Endocrinology Flashcards
Which hormones does the anterior pituitary gland release ?
- Thyroid stimulating hormone (TSH)
- Adrenocorticotropic hormone (ACTH)
- Follicle stimulating hormone (FSH) and luteinising hormone (LH)
- Growth hormone (GH)
- Prolactin
Which two hormones does the posterior pituitary gland release ?
- Antidiuretic hormone (ADH)
- Oxytocin
The hypothalamus releases thyrotropin-releasing hormone (TRH). This stimulates the anterior pituitary to release thyroid stimulating hormone (TSH). This in turn stimulates to thyroid gland to release what ?
Triiodothyronine (T3) and thyroxine (T4)
What effect do T3 and T4 have on the hypothalamus and anterior pituitary? What type of feedback is this ?
They suppress the release of TRH and TSH resulting in lower amounts of T3 and T4. If there are lower levels of T3 and T4 there is less suppression of TRH and TSH thus T3 and T4 levels go up. This is negative feedback.
The hypothalamus releases corticotrophin release hormone (CRH), what other hormones does this stimulate ?
CRH > Adrenocorticotropic hormone (ACTH) > Cortisol
What type of feedback controls the adrenal axis ?
Negative feedback
Cortisol is released in pulses and in response to stressful stimuli (it is a “stress hormone”). It has diurnal variation where it typically peaks in the morning and is at its lowest rate in the evening. Name 5 actions of cortisol within the body ?
- Inhibits the immune system
- Inhibits bone formation
- Raises blood glucose
- Increases metabolism
- Increases alertness
Growth hormone axis ?
Growth hormone releasing hormone (GHRH) is released from the hypothalamus > This stimulates growth hormone (GH) release form the pituitary > Growth hormone stimulates the release of insulin-like growth factor 1 (IGF-1) from the liver.
4 main functions of growth hormone ?
- Stimulates muscle growth
- Increases bone density and strength
- Stimulates cell regeneration and reproduction
- Stimulates growth of internal organs
Parathyroid hormone (PTH) is released form the four parathyroid glands usually in response to what + what else can it be released in response to?
Low serum calcium. It is also released in response to low magnesium and high serum phosphate.
Role of PTH ?
To increase serum calcium concentration
Name 3 ways that PTH increases serum calcium concentration ?
- PTH increases the activity and number of osteoclasts in bone, causing reabsorption of calcium from the bone into the blood thereby increasing serum calcium concentration
- PTH stimulates an increase in calcium reabsorption in the kidney meaning that less calcium is excreted in the urine
- PTH also stimulates the kidneys to convert vitamin D3 into calcitriol, which is the active form of vitamin D that promotes calcium absorption from food in the small intestine
Cholecalciferol is made in the skin following UVB light exposure. How can it end up as calcitriol ?
It is converted into calcifediol in the liver. Then this is converted into calcitriol in the kidneys.
When serum calcium is high this suppresses the release of PTH. This is an example of what type of feedback ?
Negative feedback
Where in the kidney is renin secreted ?
The juxtaglomerular cells that sit in the afferent (and some in the efferent) arterioles in the kidney.
What do the juxtaglomerular cells sense in relation to renin secretion ?
Blood pressure
What is renin ? Explain the RAAS ?
Renin is an enzyme that converts angiotensinogen (released by the liver) into angiotensin I. Angiotensin I is converted to angiotensin II in the lungs by ACE. Angiotensin II acts on blood vessels to cause vasoconstriction and it also stimulates the release of aldosterone from the adrenal glands.
Aldosterone is a mineralocorticoid steroid hormone. It acts on the nephrons of the kidneys to ?
- Increase sodium reabsorption from the distal tubule
- Increase potassium secretion from the distal tubule
- Increase hydrogen secretion from the collecting ducts
Why does increased sodium reabsorption increase blood pressure ?
Water follows it by osmosis. This leads to an increase in intravascular volume and subsequently BP.
