Flashcards in Endocrinology Deck (168):
What is the cause of cushing's disease?
Pituitary adenoma secreting ACTH causing bilateral adrenal hyperplasia
Name 2 common sources of ectopic ACTH secretion
Small cell carcinoma of the lung
Carcinoid tumour of the bronchus
What are the features of ectopic production of ACTH?
Name 2 causes of ACTH independent cushing's syndrome
Exogenous steroid use
How is a diagnosis of cushing's syndrome confirmed?
U&Es and ABG
24 hour urinary free cortisol - need at least 2 samples with cortisol over 3 times normal amount
Low dose dexamethasone suppression test - give 1mg at 11pm and measure cortisol at 8am. Should be suppressed to less than 50nmol/l
How can the cause of cushing's syndrome be localised?
Plasma ACTH - if undetectable then is an ACTH independent cause eg steroid use or adrenal tumour
If detectable then do a high dose dexamethasone suppression test. If origin is pituitary, will still be under some control so cortisol will be suppressed at very high doses (>90%)
Ectopic secretion will show less reactivity and won't be as suppressed
How is cushing's syndrome treated?
If due to excess steroid use, stop drugs if possible
If pituitary, then remove trans-sphenoidally
If adrenal then bilateral adrenectomy
If ectopic, then remove source if possible
Cortisol will need reducing pre-operatively to reduce risk. Use ketoconazole or metyrapone short term. Mitotane long term
What condition can occur after bilateral removal of adrenal glands?
Growth of pituitary and excess ACTH production due to loss of negative feedback from the adrenal glands - nelson's syndrome with hyperpigmentation and headaches
Name give complications of untreated cushing's syndrome
Perforation of viscera
What is secondary adrenal insufficiency caused by?
Insufficient ACTH due to suppression of the HPA axis, eg in long term steroid use
Name three causes of addison's disease
COngenital adrenal hyperplasia
Give 5 symptoms of addison's disease
Loss of appetite and premature satiety
Nausea and vomiting
How should suspected addison's disease be investigated?
Serum cortisol in the morning/soon after waking
AXR/CXR if TB/adrenal haemorrhage/malignancy is suspected
How does the synacthen test work?
Serum cortisol is given then dose of synthetic ACTH and cortisol is remeasured 30-60mins later. Cortisol should increase to >550nmol if normal
What U&Es abnormalities are present in addison's disease?
How is Addison's disease treated?
Replace glucocorticoids with hydrocortisone TDS
Replace mineralocorticoids with fludrocortisone
How is an addisonian crisis managed?
100mg IV hydrocortisone stat
What is the difference between primary and secondary hyperthyroidism?
Primary is due to an abnormality of the thyroid gland
Secondary is due to abnormal stimulation of a normal thyroid gland, eg by a TSH secreting pituitary tumout
What abnormalities in thyroid function tests are found in overt hyperthyroidism?
Low TSH, High free T4 and free T3
What is subclinical hyperthyroidism?
Low TSH but normal T4 and T3
Name 2 causes of hyperthyroidism
Graves' disease (autoimmune)
Toxic multinodular goitre
Exogenous eg drugs
De Quervain's thyroiditis
What is the immunological abnormality in Graves' disease?
Circulating IgG autoantibodies activate thyroid receptors causing enlargement, hormone production and orbital swelling
In which populations is toxic multinodular goitre most common?
The elderly and iodine deficient populations,eg denmark
What is De Quervain's thyroiditis?
Post viral cause of hyperthyroidism with painful goitre and raised temperature
What are the sign's of Graves' eye disease?
Proptosis, uncomfortable, red, gritty eye with increased tear production
Lid lad or retraction
Risk of corneal ulceration
Opthalmoplegia on looking up
What is the main pharmacological management of hyperthyroidism?
Carbimazole or propylthiouracil
When should radioiodine use be avoided?
Graves' eye disease
What are the signs of thyrotoxic storm?
Cardiovascular collapse, raised temperature
Agitation and confusion
Diarrhoea and vomiting
How should a thyrotoxic storm be managed?
