Endocrinology Flashcards
Briefly describe what type 1 diabetes mellitus is
An autoimmune disease that causes the destruction of beta cells in the islets of Langerhans in the pancreas. This leads to chronic hyperglycemia due to insulin dysfunction.
What is the epidermology of type 1 diabetes mellitus?
- Usually presents ages 5-15
- 10% of diabetes = T1DM
- Lean
- Mostly north European ancestry
What is the aetiology of type 1 diabetes?
- Mutations occur in HLA (human leukocyte antigen) -DR3/4 gene in >90% cases
- It may be triggered by the Coxsackie B virus and enterovirus
Describe the pathophysiology of type 1 diabetes
Autoantibodies attack beta cells in the Islets of Langerhans leading to Insulin deficiency = chronic hyperglycaemia
As the body cannot use glucose as fuel, cells think the body is starved. So continuous breakdown of glycogen from liver (gluconeogenesis) > glycosuria (glucose in urine)
What are the risk factors for type 1 diabetes?
- Northern European ancestry
- Genetic suspeciability
- Certain viral infections (e.g. coxsackie B virus or enterovirus)
How would a patient with type 1 diabetes present in clinic?
They would complain of
- Polydipsia (abnormally thirsty)
- Polyuria
- Rapid weight loss (BMI <25)
The patient will be young (<30), and may note personal or family history of autoimmune diseases
What tests are used to diagnose type 1 diabetes?
Random plasma glucose >11.1 mmol/L (along with symptoms, this alone is enough for a diagnosis)
Fasting plasma glucose >7 mmol/L
HbA1c (glycated haemoglobin) > 6.5% / 48mmol/mol.
What is the management plan (treatment) for type 1 diabetes?
Glycaemic control through diet (low sugar, low saturated and trans fat, high starch) and basal-bolus insulin
- Basal = Long-acting (12 -14 hours) once daily
- Bolus = Short-acting (4 -6 hours) twice daily with meals
Exercise encouraged.
Define hypoglycaemia
Hypoglycaemia is a low blood sugar level (below 4mmol/L)
In diabetes, this is caused by too much insulin, insufficient carbohydrates or not processing the carbohydrates properly, for example, in malabsorption, diarrhoea, vomiting and sepsis.
What early symptoms of a low blood sugar level might a patient with T1DM experience?
- Sweating
- Feeling tired
- Dizziness
- Feeling hungry
- Tingling lips
- Feeling shaky or trembling
- A fast or pounding heartbeat (palpitations)
- Becoming easily irritated, tearful, anxious or moody
- Turning pale
Please note that some patients might be unaware of their symptoms until they are severely hypoglycaemic
What symptoms might a patient with T1DM experience if they were experiencing a more serious hypoglycaemic episode?
- Confusion or difficulty concentrating
- Unusual behaviour, slurred speech or clumsiness (like being drunk)
- Feeling sleepy
- Collapsing or passing out
- Seizure
- Coma
How is hypoglycaemia treated?
Hypoglycaemia is usually treated with rapid-acting glucose e.g., Lucozade and slower-acting carbohydrates, such as biscuits and toast.
For severe hypoglycaemia where the patient is unconscious, having seizures or in a coma and oral glucose would not be safe, treatment is IV dextrose and intramuscular glucagon.
How are patients with type 1 diabetes monitored?
- HbA1c tests - 3 to 6 monthly
- Capillary blood glucose (finger prick) - immediate glucose reading, for self monitoring in T1DM and T2DM
- Flash glucose monitoring (e.g. Freestyle Libre) - sensor placed in patient’s arm allows reader to measure glucose levels of interstitial fluid. Reading lags 5 mins behind blood glucose levels. Need to change every 2 weeks.
What are the complications of uncontrolled T1DM/T2DM?
- Diabetic ketoacidosis
Microvascular
- Diabetic neuropathy leads to lack of sensation in feet > occult foot ulcers
- Diabetic retinopathy
- Diabetic nephropathy
Macrovascular:
- Strokes
- Renovascular disease
- Limb ischaemia
- Heart disease
- Hyperosmolar hyperglycaemic nonketotic coma (mostly in type 2s)
Briefly describe what type 2 diabetes mellitus is
A disease characterised by abnormally low insulin secretions and peripheral insulin resistance, which leads to chronic hyperglycemia due to insulin dysfunction
What is the epidemiology of T2DM?
- Onset older (>30 years)
- Usually overweight
- More common in certain ethnic groups (Black African, Afro-Caribbean, Chinese, South Asian)
- 90% of diabetes = T2DM
What is the aetiology of T2DM?
Genetic susceptibility, but no HLA gene link like in T1DM
What are the risk factors for T2DM?
Non-Modifiable:
- Older age
- Ethnicity (Black, Chinese, South Asian)
- Family history
Modifiable:
- Obesity
- Sedentary lifestyles
- High carbohydrate (particularly refined carbohydrate) diet
How would a patient with T2DM typically present in clinics? What signs and symptoms are present?
Consider T2DM in any patients with risk factors.
Additional symptoms:
- Fatigue
- Polydipsia and polyuria (thirsty and urinating a lot)
- Unintentional weight loss
Signs
- Opportunistic infections
- Slow healing
- Glucose in urine (on dipstick)
What tests are used to diagnose T2DM?
- Fasting plasma glucose (≥7.0 mmol/L)
- HbA1c (≥48 mmol/mol (≥ 6.5%)
Oral glucose tolerance test:
- Takes baseline fasting plasma glucose before breakfast
- Give 75g glucose drink
- Measure glucose 2 hours after - ≥ 11.1 mmol/L
What is pre-diabetes?
Pre-diabetes is an indication that the patient is heading towards developing T2DM. They do not fully fit the diagnostic criteria for T2DM but should be educated on diabetes and lifestyle changes
Not recommended to start treatment
What tests are used to diagnose pre-diabetes?
- HbA1c test – 42-47 mmol/mol
- Impaired fasting glucose – fasting glucose 6.1 – 6.9 mmol/l
- Oral glucose tolerance test:
Impaired glucose tolerance – plasma glucose at 2 hours 7.8 – 11.0 mmol/l on an OGTT
What is the management plan for T2DM?
Two-pronged approach:
Lifestyle:
- Dietary change (veg, oily fish, low GI, high fibre foods)
- Exercise
- Stop smoking
- Weight loss
Target HbA1c = 48mmol/mol (6.5%), if above, start metformin
Medical
- First line: metformin
- Second line: metformin + SGLT-2 inhibitor/ GLP-1 receptor agonist
- Third line: triple therapy with metformin and two of the second line drugs combined, or metformin plus insulin
What is the mechanism of action of metformin?
