Endocrine Flashcards
1
Q
The anterior pituitary gland releases:
A
- Thyroid Stimulating Hormone (TSH)
- Adrenocorticotropic Hormone (ACTH)
- Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH)
- Growth Hormone (GH)
- Prolactin
2
Q
The posterior pituitary releases:
A
Oxytocin
Antidiuretic Hormone (ADH)
3
Q
Explain the hormone cycle in the thyroid
A
The hypothalamus releases thyrotropin-releasing hormone (TRH). This stimulates the anterior pituitary to release thyroid stimulating hormone (TSH). This in turn stimulates the thyroid gland to release triiodothyronine (T3) and thyroxine (T4).
T3 and T4 are sensed by the hypothalamus and anterior pituitary, and they suppress the release of TRH and TSH. This results in lower amounts of T3 and T4. In this way, the level of thyroid hormone is closely regulated to keep it within normal limits. This is called negative feedback.
4
Q
Explain the hormonal cycle of the adrenal gland
A
Cortisol is secreted by the two adrenal glands, which sit above each kidney. The release of cortisol is controlled by the hypothalamus. Cortisol is released in pulses and in response to a stressful stimulus (it is a “stress hormone“). It has diurnal variation, which basically means that it is high and low at different times of the day. Typically cortisol peaks in the early morning, triggering us to wake up and get going, and is at it’s lowest late in the evening, prompting us to relax and fall asleep.
The hypothalamus releases corticotrophin release hormone (CRH). This stimulates the anterior pituitary to release adrenocorticotrophic hormone (ACTH). This in turn stimulates the adrenal gland to release cortisol.
The adrenal axis is also controlled by negative feedback. Cortisol is sensed by the hypothalamus and anterior pituitary, and it suppresses the release of CRH and ACTH. This results in lower amounts of cortisol. In this way, cortisol is closely regulated to keep it within normal limits.
5
Q
Cortisol has several actions within the body
WHat are these actions:
A
- Inhibits the immune system
- Inhibits bone formation
- Raises blood glucose
- Increases metabolism
- Increases alertness
6
Q
What is the phsyiology of GH
A
Growth hormone releasing hormone (GHRH) is released from the hypothalamus. This stimulates growth hormone (GH) release from the anterior pituitary. Growth hormone stimulates the release of insulin-like growth factor 1 (IGF-1) from the liver.
7
Q
Through this mechanism growth hormone works directly and indirectly on almost all cells of the body and has many functions. Most importantly growth hormone:
A
Stimulates muscle growth
Increases bone density and strength
Stimulates cell regeneration and reproduction
Stimulates growth of internal organs
8
Q
Explain the physiology of PTH
A
Parathyroid Hormone (PTH) is released from the four parathyroid glands (situated in four corners of the thyroid gland) in response to low serum calcium. It is also released in response to low magnesium and high serum phosphate. It’s role is to increase the 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 also stimulates an increase in calcium reabsorption in the kidneys meaning that less calcium is excreted in the urine.
Additionally, it 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.
These three effects of PTH (increased calcium absorption from bone, the kidneys and the small intestine) all help to raise the level of serum calcium. When serum calcium is high this suppresses the release of PTH (via negative feedback) helping to reduce the serum calcium level.
9
Q
Angiotensin II acts on blood vessels to cause ___________ This results in an increase in blood pressure.
Angiotensin II also stimulates the release of ___________ from the adrenal glands.
A
Angiotensin II acts on blood vessels to cause vasoconstriction. This results in an increase in blood pressure.
Angiotensin II also stimulates the release of aldosterone from the adrenal glands.
10
Q
Aldosterone is a mineralocorticoid steroid hormone. It acts on the nephrons in 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
11
Q
When sodium is reabsorbed in the kidneys water follows it by osmosis. This leads to an increase in _________ ________ and subsequently blood pressure.
A
When sodium is reabsorbed in the kidneys water follows it by osmosis. This leads to an increase in intravascular volume and subsequently blood pressure.
12
Q
The body ideally wants to keep blood glucose concentration is between?
A
4.4. and 6.1 mmol/l.
13
Q
What type of hormone is glucagon
A
catabolic
14
Q
Explain Ketogenesis
A
Ketogenesis occurs when there is insufficient glucose supply and glycogens stores are exhausted, such as in prolonged fasting.
The liver takes fatty acids and converts them to ketones. Ketones are water soluble fatty acids that can be used as fuel. They can cross the blood brain barrier and be used by the brain as fuel. Producing ketones is normal and not harmful in healthy patients when under fasting conditions or on very low carbohydrate, high fat diets. Ketones levels can be measured in the urine by “dip-stick” and in the blood using a ketone meter. People in ketosis have a characteristic acetone smell to their breath.
Ketone acids (ketones) are buffered in normal patients so the blood does not become acidotic. When underlying pathology (i.e. type 1 diabetes) causes extreme hyperglycaemic ketosis this results in a metabolic acidosis that is life threatening. This is called diabetic ketoacidosis.
15
Q
What i sType 1 Diabetes
What is triggered by?
