Endocrine Flashcards

1
Q

What is adrenal insufficiency?

A

the adrenal glands do not produce enough steroid hormones, particularly cortisol and aldosterone.

Steroids are essential for life = life-threatening unless the hormones are replaced.

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2
Q

What is Addison’s disease?

A

PRIMARY ADRENAL INSUFFICIENCY

specific condition where the adrenal glands have been damaged, resulting in a reduction in the secretion of cortisol and aldosterone

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3
Q

Most common cause of Addison’s disease

A

autoimmune

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4
Q

what is secondary adrenal insufficiency?

A

inadequate ACTH stimulating the adrenal glands, resulting in low cortisol release

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5
Q

What is ACTH

A

Adrenocorticotrophic hormone

secreted by the pituitary gland

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6
Q

causes of secondary adrenal insufficiency

A

damage to pituitary gland:

  • pituitary tumour
  • infection
  • loss of blood flow
  • radiotherapy
  • Sheehan’s syndrome = massive blood loss in childbirth that leads to necrosis of the pituitary gland
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7
Q

what is tertiary adrenal insufficiency?

A

inadequate CRH release by the hypothalamus

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8
Q

what is CRH

A

Corticotrophin releasing hormone, released by the hypothalamus

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9
Q

Describe the HPA axis

A

hypothalamic-pituitary-adrenal axis:

  1. hypothalamus releases corticotrophin releasing hormone
  2. causing anterior pituitary to release adrenocorticotrophic hormone
  3. causing the adrenal cortex in the adrenal glands to release cortisol
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10
Q

causes of tertiary adrenal insufficiency

A

long term oral steroids - suppress the hypothalamus

This is why you shouldn’t suddenly withdraw exogenous steroids - hypothalamus is suppressed so no endogenous steroids will be produced

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11
Q

symptoms of adrenal insufficiency

A
Fatigue
Nausea
Cramps
Abdominal pain
Reduced libido
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12
Q

Signs of adrenal insufficiency

A

Bronze hyperpigmentation to skin (ACTH stimulates melanocytes to produce melanin)

Hypotension (particularly postural hypotension)

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13
Q

Ix for adrenal insufficiency

A

Hyponatraemia
Hyperkalaemia
Early morning cortisol - often falsely normal

Short synacthen test = FOR DIAGNOSIS

ACTH

  • High in primary adrenal insufficiency
  • low in secondary adrenal insufficiency

Adrenal cortex antibodies & 21-hydroxylase antibodies - in autoimmune adrenal insufficiency

CT/MRI adrenals
MRI pituitary

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14
Q

What is the short synacthen test?

A

For diagnosing adrenal insufficiency

Give synacthen (synthetic ACTH)
blood cortisol measured at baseline, 30 mins and 60 mins 
Synthetic ATCH wil stimulate healthy adrenal glands & the cortisol should at least double 

Failure of cortisol to at least double = primary adrenal insufficiency (Addison’s)

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15
Q

tx of adrenal insuffiency

A

hydrocortisone to replace cortisol

fludrocortisone to replace adolesterone

Patients need: steroid card & double doses on sick days (don’t STOP)

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16
Q

What is an addisonian crisis?

A

Adrenal crisis

Acute presentation of severe Addison’s disease
The absence of steroid hormones leads to a life threatening presentation

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17
Q

Symptoms of addisonian crisis

A

Reduced consciousness
Hypotension
Hypoglycaemia, hyponatraemia, hyperkaemia
Patients can be very unwell

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18
Q

what triggers an addisonian crisis

A

infection
trauma
other acute illness
sudden steroid withdrawal

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19
Q

mx of addisonian crisis

A
Intensive monitoring 
IV hydrocortisone
IV fluid resuscitation 
Correct hypoglycaemia
Careful monitoring of electrolytes
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20
Q

What is cushings syndrome?

A

the signs and symptoms that develop after prolonged abnormal elevation of cortisol.

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21
Q

What is Cushings disease?

A

the specific condition where a pituitary adenoma (tumour) secretes excessive ACTH.

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22
Q

Difference between cushings syndrome and cushings disease

A

Cushings disease causes cushings syndrome

but cushings syndrome isn’t always caused by cushings disease

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23
Q

symptoms of cushings syndrome

A
round 'moon' face
central obesity
abdo striae
buffalo hump - fat pad on upper back
proximal limb muscle wasting
HTN
cardiac hypertrophy
hyperglycaemia (T2DM)
depression
insomnia

osteoporosis
easy bruising
poor skin healing

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24
Q

causes of cushings syndrome

A

exogenous steroids
cushings disease = pituitary adenoma releasing excessive ACTH
adrenal adenoma
paraneoplastic cushings - ACTH released from small cell lung cancer

