Endocrinology Flashcards
Which hormones are released by the anterior pituitary
TSH
ACTH
FSH
LH
GH
Prolactin
Which hormones are released by the posterior pituitary
Oxytocin
ADH
Give an overview of the thyroid axis
Hypothalamus releases TRH (thyrotropin releasing hormone)
Anterior pituitary releases TSH
Thyroid gland releases T3 and T4
T3 and T4 suppress release of TRH and TSH
Give an overview of the adrenal axis
Hypothalamus releases CRH (corticotrophin releasing hormone)
Anterior pituitary releases ACTH
Cortisol released (pulsatile) by both adrenal glands
Controlled by negative feedback
What are the actions of cortisol
Inhibition of immune system
Inhibition of bone formation
Raised blood glucose
Increased metabolism
Increased alertness
Give an overview of the growth hormone axis
Hypothalamus releases GHRH (growth hormone releasing hormone)
Anterior pituitary releases GH
What are the actions of growth hormone
Releases insulin-like growth factor 1 (IGF-1) from liver
Stimulates muscle growth
Increases bone density and strength
Stimulates cell regeneration and reproduction
Stimulates growth of internal organs
Give an overview of the parathyroid axis
PTH released from all 4 parathyroid glands in response to: low calcium, low magnesium, high phosphate
Controlled by negative feedback
What are the actions of PTH
Increases serum calcium
Increases number and activity of osteoclasts
Increases calcium reabsorption from kidneys
Stimulates kidneys to convert vit D3 to calcitriol
Give an overview of the renin-angiotensin-aldosterone system
Renin released by juxtaglomerular cells in afferent arterioles (more renin in response to lower blood pressure)
Renin converts angiotensinogen to angiotensin 1
Angiotensin 1 converted to angiotensin 2 by ACE (in lungs)
What are the actions of angiotensin 2
Vasodilation
Aldosterone release:
Increases sodium reabsorption from distal tubule
Increases potassium secretion from distal tubule
Increases hydrogen secretion from collecting ducts
What is Cushing’s syndrome
Signs and symptoms that develop following prolonged abnormally elevated cortisol levels
What are the clinical features of Cushing’s syndrome
Round middle with thin limbs: moon face, central obesity, abdominal striae, buffalo hump, proximal limb muscle weakness
High levels of stress hormone: hypertension, cardiac hypertrophy, hyperglycaemia, depression, insomnia
Other: osteoporosis, easy bruising, poor skin healing
What are the causes of Cushing’s syndrome
Long term steroid use
Cushing’s disease (pituitary adenoma releasing excess ACTH)
Adrenal adenoma
Paraneoplastic Cushing’s (excess ACTH from cancer)
What investigations are needed for Cushing’s syndrome
Dexamethasone suppression test
24 hour urine free cortisol
FBC, U&Es
MRI brain (pituitary adenoma)
CT chest/abdo (lung/adrenal cancer)
Explain the dexamethasone suppression test
Give dexamethasone at night, measure ACTH and cortisol in morning
Low dose:
- Cortisol level not suppressed
High dose (if low dose positive, do high dose to find cause):
- Low cortisol: Cushing’s disease
- Normal/high cortisol and low ACTH: Adrenal Cushing’s
- Normal/high cortisol and high ACTH: ectopic ACTH
What is the management for Cushing’s syndrome
Remove tumour
Remove adrenal glands (give replacement steroids for life)
What is adrenal insufficiency
Not enough cortisol or aldosterone produced
What is primary adrenal insufficiency
Addison’s disease
Adrenal glands damaged
Mostly autoimmune
All 3 zones affected
What is secondary adrenal insufficiency
Inadequate stimulation of ACTH by adrenal glands
Loss/damage of pituitary gland (surgery, infection, radiotherapy, Sheehan’s syndrome)
What is tertiary adrenal insufficiency
Inadequate CRH release from hypothalamus
Long term steroid use (> 3 weeks)
What are the clinical features of adrenal insufficiency
Fatigue
Nausea
Cramps
Abdominal pain
Reduced libido
Dizziness
Bronze hyperpigmentation of skin
Hypotension (especially postural)
What investigations are needed for adrenal insufficiency
U&Es
Early morning cortisol
Short synacthen test (gold standard)
ACTH (high in primary, low in secondary)
Antibodies (adrenal cortex antibody, 21-hydroxylase antibody)
CT/MRI adrenal
MRI pituitary