What is Cushing’s syndrome and what is Cushing’s disease ?
Cushing’s syndrome is used to refer to the signs and symptoms that develop after prolonged abnormal elevation of cortisol. Cushing’s disease is used to refer to the specific condition where a pituitary adenoma (tumour) secretes excessive ACTH. Cushing’s disease causes a Cushing’s syndrome, but Cushing’s syndrome is not always caused by a Cushing’s disease.
Features of Cushing’s syndrome ?
Round in the middle with thin limbs:
- Round “moon” face
- Central obesity
- Abdominal striae (stretch marks)
- “Buffalo hump” (fat pad on upper back)
- Proximal limb muscle wasting
High levels of stress hormone:
- HTN
- Cardiac hypertrophy
- Hyperglycaemia (type 2 diabetes)
- Depression
- Insomnia
Extra effects:
- Osteoporosis
- Easy bruising and poor skin healing
Causes of Cushing’s syndrome (name four) ?
- Exogenous steroids (in pts on long term high dose steroid medications)
- Cushing’s disease (a pituitary adenoma releasing excessive ACTH)
- Adrenal adenoma (a hormone secreting adrenal tumour
- Paraneoplastic Cushing’s
What is Paraneoplastic Cushing’s and what is the most common cause ?
When excess ACTH is released from a cancer (except in the pituitary) and stimulates excessive cortisol release. ACTH from somewhere other than the pituitary is called “ectopic ACTH”. Small cell lung cancer is the most common cause.
Test for diagnosing Cushing’s syndrome ?
Dexamethasone suppression test (DST)
Briefly describe how the dexamethasone suppression test works ?
Initially the pt is given the “low dose” test. If the low dose test is normal, Cushing’s can be excluded. If the low dose test is abnormal, then a high dose test is performed to differentiate between the underlying causes.
To perform the test the pt takes a dose of dexamethasone (a synthetic glucocorticoid steroid) at night and their cortisol and ACTH are measured in the morning. The intention is to find out whether the dexamethasone suppresses their normal morning spike of cortisol.
Normal response for low dose DST ?
Dexamethasone suppresses the release of cortisol by effecting negative feedback on the hypothalamus and pituitary. This means less CRH and ACTH are produced resulting in a low cortisol level. When the cortisol level is not suppressed, this is the abnormal result seen in Cushing’s syndrome
Effects of high dose DST on different causes of Cushings syndrome (include results in table at the end) ?
- In Cushing’s disease (pituitary adenoma) the pituitary still shows some response to negative feedback and the high dose (8mg) of dexamethasone is enough to suppress cortisol
- Where there is an adrenal adenoma, cortisol production is independent from the pituitary. Therefore, cortisol is not suppressed, however ACTH is suppressed by negative feedback on the hypothalamus and pituitary gland.
- Where there is ectopic ACTH , neither cortisol or ACTH will be suppressed because the ACTH production is independent of the hypothalamus or pituitary gland
- Pituitary adenoma, ACTH = suppressed, Cortisol = suppressed
- Adrenal adenoma, ACTH = suppressed, Cortisol = not suppressed
- Ectopic ACTH, ACTH = not suppressed, cortisol = not suppressed
Other investigations for Cushing’s syndrome ?
24 hr urinary free cortisol can be used as an alternative to the dexamethasone suppression test to diagnose Cushing’s syndrome but it does not indicate the underlying cause and is cumbersome to carry out.
Other investigatons:
- FBC (raised WCC) and electrolytes (potassium may be low if aldosterone is also secreted by an adrenal adenoma)
- MRI brain for pituitary adenoma
- Chest CT for small cell lung cancer
- Abdominal CT for adrenal tumours
Treatment of Cushing’s syndrome ?
The main treatment is to remove the underlying cause (surgically remove the tumour)
- Trans-sphenoidal (through the nose) removal of pituitary adenoma
- Surgical removal of adrenal tumour
- Surgical removal of tumour producing ectopic ACTH
If surgical removal of the cause is not possible another option is to remove both adrenal glands and give the pt replacement steroid hormones for life
What is Addison’s disease + what else is it called?
