Endocrinology Flashcards
Diagnosis of diabetes
Fasting >7
Random/OGTT >11.1
HbA1c >48
Diagnosis of impaired glucose tolerance
Fasting 6.1-7
Random/OGTT 7.8-11.1
HbA1c 42-47
Normal fasting, random/OGTT, HbA1c
Fasting 4-5.4
Random/OGTT <7.8
HbA1c <42
Symptoms of hyperglycaemia
Polyuria Polydipsia Blurred vision Lethargy Weight loss Headache Thrush
Symptoms of hypoglycaemia
Hungry Weak Sweaty Shaky Confusion Decreased GCS Coma
What is LADA
Latent autoimmune diabetes of adulthood
Think of this in older patient with T1DM type presentation or not responding to anti-hyperglycaemic agents
What is MODY
Maturity onset diabetes of the young
Like T2DM but young
Will have a strong FH
What are HbA1c targets
48 if on one med
53 if on two or more meds or hypo risk
If >58 step up management
If >80 need insulin
What are the features of Charcot neuropathy
Pes cavus, claw toes, loss of transverse arch, rocker-bottom deformity
What are the features of diabetic retinopathy
Hard exudates Haemorrhage Aneurysms Macular oedema Cotton wool spots Neovascularisation
Which DM meds work by increasing insulin sensitivity
Metformin (biguanide)
Pioglitazone (thiazolidinedione)
Which DM meds work by increasing insulin secretion
DPP4 inhibitors (gliptin)
GLP1 agonists (glutide)
Meglitinides (glinide)
Sulphonylureas (zide)
Which DM med works by increasing renal excretion of glucose
SGLT2 inhibitors (flozin)
Name of DPP4 inhibitors
Gliptins
Linagliptin
Sitagliptin ect
Name of GLP1 agonists
Glutides
Dulaglutide
Liraglutide ect
Name of Metaglitinides
Glinides
Repaglinide
Nateglinide ect
Name of Sulphonylureas
Zide
Glipizide
Tolazamide
Tolbutamide
Name of SGLT2 inhibitors
Gliflozin
Dapagliflozin
Canagliflozin
Which DM meds increase weight
Sulphonylureas
Insulin
Pioglitazone
Which DM meds reduce weight
GLP1 agonists
SGLT2 inhibitors
Which DM meds have the highest risk of hypos
Insulin
Sulphonylureas
Which antibodies are associated with T1DM
ICA - islet cell antibodies
GAD - glutamic acid decarboxylase
What are the microvascular complications of diabetes
Retinopathy
Nephropathy
Neuropathy - peripheral and autonomic
What are the macrovascular complications of diabetes
Stroke
MI
Peripheral vascular disease
Which genes are associated with T1DM
HLA D3/4
Describe the pathophysiology of DKA
Associated with T1DM, develops quickly (<24hrs)
Insufficient insulin replacement or increased demand - hyperglycaemia but inability to utilise it
Increased vascular osmolality so urinary loss of fluids and electrolytes leads to dehydration and reduced total body potassium
Lipolysis leads to increased free fatty acids and lipolysis which causes metabolic acidosis with an increased anion gap
Signs and symptoms of DKA
Nausea, vomiting, abdo pain
Kussmaul breathing, sweet/fruity breath
Sx of hyperglycaemia
Sx of dehydration
Diagnostic criteria of DKA
Ketonaemia >3 or ketonuria 2+
Hyperglycaemia >11 or known T1DM
Acidosis HCO3 <15 +/ venous pH >7.3
What are the potential triggers of DKA
Infection Lack of adherence to medication Alcohol Steroids Injury/surgery Pregnancy Menstruation
How do you manage DKA
Lots of fluid replacement
Fixed rate short acting insulin
Potassium replacement if <5.5 and passing urine
When glucose falls below 14 start IV glucose 10%
Describe the pathophysiology of HHS
Associated with T2DM, develops slowly
Hyperglycaemia (>35) intravascular osmolality (>320) leading to severe dehydration and a thrombotic state
Develops as a result of illness/dehydration
Don’t get ketosis or acidosis like you do in DKA
How do you manage HHS
Rehydration
Prophylactic LMWH
Fixed rate insulin infusion
Management of hypoglycaemia
If able to swallow: 5-7 glucose tablets or 150ml lucozade and a long acting carb
If conscious but can’t swallow: 1.5-2 tubes of glucose gel around the teeth