Metformin is a biguanide, and it lowers blood glucose by increasing the response (sensitivity) to insulin.
It suppresses hepatic glucose production (gluconeogenesis), increases glucose uptake and utilisation by skeletal muscle and suppresses intestinal glucose absorption.
Does not stimulate pancreatic insulin secretion and so does not cause hypoglycemia
Can stimulate weight loss
What are the side effects of metformin?
Common: Abdominal pain; appetite decreased; diarrhoea; gastrointestinal disorder; nausea; taste altered; vitamin B12 deficiency; vomiting
Rare or very rare: hepatitis; lactic acidosis (discontinue); skin reactions
How is metformin excreted from the body? How does this affect how it is prescribed?
Excreted unaltered by the kidneys
Therefore contraindicated in patients with severe renal impairment.
Dose reduction needed in patients with moderate renal impairment
Sodium-glucose co-transporter-2 (SGLT2) inhibitors (e.g. Dapagliflozin)
1) Use
2) MOA
3) Side effects
1) Type 2 diabetes mellitus
2) SGLT2 inhibitors reduce the amount of glucose being reabsorbed in the kidneys so that it is passed out in the urine
3) UTI
GLP-1 receptor agonists (glucagon-like receptor agonists) e.g. semaglutide
1) Use
2) MOA
3) Side effects
1) Type 2 diabetes mellitus
2) GLP-1 receptor agonists stimulate the release of insulin and suppress glucagon secretion only when blood glucose concentrations are elevated; thus, the risk of hypoglycaemia is low
3) GI: decreased appetite, N + V, headache, renal impairment
How are patients with T2DM monitored?
Same as T1DM
- HbA1c tests - 3 to 6 monthly
- Capillary blood glucose (finger prick) - immediate glucose reading. Patients with T1DM and T2DM use these to self-monitor
- Flash glucose monitoring (e.g. Freestyle Libre) - sensor placed in patient’s arm allows reader to measure glucose levels of interstitial fluid. Reading lags 5 mins behind blood glucose levels. Need to change every 2 weeks.
What is diabetic ketoacidosis?
In type 1 DM, cells cannot use glucose as fuel and think they are starving. They undergo ketogenesis so that they have 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 becomes acidic > metabolic acidosis (pH < 7.3). This is called ketoacidosis.
How would a patient with diabetic ketoacidosis present?
Symptoms
- Polyuria
- Polydipsia
- Nausea and vomiting
Signs
- Acetone smell to their breath
- Dehydration and subsequent hypotension
- Altered Consciousness
- They may have symptoms of an underlying trigger (i.e. sepsis)
What can diabetic ketoacidosis lead to?
DEATH! The most dangerous aspects are dehydration, potassium imbalance and acidosis which can kill the patient
How is diabetic ketoacidosis diagnosed?
Hyperglycaemia (i.e. blood glucose > 11 mmol/l)
Ketosis (i.e. blood ketones > 3 mmol/l)
Acidosis (i.e. pH < 7.3)
How is diabetic ketoacidosis treated?
FIG-PICK - follow local protocols carefully
- F – Fluids – IV saline
- I – Insulin – IV insulin
- G – Glucose – monitor and add a dextrose infusion if too low (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/bicarbonate
Establish the patient’s normal subcutaneous insulin regime before stopping the insulin and fluid infusion.
Briefly describe diabetic ketoacidosis and its aetiology
DKA is a complete lack of insulin that results in high ketone production
Medical emergency!
Results from untreated T1DM or infections/illness
Briefly describe hyperosmolar hyperglycaemic state (HHS) and its aetiology
A disease characterised by marked hyperglycemia, hyperosmolality and mild/no ketosis
Results from untreated T2DM usually
What is the pathophysiology of HHS?
Low blood insulin means cells think the body is starving, increased gluconeogenesis which leads to hyperglycaemia, but enough insulin to inhibit ketogenesis
Hyperglycemia -> osmotic diuresis (presence of increased glucose leads to increased urination) -> dehydration
What are the signs and symptoms of HHS?
Extreme diabetes symptoms and:
- Confusion and reduced mental state
- Lethargy
- Severe dehydration
What is the treatment for HHS?
Replace fluid - 0.9% saline IV
Insulin - at low rate of infusion!
Restore electrolytes - e.g. K+
Low-moecular weight heparin (anti-coagulant)
Briefly describe hyperthyroidism
Hyperthyroidism is a disease characterised by the over-production of thyroid hormones T3 and T4 by the thyroid gland.
What is the aetiology of hyperthyroidism?
- Graves disease - 65-75%, Autoimmune
- Toxic multi-nodular goitre
- Toxic adenoma
- Metastatic follicular thyroid cancer
- Iodine excess (e.g. IV contrast)
- Secondary causes - TSH secreting pituitary tumour
What is Graves disease?
An autoimmune condition where TSH receptor antibodies cause a primary hyperthyroidism (thyroid dysfunction)
These TSH receptor antibodies are abnormal antibodies that mimic TSH and stimulate the TSH receptors on the thyroid.
What is the epidemiology of hyperthyroidism?
Mainly young women 20 - 40
Ratio F to M 9:1
What are the risk factors for hyperthyroidism?
- Smoking
- Stress
- HLA-DR3 (susceptibility gene)
- Other autoimmune diseases e.g. T1DM, Addisons, Vitiligo
What is the pathophysiology of hyperthyroidism?
Excess blood levels of T3 increases metabolic rate, cardiac output, bone resorption and stimulates the sympathetic nervous system
What signs and symptoms might a patient with hyperthyroidism present with?
Everything goes faster than it should :(
Symptoms:
- Hot + sweaty
- Diarrhoea
- Hyperphagia (excessive eating)
- Weight loss
- Palpitations
- Tremor
- Irritability
- Anxiety/restlessness
Signs
- Oligomenorrhoea (infrequent mensuration)
- Goitre
What is the treatment for hyperthyroidism?
- Beta-blockers - rapid relief from adrenaline related symptoms
- 1st line Carbimazole - bocks synthesis of T4 (TETRAOGENIC!)
- 2nd line Propylthiouracil - prevents T4->T3 conversion
- Radioactive iodine is first-line definitive treatment in more-than-mild Graves’ - destroys part of thyroid
- Thyroidectomy - hemi or total
What is De Quervain’s thyroiditis?
Swelling of the thyroid glands due to viral infection, patient will present with fever, neck pain and tenderness, dysphagia and features of hyperthyroidism.