A
Type 1 diabetes mellitus (T1DM) is a disease where the pancreas stops being able to produce insulin. What causes the pancreas to stop producing insulin is unclear. There may be a genetic component. When there is no insulin being produced, the cells of the body cannot take glucose from the blood and use it for fuel. Therefore the cells think the body is being fasted and has no glucose supply. Meanwhile the level of glucose in the blood keeps rising, causing hyperglycaemia.
It may be triggered by certain viruses, such as the Coxsackie B virus and enterovirus
16
Q
When does DKA occur
A
Diabetic ketoacidosis occurs in type 1 diabetes where the person is not producing adequate insulin themselves and is not injecting adequate insulin to compensate for this. It occurs when they body does not have enough insulin to use and process glucose. The main problems are ketoacidosis, dehydration and potassium imbalance.
17
Q
What is Ketoacidosis
A
As the cells in the body have no fuel and think they are starving they initiate the process of ketogenesis so that they have a usable fuel. Over time the patient gets higher and higher glucose and ketones levels. Initially the kidneys produce bicarbonate to counteract the ketone acids in the blood and maintain a normal pH. Over time the ketone acids use up the bicarbonate and the blood starts to become acidic. This is called ketoacidosis.
18
Q
How are people dehydrated in DKA
A
Hyperglycaemia overwhelms the kidneys and glucose starts being filtered into the urine. The glucose in the urine draws water out with it in a process called osmotic diuresis. This causes the patient to urinate a lot (polyuria). This results in severe dehydration. The dehydration stimulates the thirst centre to tell the patient to drink lots of water. This excessive thirst is called polydipsia.
19
Q
Explain the potassium imblance in people with DKA
A
Insulin normally drives potassium into cells. Without insulin potassium is not added to and stored in cells. Serum potassium can be high or normal as the kidneys continue to balance blood potassium with the potassium excreted in the urine, however total body potassium is low because no potassium is stored in the cells. When treatment with insulin starts patients can develop severe hypokalaemia (low serum potassium) very quickly and this can lead to fatal arrhythmias.
20
Q
Presentation of DKA
This is a life threatening medical emergency. The pathophysiology described above leads to:
A
- Hyperglycaemia
- Dehydration
- Ketosis
- Metabolic acidosis (with a low bicarbonate)
- Potassium imbalance
The patient will therefore present with symptoms of these abnormalities:
- Polyuria
- Polydipsia
- Nausea and vomiting
- Acetone smell to their breath
- Dehydration and subsequent hypotension
- Altered Consciousness
- They may have symptoms of an underlying trigger (i.e. sepsis)
21
Q
The most dangerous aspects of DKA are ________ ________ ________ and _______. These are what will kill the patient. Therefore the priority is _____ __________ to correct the dehydration, electrolyte disturbance and acidosis. This is followed by an insulin infusion to get the cells to start taking up and using glucose and stop producing ketones.
A
The most dangerous aspects of DKA are dehydration, potassium imbalance and acidosis. These are what will kill the patient. Therefore the priority is fluid resuscitation to correct the dehydration, electrolyte disturbance and acidosis. This is followed by an insulin infusion to get the cells to start taking up and using glucose and stop producing ketones.
22
Q
Diagnosing DKA
Check the local DKA diagnostic criteria for your hospital. To diagnose DKA you require:
A
- Hyperglycaemia (i.e. blood glucose > 11 mmol/l)
- Ketosis (i.e. blood ketones > 3 mmol/l)
- Acidosis (i.e. pH < 7.3)
23
Q
Treating DKA (FIG-PICK)
A
- F – Fluids – IV fluid resuscitation with normal saline (e.g. 1 litre stat, then 4 litres with added potassium over the next 12 hours)
- I – Insulin – Add an insulin infusion (e.g. Actrapid at 0.1 Unit/kg/hour)
- G – Glucose – Closely monitor blood glucose and add a dextrose infusion if below a certain level (e.g. 14 mmol/l)
- P – Potassium – Closely monitor serum potassium (e.g. 4 hourly) and correct as required
- I – Infection – Treat underlying triggers such as infection
- C – Chart fluid balance
- K – Ketones – Monitor blood ketones (or bicarbonate if ketone monitoring is unavailable)
24
Q
DKA
Remember as a general rule potassium should not be infused at a rate of more than __ mmol per hour.
A
Remember as a general rule potassium should not be infused at a rate of more than 10 mmol per hour.
25
What are the long term management of TYpe 1 Diabetes
**Patient education** is essential. Monitoring and treatment is relatively complex. The condition is life-long and requires the patient to fully understand and engage with their condition. It involves the following components:
* Subcutaneous insulin regimes
* Monitoring dietary carbohydrate intake
* Monitoring blood sugar levels on waking, at each meal and before bed
* Monitoring for and managing complications, both short and long term
Insulin is usually prescribed as a combination of a background, **long acting insulin given once a day** and **a short acting insulin injected 30 minutes before intake of carbohydrate (i.e. at meals).** Insulin regimes are initiated by a **diabetic specialist.**
Injecting into the same spot can cause a condition called **“lipodystrophy”,** where the subcutaneous fat hardens and patients do not absorb insulin properly from further injections into this spot. For this reason patients should cycle their injection sites.
26
Short term complications relate to immediate insulin and blood glucose management
Type 1 DM.