Unconscious: 150ml 10% glucose STAT, IM glucagon, BM in 10 mins, give long acting carbohydrate when able to swallow
Indications for OGTT at 26 weeks
BMI >30 Previous baby >4.5kg 1st degree relative DM Family origin high risk Previous FDIU or congenital malformations PCOS
Indications for OGTT at 16 weeks
Previous GDM
PCOS
Describe the pathophysiology of GDM
Thought to be the placenta that causes increased insulin requirements and resistance, if the pancreas can’t compensate enough you get GDM
How does pregnancy affect women with existing DM
Insulin resistance increases so may need higher med doses, risk of hypos is higher, and complications (e.g. retinopathy) progress more quickly
What is the extra care for women with existing DM in pregnancy
5mg folic acid (NTD risk)
Aspirin (pre-eclampsia risk)
Growth scans 4wkly after 28/40
When do you aim to deliver for a woman with existing DM
37-39 weeks
When do you aim to deliver for a woman with GDM
Before 41 weeks
Diagnosis of GDM
Fasting 5.6
Random/OGTT 7.8
Glucose targets for GDM/EDM in pregnancy
4-7 throughout the day
<5.3 fasting
<7.8 after meals
What endocrine diseases can cause diabetes
Cushings
Acromegaly
Phaeochromocytoma
What is the difference between ACTH-dependant and ACTH-independant Cushings disease
ACTH-dependent disease — In these diseases, the body is making too much ACTH which leads to too much cortisol production. Pituitary tumors and ectopic ACTH producing tumors are examples. ACTH-independent disease — In this case, the adrenal gland is making too much cortisol and the ACTH is low.
What are the main hormones released by the adrenal glands
Aldosterone (mineralocorticoid)
Cortisol (glucocorticoid)
Androgens
Adrenaline/noradrenaline
What are the ACTH dependant causes of Cushings syndrome
Cushings disease (pituitary adenoma)
Ectopic ACTH production (SCLC)
Rarely - ectopic CRH (medullary thyroid cancer)
What are the ACTH independant causes of Cushings syndrome
Adrenal tumour
Adrenal nodular hyperplasia
Are ACTH levels low or high in ACTH-independant Cushings syndrome
Low - the problem is excess cortisol so ACTH is low due to negative feedback
Describe the possible outcomes of the dexamethasone suppression test
Decreased cortisol with low dose = normal
No change in cortisol with low dose = Cushings syndrome
Decreased cortisol with high dose = Cushings disease (pituitary tumour)
Normal cortisol with high dose = ectopic ACTH secretion
Describe the possible outcomes of the CRH test
Big increase in plasma ACTH + cortisol = Cushings disease
Not much change = ectopic ACTH secretion
Signs/symptoms of raised cortisol
Weight gain/truncal obesity/facial fullness/dorsal fat pad Low mood Amenorrhoea High BP Increased skin pigmentation Red/purple striae Gynaecomastia Ance Bruising Osteoporosis Hypokalaemia Hirsutism Muscle wasting Infection susceptibility/poor wound healing Proximal weakness
What is Nelsons syndrome
A complication of bilateral adrenalectomy - really high ACTH and skin pigmentation
What are the possible causes of primary adrenocortical insufficiency
Addisons/Autoimmune (80%) TB HIV Cancer Adrenal bleed
What is the cause of secondary adrenocortical insufficiency
Withdrawal of long term steroid therapy (you get suppression of pituitary-adrenal axis)
Are cortisol and aldosterone high or low in Addisons disease
Low
What does low cortisol cause
Hypoglycaemia
What does low aldosterone cause
Low Na
High K
What are the signs and symptoms of Addisons disease
Lean, tanned, tired/fatigued, weak, tearful, anorexia, dizzy/faints, flu-like aches and pains, low mood, nausea and vomiting, abdo pain, constipation/diarrhoea, pigmented palmar creases/buccal mucosa, postural hypotension
What happens to Na, K and glucose in Addisons disease
Low Na
High K
Low glucose
Explain the short synacthen test
