Adrenal Gland Physiology & Disorders Flashcards

1
Q

Where are the adrenal glands located ?

A

Sit superior and medial to upper pole of kidneys

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2
Q

What are the 2 main anatomical areas of the adrenal glands ?

A

outer Cortex and a central medulla

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3
Q

What is produced in the cortex of the adrenal gland ?

A

Cortex has 3 zones:

  1. Zona Glomerulosa produces - Mineralocorticoids (mainly aldosterone)
  2. Zona Fasciculata produces - Glucocorticoids (mainly Cortisol)
  3. Zona Reticularis produces - Sex Steroids + Glucocorticoids (mainly cortisol)
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4
Q

What are the main hormones produced by the adrenal medulla ?

A

Catecholamines by chromaffin cells :

  • Adrenaline
  • Noradrenaline
  • Dopamine
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5
Q

What are the affects of adrenaline & noradrenaline on the body (hint they bascially function the same way)

A
  • Increase HR & force of heart contractions, increasing blood flow to the muscles and brain
  • Relax airway smooth muscles
  • Assisting in glucose (sugar) metabolism.
  • They also control the squeezing of the blood vessels (vasoconstriction), helping maintain blood pressure and increasing it in response to stress.
  • Also often activated in physically and emotionally stressful situations when your body needs additional resources and energy to endure unusual strain.
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6
Q

Describe the hypothalmic, anterior pituitary gland axis in the control of cortisol and androgens

A
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7
Q

What is the release of aldosterone controlled by ?

A

Renin-angiotensin system

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8
Q

What are the major actions of glucorticoids on the metabolic system, bones/connective tissues and circulatory/renal system - cortisol in particular ?

A

Metabolic:

  • Carbohydrate:­ increase blood sugar
  • Lipid: ­increase lipolysis, central redistribution
  • Protein: ­ increase proteolysis

Bone/connective tissues:

  • Accelerates osteoporosis
  • Decreases serum calcium
  • Decreases collagen formation
  • Decreases wound healing

Circulatory/renal system:

  • Increase CO
  • Increase BP
  • Increase renal blood flow and GFR
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9
Q

What are the 2 main classifications of pathology of the adrenal glands ?

A
  • Hyperfunction or hypofunction
  • This can be of either the adrenal cortex or medulla
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10
Q

What may adrenal pathology also be a manfiestation of ?

A
  • Pituitary disease (ACTH secretion from functional pituitary adenoma)
  • Shock / DIC
  • Various conditions that may damage / destroy adrenal tissue
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11
Q

What are the main hyperfunction adrenocortical (affecting cortex of adrenal gland) problems ?

A
  1. Primary hyperaldosteronism
  2. Hypercortisolism (cushing’s syndrome - covered in other decks)
  3. Congenital adrenal hyperplasia (CAH)
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12
Q

What are the main underlying causes of adrenocortical hyperfunction

A
  • Hyperplasia
  • Adenoma
  • Carcinoma
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13
Q

Describe the characteristic features of an adrenocortical adenoma

A
  • Well-circumscribed, encapsulated lesions
  • Usually small - upto 2-3cm
  • Yellow/yellow-brown surface
  • Unilateral
  • Less likely to be functional
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14
Q

Describe the characteristic features of an adrenocortical carcinoma

A
  • They are rare
  • More likely to be functional than adenomas
  • If causing virilisation then likely malignant
  • Larger size than andeomas
  • Haemorrhage & necrosis seen
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15
Q

What are the 2 types of adrenocortical hyperplasia ?

A

Congenital adrenal hyperplasia (CAH)

Acquired due to:

  1. Endogenous ACTH - pituitary adenoma (Cushing’s)
  2. Ectopic ACTH e.g. SCLC
  3. Bilateral adrenal enlargement
  4. Diffuse or nodular adrenal enlargement
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16
Q

What is CAH ?

