Flashcards in Disorders of Adenocorticol Function Deck (76):
What is characterised by decreased activity of the adrenal cortex?
What may Addison's disease be due to?
What can cause disease of the adrenal cortex?
What is the result of reduction in activity of the adrenal cortex?
Reduces glucocorticoids and mineralocorticoid secretion
What do disorders of the pituitary and hypothalamus leading to decreased secretion of ACTH affect?
What is characterised by increased secretion of glucocorticoids?
What may Cushing’s syndrome be due to?
- Increased activity of the adrenal cortex due to tumour (adenoma)
- Disorders in secretion of ACTH caused by pituitary adenoma
- Ectopic secretion of ACTH
What is the disease caused by pituitary adenoma causing increased ACTH secretion?
What is congenital adrenal hyperplasia?
A number of clinical conditions that arise as a consequence of a genetic defect in one or more of the enzymes required for synthesis of cortisol
What happens due to the lack of cortisol in congenital adrenal hyperplasia?
The pituitary is not subjected to negative feedback control
What is the result of the pituitary not being subject to negative feedback?
It secretes large amounts of ACTH
What does excess ACTH secretion in congenital adrenal hyperplasia’s cause?
An enlargement of the adrenal cortex (hyperplasia)
What does the severity of the consequences of congenital adrenal hyperplasias depend on?
Which enzyme(s) is affected
What are the effects of excess cortisol secretion?
- Increased muscle proteolysis and hepatic gluconeogenesis
- Increased lipogenesis in adipose tissue
- Purple striae on lower abdomen, upper arms and thighs
- Immuno-suppressive, anti-inflammatory and anti-allergic reactions of cortisol
- Back pain and collapse of ribs
What can increased muscle proteolysis and hepatic gluconeogenesis lead to?
Hyperglycaemia, and associated polyuria and polydipsia
What is hyperglycaemia due to excess cortisol secretion called?
What does increased muscle proteolysis cause?
Wasting of proximal muscle
What is the result of proximal muscle wastage?
What does the increased lipogenesis in adipose tissue on excess cortisol secretion lead to?
Deposition of fate in abdomen, neck and face
What does the deposition of fat in excess cortisol secretion lead to?
The characteristic body shape, moon-shaped face and weight gain
What do the purple striae caused by excess cortisol secretion reflect?
The catabolic effects of protein structures in skin
What does the decreased protein integrity in skin caused by excess cortisol secretion lead to?
Why does excess cortisol secretion lead to easy bruising?
Because there is thinning of the skin and subcutaneous tissue
What does the immunological effects of excess cortisol secretion lead to?
Increased susceptibility to bacterial infections, anda cne
Why may excess cortisol secretion cause back pain and rib collapse?
Due to osteoporosis
Why does excess cortisol production lead to osteoporosis?
Because of disturbances to calcium metabolism, and loss of bone matrix proteins
Why may mineralocorticoid effects of excess cortisol lead to hypertension?
Due to sodium and fluid retention
Where else may the symptoms of excess cortisol secretion occur?
In patients receiving long-term treatment with glucocorticoids for various chronic conditions
What would autoimmune destruction of the adrenal gland?
Involve loss of cortisol and mineralocorticoids
How does the loss of cortisol and mineralocorticoids present?
It is a complex situation, that may present as an acute emergency (Addisonian Crisis), or as a chronic debilitating disorder (Addison’s disease)
How does Addison’s disease onset?
Insidious onset, with initial non-specific symptoms of tiredness, extreme muscular weakness, anorexia, vague abdominal pain, weight loss and occasional dizziness
What symptoms of Addison’s disease are extreme?
The muscular weakness and dehydration
What is a more specific sign of Addison’s disease?
Where does increased pigmentation occur especially in Addison’s disease?
- Exposed areas of the body
- Points of friction
- Buccal mucosa
- Palmar creases
Why does Addison’s disease cause increased pigmentation?