Hypoglycaemia
Hyperglycaemia (and DKA)
27
How can a type 1 diabteic patient become hypoglycaemic
Hypoglycaemia is a low blood sugar level. Most patients are aware of when they are hypoglycaemic by their symptoms, however some patients can be unaware until severely hypoglycaemic. Typical symptoms are tremor, sweating, irritability, dizziness and pallor. More severe hypoglycaemia will lead to reduced consciousness, coma and death unless treated.
Hypoglycaemia needs to be treated with a combination of **rapid acting glucos**e such as lucozade and **slower acting carbohydrates** such as biscuits and toast for when the rapid acting glucose is used up. Options for treating severe hypoglycaemia are **IV dextrose** and **intramuscular glucagon.**
28
How can a type 1 diabteic patient become hyperglycaemic
If the patient is hyperglycaemic but not in DKA then they may require their insulin dose to be increased. Patients will get to know their own individual response to insulin and be able to administer a dose to correct the hyperglycaemia. For example, they may learn that 1 unit of novorapid reduces their sugar level by around 4 mmol. Be conscious that it can take several hours to take effect and repeated doses could lead to hypoglycaemia.
If they meet the criteria for DKA then they need admission for treatment of DKA.
29
Macrovascular Complications of DM
Coronary artery disease is a major cause of death in diabetics
Peripheral ischaemia causes poor healing, ulcers and “diabetic foot”
Stroke
Hypertension
30
Microvascular Complications of DM
Peripheral neuropathy
Retinopathy
Kidney disease, particularly glomerulosclerosis
31
Infection Related Complications of DM
Urinary Tract Infections
Pneumonia
Skin and soft tissue infections, particularly in the feet
Fungal infections, particularly oral and vaginal candidiasis
32
What do we monitor in patients with DM
**HbA1c**
When we check HbA1c we are counting **glycated haemoglobin,** which is how much glucose is attached to the haemoglobin molecule. This is considered to reflect the average glucose level over the last 3 months because red blood cells have a lifespan of around 3-4 months. We measure it **every 3 – 6 months** to track progression of the patient’s diabetes and how effective the interventions are. It requires a blood sample sent to the lab, usually red top EDTA bottle.
**Capillary Blood Glucose**
This is measured using a little machine called a glucose meter that gives an immediate result. Patients with type 1 and type 2 diabetes rely on these machines for self-monitoring their sugar levels.
**Flash Glucose Monitoring (e.g. FreeStyle Libre)**
This uses a **sensor** on the skin that measures the glucose level of **interstitial** **fluid**. There is a **lag of 5 minutes** behind blood glucose. This sensor records the glucose readings at short intervals so you get a really good impression of what the glucose levels are doing over time. The user needs to use a “**reader**” to swipe over the sensor and it is the reader that shows the blood sugar readings. Sensors need replacing every 2 weeks for the **FreeStyle** **Libre** system. It is quite expensive and NHS funding is only available in certain areas at the time of writing. The 5 minute delay also means it is necessary to do capillary blood glucose checks if **hypoglycaemia** is suspected.
33
Describe some Non modifiable and modifiable RF of Type 2 DM
Non-Modifiable
* Older age
* Ethnicity (Black, Chinese, South Asian)
* Family history
Modifiable
* Obesity
* Sedentary lifestyles
* High carbohydrate (particularly refined carbohydrate) diet
34
Presentation
Consider type 2 diabetes
* Consider RF
* Fatigue
* Polydipsia and polyuria (thirsty and urinating a lot)
* Unintentional weight loss
* Opportunistic infections
* Slow healing
* Glucose in urine (on dipstick)
35
What is Oral Glucose Tolerance Test (OGTT)
An oral glucose tolerance test (OGTT) is performed in the morning prior to having breakfast. It involves taking a baseline **fasting plasma glucose result**, giving a **75g glucose drink** and then measuring plasma glucose 2 hours later. It tests the ability of the body to cope with a carbohydrate meal.
36
What is Pre diabetes
Pre-diabetes is an indication that the patient is heading towards diabetes. They do not fit the full diabetic diagnostic criteria but should be educated regarding diabetes and implement lifestyle changes to reduce their risk of progressing to diabetes. They are not currently recommended to start medical treatment at this point.
37
Pre-diabetes Diagnosis
Pre-diabetes can be diagnosed with a HbA1c or by “impaired fasting glucose” or “impaired glucose tolerance”. Impaired fasting glucose means that their body struggles to get their blood glucose levels in to normal range, even after a prolonged period without eating carbohydrates. Impaired glucose tolerance means their body struggles to cope with processing a carbohydrate meal.
* HbA1c – 42-47 mmol/mol
* Impaired fasting glucose – fasting glucose 6.1 – 6.9 mmol/l
* Impaired glucose tolerance – plasma glucose at 2 hours 7.8 – 11.1 mmol/l on an OGTT
38
Diabetes Diagnosis
Diabetes can be diagnosed if the patient fits the criteria on plasma glucose, an oral glucose tolerance test or HbA1c.
