Theme 5: investigating the endocrine system Flashcards
What are the 3 types of hormones?
- Peptide hormones e.g PTH, ACTH, TSH are generally released from anterior pituitary
- Steroid hormones e.g testerosterone, cortisol are released from gonads and adrenal glands
- Tyrosine-based hormones e.g thyroxine, T3, T4 released from thyroid gland
Explain feedback regulation in endocrine systems
- Hypothalamus produces a signal that tells the anterior pituitary to produce another signal or hormone that travels to the endocrine organ and produce the end-hormone (positive feedback)
- end-hormone will feedback and inhibit the stimulus from the hypothalamus (negative feedback)
Hypothalamus –> pituitary –> target organ
How do we measure thyroid function?
we measure TBG (thyroxine-binding globulin)
if the level of TBG changes, this results in a change in the level of free hormone
What are some causes of a decreased plasma TBG concentration
- genetic causes
- malnutrition
- malabsorption
- acromegaly
- cushings disease
- high dose corticosteroids
- severe illness
- androgens
What are some causes of a increased plasma TBG concentration
- genetic causes
- pregnancy
- oestrogen
What would you expect of thyroid hormones in pituitary failure?
low TSH and low thyroxine
What would you expect of thyroid hormones in an unresponsive thyroid?
high TSH and low thyroxine
primary hypothyroidism –> thyroid cannot produce enough thyroxine
What would you expect to see of thyroid hormones in pituitary gland overproduction or feed back fails?
increase TSH and thyroxine
primary hyperthyroidism
What would you expect to see of thyroid hormones in secondary hypothyroidism?
normal TSH with a low free T4
most patients with secondary hypothyroidism have a normal TSH so you can miss this with just TSH testing
Why should TFTs only be requested if thyroid dysfunction is suspected?
- patients suffering from non-thyroidal illness may show abnormalities within their thyroid function tests, despite being euthyroid
- “sick euthyroid disease”
- so there is a poor predictive value in ill patients
How often should we repeat TFTs in healthy persons?
3 years
What is the standard frequency of TFT testing in a patient with hyperthyroid caused by grave’s disease?
- 1-2 months after radioactive iodine
- if patient remains thyrotoxic then biochemical monitoring to continue at 4-6 week intervals
- OR following thyroidectomy for grave’s disease, serum TSH should be measured 6-8 weeks after post op
In hypothyroidism, what is the minimum length of time to achieve stable concentrations after a change in dose of thyroxine?
2 months so TFTs should not normally be assessed before this period has elapsed
How often should patients on longterm thyroxine therapy have their TSH checked?
Annually
in non-competitive assays, what is the relationship between tracer binding and concentration?
directly proportional
in competitive assays, what is the relationship between tracer binding and concentration?
Labelled antibody competes with hormone to bind to captured antibody so as concentration increases, the quantity of labelled antibody binding decreases.
How can interference occur in immunoassays?
- due to cross linking antibodies found in patients serum
- different type of antibody binds to capture antibody and block the binding site for the epitope on the hormone
What are the two types of adrenal medullary tumours?
- pheochromocytomas (adults)
2. neuroblastoma (children)
Which cells become cancerous in pheochromocytoma?
tumour of neuroendocrine chromaffin cells
What are the clinical features of a pheochromocytoma and why?
excessive and often episodic release of catecholamines may result in:
- hypertension
- sweating, pallor
- panic attacks
- headaches
- abdominal pain
How do we diagnose pheochromocytoma?
- plasmametanephrines
unstable, collect on ice, not available in many labs - 24 hour urine fractionated metanephrines
usual problems of 24 hr collections
What is Whipple’s triad?
Triad determining if a patient is hypoglycaemic
- Signs and symptoms of hypoglycaemia
- Resolution of symptoms once glucose level rises
- Low plasma glucose level
What are the autonomic signs and symptoms of hyperglycaemia?
Symptoms:
- hunger
- sweating
- anxiety
- paraesthesias
- palpitations
- tremulousness
Signs:
- pallor
- tachycardia
- widened pulse pressure
What are the neuroglycopenic signs and symptoms of hyperglycaemia?
Signs:
- cortical blindness
- hypothermia
- seizures
- coma
Symptoms:
- weakness, fatigue
- dizziness
- headache
- confusion
- behavioural changes
- blurred vision, diplopia
What are some endogenous causes of hyperglycaemia?
- critical organ failure
- sepsis
- hormone deficinecies
- insulinoma
What are some exogenous causes of hyperglycaemia?
most common is the management of diabetes - these patients are at high risk of hyperglycaemia
other causes are alcohol and toxins
What is an insulinsoma?
- insulin secreting tumour
- most common tumours arising from islets of langerhans
- highest incidence between 40-60yr, F»M
How do we diagnose an insulinoma?
a simple fasting blood test. take blood when patient is hyperglycaemia
can be diagnosed by low blood sugar, high insulin or high levels of C-peptide
What is the difference between cushing’s syndrome and cushings disease?
disease - specifically denotes the ACTH pituitary secreting cause
syndrome - nomenclature to describe any form of cushings
Why does cushings lead to obesity?
because the excess cortisol effects the metabolism of proteins, carbohydrates and fats
Explain the hypothalamic-pituitary-adrenal axis
- In hypothalamus, CRH is released
- Tells pituitary to produce ACTH which tells adrenal gland to produce glucocorticoids
- negative feed back on higher centres
What are the 4 causes of excess cortisol production?
- ACTH pituitary tumour/ Cushing’s disease
- Adrenal adenoma or carcinoma produces excess cortisol autonomously (not under the influence of ACTH)
- Ectopic (outside pituitary) –> ACTH producing tumour often from lung
- exogenous cause
Why is there no negative feedback in an ACTH pituitary tumour or cushing’s disease?
-adrenal glands are told to produce more cortisol
-there is no negative feedback –> the ACTH secreting tumour is autonomous and will not be subjected to negative feedback
=secondary cortisol excess
How can an adrenal adenoma or carcinoma on the left lead to atrophy of the contralateral adrenal gland?
Adrenal adenoma or carcinoma produces excess cortisol autonomously (not under influence of ACTH) so we get suppression of ACTH from the pituitary gland which can lead to atrophy of the contralateral adrenal gland
=primary cortisol excess
What is ectopic ACTH secretion commonly associated with?
- benign carcinoid tumours of the lung
- small cell tumours of the lung
- islet cell tumours of the pancreas
- medullary carcinoma of the thyroid
- tumours of the thymus gland
What is meant by a primary disorder?
problem with end organ e.g primary hypothyroid means problem is in thyroid
What is meant by a secondary disorder?
problem further away from organ usually in pituitary
How can we confirm cushings?
- 9am cortisol
- overnight dexamethoasone