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25
ix for cushings syndrome
``` dexamtheasone suppression test 24 hour urinary free cortisol FBC - raised WCC U&E - hypokalaemia if aldosterone also secreted by adrenal adenoma MRI brain - pituitary adenoma chest CT - SCLC Abdo CT - adrenal tumour ```
26
Tx for cushings syndrome
remove underlying cause 1. trans-sphenoidal removal of pituitary adenoma (cushings disease) 2. surgical removal of adrenal tumour 3. surgical removal of tumours producing ectopic ACTH If you can't remove the cause - remove the adrenal glands and give replacement steroids for life
27
what is the dexamethasone suppression test used for?
used to diagnose cushings syndrome and find the cause 1. Give dexamethasone at 10pm at night, measure cortisol and ACTH in the morning 2. do low dose test first - give 1mg of dexamethasone = used to see if they have a normal HPA axis or if they have cushings syndrome 3. do high dose test second if they have an abnormal low dose test to look for the cause of cushings syndrome
28
how does the low dose dexamethasone test work and what is a normal result/a result showing cushings syndrome?
Give 1mg dexamethasone at 10pm In the morning measure cortisol and ACTH In a normal person, the addition of steroids causes negative feedback on the hypothalamus and pituitary = low cortisol and ACTH in the morning In someone with cushings syndrome, the addition of a small amount of steroids makes no difference as they already have high levels of cortisol. Therefore cortisol will be high/normal in the morning
29
how does the high dose dexamethasone test work and what do the results show?
high dose test is performed following an abnormal result on the low dose test give 8mg of dexamethasone at 10pm, measure the cortisol and ACTH the next morning In cushings disease (pituitary adenoma) = pituitary shows some response to negative feedback. 8mg of dex is enough to suppress cortisol & ACTH In adrenal adenoma = cortisol production is independent on the pituitary. So cortisol is not suppressed but ACTH is Ectopic ACTH production (SCLC) = cortisol and ACTh won't be suppressed because ACTH production is independent of the hypothalamus and pituitary gland
30
What is diabetes insipidus?
a lack of ADH or lack of response to ADH = prevents the kidneys from concentrating the urine so there's polyuria and polydipsia
31
how can diabetes insipidus be classified?
nephrogenic | cranial
32
what is nephrogenic diabetes insipidus?
when the collecting ducts of the kidneys do not respond to ADH
33
causes of nephrogenic diabetes insipidus
- lithium - mutations in AVPR2 gene on X chromsome - Intrinsic kidney disease - Hypokalaemia - Hypercalcaemia
34
what is cranial diabetes insipidus?
when the hypothalamus does not produce ADH for the pituitary gland to secrete
35
Causes of cranial diabetes insipidus
``` idiopathic brain tumours head injury brain malformations brain infections - meningitis, encephalitis, TB Brain surgery/chemotherapy ```
36
presentation of diabetes insipidus
``` Polyuria polydipsia dehydration postural hypotension HYPERNATRAEMIA ```
37
ix for diabetes insipidus
low urine osmolality high serum osmolality water deprivation test
38
what is the water deprivation test and how is it done?
used to diagnose diabetes insipidus 1) no fluids for 8 hours = fluid deprivation 2) measure urine osmolality 3) give synthetic ADH (desmopressin) 4) 8 hours later measure urine osmolality again
39
What do the results of the water deprivation test show?
For cranial diabetes insipidus = urine osmolality starts low as the brain isn't producing any ADH, then after giving desmopressin the usine osmolality is high because the kidneys can still respond to ADH For nephrogenic diabetes insipidus = the urine osmolality is low to start and stays low after desmopressin is given as the kidneys can't respond to ADH for primary polydipsia = the 8 hours of water deprivation will cause a high urine osmolality even before desmopressin is given
40
whats another name for the water deprivation test?
desmopressin stimulation test
41
management of diabetes insipidus
desmopressin in cranial DI High doses of desmopressin in nephrogenic DI under close monitoring
42
what are the short synacthen test, dexamethasone suppression test and water deprivation test/desmopressin stimulation test each used for?
short synacthen test = low cortisol/adrenal insufficiency ie Addisons disease dexamethasone suppression test = high cortisol ie cushings syndrome/disease water deprivation test = diabetes insipidus (nephrogenic/cranial)
43
Symptoms/signs of Hypercalcaemia
'bones, stones, groans and psychic moans' - abnormal bone remodelling/fracture risk - kidney stones - abdo cramps/nausea/ileus/constipation - lethargy, depression, psychosis corneal calcification shortened QT interval on ECG hypertension
44
causes of Hypercalcaemia
1) primary hyperparathyroidism (most common in the community) 2) malignancy (most common in hospital) = SCLC, bone mets, myeloma ``` Other causes: sarcoidosis vitamin D intoxication acromegaly thyrotoxicosis thiazides dehydration Addisons disease ```
45
mx for Hypercalcaemia
rehydration with NaCl - 3-4L /day after rehydration = bisphosphonates (take 2-3 days to work) calcitonin is quicker than bisphosphonates steroids in sarcoidosis
46
symptoms of hypocalcaemia
NEUROMUSCULAR EXCITABILITY tetany - muscle twitching, cramping and spasm perioral paraesthesia chronic hypocalcaemia = depression, cataracts ECG = prolonged QT interval Trousseau's sign Chvosteks sign
47
