Endocrine Flashcards
What is the ideal blood glucose concentration?
4.4-6.1 mmol/l.
What is insulin produced by?
by beta cells in the Islets of Langerhans in the pancreas
Is insulin an anabolic or catabolic hormone?
anabolic (building)
What causes insulin to be produced?
Rise in blood glucose (e.g. after meal)
2 main mechanisms by which insulin reduces blood glucose?
- Causes cells in body to absorb glucose and use it as fuel
- Causes muscle and liver cells to absorb glucose from blood and store it as glycogen
How is glucose stored?
As glycogen
What is glucagon produced by?
alpha cells in the Islets of Langerhans in the pancreas
Is glucagon an anabolic or catabolic hormone?
Catabolic (breakdown)
Function of glucagon?
Increases blood glucose levels
What 2 situations is glucagon released in response to?
- Low blood glucose
- Stress
Glucagon increases blood glucose levels via which 2 mechanisms?
- Tells liver to break down glycogen stores into glucose (glycogenolysis)
- Tells liver to convert protein and fats into glucose (gluconeogenesis)
Pathophysiology behind T1DM?
An autoimmune metabolic disorder in which the immune system targets and destroys the insulin-producing cells of the pancreas.
Insufficient production of insulin means cells of body cannot take glucose from blood and use it as fuel. Cells therefore think that body is being fasted and has no glucose supply. Levels of glucose in body keep rising → leading to hyperglycaemia.
What random plasma glucose defines T1DM?
>11 mmol/L
Approx how many people in UK have diabetes?
4.7 million
Who does T1DM most commonly present in?
Most commonly presents in children and young people, but can persist into (and start in) adult life.
What are complications of T1DM due to?
High circulating glucose levels
Symptoms of hyoglycaemia?
Tremor, sweating, irritability, dizziness and pallor
Treatment of hypoglycaemia (at home)?
combination of rapid acting glucose (e.g. lucozade) and slower acting carbohydrates (e.g. biscuits and toast) for when the slower acting glucose is used up
Emergency pharmacological treatment of severe hypoglycaemia (in hospital)?
- IV glucose/dextrose OR
- IM glucagon
What are the 3 major short term complications of T1DM?
- Hypoglycaemia
- Hyperglycaemia
- DKA
The vascular complications of T1DM can be split into microvascular (i.e. damage to small vessels) and macrovascular (i.e. damage to larger vessels).
What are some microvascular complications?
- Nephropathy
- Retinopathy
- Neuropathy
What % of people with diabetes will need treatment for kidney disease in their lifetime?
20%
What is the leading cause of kidney disease?
Diabetes
How can diabetes affect the eyes?
Diabetic retinopathy:
- Small blood vessel damage to retina, leading to progressive loss of vision and possible blindness
- Also, more likely to get glaucoma and cataracts (can lead to blindness)
How can diabetes lead to diabetic neuropathy?
direct damage by hyperglycaemia as well as decreased blood flow to nerves by damaging small blood vessels
In what distribution does diabetic neuropathy present?
glove and stocking distribution
2 major manifestations of diabetic neuropathy?
- Diabetic foot disease → can lead to ulceration & subsequent limb amputation
- Sexual dysfunction
What are the macrovascular complications of diabetes?
- Coronary artery disease (major cause of death in diabetics)
- Atherosclerosis – increases risk of CVS diseases
- Hypertension
- Stroke
- Peripheral ischaemia causes poor healing, ulcers and ‘diabetic foot’
Most common cause of death in diabetes?
CVS disease
Diabetes can lead to infection related complications. Why?
due to suppression of the immune system
How does diabetes affect the immune system?
Patients with uncontrolled diabetes are considered immunosuppresseddue to the negative effects of elevated blood sugars on the immune system.
What infection related complications are common in diabetes?
- UTIs
- Pneumonia
- SSTIs particularly in the feet
- Fungal infections, particularly oral and vaginal candidiasis
How many T1DM present in children?
- Polyuria (can present as bed wetting in children)
- Polydipsia
- Weight loss
- Excessive tiredness
- Blurred vision
- Nausea
As T1DM progresses and insulin production grinds to a halt, a complete lack of insulin can precipitate what condition?