* HbA1c \> 48 mmol/mol
* Random Glucose \> 11 mmol/l
* Fasting Glucose \> 7 mmol/l
* OGTT 2 hour result \> 11 mmol/l
39
Name some dietary modification in type 2 DM
Vegetables and oily fish
Typical advice is low glycaemic, high fibre diet
A low carbohydrate may in fact be more effective in treating and preventing diabetes but is not yet mainstream advice
40
Lifestyle modifications for Type 2 DM
* Exercise and weight loss
* Stop smoking
* Optimise treatment for other illnesses, for example hypertension, hyperlipidaemia and cardiovascular disease
**Monitoring for Complications**
* Diabetic retinopathy
* Kidney disease
* Diabetic foot
41
SIGN Guidelines 2017 and NICE Guideline 2015 recommend the following HbA1c treatment targets:
* 48 mmol/mol for new type 2 diabetics
* 53 mmol/mol for diabetics that have moved beyond metformin alone
42
Explain the medical management for type 2 DM
* First line: **metformin titrated from initially 500mg** once daily as tolerated.
* Second line add: **sulfonylurea, pioglitazone, DPP-4 inhibitor or SGLT-2 inhibitor.** The decision should be based on individual factors and drug tolerance.
* Third line: T**riple therapy with metformin and two of the second line drugs** combined, or;
* **Metformin plus insulin**
SIGN Guidelines 2017 suggest the use of **SGLT-2 inhibitors and GLP-1 mimetics** (e.g. liraglutide) preferentially in patients with **cardiovascular disease.**
43
Metformin
Class:
Mechanism:
S/E:
Class: biguanide
Mechanism: increases insulin sensitivity and decreases liver production of glucose.
S/E:
* **Diarrhoea and abdominal pain**. This is dose dependent and reducing the dose often resolves the symptoms
* **Lactic acidosis**
* Does **NOT typically cause hypoglycaemia**
44
Does Metformin cause weight loss
No
It is considered to be “weight neutral” and does not increase or decrease body weight.
45
Pioglitazone
Class:
Mechanism:
S/E:
Class:thiazolidinedione
Mechanism: It increases insulin sensitivity and decreases liver production of glucose.
S/E:
* Weight gain
* Fluid retention
* Anaemia
* Heart failure
* Extended use may increase the risk of bladder cancer
* Does NOT typically cause hypoglycaemia
46
Sulfonylurea
Common drug:
Mechanism:
S/E:
Common drug:gliclazide
Mechanism: Sulfonylureas stimulate insulin release from the pancreas.
S/E:
* Weight gain
* Hypoglycaemia
* **Increased risk of cardiovascular disease and myocardial infarction** when used as monotherapy
47
Incretins (relevant for DPP-4 inhibitors and GLP-1 mimetics)
Mechanism
Incretins are hormones produced by the GI tract. They are secreted in response to large meals and act to reduce blood sugar. They:
* Increase insulin secretions
* Inhibit glucagon production
* Slow absorption by the GI tract
48
The main incretin is\_\_\_\_\_\_ _____ \_\_\_\_\_\_ Incretins are inhibited by an enzyme called “\_\_\_\_\_ _____ \_\_\_\_\_\_” (DPP-4).
The main incretin is **“glucagon-like peptide-1”** (GLP-1). Incretins are inhibited by an enzyme called **“dipeptidyl peptidase-4”** (DPP-4).
49
DPP-4 inhibitor
Common Drug
Mechanism
S/E
Common Drug: sitagliptin
Mechanism: It inhibits the DPP-4 enzyme and therefore increases GLP-1 activity.
S/E:
* GI tract upset
* Symptoms of upper respiratory tract infection
* Pancreatitis
50
GLP-1 mimetics
Examples
S/E
These medications mimic the action of GLP-1. A common GLP-1 mimetic is **“exenatide”. Exenatide** is given as a subcutaneous injection either twice daily by the patient or once weekly in a **modifiable-release** form. Another GLP-1 mimetic is **liraglutide**, which is given daily as a subcutaneous injection. They are sometimes used in combination with metformin and a sulfonylurea in overweight patients.
Notable Side Effects:
* GI tract upset
* Weight loss
* Dizziness
* Low risk of hypoglycaemia
51
SGLT-2 Inhibitors
Examples:
Mechamism:
S/E:
Examples: SGLT-2 inhibitors end with the suffix “-gliflozin”, such as empagliflozin, canagliflozin and dapagliflozin
Mechamism: The SGLT-2 protein is responsible for reabsorbing glucose from the urine in to the blood in the proximal tubules of the kidneys. SGLT-2 inhibitors block the action of this protein and cause glucose to be excreted in the urine.
S/E:
* **Glucoseuria** (glucose in the urine)
* Increased rate of urinary tract infections
* Weight loss
* **Diabetic ketoacidosis**, notably with only moderately raised glucose. This is a rare complication
* **Lower limb amputation** appears to be more common in patients on canagliflozin. It is not clear if this applies to other SGLT-2 inhibitors
52
Example of Rapid-acting Insulins
These start working after around 10 minutes and last around 4 hours
Novorapid
Humalog
Apidra
53
Example of Short-acting Insulins
These start working in around 30 minutes and last around 8 hours
Actrapid
Humulin S
Insuman Rapid
54
Example of Intermediate-acting Insulins
These start working in around 1 hour and last around 16 hours:
Insulatard
Humulin I
Insuman Basal
55
Example of Long-acting Insulins
These starts working in around 1 hour and lasts around 24 hours:
Lantus
Levemir
Degludec (lasts over 40 hours)
56
Examples of Combinations Insulins
These containing a rapid acting and an intermediate acting insulin. In brackets is the proportion of rapid to intermediate acting insulin:
Humalog 25 (25:75)
Humalog 50 (50:50)
Novomix 30 (30:70)
57
What is Cushing Syndrome and Cushings 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 Cushing’s Disease.