Hyperthyroid phase followed by a hypothyroid phase as the TSH level falls due to negative feedback.
- Self-limiting condition
- Treat with NSAIDs for pain and inflammation
- Beta-blockers for symptom relief of hyperthyroidism
Which 2 drugs can cause hypothyroidism?
- Lithium (mood stabiliser)
- Amiodarone (cardiac arrhythmia)
What is post-partum thyroiditis?
Post-partum women (around 8%) can develop lymphocytic thyroiditis, which causes transient primary hypothyroidism
What are symptoms specific to Graves disease?
- Hyperthyroidism symptoms plus:
- Thyroid eye disease (25-50%)
- Eyelid retraction
- Periorbital swelling (swollen eyes)
- Proptosis/Exophthalmos (bulging eyes)
- Pretibial myxoedema (skin disorder associated with Graves disease)
- Thyroid acropachy (signs associated with autoimmune thyroid disease)
What are some complications that can arise from hyperthyroidism?
Cardiovascular: heart failure, atrial fibrillation
Musculoskeletal: osteoporosis
Thyrotoxic crisis (thyroid storm):
- Life-threatening, more severe form of hyperthyroidism, medical emergency!
- Often occurs secondary to infection or trauma in patients with known hyperthyroidism
What is the treatment for a thyroid storm?
- Admission for monitoring
- Supportive care with:
- Fluid resuscitation
- Antithyroid drugs: propylthiouracil
- Corticosteroid: IV hydrocortisone
- Beta-blockers: propanolol
Briefly describe hypothyroidism
Hypothyroidism is a pathological state reflecting a reduction in circulating T3 and T4.
- Primary - abnormal decreased thyroid function resulting in failure to produce thyroid hormones
- Secondary - abnormal decreased TSH production by the pituitary gland
What is the pathophysiology of hypothyroidism?
Aggressive destruction of thyroid cells by various cell and antibody mediated immune processes. Antibodies bind and block TSH receptors -> inadequate thyroid hormone production and secretion
What is the epidemiology of hypothyroidism?
4/1,000 per year
Mainly >40 years old
Ratio of affected female: male - 6:1
What is the main cause of hypothyroidism?
- Hashimoto’s (inflammation and goitre)
- Autoimmune disease where immune system attacks thyroid cells
- More common in females 60-70 years old
Primary atrophic hypothyroidism (atrophy -> no goitre)
What are symptoms (experienced by patient) might a patient with hypothyroidism present with?
Everything goes slower than it should!
Fatigue
Weight gain
Loss of appetite
Cold
Lethargy
Constipation
Low mood/depression
Menorrhagia (heavy periods)
Goitre
What are SIGNS (found through examination or investigation) might a patient with hypothyroidism present with?
- Bradycardia
- Reduced Reflexes (deep tendon)
- Dermatological: hair loss, loss of lateral eyebrows, dry and cold skin, coarse hair
- Goitre
- Carpal tunnel syndrome
- Hoarse voice: rare
What are the investigations/tests used to diagnose hypERthyroidism?
1st line: thyroid function tests - increased T4/T3, but:
Primary hyperthyroidism (e.g. Graves): lower TSH than normal
Secondary hyperthyroidism: higher TSH than normal
Thyroid autoantibodies (anti-TSH receptor)
Ultrasound and CT of the head (if serology cannot confirm_
What are the investigations/tests used to diagnose hypOthyroidism?
TFTs - ↓T4 ↓T3
Primary: ↑TSH
Secondary ↓TSH
TPO (thyroid peroxidase) antibodies - associated with Hashimoto’s
What is the treatment for hypothyroidism?
Levothyroxine (T4 analogue)
Briefly describe Cushing’s syndrome
The clinical manifestation of pathological hypercortisolism from any cause
What is the aetiology of Cushing’s syndrome?
Adrenocorticotropic hormone (ACTH) dependent:
- Cushing’s Disease - ACTH secreting from pituitary adenoma
- Ectopic ACTH production from small-cell lung cancer
ACTH independent:
- Iatrogenic- steroid use (most common)
- Adrenal adenoma
What signs and symptoms may a patient with Cushing’s syndrome present with?
- Moon face
- Central obesity
- Buffalo hump
- Acne
- Hypertension
- Abdominal striae (stretch marks)
- Hirsutism (excessive hair growth in women)
- weight gain
What are the risk factors for Cushing’s syndrome?
- Exogenous corticosteroid use (e.g. steroids)
- Pituitary adenoma
- Adrenal adenoma
- Adrenal adenocarcinoma
What are the investigations/tests used to diagnose Cushing’s syndrome?
- Random plasma cortisol- raised
- Overnight dexamethasone suppression test- most sensitive
- Low-dose dexamethasone suppression (1mg), normal/high cortisol with high-dose (8mg) dexamethasone - low cortisol > Cushing’s syndrome
- Urinary free cortisol (24 hr) (most commonly performed) - elevated
- Plasma ACTH
Hypercortisolism: what is a raised plasma ACTH suggestive of?
An ACTH-dependent cause > high dose dexamethasone suppression test (8mg)
If high-dose dexamethasone suppresses cortisol levels, then the diagnosis is Cushing’s disease.
Hypercortisolism: what is a low plasma ACTH suggestive of?
Suggests an ACTH-independent cause and warrants CT adrenals to look for adrenal pathology
What is a high-dose dexamethasone suppression test?
Given at night (10pm), measured in the morning (9am)
8mg dexamethasone administered to patient, suppression of cortisol occurs in Cushing’s disease (pituitary adenoma), but not in an ectopic ACTH source
What is the differential diagnosis (DDx) for Cushing’s syndrome?
Pseudo-Cushing’s syndrome - caused by excess alcohol, resolves after 1-3 weeks of alcohol abstinence
What is the management plan/treatment for Cushing’s syndrome?
Depending on the underlying cause:
ACTH-dependent causes:
- Cushing’s disease (pituitary adenoma): 1st line treatment is with trans-sphenoidal resection of the pituitary tumour.
- Medical therapy (e.g. glucocorticoid antagonists) or radiotherapy if surgery fails
- Ectopic ACTH source: treatment of underlying cancer
ACTH-independent causes:
- Iatrogenic: review the need for medication and try weaning if possible
- Adrenal tumour: tumour resection or adrenalectomy
Briefly describe acromelogy
Release of excess growth hormone(GH)causing overgrowth of all systems
What is the epidemiology of acromelogy?
- Rare (3 per million/year)
- Equal prevalence between males and females
- Incidence is highest in people 40 +
What is the aetiology of acromelogy?