DKA
What % of T1DM are first diagnosed when children present acutely with DKA?
10%
How can T1DM initially present in adults?
- Ketosis
- Rapid weight loss
- Age of onset <50 y/o
- BMI below 25
- Personal and/or FH of autoimmune disease
3 main bedside investigations to do in T1DM?
- Capillary blood glucose
- Fasting glucose
- Urinalysis
What capillary blood glucose indicates T1DM?
hyperglycaemia (random plasma glucose >11 mmol/L)
What fasting glucose indicates T1DM?
>7.0 mmol/L
Purpose of urinalysis in T1DM?
Assess for urine ketones
Important lab test in T1DM?
HbA1c
Long-term mangement for T1DM?
- 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
- Detecting and managing hypoglycaemia, hyperglycaemia and ketosis
- Measure HbA1c levels every 3-6 months
Target HbA1c for adults with T1DM?
HbA1c level of 48mmol/mol or lower to minimise risk of complications
Insulin is usually prescribed as a combination of what?
- 1) A background, long-acting insulin given once a day
- 2) A short acting insulin injected 30 minutes before intake of carbohydrate (i.e. at meals)
If a patient is hyperglyaemic but NOT in DKA, how may the insulin need to be adjusted?
May need to be increased
What is ketogenesis?
The liver takes fatty acids and converts them to ketones
When does ketogenesis occur?
Occurs when there is insufficient glucose supply and glycogen stores are exhausted e.g. in prolonged fasting
Producing ketones is normal and not harmful in healthy patients when under fasting conditions or on very low carbohydrate, high fat diets.
Purpose of ketogenesis?
- Ketones are water soluble fatty acids that can be used as fuel.
- Ketones can cross the blood brain barrier and can be used by the brain as fuel (unlike other fatty acids).
Can ketones cross the BBB?
Yes (can be used by brain as fuel)
1st line investigation in potential DKA?
Ketones can be measured in the urine by dipstick, and in the blood using a ketone meter.
Characteristic smell of breath of people in ketosis?
People in ketosis have a characteristic acetone smell to their breath
What occurs in ketoacidosis?
- Ketone acids (ketones) are buffered in normal patients so that blood does not become acidic.
- When underlying pathology (e.g. type 1 diabetes) causes extreme hyperglycaemic ketosis, this results in metabolic acidosis (from buildup of ketones) that is life threatening → diabetic ketoacidosis
Pathophysiology behind T1DM leading to DKA?
- DKA occurs in T1DM when the person is not producing adequate insulin themselves and is not injecting adequate insulin to compensate for this. The body does not have enough insulin to use and process glucose.
- As the cells in the body have no fuel and think they are starving (due to lack of insulin), they initiate the process of ketogenesis so that they have a usable fuel.
- Over time, the patient gets higher and higher glucose & ketones levels
- Initially, the kidneys produce bicarbonate to counteract the ketone acids but over time the blood becomes acidic → ketoacidosis
Initially, how are ketone acids counteracted in DKA?
Kidney produces bicarb
Does DKA cause blood to become acidic or alkaline?
Acidic
How does DKA lead to dehydration?
- Hyperglycaemia overwhelms the kidneys and glucose starts being filtered into the urine → pulls water out with in via osmotic diuresis
- This results in polyuria → severe dehydration
- Dehydration stimulates thirst centre → polydipsia
Major electrolyte imbalance seen in DKA?
Hyperkalaemia
How does DKA lead to hyperkalaemia?
- Insulin normally drives potassium into cells (without insulin, potassium is not added to and stored in cells)
- When circulating insulin is lacking (DKA), potassium moves out of cells, causing hyperkalaemia
Compare serum vs total body potassium in DKA
Serum → high
Total body → low (as none is stored in cells)
When a patient with DKA is started on insulin, how can this affect potassium levels?
When treatment with insulin starts, patient can develop severe hypokalaemia very quickly, leading to fatal arrhythmias
Presentation of DKA?
- Polyuria
- Polydipsia
- N&V
- Acetone smell to their breath
- Dehydration and subsequent hypotension
- Altered consciousness
- Symptoms of underlying trigger (i.e. sepsis)
- Hyperglycaemia
ABG findings in DKA?
