Endocrine Flashcards
What is the other term for primary adrenal insufficiency?
Addison’s disease
What does Addison’s disease cause?
Reduced production of glucocorticosteroids e.g. cortisol and mineralocorticoids e.g. aldosterone, and adrenal androgens
The absence of cortisol leads to increased production of adrenocorticotrophic hormone (ACTH) because negative feedback to the pituitary gland is reduced.
In the UK what is the most common cause of Addisons disease?
Autoimmune disease - 70-90% of cases - in 60% of these cases it is a multi-organ autoimmune polyendocrine syndrome
Worldwide, what is the most common cause of Addisons disease?
Infection - tuberculosis
Which two other autoimmune conditions are associated with Addisons disease (in about 50% of people)?
- Type 1 diabetes
2. Hypothyroidism
What is polyglandular autoimmune syndrome type 1 a triad of?
- Addisons disease
- Hypoparathyroidism
- Chronic candidiasis (fungal infections)
What is polyglandular autoimmune syndrome type 2?
This is more common than type 1, and is a complex genetic trait with links to HLA major histocompatibility - HLA DR3 and DR4
- Usually involves Addisons disease, thyroid disease and T1DM
(can also be associated with vitiligo, vitamin B12 deficiency, coeliac disease and hypoparathyroidism)
What is the most serious complication of Addisons disease?
Adrenal crisis - when the adrenal glands can’t supply the extra corticosteroids needed to cope with physical stress and life-threatening symptoms develop - severe dehydration, hypotension, hypovolaemic shock, altered consciousness, seizures, stroke or cardiac arrest
What are the typical features of Addison’s disease? (6)
- Anorexia, weight loss
- Dizzy, syncope
- Postural hypotension
- Bronze skin and pigmented palmar crease
- Fatigue, depression
- Nausea, vomiting, abdominal pain, diarrhoea or constipation
What are the three key features of DKA?
- Hyperglycaemia >11mmol/L (often >30)
- Positive ketones on dipstick or fingerprick
- Metabolic acidosis pH <7.3
What is the clinical presentation for DKA? (7)
- Polyuria
- Polydipsia
- N&V
- Weight loss
- Confusion and drowsiness
- Kussmaul breathing (deep hyperventilation)
- Vague abdominal pain
What investigations are carried out for DKA?
- Urine dipstick +++ ketones ++ glucose
- Blood glucose
- Capillary ketones >3mmol
- ABG - metabolic acidosis
- Bloods - FBC, U&Es, LFTs
What is the management for DKA? (4)
A-E assessment
- Fluid regimen
- Insulin - 50 units of act rapid with 50ml saline - fixed rate 0.1 units/kg/hour
- Once glucose <14, start 10% glucose
- K+ sulphate (must never give >10mmol K+ over 1 hour)
What does HONK AKA HHS refer to?
Hyperglycaemic hyperosmolar non-ketotic state
What is HHS?
A severe uncorrected hyperglycaemia in the presence of residual insulin production (T2DM) leading to dehydration but not ketoacidosis
What is the concern/risk with HHS?
High risk of thrombosis
What are the precipitants for HHS? (8)
- Infection
- MI
- CVA
- GI bleed
- Poor med compliance
- High sugar diet
- Neglect
- Diuretics/BBs/Antihistamines
How can HHS present? (5)
- Unknown history of diabetes
- Insidious onset of polyuria and polydipsia
- Severe dehydration
- Weakness, leg cramps and visual disturbances
- Reduced consciousness - related to plasma osmolality (>440 = coma)
What is the management for HHS?
- A-E assessment
- Fluid replacement - half the rate of DKA e.g. 1 litre of saline over 30 minutes, then 1 litre + potassium every 2-4 hours
- Treat causes e.g. infection
- Thromboprophylaxis e.g. LMWH
only if ketonuria - then insulin infusion
What happens in the body with Addisons disease, as a result of low aldosterone?
- Hyperkalaemia
- Hyponatraemia
- Hypovolaemia
- Metabolic acidosis
How does hypoglycaemia tend to present? (7)
- Sweating
- Pallor
- Tachycardia/palpitations/anxiety
- Confusion
- Slurred speech/blurred vision
- Seizures
- Coma
What is the management for hypoglycaemia?
- ABCDE
- Blood guclose - before glucose administration!