- Most commonly caused by benign GH-producing pituitary tumours
- Rare case caused by cancers that secrete ectopic GH release
What are the risk factors for acromology?
5% are associated with the inherited disorder MEN-1 (multiple endocrine neoplasia-1)
What are the signs and symptoms of acromology?
- Prominent forehead and brow
- Increased jaw size
- Large hands, nose, tongue, feet
- Visual field defect (bitemporal hemianopia)
- Polyuria and polydipsia: due to T2DM
- Profuse sweating
- Lower pitch of voice
- Obstructive sleep apnoea
What is the pathophysiology of acromlogy?
- Increased GH either secreted by pituitary tumour or ectopic carcinoid tumour travels to tissues such as the liver and results in an increase in insulin-like Growth Factor-1
- This stimulates skeletal and soft tissue growth giving rise to ‘giant-like’ appearance and symptoms
What are the investigations/tests for diagnosing acromlogy?
1st line: Insulin-like Growth Factor 1 test = raised
Gold standard: Oral glucose tolerance test while measuring GH levels (high glucose suppresses GH)
What are the treatments for acromology?
- 1st line: Transsphenoidal resection surgery (if cause is adenoma)
- 2nd line: Somatostatin analogue eg. Octreotide
Briefly describe prolactinoma
Benign adenoma of anterior pituitary gland producing excess prolactin.
What is the epidemiology of prolactinoma?
- Most common hormonal disturbance of the pituitary
- More common in females than males
- Presents earlier in women ( with menstrual disturbance) but later in men (with erectile dysfunction)
What is the aetiology of prolactinoma?
- Micro tumour (less than 10mm diameter on MRI - 90%)
- Macro tumour (more than 10mm diameter on MRI- 10%)
- Non-functional tumour that compresses the pituitary gland, inhibiting dopamine release > disinhibition of prolactin release
- Antidopaminergic drugs
What is the pathophysiology of prolactinoma?
Increased release of prolactin from the benign tumour in anterior pituitary gland can cause galactorrhoea (breast milk production not associated with pregnancy or breast-feeding) by stimulating milk production from the mammary gland and inhibiting FSH (follicle-stimulating hormone) and LH (luteinizing hormone)
What signs and symptoms may a patient with prolactinoma present with?
- Visual field defect
- Headache
- Menstrual irregularity
- Infertility
- Galactorrhoea (milky discharge from nipples)
What investigations/tests are used to diagnose prolactinoma?
The baseline level of prolactin is measured and will be very high
What is the treatment for prolactinoma?
Gold standard
- Transsphenoidal resection surgery of pituitary gland
1st line
- Dopamine agonists: Bromocriptine/cabergoline (Dopamine has an inhibitory effect on prolactin)
Briefly describe Conn’s syndrome
Primary hyperaldosteronism due to an aldosterone producing adrenal adenoma
What are the risk factors for Conn’s syndrome?
Hypertension in patients:
- Under 35 yrs with no family history of hypertension
- With accelerated (malignant) hypertension
- With hypokalaemia before diuretic therapy (helps rid the body of sodium and water)
- Resistant to conventional antihypertensive therapy e.g. more than 3 drugs
- With unusual symptoms e.g. sweating attacks or weakness
What is the pathophysiology of Conn’s syndrome?
Excess production of aldosterone from the adrenal cortex, independent of the renin-angiotensin system leads to:
- High Sodium and water retention
- Increased potassium excretion in kidneys
- Low renin release
What signs and symptoms may a patient with Conn’s syndrome present with?
Symptoms:
- Lethargy
- Mood disturbance
- Paresthesia and muscle cramps (due to hypokalemia)
Signs:
- Hypokalaemia (< 3.5mmol/l)
- Refractory hypertension
What investigations/tests are used to diagnose Conn’s syndrome?
1) 1st line screening test:
- Plasma aldosterone: renin ratio (ARR) > increased aldosterone, low renin > CT
High-resolution CT abdomen: useful to exclude carcinoma
What is the treatment for Conn’s syndrome?
1st line:
- Spironolactone - a potassium sparing diuretic for pre-op controls of BP and K+ levels
Gold standard:
- Laparoscopic Adrenalectomy
The aim is to lower BP, decrease aldosterone levels and resolve electrolyte imbalance
Briefly describe Addison’s disease
Primary adrenal insufficency
What is the epidemiology of Addison’s disease?
- Very rare - 0.8 per 100,000
- Can be fatal
- Marked female preponderance
What is the aetiology of Addison’s disease?
- Autoimmune adrenalitis - most common 80% of cases in the UK
- TB (most common cause worldwide)
- Adrenal metastases
What is the pathophysiology of Addison’s disease?
Destruction of the entire adrenal cortex resulting in mineralocorticoid (aldosterone, zona glomerulosa), glucocorticoid (cortisol, zona fasciculata) and androgens (precursors of sex hormones, zona reticularis) deficiency.
Corticosteroids (glucocorticoids and mineralocorticoids) are involved in renal excretion of potassium and acid as well as sodium reabsorption. Hence, adrenal insufficiency results in a metabolic acidosis coupled with hyperkalaemia and hyponatraemia.
What are some risk factors for Addison’s disease?
Autoimmune adrenalitis is associated with other autoimmune diseases including DMT1, pernicious anaemia and hypothyroidism
If the patient has one of the above and present with symptoms of Addison’s, it is worth considering
What signs and symptoms might a patient with Addison’s disease present with?
- Tanned skin
- Lean
- Fatigue
- Pigmentation especially of palmar creases (increased ACTH cross-reacts with melanin receptors)
- Postural Hypotension
- Vomiting and nausea
What investigations/tests are used to diagnose Addison’s disease?
1st line:
- Morning serum cortisol (8 - 9am sample as peak cortisol levels) - abnormally low at <100 nanomols/L
- 100 - 500nmol/L = refer to ACTH stimulation test
- > 500nmol/L = normal
Gold standard:
- ACTH stimulation test:
- Measure plasma cortisol before and 30 mins after IM TETRACOSACTIDE (Synacthen - ACTH analogue)
- Addison’s is excluded if 30 min cortisol > 550nmol/L (diagnostic if below 550nmol/L)
8am plasma adrenocorticotrophic hormone (ACTH): increased due to loss of negative feedback from cortisol
Serum electrolytes: hyponatraemia & hyperkalaemia due to a decrease in aldosterone
What are some DDx for Addison’s disease?
- Adrenal suppression due to the use of glucocorticoid
- Central (secondary or tertiary) adrenal insufficiency (pituitary or hypothalamic lesions)
What is the treatment/management plan for Addison’s disease?