Its an ACTH stimulation test
You give an ACTH analogue
If cortisol rises to >550 then this excludes Addisons
Because in adrenal insufficiency the adrenals don’t respond to ACTH
9am ACTH levels in primary Vs secondary adrenal insufficiency
Inappropriately high in primary
Low in secondary
Treatment for Addisons disease
Replace cortisol with hydrocortisone
Replace aldosterone with fludrocortisone
Add 5-10mg hydrocortisone before strenuous activity/exercise
Double steroids in febrile illness, injury or stress
Precipitators of Addisonian crisis
Infection Trauma Surgery Missed medication Bilateral adrenal haemorrhage
Clinical features of Addisonian crisis
Hypovolaemic shock - low BP, high HR
High temp
Weak/confused/coma
Possible high K, low Na, low glucose
Management of Addisonian crisis
Check cortisol and ACTH
Check Na and K and treat accordingly (consider rehydration and ECG)
Check blood glucose
Hydrocortisone 100mg IV STAT and fluid bolus
Causes of primary hyperaldosteronism
Conns syndrome (aldosterone producing adenoma) Bilateral adrenocortical hyperplasia
Causes of secondary hyperaldosteronism
Increased renin release secondary to decreased renal perfusion
Some causes of decreased renal perfusion are renal artery stenosis, accelerated HTN, diuretics, CCF, hepatic failure
Features of hyperaldosteronism
Increased Na and H2O retention - high BP
Low K - weakness, cramps, paraesthesia, polyuria, polydipsia
Describe the renin-angiotensin system
Decreased renal artery pressure/Na or sympathetic stimulation causes renin to be released by kidneys
Renin converts angiotensinogen from the liver to angiotensin I
ACE from the lungs converts ANGI to ANGII
ANGII causes vasoconstriction and aldosterone release from the adrenal cortex (to retain Na)
Where is ADH (vasopressin) released from and how does it work
Secreted by the posterior pituitary
Increases water reabsorption by the collecting ducts
In what disease is ADH high and in which disease is ADH low
High in SIADH
Low in diabetes insipidus
SIADH - high or low?: urine osmolality, serum osmolality, serum Na
Urine osmolality > serum osmolality by at least 100 High urine osmolality Low serum osmolality Dilutional hyponatraemia (low serum Na) Euvolaemic/Hypervolaemic
Decrease in volume and an increase in osmolality (concentration) of the urine excreted. The extra water that has been reabsorbed re-enters the circulatory system, reducing the serum osmolality.
Diabetes insipidus - high or low?: urine osmolality, serum osmolality, serum Na
Low urine osmolality
High serum osmolality
Low serum Na
Causes of SIADH
Primary brain injury – e.g. meningitis. subarachnoid haemorrhage (SAH), abscess, stroke, trauma, SLE, vasculitis
Malignancy – e.g. small-cell lung cancer, pancreas, prostate, thyroid, lymphoma
Drugs – e.g. opiates, psychotropics, carbamazepine, SSRIs, amitriptyline
Infectious – e.g. atypical pneumonia, cerebral abscess
Hypothyroidism
TB, pneumonia, abscess, aspergillosis
Symptoms of SIADH
Mild – nausea, vomiting, headache, anorexia, lethargy
Moderate – muscle cramps, weakness, confusion, ataxia
Severe – drowsiness, seizures, coma
Signs of SIADH
Decreased level of consciousness
Cognitive impairment – short-term memory loss, disorientation, confusion
Focal or generalised seizures
Brain stem herniation (severe acute hyponatraemia) – coma, respiratory arrest
Hypervolaemia – pulmonary oedema, peripheral oedema, raised JVP, ascites
What criteria are required to make a diagnosis of SIADH
Concentrated urine: Na >20, osmolality >100
Hyponatraemia <125
Low plasma osmolality <260
Absence of: hypovolaemia, oedema, diuretics
Causes of neurogenic diabetes insipidus
Diabetes insipidus can occur as a result of decreased circulating levels of vasopressin (ADH). Consider hypothalamic or posterior pituitary damage.
