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General Medicine Pt2 > Disorders of adrenal glands > Flashcards

Disorders of adrenal glands Flashcards

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1
Q

Describe the anatomy and function of the adrenal glands

A

The adrenal glands are located above the kidneys. It consist of cortex (3 layers) and medulla:

  • Zona glomerulosa ➔Mineralocorticoids: Aldosterone
  • Zona fasciculata ➔ Glucocorticoids: Cortisol
  • Zona reticularis ➔ Androgens: DHEA
  • Medulla ➔ Catecholamines: Adrenaline, NA
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2
Q

Name and describe the function of mineralocorticoids

A

Aldosterone, acts on the kidneys to control blood pressure and volume.

It upregulates Na-K-ATPase and ENaC channels. This increases renal sodium reabsorption and subsequent water reabsorption, and renal potassium excretion.

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3
Q

Name and describe the function of glucocorticoids

A

Cortisol

Increases: Gluconeogenesis, glycogen deposition, protein catabolism, fat deposition, sodium retention, potassium loss, free water clearance, neutrophils, uric acid

Decreases: Protein synthesis, host response to infection, delayed hypersensitivity, lymphocytes, eosinophils

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4
Q

Name and describe the function of androgens

A

Dehydroepiandrosterone (DHEA), is a precursor to testosterone and estradiol

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5
Q

What is the metabolic precursor to all steroid hormones?

A

Cholesterol

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6
Q

How do cortisol levels differ throughout the day?

A

Cortisol release is influenced by the circadian rhythm, displaying a diurnal rhythm. It is high in the morning, and falls throughout the day.

Stress can stimulate the release of extra cortisol throughout the day.

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7
Q

Describe the investigations used to assess cortisol levels and adrenal function

A

Basal test
Dexamethasone suppression test
Synacthen test

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8
Q

What factors must be accounted for to ensure accurate measure of basal cortisol?

A

Basal level:

  • taken between 8am-9am at peak of circadian variation
  • minimal stress
  • appropriate reference ranges (for time/assay)
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9
Q

Describe the indication, process, and results of an overnight dexamethasone suppression test

A

Diagnosis or exclusion of Cushing’s syndrome in an outpatient setting (some false positives)

Patient takes 1mg oral dexamethasone at 2300h
Blood sample for plasma cortisol at exactly 0900h

Normal response:
Cortisol suppression <100nmol/L

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10
Q

Describe the indication, process, and results of a short Synacthen test

A

Diagnosis or exclusion of adrenal insufficiency

Basal sample of cortisol
Give 250mcg Synacthen IV/IM
Sample for cortisol at time 30 and 60

Normal response:
Basal cortisol >170nmol/L
Cortisol increase to at least 580 nmol/L

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11
Q

Define Cushing’s syndrome

A

A collection of symptoms caused by excessive cortisol levels

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12
Q

Define Cushing’s disease

A

Cushing’s syndrome due to a pituitary tumour causing excessive production of ACTH

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13
Q

Describe the pathophysiology of Cushing’s syndrome

A

ACTH-dependent Cushing’s:
Increased circulating ACTH from the pituitary gland [Cushing’s disease] (65%) or an ectopic ACTH-producing tumour (10%), resulting in excess cortisol.

Non-ACTH-dependent Cushing’s:
Primary excess cortisol secretion (25%) by an adrenal tumour (Adrenal adenoma, adrenal carcinoma) or nodular hyperplasia with subsequent suppression of ACTH, or exogenous steroids

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14
Q

Define pseudo-Cushing’s

A

A collection of conditions that mimic the clinical and biochemical features of Cushing’s syndrome without hypercortisolaemia being the primary factor.