- Metabolic acidosis
- Low pH
- Low bicarb
Management of emergency DKA? (FIG-PICK)
- F - Fluid resuscitation with normal saline
- I - Insulin infusion
- G - Glucose (monitor blood glucose and add dextrose infusion if low)
- P - Potassium (monitor serum K and correct)
- I - Infection (treat underlying triggers)
- C - Chart (chart fluid balance)
- K - Ketones (monitor blood ketones)
Purpose of insulin infusion in DKA?
To get the cells to start taking up and using glucose and stop producing ketones
Purpsoe of fluid resuscitation in DKA?
to correct the dehydration, electrolyte disturbance and acidosis
Diagnostic criteria for DKA:
a) blood glucose
b) blood ketones
c) pH
a) hyperglycaemia - blood glucose >11 mmol/l
b) ketosis - blood ketones >3mmol/l
c) acidosis - pH <7.3
Pathophysiology behind T2DM?
- Repeated exposure to glucose and insulin makes the cells in the body become resistant to the effects of insulin.
- Pancreatic beta cell production of insulin becomes insufficient due to insulin resistance. This leads to chronic hyperglycaemia.
Typical age of onset in T2DM?
Adults
Non-modifiable risk factors for T2DM?
- Older age
- Ethnicity (black, Chinese, south Asian)
- FH
Prognosis of T2DM?
It is possible to cure type 2 diabetes with right management steps.
If symptomatic, one of the following results is sufficient for a diagnosis of T2DM to be made:
- Random blood glucose?
- Fasting plasma glucose?
- 2 hour glucose tolerance?
- HbA1c?
- > 11.1 mmol/l
- > 7 mmol/l
- > 11.1 mmol/l
- > 4 mmol/mol
Note - If patient is asymptomatic, two results are required from different days.
Define ‘impaired fasting glucose’
Body struggles to get their blood glucose levels to normal range, even after a prolonged period without eating carbohydrates
Define ‘impaired glucose tolerance’?
Body struggles to cope with processing a carbohydrate meal (i.e. OGTT)
Diagnosis of pre-diabetes?
Can be diagnosed by a) HbA1c, or b) ‘impaired fasting glucose’ or ‘impaired glucose tolerance’:
- 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 a OGTT
HbA1c range for pre-diabetes?
42-47 mmol/mol
Diabetes can cause gastroparesis. What is this? How can diabetes cause this?
Gastroparesis is a chronic condition that affects the motility of the stomach, causing delayed gastric emptying.
Arecognised GI complication of diabetes related to poor glycaemic control.
Main GI complication of diabetes?
Gastroparesis
Diabetes can lead to autonomic neuropathy. How does this present?
Postural hypotension → dizziness, falls, loss of consciousness
Define postural hypotension
a fall in systolic BP by 20mmHg or more after changing position posture (i.e. lying to standing):
Diabetes can lead to peripheral arterial disease. How may this manifest?
Foot discolouration, gangrene, intermittent claudication, rest pain, night pain, absent pulses, ulceration
How does diabetes lead to diabetic foot infections?
Due to vascular and neuropathic complications of diabetes
What severe complication can diabetic foot infections progress to?
Ostseomyelitis
Most common organism causing diabetic foot infections?
Staph. aureus
What sexual complication can diabetes manifest as?
Erectile dysfunction - is a common presenting complaint
Why can diabetes lead to ED?
Due to poor glycaemia control, neuropathy, microvascular complications etc
ED is an important independent predictor of what in T2DM?
Coronary heart disease risk
Clinical presentation of T2DM?
Consider T2DM in any patient fitting the risk factors.
- Fatigue
- Polydipsia
- Polyuria and nocturia
- Unintentional weight loss
- Opportunistic infections e.g. fungal infections
- Slow healing e.g. foot ulcers
- Glucose in urine (on dipstick)
- Blurred vision
- Tingling in hands/feet
- Muscle weakness
Bedside investigations in T2DM?
- Urinalysis
- Capillary blood glucose
- Oral glucose tolerance test (OGTT)
When is an oral glucose tolerance test performed?
Performed in the morning prior to having breakfast (fasted overnight)
Purpose of oral glucose tolerance test?
Tests ability of body to cope with a carbohydrate meal
What is involved in an OGTT?