- GCS 15 and safe swallow = fast acting glucose 10-20g orally in frequent and small doses, recheck blood glucose 10-15 mins after and repeat if not >4mmol
- When patient can eat give carbohydrate rich snack
- If alcoholic - consider pabrinex
What happens if the patient with hypoglycaemia cannot take oral glucose e.g. if GCS <15?
Give IV 100mls of 20% glucose or 50ml of 50%. If IV access is unattainable then give IM glucagon 1mg.
What are the two main types of diabetes insulin treatment regimen?
- Premix
2. Basal-bolus
What are the names of the premix drugs?
- Humalog mix 25
- Humalog mix 50
- Humalog M3
- Novomix 30
the numbers refer to the % of short-acting insulin in each mix
In general, how many grams of carbohydrate are recommended for 1 unit of insulin?
10 grams
In general, what can the correction be for 1 unit of insulin, in terms of capillary blood glucose?
1 unit of insulin can equate to for example 3mmol/L of capillary blood glucose
How is type 1 diabetes investigated, what is the test?
Oral glucose tolerance test - 75g of glucose is given to a fasting patient, the baseline fasting glucose is measured and then 2 hours post glucose load.
What is the expected fasting blood glucose for a person without diabetes and with diabetes?
Without - <6
With - >6
What is the expected 2h post-glucose load for someone with and someone without diabetes?
Without - <7.8
With - >11.1
What are the macrovascular complications of diabetes?
CVA, MI, peripheral vascular disease
What are the microvascular complications of diabetes?
Retinopathy, nephropathy and neuropathy
What causes type 1 diabetes?
It is an autoimmune destruction of beta cells in the islets of langerhans, leading to absolute insulin deficiency.
There is a strong association with which HLA types and T1DM?
HLA-DR3 and DR4
What is the peak age of onset for T1DM?
Age 12
What are the classic symptoms associated with T1DM? (4)
- Polyuria
- Polydipsia
- Weight loss
- sometimes DKA is the presenting feature
What investigations are important to request/perform when someone presents with the symptoms indicative of T1DM? (4)
Bloods - FBC, U&Es, glucose, antibodies
Immunology - anti-islet cell Ab, anti-GAD Ab
Urine - ketones
ABG
Which annual reviews need to be performed in someone with diabetes? (9)
- Weight + BMI
- Creatinine
- Urinary ACR
- Cholesterol
- HbA1c (biannual)
- BP (aim <140/90)
- Smoking status
- Fundoscopy
- Feet examination
In addition to the annual reviews, what else needs to be checked more regularly in people with T1DM? (4)
- Injection sites
- BP monitoring
- Renal function
- Thyroid function
What are the complications of DKA? (5)
- Cerebral oedema
- Hypoglycaemia
- Hypokalaemia
- Hyperkalaemia
- Pulmonary oedema
What are the 4 different classes of drugs used in the treatment of T2DM?
- Biguanides (metformin)
- Sulphonylureas (gliclazide, glimepiride)
- Thiazolidinediones (rosiglitazone)
- alpha-Glucosidase inhibitors (acarbose)
What is the mechanism of action of metformin (biguanides)?
Improves the body’s sensitivity to insulin
What is the mechanism of action of sulphonylureas?
Stimulates the pancreatic insulin release
What is the mortality rate as a % for people who experience HONK/hyperosmolar non-ketotic coma/HHS?
20-40%
What are the triggers for hypoglycaemia?
- Sulphonylureas
- Alcohol/Addison’s
- Insulinomas/insulin/infection
- Liver failure
SAIL
What are the signs/symptoms that can indicate hypoglycaemia? (8)
- Cold sweat
- Fatigue
- Irritability
- Confusion
- Loss of consciousness
- Collapse
- Tachycardia
- Seizures
Which hormones do the posterior pituitary gland produce? (2)
- ADH
2. Oxytocin
Which hormones are produced by the anterior pituitary gland? (6)
- ACTH - adrenocorticothrophic hormone
- TSH
- LH
- FSH
- GH
- Prolactin
Why does insulin resistance in T2DM lead to heart disease and stroke?
Insulin resistance has pro-thrombotic effects leading to a higher risk of emboli in coronary arteries
In addition to insulin resistance, what are the other two components than contribute to diabetic heart disease?
