Endocrinology Flashcards
acromegaly
- due to what hormone?
- main cause? other cause?
- 1st line Ix
- Ix to confirm dx
- 1st line tx? other option?
Excess GH
Usually due to pituitary adenoma
Can be due to tumours EG pancreatic - producing GHRH or GH
1st line Ix: serum IgF-1 levels.
- If high/equivocal, confirm w OGTT & serial GH measurements (lack of suppression of GH to <1 after hyperglycaemia)
1st line tx: trans-sphenoidal surgery
If tumour inoperable or surgery unsuccessful: octreotide (somatostatin analogue; directly inh release of GH)
octreotide
- what is it?
- what effect does it have?
- 1 SE
- uses?
- Long acting analogue of somatostatin
- Somatostatin released by D cells of pancreas
○ Inhibits release of GH, glucagon and insulin - SE: gallstones (due to biliary stasis)
- Somatostatin released by D cells of pancreas
Uses
- Acromegaly - Variceal haem (acute) - Carinoid syndrome - Prevent comps after panc surgery - VIPomas - Refractory diarrhoea
bromocriptine - what is it?
dopamine agonist
pegvisomant what is it? what used for?
GH receptor antagonist
acromegaly
fasting glucose
- normal
- prediabetic
- diabetes
Normal 6 and under
Prediabetes: 6.1-6.9
Diabetes: 7 and more
HbA1c normal, prediabetic, diabetic
Normal 41 and under (5.9%)
Prediabetes: 42-47 (6-6.4%)
Diabetic = 48 and above (6.5%)
do you ever treat prediabetes?
Start metformin - If HbA1c or fasting blood glucose still rising despite intensive lifestyle change in those with IFG/IGT
type 1 renal tubular acidosis
- where does it effect?
- features?
causes
distal tubule
- low K, nephrocalcinosis, renal stones
- Can’t generate acid urine (secrete H)
Causes: RA, SLE, sjogren’s, amphotericin B, analgesic nephropathy, idiopathic
type 2 rta
where does it affect
2 fts
causes
Type 2 (proximal) - Low K - Osteomalacia - Causes: fanconi syn, wilson's disease, cystinosis, old tetracyclines, topiramate/acetazolamide (carbonic anhydrase inh) Decreased bicarb reabs
ABG pic for rta
high chloride metabolic acidosis (normal anion gap)
type 4 rta
- 1 main ft
- 2 causes
- High K
- Cause: low aldosterone, diabetes
- Low aldosterone > reduction in ammonia exc from proximal tubule
diagnostic ix for diabetes
If has symptoms, dx:
- Fasting glucose of 7 or more
- Random glucose of 11.1 or more (or after OGTT)
If asym: need to show this on 2x occasions
HbA1c: 48 (6.5%) or above = diagnostic if syms (asym: repeat to confirm)
But below that doesn’t rule it out.
if metformin is tolerated, mx path for diabetes
- Metformin
- HbA1c >58 (7.5%): add gliptin, sulfonylurea, pioglitazone or SGLT2 inh
- Still >58: insulin or triple therapy
a. Metformin + sulfonylurea + gliptin
b. Metformin + sulfonylurea + pioglitazone
c. Metformin + sulfonylurea + SGLT 2 inh
d. Metformin + pioglitazone + SGLT2 inh
If triple therapy not effective/tolerated/CI and BMI >35: metformin + sulfonyulrea + GLP-1 mimetic
if metformin not tol/ci: mx path for t2dm
- Gliptin, sulfonylurea or pioglitazone
- HbA1c >58: 2 of those 3
>58: insulin
- HbA1c >58: 2 of those 3
exenatide - what is it? has what effect? SE? effect on wt?
