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Year 2 Clinical > Adrenal Gland Physiology and Disorders > Flashcards

Adrenal Gland Physiology and Disorders Flashcards

1
Q

Histology of the adrenal gland?

A

From superficial to deep:
• Capsule
• Cortex (consists of zona glomerulosa, fasciculata and reticularis)
• Medulla (consists of chromaffin cells, medullary veins and splanchnic nerves)

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2
Q

Function of each region of the adrenal gland?

A

Cortex:
• Zona glomerulosa - produces mineralocorticoids (aldosterone) and is regulated by angiotensin 2 and K+
• Zona fasciculata - produces glucocorticoids (cortisol and corticosterone) and is regulated by ACTH
• Zona reticularis - produces adrenal androgens (DHEA and DHEA-sulfate)

Medulla - produces catecholamines (epinephrine and norepinephrine)

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3
Q

Biosynthetic pathway of corticosteroid production in the adrenal cortex?

A

All have a CHOLESTEROL precursor; rate-limiting step is the conversion of cholesterol to pregnenolone

21-hydroxylase converts progesterone to deoxycorticosterone

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4
Q

Regulation of adrenal corticosteroid production?

A

Cortisol and androgens regulated by hormones produced by hypothalamus and anterior pituitary gland

Aldosterone regulated by RAAS and plasma K+

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5
Q

Mechanism of action of the RAAS system?

A

Major regulator of aldosterone production and it is activated in response to decreased BP, leading to:
• Ang II production (vasoconstriction)
• Aldosterone release

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6
Q

Mechanism of action of corticosteroids?

A

Binds to intracellular receptors and the receptor/ligand complex binds DNA to affect transcription

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7
Q

6 classes of steroid receptors?

A
  1. Glucocorticoid
  2. Mineralocorticoid
  3. Progestin
  4. Oestrogen
  5. Androgen
  6. Vitamin D
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8
Q

Major actions of glucocorticoid (cortisol)?

A

Bone/CT tissue - accelerates osteoporosis by decreasing Ca2+, collagen formation and wound healing

CNS:
• Mood lability
• Euphoria/psychosis
• Decreased libido

Immunological - decreased:
• Capillary dilatation/permeability
• Leukocyte migration
• Macrophage activity
• Inflammatory cytokines

Metabolic:
• Carb - increased BG
• Lipid - increase lipolysis, central redistribution
• Protein - increased lipolysis

Circulatory/renal - increased:
• CO
• BP
• Renal blood flow and GFR

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9
Q

3 main clinical uses of corticosteroids?

A
  1. Suppress inflammation
  2. Suppress immune system
  3. Replacement therapy
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10
Q

Where is the mineralocorticoid receptor (MR) located?

A

Kidneys, salivary glands, gut and sweat glands

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11
Q

Effects of aldosterone via MR?

A

Na+/K+ balance:
• K+/H+ excretion
• Increased Na+ reabsorption

BP regulation

Regulation of EC volume

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12
Q

Types of adrenal insufficiency?

A

Primary:
• Addison’s disease
• Congenital Adrenal Hyperplasia (CAH)
• Adrenal TB/malignancy

Secondary:
• Due to lack of CRH/ACTH stimulation
• Iatrogenic (excess exogenous steroid) - most common cause; steroids feedback and reduce ACTH release
• Pituitary/hypothalamic disorders

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13
Q

Occurrence of Addison’s disease?

A

Commonest cause of primary adrenal insufficiency

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14
Q

What is Addison’s disease?

A

Autoimmune destruction of the adrenal cortex; around 90% is destroyed before the patient becomes symptomatic

Tends to be assoc. with autoimmune diseases

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15
Q

Signs and symptoms of Addison’s disease?

A

Anorexia and weight loss

Abdominal pain, vomiting and diarrhoea

Fatigue/lethargy

Dizziness and low BP

Dehydration

Skin pigmentation, due to high ACTH (part. in palmar creases and buckle mucosa)

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16
Q

Ix results in adrenal insuffiency?