A
  • It is a group of autosomal recessive disorders where there is a def./lack of the enzyme required for steroid biosynthesis in the adrenal gland
  • This results in blood cortisol levels being low & there never being enough to provide neg. feedback to slow/regulate the release of ACTH
  • This then results in the adrenal glands being constantly stimulated resulting in hyperplasia of the adrenal gland. This stimulation also results in increased androgen production ==> resulting in virilisation (development of male physical characteristics) in females & precosious puberty in males
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17
Q

What are the enzyme deficiency causes of CAH?

A
  • 21-hydroxylase deficiency (90%)
  • 11-beta hydroxylase deficiency (5%)
  • 17-hydroxylase deficiency (very rare)
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18
Q

What are the clinical features of CAH?

A
  • Virilisation in females
  • Precocious puberty in males
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19
Q

How is CAH diagnosed ?

A

Blood tests showing high serum 17-hydroxyprogesterone is diagnostic

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20
Q

What is the management of CAH?

A
  • Children tx = hydrocortisone
  • Adults tx = prednisolone or dexamethasone

+/- fludrocortisone if needed to control Na & renin levels (if aldosterone levels low)

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21
Q

What is hyperaldosteronism ?

A

This can be defined as excessive levels of aldosterone which may be either independant of the RAAS (known as primary hyperaldosteronism) or due to high renin levels (known as secondary hyperaldosteronism)

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22
Q

Describe the unlderlying physiology of primary hyperaldosteronism

A
  1. Excessive aldosteronism acts at the distal renal tubule
  2. This results in Na+ retention ==> H20 retention & ==> volume expansion with HTN
  3. Excretion of K+ also occurs resulting in hypokalaemia
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23
Q

What are the causes of primary hyperaldosteronism ?

A
  • Adrenal adenoma also known as conn’s syndrome - this will unilateral hyperplasia
  • Adrenal hyperplasia - this is usually bilateral adrenal hyperplasia (diffuse or nodular)
  • Adrenal carcinoma (rare)
  • Familial - glucoocrticoid remediable aldosteronism (GRA), characterised by inherited aldosterone producing adenoma or inherited BAH. In this one there is excessive Aldosterone produced in response to normal ACTH
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24
Q

What are the clinical features of primary hyperaldosteronism ?

A
  • Hypertension
  • Hypokalaemia - classically causing muscle weakness, also cramps & paraesthesia
  • Metabolic alkalosis
  • +/- headaches, lethargy, polyuria & normal or increased Na+
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25
Q

How is primary hyperaldosteornism investigated ?

A
  • 1st line = plasma aldosterone/renin ratio (should show high aldosterone & low renin levels)
  • 2nd line = high res. CT of abdo & adrenal vein - used to differentiate between BAH & unilateral (adrenal adenoma) hyperaldosteronism
  • 3rd line = adrenal venous sampling (AVS) can be done to identify the gland secreting excess hormone (gold-standard)
26
Q

What is the management of primary hyperaldosteornism ?

A

Adrenal adenoma tx = surgery (adrenalectomy)

BAH tx - aldosterone antagonist e.g. spironolactone

GRA tx:

  • 1st line = steroids + dexamethasone
  • 2nd line = spironolactone
27
Q

List the causes of secondary hyperaldosteronism ?

A
  • Diuretics
  • CCF
  • Hepatic failure
  • Nephrotic syndrome
  • Renal artery stenosis
  • Malignant HTN

Note - investigation & treatment should be directed at the underlying cause

28
Q

What are the 2 main classifications of adrenocortical hypofunction ?

A
  1. Primary insufficiency = there is inability of the adrenal glands to produce enough steroid hormones. May be acute (adisonian crisis) or chronic (addisons disease)
  2. Secondary insufficiency = inadequate pituitary or hypothalamic stimulation of the adrenal glands
29
Q

What are the causes of acute adrenocortical insufficiency (addisonian crisis) ?

A
  • Rapid withdrawl of long-term steroid tx
  • Patients with addisons disease who develop stress, trauma/surgery, infections/sepsis (times when they should increase their steroid dose) or have missed doses
  • Massive adrenal haemorrhage - newborn, on anti-coag tx, DIC, septicaemic infection (waterhouse fredirchsen)
30
Q

What are the clinical features of an addisonian crisis ?

