominant hormone produced by the adrenal medulla
Outline, in detail, the biological signalling pathway induced at adrenergic receptors
Outline the various hormonal actions of adrenaline
Outline the cellular mechanism by which adrenaline increases heart rate
What is a phaeochromocytoma?
- A phaeochromocytoma is a chromaffin cell tumour which secretes catecholamines (mainly adrenaline)
- It may precipitate life-threatening hypertension
How do phaeochromocytomas present?
- Severe hypertension
- Headaches
- Palpitations
- Diaphoresis (excessive sweating)
- Weight loss
- Elevated blood glucose
Compare and contrast adrenal hormones in terms of the following:
- Synthesis
- Precursor
- Mode
- Storage
- Solubility
- Receptors
- Typical effect on enzymes
- Speed of response
- Effect of bilateral adrenalectomy
What are the clinical tests of adrenocortical function used in the differential diagnosis of adrenocortical disease?
- Plasma cortisol levels
- ACTH level
- 24hr urinary excretion of cortisol and its breakdown products (17-hydroxysteroids)
- Dynamic function tests e.g. dexamethasone suppression tests and ACTH stimulation tests
Describe the action of dexamethasone
Dexamethasone is a potent synthetic steroid that, when given orally would normally suppress (by feedback inhibition) the secretion of ACTH and thus cortisol
Describe the role of dynamic function tests in diagnosing adrenocortical diseases
- Dexamethasone suppression of plasma cortisol by >50% is characteristic of Cushing’s disease
- A normal response to, Synacthen, a synthetic analogue of ACTH which normally increases plasma cortisol by >200 nmol/L, indicates Addison’s disease
