Investigations of Endocrine System Flashcards
What are hormones secreted by?
endocrine glands
A hormone can only influence cells that have…?
specific target receptors for that particular hormone
Peptide hormones:
- examples?
- where are they generally released from?
- PTH, ACTH, TSH
- Generally released from anterior pituitary lobe
Steroid hormones:
- examples?
- where are they generally released from?
- precursor?
- Testosterone, Oestradiol, Cortisol
- Released from gonads and adrenal glands
- precursor is generally cholesterol
What are the 2 types of tyrosine-based hormones?
Thyroxine (T4) and Triiodothyronine (T3)
What are the 3 ways in which a steroid hormone can interact with a cell?
- The classical model
- Receptor-mediated endocytosis
- Signalling through cell-surface receptors
Describe the ‘classical model’ method in which a steroid hormone can interact with a cell?
- The steroid hormone dissociates from its plasma carrier protein and diffuses across the cell membrane.
- After gaining entry to the cell, the free hormone binds to an intracellular receptor and alters gene transcription.
Describe how a steroid hormone can interact with a cell via receptor-mediated endocytosis
- The steroid hormone, bound to its plasma carrier protein, is brought into the cell via a cell-surface receptor.
- The complex is broken down inside the lysosome, and free steroid hormone diffuses into the cell, where it subsequently exerts its action at the genomic level or undergoes metabolism
Describe how a steroid hormone can interact with a cell via signalling through cell surface receptors
- The free steroid hormone alters intracellular signalling by binding to cell-surface receptors.
- The steroid hormone could exert these effects directly or could alter signalling by blocking the actions of peptide hormones.
What is TBG? Where is it produced
Thyroxine-binding globulin; a globulin protein that reversibly binds thyroid hormones in circulation. Produced in liver.
How does TBG affect thyroid function tests?
- Only the ‘free’, unbound forms of thyroid hormones are physiologically active
- TBG binds thyroid hormones; if the level of TBG changes (e.g. due to conditions), this results in a change in the level of the free hormones.
- Therefore, measurement of total hormone levels can be misleading
Causes of abnormal plasma TBG concs:
Describe TSH and T4 levels in:
- 2ary hypothyroidism
- 1ary hypothyroidism
- 1ary hyperthyroidism
- low TSH and low T4
- high TSH and low T4
- low TSH and high T4
What does high TSH and high T4 levels indicate?
pituitary gland overproduction or failure of feedback
TSH front line testing
Why isnt free T4 tested in front line testing?
- Cost
- 2ary hypothyroidism is very rare
N.B. 2ary hypothyroidism can have a normal TSH with a low fT4.
What is non-thyroidal illness?
- Also known as Euthyroid sick syndrome
- Patients suffering from non-thyroidal illness may show abnormalities within their thyroid function tests, despite being euthyroid.
- TSH levels may be suppressed (<0.1 mU/L) in acute phases of illness
How often should we repeat TFTs in healthy people?
Every 3 years
How often should we repeat TFTs for those with hyperthyroid problems
How often should we repeat TFTs for those with hypothyroid problems
Which type of biochemical test is used for TFTs?
Immunoassays
Interference in immunoassays
What is a pheochromocytoma ?
a rare, usually benign tumour that develops in an adrenal gland (can be bilateral); tumour of the neuroendocrine chomaffin cells
What are the 2 types of adrenal medullary tumours (adults and children)?
- Phaeochromocytoma (adults)
- Neuroblastoma (children)
What is a neuroblastoma?
Neuroblastoma is a cancer that develops from immature nerve cells found in several areas of the body. Neuroblastoma most commonly arises in and around the adrenal glands, which have similar origins to nerve cells and sit atop the kidneys.
Which hormones are overproduced in pheochromocytomas?
Catecholamines (due to tumour being in adrenal medulla)
Clinical features of pheochromocytomas?
- Hypertension
- Sweating, pallor
- Panic attacks
- Headaches
- Abdominal pain
- Nothing
Which test is used to diagnose pheochromocytomas?
Plasma metanephrine test OR 24-hour urine fractionated metanephrines
What is a plasma metanephrine test?
A test to diagnose a condition of the adrenal glands. Measures the amount of metadrenaline and normetadrenaline in the blood. Metanephrine is a metabolite of epinephrine.
What follow up tests are used to diagnose pheochromocytomas?
- Clonidine suppression test
- Plasma Chromogranin A
- MRI or CT of adrenals
- MIBG scan
- Genetic counselling and screening forMEN mutations in young patients, or those with a family history
What is a clonidine suppression test?
- Used to diagnose pheochromocytomas
- Clonidine stimulates alpha adrenoceptors in the brainstem
- This results in reduced sympathetic outflow from CNS (i.e. suppress plasma normetadrenaline)
- Failure to suppress plasma normetadrenaline indicates autonomous release from tumour
What is a plasma chromogranin A test?