Replace steroids depending on signs, and symptoms:
- Hydrocortisone (glucocorticoid) - replaces cortisol
- Fludrocortisone (mineralocorticoid) - replaces aldosterone
- Treat the underlying cause and warn against abruptly stopping steroids
- Double hydrocortisone dose if intercurrent illness
What is an adrenal crisis?
Adrenal crisis or Addisonian crisis, is a state of acute insufficiency of adrenocortical hormones.
Most often occurs in patients with established Addison’s disease due to poor medication compliance, infection, trauma, surgery, or myocardial infarction.
What signs and symptoms might a patient with an adrenal crisis present with?
Symptoms
- Nausea and vomiting
- Abdominal pain
- Trigger e.g. infection or MI
Signs
- Hypotension
- Hypovolemic shock
- Reduced GCS
What is the management plan for an adrenal crisis?
- Corticosteroid: hydrocortisone 100 mg IV STAT!
- IV saline and dextrose if hypoglycemic
Briefly describe SIADH
Syndrome of inappropriate ADH: abnormally increased ADH secretion from the posterior pituitary or an ectopic source, causing water retention and hypernatremia
What is the aetiology of SIADH?
- Tumours (SCLC, prostate, pancreatic)
- Post-operative from major surgery
- Infection (TB and pneumonia which causes lung abscess)
- Head injury
- Medications (thiazide diuretics) are the most common cause
What is the pathophysiology of SIADH?
Excess release of ADH will result in the increased aquaporin 2 channels in the collecting duct
Excess water retention > dilute plasma > hyponatraemia < 135 mmol/L (more water so lower concentration of sodium)
There is a loss of an effective feedback mechanism > continuous ADH production irrespective of serum osmolality > a low serum sodium and relatively high urinary sodium with concentrated urine.
What signs and symptoms might a patient with SIADH present with?
Symptoms are a result of hyponatraemia:
- Headache
- Nausea
- Fatigue
- Muscle cramps
- Confusion
If severe > seizures and coma
Fluid status:
- Euvolaemic: no features of hypervolaemia or hypovolaemia as water reabsorbed is distributed evenly across the extra and intravascular compartment
What investigations/tests are used to diagnose SIADH?
SIADH is a diagnosis of exclusion as we do not have a reliable test to measure ADH activity directly.
Clinical examination will show
- Euvolaemia.
- U+Es will show hyponatraemia (< 135mmol/L)
- Urine sodium and osmolality will be high.
Other causes of hyponatraemia need to be excluded:
- Negative short synacthen (ACTH analogue) 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
What is the management plan for SIADH?
- Stop causative medication
- Fluid restriction to 500mls – 1litre. This may be enough to correct hyponatraemia without medications.
- Tolvaptan. “Vaptans” are ADH receptor blockers. Causes a rapid increase in sodium. So initiated by a specialist endocrinologist and require close monitoring.
Briefly describe arginine vasopressin deficiency (previously diabetes insipidus - includes pathophysiology)
2 types: cranial and nephrogenic
The passage of large volumes (>3L/day) of dilute urine due to impaired water reabsorption in the kidney either because of:
- Reduced ADH secretion from the posterior pituitary - cranial AVD/DI
- Impaired response of the kidney to ADH - nephrogenic AVD/DI
What is the aetiology of cranial AVD/DI?
- Idiopathic (unknown cause)
- Congenital
- Tumour
- Trauma
- Infection
What is the aetiology of nephrogenic DI?
- Inherited
- Metabolic (low potassium, high calcium)
- Drugs (lithium)
- Chronic renal disease
What signs and symptoms might a patient with AVD/DI present with?
Symptoms
Polyuria (excessive urine production)
Polydipsia (excessive thirst)
Signs
Dehydration
Postural hypotension
Hypernatraemia
What are some DDx for DI?
Polyuria and polydipsia can also be indicative of diabetes mellitus
What investigations/tests are used to diagnose DI?
GOLD STANDARD!
Water deprivation test to determine if it is DI and desmopressin stimulation test to determine if cranial or nephrogenic
- Patient goes without fluids for 8 hours
- Urine osmolarity measured
If cranial - urine osmolarity:
- After water deprivation - low (still dilute)
- After ADH analogue - high (back to normal) as kidneys can still respond to ADH
If nephrogenic - urine osmolarity:
- After water deprivation - low (still dilute)
- After ADH analogue - low (still dilute) as kidneys cannot respond to ADH
What is the management plan/treatment for DI?
- 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
What is the risk factor AVD/DI?
Family history
Briefly describe hyperparathyroidism (primary, secondary and tertiary)
Parathyroid hormone (PTH) elicits several functions that increase plasma Ca2+ levels
Hyperparathyroidism is the excessive secretion of PTH and can be primary, secondary or tertiary
Primary hyperparathyroidism - excessive PTH secretion from the parathyroid glands
Secondary hyperparathyroidism - hypertrophy of parathyroid glands to compensate for hypocalcemia
Tertiary hyperparathyroidism - autonomous secretion of PTH from parathyroid glands due to hyperplasia.
What is the aetiology of primary, secondary and tertiary hyperparathyroidism?
Primary hyperparathyroidism - tumour of the parathyroid glands causing excessive secretion of PTH
Secondary hyperparathyroidism - chronic kidney disease, and vitamin D deficiency due to diet or GI diseases (e.g. Crohn’s) > hypocalcaemia
Tertiary hyperparathyroidism - occurs after persistent parathyroid hyperplasia (as in secondary HPT) after correction of underlying cause, often seen in chronic renal failure
What are the risk factors for developing hyperparathyroidism?
- Female sex: 3:1 female to male ratio in primary hyperparathyroidism
- Radiation therapy to the neck
- Severe vitamin D or calcium deficiencies
- Familial rare conditions: MEN1 and 2A
What is the pathophysiology of hyperparathyroidism?
Primary hyperparathyroidism - caused by uncontrolled parathyroid hormone produced by a parathyroid tumour which leads to hypercalcemia.
- Serum calcium = high, PTH = high
Secondary hyperparathyroidism - insufficient vitamin D or chronic renal failure leads to low calcium absorption from the intestines, kidneys and bones > hypocalcemia
Parathyroid glands respond by releasing more PTH, and this leads to hyperplasia over time.
- Serum calcium = low/normal, PTH = high
Tertiary hyperparathyroidism is as a result of secondary hyperparathyroidism > hyperplasia of parathyroid gland > baseline PTH level inappropriately high even after the cause of SHP treated > high absorption of calcium in the intestines, reabsorption from kidneys and release from bones > hypercalcaemia.
