Adrenal disorders Flashcards
Describe primary hyperaldosteronism
Primary Hyperaldosteronism
- First described in the literature in 1956 by Jerome Conn (Conn’s syndrome)
- 5-12% of all hypertension
- Most common cause of secondary hypertension
- Usually presents in 20s-50s
- Hypokalaemia common (<50% cases)
- Pathophysiology:
- Adrenocortical hyperplasia (usually bilateral, men, older)
- Aldosterone producing adrenal adenoma (unilateral, women, younger)
- Familial hyperaldosteronism
- Glucocorticoid remediable
- Mineralocorticoid excess has additional negative cardiovascular effects
- Left ventricular hypertrophy
- Cardiovascular events
- Myocardial fibrosis
- Coronary vasculitis
Describe the diagnosis of primary hyperaldosteronism
Diagnosis
- Screening:
- Aldosterone to renin ratio
- >70 abnormal
- Renin should be suppressed (or low)
- Confirmatory testing (must have normal BP & K+):
- Saline suppression test
- 2L IV saline over 4 hours
- Normal response is to suppress aldosterone
- Diagnostic if aldosterone >280 pmol/L
- Fludrocortisone suppression test
- Oral salt suppression test
- Note – most antihypertensives interfere with results
- Should only be tested on prazosin, verapamil, or hydralazine (4-6 weeks prior)
Describe the localisation and management of primary hyperaldosteronism
Localisation
- CT adrenals
- Remember that 10% of 70 year olds have an incidental adrenal adenoma
Adrenal vein sampling
- Interventional radiology
- Cannulate both adrenal veins (technically challenging)
- Samples from adrenal veins & periphery
- Looking for a ratio which lateralizes aldosterone excess
- Genetic testing for familial hyperaldosteronism
-
Adrenocortical hyperplasia
- Mineralocorticoid antagonists
- Spironolactone
- Eplerenone, amiloride, triamterene
- Salt-restricted diet, regular exercise, no smoking
- Mineralocorticoid antagonists
-
Unilateral adrenal adenoma
- Adrenalectomy
- If unsuitable for surgery, use mineralocorticoid antagonists
-
Familial hyperaldosteronism
- Low-dose glucocorticoids (for type 1)
- Dexamethasone or prednisolone
- Mineralocorticoid antagonists
- Low-dose glucocorticoids (for type 1)
Describe Cushing’s syndrome
Cushing’s Syndrome
- **Excess in cortisol production
- Incidence of 13 per million annually (all causes)
- Females : males ~5:1
- **First described by Harvey Cushing (neurosurgeon) in 1912
- Pathophysiology
- Pituitary (70%)
- Ectopic causes (1%)
- Adrenal causes (30%)
- Adenoma
- Carcinoma
- Hyperplasia
- Micro- or macro-nodular, or primary pigmented
Describe the symptoms and signs of Cushing’s syndrome
- Weight gain
- Moon face
- Dorsocervical and supraclavicular fat pads (buffalo hump)
- Dark purple striae
- Thin skin and easy bruising
- Acne
- Proximal myopathy
- Mood changes – depression, anxiety, irritability
- Hypertension
- Hyperglycaemia
- Hirsutism and irregular menses in women
- Erectile dysfunction in men
- Osteoporosis
Describe the diagnosis of Cushing’s syndrome
- Screen for cortisol excess (with multiple samples)
- 24 hour urinary free cortisol
- Normal: 100-300 nmol/24 hrs
- Must be a complete collection (check urine creatinine)
- 1mg overnight dexamethasone suppression test
- Give 1mg dexamethasone at ~2300hrs and check serum cortisol at ~0800 the following morning
- Normal: cortisol <50 nmol/L
- Oral contraceptive pill will interfere with result
- Midnight salivary cortisol
- Cotton pad between gum and cheek until soaked
- Should be low (reference range varies between labs)
- 24 hour urinary free cortisol
Describe the management of Cushing’s syndrome
Management
- Surgery
- Unilateral or bilateral adrenalectomy
- Medications
- Ketoconazole (blocks production)
- Metyrapone (blocks production)
- Mitotane (blocks production)
- Mifepristone (blocks tissue effects)
- Post-operatively need glucocorticoid ± mineralocorticoid replacement
Describe androgen-secreting tumours
- Excess in DHEAS, androstenedione, testosterone
- Incidence of < 0.2 cases per million annually
-
Signs and Symptoms:
- Hirsutism ± male pattern balding
- Ovarian hyperthecosis or tumour
- Deep voice
- Change in muscle bulk