Reduce peripheral effects of excess hormones by giving fluids, IV beta blockers, high dose digoxin and cooling
Inhibit further hormone synthesis with carbimazole
Treat systemic complications with 100mg IV hydrocortisone
What autoantibodies should be tested for in suspected hyperthyroidism?
THyroid peroxidase (TPO)
TSH receptor autoantibodies confirms graves'
What TFT abnormalities are found in overt hypothyroidism?
High TSH and low T4
What are the two causes of autoimmune hypothyroidism?
Hashimoto's and primary atrophic hypothyroidism
Give three conditions associated with Hypothyroidism
Primary billiary cirrhosis
Type 1 diabetes
How is hypothyroidism treated?
How is a myxoedema coma managed?
Give O2 if cyanotic
5-20micrograms of liothyronine (T3)
100mg IV hydrocortisone
What is the target HbA1c for a type 1 diabetic?
48mmol or less (6.5%)
What is the target HbA1c for a type 2 diabetic on medication associated with hypoglycaemia?
53mmol/mol or less (7%)
Give 3 side effects of insulin therapy
Lipohypertrophy at injection sites
What class of agent is metformin?
What are the effects of metformin?
Reduce insulin resistance
Reduce hepatic gluconeogenesis
Increase uptake and oxidation of glucose by skeletal muscle
Which hypoglycaemic agents are not associated with weight gain?
GLP1 agonists eg exenatide
DPP-4inhibitors eg sitagliptin
SGLT2 inhibitors, eg dapagliflozin
What is the main serious side effect of metformin?
Give an example of a sulphonylurea?
Gliclazide or tolbutamide
How do sulphonylureas interact with warfarin?
Strongly bound to warfarin so can affect levels of other highly protein bound agents, eg warfarin
Give three side effects of sulphonylureas
Bone marrow suppression
What is the action of sulphonylureas?
Inhibit potassium pump of beta cells to increase insulin secretion
Give 2 contraindications to the use of sulphonylureas
Severe hepatic impairment
Severe renal impairment
Which anti-diabetic medications can cause hypoglycaemia?
What is the mechanism of action of glitazones?
Increase sensitivity to insulin by increasing transcription of insulin sensitive genes
How are glitazones excreted?
In the bile, after metabolism by the liver
Give three side effects of glitazones
Give a contraindication of glitazone use
Liver failure due to fluid retention
How do GLP-1 agonists work?
Resistant to degradation by DPP-4, unlike GLP-1, so can act to increase insulin secretion in response to oral ingestion of glucose
How are GLP-1 agonists administered?
Give two side effects of GLP-1 agonists?
Give three side effects of DPP-4 inhibitors
How do SGLT2 inhibitors work?
Inhibit the SGLT2 channel in the proximal convoluted tubule to decrease glucose reabsorption and increase excretion
Give three side effects of SGLT2 inhibitors
Dysuria and polyuria
What are the actions of parathyroid hormone (PTH)?
Increase osteoclast activity to Increase release of calcium and phosphate
Increase renal reabsorption of calcium and increase renal excretion of phosphate
Increase renal production of vitamin D3 to increase intestinal absorption of calcium
What is the most common cause of primary hyperparathyroidism?
Solitary parathyroid adenoma
What are the features of osteitis fibrosa cystica?
Subperiosteal resorption of distal phalanges
Distal clavicle tapering
'salt and pepper' skull
Brown tumours of long bones
Give five features of hypercalcaemia
Proximal myopathy and fatigue
Depression, dementia and confusion
Peptic ulcer disease
Reduced QT interval
What are the biochemical abnormalities in primary hyperparathyroidism?
Reduced Vit D
What cancers can lead to malignant hyperparathyroidism?
Squamous cell lung cancers
What abnormalities are present in malignant hyperparathyroidism?
Low PTH (caused by parathyroid related protein, which doesn't show up in assay)
Other than hyperparathyroidism, give three differentials for hypercalcaemia
Familial benign hypocalciuric hypercalcaemia
Paget's bone disease
What are the indications for parathyroidectomy in hyperparathyroidism?
Calcium more than 0.25mmol.l above the reference range
Renal calculi present
Creatinine clearance <60ml.min
How can primary hyperparathyroidism be medically managed?