- serum calcium = high, PTH = high
What signs and symptoms might a patient with hyperparathyroidism present?
Stones, bones, groans and moans!
Renal stones
Painful bones
Abdominal groans - constipation, nausea and vomiting
Psychiatric moans - fatigue, depression and psychosis
What investigations/tests are used to diagnose hyperparathyroidism?
Measuring serum calcium and PTH levels
Primary: serum calcium = high, PTH = high
Secondary: serum calcium = low/normal, PTH = high
Tertiary: serum calcium = high, PTH = high
What are the treatments for hyperparathyroidism?
Primary: surgical removal of the causative tumour
Secondary: correcting the vitamin D deficiency or performing a renal transplant to treat renal failure.
Tertiary: surgical removal of part of the parathyroid tissue to return the parathyroid hormone to an appropriate level or removal of whole gland
Briefly describe hypoparathyroidism (includes aetiology)
Primary hypoparathyroidism: low PTH due to parathyroid gland failure, autoimmune destruction or congenital DiGeorge syndrome (22q11 del)
Secondary hypoparathyroidism: low PTH after parathyroidectomy or thyroidectomy surgery. This is the most common form of hypoparathyroidism
What is the pathophysiology of hypoparathyroidism?
Low PTH results in:
- Hypocalcaemia
- Hyperphosphatemia (as PTH usually inhibits phosphate resorption at the kidneys)
What signs and symptoms might a patient with hypoparathyroidism present with?
It causes increased excitability of muscles and nerves so many symptoms are a result of this:
Symptoms (experienced by patient): CATS Go Numb
- Convulsions
- Arrhythmia
- Tetany (intermittent muscle spasms)
- Spasm
- Numbness
Signs (found through examination/investigation):
Chvostek’s sign - tapping on the facial nerve in the parotid gland (salivary gland below ears) causes ipsilateral twitching of facial muscles
Trousseau’s sign - spasm of the wrist/hand caused by inflating the blood pressure cuff at the brachial artery above systolic pressure. Causes wrist flexion and fingers to pull together
What are some risk factors for hypoparathyroidism?
- Thyroid surgery
- Parathyroid surgery
- Hyper- and hypomagnesaemia (magnesium needed for PTH production, but high levels can suppress process)
- Moderate and chronic maternal hypercalcaemia (neonatal hypocalcaemia)
What are the investigations/tests used to diagnose hypoparathyroidism?
Bloods - Bone profile
- Decreased Ca2+
- Decreased PTH
- Increased/normal phosphate
- Vitamin D - confirm/exclude deficiency as a cause for hypoparathyroidism
ECG
- Prolonged QT interval (time taken for ventricular depolarisation and repolarisation)
What are some DDx for hypoparathyroidism?
- Vitamin D deficiency
- Hypomagnesaemia (low serum magnesium)
- Hypoalbuminemia (low serum albumin)
What is the management plan/treatment for hypoparathyroidism?
- Severe symptomatic hypocalcemia: IV calcium
- Vitamin D deficiency: calcitriol
- Hypoparathyroidism: oral calcium + calcitriol
- Synthetic PTH if required
Briefly describe phaeochromocytoma
Adrenaline is a catecholamine produced by the “chromaffin cells” in the adrenal medulla of the adrenal glands.
A phaeochromocytoma is a tumour of the chromaffin cells that secrete unregulated and excessive amounts of adrenaline.
What is the epidemiology of phaeochromocytoma?
Rare condition
Annual incidence: ~0.6 per 100,000 person-years
What is the aetiology of phaeochromocytoma?
- Most sporadic
- 25% familial and associated with multiple endocrine neoplasia type 2 (MEN 2) syndrome.
There is a 10% rule to describe the patterns of tumours:
- 10% bilateral
- 10% cancerous
- 10% outside the adrenal gland
What is the pathophysiology of phaeochromocytoma?
Usually, adrenaline stimulates the sympathetic nervous system and is responsible for the “fight or flight” response.
In patients with pheochromocytoma, the adrenaline is secreted in bursts giving periods of worse symptoms followed by more settled periods.
What signs and symptoms might a patient with phaeochromocytoma present with?
Signs and symptoms tend to fluctuate with periods when the tumour is secreting adrenaline:
- Anxiety
- Sweating
- Headache
- Hypertension
- Palpitations, tachycardia and paroxysmal atrial fibrillation (irregular heartbeat that returns to normal within 7 days)
What investigations/tests are used to diagnose phaeochromocytoma?
1) 1st line:
- 24 hr urinary metanephrine (a breakdown product of catecholamines) collection
- Plasma-free metanephrines: first-line along with urine metanephrines
Results = elevated
2) CT abdomen and pelvis: if there is biochemical evidence of a phaeochromocytoma, then CT imaging can be performed to look at the adrenals
What is the management plan/treatment for phaeochromocytoma?
Alpha blockers (i.e. phenoxybenzamine) - to lower blood pressure
Beta blockers once established on alpha blockers - to slow down the heart
Adrenalectomy to remove tumour is the definitive management
Patients should have symptoms controlled medically before surgery to reduce the risk of the anaesthetic and surgery.
Briefly describe hypercalcaemia
Abnormally high serum calcium
Normal serum calcium range is 2.13 to 2.63mmo/l and ionised calcium range is 1.15 to 1.27mmol/l
Hypercalcemia = 2 standard deviations above normal range
What is the epidemiology of hypercalcaemia?
- Mild asymptomatic hypercalcaemia occurs in 1 in 1000 of the population
- Occurs especially in elderly women
- Hypercalcaemia occurs in 20% to 30% of patients with cancer.
What is the aetiology of hypercalcaemia?
- Primary hyperparathyroidism and malignancy are the most common causes and account for 90% of cases
- Secondary hyperparathyroidism
- Tertiary hyperparathyroidism
What is the pathophysiology of hypercalcaemia?
Pathophysiology of primary, secondary and tertiary hyperparathyroidism is covered in the “hyperparathyroidism” flashcards
Malignancies cause hypercalcaemia by:
- Bony involvement by the tumour: may lead to massive osteoclastic activity (osteolytic lesions)
Common malignancies leading to hypercalcaemia include multiple myeloma, leukaemia, lung cancer, and breast cancer.
When malignancies cause hypercalcaemia, the tumour = advanced.
What signs and symptoms might a patient with hypercalcemia present with?
Hyperparathyroidism
Stones, bones, groans and moans!
