Endocrinology Flashcards
1
Q
Which hormones does the anterior pituitary gland release ?
A
- Thyroid stimulating hormone (TSH)
- Adrenocorticotropic hormone (ACTH)
- Follicle stimulating hormone (FSH) and luteinising hormone (LH)
- Growth hormone (GH)
- Prolactin
2
Q
Which two hormones does the posterior pituitary gland release ?
A
- Antidiuretic hormone (ADH)
- Oxytocin
3
Q
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 ?
A
Triiodothyronine (T3) and thyroxine (T4)
4
Q
What effect do T3 and T4 have on the hypothalamus and anterior pituitary? What type of feedback is this ?
A
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.
5
Q
The hypothalamus releases corticotrophin release hormone (CRH), what other hormones does this stimulate ?
A
CRH > Adrenocorticotropic hormone (ACTH) > Cortisol
6
Q
What type of feedback controls the adrenal axis ?
A
Negative feedback
7
Q
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 ?
A
- Inhibits the immune system
- Inhibits bone formation
- Raises blood glucose
- Increases metabolism
- Increases alertness
8
Q
Growth hormone axis ?
A
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.
9
Q
4 main functions of growth hormone ?
A
- Stimulates muscle growth
- Increases bone density and strength
- Stimulates cell regeneration and reproduction
- Stimulates growth of internal organs
10
Q
Parathyroid hormone (PTH) is released form the four parathyroid glands usually in response to what + what else can it be released in response to?
A
Low serum calcium. It is also released in response to low magnesium and high serum phosphate.
11
Q
Role of PTH ?
A
To increase serum calcium concentration
12
Q
Name 3 ways that PTH increases serum calcium concentration ?
A
- 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
13
Q
Cholecalciferol is made in the skin following UVB light exposure. How can it end up as calcitriol ?
A
It is converted into calcifediol in the liver. Then this is converted into calcitriol in the kidneys.
14
Q
When serum calcium is high this suppresses the release of PTH. This is an example of what type of feedback ?
A
Negative feedback
15
Q
Where in the kidney is renin secreted ?
A
The juxtaglomerular cells that sit in the afferent (and some in the efferent) arterioles in the kidney.
16
Q
What do the juxtaglomerular cells sense in relation to renin secretion ?
A
Blood pressure
17
Q
What is renin ? Explain the RAAS ?
A
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.
18
Q
Aldosterone is a mineralocorticoid steroid hormone. It acts on the nephrons of the kidneys to ?
A
- Increase sodium reabsorption from the distal tubule
- Increase potassium secretion from the distal tubule
- Increase hydrogen secretion from the collecting ducts
19
Q
Why does increased sodium reabsorption increase blood pressure ?
A
Water follows it by osmosis. This leads to an increase in intravascular volume and subsequently BP.
20
Q
What is Cushing’s syndrome and what is Cushing’s disease ?
A
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.
21
Q
Features of Cushing’s syndrome ?
A
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
22
Q
Causes of Cushing’s syndrome (name four) ?
A
- 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
23
Q
What is Paraneoplastic Cushing’s and what is the most common cause ?
A
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.
24
Q
Test for diagnosing Cushing’s syndrome ?
A
Dexamethasone suppression test (DST)
25
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.
26
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
27
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
28
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
29
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
30
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.
31
Most common cause of Addison's disease ?
Autoimmune.
32
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.
33
What is Sheehan's syndrome ?
Pituitary gland necrosis due to massive blood loss during childbirth.
34
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.
35
Name 5 symptoms of adrenal insufficiency ?
- Fatigue
- Nausea
- Cramps
- Abdominal pain
- Reduced libido
36
Name 2 signs of adrenal insufficiency ?
- Bronze hyperpigmentation of the skin (ACTH stimulates melanocytes to produce melanin)
- Hypotension (particularly postural hypotension)
37
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.
38
Test of choice to diagnose primary adrenal insufficiency ?
Short synacthen test.
39
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)
40
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.
41
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.
42
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.
43
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
44
Screening test for possible thyroid disease ?
Measure TSH levels. When TSH is abnormal, then you can measure T3 and T4 to find out more.
45
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.
46
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.
47
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
48
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.
49
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.
50
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.
51
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.