GLP1 mimetic = exenatide, liraglutide
increase insulin secretion, inhibit glucagon secretion
N+V, severe pancreatitis, renal impairment
wt loss
gliptins
what are they
what do they do
what effect on wt
DPP4 inh = gliptins: Increase levels of incretins (GIP and GLP-1) by decreasing their peripheral breakdown»_space; inh glucagon sec
wt neutral
Risk of pancreatitis
pioglitazone what is it what does it do effect on wt se
Pioglitazone (thiazolidinedione) = agonists of PPAR-gamma receptors»_space; reduce peripheral insulin resistance
– Activate PPAR-gamma rec in adipocytes > promote adipogenesis and fatty acid uptake
- wt gain
Adverse effects • wt gain • liver impairment: monitor LFTs • fluid retention - CI in HF (increased risk if on insulin) • increased risk of fractures bladder cancer (pioglitazone)
metformin
- actions?
- SE
when can’t it be used
Increases insulin sens, decreases hepatic gluconeogenesis
- SE: GI upset, lactic acidosis
Can’t use if eGFR <30
sulfonylureas
- 2 examples
- what do they do
effect on wt? glucose?
(gliclazide, glimepiride) = stim beta cells to sec insulin
wt gain
hypoglycaemia
low Na
-gliflozins what are they action effect on wt SE
- SGLT2 inhibitors (-gliflozins): Inh reabs of glucose in kidney
wt loss
UTIs
low K with alkalosis: 4
low K w acidosis: 4
alkalosis: vomiting, thiazides/loop diuretics, cushing’s, conn’s
acidosis: diarrhoea, renal tubular acidosis, acetazolamide, partially tx DKA
cushings
- underlying problem
- main causes 2
- abg pic
- dx
- localisation?
Cushing’s syndrome = sustained overproduction of cortisol
- Most common cause: steroids
- Cushing’s disease (80%): pituitary tumour secreting ACTH»_space; adrenal hyperplasia
Low K, metabolic alkalosis
dx: Overnight dex suppression test (if have cushing’s don’t get a morning cortisol spike)
localisation
1. 9am and midnight plasma ACTH (and cortisol) levels - If ACTH suppressed: non-ACTH dep cause is likely 2. Or high dose dex suppression test - Both cortisol and ACTH suppressed: cushing's disease - Neither suppressed: ectopic ACTH syndrome - Cortisol not suppressed, ACTH supp: adrenal adenoma etc
what effect does alcohol binge drinking have on ADH and Na
Alcohol binge drinking»_space; ADH suppression > polyuria
- Similar to cranial DI - High Na w high serum osm + low urine osm
SIADH fts and tx
SIADH
- Stimuli»_space; excess ADH secretion»_space; low Na
- High Na concentration in urine
Tx: fluid restriction (or if need: demeclocycline)
kallman’s
- Low sex hormones, LH+FSH low/normal
- Normal or tall
- Anosmia
- Delayed puberty due to hypogonadotropic hypogonadism
klinefelters
- 47xxy in men
- Infertility, small testicles
Low testosterone, high FSH & LH
- Infertility, small testicles
androgen insensitivity syndrome
- X-linked recessive
- End ogran res to testosterone
- Genotypically male children have a female phenotype
gdm
diagnosis?
mx?