- Renal stones
- Painful bones
- Abdominal groans - constipation, nausea and vomiting
- Psychiatric moans - fatigue, depression and psychosis
Malignancy
Hypercalcemia usually occurs in advanced cancers
What are the risk factors for hypercalcaemia of malignancy?
- Familial Multiple endocrine neoplasia (MEN) type 1 and MEN type 2a (Sipple) or isolated familial hyperparathyroidism.
- There is an association of primary hyperparathyroidism with neurofibromatosis (syndrome where multiple tumours affect brain and spinal cord) and von Hippel-Lindau disease (condition that causes tumous to grow in parts of the body).
What are the investigations/tests used to diagnose hypercalcaemia of malignancy?
PTH/bone profile:
- Low/undetectable PTH since tumour may be secreting parathyroid-like protein > hypercalcaemia but PTH levels will not increase
- Low albumin (some serum calcium is bound to albumin)
- Increased alkaline phosphatase
- Protein electrophoresis to look for myeloma - B2-microglobulin will be present
What is management plan/treatment for hypercalcaemia of malignancy?
Mild hypercalcaemia or asymptotic: treatment of underlying malignancy + supportive measures + monitoring
Moderate/severe hypercalcaemia or symptom without advanced kidney disease: IV saline and IV biphosphonate/denosumab (prevents cancer related bone fractures and problems)
Moderate/severe hypercalcaemia or symptom with advanced kidney disease: renal dialysis +- denosumab
What is the monitoring strategy for hypercalcaemia of malignancy?
Serum calcium will fall to its lowest within 7 days following bisphosphonate administration. Responses last 1 to 4 weeks, so constant calcium monitoring calcium is important.
What are the complications of hypercalcaemia caused by malignancy?
- Acute kidney injury
- Coma
Briefly describe hypocalcaemia
Hypocalcaemia is a state of electrolyte imbalance in which the circulating serum calcium level is low (please note that hypocalcaemia usually has an underlying cause which should be investigated)
What is the aetiology of hypocalcaemia?
Chronic kidney disease is the most common cause of hypocalcaemia
Severe vitamin D deficiency from:
- Reduced UV exposure
- Malabsorption
- Anti-epileptic drugs - induce enzymes that increase vitamin D metabolism
Primary or secondary hypoparathyroidism (see hypoparathyroidism flashcards)
What signs and symptoms might a patient with hypocalcaemia present with?
It causes increased excitability of muscles and nerves because the threshold needed for neuron activation is decreased. Symptoms related to this.
Symptoms (experienced by patient): CATS Go Numb
Convulsions
Arrhythmia
Tetany
Spasm
Numbness
Signs (found through examination/investigation):
Chvostek’s sign - tapping on the facial nerve in the parotid gland causes ipsilateral twitching of facial muscles
Trousseau’s sign - Carpopedal spasm caused by inflating BP cuff above systolic BP, causes wrist flexion and fingers to pull together
What investigations/tests are used to diagnose hypocalcaemia?
- ECG: prolongation of QT intervals (hypocalcaemia)
- Decreased calcium and increased phosphate levels
- LFTs: Alkaline phosphate raised in vitamin D deficiency and bone metastases
- PTH
- Vitamin D
- U&Es: chronic kidney disease
What is the treatment/management plan for hypocalcaemia?
- Aggressive IV fluids
- Consider IV bisphosphonates if no response to fluids
- Treat the underlying cause
What is the normal range of serum potassium levels?
3.5 – 5.3mmol/l
Briefly describe hyperkalaemia
Hyperkalaemia is high serum potassium >5.5mmol/L
Serum K+ > 6.5mmol/L = MEDICAL EMERGENCY!
What is the aetiology of hyperkalaemia?
Conditions:
- Acute kidney injury (common)
- Chronic kidney disease
- Rhabdomyolysis (muscle cell (myocyte) lysis)
- Adrenal insufficiency
- Tumour lysis syndrome
Medications:
- Aldosterone antagonists aka potassium sparing diuretics) (spironolactone and eplerenone) (common)
- ACE inhibitors (common)
- Angiotensin II receptor blockers
- NSAIDs (common)
- Potassium supplements
What is the pathophysiology of hyperkalaemia?
The amount K+ in the blood determines the excitability of nerve and muscle cells, including the heart muscle or myocardium
- Raised K+ levels in the blood reduces the difference in electrical potential between cardiac myocytes and outside of the cells
- Threshold for action potential is significantly decreased
- Increased abnormal action potentials
- Thus abnormal heart rhythms that can result in ventricular fibrillation and cardiac arrest
What signs and symptoms might a patient with hyperkalaemia present with?
Symptoms:
- Muscle weakness
- Muscle cramps
- Paresthesia
- Palpitations
Signs:
- Tachycardia associated with arrhythmias (Potential cardiac arrest)
What investigations/tests are used to diagnose hyperkalaemia?
- ECG
- Bloods - full blood count & U and E (diagnostic)
- Urine osmolality and electrolytes
ECG:
- Go - absent P wave
- Go long - Prolonged PR interval (conduction through AV node >200ms))
- Go tall - Tall tented T waves
- Go under - wide QRS interval (>120ms)
Abnormal creatinine, urea and eGFR = hyperkalemia caused by acute or chronic renal failure
What is the treatment for hyperkalaemia?
Medical emergency: >= 6.5mmol/L - IV 10ml 10% calcium gluconate - stabilises the cardiac muscle cells and reduces the risk of arrhythmias
≥ 6 mmol/L and ECG changes need urgent treatment
≤ 6 mmol/L with stable renal function = a change in diet and medications (i.e. stopping their spironolactone or ACE inhibitor).
If non-urgent, then insulin and dextrose infusion. Insulin and dextrose drives carbohydrates into cells and takes potassium with it, reducing the blood potassium.
Briefly describe hypokalaemia
Low serum potassium of <3.5mmol/L
Serum K+ < 2.5 mmol/L = MEDICAL EMERGENCY!
What is the aetiology of hypokalaemia?
1) Increased secretion
- Most common cause = diuretic treatment: thiazide diuretics e.g. bendroflumethiazide, loop diuretics e.g. furosemide
- Renal disease
- Conn’s syndrome (excess aldosterone)
2) Decreased intake:
- Dietary deficiency or fasting
3) Redistribution to intracellular:
- Metabolic alkalosis
- Drug effect (Insulin, B2 agonists)
4) GI losses:
- Vomiting, severe diarrhoea and laxative abuse
What signs and symptoms might a patient with hypokalaemia present with?
Symptoms:
- Usually asymptomatic
- Fatigue and light-headedness
- Weakness
- Cramps
- Palpitations
- Constipation
Signs:
- Arrhythmias (especially AF)
- Hypotonia
- Hyporeflexia
What investigations/tests are used to diagnose hypokalaemia?