A

Suspicious biochemistry:
• LOW Na+ and HIGH K+
• Hypoglycaemia (more suspicious in children)

Adrenal auto-antibodies (only +ve in 70% of people so cannot exclude diagnosis)

Short SYNACTHEN test (clearly abnormal if the cortisol is low to start with and increases by only a small amount)

ACTH levels (should be high)

Renin/aldosterone levels (abnormal if there is INCREASED RENIN but DECREASED ALDOSTERONE)

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17
Q

Describe how the short synacthen test is done

A

Measure plasma cortisol before (in the morning, should be >250 nmol/L) and then give synthetic ACTH

Cortisol should increase to >550 nmol/L

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18
Q

Mx of adrenal insufficiency?

A

DO NOT DELAY TREATMENT to confirm diagnosis; requires life-long cortisol and aldosterone replacement

Hydrocortisone (cortisol replacement):
• If unwell, this is given IV first but, if they are well, daily 15-30mg oral is given in divided doses (mimic diurnal rhythm, so largest dose in morning)

Fludrocortisone as aldosterone replacement (monitor BP and K+)

Educate patient:
• Sick day rules
• Must not suddenly stop hydrocortisone
• Must wear steroid ID card

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19
Q

Exogenous steroids that can suppress CRH and ACTH release?

A

High dose prednisolone

Dexamethasone

Inhaled corticosteroid

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20
Q

Clinical features of secondary adrenal insufficiency?

A

Pale skin (as there is no increase in ACTH)

Aldosterone production is intact (regulated by RAAS)

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21
Q

Treatment of secondary adrenal insufficiency?

A

For tumours, surgery or radiotherapy

Treat with hydrocortisone replacement (fludrocortisone is unnecessary as ACTH does not affect aldosterone production)

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22
Q

Symptoms and signs of Cushing’s disease/syndrome?

A

Central weight gain

Acne

Facial plethora

Amenorrhoea

Hypertension (only 10% is secondary to a disoder like Cushing’s)

Severe osteoporosis

Easy bruising

Proximal myopathy (weakness) and muscle wasting in this region

Striae that are deep in colour

Testicular atrophy in males

Typical “lemon on matchsticks” appearance

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23
Q

Occurrence of Cushing’s syndrome?

A

Rare but it is more common in women aged 20-40 years

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24
Q

2 types of Cushing’s syndrome and causes of each type?

A

ACTH-dependent:
• Pituitary adenoma (most common), which causes Cushing’s DISEASE
• Ectopic ACTH, from carcinoid/carcinoma
• Ectopic CRH

ACTH-independent:
• Adrenal adenoma
• Adrenal carcinoma
• Nodular hyperplasia 
• Exogenous steroids
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25
Q

Ix for Cushing’s disease/syndrome?

A

Establish cortisol excess:
• Overnight dexamethasone suppression test
• 24 hour urinary free control
• Late night salivary control (rarely done as inconvenient and difficult)

Low dose

26
Q

Method of doing overnight dexamethasone suppression test?

A

Give dexamethasone 1mg; if the result is abnormal, repeat

If it is still abnormal, continue on to do a 2 day dexamethasone test

27
Q

Occurrence of iatrogenic Cushing’s syndrome?

A

Commonest cause of cortisol excess, usually due to prolonged high dose steroid therapy, e.g: in asthma, RA, IBD; the therapy is normally oral but it may occur with high dose inhaled or injections

28
Q

Describe iatrogenic Cushing’s syndrome

A

Chronic suppression of pituitary ACTH and adrenal atrophy

29
Q

Consequences of adrenal suppression?

A

Unable to respond to stress, e.g: during illness or surgery

Require extra steroid doses when ill/surgical procedure

Cannot stop steroids suddenly; gradual withdrawal is requires if >4-6 weeks use

30
Q

When is hypertension very suspicious?

