Endocrine Flashcards
What are the 5 classes of hormone? Give 2 examples of each.
- Amino acid derivatives e.g. dopamine, catecholamines 2. Small neuropeptides eg. GnRh, TRH, ADH 3. Large proteins eg. insulin, PTH 4. Steroid hormones eg. cortisol, oestrogen 5. Vitamin derivatives eg. vitamin A,D
What are the functions of hormones?
Growth Maintenance of homeostasis Reproduction
What is the difference between primary and secondary endocrine disease?
Primary - target organ dysfunction Secondary - pituitary dysfunction
In what zone are mineralocorticoids produced?
Zona glomerulosa
In what zone are glucocorticoids produced?
Zona fasciculata
In what zone are androgens produced?
Zona reticularis
What does the adrenal medulla produce?
Epinephrine, norepinephrine and dopamine
TSH stimulates the thyroid to produce…
T3 - potent T4 - converted to T3 at certain tissue sites (by deiodinisation)
LH stimulates the leydig cells to produce…
Testosterone (95% produced in tested, other 5% in adrenal)
LH stimulates production of…
Progesterone
FSH stimulates production of…
Oestrogen
What are the roles of progesterone?
- Maintenance of uterine lining - Decreased contractility of uterine smooth muscle - Skin elasticity and bone strength
What are the roles of oestrogen?
- Secondary sex characteristics - Inhibition of bone resorption - Altered lipid profile - Vascular endothelium
What is the pathology of congenital adrenal hyperplasia?
21 hydroxylase deficiency resulting in reduced or absent production of cortisol and aldosterone. This means that the androgen pathway, which is unaffected, is favoured.
What are the symptoms of congenital adrenal hyperplasia?
Presents with ambiguous genitalia, hyponatremia, and arrhythmias, soon after birth
What is the definition of hyponatremia?
Sodium < 135 mmol/L
What are the symptoms and signs of hyponatraemia?
Symptoms: none, lethargy, cramps, headache, N&V Signs: disorientation, cerebral oedema, seizures, death
What are the categories of causes of hyponatraemia?
- Pseudohyponatremia
- Sodium depletion
- Excess water intake
- Reduced renal free water clearance
What causes pseudohyponatremia?
Hyperglycaemia Hypertriglyceridaemia
What causes sodium depletion?
Renal loss - diuretics, salt wasting, nephropathy, hypoadrenalism
Non-renal - gut loss
What causes excess water intake?
Diabetes insipidus IV fluids
What causes reduced renal free water clearance?
Hypovolaemia - sepsis, portal HTN, renal failure, hypoalbuminaemia
Cardiac failure
Nephrotic syndrome
Hypothyroid
SIAD
How is hyponatremia treated?
Give hypertonic saline
Restrict fluid intake - this is because hyponatremia will mean there will be more water and cells will swell.
What is the pathology of SIADH?
Syndrome of Inappropriate ADH Inappropriate continued secretion of ADH from the posterior pituitary or ectopic. Symptoms of hyponatremia!!
How is SIADH diagnosed?
Hyponatraemia < 135mmol/L
Urine Na > 20mmol/L
Urine osmol >100mOsm/kg
in absence of
- adrenal failure
- oedema
- hypotension
- non-osmotic ADH release
Plasma osmol < 280mOsm/kg
Also renal AQP2 excretion
What causes SIADH?
Brain damage (meningitis/SAH) Malignancy (SCLC) Drugs (carbamazepine, SSRIs, amitriptylline) Infection (pneumonia) Hypothyroidism
How should SIADH be managed?
Fluid restriction
Sodium replacement SLOW
Treatment of underlying cause
NB - patients can tolerate chronic low sodium but the correction needs to be slow or the patient is at risk of osmotic demyelination syndrome
What is osmotic demyelination syndrome?
Severe damage and necrosis of the myelin sheath from rapid correction of hyponatremia
What are the symptoms of osmotic demyelination syndrome?
- Quadriplegia - Opthalomoplegia - Pseudobulbar palsy - Coma
How can osmotic demyelination syndrome be prevented?
Dont let sodium rise more than 10mmol/L/24h
A patient has hyponatremia with urine >100mOsmol/kg and urine >30mmol Na What are your differentials?
Drugs (ACEis diuretics) SIAD Salt wasting nephropathy Hypoadrenalism Vomiting
A patient has hyponatremia with urine >100mOsmol/kg and urine <30mmol Na What are your differentials?
Low arterial volume Heart failure Cirrhosis Nephrotic syndrome Hypoalbuminaemia Third space loss GI loss
What is the definition of hypernatremia?
>144 Na
What are the symptoms and signs of hypernatremia?
Symptoms: THIRST, confusion, weakness, appetite loss, nausea Signs - muscle twitching, spasms, seizures
What causes hypernatremia?
Excess sodium in IV therapy Dehydration (elderly, terminally ill)
What is the management of hypernatremia?
Hypotonic fluids IV If hyper<24 hrs - rapidly If hyper >48 hr - slowly Hypotonic means that fluid will move into the cells along a concentration gradient
What is the definition of hypokalemia?
