Endocrinology Flashcards
What features do you expect to see in MEN1, and what is the associated gene? Name 3 features.
“3 Ps”
Parathyroid (95%) - hyperparathyroidism
Pituitary (70%)
Pancreas (50%)
MEN1 gene
Also adrenal and thyroid
What features do you expect to see in MEN1, and what is the associated gene? Name 3 features.
“3 Ps”
Parathyroid (95%) - hyperparathyroidism
Pituitary (70%)
Pancreas (50%)
MEN1 gene
Also adrenal and thyroid
What features do you expect to see in MEN2A, and what is the associated gene? Name 2 features.
“2 Ps”
Parathyroid (60%)
Phaeochromocytoma
RET oncogene
What features do you expect to see in MEN2B, and what is the associated gene? Name 3 features.
Phaeochromocytoma
Marfanoid body habitus
Neuromas
RET oncogene
Name 5 autoantibodies you might expect to see in T1DM
Anti-GAD (glutamic acid decarboxylase)
Anti-IAA (insulin autoantibodies)
Anti-ICA (islet cell antibodies)
Anti-IA2A
Anti-ZnT8
T1DM generally starts when patients have 2 or more autoantibodies
Name 3 potential “triggering” factors for T1DM
Congenital rubella
Hygiene (possibly)
Obesity (probably)
What HbA1c level ought to be targeted in T1DM?
<7.0
<8.0 if severe hypoglycaemia
In diabetes, what are the reference ranges for microalbuminuria and macroalbuminuria with urine ACR?
Micro - 2.5 to 25 M; 3.5 to 35 F
Macro - > 25 M, >35 F
What 3 parameters are required to diagnose DKA?
Glucose >14
Ketosis
pH < 7.30 (bicarbonate <20)
What 3 parameters are required to diagnose HHS?
Glucose > 30
Minimal ketosis
Osmolality > 320
Usually glucose is >56 and age is >65
How do DPP4 (gliptin) inhibitors work?
Boost endogenous GLP-1/GIP (incretin), inhibiting glucagon release and and in turn increasing insulin secretion
Works only at mealtimes; no CV benefit
How do GLP-1 analogues (e.g. exenatide) work?
Direct stimulation of beta islet cells
Often results in weight loss
Risks of pancreatitis and nausea
For T2DM, after inadequate control following conservative measures and metformin, what medications would you consider in patients with CVD? Name 2
GLP-1
SGLT2i
Either one will do. Give both if one isn’t working, or consider insulin, TZD, SU or DPP4 if not on GLP-1.
For T2DM, after inadequate control following conservative measures and metformin, what medications would you consider in patients with CKD or HF? Name 2
Preferably SGLT2i
If eGFR does not allow that, then GLP-1
Following that, consider insulin, SU or DPP4 (if not on GLP-1)
Do NOT give TZD in setting of HF
For T2DM, after inadequate control following conservative measures and metformin, what medications would you consider in patients who have a compelling need to minimise hypoglycaemia? Name 4
DPP4i
GLP-1
SGLT2i
TZD
Add the others as needed; if still inadequate, consider later generation sulphonylureas or insulin
For T2DM, after inadequate control following conservative measures and metformin, what medications would you consider in patients with a compelling need to minimise weight gain or promote weight loss? Name 2
SGLT2i
GLP-1
Which GLP-1 agonists are proven to significantly reduce CVD?
Albiglutide
Dulaglutide
Exenatide and lixosenatide are not shown to reduce CVD - unclear why
What BP should be aimed for in diabetic patients?
140/90
What are the risks and benefits of intensive glycaemic control in diabetic patients?
Decreased HbA1c and macrovascular complications
22% increase in mortality, however
What are the risks and benefits of intensive glycaemic control in diabetic patients?
Decreased HbA1c and macrovascular complications
22% increase in mortality, however
When should diabetic patients be given statins?
<40 years, no risk factors for CVD - no statins
<40 with risk factors, start moderate-high dose
All else, give
Ezetimibe with statin is recommended
In which diabetic patients is fenofibrate beneficial alongside ezetimibe/statin?
Patients with increased triglycerides and decreased HDL
No significant CV benefit for other patients otherwise
What are the benefits of using GFR rather than ACR in diabetic patients to monitor renal function? Name 3 benefits.