what is trousseau's sign?
seen in hypocalcaemia carpal spasm if the brachial artery occulded by inflating BP cuff to a pressure above their systolic BP
48
what is chvostek's sign?
seen in hypocalcaemia tapping over parotid causes facial muscles to twitch
49
causes of hypocalcaemia
``` vitamin D deficiency (osteomalacia) CKD hypoparathyroidism pseudohypoparathyroidism rhabdomyolysis magnesium deficiency massive blood transfusion acute pancreatitis ``` contamination of blood samples with EDTA = falsely low calcium
50
mx of hypocalcaemia
IV replacement for severe hypocalcaemia - IV calcium gluconate 10ml of 10% solution over 10 mins ECG monitoring
51
ECG changes seen in hyperkalaemia
Tall tented T waves Small/loss of P waves Widened QRS complex - leads to sinusoidal pattern Asystole
52
Causes of hyperkalaemia
``` AKI Potassium sparing diuretics ACEi ARBs Spironolactone Ciclosporin Heparin Metabolic acidosis Addison's disease (primary adrenal insufficiency) Rhabdomyolysis Massive blood transfusion ```
53
Mx of hyperkalaemia
Stabilise cardiac membrane = IV CALCIUM GLUCONATE (this doesn't lower serum K) Short term shift of K from extracellular to intracellular space = INSULIN/DEXTROSE INFUSION & NEB SALBUTAMOL Removal of K from body = CALCIUM RESONIUM (oral/enema), LOOP DIURETICS, DIALYSIS (haemofiltration/haemodialysis for patients with AKI & persistent hyperkalaemia) Stop any exacerbating drugs Treat underlying cause
54
classification of hyperkalaemia
``` mild = 5.5 to 5.9 moderate = 6.0 to 6.4 severe = >6.5 ```
55
how should you classify hypokalaemia?
with or without hypertension
56
causes of hypokalaemia with hypertension
cushings syndrome conn's syndrome (primary hyperaldosteronism) liddle's syndrome 11-beta hydroxyls deficiency - congenital adrenal hyperplasia
57
causes of hypokalaemia without hypertension
``` diuretics GI loss - diarrhoea and vomiting renal tubular acidosis bartter's syndrome - inherited cause of severe hypokalaemia gitelman syndrome ```
58
symptoms of hypokalaemia
muscle weakness hypotonia predisposes to digoxin toxicity
59
ECG changes in hypokalaemia
U waves small/absent t waves prolonged PR interval ST depression
60
causes of hypokalaemia with alkalosis
vomiting thiazide and loop diuretics cushings syndrome conn's syndrome (primary hyperaldosteronism)
61
causes of hypokalaemia with acidosis
diarrhoea renal tubular acidosis acetazolamide partially treated DKA
62
mx of hypokalaemia
Check and replete Magnesium Treat underlying cause mild = oral KCl if no acidosis or ora potassium bicarbonate if there's acidosis moderate = oral KCl unless can't have PO or there's ECG changes Severe = IV KCl. Do not give more than 20mmol/hr. concentration should not exceed 40mmol/L. Faster transfusion than 20mmol/hr through a central line in ICU. Need continuous cardiac monitoring and check K levels every 2-4 hrs
63
what are the causes of hyponatraemia?
URINARY SODIUM >20 MMOL/L - thiazide / loop diuretics - addison's disease - diuretic stage of renal failure - SIADH - hypothyroidism URINARY SODIUM <20 MMOL/L - diarrhoea - vomiting - sweating - burns - adenoma of rectum - HF - liver cirrhosis - nephrotic syndrome - IV dextrose - psychogenic polydipsia
64
complication of untreated hyponatraemia
cerebral oedema = brain herniation
65
symptoms of hyponatraemia
early = headache, lethargy, nausea, vomiting, dizziness, confusion, muscle cramps late = seizures, coma, respiratory arrest
66
causes of hyponatraemia by volume status
hypovolemic hyponatraemia/clinically dehydrated: diuretic stage of renal failure, diuretics, Addisonian crisis euvolemic hyponatraemia: SIADH heart failure, liver failure, nephrotic syndrome
67
mx of hyponatraemia
hypovolaemic cause: - 0.9% NaCl euvolemic cause: fluid restrict to 500-1000ml/day. consider demeclocycline / vaptans hypervolemic cause: fluid restrict to 500-1000ml/day. consider loop diuretic/vaptans severe hyponatraemia with symptoms (<120mmol/L): HDU & give hypertonic saline (3% NaCl)
68
complications of mx of hyponatraemia
central pontine myelinolysis (osmotic demyelination syndrome) don't correct Na by more than 6-12 mmol/l in a 24 hour period symptoms = dysarthria, dysphagia, paraparesis or quadriparesis, seizures, confusion, and coma (locked in syndrome)
69
causes of hypernatraemia
dehydration osmotic diuresis e.g. hyperosmolar non-ketotic diabetic coma diabetes insipidus excess IV saline
70
mx of hypernatraemia
a rate of no greater than 0.5 mmol/hour correction is appropriate = helps avoid cerebral oedema (seizures, coma and death) IV 5% dextrose
71
causes of hyperlipidaemia
``` Predominantly hypertriglyceridaemia = diabetes mellitus (types 1 and 2) obesity alcohol chronic renal failure drugs: thiazides, non-selective beta-blockers, unopposed oestrogen liver disease ``` ``` predominantly hypercholesterolaemia = nephrotic syndrome cholestasis hypothyroidism familial hypercholesterolaemia ```
72
mx of hyperlipidaemia
for primary prevention: - give to people with 10 year cardiovascular risk of >10% OR T1DM OR eGFR <60 ATROVASTATIN 20MG OD (titrate up to 80mg if reduction in non-HDL cholesterol hasn't fallen by at least 40%) for secondary prevention: - give if known IHD OR CVA OR PAD ATROVASTATIN 80MG OD
73
How to assess 10 year cardiovascular risk
QRISK2 - age - gender - ethnicity - postcode - BMI - smoker - family hx CAD - HTN, ?treated - total cholesterol:HDL cholesterol - DM - AF - Renal disease - RA
74
lifestyle advice for hyperlipidaemia