A

HYPERTENSION WITH HYPOKALAEMIA is suspicious of primary aldosteronism

31
Q

What is primary aldosteronism?

A

AKA Conn’s syndrome - most common cause of secondary hypertension

Autonomous production of aldosterone, independent of its regulators, i.e: Ang II and K+

32
Q

CV actions of aldosterone?

A

Increased cardiac collagen

Increased sympathetic outflow

Altered endothelial function with an increased pressor response

Sodium retention

Cytokines and reactive oxygen species generation

ALL CAN LEAD TO CV DAMAGE AND ATHEROMA, etc

33
Q

Clinical features of Conn’s syndrome?

A

Significant hypertension

HYPOKALAEMIA

Alkalosis

34
Q

Sub-types of primary aldosteronism?

A

Adrenal adenoma (Conn’s syndrome) - usually younger people

Bilateral adrenal hyperplasia - usually older people

Rare causes:
• Genetic mutations (can be acquired or congenital)
• Unilateral hyperplasia

35
Q

Cause of adrenal aldosterone producing adenomas and hereditary hypertension?

A

Most common mutation is a somatic one in KCNJ5 channel (rectifying selective channel which maintains membrane hyperpolarisation)

Mutation leads to loss of ion selectivity, allowing Na+ entry and depolarisation instead

36
Q

Steps in diagnosis of Conn’s syndrome?

A

Step 1 - confirm aldosterone excess

Step 2 - confirm sub-type

37
Q

Methods of confirming aldosterone excess?

A

Measure plasma aldosterone and renin and express as a ratio (aldosterone : renin ratio); demonstrate that their is an excess of aldosterone compared to renin

If ratio raised (assay dependent) then Ix further with saline suppression test; failure of plasma aldosterone to suppress by > 50% with 2 litres of normal saline confirms PA

38
Q

Methods of confirming sub-type?

A

Adrenal CT to demonstrate adenoma

Can use adrenal vein sampling to confirm adenoma is the true source of the aldosterone excess; in this cases, the aldosterone : cortisol ratio must be found for both R and L adrenal veins
Then find an R : L ratio

39
Q

Mx of Conn’s syndrome?

A

Surgical (for an adrenal adenoma confirmed with adrenal vein sampling) - unilateral laparoscopic adrenalectomy; it cures:
• Hypokalaemia
• Hypertension (in some cases)

Medical treatment (if there is bilateral adrenal hyperplasia):
• Use MR antagonists (spironolactone or eplerenon)
40
Q

What is congenital adrenal hyperplasia?

A

Rare conditions assoc. with enzyme defects in the steroid pathyway

41
Q

Most common type of CAH?

A

95% of cases have a 21α-hydroxylase deficiency, which has autosomal recessive inheritance (i.e: both parents are carriers)

42
Q

Variants of 21α-hydroxylase deficiency?

A

Classical which shows:
• Salt wasting
• Simple virilisation

Non-classical:
• Hyperandrogenaemia

43
Q

Ix results of CAH?

A

Basal/stimulated 17-OH progesterone (there are increased levels of this precursor as well as of progesterone, androstenedione, testosterone and dihydrotestosterone)

44
Q

Presentation of classical CAH in males and females?

A

Males:
• Adrenal insufficiency (often around 2-3 weeks)
• Poor weight gain
• Biochemical pattern (low Na+ and high K+)

Females:
• Ambiguous genitalia

45
Q

Presentation of non-classical CAH in males and females?

A

Hirsute

Acne

Oligomenorrhoea

Precocious puberty

Infertility or sub-fertility

46
Q

Principles of CAH treatment in children?

A

Glucocorticoid (cortisol) replacement and, in some, mineralocorticoid (aldosterone) replacement

Surgical correction

47
Q

Principles of CAH treatment in adults?

A

Control androgen excess

Restore fertility

Avoid steroid over-replacement

48
Q

How are the catecholamines produced?