HRT to protect bone density
Calcimometic eg cinacalcet to lower calcium
What is secondary hyperparathyroidism?
High levels of parathyroid hormone due to hypocalcaemia
What are the most common causes of secondary hyperparathyroidism?
Chronic kidney disease
Vitamin D deficiency
What are the phosphate levels like in secondary hyperparathyroidism?
High in renal disease
Low in vitamin D deficiency
How should secondary hyperparathyroidism of CKD be managed?
Calcium and vitamin D supplementation
Phosphate restriction or binders eg lanthanon
Calcimimetics eg cinacalcet
How does tertiary hyperparathyroidism occur?
After prolonged secondary hyperparathyroidism, parathyroid glands become autonomous and hyperplastic so no longer respond to negative feedback
What are the biochemical abnormalities of tertiary hyperparathyroidism?
How is tertiary hyperparathyroidism managed?
Either surgery or calcimimetics
What are the biochemical features of primary hypoparathyroidism?
What is the cause of primary hypoparathyroidism?
Gland failure, either congenital or autoimmune
Give three ways of acquiring hypoparathyroidism
Drugs eg chemo
What is pseudohypoparathyroidism?
High levels of PTH but hypocalcaemia due to PTH resistance at the tissues
What are the clinical features of pseudohypoparathyroidism?
Basal ganglia calcification
What is Chvostek's sign?
Sign of latent tetany.
When mouth is slightly open, mouth twitched upon tapping the facial nerve over the parotid gland
Give 6 features of hypocalcaemia
Neuromuscular irritability with cramping, tetany and seizures
Muscle and bone pain
Dry hair and skin
Give three hypothalamic causes of hypopituitarism
Give three pituitary stalk causes of hypopituitarism
Mass lesion, eg craniopharyngoma
Carotid artery aneurysm
Give three pituitary causes of hypopituitarism
Autoimmune eg lymphocytic hypophysitis
Give 5 features of growth hormone deficiency
Reduced muscle mass and strength
Reduced attention and memory
Reduced cardiac output
What are the histological classifications of pituitary tumours?
Chromophobe are either non-secretory/hypopituitary or secrete prolactin. Commonly cause mass effect
Basophilic tumours secrete ACTH and rarely cause mass effect
Eosinophilic tumours secrete prolactin or growth hormone
Give three symptoms of local pressure exerted by a pituitary tumour
Bitemporal/retrooribital headache that's worse on waking
In which order are pituitary hormones affected?
What are cranipharyngomas?
Tumours originating from rathke's pouch causing amenorrhoea, reduced libido and mass effect
What are the actions of prolactin?
Production of milk and secretory alveoli
Inhibition of reproductive system
Name three physiological causes of hyperprolactinaemia
Name three intracranial causes of hyperprolactinaemia
Name three endocrine/metabolic causes of hyperprolactinaemia
Chronic renal failure
What stimulates the production of prolactin?
What inhibits the production of prolactin?
Give 5 drugs that causes hyperprolactinaemia
Antidepressants eg citalopram
What symptoms are experienced by women with hyperprolactinaemia?
Amenorrhoea or oligomenorrhoea
Reduced vaginal lubrication
How is hyperprolactinaemia managed?
surgery if intolerant
What are the side effects of cabergoline/bromocriptine?
Fibrosis of heart/lungs/retroperitoneum
Name three cancers that may ectopically secrete growth hormone
What hormones are indicated in acromegaly?
Insulin like Growth Factor 1 (IGF-1)
What blood chemistry abnormalities are found in acromegaly?
High calcium, phosphate and triglycerides
How is acromegaly diagnosed?
Screening for by IGF-1
Diagnosed with glucose tolerance test. If Growth hormone stays above 1mcg/L then there is acromegaly
How is acromegaly managed?
If not then somatostatin analogues eg octreotide
If not tolerated then growth hormone antagonist or dopamine agonist eg pegvisomant or cabergoline
Name three complications of acromegaly
Obstructive sleep apnoea
Risk of colonic adenocarcinoma
Risk of thyroid cancer
Hypopituitarism once treated
Reduced self esteem
Give 5 causes of cranial diabetes insipidus
Infection eg meneingitis
What is the difference between cranial and nephrogenic diabetes insipidus?