- Coronary atherosclerosis - due to smoking, poor diets, hypertension and damage to vessels from glucose
- Metabolic syndrome - large waistline, triglycerides
How is the risk of diabetic heart disease managed? (3)
- Lifestyle changes - smoking cessation, diet and exercise advice
- Statins
- Anti-hypertensives
If someone is on metformin but their HbA1c is still greater than 58mmol/mol (7.5%), what is the next step in treatment?
Add a gliptin or sulphonylurea
What treatment can be used to protect the kidneys in someone at risk of diabetic nephropathy?
Either an ACE inhibitor or losartan - even if BP is normal, as they inhibit RAAS
What is the primary cause of adrenal insufficiency?
Addison’s disease - autoimmune destruction of the adrenal gland. (typically 30-50 year old females)
Destruction of the adrenal cortex results in which adrenal hormones not being produced? (3)
- Mineralcorticosteroids (aldosterone)
- Glucocorticosteroids (cortisol)
- Androgens (mildly testosterone - mainly produced in the testes)
What are the two main categories of diabetic foot problems?
- Neuropathy
2. Ischaemia
What is the condition that can occur in foot neuropathy?
Charcot foot/joint
What is Charcot foot AKA Charcot arthropathy?
Charcot arthopathy is a serious condition, more common if people lose feeling in their feet. The bones in the foot can become weak and lead to dislocations, fractures and changes in the shape of the foot or ankle. It can develop in diabetes, and if it is not treated quickly, ulcers or other sores can develop.
What are the symptoms of Charcot arthropathy?
Foot feeling hot, painful and looking swollen or red. Additionally they will lose function, the arch may collapse and neuropathy may occur
What is the management of suspected Charcot arthropathy?
Referral to an MDT foot service within 1 working day, do not put any weight on that foot until the appointment and normally the person will receive X-rays/MRI scans. Treatment includes having a plaster cast fitted.
What are the typical features of Addison’sdisease?
It is often diagnosed late due to the vague symptoms that can present.
Lead + tired: anorexia, weight loss, dizzy, syncope, postural hypotension
Tanned: bronze skin, pigmented palmar crease + buccal mucosa
Tearful + wear: fatigue, depression, low self-esteem, psychosis
GI: nausea, vomiting, abdominal pain, diarrhoea or constipation
What are in the kidneys that act as receptors to ADH?
Aquaporins
Drinking water does has what effect on plasma osmolality?
Decreases plasma osmolality (diluting blood with water)
What happens when there is decrease in plasma osmolality due to an increase in water intake?
The hypothalamus tells the pituitary gland to not produce as much ADH, so that more water can be excreted in the urine (dilute urine)
What happens if ADH continues not to be released, even if the plasma osmolality has returned to normal?
The body recognises that the blood is getting dilute with water as it takes up more space in vessels, and causes aldosterone to stop being released. Less aldosterone floating around in the blood causes sodium to be released into urine. Concentration gradients cause water to follow the sodium, which normalises the water volume in the blood.
What is the problem with our body regulating water through aldosterone and sodium output?
The sodium is released into the urine from the blood, yet the sodium was already low in the blood to begin with. This means plasma sodium osmolality is dropping significantly. This is SIADH.
There are four patterns of SIADH, what are the 4 types?
Type A - erratic, independent of plasma osmolality. ADH levels tend to be very high, so the maximum amount fluid is retained, causing urine osmolality to be very high too.
Type B - constant release of moderate amount of ADH
Type C - this is when the baseline plasma concentration of sodium level is set lower than normal. This type is unique as the plasma sodium concentration is stable, but low.
Type D - ADH secretion is normal yet urine osmolality is still high
What are the symptoms of SIADH caused by?
Low sodium levels
What are the symptoms of SIADH? (5)
- Headache
- Nausea and vomiting
- Muscle cramps
- Tremors
- Cerebral oedema - hallucinations, mood swings, confusion
If SIADH symptoms are missed, what are the potential serious complications? (3)
- Seizure
- Coma
- Death
What would indicate SIADH using blood test results?
- Low blood sodium
- Low plasma osmolality
- High urine osmolality
- High urine sodium
What are the causes of SIADH?
Anything that disrupts the secretion of ADH.
- Stroke, haemorrhage, trauma to the brain
- Drugs - mood stabilisers or anti-epileptics
- Surgery
- Ectopic ADH release by tumours - small cell carcinoma
- Family history
What is the treatment for SIADH?
