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MET3B > Endocrine hypertensive disorders > Flashcards

Endocrine hypertensive disorders Flashcards

1
Q

What are the secondary causes of hypertension?

A

Cardio/ reso-

  • Coarctation
  • Obstructive sleep apnea
Renal:
- CKD
- glomerulonephritis
- Chronic pyelonephritis 
- polycystic  kidneys 
- Renovascular disease (renal
artery stenosis, fibromuscular dysplasia, arthromatous)
Endocrine:
- Conns
- Cushings, 
- Phaeochromocytoma, -Acromegaly
(Hypothyroidism, Hyperparathyroidism)
- Hyperthyroidism

Pre-eclampsia and hypertension in pregnancy

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2
Q

What are the risk factors for secondary causes of hypertension?

A 
Younger Age
-
 Strong Family History
-
 Requirement for multiple anti-hypertensives
  • Physical signs of secondary hypertension:
  • Renovascular, endocrine
    Other factors:
  • Electrolytes, glucose, calcium
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3
Q

What is conns syndrome

A

Another name for Primary aldosteronism

caused by an excess of the adrenal hormone aldosterone independent of the renin-angiotensin-aldosterone axis

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4
Q

What are the hall marks of conns disease?

A

hypertension and hypokalaemia - though hypokalaemia is often absent

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5
Q

List 5 subtypes of conn syndrome

A
  • Bilateral idiopathic hyperaldosternism
  • Aldosterone-producing adenoma
  • Unilateral hyperplasia
  • Other (familial hyperaldosteronism, adrenal carcinoma)
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6
Q

What are the 2 distinct components of the adrenal gland?

A

outer cortex and an inner medulla

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7
Q

How does the left and right adrenal gland differ?

A

right gland a pyramidal shape whilst the left is more semilunar

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8
Q

What are the 3 layers of the adrenal cortex? What does each component produce?

A

Zona Glomerulosa - mineralocorticoids - aldosterone

Zona Fasciculata - glucocorticoids

Zona Reticularis: androgens - produces dehydroepiandrosterone (DHEA).

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9
Q

Which 3 hormones does the adrenal medulla produce?

A

Adrenaline
Noradrenaline
Dopamine

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10
Q

Under normal circumstances aldosterone release is primarily controlled by the renin-angiotensin system. How does this system function to produce aldosterone?

A

Renin - (from granular cells of the juxtaglomerular apparatus)
Released in response to
- Renal artery hypotension
- Sympathetic stimulation
- Reduced sodium levels in the distal tubal

In the blood - Renin cleaves angiotensinogen into angiotensin I.

Angiotensin
ACE cleaves angiotensin I to give angiotensin II

  • Stimulates adrenal cortex to release aldosterone
  • Causes vasoconstriction
  • Increases sodium reabsorption
  • Stimulates the release of anti-diuretic hormone (ADH)

Aldosterone -
Released in response to - Angiotensin II (primary stimulus)
- ACTH
- Potassium levels

primary action is to increase the number of epithelial sodium channels in the distal tubule. This results in sodium and water reabsorption and potassium excretion.

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11
Q

What happens when too much aldosterone is secreted?

A

Increased sodium and water absorption = increased systemic fluid + hypertension

There is increased potassium excretion - Hypokalaemia

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12
Q

What is the aldosterone escape phenomenum?

A

a diuresis that occurs in response to the water and sodium retention caused by raised aldosterone

Leads to polyuria

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13
Q

What is the MOST COMMON cause of primary aldosteronism (conns)?

A

adrenal adenomas or idiopathic adrenal hyperplasia

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14
Q

There are 3 kinds of Familial hyperaldosteronism. Which gene mutation is responsible for type 2?

A

KCNJ5 gene

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15
Q

What are the longer term consequences of hypertension?

A

Chronic kidney disease
Cerebrovascular disease
Heart failure
Retinopathy

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16
Q

What are the longer term consequences of Hypokalaemia?

A

Muscle weakness
Paraesthesia
Mood disturbance
Polyuria/nocturia

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17
Q

Which 3 pathologies can you see in patients with conns disease?

A

Hypertension, hypokalaemia and metabolic alkalosis

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18
Q

Why can metabolic alkalosis develop in conns disease?

A

Due to hydrogen being excreted in the urine. Occurs for 2 reasons

  • hypokalaemia
  • Direct effect of aldosterone on intercalated cells.
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19
Q

Primary aldosteronism can present in young women in a very different way. Which way is this?

A

hypokalaemia but an absence of hypertension

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20
Q

What are the triggers which should cause you to tests for conns disease?