Cranial is a reduced secretion of ADH from the hypothalamus
Nephrogenic is a renal insensitivity to ADH
Give 5 causes of nephrogenic diabetes insipidus
Durgs eg lithium
Renal tubular acidosis
What are the symptoms of diabetes insipidus?
Marked polyuria (>3l/day)
How is diabetes insipidus diagnosed?
Suspect if urine output >3l/day
Do plasma and urine osmolality. If P:U ratio is >2 then exclude
Do fluid deprivation test
What results are found in diabetes insipidus on doing a fluid deprivation test?
Osmolality should be >800 after 8 hours of fluid deprivation.
Give 2micrograms of desmopressin. If osmolality increases in four hours to >800 then it is cranial DI
If osmolality doesn't increase, it is nephrogenic DI
How is diabetes insipidus managed?
If cranial, give desmopressin
If nephrogenic, correct the cause and give desmopressin if necessary
When is type 1 diabetes diagnosed?
Random plasma glucose of >11 or fasting >7 + symptoms of hypergylcaemia
aysymptomatic with 2 x fasting glucose of >7
Give 5 features that suggest a diagnosis of type 1 diabetes rather than type 2
Rapid weight loss
Age of onset <50 years
Personal or family history of autoimmune disease
HLA D3 or D4 associated
What investigations should be done when diabetes is diagnosed?
U&Es and eGFR
What is the target HbA1c for someone with type 1 diabetes?
48mmol or 6.5%
What is the first line antihypertensive in diabetes?
When should a statin be started in diabetes?
If any of:
>40 years old
Diabetes for >10 years
Cardiovascular disease risk factors
What should be monitored at a type 1 diabetic review?
height, weight and waist circumference and BMI
Depression, anxiety and eating disorders
Neuropathy by asking about erectile dysfunction, gastroparesis, neuropathic pain
Check injection sites
Screen for retinopathy
Cardiovascular risk factors
How is diabetic ketoacidosis managed?
IV fluids of 1-1.5l of 0.9%NaCl per hour reduced to 1l every 2-4 hours until glucose is <11.1 and switch to 5% dextrose with 0.45%NaCl at 1l every 4 hours
Correct any hypokalaemia
0.1units/kg/hour of IV insulin and aim for 8.3-11.1mmol/l
What is the consequence of starting IV insulin therapy when there is hypokalaemia?
Can cause respiratory paralysis, cardiac arrhythmias and death
What is the diagnostic criteria for DKA?
Acidosis (pH<7.3) + hyperglycaemia (>11.1) + ketosis
Give 5 risk factors for the development of hypoglycaemia in diabetes
Tight glycaemic control
injection into lipohypertrophy site
Insulin prescription error
Long duration of diabetes
Reducing renal function
How is hypoglycaemia acutely managed?
10-20g glucose PO or 75ml 20% dextrose or 150 ml 10% dextrose IV
Something to eat and drink once conscious
Name 3 drugs that can precipitate hyperosmolar hyperglycaemic state
Calcium channel blockers
How is hyperosmolar hyperglycaemic state managed?
Iv fluids 0.9% NaCl to correct 6-9l fluid loss in 48 hours
wait an hour before giving insulin or until glucose levels stabilise on fluid therapy then give 0.05units/kg/hour
Identify and correct any precipitant
LMWH to reduce risk of occlusive event
What is hyperosmolar hyperglycaemic state?
Sever hyperglycaemia with markedly increased osmolarity and without ketosis
What is phaeochromocytoma?
A rare, catecholamine producing tumour of sympathetic preganglionic collections of adrenaline-secreting chromaffin cells
Give 5 symptoms of phaeochromocytoma
Give 5 signs of phaeochromocytoma
What may precipitate symptoms of phaeochromocytoma?
Straining or abdominal pressure
Drugs eg beta blockers and TCAs
What familial conditions are associated with phaeochromocytoma?