Explain the short synacthen test
For adrenal insufficiency
Give synthetic ACTH
Measure blood cortisol at 0, 30, 60 mins
Failure of cortisol to at leas double is Addison’s
What is the management for adrenal insufficiency
Steroid replacement (hydrocortisone for cortisol, fludrocortisone for aldosterone)
Give steroid cards and emergency ID tags
Double steroid dose during acute illness
What is an Addisonian crisis
Acute presentation of severe Addison’s
Absence of steroids can kill
Presentation: reduced consciousness, hypotension, hyperglycaemia, hyponatraemia, hyperkalaemia
Management: do not wait to confirm, intensive monitoring, parenteral steroids, IV fluids, correct hypoglycaemia, monitor electrolytes and fluid balance
What happens to TSH, T3 and T4 in hyperthyroidism
Low TSH
High T3 and T4
What happens to TSH, T3 and T4 in primary hypothyroidism
High TSH
Low T3 and T4
What happens to TSH, T3 and T4 in secondary hypothyroidism
Low TSH
Low T3 and T4
What are the antibodies that can affect thyroid function
Antithyroid peroxidase (anti-TPO) antibodies: against thyroid gland, found in Grave’s and Hashimoto’s
Antithyroglobulin antibodies: against thyroglobulin, can be found in normal thyroid/Grave’s/Hashimoto’s/thyroid cancer
TSH receptor antibodies: mimic TSH, found in Grave’s
What imaging is needed for thyroid pathology
Ultrasound
Radioisotope scan
What are the causes of hyperthyroidism
Garve’s disease
Toxic multinodular goitre
Solitary toxic thyroid nodule
Thyroiditis (viral infection, medications, post-partum)
What are the universal clinical features of hypothyroidism
Anxiety
Irritability
Sweating
Heat intolerance
Tachycardia
Weight loss
Fatigue
Frequent loose stools
Sexual dysfunction
Resting tremor
Hyper-reflexia
Lid lag
What are the clinical features of hyperthyroidism specific to Grave’s disease
Diffuse goitre
Grave’s eye disease
Bilateral exopthalmos
Pretibial myxoedema
Nail changes
What are solitary toxic thyroid nodules
Single nodule releasing thyroid hormone
Usually benign adenomas
Surgically remove
What is De Quervain’s thyroiditis
Viral infection presenting with: fever, neck pain, neck tenderness, dysphagia, features of hyperthyroidism
Get a hyperthyroid phase, then a hypothyroid phase
Self limiting: give NSAIDs and beta blockers for symptoms
What is thyroid storm
Rare presentation of hyperthyroidism
Presentation: hyperthyroidism, pyrexia, tachycardia, delirium
Admit for monitoring
What would the T3, T4 and TSH levels be in subclinical hyperthyroidism
Normal T3 and T4
Low TSH
What is the management for hyperthyroidism
Carbimazole
Propylthiouracil
Radioactive iodine
Beta blockers
Surgery (may need levothyroxine treatment for life)
What are the causes of hypothyroidism
Hashimoto’s
Iodine deficiency
Hyperthyroid treatment
Medications (lithium, amiodarone)
Secondary to tumour/infection/radiation/Sheehan’s
Which antibodies are found in Hashimoto’s
Antithyroid peroxidase (anti-TPO) antibody
Antithyroglobulin antibody
What are the clinical features of hypothyroidism
Weight gain
Fatigue
Dry skin
Coarse hair
Hair loss
Fluid retention
Heavy/irregular periods
Constipation
What would the TSH, T3 and T4 levels be like in primary hypothyroidism
High TSH
Low T3 and T4
What would the TSH, T3 and T4 levels be like in secondary hypothyroidism
Low TSH
Low T3 and T4
What is the management for hypothyroidism
Replace with levothyroxine
Synthetic T4, metabolised into T3
What is the normal range for blood glucose
4.4 - 6.1
What is glucagon
Pancreatic hormone
Produced by alpha cells of islets of Langerhans
Released in response to low blood sugar and stress
What are the main problems associated with diabetic ketoacidosis
Hyperglycaemia
Ketoacidosis
Dehydration
Potassium imbalance
How might diabetic ketoacidosis present
Polyuria
Polydipsia
Nausea and vomiting
Acetone smell to breath
Dehydration
Hypotension
Altered consciousness
Symptoms of underlying trigger (eg sepsis)
What is the diagnostic criteria for diabetic ketoacidosis
Hyperglycaemia: glucose > 11
Ketosis: ketones > 3
Acidosis
What is the treatment for diabetic ketoacidosis
FIG-PICK
Fluids
Insulin
Glucose
Potassium
Infection (treat)
Chart (fluid balance)
Ketones (monitor)
What is the long term management for type 1 diabetes