- Serum K+ < 3.5mmol/L = hypokalaemia
- Serum K+ < 2.5mmol/L = URGENT TREATMENT!
ECG:
- Small or inverted T waves
- Depressed ST segments
- Prominent U waves (after T waves)
- Long PR interval
What is the treatment for hypokalaemia?
- K+ replacement (oral or IV)
- Aldosterone antagonist (K+ sparing diuretics)
- Identify and treat the underlying cause
- Acute can resolve on own, majority just need withdrawal from diuretics or laxatives
What is thyroid cancer?
Cancer of the thyroid glands:
4 types account for 98% of cases:
- Papillary
- Follicular
- Anaplastic (worst prognosis :( )
- Medullary
Papillary most common ~80% of cases
What signs and symptoms might a patient with thyroid cancer present with?
Symptoms
Asymptomatic neck lump - most common presentation
Hoarseness - suggests local invasion and recurrent laryngeal nerve involvement
Signs:
Dyspnoea: due to pressure on the trachea
Cervical lymphadenopathy (abnormal enlargement of lymph nodes in head and neck - indicates lymphatic metastasis.
Tracheal deviation: due to pressure effect
What investigations/tests are used to diagnose thyroid cancer?
Thyroid function tests: usually normal - most cancers do not affect thyroid function
Neck ultrasound: first-line imaging to visualise the thyroid and can be highly specific for certain subtypes e.g. papillary
Fine needle biopsy: key procedure to confirm/exclude malignancy and performed under ultrasound guidance
What is the management plan for thyroid cancer?
Papillary, follicular and medullary:
- Total thyroidectomy
- Radioiodine ablation (I-131) - papillary and follicular subtypes
- Lifelong levothyroxine (synthetic thyroxine T4)
- Tyrosine kinase inhibitors in aggressive/metastatic disease
Anaplastic:
- Resection (if possible)
- Palliative: isthmusectomy and radiotherapy
What are the most common metastatic sites for anaplastic thyroid cancer?
- Lung (50%)
- Bone (30%)
- Liver (10%)
- Brain (5%)
Define hypernatremia
Serum sodium concentration > 145 mmol/L
Normal range is 135 - 145 mmol/l
Define hyponatremia
Serum sodium concentration < 135 mmol/L
Define carcinoid syndrome
Carcinoid syndrome occurs due to release of serotonin (5-hydroxytryptamine) and other vasoactive peptides into the systemic circulation from a carcinoid tumour (type of neuroendocrine tumour that grows from neuroendocrine cells - cells in the body that release hormones).
What are the most common sites for carcinoid syndrome to occur?
Most commonly arise from GI tract followed by lungs, liver, ovaries thymus
- Small intestine malignancy (Most common)
- Appendix most common GI tract site
- Liver most common site for metastasis from ileal tumours
What is the pathophysiology of carcinoid syndrome?
- Neuroendocrine tumours normally secrete serotonin into the circulation.
- With GI tract tumours, hormones secreted> enters enterohepatic circulation> liver inactivates hormones> No symptoms.
- However, when liver metastases are present (liver tumour) > hormone secretion> released into circulation + liver dysfunction> symptoms.
What signs and symptoms might a patient with carcinoid syndrome present with?
Symptoms
- Flushing of the skin (particularly face),
- Diarrhoea
- Abdominal cramps
- Breathlessness and wheezing
- Palpitations
Signs
Fibrosis (heart valve dysfunction)
What investigations are used to diagnose carcinoid syndrome?
1st line: Urinary 5-hydroxyindoleacetic acid test - elevated levels
Chest X-ray + Chest/pelvic MRI/CT- helps locate primary tumours
What is the treatment/management plan for carcinoid syndrome?
- Surgery- Resection of tumour is the only cure for carcinoid tumours
- Somatostatin analogues- Octreotide, blocks release of tumour mediators and counters peripheral effects
- Debulking, embolization, or radiofrequency ablation for hepatic masses/metastases can decrease symptoms
DDx for carcinoid syndrome
- IBS
- Crohn’s
- Menopause
DDx for diabetes mellitus type 2
- Non-diabetic hyperglycaemia (pre-diabetes)
- Diabtes mellitus type 1
- Gestational diabetes
What is Maturity-onset diabetes of the young (MODY)
MODY describes a group of conditions characterised by an autosomal dominant mutation in a single gene, which leads to impaired beta-cell function. This is in contrast to T1DM and T2DM, which are polygenetic conditions.
MODY does not involve autoimmune pathology or insulin resistance. Rather, the mutations involved lead to impaired glucose sensing and insulin secretion.
What type of MODY is most common?
Type 3 (50-65%)
Due to mutations in Hepatocyte nuclear factor-1-alpha
Very responsive to Sulfonylurea (80% response)
What are the typical features of MODY?
- Presentation < 25 years of age
- Strong family history
- Normal BMI
- Lack autoantibodies
- No ketosis
- Insulin not usually required
What is MODY often misdiagnosed as and what tests can help?
Often misdiagnosed as DM type 1 or young onset type 2.
So genetic testing may be indicated in the following situations:
- Young patient
- Autosomal dominant mode of inheritance
- Non-acute presentation
- Lack of evidence of autoimmunity, e.g. autoantibody negative
- Lack of evidence of insulin resistance, e.g. normal BMI
DDx for Graves disease (hyperthyroid)
- Toxic nodular goitre
- Painless, postnatal thyroiditis
DDx for Hashimoto’s thyroiditis (hypothyroid)
- Painless thyroiditis - variant presentation of Hashimoto’s thyroiditis
- Graves disease
DDx for pituitary adenoma
- Prolactinoma
- Acromegaly
- Cushing’s syndrome
DDx for Cushing’s syndrome
- Obesity
- Metabolic syndrome
DDx Conn’s
Essential hypertension
DDx SIADH
- Hypovolaemia
- Pseudohyponatraemia
DDx primary hyperparathyroidism
- Secondary hyperparathyroidism (DDx for this is primary hyperparathyroidism)
- Hypercalacaemia of malignancy
DDx for hypocalcaemia
- Iatrogenic post-surgery hypoparathyroidism
- Vitamin D deficiency
DDx diabetes insipidus
Diabetes mellitus
DDx hyperkalaemia
- CKD
- Diabetic ketoacidosis/hyperosmolar hyperglycaemic state (potassium shifts from the intracellular to the extracellular space due to a lack of insulin, resulting in hyperkalemia.)