Familial mutations in the vasopressin gene (autosomal dominant)
Tumours - pituitary adenoas
Trauma
Neurosurgery
Infections - meningitis
Sheehan’s syndrome
Sarcoidosis (granuloma formation in pituitary)
Haemochromatosis (iron deposition in pituitary/hypothalamus_
Idiopathic
Causes of nephrogenic diabetes insipidus
Familial mutations in ADH receptor gene (X linked recessive)
Familial mutation in aquaporin 2 gene (autosomal recessive)
Metabolic: hypercalcaemia, hyperglycaemia, hypokalaemia
Drugs: lithium, demeclocyline
Chronic renal disease
Amyloidosis
Post obstructive uropathy
Signs and symptoms of diabetes insipidus
Polyuria >3L/24hrs Polydipsia Nocturia Dehydration - headache, dizziness, dry mouth Hypotension Dilute urine Reduced cap refill
Water deprivation test results for diabetes insipidus a) neurogenic b) nephrogenic c) primary polydipsia
Urine osmolality
Neurogenic: <300 after deprivation, >800 after desmopressin
Nephrogenic: <300 after deprivation, <300 after desmopressin
Primary polydipsia: >800 after deprivation, >800 after desmopressin
Describe the pathway for thyroid hormone release
Hypothalamus releases TRH
Anterior pituitary releases TSH
Thyroid releases T4
T4 converted to T3 in the periphery and bound to thyroxine binding globulin
Signs and symptoms of hyperthyroidism
Increased HR, irregular pulse, warm/moist skin, fine tremor, fine hair, palmar erythema, lid lag, lid retraction, goitire, thyroid nodules, bruit
Diarrhoea, weight loss, increased appetite, sweating, proximal myopathy, heat intolerance, palpitations, tremor, irritability, oligomenorrhoea/amenorrhoea/infertility
Causes of hyperthyroidism
Graves disease Toxic multinodular goitre Toxic adenoma Drugs - amiodarone, interferon Sub-acute De Quervain's thyroiditis
Antibody associated with Graves disease
TSH receptor stimulating antibodies
Three features that are unique to Graves disease
Eye disease - exophthalmos, ophthalmoplegia
Pretibial myxoedema
Thyroid acropachy - clubbing, painful swellings on fingers and toes
Treatment options for hyperthyroidism
Carbimazole - titrate vs block and replace
Radioiodine
Thyroidectomy
What is the main risk you need to warn patients about regarding carbimazole
Agranulocytosis - so seek medical advice if sore throat/signs of infection
Features of hyperthyroid crisis/thyrotoxic storm
Increased temperature, agitation, confusion/coma, tachycardia, AF, diarrhoea and vomiting, goitre, thyroid bruit, heart failure
Three medications you can use to treat thyroid storm
Propanolol
Carbimazole
Hydrocortisone/dexamethasone (stops peripheral conversion of T4 to T3)
Signs and symptoms of thyroid eye disease
Exophthalmos (appearance of protrusion), proptosis (protrusion beyond the orbit), ophthalmoplegia, conjunctival oedema
Discomfort, grittiness, increased tear production, photophobia, diplopia, decreased acuity, afferent pupillary defect if optic nerve is compressed
Causes of a nodular goitre
Toxic multinodular goitre
Toxic adenoma
Carcinoma
Causes of a diffuse goitre
Physiological
Graves disease
Hashimotos thyroiditis
De Quervains thyroiditis (painful)
Signs and symptoms of hypothyroidism
Tired/lethargic, low mood, cold intolerance, weight gain, constipation, menorrhagia, hoarse voice, decreased memory/cognition, myalgia, cramps, weakness
Bradycardia, reflexes relax slowly, cerebellar ataxia, dry/thin hair and skin, cold, round/puffy face, goitre
Causes of hypothyroidism
Primary atrophic hypothyroidism
Hashimotos thyroiditis
Post-thyroidectomy/radioiodine
Drugs - amiodarone, lithium, iodine, antithyroid meds
De Quervains thyroiditis (second phase)
Secondary hypothyroidism due to pituitary disease
Which antibodies are associated with Hashimotos thyroiditis
Anti-TPO
Anti-Tg
What problems can hypothyroidism cause in pregnancy