A
  • Shock (increased HR, vasoconstriction, postural hypotension, oligouria, weak, confused, comatosed)
  • Vomiting
  • Abdo pain
31
Q

What is the management of an addisonian crisis ?

A
  • Hydrocortisone 100mg IM or IV stat & continue until stable. Then start transitioning to PO after 24hrs & complete transition by 72hrs for maintanence
  • 1L of NaCl (Saline) or dextrose if hypoglycaemic
32
Q

Define what addisons disease is

A

This is chronic adrenocortical insufficiency most commonly caused by autoimmune destruction of the adrenal glands leading to glucocorticoid (cortisol) & mineralocorticoid (aldosterone) deficiency

33
Q

List the causes of addisons disease

A
  • Autoimmune destruction (most common)
  • Infections - TB, opportunisitic infections in those with HIV e.g. CMV, mycobacterium avium, fungal infections
  • Malignancy - adrenal mets (mainly from lung, breast & renal) or lymphoma
  • Unusual - amyloid, sarcoidosis, haemochromatosis
34
Q

What are the clinical features of addisons disease ?

A
  • Vague symptoms - weakness, fatigue, anorexia, N&V, weight loss, diarrrhoea
  • Hyperpigmentation (esp palmar creases & buccal mucosa)
  • Vitiligo
  • Loss of pubic hair
  • Decreased aldosterone ==> Hyperkalaemia, hyponatraemia (causing volume depletion as H20 follows ==> hypotension)
  • Decreased cortisol ==> hyperglycaemia
  • May present in addisonian crisis
35
Q

How is addisons disease diagnosed ?

A
  • 1st line = ACTH stimulation test (short synacthen test)
  • If 30 min cortisol > 550 then addisons is excluded
36
Q

If syncathen test is not available what can be done to help diagnosed addisons disease?

A

Serum cortisol:

  • >500 addisons unlikely
  • < 100 definitley abnormal
  • 100-500 should prompt short synacthen test
37
Q

What autoantibody is often seen in addisons disease ?

A

Anti-21-hydroxylase

38
Q

What is the management of addisons disease (& secondary insufficiency)

A

Glucocorticoid + Mineralocorticoid replacement therapy = hydrocortisone (for cortisol) + fludrocortisone (for aldosterone)

39
Q

During intercurrent illness what should be done to the dose of glucocorticoid treatment in someone with addisons disease?

A

Generally double the dose

40
Q

What are the causes of secondary adrenal insufficiency ?

A
  • Most commonly iatrogenic long-term steroid therapy leading to pituitary-adrenal axis supression
  • Other causes rare e.g. hypothalamic-pituitary disease leading to decreased ACTH production
41
Q

How is secondary adrenal insufficiency differentiated from addisons disease?

A
  • Measure ACTH - levels are raised in addisons & low in secondary insufficiency
  • No hyperpigmentation seen in secondary insufficiency
42
Q

What is the treatment of secondary adrenal insufficiency due to pituitary/hypothalmic tumours ?

A

Surgery/radiotherapy

43
Q

What test is sometimes used to confirm secondary adrenal insufficiency?

A

Insulin tolerance test

44
Q

What are the 2 main problems affecting the adrenal medulla ?

A

Adrenal medulla tumours:

  1. Phaechromocytoma
  2. Neuroblastoma
45
Q

What is a neuroblastoma ?

A
  • It is a tumour which arises from neural crest tissue of the adrenal medulla (most common site) & sympathetic nervous system
  • It is one of the 5 top causes of cancer in children (usually diagnosed around 18 months old)
46
Q

What are the clinical features of neuroblastomas?

A
  • Abdo mass - may cause discomfort/pain
  • Pallor & weight loss
  • Bone pain/limp - spreads to bones most commonly
  • Hepatomegaly
  • Paraplegia or numbness/weakness (can compress the spinal cord)
  • Proptosis
  • If producing catecholamines - Weight loss, increased sweating, skin flushing, fast HR & watery diarrhoea
  • Constitutional symptoms - fever, weight loss, fatigue, loss of appetite
47
Q

How is neuroblastoma diagnosed ?