Treat the underlying cause, but also restricting fluid and increasing salt and protein in the diet.
Drugs that can inhibit ADH secretion can also work.
What the other term used to describe a hyperthyroid crisis?
A thyrotoxic storm
What are the symptoms of a thyrotoxic storm?
- Tachycardia
- Raised temperature
- Hypotension
- Confusion
What is the treatment for a thyrotoxic storm?
- Beta blockers
- Propylthiouracil (an anti-thyroid treatment to help reduce the effect of raised serum thyroid hormones)
- Hydrocortisone - treat any underlying adrenal insufficiency which is more common in patients suffering form hyperthyroidism and can also help reduced the serum thyroid hormone levels
6% of people with acromegaly have what inherited syndrome - characterised by the occurrence of tumours in the parathyroid, pituitary and adrenal glands?
MEN-1
What are the features of acromegaly? (5)
- Coarse facial appearance
- Spade-like hands
- Increase in shoe size
- Large tongue
- Excessive sweating and oily skin
What are the complications of acromegaly? (4)
- Hypertension
- Diabetes (>10%)
- Cardiomyopathy
- Colorectal cancer
What is the first line antihypertensive drug for all people with diabetes?
ACE inhibitors
What is the most likely diagnosis for an older female patient with polydipsia, polyuria, inappropriately normal or raised parathyroid hormone level and a raised calcium?
Primary hyperparathyroidism - 80% solitary adenoma
What are the symptoms of raised calcium? (6)
Bones, stones, abdominal groans and psychic moans
- Polydipsia, polyuria
- Peptic ulceration/constipation/pancreatitis
- Bone pain/fracture
- Renal stones
- Depression
- Hypertension
What might be found on investigation for hyperparathyroidism?
- Raised calcium, low phosphate
- PTH may be raised or normal
- Pepperpot skull is characteristic X-ray finding of hyperparathyroidism
What is the name for the appearance of lytic lesions in the brain associated with multiple myeloma?
Raindrop skull
What % of primary hyperparathyroidism are caused by parathyroid adenoma?
80%
What is the mechanism of action of empagliflozin - an SGLT-2 inhibitor?
It increases urinary glucose excretion - which causes the following side effects: increased urine output, weight loss and risk of UTIs
What is the recommended amount of carbohydrate to treat a hypoglycaemic state?
10-20grams
What can be given to someone in a hypoglycaemic state?
- If they have a safe swallow and normal GCS, Lucozade, glucose gel or tabs to chew.
- If reduced GCS - IV access is preferred to give 20% glucose approx. 50-100ml (don’t give 50% as it damages veins)
- Last resort is IM glucagon (high chance of inducing sickness so not recommended unless vital)
What are the signs of a hypoglycaemic state? (8)
- Palpitations
- Shaking
- Hunger
- Irritability
- Headache
- Sweating
- Dizziness
- Unconscious
What is hyperparathyroidism?
When there is excessive sections of parathyroid hormone from the parathyroid glands located in the neck.
What are the parathyroid hormone do?
Regulates serum calcium and phosphate levels and also plays a part in bone metabolism
What are the different types of parathyroidism?
- Primary - one parathyroid gland (or more) produces excess PTH. This may be asymptomatic
- Secondary - there is increased secretion of PTH in response to low calcium because of kidney, liver or bowel disease
- Tertiary - there is autonomous secretion of PTH, usually because of CKD
What does the parathyroid gland do?
- Increases the release of calcium from the bone matrix
- Increases calcium reabsorption by the kidneys
- Increases renal production of 1,25-dihydroxyvitamin D3, which increases intestinal absorption of calcium
Where is calcium homeostasis regulated? (3)
- Intestinal tract
- Kidneys
- Bone
What is 1,25-dihydroxyvitain D3 also known as?
Calcitriol
Calcitonin can also affect calcium homeostasis. What is it produced by and where from?
Produced by C cells of the thyroid gland
What does calcitonin do?
Inhibits osteoclast activity and reduces the release of calcium and phosphate from bone
Primary hyperparathyroidism is the third most common endocrine disorder. Who does it most commonly affect?
Postmenopausal women
What causes primary hyperparathyroidism?