- 1) Baseline fasting plasma glucose
- 2) Give them a 75g glucose drink
- 3) Measure plasma glucose 2 hours later
Target HbA1c for new T2DM?
<48 mmol/mol
Target HbA1c for diabetics that have moved beyond metformin alone?
53 mmol/mol
3 major complications to monitor for in T2DM?
- Diabetic retinopathy
- Diabetic foot
- Kidney disease
1st line pharmacological management of T2DM (after lifestyle changes)?
Metformin
What class of drug is metformin?
Biguanide
2nd line pharmacological treattent of T2DM?
Metformin + sulfonylurea (e.g. glilazide)
OR + pioglitazone, DPP-4 inhibitor or SGLT-2 inhibitor (based on individual factors)
Stepwise management of T2DM:
- 1st line - Metformin (a biguanide)
- 2nd line - Dual therapy
- Addition of a gliclazide (a sulfonylurea), pioglitazone, DPP-4 inhibitor or SGLT-2 inhibitor (based on individual factors)
- 3rd line - Triple therapy
- 4th line - Insulin therapy
Define overt hypothryoidism
TSH level above normal range (10mU/L) and free T4 below normal range
Define subclinical hypothyroidism
TSH levels are slightly above normal range, but T3/T4 levels are within normal range
Define 2ary hypothyroidism
TSH levels are inappropriately low or normal (or rarely raised), but free T4 is below normal range
Are men or women more prone to hypothyroidism?
Women (5-10x)
Risk factors for hypothyroidism?
- Female
- > 60y/o
- Family history of thyroid disease
- Have an autoimmune disease e.g. type 1 diabetes or celiac disease
- Have been treated with radioactive iodine or anti-thyroid medications
- Received radiation to neck or upper chest
- Have had thyroid surgery (partial thyroidectomy)
- Pregnancy within past 6 months
What is the most common cause of hypothyroidism in the developed world?
Hashimoto’s thyroiditis
Pathophysiology of Hashimoto’s?
- Caused by autoimmune inflammation of the thyroid gland
- Associated with antithyroid peroxidase (anti-TPO) antibodies (90-95% of patients), antithyroglobulin antibodies (35-60%) or anti-TSH receptor blockers (10%)
What Abs is Hashimoto’s associated with?
antithyroid peroxidase (anti-TPO) antibodies
How does Hashimoto’s affect the thyroid gland?
Initially causes goitre, followed by atrophy of thyroid gland
What is the most common cause of hypothyroidism in the developing world?
Iodine deficiency
Give some iatrogenic causes of hypothyroidism
- Surgical
- Post-ablative therapy
- Radiation
- 2ary to treatment of hyperthyroidism:
- Carbimazole
- Propylthiouracil
- Radioactive iodine
- Thyroid surgery
Give 3 major medications that can cause hypothyroidism
- Hyperthyroid medications e.g. methimazole, carbimazole
- Litium
- Amiodarone
How can lithium cause hypothyroidism?
inhibits production of thyroid hormones in thyroid gland
How can amiodarone cause hypothyroidism?
interferes with thyroid hormone production and metabolism
Give 2 congenital causes of hypothyroidism
- Thyroid aplasia
- Pendred syndrome (defect in thyroxine synthesis)
What is Pendred syndrome?
defect in thyroxine synthesis
What occurs in 2ary hypothyroidism?
This is where the pituitary gland is failing to produce enough TSH (often associated with a lack of pituitary hormones e.g. ACTH):
- Tumours
- Infection
- Vascular (e.g. Sheehan syndrome)
- Radiation
What is euthyroid sick syndrome?
Results in abnormal TFTs which are not due to true thyroid dysfunction
Most common symptoms of hypothyroidism?
- Fatigue/lethargy
- Low mood & poor concentration
- Cold intolerance
- Weight gain
- Constipation
Head & neck signs/symptoms in hypothyroidism?
- Macroglossia
- Puffy face
- Loss of lateral 1/3 of eyebrow
- Goitre (depending on cause)
- Hoarseness or deepening of voice
Cardiac signs of hypothyroidism?
- Bradycardia
- Cardiomegaly
neurological features of hypothyroidism?