<3.5 potassium
What are the symptoms and signs of hypokalemia?
Symptoms: ASYMPTOMATIC, constipation, fatigue, weakness/neuromuscular, cramps, palps Signs: ARRHYTHMIA on ECG, paralysis
What causes hypokalemia?
Diuretics Conns syndrome Barrters syndrome Gitelmans syndrome Diarrhoea/laxative use
What are the complications of hypokalemia?
Cardio -arrhythmias
Neuromuscular - tetany, paralysis, rhabdomyolysis
Renal - decreased GFR, nephritis, metabolic alkalosis
Endocrine - growth retardation, decreased insulin secretion
What is the definition of hyperkalemia and what causes it?
>5 potassium
Decreased excretion - renal failure, drugs, hypoaldosteronism, acidosis
Increased release from cell - acidosis, tissue damage, digoxin, vigorous exercise
Increased extraneous load - potassium chloride, blood transfusion
What are the symptoms and signs of hyperkalemia?
Symptoms: Parasthesia, weakness Signs: ARRHYTHMIA, paralysis
What are the complications of hyperkalemia?
Cardio - arrhythmias Neuromuscular - parasthesia, weakness Renal - decreased renal NH4 production Endocrine - increased insulin secretion
How is hyperkalemia managed? (think rule of 10s)
- IV calcium gluconate 10% 10mg
- IV actrapid (10units) and dextrose (25g)
- IV saline 50ml
- Salbutamol neb 10-20mg
Stop potassium containing/sparing meds. Dialysis if no response
What is given to stabilise the membrane in hyperkalemia ?
IV calcium gluconate 10% 10ml over 10 min IV saline 50ml
What is given to push potassium back into the cells in hyperkalemia?
Salbutamol 10-20mg nebulised IV actrapid 10units (and IV dextrose 25g to prevent hypoglycaemia)
What are the ECG features of hypokalemia?
- ST depression - Flat T wave - Prominent U wave
What are the ECG features of hyperkalemia?
Tented T waves
Where is potassium primarily stored?
Muscles, liver, RBCs
Where is the main place of potassium reabsorption in the kidney?
Proximal convoluted tubule
How is hypokalemia treated?
Sando potassium tablets
Mild (3-4) - TDS
Moderate (2.5-2.9)- QDS
Severe (<2.5) - IV 40mmol KCL in 1L saline (1mmol/hr)
If IV, give in central line as K irritates tissues
Dont give bolus as risk of arrhythmia
What is Barrters syndrome?
A range of inherited defects in the loop of hence in TAL Na+ and Cl- transport that causes hypokalemia and metabolic alkalosis
What is Gitelmans syndrome?
An inherited thiazide-like defect in DCT Na+/Cl- transport that causes hypokalaemia and metabolic alkalosis
What hormones does the anterior pituitary produce?
ACTH TSH FSH/LH Prolactin GH
What hormones does the posterior pituitary produce?
ADH (vasopressin) Oxytocin
In general, what causes pituitary hormone deficiency?
Congenital Acquired - SOL - Trauma - Iatrogenic - Infection - Infiltrative/inflam disease - Vascular - Idiopathic
In general what causes pituitary hormone excess?
- Benign pituitary adenoma - Ectopic secretion
What are ‘mass effect’ symptoms when referring to pituitary disease, and what causes them?
Headaches, nausea and visual disturbances
You get a mixture of hormone excess and deficiency - hard to diagnose
Large pituitary adenomas (functioning/non-functioning)
What is pituitary apoplexy?
Infarction/haemmorhage of the anterior pituitary causing headache, collapse, visual loss (bitemporal quadrantopia) and death.
How is pituitary apoplexy managed?
- Resus with fluids and IV steroids
- MRI to diagnose
- Surgical decompression
- Replace deficient hormones
What are the primary causes of hypoadrenalism?
Addisons disease (autoimmune) Glucocorticoid + mineralocorticoid deficiency
What are the secondary causes of hypoadrenalism?
ACTH pituitary deficiency Only glucocorticoid deficiency as mineralocorticoids are controlled by RAAS
What are the clinical features of hypoadrenalism?
Malaise Weight loss N&V Abdo pain Postural hypotension Hypoglycaemia Adrenal crisis
What electrolyte disturbance do you get in hypoadrenalism?
Low sodium, high potassium
How can you distinguish between a primary and secondary cause of hypoadrenalism?
Do synacthen test (synthetic form of ACTH) Measure baseline cortisol, give 250mcgrams synachten IM, measure cortisol at 0,30,60 mins
Healthy - cortisol levels should double
Primary - subnormal response to ACTH as the problem lies within the adrenal gland
Secondary - dramatic increase in cortisol levels as problem lies with pituitary ACTH deficiency
Which individuals would get pigmented skin and salt cravings?
Primary adrenal insufficiency Skin - due to increased ACTH Salt cravings - mineralocorticoid deficiency
How is adrenal insufficiency managed?