52
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
53
What is hyperthyroidism ?
When there is over-production of thyroid hormone by the thyroid gland.
54
What is thyrotoxicosis ?
Thyrotoxicosis refers to an abnormal and excessive quantity of thyroid hormone in the body
55
What is primary hyperthyroidism ?
Hyperthyroidism due to thyroid pathology. It is the thyroid itself that is behaving abnormally and producing excessive thyroid hormone
56
What is secondary hyperthyroidism ?
When the thyroid is producing excessive thyroid hormone as result of overstimulation by TSH. The pathology is in the hypothalamus or pituitary.
57
What is Grave's disease ?
An autoimmune condition where TSH receptor antibodies cause a primary hyperthyroidism. These TSH receptor antibodies are abnormal antibodies produced by the immune system that mimic TSH and stimulate the TSH receptors on the thyroid. This is the most common cause of hyperthyroidism in the developed world
58
What is toxic multinodular goitre (also known as Plummer's disease) ?
A condition where nodules develop on the thyroid gland that act independently of the normal feedback system and continuously produce excessive thyroid hormone.
59
What is exophthalmos, which thyroid disease causes it and how does it happen?
A term used to describe bulging of the eyeball out of the socket caused by Grave's disease. It is due to inflammation, swelling and hypertrophy of the tissue behind the eyeball that forces the eyeball forward.
60
What is pretibial myxoedema and what disease causes it ?
It is a dermatological condition where there are deposits of mucin under the skin on the anterior aspect of the leg (the pre-tibial area). This gives a discoloured, waxy, oedematous appearance to the skin over this area. It is specific to Grave's disease and is a reaction to the TSH receptor antibodies.
61
Name 7 universal features of hyperthyroidism ?
- Anxiety and irritability
- Sweating and heat intolerance
- Tachycardia
- Weight loss
- Fatigue
- Frequent loose stools
- Sexual dysfunction
62
Name 4 unique features of Grave's disease ? These features all relate to the presence of TSH receptor antibodies
- Diffuse goitre (without nodules)
- Graves eye disease
- Bilateral exopthalmos
- Pretibial myxoedema
63
Name 3 unique features of toxic multinodular goitre ?
- Goitre with firm nodules
- Most pts are aged over 50
- Second most common cause of thyrotoxicosis (after Grave's)
64
What is a solitary thyroid nodule and how are they treated ?
This is where a single abnormal thyroid nodule is acting alone to release thyroid hormone. The nodules are usually benign adenomas. They are treated with surgical removal of the nodule.
65
What is De Quervain's thyroiditis ?
The presentation of a viral infection with fever, neck pain and tenderness, dysphagia and features of hyperthyroidism. There is a hyperthyroid phase followed by a hypothyroid phase as the TSH level falls due to negative feedback. It is a self-limiting condition and supportive treatment with NSAIDs for pain and inflammation and beta blockers for symptomatic relief of hyperthyroidism is usually all that is necessary.
66
What is a thyroid storm and how is it treated ?
It is a rare presentation of hyperthyroidism. It is also known as a "thyrotoxic crisis". It is a more severe presentation of hyperthyroidism with pyrexia, tachycardia and delirium. It requires admission for monitoring and is treated the same way as any other presentation of thyrotoxicosis, although they may need supportive care with fluid resuscitation, anti-arrhythmic medication and B blockers
67
What is is the first line anti-thyroid drug for hyperthyroidism management, how does it work and when is remission achieved ?
Carbimazole.
It is usually successful in treating pts with Grave's disease, leaving them with normal thyroid function after 4 to 8 weeks. Once the pt has normal thyroid hormone levels, they continue on maintenance carbimazole and either:
- The dose is carefully titrated to maintain normal levels (known as "titration-block"
- The dose is sufficient to block all production and the pt takes levothyroxine titrated to effect (known as "block and replace")
Complete remission and the ability to stop taking carbimazole is usually achieved within 18 months of treatment.
68
What is the second line anti-thyroid drug, how is it used and why is carbimazole preferred?
Propylthiouracil. It is used in a similar way to carbimazole. There is a small risk of severe hepatic reactions, including death, which is why carbimazole is preferred.
69
Radioactive iodine is treatment option for hyperthyroidism. How does this work, how long can remission take/ are the any problems that can occur and what are the three strict rules ?