cardioprotective diet - reduce fats, wholegrain starches, 5 portion fruit/veg, 2 portions fish per week, 4-5 portions unsalted nuts/seeds/legumes per week physical activity - 150 mins cardio per week weight management alcohol intake to <14 units per week smoking cessation
75
what secretes parathyroid hormone and what is it secreted in response to?
chief cells in the parathyroid glands PTH secreted in response to hypoclacaemia
76
What does PTH do?
Increases serum calcium by - - increasing osteoclast activity - increasing calcium absorption from gut - increasing calcium absorption from kidneys - increasing vitamin D activity = increases calcium absorption from intestines
77
symptoms of hyperparathyroidism
symptoms of hypercalcaemia = painful bones, kidney stones, abdominal groans and psychiatric moans
78
causes of primary hyperparathyroidism
tumour of the parathyroid glands = releases uncontrolled amounts of PTH High PTH & high calcium
79
causes of secondary hyperparathyroidism
parathyroid gland hyperplasia in response to hypocalcaemia from low vitamin D/chronic renal failure High PTH & low/normal calcium
80
causes of tertiary hyperparathyroidism
cause of secondary hyperparathyroidism is treated but the enlarged parathyroid gland continues to produce large amounts of PTH High PTH and high calcium
81
mx of primary hyperparathyroidism
surgical removal of parathyroid gland tumour
82
mx of secondary hyperparathyroidism
correct vitamin D deficiency or renal transplant for renal failure
83
mx of tertiary hyperparathyroidism
surgically remove part of the parathyroid tissue
84
cause of hyperthermia
malignant hyperthermia
85
what is malignant hyperthermia?
condition often seen following administration of anaesthetic agents characterised by hyperpyrexia and muscle rigidity cause by excessive release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle
86
genetics associated with malignant hyperthermia
autosomal dominant inheritance defects in a gene on chromosome 19 encoding the ryanodine receptor, which controls Ca2+ release from the sarcoplasmic reticulum
87
causative agents of malignant hyperthermia
halothane suxamethonium antipsychotics - neuroleptic malignant syndrome
88
ix for malignant hyperthermia
CK raised | contracture tests with halothane and caffeine
89
mx of malignant hyperthermia
dantrolene - prevents Ca2+ release from the sarcoplasmic reticulum
90
what classifies as hypothermia?
Mild hypothermia: 32-35°C | Moderate or severe hypothermia: < 32°C
91
causes of hypothermia
Exposure to cold in the environment is the major cause Inadequate insulation in the operating room Cardiopulmonary bypass Newborn babies.
92
risk factors for hypothermia
``` General anaesthesia Substance abuse Hypothyroidism Impaired mental status Homelessness Extremes of age ```
93
symptoms of hypothermia
shivering cold and pale skin. Frostbite occurs when the skin and subcutaneous tissue freeze, causing damage to cells. slurred speech tachypnoea, tachycardia and hypertension (if mild) respiratory depression, bradycardia and hypothermia (if moderate) confusion/ impaired mental state
94
ix in hypothermia
``` temperature ECG FBC & U&Es - high hb and haematocrit, platelets & WCC low due to sequestration in the spleen, can be hypokalaemic BMs Arterial blood gas Coagulation factors CXR ```
95
ECG changes seen in hypothermia
``` bradycardia 'J' wave - small hump at the end of the QRS complex first degree heart block long QT interval atrial and ventricular arrhythmias ```
96
what not to do when someone if hypothermic
Don't put the person into a hot bath. Don't massage their limbs. Don't use heating lamps. Don't give them alcohol to drink.
97
what causes primary hypoparathyroidism?
primary hypoparathyroidism: | - secondary to thyroid surgery
98
symptoms of hypoparathyroidism and ECG changes
the symptoms of hypocalcaemia - tetany - perioral paraesthesia - Trousseau's sign - Chvostek's sign ECG - prolonged QT interval
99
ix for primary hypoparathyroidism
hypocalcaemia high phosphate low PTH
100
mx for primary hypoparathyroidism
alfacalcidol
101
what is pseudohypoparathyroidism?
the target cells are insensitive to PTH due to abnormality in a G protein
102
what is pseudohypoparathyroidism associated with?
associated with low IQ, short stature, shortened 4th and 5th metacarpals
103
ix for pseudohypoparathyroidism
low calcium high phosphate high PTH measure urinary cAMP and phosphate following an infusion of PTH - in hypoparathyroidism this causes an increase in cAMP and phosphate levels, in pseudohypoparathyroidism type I cAMP and phosphate don't increase, pseudohypoparathyroidism type II cAMP increases but phosphate doesn't
104
causes of hypothyroidism
Hashimoto's thyroiditis - autoimmune Iodine deficiency carbimazole propylthiouracil radioactive iodine thyroid surgery Lithium Amiodarone secondary hypothyroidism: - tumours in pituitary gland - infection in pituitary gland - vascular e.g. sheehan syndrome - radiation to pituitary gland
105
symptoms of hypothyroidism
``` Weight gain Fatigue Dry skin Coarse hair and hair loss Fluid retention (oedema, pleural effusions, ascites) Heavy or irregular periods Constipation ```
106
symptoms of hypothyroidism
``` Weight gain Fatigue Dry skin Coarse hair and hair loss Fluid retention (oedema, pleural effusions, ascites) Heavy or irregular periods Constipation Decreased deep tendon reflexes carpal tunnel syndrome occasionally - hoarse voice ```
107
Ix for hypothyroidism
primary hypothyroidism = low T3 and T4, high TSH secondary hypothyroidism = low T3, T4, TSH
108
mx of hypothyroidism