A
  • Screen with urine tests (for catecholamine secreting tumours) - raised urinary vanillylmandelic acid (VMA) & monovanillic acid (HVA) levels
  • Scans e.g. MRI, CT abdo, X-ray etc
  • Biopsy
48
Q

What is a phaechromocytoma ?

A

It is a rare catecholamine secreting tumour, which arises from collections of chromaffin cells & are usually found within the adrenal medulla

49
Q

What is the basic rule about phaechromocytomas ?

A

10% rule:

  • 10% are malignant
  • 10% are extra-adrenal (most commonly the bifrucation of the aorta)
  • 10% are bilateral
  • 10% are familial (part of hereditary cancer syndromes)
50
Q

What conditions are phaechromocytomas associated with ?

A
  • 90% are sporadic
  • 10% are part of hereditary cancer syndromes e.g. thyroid, MEN 2a & 2b, neurofibromatosis & von-hippel lundau syndrome
51
Q

What are the characterisitc features of phaechromocytoma ?

A

Symptoms are episodic (vary from once a month to several times a day with duration from secs to hrs):

  • Classic traid of headache, profuse sweating & tachycardia
  • Palpitations
  • HTN
  • Anxiety
  • Tremor
52
Q

How is phaechromocyomta diagnosed ?

A

1st line = 24hr urinary collection of metanephrines (breakdown products of catecholamines) +/- clonidine suppression test if levels are borderline

Localisation then done on CT/MRI abdo or MIBG isotope scan

53
Q

What is the treatment of phaechromocytomas?

A

Pre-op:

  • 1st do alpha-blockade with an alpha-blocker e.g. phenoxybenzamine
  • 2nd then add beta-blockade e.g. propanolol

Following blockade definitive management is surgery

54
Q

What complications can arise as a result of phaechromocytomas ?

A
  • Cardiac failure
  • Infarction
  • Arrhythmias
  • CVA
55
Q

What is the inheritance of MEN & what is it ?

A

It is an autosomal dominant syndrome where there are functioning hormone producing tumours in multiple organs

56
Q

What are the 3 main types of MEN?

A
  • MEN type 1
  • MEN type 2a
  • MEN type 2b
57
Q

What are the features of MEN type 1 ?

A

Think 3 P’s:

  1. Parathyroid hyperplasia - causes hypercalcaemia (main presenting feature of MEN 1)
  2. Pituitary tumours e.g. prolactinoma or acromegaly
  3. Pancreatic endocrine tumours e.g. insulinoma, gastrinoma leading to recurrent peptic ulceration

Also associated with causing adrenal & carcinoid tumours

58
Q

What mutation causes MEN type 1 ?

A

MEN 1 gene

59
Q

What are the features of MEN type 2a ?

A

Think 2 P’s:

  1. Phaechromocytoma
  2. Parathyroid hyperplasia - less commonly causinf hypercalaemic (only in 20% it does)

100% of patients have medullary thyroid cancer

60
Q

What are the features of MEN type 2b?

A

Think 1 P:

  1. Phaechromocytoma

100% have medullary thyoid cancer & also they have mucosal neuromas (‘bumps’ on lips, cheeks, tongue, glottis, eyelids & visible corneal nerves) & marfanoid body habitus

61
Q

What mutation causes MEN type 2a & 2b?

A

RET oncogene

62
Q

What is von-hippel lindau syndrome ?

A

Von Hippel-Lindau (VHL) syndrome is an autosomal dominant condition predisposing to neoplasia. It is due to an abnormality in the VHL gene located on short arm of chromosome 3

Features:

  • cerebellar haemangiomas: these can cause subarachnoid haemorrhages
  • retinal haemangiomas: vitreous haemorrhage
  • renal cysts (premalignant)
  • phaeochromocytoma
  • extra-renal cysts: epididymal, pancreatic, hepatic
  • endolymphatic sac tumours
  • clear-cell renal cell carcinoma