It involves drinking a single dose of radioactive iodine. This is taken up by the thyroid gland and the emitted radiation destroys a proportion of the thyroid cells. The reduction in the number of cells results in a decrease in thyroid hormone production and thus remission from the hyperthyroidism. Remission can take 6 months and pts can be left hypothyroid afterwards and require levothyroxine replacement.
There are strict rules where the pt:
- Must not be pregnant and are not allowed to get pregnant within 6 months
- Must avoid close contact with children and pregnant women for 3 weeks (depending on the dose)
- Limit contact with anyone for several days after receiving the dose
70
Why are B blockers used in hyperthyroidism management (include which drug is a good choice and why) ?
They are used to block the adrenalin related symptoms of hyperthyroidism. Propanolol is a good choice because it non-selectively blocks adrenergic activity as opposed to more "selective" b blockers that only act on the heart. They do not actually treat the underlying problem but control the symptoms whilst the definitive treatment takes time to work. They are particularly useful in pts with thyroid storm.
71
Definitive option for treating hyperthyroidism ?
Surgery to remove the whole thyroid or toxic nodules. This effectively stops the production of thyroid hormone, however the pt will be left hypothyroid post thyroidectomy and require levothyroxine replacement for life.
72
Name 5 treatment options for hyperthyroidism ?
- Carbimazole
- Propylthiouracil
- Radioactive Iodine
- B blockers
- Surgery
73
What is hypothyroidism ?
A term used to describe inadequate output of thyroid hormones by the thyroid gland.
74
Name 5 causes of hypothyroidism (give examples where possible) ?
Hashimotos thyroiditis
Iodine deficiency
Secondary to treatment of hyperthyroidism:
-Carbimazole
-Propythiouracil
-Radioactive iodine
-Thyroid surgery
Medications:
-Lithium - inhibits the production of thyroid
hormones in the thyroid gland and can cause a
goitre and hypothyroidism
-Amiodarone - interferes with thyroid hormone
production and metabolism, usually causing
hypothyroidism but it can also cause
thyrotoxicosis
Central causes (secondary hypothyroidism)
-This is where the pituitary gland is failing to
produce enough TSH. This is often associated
with a lack of other pituitary hormones such as
ACTH. This is called hypopituitarism and has
many causes:
-Tumours
-Infection
-Vascular (e.g. Sheehan syndrome)
-Radiation
75
What is Hashimoto's Thyroiditis (include what antibodies it is associated with ?
The most common cause of hypothyroidism in the developed world. It is caused by autoimmune inflammation of the thyroid. It is associated with antithyroid peroxidase (anti-TPO) antibodies and antithyroglobulin antibodies. Initially it causes a goitre after which there is atrophy of the thyroid gland
76
Most common cause of hypothyroidism in the developing world ?
Iodine deficiency
77
Name 7 presenting features of hypothyroidism ?
- Weight gain
- Fatigue
- Dry skin
- Coarse hair and hair loss
- Fluid retention (including oedema, pleural effusions and ascites)
- Amenorrhoea
- Constipation
78
Investigations for hypothyroidism with explanations and table ?
Primary hypothyroidism is caused by thyroid gland insufficiency. Thyroid hormones (i.e. free T3 and T4) will be low. TSH will be high because there is no negative feedback to the brain, so the pituitary, so the pituitary produces lots of TSH to try and get the thyroid working.
Secondary hypothyroidism is caused by pituitary pathology that results in a low production of TSH. Thyroid hormones will be low due to the low TSH.
PH, site of pathology = thyroid gland, TSH = high, T3&T4 = low
SH, site of pathology = pituitary gland, TSH = low, T3&T4 = low
79
Management of hypothyroidism (include drug, how it works and monitoring ) ?
Replacement of thyroid hormone with oral levothyroxine. Levothyroxine is synthetic T4, and metabolises to T3 in the body. The dose is titrated until TSH levels are normal. When starting levothyroxine, initially measure TSH levels monthly until stable, then once stable it can be checked less frequently unless they become symptomatic.
If the TSH level is high, the dose is too low and needs to be increased. If the TSH is low, the dose is too high and needs to be reduced.
80
What is acromegaly ?