Diagnosed if either:
• fasting glucose is >= 5.6 mmol/L
• 2-hour glucose is >= 7.8 mmol/L
Fasting plasma glucose level < 7: trial of diet and exercise
○ if glucose targets are not met within 1-2 wks: metformin
○ still not met: add insulin to diet/exercise/metformin (short-acting insulin)
if at the time of diagnosis the fasting glucose level is >= 7 mmol/l insulin should be started
if the plasma glucose level is between 6-6.9 mmol/l, and there is evidence of complications such as macrosomia or hydramnios, insulin should be offered
primary hyperparathyroidism
- bloods, urine, features
- cause
- indications for surgery
• Bloods: high PTH, high calcium, low phosphate
• Urine calcium : creatinine clearance ratio > 0.01
Features:
• Mild: can be asym
• Recurrent abdo pain (pancreatitis, renal colic)
• Changes to emotional or cognitive state
Cause:
• solitary adenoma (80%)
• multifocal disease occurs in 10-15% and parathyroid carcinoma in 1% or less
Indications for surgery
• Elevated serum Calcium > 1mg/dL above normal
• Hypercalciuria > 400mg/day
• Creatinine clearance < 30% compared with normal
• Episode of life threatening hypercalcaemia
• Nephrolithiasis
• Age < 50 years
• Neuromuscular symptoms
Reduction in bone mineral density of the femoral neck, lumbar spine, or distal radius of more than 2.5 standard deviations below peak bone mass (T score lower than -2.5)
secondary parathyroidism - bloods features cause tx indications for surgery
• Bloods: high PTH, high phosphate, calcium low-normal, low vit D
Features: Relatively asym»_space; bone disease, osteitis fibrosa cystica and soft tissue calcifications
• Cause: Parathyroid gland hyperplasia as a result of low calcium, almost always with CKD
• Tx: medical tx
• Indications for surgery: bone pain, persistent pruritus, soft tissue calcifications
tertiary parathyroidism - bloods ft cause mx indications for surgery
• Bloods: normal-high calcium, high PTH, high ALP, normal-low phosphate, normal-low vit D
Features
• Metastatic calcification
• Bone pain and / or fracture
• Nephrolithiasis
• Pancreatitis
Cause: a result of ongoing hyperplasia of the parathyroid glands after correction of underlying renal disorder, hyperplasia of all 4 glands is usually the cause
Mx: wait a year after transplant as many self-resolve
- The presence of an autonomously functioning parathyroid gland may require surgery
○ If the culprit gland can be identified then it should be excised.
Otherwise total parathyroidectomy and re-implantation of part of the gland may be required.
hypercalcaemia
most useful Ix
2 main causes
other causes
Most important Ix for determining cause: PTH
- normal or high PTH = primary hyperparathyroidism
Two conds cause 90%
• 1. Primary hyperparathyroidism: most common cause in non-hospitalised pts
• 2. Malignancy: commonest cause in hospitalised patients
○ due to: bone mets, myeloma, PTHrP from squamous cell lung cancer
Other causes include
- sarcoidosis - vitamin D intoxication - acromegaly - thyrotoxicosis - Milk-alkali syndrome - drugs: thiazides, calcium containing antacids - dehydration - Addison's disease - Paget's disease of the bone
Evolocumab - mech of action
prevents PCSK9-mediated LDL rec degradation
familial hypercholesterolaemia
- inheritance
- mx
- AD
Mx
Specialist lipid clinic
High dose statins
- high levels of LDL-cholesterol - if untreated > early CV disease - Cause: mutations in the gene which encodes the LDL-receptor protein.
graves features & Abs
• eye signs (30%) ○ exophthalmos ○ ophthalmoplegia • pretibial myxoedema • thyroid acropachy, a triad of: ○ digital clubbing ○ soft tissue swelling of the hands and feet periosteal new bone formation
Autoantibodies
• TSH receptor stimulating antibodies (90%)
• anti-thyroid peroxidase antibodies (75%)
Thyroid scintigraphy: diffuse, homogenous, increased uptake of radioactive iodine
high prolactin
- drug causes (4)
- other causes 7
Causes of raised prolactin: the P's • prolactinoma • pregnancy • oestrogens • physiological: stress, exercise, sleep • acromegaly: 1/3 of patients • PCOS • primary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release)
Drug causes of raised prolactin • metoclopramide, domperidone • phenothiazines • haloperidol • very rare: SSRIs, opioids
hashimoto’s
- ass w dev of?
- fts
- Abs
Ass w dev of MALT lymphoma
NOTES
- Causes hypothyroid - But can be a transient hyperthyroid phase in acute phase
Hypothyroid fts + firm painless goitre
- Anti-TPO Abs, anti-thyroglobulin Abs
Ass w other AI conditions (coeliac, T1DM, vitiligo)
DETAILS
= chronic autoimmune thyroiditis
- 10x more in women
More
Presence of new thyroid mass on bg of longterm hashimoto’s = MALT
- Usually women 65-75y old
- Usually neck lump w no other syms (can get dysphagia/dyspnoea from compression)
- Dx: US + fine needle aspiration cytology
HHS fts
- serum osm >320
- Also: trace of ketones can be seen; glucose >30
The goals of management:
- 1. Normalise the osmolality (gradually)
○ 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
○ Intravenous (IV) 0.9% NaCl 1st line
- 3. Normalise blood glucose (gradually)
NB if no sig ketaemia: don’t start insulin
Monitoring response to tx
Rapid changes must be avoided. A safe rate of fall of plasma glucose of between 4 and 6 mmol/hr is recommended. The rate of fall of plasma sodium should not exceed 10 mmol/L in 24 hours.
