Disorders of adrenal glands Flashcards
Describe the anatomy and function of the adrenal glands
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
Name and describe the function of mineralocorticoids
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.
Name and describe the function of glucocorticoids
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
Name and describe the function of androgens
Dehydroepiandrosterone (DHEA), is a precursor to testosterone and estradiol
What is the metabolic precursor to all steroid hormones?
Cholesterol
How do cortisol levels differ throughout the day?
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.
Describe the investigations used to assess cortisol levels and adrenal function
Basal test
Dexamethasone suppression test
Synacthen test
What factors must be accounted for to ensure accurate measure of basal cortisol?
Basal level:
- taken between 8am-9am at peak of circadian variation
- minimal stress
- appropriate reference ranges (for time/assay)
Describe the indication, process, and results of an overnight dexamethasone suppression test
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
Describe the indication, process, and results of a short Synacthen test
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
Define Cushing’s syndrome
A collection of symptoms caused by excessive cortisol levels
Define Cushing’s disease
Cushing’s syndrome due to a pituitary tumour causing excessive production of ACTH
Describe the pathophysiology of Cushing’s syndrome
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
Define pseudo-Cushing’s
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
List 8 symptoms of Cushing’s syndrome
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
List 8 signs of Cushing’s syndrome
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
Explain why hyperpigmentation may be seen in Cushing’s disease
Cushing’s disease features increased ACTH secretion. The excess ACTH is converted to melanocyte-stimulating hormone (MSH) which increases melanin production and pigmentation.
What are the indications for the different types of Dexamethasone suppression tests?
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.
Name 4 investigations used in Cushing’s syndrome?
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
Name an ectopic cancer that causes Cushing’s syndrome
Small-cell lung cancer*
Pancreatic carcinoma
What are the underlying causes of death in untreated Cushing’s syndrome?
Hypertension
Myocardial infarction
Infection
Heart failure
What is the potential impact of surgical patients with Cushing’s syndrome?
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.
How is cortisol hypersecretion controlled prior to surgery?
Metryapone (11 Beta-hydroxlase inhibitor)
Outline the definitive treatment of Cushing’s disease
Trans-sphenoidal removal of tumour* (75-80% success)
External pituitary irradiation (50-60% success, primarily used after failed surgery)
Laparoscopic bilateral adrenalectomy (last resort)
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.
Define Addison’s disease
Primary hypoadrenalism due to destruction of the adrenal cortex, reducing production of mineralocorticoids, glucocorticoids, and androgens.
What is the commonest cause of Addison’s disease in developed countries?
Autoimmune disease (85%)
Name a common cause of Addison’s disease in developing countries?
Tuberculosis
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
Describe the epidemiology of Addison’s disease
Rare condition - incidence 1 in 10,000
Most common onset between 30-50yrs
F>M
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
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
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.
How might Addisonian crisis present?
Shock - tachycardia, hypotension, oliguria, weakness, confusion, coma
Hypoglycaemia - sweating, fatigue, dizziness, tachycardia, blurred vision, confusion, convulsion, coma
What can precipitate Addisonian crisis?
Infection
Trauma
Surgery
Missed medication
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
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
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
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
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
Which 2 medications should be considered if taking long-term corticosteroids?
PPI
Bisphosphonates
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.
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.
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.
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)
Define Phaeochromocytoma
A rare catecholamine-secreting tumour originating from chromaffin cells of the adrenal medulla
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)
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
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.
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.
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.
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
How is Conn’s syndrome managed?
Laparoscopic resection - BP falls in 70% of cases
Spironolactone for hyperplasia
Define acromegaly
Excessive growth hormone secretion in adults due to GH-secreting pituitary adenomas
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
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
How is acromegaly investigated?
GH levels Glucose tolerance test - diagnostic if fail suppress GH Raised IGF-1 Visual field examination MRI scan - pituitary adenoma
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)
What U&Es results are visible in Cushing’s syndrome?
Hypernatraemia
Hypokalaemia
Metabolic alkalosis (due to hypokalaemia)
Excess corticosteroids exert a mineralocorticoid effect