The clinical manifestation of excessive growth hormone (GH)
81
Most common cause of acromegaly ?
A pituitary adenoma. This can be microscopic or can be a significantly sized tumour that causes compression of local structures.
82
Other cause of acromegaly ?
Rarely it can be secondary to a cancer, such as a lung or pancreatic cancer, that secretes ectopic growth hormone releasing hormone (GNRH) or GH.
83
The optic chiasm sits just above the pituitary gland. A pituitary tumour of sufficient size will start to press on the optic chiasm. What will this lead to ?
Bitemporal hemianopia
84
Presentation of acromegaly (three headings) ?
Space occupying lesion
- Headaches
- Visual field defect (bitemporal hemianopia)
Overgrowth of tissues
- Prominent forehead and brow ("frontal bossing")
- Large nose
- Large tongue ("macroglossia")
- Large hands and feet
- Large protruding jaw ("prognathism")
- Arthritis from imbalanced growth of joints
GH can cause organ dysfunction
- Hypertrophic heart
- Hypertension
- Type 2 diabetes
- Colorectal cancer
85
Treatment of acromegaly (definitive treatment and medications)?
Trans-sphenoidal (through the nose and sphenoid bone) surgical removal of the pituitary tumour is the definitive treatment of acromegaly secondary to pituitary adenomas. Where acromegaly is caused by ectopic hormones from a pancreatic or lung cancer, surgical removal of these cancers is the treatment.
Medications:
- Pegvisonant - is a GH antagonist given daily by subcutaneous injection
- Somatostatin analogues - block GH release e.g. ocreotide
- Dopamine agonists - block GH release e.g. bromocriptine
Somatostatin is known as growth hormone inhibiting hormone. It is normally secreted by the brain, GI tract and pancreas in response to complex triggers. One of the functions of somatostatin is to block GH release from the pituitary gland. Dopamine also has an inhibitory effect on GH release, however not as potent as somatostatin.
86
How many parathyroid glands are there and where are they situated ?
There are four parathyroid glands situated in the four corners of the thyroid gland.
87
Which cells produce parathyroid hormone and what is it released in response to ?
The chief cells in the parathyroid glands. In response to hypocalcaemia
88
How does parathyroid hormone act to raise the blood calcium level (four points) ?
- Increasing osteoclast activity in bones (reabsorbing calcium from bones)
- Increasing calcium absorption form the kidneys
- Increasing calcium absorption from the gut
- Increasing vitamin D activity
Vit D acts to increase calcium absorption from the intestines. PTH acts on vit D to convert it into active forms. Therefore, vit D and parathyroid hormone act together to raise blood calcium levels.
89
Name some symptoms of hypercalcaemia ?
Note: In primary hyperparathyroidism, about 75% of people have no symptoms.
- Weakness and fatigue
- Depression
- Bone pain
- Muscle soreness (myalgias)
- Decreased appetite
- Feelings of nausea and vomiting
- Constipation
- Polyuria
- Polydipsia
- Cognitive impairment
90
Name four complications of long term hypercalcaemia ?
- Kidney stones
- Osteoporosis
- Cardiac arrhythmia's
- HTN
91
What causes primary hyperparathyroidism, what does it lead to and how is it treated ?
It is caused by uncontrolled PTH produced directly by a tumour of the parathyroid glands. This leads to hypercalcaemia: an abnormally high level of calcium in the blood. This is treated by surgically removing the tumour.
92
What is secondary hyperparathyroidism, what does it cause, how does this affect the parathyroid glands and how is it treated ?
This is where insufficient vit D or chronic renal failure leads to a low absorption of calcium from the intestines, kidneys and bones. This causes hypocalcaemia.
The PT glands react to the low serum calcium by producing more PTH. Over time the PT glands undergo hyperplasia so that they can produce more PTH. The glands become more bulky. The serum calcium level will be low or normal but the PTH will be high. This is treated by correcting the vit D deficiency or performing a renal transplant to treat renal failure.
93
What is tertiary hyperparathyroidism ?
This happens when secondary HPT continues for a long period of time. It leads to hyperplasia of the glands. The baseline level of PTH increases dramatically. Then when the cause of the secondary HPT is treated the PTH level remains high. This high level of PTH in the absence of the previous pathology leads to inappropriately high absorption of calcium in the intestines, kidneys and bones causing hypercalcaemia. This is treated by surgically removing part of the PT tissue to return the PTH level to normal.