A specific condition where the adrenal glands have been damaged, resulting in a reduction in the secretion of cortisol and aldosterone. It is also called primary adrenal insufficiency.
Most common cause of Addison’s disease ?
Autoimmune.
What is secondary adrenal insufficiency, what is it the result of and what can cause this ?
Inadequate ACTH stimulating the adrenal glands, resulting in the low cortisol release. It is the result of loss or damage to the pituitary gland and can be caused by surgery to remove a pituitary tumour, infection, loss of blood flow or radiotherapy.
What is Sheehan’s syndrome ?
Pituitary gland necrosis due to massive blood loss during childbirth.
What is tertiary adrenal insufficiency, what is it normally caused by + how does this happen and how can this be prevented from happening ?
Inadequate CRH release by the hypothalamus. This is usually caused by pts being on long term oral steroids (for more than 3 weeks) causing suppression of the hypothalamus. When the exogenous steroids are suddenly withdrawn the hypothalamus does not “wake up” fast enough and endogenous steroids are not adequately produced. Therefore long term steroids should be tapered slowly to allow time for the adrenal axis to regain normal function.
Name 5 symptoms of adrenal insufficiency ?
- Fatigue
- Nausea
- Cramps
- Abdominal pain
- Reduced libido
Name 2 signs of adrenal insufficiency ?
- Bronze hyperpigmentation of the skin (ACTH stimulates melanocytes to produce melanin)
- Hypotension (particularly postural hypotension)
Investigations for adrenal insufficiency ?
- Hyponatraemia is a key biochemical clue. Sometimes it is the only presenting feature of adrenal insufficiency.
- Hyperkalaemia is also possible
- The short synacthen test is the test of choice to diagnose primary adrenal insufficiency
- ACTH levels - In primary adrenal failure the ACTH level is high as the pituitary is trying very hard to stimulate the adrenal glands without any negative feedback in the absence of cortisol. In secondary adrenal failure the ACTH level is low as the reason the adrenal glands are not producing cortisol is that they are not being stimulated by ACTH.
- Adrenal autoantibodies - are present in 80% of autimmune adrenal insufficiency: adrenal cortex antibodies and 21-hydroxylase antibodies
- CT or MRI adrenal glands if suspecting an adrenal tumour, haemorrhage or other structural pathology. this is not routinely recommended by NICE for autimmune adrenal insufficiency.
- MRI pituitary gives further info about pituitary pathology.
Test of choice to diagnose primary adrenal insufficiency ?
Short synacthen test.
What is the short synacthen test (ACTH stimulation test) ?
It is ideally performed in the morning when the adrenal glands are most “fresh”. The test involves giving synacthen, which is synthetic ACTH. The blood cortisol is measured at baseline, 30 and 60 minutes after administration. The synthetic ACTH will stimulate healthy adrenal glands to produce cortisol and the cortisol level should at least double. A failure of cortisol to rise (less than double the baseline) indicates primary adrenal insufficiency (Addison’s disease)
What is the long synacthen test and why is it rarely used anymore ?
It was used to distinguish between primary adrenal insufficiency and adrenal atrophy secondary to prolonged under stimulation in secondary adrenal insufficiency. It involves giving an infusion of ACTH over a long period.
- In primary adrenal failure there is no cortisol response as the adrenals no longer function
- In adrenal atrophy (secondary adrenal insufficiency), the prolonged ACTH eventually gets the adrenals going again and cortisol rises.
This test is rarely used anymore because we can now measure ACTH levels and this indicates the underlying cause.
Treatment of adrenal insufficiency ?
Replacement steroids titrated to signs, symptoms and electrolytes. Hydrocortisone is a glucocorticoid hormone and is used to replace cortisol. Fludrocortisone is a mineralcorticoid hormone and is used to replace aldosterone if aldosterone is also insufficient.