Examples: Severe stress, alcoholism and withdrawal, psychiatric conditions

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15
Q

List 8 symptoms of Cushing’s syndrome

A 
Central weight gain
Peripheral wasting
Buffalo hump, Moon face
Acne, hair growth, hirsutism
Depression, psychosis, insomnia, poor libido
Amenorrhoea/oligomenorrhoea
Thin skin/easy bruising
Back pain
Polyuria/polydipsia
Growth arrest in children
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16
Q

List 8 signs of Cushing’s syndrome

A 
Facial plethora (red fullness)
Central obesity
Thin skin, bruising
Striae
Proximal myopathy
Hypertension
Pathological fractures (esp vertebrae and ribs)

Moon face
Depression, psychosis
Acne, hirsutism, frontal balding
Poor wound healing, skin infections
Osteoporosis
Pigmentation - only with Cushing's disease
Kyphosis
Glycosuria - common with ectopic ACTH syndrome

Hypernatraemia and hypokalaemia - common with ectopic ACTH secretion due to cross reactivity with mineralocorticoid receptors

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17
Q

Explain why hyperpigmentation may be seen in Cushing’s disease

A

Cushing’s disease features increased ACTH secretion. The excess ACTH is converted to melanocyte-stimulating hormone (MSH) which increases melanin production and pigmentation.

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18
Q

What are the indications for the different types of Dexamethasone suppression tests?

A

Overnight dexamethasone: Outpatient screening for Cushing’s syndrome (some false positives). Normal suppression <100nmol/L.

Low-dose dexamethasone: Diagnosis of Cushing’s syndrome. Normal suppression <50nmol/L.

High-dose dexamethasone: Differential diagnoses of Cushing’s syndrome. This suppresses pituitary causes that would indicate Cushing’s disease. Cortisol <50% after 2 days suggests Cushing’s disease.

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19
Q

Name 4 investigations used in Cushing’s syndrome?

A

Dexamethasone suppression test
Plasma ACTH
Adrenal CT or MRI -> adrenal adenomas or carcinomas
Pituitary MRI
Plasma potassium -> Hypokalaemia common in ectopic ACTH secretion
CRH test -> suggests Cushing’s disease
CXR -> Small-cell lung cancer secreting ACTH

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20
Q

Name an ectopic cancer that causes Cushing’s syndrome

A

Small-cell lung cancer*

Pancreatic carcinoma

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21
Q

What are the underlying causes of death in untreated Cushing’s syndrome?

A

Hypertension
Myocardial infarction
Infection
Heart failure

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22
Q

What is the potential impact of surgical patients with Cushing’s syndrome?

A

Uncontrolled cortisol hypersecretion is associated with considerable morbidity and mortality if operated on, especially abdominal surgery.

Therefore, it is crucial to control cortisol secretion prior to surgery or radiotherapy.

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23
Q

How is cortisol hypersecretion controlled prior to surgery?

A

Metryapone (11 Beta-hydroxlase inhibitor)

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24
Q

Outline the definitive treatment of Cushing’s disease

Study These Flashcards
A

Trans-sphenoidal removal of tumour* (75-80% success)
External pituitary irradiation (50-60% success, primarily used after failed surgery)
Laparoscopic bilateral adrenalectomy (last resort)