insulinoma dx
Dx: supervised prolonged fasting (up to 72h)
- If no option for this: insulin + c-peptide levels during an acute hypo
High insulin
High c-peptide
Raised proinsulin: insulin ratio
acute phase proteins 10
negative apps 5
Acute phase proteins • CRP • procalcitonin • ferritin • fibrinogen • alpha-1 antitrypsin • caeruloplasmin • serum amyloid A • serum amyloid P component • haptoglobin • complement
Negative acute phase proteins • albumin • transthyretin (formerly known as prealbumin) • transferrin • retinol binding protein • cortisol binding protein
hypocalcaemia ECG
ECG: prolonged QT interval
hypocalcaemia
- causes
- mx
- fts
- MX: IV Calcium gluconate 10ml of 10% over 10mins
Causes:
1. Vit D def (osteomalacia) 2. CKD (increased serum phosphate) 3. Hypoparathyroid (eg post thyroid or parathyroid surgery) 4. Pseudohypoparathyroid (target cells insens to PTH) 5. Rhabdomyolysis (at the start) 6. Mg def (due to end organ PTH res) 7. Massive blood transfusion 8. Acute pancreatitis
Features
• tetany: muscle twitching, cramping and spasm
• perioral paraesthesia
• if chronic: depression, cataracts
• ECG: prolonged QT interval
• Trousseau’s sign: carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systolic
• Chvostek’s sign: tapping over parotid causes facial muscles to twitch
what elec disturbance can you get after parathyroidectomy
what elec disturbance can you get after parathyroidectomy
- Due to sudden drop in prev high PTH levels
- Leads to low calcium
NOTES
DETAILS
- Uncommon - can occur after parathyroidectomy if the hyperparathyroidism has been long-standing.
Mechanism:
- high pre-operative levels of PTH > constant stimulus for osteoclast activity creating the hypercalcaemic state by de-mineralizing the bones.
- This process can result in x-ray changes very similar to metastatic lytic lesions if left untreated.
- Upon removal of the parathyroid adenoma > hormone levels fall rapidly (they have a very short half-life) > osteoclast activity is subsequently diminished > bones rapidly begin re-mineralisation - ‘hungry bone syndrome’.
This process can be uncomfortable and also result in systemic hypocalcaemia.
raised ALP w raised calcium (2)
w low calcium (2)
regardless of calcium (3)
RAISED ALP • liver: cholestasis, hepatitis, fatty liver, neoplasia • Paget's • osteomalacia • bone metastases • hyperparathyroidism • renal failure • physiological: pregnancy, growing children, healing fractures
Raised ALP w raised calcium
- Bone mets - Hyperparathyroidism
Raised ALP w low calcium
- Osteomalacia
Renal failure
how can you tell if secondary amenorrhoea is due to ovarian or hypothalamic cause
• Excessive exercise: hypothalamic hypogonadism (low oestradiol; FSH/LH low/normal) - secondary amenorrhoea
Premature ovarian failure: high FSH/LH
which pit hormone is continually inhibited
Prolactin = under continuous inhibition by hypothal
what causes ovulation
LH surge
metabolic syn ass w 3 things
nafld, pcos, raised uric acid levels
thyroid eye disease - need urgent review by opth (6)
urgent review by an ophthalmologist:
• unexplained deterioration in vision
• awareness of change in intensity or quality of colour vision in one or both eyes
• history of eye suddenly ‘popping out’ (globe subluxation)
• obvious corneal opacity
• cornea still visible when the eyelids are closed
disc swelling