94
Table for types of hyperparathyroidism with cause, PTH level and serum calcium level
Primary, cause = tumour, PTH = high, calcium = high
Secondary, cause = low vit d or ckd, PTH = high, calcium = low
Tertiary, cause = hyperplasia of PT gland, PTH = high, calcium = high
95
What is primary hyperaldosteronism (Conn's syndrome), how are serum renin levels affected /why and name 4 possible causes ?
It is when the adrenal glands are directly responsible for producing too much aldosterone. Serum renin will be low as it is suppressed by the high BP. There are several possible reasons for this:
- An adrenal adenoma secreting aldosterone (most common)
- Bilateral adrenal hyperplasia
- Familial hyperaldosteronism type 1 and type 2 (rare)
- Adrenal carcinoma (rare)
96
What is secondary hyperaldosteronism and name the main causes ?
Where excessive renin stimulates the adrenal glands to produce more aldosterone. Serum renin will be high.
There are several causes of high renin levels and they occur when the BP in the kidneys is disproportionately lower than the BP in the rest of the body:
- Renal artery stenosis (main cause)
- Heart failure
97
Renal artery stenosis is usually found in pts with atherosclerosis. How can this be confirmed (three possible investigations) ?
- Doppler US
- CT angiography
- Magnetic resonance angiography (MRA)
98
Best screening tool for someone you think has hyperaldosteronism + what would this show for primary and secondary hyperaldosteronism?
To check the renin and aldosterone levels then calculate a renin:aldosterone ratio
High aldosterone + low renin indicates primary hyperaldosteronism
High aldosterone + high renin indicates secondary hyperaldosteronism
99
3 other investigations that relate to the effects of aldosterone ?
- BP (HTN)
- Blood gases (alkalosis)
- Serum electrolytes (hypokalaemia)
100
If a high aldosterone level is found after following a hyperaldosteronism screen then you should investigate for the cause how ?
- CT or MRI to look for an adrenal tumour
| - Renal doppler ultrasound, CT angiogram or MRA for renal artery stenosis.
101
Management of hyperaldosteronism ?
Aldosterone antagonists:
- Eplerenone
- Spironolactone
Treat the underlying cause
- Surgical removal of the adenoma
- Percutaneous renal artery angioplasty via the femoral artery to treat renal artery stenosis
102
Tom Tip
Hyperaldosteronism is worth remembering as the most common cause of secondary HTN. If you have a pt with a high BP that is not responding to treatment consider screening for hyperaldosteronism with a renin:aldosterone ratio. One clue that could prompt you to test for hyperaldosteronism might be a low potassium however be aware that potassium levels may be normal.
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Where is anti-diuretic hormone (ADH) produced, where is it secreted, what is it also known as, what does it do and what is SIADH ?
It is produced in the hypothalamus and secreted by the posterior pituitary gland. It is also known as vasopressin. ADH stimulates water reabsorption from the collecting ducts of the kidneys. SIADH is a condition where there is inappropriately large amounts of ADH.
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Why can SIADH happen ?
It may be the result of the pituitary gland secreting too much ADH or the ADH may be coming from somewhere else for example a small cell lung cancer.
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What effect does SIADH have on serum sodium concentration and circulating blood volume ?
There is excessive water reabsorption in the collecting ducts due to excessive ADH. This water dilutes the sodium in the blood so you end up with hyponatraemia. This excessive water reabsorption is not usually significant enough to cause fluid overload, therefore you end up with euvolaemic hyponatraemia.
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Effect of SIADH on urine ?
The urine becomes more concentrated as less water is excreted by the kidneys therefore pts have a high urine osmolality and high urine sodium
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Symptoms of SIADH are non-specific, name 5 of these ?
- Headache
- Fatigue
- Muscle aches and cramps
- Confusion
- Severe hyponatraemia can cause seizures and reduced consciousness
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Name 6 causes of SIADH (it has many causes) and give examples where appropriate ?
