T1 L7: The Hypothalamic-pituitary adrenal axis Flashcards
What protein is 90% of cortisol bound to?
Cortisol binding globulin (CBG)
What re some effects of glucocorticooids?
- Maintenance of homeostasis during stress
- Inti-inflammatory
- Energy balance
- Formation of bone and cartilage
- Regulation of blood pressure
- Cognitive function, memory, conditioning
When are cortisol levels at the lowest and highest?
Highest just prior to waking up and lowest in the evening
What is an ultradian rhythm?
A recurrent period or cycle repeated throughout a 24-hour day
What is the affinity of the mineralocorticoid receptor (MR) for aldosterone vs cortisol?
The same
But the 11-beta-HSD-2 enzyme in the kidneys inactivates cortisol allowing more aldosterone to bind to that receptor
What is Cushing’s syndrome?
Too much cortisol
What are some symptoms of Cushing’s syndrome?
- Weight gain
- Central obesity
- Hypertension
- Insulin resistance
- Neuropsychiatric problems like depression
- Osteoporosis
What is the pathogenesis of Cushing’s syndrome?
Most common:
A pituitary adenoma affecting ACTH-secreting cells
Can also be caused by an adrenal tumour or by ‘ectopic ACTH’ caused by carcinoid tumours that secrete ACTH
Can be iatrogenic by steroid treatment
What are some clinical presentations of Cushing’s syndrome?
- Central obesity with thin arms and legs
- Fat deposition over upper back (buffalo hump)
- Rounded face
- Thin skin with easy bruising. pigmented striae
- Hirsutism
-Hypertension, diabetes, psychiatric manifestations, and osteoporosis
What is Pigmented Striae?
Stretch marks
What is Hirsutism?
Excessive hair growth
What is the pathogenesis of Addison’s disease?
Normally autoimmune in the UK but can be caused by metastases or TB which causes destruction of the adrenal glands
Can be secondary to pituitary disease (rare) or can be iatrogenic caused by high dose steroids which is suddenly stopped
What are some clinical features of Addison’s disease?
-Malaise
-Weakness
-Anorexia
-Weight loss
Increased skin pigmentation on knuckles, palmar creases, around the mouth, pressure areas, scars
-Hypotension
-Hypoglycaemia
What are type 1 autoimmune polyendocrine syndromes?
They’re rare and have an onset in infancy
Common phenotypes: Addison’s disease, Hypoparathyroidism, Candidiasis
What are type 2 autoimmune polyendocrine syndromes?
They’re more common than type 1 but still rare and have an onset during infancy or adulthood
Common phenotype: Addison’s disease, T1 diabetes, autoimmune thyroid disease
What are some autoimmune conditions that may happen together?
- T1 diabetes
- Autoimmune thyroid disease
- Coeliac disease
- Addison’s disease
- Pernicious anaemia
- Alopecia
- Vitiligo
- Hepatitis
- Premature ovarian failure
- Myasthenia gravis
What is Myasthenia gravis?
When antibodies destroy the communication between nerves and muscle, resulting in weakness of the skeletal muscles
What are some ways that the Hypothalamic-pituitary adrenal axis can be assessed?
Basal:
Blood cortisol and ACTH (Timing matters because of the circadian and ultraradian rhythm. It’s stressful)
Urine cortisol (A 24-hour collection is needed)
Salivary Cortisol (best to do because there is no stress so it just needs to be timed)
Dynamic tests:
Stimulated or suppressed tests
Describe a stimulated test to asses the Hypothalamic-pituitary adrenal axis
ACTH or CRH is injected or the patient is made hypoglycaemic to induce stress within the body
All are done to see how the body responds
Describe a supressed tests to asses the Hypothalamic-pituitary adrenal axis
Dexamethasone (a synthetic glucocorticoid) is administered to see what happens within the body
There wont be any suppression if the patient has Cushing’s syndrome
Why shouldn’t someone be investigated for endocrine conditions unless they have signs and symptoms?
Because there is a risk of false positive results
What imaging should be considered if someone has been confirmed to have Cushing’s syndrome?
Chest X-ray
MRI Pituitary
CT adrenals
When should someone with Addison’s be considered for imaging?
When there in concern it’s TB or metastatic cancer
What are some ways of managing Cushing’s syndrome?
Surgical:
Transsphenoidal adenectomy
Adrenalectomy
Or pituitary radiotherapy
What are some ways of managing Addison’s disease?
- Steroid hormone replacement therapy
- Patients with primary adrenal insufficiency also needs mineralocorticoid replacement therapy like Fludrocortisone
- Patients with secondary adrenal insufficiency will often be taking other hormone replacement therapy
When do steroid doses need to be increased when someone has Addison’s disease?
- During stress
- Operations/ post-operative period
Patients need IV of IM injections if they’re unable to take medication