- Carpal tunnel syndrome (paraesthesia)
- Slow relaxing reflexes (hyporeflexia)
- Cerebellar ataxia
- Peripheral neuropathy
What would a low TSH and low T4 indicate?
2ary hypothyroidism
What would a high TSH and normal T4 indicate?
Subclinical hypothyroidism
What would a high TSH and low T4 indicate?
1ary hypothyroidism
Why should b12 be assessed in potential hyothyroidism?
Can present similarly
1st line pharmacological management of hypothyroidism?
levothyroxine (LT4) monotherapy
Hyperthyroidism vs thyrotoxicosis?
Hyperthyroidism → Pathologically increased thyroid hormone production and secretion by the thyroid gland.
Thyrotoxicosis → The clinical manifestation of excess circulating thyroid hormones due to any cause (including hyperthyroidism).
Define thyrotoxicosis
Abnormal and excessive quantity of thyroid hormones in the body.
What is subclinical hyperthyroidism?
Normal T3/T4 but lower than normal TSH levels
Where does the pathology typically lie in 2ary hyperthyroidism?
The pathology is in the hypothalamus.
What is the most common cause of hyperthyroidism?
Grave’s disease
What occurs in Grave’s disease?
- Autoimmune condition where TSH receptor antibodies cause 1ary hyperthyroidism
- These are abnormal antibodies produced by the immune system that mimic TSH and stimulate the TSH receptors on the thyroid
What is toxic multinodular goitre also known as?
Plummer’s disease
How does TMN goitre lead to hyperthyroidism?
- Nodules develop on the thyroid gland that act independently of the normal feedback system
- Continuously produce excessive thyroid hormone
Give some potential 1ary causes for hyperthyroidism
- Grave’s disease
- TMN goitre/Plummer’s disease
- Solitary toxic thyroid nodule
- De Quervain’s thyroiditis (painful goitre)
- Radiation
Give some 2ary causes of hyperthyroidisim
- Amiodarone
- Lithium
- TSH producing pituitary adenoma
- Choriocarcinoma (beta-hCG can activate TSH receptors)
- Gestational hyperthyroidism
General features of hyperthyroidism?
- Anxiety and irritability
- Sweating
- Heat intolerance
- Tachycardia
- Weight loss
- Fatigue
- Frequent loose stools
- Sexual dysfunction
Give some peripheral features of hyperthyroidism
- Fine tremor
- Finger clubbing (thyroid acropachy)
- Sweating
- Pretibial myxoedema
What condition does pretibial myxoedema specifically indicate?
Grave’s disease (is a reaction to TSH receptor antibodies)
What is pretibial myxoedema?
Dermatological condition where there are deposits of mucin under the skin on the anterior aspect of the leg, giving a discoloured, waxy, oedematous appearance to the skin over this area
What condition would a goitre with no nodules (smooth) indicate?
Grave’s disease
What condition would a goitre with firm nodules indicate?
TMN goitre
What condition would a goitre with a single nodule indicate?
Solitary toxic thyroid nodule
What would a bruit indicate upon auscultation of the thyroid?
increased vascularity seen in Grave’s disease
Give some eye features of hyperthyroidism
- Exophthalmos (Grave’s disease) – due to inflammation, swelling and hypertrophy of tissue behind eyeball that forces eyeball forwards
- Lid retraction
- Lid lag
- Periorbital oedema (Grave’s)
- Ophthalmoplegia (Grave’s)
What condition specifically does exophthalmos indicate?
Grave’s disease
Cardiac features of hyperthyroidism?
- AF
- High output heart failure (if severe and prolonged)
Neurological features of hyperthyroidism?
- Muscle wasting
- Proximal weakness
1st line pharmacological management of hyperthyroidism?
Carbimazole
2nd line pharmacological management of hyperthyroidism?
Propylthiouracil
How can radioactive iodine be used in the management of hyperthyroidism?
Taken up by thyroid gland and proportion of thyroid cells are destroyed → can lead to hypothyroidism
Purpose of utilising beta blockers in hyperthyroidism?
Block adrenaline related symptoms of hyperthyroidism e.g. sweating, anxiety, irritability
Which beta blocker is indicated in hyperthyroidism? Why?
