Clinical aspects of adrenal function Flashcards
What types of hormones are secreted by the adrenal cortex?
Steroid hormones
What are steroid hormones derived from?
Cholesterol
What are the hormones released by the adrenal cortex?
Glucocorticoids
Mineralocorticoids
Androgens
What can happen when glucocorticoids are found in excess?
Can mineralocorticoid properties
How do steroids affect target cells?
Enter the nucleus and affect gene transcription
What is the function of mineralocorticoids?
Salt and water retention
What effects do mineralocorticoids have when found in excess?
Glucocorticoid effects
What controls androgen release from the adrenal cortex?
Puberty and pituitary gland
Why do androgens released from the adrenal cortex have little effect?
The androgens have weak effects until they are metabolised peripherally into testosterone
What types of hormones does the adrenal medulla release?
Catecholamines - amines
What receptors to catecholamines bind to on target cells?
G-protein coupled receptors
Why does a dysfunction in the adrenal medulla no affect the release of catecholamines to a large extent?
They are predominantly synthesized by the sympathetic nerve endings
What area of the adrenal cortex is affected by Cushing’s?
Zona fasciculata
What hormone is elevated in the blood in Cushing’s syndrome?
Cortisol
What is the source of high cortisol in Cushing’s syndrome?
Three main causes:
- Increase in production of ACTH from the pituitary gland = this is called Cushing’s disease and is caused by pituitary adenoma
- Ectopic tissues producing ACTH - cancers (small cell lung cancer)
- Steroid drugs for clinical use
How do you diagnose Cushing’s syndrome?
- Look for increased levels of glucocorticoids
- Measure urinary metabolites of cortisol
- Measure ACTH - distinguishes adrenal from pituitary source
- Suppression test - Dexamethasone. Synthetic steroid with glucocorticoid excess - when injected in high quantities should suppress release of ACTH
- Imaging - localise the source of ACTH via imaging or nuclear medicine scan -> label molecule that binds to ACTH receptor
Treatment of Cushing’s syndrome
Surgery
Drugs
What are possible side effects from Cushing’s disease treatment?
Removal of adrenal glands = Nelson’s disease
Pituitary gland loses its negative feedback
Grows in size = blindness
Increased production of ACTH = pigmentation. MSH (melanocortin stimulating hormone) is a precursor for ACTH
What area of the adrenal medulla does Addison’s disease affect?
Zona fasciculate and glomerulosa
What is characterised in Addison’s disease?
Inadequate secretion of hormones from the adrenal cortex
What are the causes of Addison’s disease
- Autoantibodies that attack the adrenal gland
- Bad infection - rapid adrenal failure
- Steroid drugs - if suddenly stops using. Since they have caused atrophy of the adrenal glands
What diagnostic test can be performed to diagnose Addison’s
Inject ACTH. If the adrenal glands fail to respond - intrinsic adrenal disease/ atrophy
Why does the use of steroid drugs cause the adrenal gland to atrophy?
Activates the negative feedback loop so there is a decrease in ACTH production
ACTH stimulates survival and growth of adrenal cortical cells
Suppression of ACTH therefore, leads to adrenal cortex atrophy
What are the symptoms of Addison’s?
Salt and water wasting - low blood pressure
Low blood glucose
Fatigue
Weight loss
What is congential adrenal hyperplasia?
A rare group of autosomal recessive conditions characterized by the mutation in production of steroid hormones
The most common = mutation in 21 hydroxylase enzyme - turns precursors into mineralocorticoids and glucocorticoids
What is characterised in congenital adrenal hyperplasia?
Increase in the production of sex hormones
Low level of glucocorticoids and mineralocorticoids in the blood
Why is there elevated sex hormone levels in the blood of congenital adrenal hyperplasia patients?
All the precursors that should become glucocorticoids and mineralocorticoids become sex hormones instead
Sex hormones and glucocorticoids/mineralocorticoids share the same precursors
What factors determine the symptomology of the patients?
Age and the level of blockage of metabolic pathways
What are the symptoms of congenital adrenal hyperplasia?
In females
If severe - birth, ambiguous genetalia
If milder - childhood/ adolescence, accelerated growth and hair growth
If mild - adulthood, infertility or menstrual problems
In males
If severe - problems producing glucocorticoids = salt and water retention, accelerated puberty and exaggerated growth
What tests can be done to check if baby has congentil adrenal hyperplasia?
In the US - babies screened for 17 hydroxyprogesterone intermediate
Elevated in congenital adrenal hyperplasia patients
What is Pheochromocytoma?
Benign neuroendocrine tumours in the adrenal medulla
What does Pheochromocytoma cause?
Excess secretion of catecholamines from the adrenal medulla
How do you diagnose Pheochromocytoma?
- Suspicious if patient does not respond to hypertensive drugs
- Measure the metabolites of adrenaline in the urine
- Nuclear medicine scans - look for areas secreting an excess of catecholamines
What symptoms does Pheochromocytoma cause?
There is excess sympathetic activation
This leads to excess noradrenaline and adrenaline metabolites in the urine
Palpilations, weight loss, abdonminal pain, hypertension and anxiety
How can you treat Pheochromocytoma?
Surgery
Drugs - alpha blockers to counteract hypertension problems
What causes infertility?
Many problems
- Local - sperm generation, pathology of uterine tubules
- Adrenal related - Cushings in females leads to excess androgens/ congenital adrenal hyperplasia -> ambiguous genitalia
- Conditions of the ovary - polycystic ovarian syndrome
What does Aromatase do?
P450 enzyme
In the ovary, converts androgens -> oestrogen