25
What complication is seen in 20% of bilateral adrenalectomies?
Nelson's syndrome - Hyperpigmentation associated with an enlarging pituitary tumour due to the lack of negative feedback. Rarer nowadays due to adrenalectomy being an uncommon procedure.
26
Define Addison's disease
Primary hypoadrenalism due to destruction of the adrenal cortex, reducing production of mineralocorticoids, glucocorticoids, and androgens.
27
What is the commonest cause of Addison's disease in developed countries?
Autoimmune disease (85%)
28
Name a common cause of Addison's disease in developing countries?
Tuberculosis
29
List 3 causes of Addison's disease
``` Anatomical destruction: Autoimmune (85%) Infection - TB Surgical removal Trauma Neoplasm Amyloidosis Haemachromatosis ``` Congenital adrenal hyperplasia Enzyme inhibition e.g. Metapyrone, ketoconazole CYP P450 inducers e.g. Rifampicin, phenytoin ACTH resistance
30
Describe the epidemiology of Addison's disease
Rare condition - incidence 1 in 10,000 Most common onset between 30-50yrs F>M
31
List 5 symptoms of Addison's disease
Weight loss Malaise Fatigue and weakness* Fever ``` NaV, Anorexia Diarrhoea/constipation Abdominal pain Depression, irritability, poor concentration Confusion Myalgia, arthralgia ``` Impotence, amenorrhoea Postural hypotension, syncope
32
List 3 signs of Addison's disease
General: Weight loss, cachexia Hyperpigmentation* (90%) esp of scars, palmar creases, buccal mucosa Hypotension Postural hypotension (80-90%) Vitiligo
33
What is Addisonian crisis?
Acute adrenal failure - medical emergency that can cause shock or kidney failure May develop sudden weakness, severe pain in lower back, abdomen, or legs, DaV, hypotension and syncope.
34
How might Addisonian crisis present?
Shock - tachycardia, hypotension, oliguria, weakness, confusion, coma Hypoglycaemia - sweating, fatigue, dizziness, tachycardia, blurred vision, confusion, convulsion, coma
35
What can precipitate Addisonian crisis?
Infection Trauma Surgery Missed medication
36
How should Addisonian crisis be managed?
Serum cortisol and ACTH urgently U&Es - check for hyperkalaemia and hyponatraemia Hydrocortisone 100mg IV -> Oral steroids after 72hr Fluid resus Monitor BM for hypoglycaemia Cultures +- ABX Call endocrinology
37
What investigations are used for Addison's disease?
Synacthen test - impaired response confirms hypoadrenalism 09:00hr plasma ACTH - High ACTH with low cortisol confirms Addison's disease U&E - hyponatraemia and hyperkalaemia Blood glucose - hypoglycaemia Adrenal antibodies - autoimmune adrenalitis CXR or AXR - tuberculosis Plasma renin - high due to low aldosterone
38
Describe the definitive treatment of Addison's disease
Replacement Hydrocortisone or Prednisolone Replacement mineralocorticoid: Fludrocortisone Treat any underlying TB Patient education on replacement steroid treatment
39
What patient advice should be given when taking replacement steroids for Addison's disease?
Increase steroid replacement by doubling dose for intercurrent illness (presence of fever) Carry a 'steroid card' Wear a Medic-alert bracelet Keep ampoule of hydrocortisone at home if oral therapy is impossible
40
List 10 side effects of corticosteroid therapy
Adrenal and/or pituitary suppression CV: Hypertension GI: Pancreatitis Renal: Polyuria, nocturia CNS: Depression, euphoria, psychosis, insomnia Endocrine: Weight gain, hyperglycaemia, impaired growth, amenorrhoea MSK: Osteoporosis, Proximal myopathy, aseptic necrosis of hip, pathological fractures Skin: Thin skin, easy bruising Eyes: Cataracts Increased susceptibility to infection Reactivation of TB
41
Which 2 medications should be considered if taking long-term corticosteroids?
PPI | Bisphosphonates
42
What are incidentalomas?
Incidental adrenal tumours discovered in 3-10% of scans. Although the majority are asymptomatic and benign, functional tests should be performed to exclude secretory activity.
43
What is the importance of incidentalomas?
Incidental adreal mass may be an adenoma or phaeochromocytoma. Adrenal adenomas often secrete low level cortisol (sub-clinical Cushing's) which may confer an increased cardiovascular risk. Phaeochromocytoma carries a risk of perioperative hypertensive or hypotensive crisis.
44
What management options exist for benign non-functioning incidentalomas?