levothyroxine (synthetic T4 that metabolises to T3 in the body) titrate up dose until TSH level normal measure TSH monthly until stable then less frequently check TSH 8-12 weeks after dose change
109
when should patients get a lower dose of levothyroxine?
elderly patients | IHD
110
when should you increase a patients dose of levothyroxine?
in women who get pregnant
111
SEs of levothyroxine
hyperthyroidism: due to over treatment reduced bone mineral density worsening of angina atrial fibrillation
112
interactions of levothyroxine
iron calcium carbonate (they reduce the absorption of levothyroxine so give at least 4 hours apart)
113
mx of obesity
1 diet / exercise 2 medical: - orlistat = pancreatic lipase inhibitor (causes faecal urgency/incontinence and flatulence) 3 surgical: - laparoscopic adjustable gastric banding - sleeve gastrectomy - intragastric balloon - biliopancreatic diversion with duodenal switch - roux-en-Y gastric bypass surgery
114
what are the effects of a pituitary tumour?
- large ones can compress the optic chiasm = bitemporal hemianopia (loss of outer half of vision) - acromegaly (excessive GH) - hyperprolactinaemia - cushings disease (high cortisol) - thyrotoxicosis
115
Causes of hyperthyroidism
primary hyperthyroidism - - Grave's disease (autoimmune condition) - most common cause - toxic multi nodular goitre - solitary toxic thyroid nodule - thyroiditis - e.g. de quervains, hashimotos, postpartum and drug induced secondary hyperthyroidism - - TSH secreting pituitary tumour amiodarone over treatment with levothyroxine
116
what is grave's disease?
Autoimmune condition TSH receptor antibodies cause a primary hyperthyroidism the TSH receptor antibodies mimic TSH and stimulate TSH receptors on the thyroid most common cause of hyperthyroidism
117
What is toxic multinodular goitre?
Also known as Plummer's disease Nodules develop on the thyroid gland - act independently of the normal feedback mechanism & continuously produce excessive thyroid hormone
118
symptom specific to graves disease
Exophthalmos = bulging of eyeball Pretibial myxoedema = deposits of mucin on anterior of leg - waxy discoloured oedematous appearance of skin (is a reaction to the TSH antibodies) Diffuse goitre (without nodules)
119
symptom specific to graves disease
Exophthalmos = bulging of eyeball ophthalmoplegia Pretibial myxoedema = deposits of mucin on anterior of leg - waxy discoloured oedematous appearance of skin (is a reaction to the TSH antibodies) Diffuse goitre (without nodules) digital clubbing
120
symptoms specific to toxic multi nodular goitre
Goitre with firm nodules Most patients are aged over 50 Second most common cause of thyrotoxicosis (after Grave’s)
121
what is de quervain's thyroiditis?
a viral infection with fever, neck pain and tenderness, dysphagia and features of hyperthyroidism hyperthyroid phase followed by hypothyroid phase
122
mx of de quervain's thyroiditis?
self limiting condition NSAIDs beta-blockers for symptomatic relief of hyperthyroid
123
what is thyrotoxic crisis/thyroid storm?
a more severe presentation of hyperthyroidism with pyrexia, tachycardia and delirium
124
what is Thyrotoxicosis
an abnormal and excessive quantity of thyroid hormone in the body.
125
mx of thyrotoxic crisis
admit to hospital monitoring fluid resuscitation anti-arrhythmic medication beta blockers
126
mx of hyperthyroidism
1st = Carbimazole - can do titration block or block and replace (give levothyroxine too) 2nd = propylthiouracil 3rd = radioactive iodine beta blockers for heart palpitations thyroidectomy + levothyroxine
127
how is Carbimazole used?
used in the management of thyrotoxicosis. It is typically given in high doses for 6 weeks until the patient becomes euthyroid before being reduced. blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production
128
side effects of Carbimazole
agranulocytosis | crosses the placenta, but may be used in low doses during pregnancy
129
risks associated with propylthiouracil
severe hepatic reaction - including death
130
strict rules when using radioactive iodine to treat hyperthyroidism
Must not be pregnant and are not allowed to get pregnant within 6 months Must avoid close contact with children and pregnant women for 3 weeks (depending on the dose) Limit contact with anyone for several days after receiving the dose
131
how does radioactive iodine work in hyperthyroidism?
Treatment with radioactive iodine involves drinking a single dose of radioactive iodine. This is taken up by the thyroid gland and the emitted radiation destroys a proportion of the thyroid cells. This reduction in functioning cells results in a decrease of thyroid hormone production and thus remission from the hyperthyroidism. Remission can take 6 months and patients can be left hypothyroid afterwards and require levothyroxine replacement.
132
what autoantibodies are present in graves disease?
TSH receptor stimulating antibodies (90%) | anti-thyroid peroxidase antibodies (75%)
133
what is acromegaly?
++ growth hormone | GH is produced by the anterior pituitary gland
134
cause of acromegaly
pituitary adenoma that secretes unregulated amounts of GH rarely caused by lung or pancreatic cancers that secrete GH
135
presentation of acromegaly
Space Occupying Lesion: - Headaches - Visual field defect (“bitemporal hemianopia”) Overgrowth of tissues: - Prominent forehead and brow (“frontal bossing”) - Large nose - Large tongue (“macroglossia”) - Large hands and feet - Large protruding jaw (”prognathism”) - Arthritis from imbalanced growth of joints GH can cause organ dysfunction: - Hypertrophic heart - Hypertension - Type 2 diabetes - Colorectal cancer Symptoms suggesting active raised growth hormone: - Development of new skin tags - Profuse sweating