A
  • Hypertension and hypokalaemia (spontaneous or diuretic-induced)
  • Severe hypertension (systolic > 160, diastolic > 100)
  • Hypertension resistant to treatment. >3 medications
  • Hypertension and:
    Adrenal incidentaloma
    Sleep apnea
    Family history of early onset hypertension
    Family history of early onset CVA
    Primary aldosteronism affecting all 1st degree relatives with hypertension
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21
Q

How is Conns diagnosed?

A

Screening - raised aldosterone:renin ratio
if >800 patient should be investigated further

Specialist centers can test isolated aldosterone levels. If >1000 plus raised ratio above that 90% specificty

Using both is better for Afro- Caribeans as they have a low circulating renin

Spot renin and aldosterone test = aldosterone levels should be raised and renin should be low. If renin is high or normal that virtually excludes conns

Confirmatory test -

  • Oral sodium loading test
  • patient loaded with salt for 2 weeks before test.
  • Salt should suppress aldosterone
  • Aldosterone/renin, cortisol and bicarbonate levels are measured
  • failure to suppress aldosterone = confirmation of conns
  • Saline infusion test
  • Captopril challenge test

Identify the cause
- CT of adrenal glands - look for adrenal adenoma or hyperplasia

  • Adrenal vein sampling (gold standard)
    can differentiate between bilateral and unilateral disease

General investigation finings - hypokalaemic alkalosis

  • Elevated serum aldosterone
  • Suppressed plasma renin
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22
Q

How is conns treated?

A

Medical management is used before surgery. Surgery is the definitive treatment -

Aldosterone agonists are used -
eplerenone, spironolactone

Unilateral adrenal adenoma:
- Surgery

Bilateral adrenal hyperplasia

  • aldosterone antagonist
    eplerenone, spironolactone

Alternative -
Amiloride - ENaC inhibitor
(a potassium-sparing diuretic)
Used if other dugs not tolerated

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23
Q

What is the cause of crushing’s syndrome?

A

excess of glucocorticoids

24
Q

What are the Exogenous causes of Cushing’s disease?

A

derived externally

- Aministration of glucocorticoids either as a medication or misuse.

25
Q

What are the Endogenous causes of Cushing’s disease?

A

derived internally

  • due to excess production of glucocorticoids by the body itself
  • Cushing’s disease, which refers to cases caused by a pituitary adenoma, is responsible for the majority of endogenous cases.
26
Q

What is the most common causes of Cushing’s syndrome?

A

Exogenous causes

27
Q

Describe the difference between ACTH dependant and ACTH independent causes of Cushing’s

A

ACTH dependent: cortisol excess is driven by ACTH, either from the pituitary or ectopic sources.

ACTH independent: cortisol excess is independent of ACTH. Includes exogenous causes (consumption of cortisol) and adrenal lesions (adenomas, carcinomas).

28
Q

Describe how cortisol secretion is controlled by the hypothalamus-pituitary-adrenal axis.

A

1 -
- Corticotropin-releasing hormone (CRH) is released by the paraventricular nucleus of the hypothalamus

  • It is transported via the hypophyseal portal system to the anterior pituitary where it stimulates the release of adrenocorticotropic hormone (ACTH).

ACTH stimulates the release of cortisol from the adrenal cortex

29
Q

How does ACTH cause the hyperpigmentation see in Cushing’s syndrome?

A

POMC is the precursor for ACTH and beta-melanocyte-stimulating hormone

ACTH when inn excess may be cleaved to form alpha-melanocyte-stimulating hormone. Which causes melanocyte stimulation

This causes hyperpigmentation especially in the oral mucosa and palmar creases

30
Q

Describe the diurnal variation of cortisol

A

It reaches a zenith (highest point) at around 8 am and a nadir (lowest point) at around midnight to 1 am.

31
Q

What are the ACTH dependent causes of Cushing’s?

A

Cushing’s disease: -
caused by a pituitary adenoma that results in corticotrophs (pituitary) releasing excess ACTH
(most common)

Ectopic ACTH production-
malignant cells produce ACTH and not subject to normal negative feedback mechanisms (lung cancer)

Ectopic CRH production - Rarely CRH may be produced by malignant tissue resulting in increased ACTH and cortisol production.

32
Q

What are the ACTH independent causes of Cushing’s?

A

Endogenous administration: Prolonged exposure to exogenous glucocorticoids.
Results in suppression of CRH and ACTH

Primary adrenal lesions: tumours (adenomas, carcinomas and hyperplasia) may result in cortisol excess and suppression of CRH and ACTH.

Other: Very rare causes include bilateral macronodular adrenal hyperplasia and primary pigmented nodular adrenocortical disease.

33
Q

What are the clinical signs and symptoms of Cushing’s disease?