Propanolol - non-selectively blocks adrenergic receptors as opposed to more selective beta blockers that work only on the heart
What is Cushing’s syndrome?
An endocrine disorder of glucocorticoid (cortisol) excess.
What is the main glucocorticoid?
Cortisol
What is the most common cause of Cushing’s syndrome?
Long-term, high-dose use of the cortisol-like glucocorticoids (i.e. exogenous steroids)
Give some causes of Cushing’s syndrome
- Exogenous steroids
- Cushing’s disease
- Adrenal adenoma
- Ectopic ACTH producing tumours
- Paraneoplastic Cushing’s
What is Cushing’s disease?
A pituitary adenoma releasing excessive ACTH.
Note that Cushing’s disease describes glucocorticoid excess caused by an ACTH secreting pituitary adenoma. Cushing’s disease causes Cushing’s syndrome, but Cushing’s syndrome is not always caused by Cushing’s disease.
What is an adrenal adenoma? How can it cause Cushing’s syndrome?
A hormone secreting adrenal tumour (secretes cortisol)
What is paraneoplastic Cushing’s?
When excess ACTH is released from a cancer (not of the pituitary) and stimulates excessive cortisol release
What is the most common cause of paraneoplastic Cushing’s?
Small cell lung cancer
Clinical features of Cushing’s syndrome?
- Central obesity
- Abdominal striae
- Proximal limb muscle wasting (myopathy) – thin limbs
- Buffalo hump (fat pad on upper back)
- Moon face
- Acne & hirsutism
- Bruising and poor skin healing
- Osteoporosis
How does high levels of stress hormone (cortisol) present in Cushing’s?
- Hypertension
- Cardiac hypertrophy
- Hyperglycaemia (T2DM)
- Depression
- Insomnia
- Hypokalaemia
What is the 1st line investigation in Cushing’s syndrome?
Low dose dexamethasone suppression test
What is an alternative to the dexamethasone test in Cushings?
24-hour urinary free cortisol can be used as an alternative to dexamethasone suppression test to diagnose Cushing’s syndrome but does not indicate the underlying cause and is awkward to carry out
What does successful treatment of Cushing’s disease lead to?
Cortisol deficiency and subsequently steroid replacement post operatively is essential → steroid card & medic alert bracelet
What is metyrapone used in the treatment of?
Cushing’s syndrome
Purpose of the low dose dexamethasone suppression test?
Diagnosing Cushing’s syndrome:
- If the low dose test is normal → Cushing’s can be excluded
- If the low dose test is abnormal → a high dose test can be performed to differentiate between the underlying causes
What is dexamethasone?
A synthetic glucocorticoid steroid
How does the dexamethasone suppression test work?
- Patient takes a dose of dexamethasone at night (i.e. 10pm) and their cortisol and ACTH is measured in the morning (i.e. 9am)
- Intention is to determine whether the dexamethasone suppresses their normal morning spike of cortisol
What is a normal finding in a dexamethasone suppression test?
Dexamethasone suppresses the release of cortisol by effecting negative feedback on the hypothalamus and pituitary:
Hypothalamus responds by reducing the CRH output → Pituitary responds by reducing ACTH output → lower CRH and ACTH levels result in a low cortisol level
What is an abnormal finding in a dexamethasone suppression test?
Cortisol level is NOT suppressed → indicates Cushing’s
What test can be used to try localise the pathology after an abnormal low dose dexamethasone suppression test result?
High dose dexamethasone suppression test
Result of a high dose dexamethasone suppression test in Cushing’s syndrome caused by Cushing’s disease (i.e. pituitary adenoma)?
Pituitary still shows some response to negative feedback and 8mg of dexamethasone is enough to suppress cortisol
Result of a high dose dexamethasone suppression test in Cushing’s syndrome caused by an adrenal adenoma?
Cortisol production is independent from the pituitary so cortisol is not suppressed BUT ACTH is suppressed due to negative feedback of hypothalamus and pituitary gland
Result of a high dose dexamethasone suppression test in Cushing’s syndrome caused by ectopic ACTH (e.g. from SCLC)?
Neither cortisol nor ACTH will be suppressed as ACTH production is independent of the hypothalamus or pituitary gland
Dexamethasone suppression test results:
What is adrenal insufficiency?