58
Cushing’s Syndrome Features
Round in the middle with thin limbs:
* Round “moon” face
* Central Obesity
* Abdominal striae
* Buffalo Hump (fat pad on upper back)
* Proximal limb muscle wasting
High levels of stress hormone:
* Hypertension
* Cardiac hypertrophy
* Hyperglycaemia (Type 2 Diabetes)
* Depression
* Insomnia
Extra effects:
* Osteoporosis
* Easy bruising and poor skin healing
59
Causes of Cushing’s Syndrome
* Exogenous steroids (in patients 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
**Paraneoplastic Cushing’s is when excess ACTH** is released from a cancer (not of 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 of paraneoplastic Cushing’s.**
60
what is the test used to diagnose cushings
The **dexamethasone suppression test** is the test of choice for diagnosing **Cushing’s Syndrome**. This involves initially giving the patient 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 patient takes a dose of **dexamethasone** (a synthetic glucocorticoid steroid) at night (i.e. 10pm) and their **cortisol and ACTH** is measured in the morning (i.e. 9am). The intention is to find out whether the **dexamethasone suppresses** their normal morning spike of **cortisol.**
61
What is the first line bochemical tests for cushings?
- Urine free cortisol (UFC)
**- 1mg overnight Dexamethasone Suppression test (ODST)**- If cortisol is high (\>50nmol/L): Cushing’s syndrome
**- 8mg High dose dexamethasone suppression test** - If cortisol is low: Pituitary adenoma (Cushing’s disease)
- **Plasma ACTH** - If high: Ectopic ACTH - If low: adrenal adenoma (independent of ACTH)
62
Other Ix for cushings
**24-hour urinary free cortisol c**an be used as an alternative to the dexamethasone suppression test to diagnose Cushing’s syndrome but does not indicate the underlying cause and is cumbersome to carry out.
* FBC (raised white cells) 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
63
Treatment for Cushinsh
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 patient replacement steroid hormones for life.
64
What is Addison’s Disease
Addison’s Disease refers to the specific condition where the adrenal glands have been damaged, resulting in a reduction in the secretion of cortisol and aldosterone. This is also called **Primary Adrenal Insufficiency.** The most common cause is **autoimmune.**
65
What is Secondary Adrenal Insufficiency
Secondary Adrenal Insufficiency is a result of inadequate ACTH stimulating the adrenal glands, resulting in low cortisol release. This is the result of loss or damage to the pituitary gland. This can be due to surgery to remove a pituitary tumour, infection, loss of blood flow or radiotherapy. There is also a condition called Sheehan’s syndrome where massive blood loss during childbirth leads to pituitary gland necrosis.
66
What is Tertiary Adrenal Insufficiency
**Tertiary Adrenal Insufficiency** is the result of inadequate **CRH** release by the **hypothalamus**. This is usually the result of patients 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.
67
Symptoms of adrenal insufficency
Fatigue
Nausea
Cramps
Abdominal pain
Reduced libido
68
Adrenal Insufficiency SIgns
* Bronze **hyperpigmentation** to skin (ACTH stimulates **melanocytes** to produce melanin)
* Hypotension (particularly postural hypotension)
69
Adrenal Insufficiency
Ix
* **Hyponatraemia** (low sodium) is a key biochemical clue. Sometimes the only presenting feature of adrenal insufficiency is hyponatraemia.
* **Hyperkalaemia** (high potassium) is also possible.
* **Early morning cortisol** (8-9am) has a role but is often falsely normal.
* **A short synacthen test** is the test of choice to diagnose adrenal insufficiency.
* **ACTH.** 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 autoimmune adrenal insufficiency: adrenal cortex antibodies and 21-hydroxylase antibodies
* **CT / MRI adrenals** if suspecting an adrenal tumour, haemorrhage or other structural pathology (not recommended by NICE for autoimmune adrenal insufficiency).
* **MRI pituitary** gives further information about pituitary pathology.
70
Explain Short Synacthen Test (ACTH stimulation test)
The **short synacthen test** is the test of choice for **adrenal insufficiency.** 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).**
71
What is Long Synacthen Test
The **long synacthen test** is rarely used anymore because we can now measure ACTH levels. 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.
Now we can simply measure **ACTH** and this indicates the underlying cause.
72
Treatment for adrenal insuffiency
Treatment of adrenal insufficiency is with replacement steroids titrated to signs, symptoms and electrolytes. **Hydrocortisone** is a glucocorticoid hormone and is used to replace **cortisol. Fludrocortisone** is a mineralocorticoid hormone and is used to replace aldosterone if **aldosterone** is also insufficient.
Patients 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 until they have recovered to match the normal steroid response to illness.