If no endocrine activity detected, most recommend removal only of large (>5cm) adrenal tumours due to risk of malignancy. Small, hormonally inactive lesions are usually observed, as long as no worrying radiological features.
45
Define secondary hypertension and state 3 endocrine causes
Secondary hypertension: Hypertension (BP >140/90) caused by an identifiable and potentially reversible cause. ``` Conn's syndrome (primary aldosteronism) Phaeochromocytoma (Catecholamine-secreting chromaffin cell tumour) Cushing's syndrome Acromegaly (GH excess) Hyperparathyroidism (unknown mechanism) ```
46
Define Phaeochromocytoma
A rare catecholamine-secreting tumour originating from chromaffin cells of the adrenal medulla
47
List 3 symptoms and 3 signs of phaeochromocytoma
Symptoms: Anxiety, palpitations, tremor, sweating, headache, flushing, NaV, Weight loss, bowel changes, Raynaud's, chest pain, polyuria/nocturia Signs: HTN*, tachycardia/arrhythmias, bradycardia, postural hypotension, Cafe au lait spots (NF1), pallor/flushing, glycosuria, fever, signs of HTN damage (renal, cardiac, retinal)
48
Name 2 investigations for phaeochromocytoma
Urinary catecholamines and metabolites* -Metanephines: Normal levels on three 24hr collections virtually excludes diagnosis Resting plasma metanephrines Plasma chromogranin A Genetic testing for MEN2, VHL etc. mutations in all confirmed phaeochromocytoma
49
What is the management of phaeochromocytoma?
Resection of tumour if possible. 95% 5yr survival rate. Pre- and periop alpha then beta blockade. Alpha blockade (Phentolamine and phenoxybenzamine) must be given first otherwise HTN worsens. Longterm alpha and beta blockade if surgically unfit Annual urinary catecholamine monitoring for recurrence or further tumour development.
50
Define Conn's syndrome
Primary aldosteronism: Excessive aldosterone production from the adrenal cortex, with low renin. Causes sodium retention, potassium loss, hypokalaemia (<3.5mmol/L), and hypertension.
51
Describe the presentation of Conn's syndrome
Usually presents with hypertension alone. Hypokalaemia (<3.5mmol/L) frequently not present. A few rare non-specific symptoms: muscle weakness, nocturia, tetany.
52
How may Conn's syndrome be investigated? What medications need to be stopped when investigating Conn's syndrome?
Stop Beta-blockers and drugs that interfere with renin. Stop spironolactone, ACEi, and ARBs ``` Plasma aldosterone:renin ratio* Elevated plasma aldosterone - not suppressed by saline or fludrocortisone (mineralocorticoid) Suppressed plasma renin activity Hypokalaemia Urinary potassium loss >30mmol/d ``` Adrenal CT/MRI to differentiate adenoma and hyperplasia
53
How is Conn's syndrome managed?
Laparoscopic resection - BP falls in 70% of cases | Spironolactone for hyperplasia
54
Define acromegaly
Excessive growth hormone secretion in adults due to GH-secreting pituitary adenomas
55
List 5 symptoms of acromegaly
HaN: Change in facial appearance, headaches, visual distortion, deep voice, goitre General: Tiredness, weight gain, SoB, Excessive sweating, muscular weakness, joint pain Hormonal: Amenorrhoea or oligomenorrhoea, galactorrhoea, impotence, poor libido Increased hat, glove, shoe size
56
List 5 signs of acromegaly
Facial: Prognathism* (protruding jaw), interdental separation*, large tongue*, prominent supraorbital ridge, visual field defects General: Hirsutism, thick greasy skin Hands: Spade-like hands and feet*, tight rings, carpal tunnel syndrome Other: Galactorrhoea, HTN, heart failure, oedema, arthopathy/OA, proximal myopathy, glycosuria
57
How is acromegaly investigated?
``` GH levels Glucose tolerance test - diagnostic if fail suppress GH Raised IGF-1 Visual field examination MRI scan - pituitary adenoma ```
58
Outline the management of acromegaly
Aim to achieve mean GH level <2.5mcg/L Trans-sphenoidal surgery External pituitary radiotherapy Medical: -Somatostatin agonists (Octreotide, lanreotide) -Dopamine agonists (Bromocriptine, cabergoline) -GH antagonists (Pegvisomant)
59
What U&Es results are visible in Cushing's syndrome?
Hypernatraemia Hypokalaemia Metabolic alkalosis (due to hypokalaemia) Excess corticosteroids exert a mineralocorticoid effect

General Medicine Pt2 (15 decks)

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