Patient education
Monitoring: carb intake, blood sugar levels, for complications
Insulin
What are the short term complications of type 1 diabetes
Hypoglycaemia:
- Symptoms: tremor, sweating, irritability, dizziness, pallor, reduced consciousness, coma, death
- Treatment: rapid acting glucose, slow acting carbs, IV dextrose, IM glucagon
Hyperglycaemia:
- If not DKA, increase insulin
- If DKA, admit
What are the long term complications of type 1 diabetes
Macrovascular: coronary artery disease, peripheral ischaemia, stroke, hypertension
Microvascular complications: peripheral neuropathy, retinopathy, kidney disease
Infection-related: UTIs, pneumonia, skin/soft tissue infections, fungal infections
How can type 1 diabetes be monitored
HbA1c
Capillary blood glucose
Flash glucose monitoring
What are the risk factors for type 2 diabetes
Old age
Black, chinese, south asian
Family history
Obesity
Sedentary lifestyle
High carbohydrate diet
How might type 2 diabetes present
Fatigue
Polydipsia
Polyuria
Unintentional weight loss
Opportunistic infections
Slow healing
Glucoseuria
Explain the oral glucose tolerance test
Measure blood glucose in morning, before breakfast
Give 75g glucose drink
Measure plasma glucose at 2 hours
Tests ability of body to deal with carbohydrates
What is pre-diabetes
HbA1c: 42 - 47
Impaired fasting glucose: 6.1 - 6.9
Impaired glucose tolerance: 7.8 - 11.1 on OGTT
Educate to stop progression to diabetes
What is the diagnostic criteria for type 2 diabetes
HbA1c: > 48
Random glucose: > 11
Fasting glucose: > 7
OGTT: > 11 at 2 hours
What are the treatment targets for type 2 diabetes
HbA1c
48 for newly diagnosed
53 for those on more than just metformin
What is the first line medical management for type 2 diabetes
Metformin
A biguanide
Increases insulin sensitivity
Side effects: diarrhoea, abdominal pain, lactic acidosis
What are the second line medical managements for type 2 diabetes
Gliclazide (a sulfonylurea)
Pioglitazone (a thiazolidinedione)
Sitagliptin (a DPP4 inhibitor)
Empagliflozin (an SGLT-2 inhibitor)
What is the third line medical management for type 2 diabetes
Triple therapy
Metformin + a second line
Metformin + insulin
Give an overview of rapid acting insulins
10 mins - 4 hrs
Novorapid, humalog, apidra
Give an overview of short acting insulins
30 mins - 8 hrs
Actrapid, humulin S, insuman rapid
Give an overview of intermediate acting insulins
1 hr - 16 hrs
Insulatard, humulin I, insuman basal
Give an overview of long acting insulins
1 hr - 24 hrs
Lantus, levemir, degludec
Give an overview of combination insulins
Mixture of rapid and intermediate
Humalog 25, humalog 75, novomix
What is acromegaly
Excess growth hormone
Mostly due to pituitary adenomas (often cause bitemporal hemianopia)
May be due to cancer secreting GHRH/GH
Complications: premature death (cardiovascular disease, bowel cancer)
How might acromegaly present
Space occupying lesion: headache, visual disturbance
Overgrowth of tissue: frontal bossing, large nose, large tongue, large hands and feet, large protruding jaw, arthritis
Organ dysfunction: hypertrophic heart, hypertension, type 2 diabetes, colorectal cancer
Symptoms of excess growth hormone: new skin tags, profuse sweating
What are the investigations for acromegaly
Do not use random GH measurement (fluctuates)
Insulin-like growth factor 1
OGTT whilst measuring GH (high glucose suppresses GH)
MRI brain (pituitary tumours)
Refer to ophthalmology
What is the management for acromegaly
Trans-sphenoidal surgical removal of pituitary
Remove cancers
Medications to block GH: pegvisomant (GH antagonist), somatostatin analogues (inhibits GH release), dopamine antagonists (inhibit GH release)
Gamma knife radiotherapy
What are the symptoms of hypercalcaemia
Renal stones
Painful bones
Abdominal groans (constipation, nausea, vomiting)
Psychiatric moans (fatigue, depression, psychosis)
Give an overview of primary hyperparathyroidism
Uncontrolled PTH production by parathyroid cells
Get hypercalcaemia
Treat by surgically removing tumour
Give an overview of secondary hyperparathyroidism
Vit D deficiency/chronic renal failure lead to low calcium absorption from gut, kidneys, and bones
Get hypocalcaemia