73
What is Addisonian Crisis (AKA Adrenal Crisis)
**Addisonian crisis** is the 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, hyperkaemia
* Patients can be very unwell
It can be the **first presentation** of **Addisons Disease** or triggered by infection, trauma or other acute illness in someone with established Addisons. It can present in someone on long term steroids suddenly withdrawing those steroids.
Do not wait to perform investigations and establish a definitive diagnosis before treating someone with suspected Addisonian Crisis as this is life threatening and they need immediate treatment.
74
Management of Addisonian Crisis
* 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
75
Definitions
Hyperthyroidism
Primary hyperthyroidism
Secondary hyperthyroidism
**Hyperthyroidism** is where there is over-production of thyroid hormone by the thyroid gland. Thyrotoxicosis refers to an abnormal and excessive quantity of thyroid hormone in the body.
**Primary hyperthyroidism** is due to thyroid pathology. It is the thyroid itself that is behaving abnormally and producing excessive thyroid hormone.
**Secondary hyperthyroidism** is the condition where the thyroid is producing excessive thyroid hormone as a result of overstimulation by thyroid stimulating hormone. The pathology is in the hypothalamus or pituitary
76
MC of hyperthyroidism and its patho
**Grave’s disease** is 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.**
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What is Toxic multinodular goitre also known as?
Plummer’s disease)
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What is a Toxic multinodular goitre
Toxic multinodular goitre (also known as Plummer’s disease) is a condition where **nodules** develop on the thyroid gland that **act independently of the normal feedback system** and continuously produce **excessive thyroid hormone.**
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What is Exophthalmos i
Exophthalmos is the term used to describe bulging of eyeball out of the socket caused by Graves Disease. This is due to inflammation, swelling and hypertrophy of the tissue behind the eyeball that forces the eyeball forward.
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What is Pretibial myxoedema
Pretibial myxoedema 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.**
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Causes of Hyperthyroidism
Grave’s disease
Toxic multinodular goitre
Solitary toxic thyroid nodule
Thyroiditis (e.g. De Quervain’s, Hashimoto’s, postpartum and drug-induced thyroiditis)
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What is Universal Features of Hyperthyroidism
Anxiety and irritability
Sweating and heat intolerance
Tachycardia
Weight loss
Fatigue
Frequent loose stools
Sexual dysfunction
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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 **exophthalmos**
* Pretibial **myxoedema**
*
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Unique Features of Toxic Multinodular Goitre
* Goitre with firm nodules
* Most patients are aged over 50
* Second most common cause of thyrotoxicosis (after Grave’s)
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What is Solitary Toxic Thyroid Nodule
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.
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What is De Quervain’s Thyroiditis
De Quervain’s Thyroiditis describes 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.
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What is Thyroid Storm
Thyroid storm is a rare presentation of hyperthyroidism. It is also known as “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 beta-blocker
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Hyperthyroidism Management
Carbimazole- first line
Propylthiouracil- second line
Radioactive Iodine
Beta-blockers- propranolol
Surgery
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Explain further about carbimazole on management of hyperthyroidism
**Carbimazole** is the **first line** anti-thyroid drug. It is usually successful in treating patients with Grave’s Disease, leaving them with normal thyroid function after 4-8 weeks. Once the patient 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 patient 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.
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Propylthiouracil has a risk of ...
There is a small risk of severe hepatic reactions, including death, which is why carbimazole is preferred.
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Explain futher Radioactive Iodine
Treatment with **radioactive iodine** 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. This reduction in functioning cells results in a decrease of thyroid hormone production and thus remission from the hyperthyroidism. Remission can take 6 months and patients can be left **hypothyroid** afterwards and require **levothyroxine** replacement.
There are strict rules where the patient:
* 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
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how are beta blockers used in hyperthyroidism
Beta blockers are used to block the adrenalin related symptoms of hyperthyroidism. **Propranolol** is a good choice because it non-selectively blocks adrenergic activity as opposed to more “selective” beta blockers the work only 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 patients with **thyroid storm.**
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Explain Surgery in hyperthyroidism
A definitive option is to surgically remove the whole thyroid or toxic nodules. This effectively stops the production of thyroid hormone, however the patient will be left hypothyroid post thyroidectomy and require **levothyroxine** replacement for life.
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Causes of Hypothyroidism
Hypothyroidism
Iodine Deficiency
Secondary to Treatment of Hyperthyroidism
Medications
Central Causes (Secondary Hypothyroidism)
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What is Hashimoto’s Thyroiditis
This is the most common causes of hypothyroidism in the developed world. It is caused by autoimmune inflammation of the thyroid gland. 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.
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Secondary to Treatment of Hyperthyroidism
All of the treatments for hyperthyroidism have the potential to cause hypothyroidism:
Carbimazole
Propylthiouracil
Radioactive iodine
Thyroid surgery
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Medications caused to hypothyroidism
**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.
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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
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Presentation and Features of hypothyroidism
Weight gain
Fatigue
Dry skin
Coarse hair and hair loss
Fluid retention (oedema, pleural effusions, ascites)
Heavy or irregular periods
Constipation
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Investigations of hypothyroidism
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Management of hypothyroidism
Replacement of thyroid hormone with oral **levothyroxine** is the treatment of hypothyroidism. Levothyroxine is **synthetic T4,** and metabolises to **T**3 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.