Due to ACTH-mediated melanocyte stimulation
What happens to blood pressure in Addison’s disease?
Why does Addison’s disease decrease blood pressure?
Due to sodium and fluid depletion
What causes postural hypotension in Addison’s disease?
What kind of episodes does Addison’s disease cause?
When do the hypoglycaemic episodes caused by Addisons disease particularly occur?
What can exacerbate the effects of Addison’s disease?
Stress, such as trauma of severe infection
What can the exacerbation of the symptoms of Addison’s disease with stress cause?
- Extreme dehydration
What is the exacerbation of the symptoms of Addison’s disease with stress called?
An Addisonian crisis
What does an Addisonian crisis constitute?
A clinical emergency
How is an Addisonian crisis treated?
IV cortisol and fluid replacement
How is adrenocortisol function measured clinically?
- Plasma cortisol
- ACTH levels
- 24hr urinary secretion of cortisol and its breakdown products
- Dynamic function tests
What are the breakdown products of cortisol?
Give 2 examples of dynamic function tests
- Dexomethasone surpression tests
- ACTH stimulation tests
What can clinical tests of adrenocortisol function be used in?
Differential diagnosis of adrenocortisol disease
What is dexamethasone?
A potent steroid
What would normally happen when dexamethasone is given orally?
Would suppress the secretion of ACTH and therefore cortisol
How does dexamethasone suppress?
What dexamethasone suppression of plasma cortisol is characteristic of Cushing’s disease?
Why is a dexamethasone suppression of >50% characteristic of Cushing’s disease?
Because for the diseases pituitary, even though its relatively insensitive to cortisol, it does retain some sensitivity to potent synthetic steroids
Where does dexamethasone suppression not normally occur?
In adrenal tumours or ectopic ACTH production
What is the result of dexamethasone suppression not normally occurring in adrenal tumours or ectopic ACTH production mean?
Rules them out, suggesting the result is due to a pituitary tumour
What is Synacthen?
A synthetic analogue of ACTH
What does the intramuscular administration of Synacthen normally cause?
An increase in plasma cortisol by >200nmol/L
What does a normal response to Synacthen achieve?
The exclusion of Addison’s disease
What do the steroid receptors form?
Part of a family of nuclear DNA-binding proteins
What does the family of nuclear DNA-binding proteins formed by steroid receptors include?
The thyroid and vitamin D receptors
What do all steroid receptors have?
3 main regions
What are the 3 main regions of a steroid receptor?
- A hydrophobic hormone-binding region
- A DNA binding region
- A variable region
What is the DNA binding region of a steroid receptor rich in?
Cysteine and basic amino acids
What exists in the hormone binding regions of steroid receptors?
What is the % homology of the hormone bind region of the glucocorticoid receptor with the mineralocorticoid receptor?
What is the % homology of the hormone bind region of the glucocorticoid receptor with the androgen receptor?
What is the % homology of the hormone bind region of the glucocorticoid receptor with the oestrogen receptor?
What is the % homology of the hormone bind region of the glucocorticoid receptor with the thyroid receptor?
What is the result of the sequence homology of steroid receptors?
Cortisol will bind to the mineralocorticoid and androgen receptors with low affinity
When may cortisol binding to mineralocorticoid and androgen receptors be significant?
When high levels of hormone present
What does aldosterone do?
- Stimulates Na + reabsorption in exchange for K + (or H + )
- Stimulates growth and development of male genital tract and male secondary sexual characteristics, including height, body shape, facial and body hair, lower voice pitch
- Anabolic effects on muscle protein
What does over-secretion of aldosterone cause?
- Increases Na + and water retention
- Loss of K +
- In females-
- Hair growth (hirsutism)
- Menstrual problems
- Increased muscle bulk
- Deepening voice
What does an increased Na + and water retention, and loss of K + cause?
Hypertension and muscle weakness
What does under secretion of aldosterone cause?