136
Ix for acromegaly
Insulin like growth factor 1 (IGF-1) Oral glucose tolerance test while measuring GH - high glucose normally suppress GH MRI brain - pituitary tumour Ophthalmology referral for visual field testing
137
Tx of acromegaly
trans-sphenoidal removal of the pituitary tumour medications used to block GH: - pegvisomant - somatostatin analogues e.g. ocreotide - dopamine agonist e.g. bromocriptine
138
how does the renin-angiotensin system work?
juxtaglomerular cells in the afferent arterioles in the kidney sense the BP if there's low BP, the kidney secrete renin the liver then secretes angiotensinogen renin converts angiotensinogen to angiotensin I angiotensin I is converted to angiotensin II in the lungs with the help of angiotensin converting enzyme (ACE) angiotensin II stimulates the release of aldosterone from the adrenal glands
139
what does aldosterone do?
it is released by the adrenal glands acts on the kidney to: - increase Na reabsorption from the distal tubule - increase potassium secretion from the distal tubule - increase hydrogen secretion from the collecting ducts
140
what is primary hyperaldosteronism?
Conn's syndrome Adrenal glands are directly responsible for producing too much aldosterone Low serum renin
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causes of primary hyperaldosteronism
``` Adrenal adenoma - that secretes aldosterone Bilateral adrenal hyperplasia Familial hyperaldosteronism Adrenal carcinoma (rare) ```
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what is secondary hyperaldosteronism
excessive renin stimulates the adrenal glands to produce more aldosterone serum renin is high
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causes of secondary hyperaldosteronism
high renin happens when blood pressure to the kidneys is disproportionately lower than blood pressure to the rest of the body renal artery stenosis renal artery occlusion heart failure
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Ix for hyperaldosteronism
do a renin / aldosterone ratio Low renin and high aldosteronism = conn's syndrome (primary hyperaldosteronism) High renin and high aldosterone = secondary hyperaldosteronism ``` Blood pressure - HTN Hypokalaemia Blood gas - alkalosis CT/MRI for adrenal tumour Renal doppler US, CT angiogram or MRA for renal artery stenosis or obstruction ```
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Mx of hyperaldosteronism
Aldosterone antagonists: - Eplerenone - spironolactone Treat underlying cause: - surgical removal of adenoma - Percutaneous renal artery angioplasty via the femoral artery
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what is the most common cause of secondary hypertension
hyperaldosteronism | if a patients HTN isn't responding to antihypertensives, do a renin:aldosterone ratio
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what is a pheochromocytoma?
a tumour of chromatin cells in the adrenal medulla that secrete an unregulated amount of adrenaline the adrenaline tends to be secreted in bursts, giving periods of worse symptoms followed by settled periods
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what is the cause of 25% of pheochromocytomas?
multiple endocrine neoplasia type 2 (MEN 2)
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what is the 10% rule used to describe pheochromocytoma?
10% bilateral 10% cancerous 10% outside the adrenal gland
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how is a pheochromocytoma diagnosed
24 hour urine catecholamines | plasma free metanephrines
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why are 24 hour urine catecholamines measured for pheochromocytoma?
adrenaline is a catecholamine serum catecholamines will naturally fluctuate throughout the day so instead measure them in the urine over 24 hours can see how much adrenaline the tumour is secreting over the 24 hours
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Why are plasma free metanephrines measured for pheochromocytomas?
adrenaline has a short half life in the blood metanephrines are the breakdown products of adrenaline - have a longer half life the levels of metanephrines are less prone to dramatic fluctuations
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symptoms of pheochromocytoma
``` Anxiety Sweating Headache Hypertension Palpitations, tachycardia and paroxysmal atrial fibrillation ```
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Mx of pheochromocytoma
``` Alpha blockers (i.e. phenoxybenzamine) Beta blockers once established on alpha blockers Adrenalectomy to remove tumour is the definitive management - need to have symptoms medically controlled before surgery to reduce anaesthetic risk ```
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What is SiADH
there's inappropriately large amounts of ADH
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What does ADH do and where is it secreted from?
secreted by posterior pituitary gland stimulates water reabsorption from the collecting ducts in the kidneys
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Electrolyte disturbances and urine changes caused by SiADH
hyponatraemia due to excessive ADH causing lots of water reabsorption in the collecting ducts get a euvolemic hyponatraemia - because the reabsorption is not significant enough to cause fluid overload urine gets more concentrated by kidneys as more water is reabsorbed - high urine osmolality and high urine sodium