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What is Acromegaly
Acromegaly is the clinical manifestation of excessive growth hormone (GH). Growth hormone is produced by the anterior pituitary gland. The most common cause is unregulated growth hormone secretion by a pituitary adenoma. This adenoma can be microscopic or can be a significantly sized tumour that causes compression of local structures. Rarely, acromegaly can also be secondary to a cancer, such as lung or pancreatic cancer, that secretes **ectopic growth hormone releasing hormone (GHRH) or growth hormone.**
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The optic chiasm sits just above the pituitary gland. The optic chiasm is the point where the optic nerves coming from the eyes crossover to different sides of the head. A pituitary tumour of sufficient size will start to press on the optic chiasm. Pressure on the optic chiasm will lead to a stereotypical _________ \_\_\_\_\_\_\_\_\_\_\_\_ visual field defect. This describes loss of vision on the outer half of both eyes.
The optic chiasm sits just above the pituitary gland. The optic chiasm is the point where the optic nerves coming from the eyes crossover to different sides of the head. A pituitary tumour of sufficient size will start to press on the optic chiasm. Pressure on the optic chiasm will lead to a stereotypical **“bitemporal hemianopia”** visual field defect. This describes loss of vision on the outer half of both eyes.
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Presentation
Acromegaly
**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
**Symptoms suggesting active raised growth hormone**
* Development of new skin tags
* Profuse sweating
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Investigations for acromegaly
A random growth hormone level is not helpful as it will fluctuate, giving false positives and false negatives
* Insulin-like Growth Factor 1 (IGF-1) is the initial screening test (raised)
* Oral glucose tolerance test whilst measuring growth hormone (high glucose normally suppresses growth hormone)
* MRI brain for the pituitary tumour
* Refer to ophthalmology for formal visual field testing
*
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Treatment for acromegaly
**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.
There are medication that can be used to block growth hormone
* **Pegvisomant** (GH antagonist given subcutaneously and daily)
* **Somatostatin** **analogues** to block GH release (e.g. ocreotide)
* **Dopamine agonists** to block GH release (e.g. bromocriptine)
Somatostatin is known as **“growth hormone inhibiting hormone”**. It is normally secreted by the brain, gastro-intestinal 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.
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The parathyroid glands, specifically the chief cells in the glands, produce parathyroid hormone in response to \_\_\_\_\_\_\_\_\_\_\_\_
The parathyroid glands, specifically the chief cells in the glands, produce parathyroid hormone in response to **hypocalcaemia (low blood calcium)**
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Parathyroid hormone acts to raise blood calcium level by:
Increasing osteoclast activity in bones (reabsorbing calcium from bones)
Increasing calcium absorption from the gut
Increasing calcium absorption from the kidneys
Increasing vitamin D activity
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Symptoms of Hypercalcaemia
It is worth remembering the “renal stones, painful bones, abdominal groans and psychiatric moans” mnemonic for the symptoms of hypercalcaemia:
* Renal stones
* Painful bones
* Abdominal groans refers to symptoms of constipation, nausea and vomiting
* Psychiatric moans refers to symptoms of fatigue, depression and psychosis
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What is Primary Hyperparathyroidism
Primary hyperparathyroidism is caused by uncontrolled parathyroid hormone produced directly by a tumour of the parathyroid glands. This leads **hypercalcaemia:** an abnormally high level of calcium in the blood. This is treated by **surgically removing the tumour.**
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What is Secondary Hyperparathyroidism
This is where insufficient **vitamin D or chronic renal failure** leads to low absorption of calcium from the intestines, kidneys and bones. This causes **hypocalcaemia:** a low level of calcium in the blood.
The **parathyroid glands** reacts to the low serum calcium by excreting more parathyroid hormone. Over time the total number of cells in the parathyroid glands increase as they respond to the increased need to produce parathyroid hormone. This is called **hyperplasia.** The glands become more bulky. The **serum calcium level will be low or norma**l but the **parathyroid hormone will be high**. This is treated by correcting the vitamin D deficiency or performing a renal transplant to treat renal failure.
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What is Tertiary Hyperparathyroidism
this happen when **secondary hyperparathyroidism** continues for a long period of time. It leads to hyperplasia of the glands. The baseline level of parathyroid hormone increases dramatically. Then when the cause of the secondary hyperparathyroidism is treated the parathyroid hormone level remains inappropriately high. This high level of parathyroid hormone in the absence of the previous pathology leads to high absorption of calcium in the intestines, kidneys and bones and causes **hypercalcaemia.** This is treated by **surgically** removing part of the parathyroid tissue to return the parathyroid hormone to an appropriate level.