- Clitoromegaly
- Pathophysiology
- **Medication
- Ovarian hyperthecosis or tumour
- Cushing’s syndrome
- Adrenal androgen-secreting tumour
Describe diagnosis and management of Cushing’s syndrome
-
Diagnosis
- Elevated testosterone, DHEAS, androstenedione (some or all)
- 2-Day dexamethasone suppression test
- Normal: testosterone suppressed by >40% or to normal range
- CT adrenals
- Imaging of ovaries (may need multiple modalities)
-
Management
- Surgical resection of the tumour
- Medications are unlikely to be effective in true virilisation
Describe CAH
- Excess in catecholamines
- Overall worldwide incidence of Classic CAH is 1 in 15000, 2/3 salt losers
- Carrier frequency 1/60
- Non-classic prevalence 1/100 – 1/1000
- Carrier frequency 1/17
- Group of autosomal recessive disorders with impairment of cortisol biosynthesis
- 21OH-deficiency accounts for 95% of CAH (CYP21A2 mutations)
- Deficiency of 11-ß hydroxylase is found in 9%
- Diagnosed based on testing of enzymes often with ACTH stimulation
List the signs and symptoms, and treatment, of CAH
-
Signs and Symptoms:
- Classic salt-losing (concomitant aldosterone deficiency)
- Classic non-salt losing (simple virilizing)
- Nonclassic (mild or late onset)
-
Treatment:
- Glucocorticoids
- Mineralocorticoids
- Surgery if needed for genital abnormalities
Describe phaechromocytoma
-
Epidemiology:
- Clinical phenotype includes: Adrenaline, noradrenaline, and/or dopamine
- <1% of all patients with hypertension, true incidence unknown
- 15% are extra-adrenal and known as paragangliomas (along sympathetic ganglia)
- Male = Female
- **Originate from the chromaffin cells in the adrenal medulla
- 15% are extra-adrenal and known as paragangliomas (along sympathetic ganglia)
- 10-15% malignant
- 25-30% familial (MEN2, VHL, NF1, SDH mutations)
-
Clinical Features:
- Hypertension, headache, sweating, palpitations, pallor, tachycardia, tremor, sense of impending doom
Describe the diagnosis and management of CAH
-
Diagnosis and Management:
-
Diagnosis
- Plasma free metanephrines
- 24-hour urinary metanephrines
- CT adrenals
- ± CT chest, abdomen, and pelvis
- MIBG scan – looking for metastatic extra-adrenal disease
- PET scan – if known metastatic disease
- ? Genetic testing
-
Management
- α-blockade
- Must be done prior to β-blockade
- ≥ 7 days pre-operatively
- Phenoxybenzamine (non-reversible)
- Prazosin
- β-blockade
- Only after α-blockade – risk of hypertensive crisis
- For control of tachycardia
- High salt and fluid intake
- Surgery – tumour resection
- α-blockade
-
Diagnosis
Describe adrenal incidentalomas
- First described in 1981
- A clinically inapparent adrenal mass lesion unexpectedly discovered when a radiological investigation is performed for another indication
- Usually >1 cm in diameter
- Prevalence increases with age
- 2-3% of 50 year olds have “benign” adrenal masses 1-2cm in size at autopsy
- 7% of 70 year olds have clinically inapparent adrenal masses
- 0.2% in patients <30 years of age – Any mass in this age group should increase suspicion for a sinister diagnosis
- In 1100 incidentalomas:
- 85% were non-functioning
- 9% secreted cortisol and caused subclinical Cushing’s syndrome
- 4% were phaeochromocytomas
- 2% were aldosteronomas
Describe primary adrenal insufficiency
- Described by Thomas Addison (physician) in 1855
- Named Addison’s disease by Trousseau
- Deficiency of glucocorticoids and mineralocorticoids
- In his day, 70-90% of cases were due to tuberculosis
- Incidence of 4 per million per year
-
Aetiology:
- Autoimmune (90%)
- Idiopathic or part of autoimmune polyglandular syndromes
- Infections (adrenalitis): TB, HIV
- Adrenal haemorrhage
- Adrenal metastases
- Infiltration: haemochromatosis, amyloidosis
- Congenital adrenal hyperplasia
- Other “fine print” conditions
- Autoimmune (90%)
-
Symptoms and Signs:
- Hypotension (postural)
- Hyponatraemia (salt craving)
- Hyperkalaemia
- Fever, abdominal pain, anorexia, weight loss
- Hyperpigmentation (skin and mucous membranes)
- Hypoglycaemia
- Anaemia, eosinophilia, lymphocytosis
- Fatigue and other nonspecific symptoms