A

Tyrosine is converted to L-DOPA and this is converted to:

  1. Dopamine
  2. Noradrenaline
  3. Adrenaline
49
Q

Gross appearance of a phaeochromocytoma?

A

Smooth, well-defined capsule

Large

50
Q

Ix for phaeochromocytoma?

A

Biochemistry:
• Mildly elevated noradrenaline but normal adrenaline
• Very high dopamine usually indicates an extra-adrenal tumour

MIBG scan

24 hour urinary catecholamines (in a minority of patients, this is normal despite having the tumour)

51
Q

Ix for phaeochromocytoma?

A

Biochemistry:
• Mildly elevated noradrenaline but normal adrenaline; very high dopamine usually indicates an extra-adrenal tumour
• Hyperglycaemia (adrenaline-secreting tumours)
• May have low K+
• High haematocrit, raised Hb
• Mild hypercalcaemia
• Lactic acidosis (in absence of shock)

Confirm catecholamine excess:
• Do 2X 24 hour urinary catecholamines (in a minority of patients, this is normal despite having the tumour)
• Plasma (ideally at time of symptoms)

Identify source of excess:
• MRI scan of abdomen (for phaeochromocytome) and of whole body (for paraganglioma)
• MIBG scan
• PET scan (may be normal with slow-growing tumours)

52
Q

Classic triad of symptoms of phaeochromocytoma?

A

LABILE hypertension

Postural hypotension

Paroxysmal sweating, headache, pallor or tachycardia

Much of the time, patients display none of these and there is often insidious onset

Other symptoms inc. palpitations, breathlessness, constipation, anxiety-fear, weight loss, flushing (uncommon)

Can be an incidental finding

53
Q

Differential diagnosis with phaeochromocytoma?

A 
Alcohol withdrawal
Angina
Anxiety
Arrhythmia, e.g: SVT
Autonomic neuropathy

Carcinoid

Drug toxicity

Factitious

Insulinoma

Hypoglycaemia

Mastocytosis
Menopause
Migraine

Pregnancy

Thyrotoxicosis

54
Q

Signs of phaeochromocytoma?

A

Hypertension

Postural hypotension (50% of cases)

Pallor

Bradycardia and tachycardia

Pyrexia

55
Q

Signs of complications in phaeochromocytoma?

A 
Left ventricular failure
Myocardial necrosis
Stroke
Shock
Paralytic ileus of bowel
56
Q

Why is phaeochromocytoma called the 10% tumour?

A 
10% malignant
10% extra-adrenal (probably 20-30%)
10% bilateral
10% assoc. with hyperglycaemia
10% in children
10% familial (probably 25%)
57
Q

Who should have Ix for phaeochromocytoma?

A

Family members with syndromes

Resistant hypertension

If young (<50) with hypertension

Classical symptoms

Consider with hypertension and hyperglycaemia

58
Q

Treatment of phaeochromocytoma?

A

A before B - full α-blockade and β-blockade:
• Phenoxybenzamine (α-blocker)
• Propranolol, atenolol or metoprolol (β-blocker)
Give both at the same time but start A first

Fluid and/or blood replacement

Surgical:
• Total excision (wherever possible)
• Tumour de-bulking
Chemotherapy if malignant

59
Q

Cautions with phaeochromocytoma genetically?

A

Genetic testing must be done and do family tracing and Ix

60
Q

Clinical syndromes assoc. with phaeochromocytoma?

A

MEN2

VHL syndrome

Succinate dehyrogenase mutations

Neurofibromatosis

Tuberous sclerosis

Others

61
Q

Pitfalls in phaeochromocytoma diagnosis?

A

Catecholamines raised in heart failure

Episodic catecholamine secretion means that the levels in plasma + urine may be normal

Malignant and extra-adrenal tumours are less efficient at catecholamine synthesis, so dopamine > noradrenaline >adrenaline

May be a part of a genetic syndromes

Year 2 Clinical (119 decks)

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