- CgA is a sensitive marker for neuroendocrine tumours
- CgA is a protein released from neuroendocrine cells
- Neuroendocrine tumours are frequently associated with increased concentrations of CgA
Catecholamines vs metanephrines?
metanephrines are made when your body breaks down catecholamines.
What is Whipple’s Triad?
A collection of three criteria that suggests a patient’s symptoms result from hypoglycemia that may indicate insulinoma:
- Symptoms known or likely to be caused by hypoglycemia, especially after fasting or heavy exercise
- A low plasma glucose measured at the time of the symptoms
- Relief of symptoms when glucose level is raised
What defines a low plasma glucose level?
- Non-diabetic <54 mg/dL (3 mmol/L)
- Diabetic < 63 mg/dL (3.5 mmol/L)
Signs and symptoms of hypoglycaemia
How does hypoglycaemia affect:
- Insulin
- Glucagon
- adrenaline
- GH
- cortisol
What are the effects of this?
- Insulin switched off
- Increased glucagon –> leads to breakdown of glycogen –> increases blood glucpse
- Increased adrenaline release; nervousness, sweating, faintness, fast heartbeat, tingling, nausea, trembling, and sometimes hunger.
- Increased GH
- Increased cortisol
What is the hormonal response to hypoglycaemia?
The hormonal response to a low blood sugar includes a rapid release of epinephrine and glucagon, followed by a slower release of cortisol and growth hormone. These hormonal responses to the low blood sugar may last for 6-8 hours – during that time the blood sugar may be difficult to control.
Why is adrenaline, GH and cortisol increased during hypoglycaemia?
- Adrenaline attempts to increase blood glucose concentration by a transient increase in hepatic glucose production and an inhibition of glucose disposal by insulin-dependent tissues.
- GH and cortisol have similar effects
All these 3 hormones attempt to increase blood glucose levels
Exogenous causes of hypoglycaemia?
- Poorly managed diabetes
- Alcohol
- Toxins
How can alcohol lead to hypoglycaemia?
- Alcohol broken down by alcohol dehydrogenase which uses the cofactor NADPH (the same used for gluconeogenesis)
- If you deplete your NAD cofactor in metabolising alcohol, then there is not enough to be used for gluconeogenesis predisposed to hypoglycaemia
Endogenous cause of hypoglycaemia?
Insulinoma
What is an insulinoma?
- An insulin secreting tumour
- Most common tumour arising from the islets of Langerhans
Diagnosis of an insulinoma?
Simple fasting blood test; blood needs to be measured when patient is hypoglycaemic. Test meaures: insulin, C-peptide and hydroxybutyrate (a chemical used by some cells of the body when sugar levels are low)
- Low blood sugar (less than 2.2 mmol/l)
- High insulin (6 microunits/ml or higher)
- High levels of C peptide (0.2nmol/l or higher)
What are the clinical features of Cushing’s syndrome?
- Obesity: moon face, central, shoulders
- Skin: thin, purple striae, bruising
- Hypertension;
- Due to stimulation of mineralocorticoid and glucocorticoid receptors
- Glucose intolerance;
- Cortisol is one of the regulators of glucose levels, high cortisol = glucose intolerance
- Menstrual disturbances/impotence
- Thin limbs/muscle weakness
- Back pain due to osteoporosis
- Psychiatric disturbances
- Depression, psychoses
CRH, ACTH and cortisol loop
What are the 4 causes of Cushing’s syndrome?
- 1ary cortisol excess
- 2ary cortisol excess
- Ectopic ACTH secretion
- Exogenous replacement of glucocorticoids
What can cause 1ary cortisol excess? Cortisol and ACTH levels?
- Adrenal adenoma/carcinoma secreting cortisol
- Autonomous production so not under influence of ACTH
- Negative feedback leads to suppression of ATCH; high cortisol but low ACTH
What can cause 2ary cortisol excess? ACTH and cortisol levels?
- ACTH secreting pituitary tumour (Cushing’s disease)
- High ACTH due to excess ACTH being produced
- Adrenal glands produce cortisol
- No negative feedback on tumour as tumour is autonomous
What is ectopic ACTH most commonly associated with?
- Benign carcinoid tumors 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
Why are random serum level tests for cortisol usually helpful?
- Follows a circadian pattern of secretion
- Peaks 30 minutes after waking
- Gradual decrease in serum cortisol throughout day reaching minimum around midnight
How can excess cortisol production (Cushing’s) be tested for?
Dexamethasone suppression test
What is the Dexamethasone suppression test?
- Dexamethasone is a glucocorticoid analogue (similar to cortisol) so should suppress ACTH
- This should, in turn, lower cortisol levels
- If cortisol is not lowered, then Cushing’s syndrome is present