A 
Symptoms 
Tiredness
Depression
Weight gain
Easy bruising
Amenorrhoea
Reduced libido
Striae
Signs 
Acne
Moon facies
Plethora
Buffalo hump
Hypertension
Proximal muscle weakness
Hyperpigmentation
34
Q

How is Cushing’s syndrome diagnosed?

A

24h urinary cortisol test
>3 collections
Levels 3-4x normal are suggest Cushing’s syndrome.
creatinine levels also need to be measured. If amount varies between samples, Test needs to be repeated

Midnight cortisol

  • Taking midnight cortisol levels helps to demonstrate a loss of the normal circadian pattern.
  • Cortisol levels can be salivary or blood based

Low-dose dexamethasone suppression

  • Demonstrates the loss of normal negative feedback on the pituitary gland and hypothalamus
  • 1 mg of dexamethasone is given at 11pm and serum cortisol is then measured at 8am.
  • Normally dexamethasone should suppress the normal rise in cortisol levels. In Cushing’s, there is no suppression. so cortisol still rises

Dexamethasone-CRH test

  • dexamethasone is given for a period, followed by the administration of CRH.
  • Serum cortisol (and ACTH) levels can then be measured.
35
Q

How is the cause of Cushing’s disease identified?

A

Plasma ACTH

  • Suppressed / undetectable ACTH: Indicative of an ACTH independent cause of Cushing’s syndrome.
  • Raised / inappropriately normal ACTH: Suggestive of an ACTH dependent cause.

ACTH independent-
CT of the adrenal glands
Further tests may include MRI adrenal glands and PET/CT.

ACTH dependent -
Pituitary adenomas (Cushing's disease): High levels of dexamethasone are able to suppress ACTH production.

Ectopic production: Despite high dose dexamethasone, ectopic tissues will not be suppressed and continue to produce ACTH.

Petrosal sinus sampling - used to help identify a microscopic pituitary adenoma or side of tumour. Asses level of ACTH in petrosal sinus. this is compared to levels in peripheral vein

36
Q

How is Exogenous Cushing’s managed?

A

withdrawal of the glucocorticoid.
Sudden stopping will cause addisonian crisis.
patient should have a gradual tapering regimen with close safety netting and monitoring.

37
Q

What can happen if glucocorticoid steroid use is suddenly stopped?

A

addisonian crisis.

38
Q

How is Cushing’s disease (from pituitary adenoma) treated?

A
  • Transsphenoidal surgery is the gold-standard for treatment
  • Microadenomectomy: where an identifiable adenoma is found this can be resected leaving residual tissue of the anterior pituitary
  • Subtotal resection of the anterior pituitary: used where no identifiable adenoma and no desire for fertility after counselling the patient. There is a risk of hypopituitarism.

Drugs
- Metyrapone - inhibitor of 11β-hydroxylase. reduction in cortisol synthesis. Used before surgery or if surgery not possible

Pituitary irradiation-used in children and young people or those in whom surgical techniques have failed. takes around 6-12 months to have maximal effect.

Adrenalectomy
When all other therapies have failed bilateral adrenalectomy may be used. This mandates lifelong glucocorticoid and mineralocorticoid replacement.

39
Q

How are adrenal lesion causes of Cushing’s treated?

A

Unilateral adrenal adenoma-
Unilateral adrenalectomy offers curative therapy. Following surgery patients will need a tapering course of exogenous steroids for a period of time as their endogenous CRH and ACTH will be suppressed.

Bilateral adrenal hyperplasia
bilateral adrenalectomy may be offered. Then replacement of glucocorticoids and mineralocorticoids.

Adrenal carcinoma
- resection is the mainstay of management. Adjuvant chemotherapy, radiotherapy or mitotane may be given.

40
Q

What is Phaeochromocytoma?

A

catecholamine-secreting tumour of chromaffin cells

41
Q

What are chromaffin cells?

A

a type of neuroendocrine cell that are involved in the formation and release of catecholamines, which include noradrenaline, adrenaline and dopamine

42
Q

Where can Chromaffin cells be found?

A

predominantly found in the adrenal medulla, but also in the sympathetic paravertebral ganglia of the thorax, abdomen, and pelvis.

43
Q

Where can Catecholamine-secreting tumours come from?

A

may arise from the adrenal medulla or from the sympathetic ganglia. They are known as phaeochromocytomas and paragangliomas

44
Q

What is the meaning of the term head and neck paragangliomas?