Eclampsia Anaemia Prematurity Low birth weight PPH Stillbirth
Medication used to treat hypothyroidism
Levothyroxine
Features of myxoedema coma
Typical hypothyroid features plus low temperature, decreased reflexes, low blood glucose, bradycardia, coma, seizures, HF, cyanosis, hypotension
What is sick euthyroidism and what would TFTs be like
Asymptomatic deranged TFTs in a systemic illness
Typical pattern is for everything to be low
What is De Quervains thyroiditis and what would TFTs be like
Post-viral thyroiditis
Painful goitre
Initial hyperthyroidism then hypothyroidism
What is subacute hyper/hypothyroidism and what would TFTs be like
Asymptomatic
TSH changed but normal T3/T4
What are the 5 types of thyroid cancer
Papillary Follicular Medullary Anaplastic Lymphoma
What is the typical presentation of papillary thyroid cancer
Young woman with lymph node metastases
In which thyroid cancer would serum calcitonin be raised
Medullary carcinoma
What is the typical presentation of anaplastic thyroid cancer
Elderly women, rapid growth and local invasion
What is the typical presentation of follicular thyroid cancer
Middle aged, solitary thyroid nodule, may have spread to lung and bone
What are the 5 possible FNAC results of thyroid biopsy
Thy 1 - non-diagnostic Thy 2 - benign Thy 3 - intermediate Thy 4 - suspicious Thy 5 - malignancy
Describe the action of parathyroid hormone
Released by the parathyroid glands in response to low serum calcium
- increases osteoclast activity
- increases renal Ca reabsorption and PO4 excretion
- increases VitD levels
So overall increases serum calcium and decreases serum phosphate
What are the 4 types of hyperparathyroidism
Primary
Secondary
Tertiary
Malignant
What are the causes of primary hyperparathyroidism
Solitary adenoma
Parathyroid gland hyperplasia
Parathyroid gland cancer (<1%)
What are the symptoms of primary hyperparathyroidism
Increased serum calcium: weak, tired, depressed, polydipsia, polyuria, dehydration, renal stones, abdo pain, pancreatitis, peptic ulcers
Bone reabsorption: pain, fractures, osteopenia, osteoporosis
Increased BP
What medication can be used to reduce PTH levels
Cinacalcet
What are the causes of secondary hyperparathyroidism
It’s a physiological/appropriate response to low serum Ca. So causes include low vitamin D intake and chronic renal failure
What is tertiary hyperparathyroidism
Inappropriately high PTH despite high serum Ca
Happens when you have had secondary hyperparathyroidism for a very long time which causes the parathyroid glands to undergo hyperplasia and start to act autonomously from serum Ca so you have high PTH unlimited by negative feedback. Seen in chronic renal failure
What is malignant hyperparathyroidism
When you get parathyroid-related-protein (PTHrP) produced by a cancer (SCLC, breast, renal cell carcinomas).
PTHrP increases Ca.
PTH serum levels wouldn’t be increased because PTHrP doesn’t show up on the assay so you need to order a special test
What can cause primary hypoparathyroidism
Autoimmune
Congenital
What can cause secondary hypoparathyroidism
Radiation
Surgery
Low Mg
Signs/symptoms of hypocalcaemia
Cramps, perioral numbness, muscle spasm, confusion, seizures, Chvostek sign (twitching of facial muscles if you tap over the facial nerve)
What are the 6 anterior pituitary hormones
Growth hormone FSH and LH (gonadotrophins) TSH ACTH Prolactin
What can cause raised prolactin levels
Pregnancy/breastfeeding
Medications - antipsychotics, dopamine antagonists
Hypothyroidism
What are the signs/symptoms of high prolactin
Raised prolactin causes low LH/FSH/testosterone/estrogen
Hypogonadism, infertility, osteoporosis, amenorrhoea/oligomenorrhea, decreased libido, anorgasmia, erectile dysfunction
Which medications are used to treat high prolactin
Dopamine agonists - Cabergoline/Bromocriptine