- A single parathyroid gland adenoma (85%)
- 4-gland hyperplasia (10-15%)
- Double adenomas (3-5%)
- Parathyroid carcinoma (<1%)
Familial cases of hyperparathyroidism can occur, what endocrine syndromes are known to be related? (3)
- Multiple endocrine syndromes e.g. MEN-1 or MEN-2a
- Hyperparathyroid-jaw tumour (HPT-JT)
- Familial isolated hyperparathyroidism (FIHPT)
How can hyperparathyroidism present?
In those who are symptomatic (20-30%) it is the features of hypercalcaemia ‘bones, stones, abdominal groans and psychic moans’
- Muscle weakness, proximal myopathy
- Abdominal pain, peptic ulcer disease
- Renal colic, haematuria
- Neuropsychiatric manifestations - depression, confusion, dementia
- Hypertension
- Bone pain from osteoporosis
Why do people with hyperparathyroidism get osteoporosis and osteopenia?
Due to the excessive calcium resorption from the bone it leads to osteoporosis and causes the bone pain and pathological fractures
What is osteitis fibrous cystica?
It occurs in severe cases of hyperparathyroidism. It presents with subperiosteal resorption of the distal phalanges, tapering of distal clavicles, salt and pepper appearances of the skull and brown tumours of the long bones.
What does excessive renal calcium excretion lead to?
Renal calculi
Why can hyperparathyroidism lead to peptic ulcer disease?
Hypercalcaemia can increase gastric acid secretion leading to ulcers
What are the differentials for hyperparathyroidism? (6)
- Lithium-induced hypercalcaemia
- Malignancy
- Thyrotoxicosis
- Sarcoidosis
- Paget’s disease of the bone
- Addison’s disease
What investigations can be carried out if someone presents with hypercalcaemia?
- Look for obvious drug causes e.g. lithium, thiazide diuretics
- Repeat plasma albumin-adjusted calcium levels
- Ensure renal function is normal
- Measure PTH, with will be raised in primary HPT.
What will phosphate levels be like in primary hyperparathyroidism?
Low - hypophosphataemia
What is the treatment for mild, asymptomatic hyperparathyroidism? (6)
- Surveillance can be used in patients with mildly elevated calcium levels and close to normal renal and bone status
- Check serum creatinine level and calcium levels every 6 months
- 3 site DEXA study every 1-2 years
- Avoid dehydration
- Avoid thiazide like diuretics
- There is no recommendation to limit calcium intake
What is the only potential cure for hyperparathyroidism?
Surgery - parathyroid surgery to remove abnormal parathyroid gland(s) is suggested in most sympathetic patients.
What are the guidelines for the surgical management of PHPT?
- Age under 50
- Serum albumin-adjusted calcium is more than 0.25mmol/L above the upper limit of normal
- Creatnine clearance <60ml/minute
- Renal calculi
- DEXA -2.5
- Vertebral fractures
- Patient request
What do they do during surgery to determine if the abnormal gland has been removed?
Intraoperative PTH is measured, PTH levels drop by 50% within 10-15 minutes of the hyper-functioning parathyroid tissue being removed
If people don’t meet the criteria for surgical treatment of PHPT, or they don’t want surgery, what is the medical management? (3)
Treatment is aimed at improving bone density and achieving calcium homeostasis.
- HRT and raloxifene may be used in postmenopausal women. They have been shown to reduced calcium levels as well as improve bone density.
- Bisphosphonates (particularly alendronate)
- Cinacalcet reduces both serum calcium and PTH levels and raises serum phosphate. Cinacalcet does not, however, reduced bone turnover or improve bone mineral density
What are the complications of PHPT surgery? (3)
- Hypocalcaemia due to ‘hungry bone syndrome’ - until the normal parathyroid glands regain sensitivity, there will be a hypoparathyroidism. Calcium and vitamin D supplements may be required.
- Recurrent laryngeal nerve injury - if a patient develops new hoarseness postoperatively. Immediate laryngoscopy is required.
- Haematoma formation - if this occurs in the pre-tracheal space, urgent evacuation is required before airway obstruction occurs.
What are the causes of secondary hyperparathyroidism?
CKD - the parathyroid gland becomes hyper plastic after long-term stimulation in response to chronic hypocalcaemia
Who is most likely to develop SHPT?
People with stage 5 CKD - those on dialysis (almost all patients on dialysis have SHPT)