- POST-OPERATIVE from major surgery (remember this for our surgical jobs)
- Infection, particularly atypical pneumonia and lung abscesses
- Head injury
- Medications (thiazide diuretics, carbamazepine, vincristine, cyclophosphamide, antipsychotics, SSRIs and NSAIDs)
- Malignancy, particularly small cell lung cancer
- Meningitis
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Initial diagnosis of SIADH ?
In a way, SIADH is a diagnosis of exclusion as we do not have a reliable test to directly measure ADH activity. Clinical examination will show euvolaemia. U&Es will show hyponatraemia. Urine sodium and osmolality will be high.
Other causes of hyponatraemia need to be excluded:
- Negative short synacthen test to exclude adrenal insufficiency
- No history of diuretic use
- No diarrhoea, vomiting, burns, fistula or excessive sweating
- No excessive water intake
- No CKD or AKI
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What is meant by establish the cause in SIADH ?
Sometimes the cause will be clear, for example a new medication, a chest infection or recent major surgery. This can be confirmed by treating the underlying cause and assessing whether the hyponatraemia resolves.
Perform a CXR as a first line investigation for pneumonia, lung abscess or lung cancer.
We have to suspect a malignancy in someone with persistent hyponatraemia with no clear cause, particularly in someone with a history of smoking, weight loss or other features of malignancy. If malignancy is suspected the NICE CKS (March 2015) recommend a CT thorax, abdomen and pelvis and MRI brain to find the malignancy.
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Management of SIADH ?
The aim is to establish and treat the cause of the SIADH. It is most common for medications to be the cause so if possible it is best to stop the causative medication. It is essential to correct the sodium slowly to prevent central pontine myelinolysis. Aim for a change in sodium of less than 10 mmol/L per 24 hours.
FLUID RESTRICTION involves restricting their fluid intake to 500mls to 1 litre. This may be enough to correct the hyponatraemia without the need for medications.
Tolvaptan. "Vaptans: are ADH receptor blockers. They are powerful and can casue a rapid increase in sodium. Therefore they are usually initiated by a specialist endocrinologist and require close monitoring, for example 6 hourly sodium levels.
Demeclocycline is a tetracycline antibiotic that inhibits ADH. It was used prior to the development of vaptans and is now rarely used for this purpose.
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What is central pontine myelinolysis ?
Usually a complication of long term severe hyponatraemia (< 120 mmols/L) being treated too quickly (> 10 mmol/L increase over 24 hours).
As blood sodium levels fall, water will move by osmosis across the B-B barrier and into the cells of the brain from the area of low concentration of solutes (the blood) to the area of high concentration of solutes (the brain). This causes the brain to swell. The brain adapts to this by reducing the solutes in the brain cells so that water is balanced across the B-B barrier and the brain does not become oedematous. This adaptation takes a few days. Therefore, if the hyponatraemia has been present and severe for a long time the brain cells will also have a low osmolality. This is not a problem until the blood sodium levels rapidly rise. When this happens water will rapidly shift out of the brain cells and into the blood. This causes two phases of symptoms:
First phase: this is due to the electrolyte imbalance. The pts presents as encephalopathic and confused. They may have a headache or nausea and vomiting. These symptoms often resolve prior to the onset of the second phase
Second phase: this is due to the demyelination of the neurones, particularly in the pons. This occurs a few days after the rapid correction of sodium. This may present as spastic quadriparesis, pseudobulbar palsy and cognitive and behavioural changes. There is a significant risk of death.
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Treatment of central pontine myelinolysis ?
Prevention is essential as treatment is only supportive once CPM occurs. A proportion of pts make a clinical improvement but most are left with some neurological deficit.
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What is diabetes insipidus ?
A lack of ADH or a lack of response to ADH. The prevents the kidneys from being able to concentrate the urine leading to polyuria and polydipsia. It can be classified as nephrogenic or cranial
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What is primary polydipsia ?
When a pt has a normally functioning ADH system but is drinking excessive quantities of water leading to excessive urine production.
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What is nephrogenic diabetes insipidus and what else can it be caused by ?
It is when the collecting ducts of the kidneys do not respond to ADH. It can also be caused by:
- Drugs, particularly lithium used in bipolar affective disorder
- Mutations in the AVPR2 gene on the X chromosome that codes for the ADH receptor
- Intrinsic kidney disease
- Electrolyte disturbance (hypokalaemia and hypercalcaemia)
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What is cranial diabetes insipidus and what causes it ?