Primary - hydrocortisone + fludrocortisone Secondary - hydrocortisone
What are the features of a patient with Addisons Disease
Lean, TANNED, tired, tearful, dizzy, faints, mood disorders - very non-specific
What causes an adrenal crisis?
Severe stress - accident/infection
What are the features of an adrenal crisis?
Hypovolaemic shock, abdo pain, vomiting, hypoglycaemia, confusion (severe low na) and fever
How is an adrenal crisis managed?
- 1 litre 0.9% saline STAT
- 100mg IV hydrocortisone STAT, then 200mg/24hr
- Correct hypoglycaemia
What is the role of aldosterone?
Promotes sodium and water retention Lowers plasma potassium levels
What are the exogenous causes of Cushing’s syndrome (adrenal excess)?
Steroids (RA, asthma)
What are the endogenous causes of Cushing’s syndrome?
Adrenal tumour (benign/malignant)
Pituitary tumour that secretes ACTH (Cushings disease)
Ectopic ACTH secreting tumours (SCLC, carcinoid)
What are the symptoms and signs of Cushings syndrome?
Moon face, plethora, buffalo hump, thin hair/skin/nails, striae, central wasting, acne, hirsutism, malaise, depression, bruising, DM
How is Cushings syndrome investigated?
24 hour urinary free cortisol excretion AND Overnight dexamethasone suppression test (levels will be >280 and no cortisol suppression respectively) If tumour is suspected, do CT/MRI to investigate.
If ectopic suspected, administer metyrapone - if cortisol is still high, the ACTH is coming from an ectopic source
How can you localise the cause of Cushing’s syndrome?
Do plasma ACTH levels Low ACTH = adrenal tumour (due to feedback mechanism) –> do CT High ACTH = pituitary or ectopic
High dose dexamethasone test:
<90% drop in urinary cortisol - ectopic ACTH
>90% drop - pituitary adenoma (cushings disease)
Then do corticotrophin releasing test, cortisol will rise with pituitary disease but not ectopic (as it is not connected)
How is Cushings syndrome managed:
a) Adrenal tumour
b) Cushings disease
c) Ectopic secretion
a) removal of adrenals, radiotherapy
b) resection of pituitary adenoma, metyrapone
c) surgery, radiotherapy
For all, treat comorbidites and stop exogenous steroids
What is the role of aldosterone?
Stimulation of sodium and water absorption Removal of potassium from circulation
What are the 3 ways in which aldosterone secretion is managed?
- RAAS - levels rise in response to low BP and renin release
- Potassium - directly stimulated aldosterone secretion
- ACTH - this is minor!!
What are the symptoms of hyperaldosteronism?
Hypertension!! Usually asymptomatic other than this
What does biochem show for hyperaldosteronism?
Decreased K and Mg
Metabolic Alkalosis
Primary - decreased renin
Secondary - increased renin
What are the primary causes of hyperaldosteronism?
Conn’s syndrome - adrenal adenoma Bilateral adrenal hyperplasia (MOST COMMON) Adrenal carcinoma
What are the secondary causes of hyperaldosteronism?
Any condition which increases renin production!! eg. renal artery stenosis, HF, liver failure, nephrotic syndrome Barrters syndrome Gitelmanns syndrome
How is Conn’s syndrome managed?
Laparoscopic adrenelectomy
Spironolactone (aldosterone antagonist) to control BP/K before op
What are the causes of primary hypothyroidism?
Hashimoto’s thyroiditis (autoimmune) Surgery (eg. for hyperthyroid) Radiotherapy Iodine deficiency Drugs (amiodarone, lithium, iodine)
What are the causes of secondary hypothyroidism?
Pituitary deficiency
What are the symptoms of hypothyroidism?
Weight gain Hair loss (particularly lateral part of eyebrow) Cold intolerance Depression Fatigue Menorrhagia Constipation Dry Ataxia Ascites Bradycardia
How is hypothyroidism diagnosed?
Primary - increased TSH, low T3/T4 Secondary - normal TSH, low T3/T4
How is hypothyroidism treated?
Levo-thyroxine NB only use TSH to guide treatment in primary
What is Hashimotos Thyroidits?
Describe typical presentation
What anitbodies would be present?
A type of primary hypothyroidism, due to autoimmune attack of the thyroid, that is associated with T1DM, Addison’s or Pernicious anaemia. It may cause transient thyrotoxicosis in the acute phase. It often presents as a goitre in women aged 60-70 years old.
Anti-TPO
What are the causes of secondary hyperthyroidism?
Pituitary TSH, usually due to a TSHoma (very rare)
What are the causes of primary hyperthyroidism?
Graves disease Toxic nodule/goitre
What are the symptoms of hyperthyroidism?
Weight loss Intolerance to heat Ammenorhea Fatigue Anxiety Palps Diarrhoea Brisk reflexes Pretibial myxoedema
Name 3 specific signs to Graves
What autoantibody would be present?
Orbitopathy
Thyroid associated dermopathy
Thyroid acropachy (clubbing)
TRab
How is hyperthyroidism diagnosed?
Primary - low TSH, high T3/T4 Secondary - normal TSH, high T3/T4
NB - patients may have a thyroid bruit