Parathyroid gland releases more PTH
Get hyperplasia of parathyroid cells
Treat underlying cause
Give an overview of tertiary hyperparathyroidism
When secondary hyperparathyroidism continues for a long time
Get hyperplasia of parathyroid
Baseline PTH increases
When cause of secondary hyperparathyroidism treated, PTH stays high
High levels of calcium absorption from intestines, kidneys, and bones
Get hypercalcaemia
Treat by surgically removing parathyroid tissue
Give an overview of primary hyperaldosteronism
Conn’s syndrome
Adrenal glands produce too much aldosterone
Serum renin levels low (suppressed by high blood pressure)
Causes: adrenal adenoma, bilateral adrenal hyperplasia, familial hyperaldosteronism, adrenal carcinoma
Give an overview of secondary hyperaldosteronism
Excess renin stimulates adrenal glands to produce more aldosterone
Causes: renal artery stenosis, renal artery obstruction, heart failure
What investigations are needed for hyperaldosteronism
Calculate renin:aldosterone
Blood pressure
Electrolytes
Blood gas (alkalosis)
What is the management for hyperaldosteronism
Aldosterone antagonists (eplerenone, spironolactone)
Treat underlying cause (remove adenoma, renal artery angioplasty…)
What is SIADH
Excess ADH
Due to: posterior pituitary producing too much ADH, ADH production by a cancer
Get hyponatraemia
Very concentrated urine (high urine osmolality and sodium)
What are the symptoms of SIADH
Headache
Fatigue
Muscle aches and cramps
Confusion
Severe hyponatraemia
How is SIADH diagnosed
Diagnosis of exclusion
Rule out other causes of hyponatraemia
What is the management for SIADH
Stop causative medications
Correct sodium slowly (prevent central pontine myelinolysis)
Fluid restriction
ADH receptor blockers (tolvaptan)
Demeclocycline (antibiotic, inhibits ADH)
What is central pontine myelinolysis
Complication of severe hyponatraemia being treated too quickly
As sodium falls, water crosses blood-brain barrier, brain swells
Phase 1 symptoms: due to electrolyte imbalance, encephalopathy, confusion, headaches, nausea and vomiting
Phase 2 symptoms: due to demyelination of neurones, a few days after sodium correction, spastic quadriparesis, pseudobulbar palsy, cognitive behavioural changes, significant risk of death
What is diabetes insipidus
Lack of ADH/lack of response to ADH
Kidneys not able to concentrate urine
Can be nephrogenic or cranial
What are the causes of nephrogenic diabetes insipidus
(Collecting ducts not responding to ADH)
Drugs: lithium
Genetic mutations
Intrinsic kidney disease
Electrolyte disturbances (hypokalaemia, hypercalcaemia)
What are the causes of cranial diabetes insipidus
(Hypothalamus does not produce ADH)
Idiopathic
Brain tumour
Head injury
Brain malformation
Meningitis, encephalitis
Brain surgery
Brain radiotherapy
How might diabetes insipidus present
Polyuria
Polydipsia
Dehydration
Postural hypotension
Hypernatraemia
What investigations are needed for diabetes insipidus
Low urine osmolality
High serum osmolality
Desmopressin stimulation test
Explain the desmopressin stimulation test
Aka water depletion test
Avoid fluid for 8 hours, measure urine osmolality, give synthetic ADH, measure urine osmolality at 8 hrs
Cranial diabetes insipidus: after deprivation is low, after ADH is high
Nephrogenic diabetes insipidus: after deprivation is low, after ADH is low
What is the management for diabetes insipidus
Treat underlying cause
Desmopressin (synthetic ADH)
What is phaeochromocytoma
Tumour of chromaffin cells
Get unregulated and excessive secretion of adrenaline
25% familial (MEN2 gene)
How is phaeochromocytoma diagnosed
24 hr catecholamines
Plasma free metanephrines
CT/MRI abdomen
How might phaeochromocytoma present
Anxiety
Sweating
Headache
Hypertension
Palpitations
Tachycardia
Paroxysmal atrial fibrillation
What is the management for phaeochromocytoma
Alpha blockers
Beta blockers
Adrenalectomy
What are the causes of hyperprolactinaemia
Firstly, exclude pregnancy
Severe hypothyroidism
PCOS
Pituitary tumours
Renal failure
Antipsychotics
Stress
What is the management for hyperprolactinaemia
Dopamine agonists
Cabergoline, bromocriptine
Side effects: nausea, postural hypotension, psychiatric disturbance