Pts are given a steroid card and an emergency ID tag to alert emergency services that they are dependent on steroids for life. Doses should not be missed as they are essential to life. Doses are doubled during an acute illness to match the normal steroid response to illness.
What is an Addisonian crisis (AKA Adrenal Crisis) and how does it present ?
A term used to describe an acute presentation of severe Addisons, where the absence of steroid hormones leads to a life threatening presentation. They present with:
- Reduced consciousness
- Hypotension
- Hypoglycaemia, hyponatraemia and hyperkalaemia
- PTs can be very unwell
It can be the first presentation of Addison’s disease or triggered by infection, trauma or other acute illness in someone with established Addison’s. It can present in someone on long term steroids suddenly stopping those steroids.
Management of an Addisonian crisis ?
Do not wait to perform investigations and establish a definitive diagnosis before treating someone with a suspected Addisonian crisis as it is life threatening and they need immediate treatment.
Management:
- Intensive monitoring if unwell
- Parenteral steroids (i.e. IV hydrocortisone 100mg stat then 100mg every 6 hours)
- IV fluid resuscitation
- Correct hypoglycaemia
- Careful monitoring of electrolytes and fluid balance
Screening test for possible thyroid disease ?
Measure TSH levels. When TSH is abnormal, then you can measure T3 and T4 to find out more.
How is a pts TSH level affected in hyperthyroidism + is there an exception?
TSH is suppressed by the high thyroid hormones so you get a low TSH level. The exception is a pituitary adenoma that secretes TSH in which case it is high.
How is a pts TSH level affected in hypothyroidism and is there any exceptions to this ?
TSH is high as it is trying to stimulate more thyroid hormone release. The exception is a pituitary or hypothalamic cause of the hypothyroid (secondary hypothyroidism), in which case the TSH level will be low.
Produce a graph indicating TSH and T3&T4 levels in pts with hyperthyroidism, primary hypothyroidism and secondary hypothyroidism ?
Hyperthyroidism, TSH = low, T3&T4 = high
Primary hypothyroidism, TSH = high, T3&T4 = low
Secondary hypothyroidism, TSH = low, T3&T4 = low
What are antithyroid peroxidase (anti-TPO) antibodies ?
Antibodies against the thyroid gland itself. They are the most relevant thyroid autoantibody in autoimmune thyroid disease. They are usually present in Grave’s disease and Hashimoto’s thyroiditis.
What are antithyroglobulin antibodies ?
Antibodies against thyroglobulin, a protein produced and extensively present in the thyroid gland. Measuring them is of limited use as they can be present in normal individuals. They are usually present in Grave’s disease, Hashimoto’s thyroiditis and thyroid cancer.
What are TSH receptor antibodies ?
Autoantibodies that mimic TSH, bind to the TSH receptor and stimulate thyroid hormone release. They are the cause of Grave’s disease and so will be present in this condition.
How can an ultrasound be useful in assessing a thyroid ?
It can be useful in diagnosing thyroid nodules and distinguishing between cystic (fluid filled) and solid nodules. US can also be used to guide a biopsy of the lesion.
What are radioisotope scans used for in relation to the thyroid and how does this work ?
They are used to investigate hyperthyroidism and thyroid cancers.
Radioactive iodine is given orally or IV and travels to the thyroid where it is taken up by the cells. Iodine is normally used by thyroid cells to produce thyroid hormones. The more active the thyroid cells, the faster the radioactive iodine is taken up. A gamma camera is used to detect gamma rays emitted from the radioactive iodine. The more gamma rays that are emitted from an area the more radioactive iodine has been taken up. This gives really useful functional information about the thyroid gland:
- Diffuse high uptake is found in Grave’s disease
- Focal high uptake is found in toxic multinodular goitre and adenomas
- “Cold” areas (i.e. abnormally low uptake) can indicate thyroid cancer