MEN 2a and 2b
Von Hippel Landau syndrome
How is non-malignant phaeochromocytoma managed?
Pre-op alpha blockers then beta blockers then adrenalectomy
What post-op monitoring should be done after an adrenalectomy for phaeochromocytoma?
24 hour urine metadrenalines
How is malignant phaeochromocytoma managed?
Chemotherapy or radio-labelled chromaffin-seeking isotope
What is primary hyperaldosteronism?
Excess production of aldosterone, independent of the RAAS system with sodium and water retention and reduced renin release
When should primary hyperaldosteronism be suspected?
If hypokalaemia, hypertension (especially resistant) and alkalosis
What are the main causes of primary hyperaldosteronism?
70% is bilateral adrenal hyperplasia
30% is aldosterone producing adenoma - Conn's syndrome
How is primary hyperaldosteronism managed?
If conn's syndrome - adrenalectomy with pre-op spironalactone
If hyperplasia - aldosterone antagonist eg spironolactone
How is primary hyperaldosteronism diagnosed?
Bloods showing hypokalaemia and alkalosis
Aldosterone:renin ratio will be increased
What is secondary hyperaldosteronism?
Excess aldosterone secretion as a result of high renin, due to reduced renal perfusion
Give 3 causes of secondary hyperaldosteronism
Renal artery stenosis
How is secondary hyperaldosteronism diagnosed?
Bloods showing hypokalaemia
Aldosterone:renin ratio will be normal
What is Barter's syndrome?
A congenital defect in the NaCl channel of the loop of henle, causing sodium loss, hypokalaemia and metabolic alkalosis
How is barter's syndrome managed?
Give 5 risk factors for the development of type 2 diabetes
history of gestational diabetes
Poor dietary habit
Low birth weight for gestational age
What are the features of metabolic syndrome?
When can type 2 diabetes be diagnosed?
If asymptomatic then 2 abnormal measurements of HbA1c (>6.5% or 48mmol) or fasting plasma glucose (>7mmol)
If symptomatic then only 1 abnormal reading is required, unless also unwell
When should HbA1c not be used as a diagnostic tool?Give 3 examples
If <18 years old
If pregnant/<2 months post partum
If symptomatic for less than 2 months
If acutely unwell
If on medication that causes hyperglycaemia
Acute pancreatic damage
End stage CKD
When should HbA1c be interpreted with caution?
Altered red cell life span
Recent blood transfusion
How should hypertension be treated in a white person with diabetes?
then add either calcium channel blocker or thiazide diuretic
Then combine all 3
How should hypertension be treated in a black person with diabetes?
ACE-1/ARB + either calcium channel blocker or diuretic
THen combine all 3
Give 5 complications of diabetes
Reduced quality of life
Reduced life expectancy
At what stage of blood sugar control should diabetes pharmacological management be stepped up?
If HbA1c consistently above 7.5%/58mmol on optimal therapy
What are the steps of drug therapy for diabetes?
Start with metformin (or gliptin/sulphonylurea/pioglitazone if contraindicated)
Add a gliptin/sulfonylurea/pioglitazone
What conditions are featured in MEN type 1?
What conditions are featured in MEN type 2a?
Medullary thyroid cancer
What conditions are featured in MEN type 2b?
Medullary thyroid cancer
Marfinoid body habitus
Name 3 features of diabetic nephropathy
In general, how does diabetic nephropathy progress?
What are the deficits involved in chronic diabetic peripheral neuropathy?
Reduced sensation of touch, proprioception, temperature and pain mostly in lower limbs
May also be reduced ankle and knee reflexes
What are the four main forms of diabetic neuropathy?
Proximal motor neuropathy
Give 5 manifestations of autonomic neuropathy in diabetes?
Orthostatic rate changes
Cardiovascular lability intra- and perioperatively
Nausea and vomiting
How is neuropathic pain in diabetes managed?
Foot cradles at night
Amitriptylline, duloxetine, gabapentin or pregabalin
What are the main features of non-proliferative diabetic retinopathy?
Cotton wool spots
What are the main features of proliferative diabetic retinopathy?
Fibrous tissue formation anterior to retinal disc