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)