When the hypothalamus does not produce ADH for the pituitary gland to secrete. It can be idiopathic, without a clear cause or it can be caused by:
- Brain tumours
- Head injury
- Brain malformations
- Brain infections (meningitis, encephalitis and TB)
- Brain surgery or radiotherapy
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Presentation of diabetes insipidus (5 points) ?
- Polyuria
- Polydipsia
- Dehydration
- Postural hypotension
- Hypernatraemia
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Investigations for diabetes insipidus ?
- Low urine osmolality
- High serum osmolality
- Water deprivation test
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What is the water deprivation test (also known as the desmopressin stimulation test) ?
The test of choice for diagnosing diabetes insipidus.
METHOD
Initially the pt should avoid taking in any fluids for 8 hours. This is referred to as fluid deprivation. Then, urine osmolality is measured and synthetic ADH (desmopressin) is administered. 8 hours later urine osmolality is measured again
RESULTS
In CRANIAL diabetes insipidus the pt lacks ADH. The kidneys are still capable of responding to ADH. Therefore initially the urine osmolality remains low as it continues to be diluted by excessive water secretion in the kidneys. Then when desmopressin is given the kidneys respond by reabsorbing water and concentrating urine, so the urine osmolality will be high.
In NEPHROGENIC diabetes insipidus the pt is unable to respond to ADH. They are diluting their urine with the excessive water secretion by the kidneys. Therefore the urine osmolality will be low initially and remain low even after the synthetic ADH is given.
In PRIMARY POLYDIPSIA the 8 hours of water deprivation will initially cause urine osmolality to be high even before the synthetic ADH is given. A high urine osmolality after 8 hours of water deprivation indicates no diabetes insipidus.
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Produce a table illustrating the results of a water deprivation test
Cranial DI, urine osmolality after deprivation = low, after ADH = high
Nephrogenic DI, after deprivation = low, after ADH = low
Primary polydipsia, after deprivation = high, after ADH = high
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Management of diabetes insipidus ?
If possible, treat the underlying cause. Mild cases can be managed conservatively without any intervention.
Desmopressin can be used in :
- Cranial DI to replace ADH
- Nephrogenic diabetes insipidus in higher doses under close monitoring
123
Which cells of the adrenal gland produce adrenaline ?
Chromaffin cells
124
What is a phaeochromocytoma ?
A tumour of the chromaffin cells that secretes unregulated and excessive amounts of adrenaline. In pts with phaeochromocyutoma the adrenaline tends to be secreted in bursts giving periiods of worse symptoms followed by more settled periods.
25% are familial and associated with multiple endocrine neoplasia type 2 (MEN 2)
125
What is the 10% rule to describe the patterns of pheochromocytomas ?
- 10% bilateral
- 10% cancerous
- 10% outside the adrenal gland
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Diagnosis of phaeochromocytomas ?
- 24 hour urine catecholamines
| - Plasma free metanephrines
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Why is measuring 24 hour urine catecholamines preferred to measuring serum catecholamines when investigating for phaeochromocytoma ?
Measuring serum catecholamines is unreliable as the level will naturally fluctuate and it will be difficult to interpret the result. Measuring 24 hour urine catecholamines gives an idea of how much adrenaline is being secreted by the tumour over the 24 hour period
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Why is plasma free metanephrines used instead of adrenaline as a test for phaeochromocytoma ?
Adrenaline has a short half life whereas metanephrines (a breakdown product of adrenaline) have a longer half life. This makes the level of metanephrines less prone to dramatic fluctuations and a more reliable diagnostic tool.
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Presentation of phaeochromocytoma ?
S+S tend to fluctuate with peaks and troughs relating to periods when the tumour is secreting adrenaline. Symptoms related to excessive adrenaline:
- Anxiety
- Sweating
- Headache
- HTN
- Tremor
- Palpitations, tachycardia and paroxysmal atrial fibrillation
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Management of phaeochromocytoma ?
- Alpha blockers (i.e. phenoxybenzamine)
- Beta blockers once established on alpha blockers
- Adrenalectomy to remove the tumour is the definitive management
Pts should have symptoms controlled medically prior to surgery to reduce the risk of the anaesthetic and surgery.