Adrenal insufficiency occurs when the adrenal glands don’t produce enough steroid hormones (particularly cortisol and aldosterone).
What is 1ary adrenal insufficiency also known as?
Addison’s disease
What is Addison’s disease?
This refers to the specific condition where the adrenal glands have been damaged, resulting in the reduction in the secretion of cortisol and aldosterone.
Most common cause of Addison’s disease?
Autoimmune
Causes of Addison’s disease:
- Autoimmune (most common)
- Surgical removal
- Trauma
- Infections (TB – more common in the developing world)
- Haemorrhage (Waterhouse-Friderichsen syndrome)
- Infarction
- Less common – neoplasm, sarcoidosis, amyloidosis
What is 2ary adrenal insufficiency?
This is a result of inadequate ACTH simulating the adrenal glands, resulting in low cortisol release. This is the result of loss or damage to the pituitary glands. stimulating the adrenal glands, resulting in low cortisol release.
Causes of 2ary adrenal insufficiency?
- Surgery to remove a pituitary tumour
- Infection or infiltration of the brain
- Loss of blood flow
- Radiotherapy
- Sheehan’s syndrome – massive blood loss during childbirth leads to pituitary gland necrosis
- Base of skull fracture
- CRH deficiency
- Congenital
What conditions will approx 60% of patients with autoimmune Addison’s disease also have?
Approx. 60% of patients with autoimmune Addison’s disease will have vitiligo or other autoimmune endocrinopathies.
What hormones are not adequately prodced in adrenal insufficiency?
Cortisol & aldosterone
Why can Addison’s disease present with hyperpigmentation of the skin?
ACTH stimulates melanocytes to produce melanin (increase in ACTH pre-cursors)
How can Addison’s disease affect BP?
Hypotension (particularly postural hypotension)
How is sodium, potassium and glucose affected in Addison’s disease?
- Hyponatraemia
- Hyperkalaemia
- Hypoglycaemia
ACTH levels in 1ary vs 2ary adrenal failure?
1ary → ACTH high as pituitary is trying very hard to stimulate the adrenal glands without any negative feedback in the absence of cortisol
2ary → ACTH low as the reason the adrenal glands are not producing cortisol is that they are not being stimulated by ACTH
How is renin affected in Addison’s?
high
What test is used to diagnose Addison’s?
ACTH (synacthen) test
1st line pharmacological management of adrenal insufficiency?
- Hydrocortisone → glucocorticoid used to replace cortisol
- Fludrocortisone → mineralocorticoid used to replace aldosterone if aldosterone is also insufficient
Is hydrocortisone a synthetic glucocorticoid or mineralocorticoid?
Glucocorticoid (increases amount of glucose in blood) i.e. replaces cortisol
Is fludrocortisone a synthetic glucocorticoid or mineralocorticoid?
Mineralocorticoid → used to replace aldosterone
What must patients dependent on steroids carry?
Patients given a steroid card and emergency ID tag
If patient’s with adrenal insufficiency have any form of intercurrent illness, what must happen to their medication dose?
They need to double their regular steroid medication dose
What is the short synacthen test/ACTH stimulation test?
This is the test of choice for adrenal insufficiency. It is ideally performed in the morning when the adrenal glands are most ‘fresh’.
Test involves giving Synacthen (synthetic ACTH) which should stimulate healthy adrenal glands to produce cortisol. The cortisol level should at least double.
A failure of cortisol to rise (less than 2x baseline) indicates 1ary adrenal insufficiency (Addison’s disease).
What is synacthen?
Synthetic ACTH
What result of the short synacthen test indicates 1ary adrenal insufficiency?
A failure of cortisol to rise (less than 2x baseline)
What is Addisonian crisis (AKA adrenal crisis)?
An acute presentation of severe Addison’s, where the absence of steroid hormones leads to a life-threatening presentation.
Presentation of addisonian crisis?
- Reduced consciousness
- Hypotension
- Hypoglycaemia, hyponatraemia & hyperkalaemia
- Patients can be very unwell
What can trigger Addisonian crisis?
- It can be the first presentation of Addison’s disease OR
- Triggered by infection/trauma or other acute ill ness in someone with established Addison’s
- It can present in someone on long-term steroids suddenly withdrawing those steroids
Management of Addisonian crisis?