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Summar of hyperparathyroidism
cause
pth
calcium
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What is Primary Hyperaldosteronism
Primary hyperaldosteronism 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 blood pressure. There are several possible reasons for this:
* **Bilateral adrenal hyperplasia** (most common)
* An **adrenal adenoma** secreting aldosterone (known as Conn’s Syndrome)
* Familial hyperaldosteronism type 1 and type 2 (rare)
* Adrenal carcinoma (rare)
*
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What is Secondary Hyperaldosteronism
Secondary hyperaldosteronism is where excessive renin stimulating 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 blood pressure in the kidneys is disproportionately lower than the blood pressure in the rest of the body:
* Renal artery stenosis
* Renal artery obstruction
* Heart failure
*
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How can renal artery stenosis be confirmed
This can be confirmed with a **doppler ultrasound, CT angiogram or magnetic resonance angiography (MRA).**
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Investigations of hyperaldosteronism
The best screening tool for someone that you suspect has hyperaldosteronism is to check the renin and aldosterone levels and calculate a **renin / aldosterone ratio:**
* **High** aldosterone and **low** renin indicates **primary hyperaldosteronism**
* **High** aldosterone and **high** renin indicates **secondary hyperaldosteronism**
Other investigations relating to the effects of aldosterone:
* Blood pressure **(hypertension)**
* Serum electrolytes **(hypokalaemia)**
* Blood gas analysis **(alkalosis)**
If a high aldosterone level is found then investigate for the cause:
* CT / MRI to look for an adrenal tumour
* Renal doppler ultrasound, CT angiogram or MRA for renal artery stenosis or obstruction
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Management of
Hyperaldosteronism
Aldosterone antagonists
* Eplerenone
* Spironolactone
Treat the underlying cause
* Surgical removal of adenoma
* Percutaneous renal artery angioplasty via the femoral artery to treat in renal artery stenosis
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Hyperaldosteronism is worth remembering as the most common cause of ......
Hyperaldosteronism is worth remembering as the most common cause of **secondary hypertension.**
If you have a patient with a high blood pressure 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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Non-Specific Symptoms for Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH)
Headache
Fatigue
Muscle aches and cramps
Confusion
Severe hyponatraemia can cause seizures and reduced consciousness
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SIADH has countless causes:
* Post-operative from major surgery
* Infection, particularly atypical pneumonia and lung abscesses
* Head injury
* Medications (thiazide diuretics, carbamazepine, vincristine, cyclophosphamide, antipsychotics, SSRIs, NSAIDSs,)
* Malignancy, particularly small cell lung cancer
* Meningitis
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Initial Diagnosis SIADH
n 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 a 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 **chronic kidney disease or acute kidney injury**
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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 correct the sodium slowly to prevent central p**ontine 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 – 1litre. This may be enough to correct the hyponatraemia without the need for medications.
**Tolvaptan. “Vaptans”** are **ADH receptor blockers.** They are very powerful and can cause 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
Central pontine myelinolysis (CPM) is also (and more accurately) known as **“osmotic demyelination syndrome”.** It is usually a complication of long term **severe hyponatraemia** (\< 120 mmols/l) being treated too quickly (\> 10 mmol/l increase over 24 hours).
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What is Diabetes insipidus
Diabetes insipidus is a lack of antidiuretic hormone (ADH) or a lack of response to ADH. This prevents the kidneys from being able to concentrate the urine leading to polyuria (excessive amounts of urine) and polydipsia (excessive thirst). It can be classified as nephrogenic or cranial.
Primary polydipsia is when the patient has a normally functioning ADH system but they are drinking excessive quantities of water leading to excessive urine production. They don’t have diabetes insipidus.
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Nephrogenic diabetes insipidus 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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Cranial diabetes insipidus is 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 tuberculosis)
* Brain surgery or radiotherapy
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Diabetes Insipidus Presentation
* **Polyuria (excessive urine production)**
* **Polydipsia (excessive thirst)**
* Dehydration
* Postural hypotension
* **Hypernatraemia**
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Diabetes Insipidus Investigations
* Low urine osmolality
* High serum osmolality
* Water deprivation test
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Water Deprivation Test
What is it
The water deprivation test is also known as the **desmopressin stimulation test.** This is the test of choice for diagnosing diabetes insipidus.
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Water Deprivation Test
Method
Initially the patient 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.
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Water Deprivation Test Results
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Diabetes Insipidus Management
If possible, treat underlying cause. Mild cases can be managed conservatively without any intervention.
**Desmopressin (**synthetic ADH) can be used in:
* Cranial diabetes insipidus to replace ADH
* Nephrogenic diabetes insipidus in higher doses under close monitoring
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Phaeochromocytoma
25% are familial and associated with .....
25% are familial and associated with **multiple endocrine neoplasia type 2 (MEN 2).**
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phaeochromocytoma
There is a 10% rule to describe the patterns of tumour:
10% bilateral
10% cancerous
10% outside the adrenal gland
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Diagnosis Phaeochromocytoma
* 24 hour urine catecholamines
* Plasma free metanephrines
Measuring serum catecholamines is unreliable as this 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.
Adrenaline has a short half life of only a few minutes in the blood, 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 Phaeochromocytoma
Signs and symptoms tend to fluctuate with peaks and troughs relating to periods when the tumour is secreting adrenaline.
* Anxiety
* Sweating
* Headache
* Hypertension
* Palpitations, tachycardia and paroxysmal atrial fibrillation
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Management Phaeochromocytoma
* Alpha blockers (i.e. **phenoxybenzamine**)
* Beta blockers once established on alpha blockers
* **Adrenalectomy** to remove tumour is the definitive management
Patients should have symptoms controlled medically prior to surgery to reduce the risk of the anaesthetic and surgery.
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