A

It refers to Paragangliomas affecting/ arising from parasympathetic ganglia
They are usually non-secretory, derived from non-chromaffin cells

45
Q

Phaeochromocytomas may be sporadic or hereditary. Describe the 3 main hereditary types of phaeochromocytomas

A

Multiple endocrine neoplasia (MEN) type 2

  • autosomal dominant
  • due to a RET proto-oncogene mutation
  • Characterised by medullary thyroid cancer, phaechromocytoma and primary hyperparathyroidism

Von Hippel-Lindau (VHL) syndrome-

  • autosomal dominant disorder
  • due to VHL genetic mutation
  • Causes multiple tumours

Neurofibromatosis (NF) type 1

  • autosomal dominant
  • due to a mutation in the NF1 gene.
46
Q

How does the excess secretion of catecholamines effect Alpha and beta adrenergic receptors?

A

Alpha -
elevated bloods pressure, increased cardiac contractility, increased glucose utilisation (glycogenolysis/gluconeogenesis)

Beta
- increased heart rate, increased cardiac contractility.

47
Q

What is a hypertensive’ or ‘phaeochromocytoma’ crisis and what can precipitate this?

A

Caused by a dramatic release in catecholamines

precipitations
- Drugs: opiates, dopamine antagonists, beta-blockers, cocaine, tricyclic antidepressants

  • Physical: direct pressure or handling during surgery
  • Anaesthesia: endotracheal intubation
48
Q

Where are most phaeochromocytomas and paragangliomas located?

A

> 95% are located within the abdomen with up to 90% of these are intra-adrenal

49
Q

Are phaeochromocytomas and paragangliomas malignant?

A

~10% of cases are malignant. Malignant spread may occur a long-time following resection.

50
Q

What are the signs and symptoms of Phaeochromocytomas ?

A

Classic triad -

  • episodic headache, sweating and tachycardia.
  • Asymptomatic (50%)
  • Palpitations
  • Dyspnoea
  • Weakness
  • Tremor
  • Nausea

Signs

  • Hypertension (paroxysmal in 50%)
  • Posturla hypotension
  • Weight loss
  • Pallor
  • Arrhythmias
  • Pulmonary oedema: crackles at both lung bases
  • Fever
  • Tremor
51
Q

What are the symptoms f a hypotensive crisis?

A 
Hypertension
Hyperthermia
Confusion
End-organ dysfunction (e.g. cardiomyopathy, pulmonary oedema)
Hypotension (if circulatory collapse)
52
Q

When investigating Phaeochromocytomas elevated metanephrines and/or catecholamines need to be identified. How is this done?

A

Metanephrines are a metabolite of adrenaline that may be measured in the urine or plasma. Urine = high risk patient
Blood = low risk patient

Urinary fractionated metanephrines
- 24-hour urinary collection for urinary metanephrines. Twice, non consecutive days

Plasma free metanephrines

  • plasma levels of metanephrines
  • reserved for patients with a personal or family history of reserved for patients with a personal or family history of phaeochromocytoma, known genetic syndrome or suspected adenoma on imagingreserved
53
Q

What are the radiological investigations for phaeochromocytoma?

A

Imaging done after biological tests

Cross-sectional imaging
using CT or MRI of the abdomen and pelvis

In patients with negative CT/MRI
- Metaiodobenzylguanidine (MIBG) scintigraphy: MIBG resembles noradrenaline and is taken up by adrenergic tissue.

Fludeoxyglucose-positron emission tomography (FDG-PET): able to evaluate metabolic activity by measuring accumulation of the radioactive fluorodeoxyglucose (FDG), which is an analogue of glucose, that is taken up by tumours. Typically used to distinguish benign and malignant tumours.

54
Q

How is phaeochromocytoma treated?

A

surgical resection following medical optimisation.
Must optimise blood pressure control due to the risk of hypertensive crisis from anaesthesia and/or surgical manipulation.

Volume expansion
Patients are encouraged to have a high sodium diet due to the volume loss with excessive catecholamines and increased risk of orthostatic hypotension with alpha-blockers.

Surgical removal.
If both adrenal glands need to be removed (family history) = lifelong glucocorticoid and mineralocorticoid replacement.

55
Q

How is hypernestion treated in thsoe with phaeochromocytoma ?

A
  • Alpha-blockers : phenoxybenzamine, prazosin or doxazosin

Beta blockers :
- introduced only once adequate alpha-blockade has been achieved - propranolol, atenolol

Calcium channel blockers -
can be used as an alternative to alpha blockers or or as a third addition

Metyrosine: inhibits catecholamine synthesis. Usually only used in patients who cannot tolerate alpha and beta-blockade

56
Q

Which never is responsible for the direct cholinergic input into the adrenal medulla?

A

splanchnic nerve

57
Q

If the phaeochromocytoma tumour is malignant, which treatment option should be considered?

A

Metaiodobenzylguanidine (MIBG) scintigraphy:

MET3B (17 decks)

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