- ABCDE
- Parenteral steroids (i.e. IV hydrocortisone 100mg stat)
- IV fluid resuscitation
- Correct hypoglycaemia glucose
- Careful monitoring of electrolytes & fluid balance
- Consider fludrocortisone if there is adrenal disease
What occurs in 1ary hyperparathyroidism?
One parathyroid gland (or more) produces excess PTH
How can 1ary hyperparathyroidisim affect calcium levels?
Can be asymptomatic or lead to hypercalcaemia
What occurs in 2ary hyperparathyroidism?
Increased secretion of PTH in response to low calcium due to kidney, liver, or bowel disease
What occurs in 3ary hyperparathyroidism?
There is autonomous secretion of PTH, usually because of CKD
What is the most common cause of 3ary hyperparathyroidism?
CKD
Give some causes of 1ary hyperparathyroidism
- Parathyroid gland adenoma (single gland)
- Hyperplasia of all four glands
- Two adenomas
- Parathyroid carcinoma (rare)
What are the 4 classic signs of hypercalcaemia?
Psychiatric moans, abdominal groans, stones, bones:
- Painful bones
- Renal stones
- Abdominal groans – GI symptoms: N&V, constipation, indigestion
- Psychiatric moans – effect on nervous system: lethargy, fatigue, memory loss, psychosis, depression
Give some causes of 2ary hyperparathyroidism
- Vitamin D deficiency
- Loss of extracellular calcium
- Calcium malabsorption
- Abnormal parathyroid hormone activity
- Inadequate calcium intake
Describe calcium, phosphate, PTH and ALP in vitamin D deficiency 2ary hyperparathyroidism
- Calcium - normal/low
- PTH - high
- Phosphate - low
- ALP - high
Why is ALP high in vitamin D deficiency?
Alkaline phosphatase (ALP) is usually elevated in response to the effect of PTH on calcium absorption from bone. The combination of a normal serum calcium, low phosphate, and elevated alkaline phosphatase is suggestive of disturbed vitamin D metabolism.
Describe calcium, phosphate, PTH and ALP in CKD
- Calcium - high
- PTH - high
- Phosphate - high
- ALP -
Why is calcium high in CKD?
CKD causes imbalances in bone metabolism and increases the risk of a type of bone disease called renal osteodystrophy.
Describe calcium, phosphate, PTH and ALP in malabsorption causing 2ary hyperparathyroidism
- Calcium - low
- PTH - high
- Phosphate - low
- ALP - normal
Describe calcium, phosphate, PTH and ALP in malabsorption causing 2ary hyperparathyroidism
- Calcium - low
- PTH - high
- Phosphate - low
- ALP - normal
What is pseudohypoparathyoridism?
Pseudohypoparathyroidism (PHP) is a genetic disorder in which the body fails to respond to parathyroid hormone.
Describe calcium, phosphate, PTH and ALP in pseudohypoparathyroidism
- Calcium - low (as not responding to PTH)
- Phosphate - high
- PTH - high
- ALP - normal/high
Pathophysiology behind 3ary hyperparathyroidism
Usually occurs are prolonged 2ary hyperparathyroidism – the glands become autonomous, producing excessive PTH ever after the cause of hypocalcaemia has been corrected
What is cinacalcet?
a calcimimetic that mimics the action of calcium on tissues
How does vitamin D affect phosphate?
Vitamin D helps the small intestine and the kidney to reabsorb phosphate back into the bloodstream, so lack of vitamin D can result in low levels of phosphate in the bloodstream.
What is deficient in rickets?
Vitamin D
How does vitamin D affect ALP?
Elevated serum alkaline phosphatase (ALP) level is an essential marker for the diagnosis of vitamin D deficiency.
Cause of osteomalacia?
Vitamin D deficiency
How does CKD affect phosphate levels?
Causes raised phosphate levels as kidneys cannot excrete it (phosphate is a waste product)
What is the effect of PTH on phosphate?
PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney, which means more phosphate is excreted through the urine (i.e. causes low phosphate levels).
What is the effect of PTH on ALP?
PTH increases ALP levels as stimulates osteoblast activity