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symptoms of SiADH
``` Headache Fatigue Muscle aches and cramps Confusion Severe hyponatraemia can cause seizures and reduced consciousness ```
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causes of SiADH
Post-operative from major surgery Infection, particularly atypical pneumonia and lung abscesses Head injury Medications (thiazide diuretics, carbamazepine, vincristine, cyclophosphamide, antipsychotics, SSRIs, NSAIDSs,) Malignancy, particularly small cell lung cancer Meningitis
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Diagnosis of SiADH
Diagnosis of exclusion (can't measure ADH directly) Euvolaemia on examination U&Es = hyponatraemia Urine sodium and osmolality high Do CXR to look for lung abscess/cancer/pneumonia Exclude other causes: - short synacthen test - no diuretic use - no diarrhoea, vomiting, burns, fistula, excessive sweating - no excessive water intake - no CKD or AKI
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Mx of SiADH
treat underlying cause or stop medications causing it correct sodium slowly by no more than 10mmol/l increase in sodium in 24 hours (reduces risk of central pontine myelinolysis)
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Mx of SiADH
treat underlying cause or stop medications causing it correct sodium slowly by no more than 10mmol/l increase in sodium in 24 hours (reduces risk of central pontine myelinolysis) fluid restriction (500-1l) Tolvaptan (a vaptan) - ADH receptor blockers Demeclocycline - tetracycline abx that inhibits ADH
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Where is insulin produced?
beta cells in the islets of langerhans in the pancreas
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what is T1DM?
a disease where the pancreas stops being able to produce insulin. When there is no insulin being produced, the cells of the body cannot take glucose from the blood and use it for fuel. Therefore the cells think the body is being fasted and has no glucose supply. Meanwhile the level of glucose in the blood keeps rising, causing hyperglycaemia.
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Causes of T1DM
Unknown cause Some theories: - Genetic component - triggered by a virus: coxsackie B / enterovirus
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presentation of DKA
``` Hyperglycaemia Dehydration Ketosis Metabolic acidosis (with a low bicarbonate) Potassium imbalance ``` The patient will therefore present with symptoms of these abnormalities: ``` Polyuria Polydipsia Nausea and vomiting Acetone smell to their breath Dehydration and subsequent hypotension Altered Consciousness They may have symptoms of an underlying trigger (i.e. sepsis) ```
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Pathology of DKA
1. Ketoacidosis - ketogenesis to make fuel 2. dehydration - hyperglycaemia causes glucose to be filtered into urine so water is drawn into urine too 3. potassium imbalance - hyperkalaemia as insulin draws K into cells, when insulin tx starts: sudden hypokalaemia
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Diagnosis of DKA
Hyperglycaemia (i.e. blood glucose > 11 mmol/l) Ketosis (i.e. blood ketones > 3 mmol/l) Acidosis (i.e. pH < 7.3)
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Mx of DKA
FIG PICK F - IV fluids with NaCl I - INsulin - fixed rate insulin infusion (act rapid 0.1 unit/kg/hour) G - glucose - add dextrose when BM <14 P - potassium (closely monitor) I - infection (treat) C - chart fluid balance K - ketones (monitor blood ketones / bicarbonate) Establish patient on normal subcut insulin regime prior to stopping insulin and fluid infusion Don't infuse K faster than 10 mmol/hr
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Long term management of T1DM
Patient education about: - Subcutaneous insulin regimes - Monitoring daily carbohydrate intake - Monitoring BMs - waking, before each meal and before bed - Monitoring & managing complications Insulin: - Background, long acting insulin once daily + short acting insulin 30 mins before a meal - rotate injection sites to avoid lipodystrophy
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short term complications of T1DM
Hypoglycaemia Hyperglycaemia (DKA)
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Typical symptoms of hypoglycaemia
``` tremor sweating irritability dizziness pallor ``` severe: reduced LOC, coma and death
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Tx of hypoglycaemia
Rapid acting glucose (10-20g in liquid, gel or tablet form) / glycogen + slow acting carbohydrate if able to swallow Reduced GCS = IM glucagon / IV dextrose (20% 125ml)
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Long term complications of T1DM
Macrovascular Complications: - Coronary artery disease is a major cause of death in diabetics - Peripheral ischaemia causes poor healing, ulcers and “diabetic foot” - Stroke - Hypertension Microvascular Complications: - Peripheral neuropathy - Retinopathy - Kidney disease, particularly glomerulosclerosis Infection Related Complications: - UTIs - Pneumonia - Skin and soft tissue infections, particularly in the feet - Fungal infections, particularly oral and vaginal candidiasis
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Monitoring of T1DM
HbA1C (to count glycerinated Hb) - check every 3-6 months Capillary BMs Flash glucose monitoring e.g. free style libre
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What happens in T2DM?
Repeated exposure to glucose and insulin makes the cells in the body become resistant to the effects of insulin. ``` It requires more insulin to produce a response from the cells and get them to take up and use glucose. The pancreas (beta cells) becomes fatigued and damaged by producing so much insulin and they start to produce less. ``` A continued onslaught of glucose on the body in light of insulin resistance and pancreatic fatigue leads to chronic hyperglycaemia.
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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
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Presentation of T2DM
``` Fatigue Polydipsia and polyuria (thirsty and urinating a lot) Unintentional weight loss Opportunistic infections Slow healing Glucose in urine (on dipstick) ```
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Ix for T2DM
HbA1C Oral glucose tolerance test - test fasting plasma glucose have a 75mg glucose drink then measure plasma glucose 2 hrs later
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What is pre-diabetes?
An indication the patient is heading towards diabetes, need education on lifestyle + no medications. HbA1c – 42-47 mmol/mol Impaired fasting glucose – fasting glucose 6.1 – 6.9 mmol/l Impaired glucose tolerance – plasma glucose at 2 hours 7.8 – 11.1 mmol/l on an OGTT
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What are the criteria for the diagnosis of T2DM?
HbA1c > 48 mmol/mol Random Glucose > 11 mmol/l Fasting Glucose > 7 mmol/l OGTT 2 hour result > 11 mmol/l
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Mx for T2DM
``` Patient education Diet modification Exercise weight loss stop smoking treat HTN/lipids ``` Medical mx: - 1st line = metformin - 2nd line = add sulfonylura / pioglitazone / DPP-4 inhibitor / SGLT-2 inhibitor - 3rd line = triple therapy with metformin and 2 of the second line drugs OR metformin + insulin
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Treatment targets for T2DM
48 mmol/mol for new type 2 diabetics 53 mmol/mol for diabetics that have moved beyond metformin alone
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What is metformin, how does it work and what are its side effects?
A biguanide Increases insulin sensitivity and decreases liver production of glucose Side effects: diarrhoea and abdo pain lactic acidosis DOES NOT CAUSE hypoglycaemia
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What is pioglitazone, how does it work and what are its side effects?
A thiazolidinedione Increases insulin sensitivity and decreases liver production of glucose ``` Side effects: weight gain fluid retention anaemia HF Increased risk of bladder ca ``` DOES NOT CAUSE hypoglycaemia
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Give an example Sulfonylurea, how it works and the side effects
Gliclazide stimulates insulin release from the pancreas Side effects Weight gain HYPOGLYCAEMIA increased risk of CVD and MI
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Give an example DPP-4 inhibitor, how it works and the side effects
Sitagliptin Works by increasing GLP-1 activity Side effects GI upset Symptoms of URTI Pancreatitis
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Give an example GLP-1 mimetic, how it works and the side effects
Exenatide (subcutaneous injection) Increase insulin secretions, inhibit glucagon production and slow absorption in GI tract ``` Side effects GI upset Weight loss Dizziness Low risk of hypoglycaemia ```
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What are example SGLT-2 inhibitors, how do they work and what are their side effects?
empagliflozin, dapagliflozin cause glucose to be excreted in the urine ``` Side effects Glucoseuria Increased UTIs Weight loss DKA ```
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What is a hyperosmolar hyperglycaemic state?
Medical emergency Hyperglycaemia results in osmotic diuresis, severe dehydration, and electrolyte deficiencies.
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Pathology of HHS
Hyperglycaemia results in osmotic diuresis with associated loss of sodium and potassium Severe volume depletion results in a significant raised serum osmolarity (typically > than 320 mosmol/kg), resulting in hyperviscosity of blood. Despite these severe electrolyte losses and total body volume depletion, the typical patient with HHS, may not look as dehydrated as they are, because hypertonicity leads to preservation of intravascular volume.
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Who gets HHS?
elderly with T2DM ncidence in younger adults is increasing can be the initial presentation of T2DM.
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Symptoms of HHS
General: fatigue, lethargy, nausea and vomiting Neurological: altered level of consciousness, headaches, papilloedema, weakness Haematological: hyperviscosity (may result in myocardial infarctions, stroke and peripheral arterial thrombosis) Cardiovascular: dehydration, hypotension, tachycardia
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Criteria for diagnosing HHS
1. Hypovolaemia 2. Marked Hyperglycaemia (>30 mmol/L) without significant ketonaemia or acidosis 3. Significantly raised serum osmolarity (> 320 mosmol/kg)
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Mx for HHS
1. Normalise the osmolality (gradually with NaCl) the serum osmolality is the key parameter to monitor if not available it can be estimated by 2 * Na+ + glucose + urea 2. Replace fluid and electrolyte losses 3. Normalise blood glucose (gradually)