More specific
Indicates renal function
Rarely regresses (ACR microalb -> normoalb-> macroalb is typical)
Name 5 hormones involved in predisposition to obesity.
MC4-R (dominant)
Ob/ObR or LEP/LEPR (leptin)
POMC (MSH)
FTO
BDNF
In which parts of the nervous system is weight regulated? Name 2 places.
Hypothalamus - Arcuate nucleus -Neuropeptide-Y nerves
POMC nerve fibres
Which 3 hormones stimulate hunger?
Neuropeptide-Y
Ghrelin
Leptin
All the other hormones suppress hunger
What drugs can be given to obese patients to encourage weight loss? Name 4.
Liraglutide
Orlistat
Duromine
Bupriopion + naltrexone
Topiramate can be used but is off-label
It’s better to use multiple low dose drugs than one high dose drug - drug use should be lifelong
Define osteoporosis with 2 criteria.
T-score < -2.5
Fractures with minimal trauma include wrist, vertebra and hip
What is the recommended daily intake of Ca?
1000mg/day
1300mg/day in women >50 and men >70
Baseline dietary intake 750mg to 1240mg daily
What is the risk associated with over supplementation of Ca?
Increased risk of MIs (30% vs placebo)
What is the risk of excessive vitamin D supplementation?
Increased risk of falls and fractures
What are the varying levels of deficiency for vitamin D?
Vit D > 50 is considered adequate
30 - 49 is mild deficiency
12.5 to 29 is moderate deficiency
<12.5 is severe deficiency
Where are atypical fractures generally seen?
Proximal third femur shaft
Incomplete fractures involve the lateral cortex
The median duration on bisphosphonates for atypical fractures is 7 years; concomitant steroid use seen in 34% of patients
Which population of patients are at increased risk of ONJ while on bisphosphonate therapy?
Oncology patients - 1-15%
Also high dose and long duration, but not to nearly the same extent
What are the indications for starting teriparatide? Name 3.
BMD < -3.0
2 or more minimal trauma fractures
AND
At least one new symptomatic # after at least 12 months of continuous antiresorptive therapy
Course is limited to 18 months
What are the contraindications for giving teriparatide? Name 5.
Malignancy
Renal stones
Gout
Paget’s
Skeletal irradiation
How are small pituitary causing acromegaly tumours managed surgically?
Selective trans-sphenoidal microadenectomy
How are large pituitary tumours causing acromegaly managed surgically?
Total hypophysectomy +/- XRT (stereotactic or megavoltage) +/- somatostatin analogue
Name 4 ACTH-independent causes of Cushing’s.
Adrenal adenoma
Adrenal carcinoma
Micronodular hyperplasia (primary pigmented nodular adrenal disease - PPNAD)
Macronodular hyperplasia (ACTH-independent macronodular adrenal hyperplasia - AIMAH)
Name 3 ACTH-dependent causes of Cushing’s.
Cushing’s disease
Ectopic ACTH syndrome
CRH syndrome
Name 2 causes of pseudo-Cushing’s
Depression
ETOH
How do you interpret test results from an evening plasma cortisol test?
<50nm/L excludes Cushing’s syndrome
> 207 excludes pseudo-Cushing’s
Next step is plasma ACTH
How do you interpret an overnight low dose dexamethasone suppression test?
<50nm/L excludes Cushing’s syndrome (can say <140 for sensitivity purposes)
Next step is plasma ACTH
How do you interpret plasma ACTH results?
<5 = ACTH-independent cause of CS
> 15 = ACTH-dependent cause of CS
5-15 = equivocal, probably ACTH-dependent
What is pre-operative prep that is given prior to pituitary surgeries, irradiation and bilateral adrenalectomies for CS? Name 3.
Metyrapone
Ketoconazole
Mifepristone
If failed other therapies, consider pasireotide
How are patients evaluated for treatment success following pituitary surgery for Cushing’s disease?
Measure 0800hrs plasma 24 hours post last hydrocortisone administration 3-7 hours post-OP
Cure if undetectable plasma cort (<28) or ACTH (<5-10)
Persistently detectable plasma cort = incomplete resection and almost certain recurrence, even in normal range
Which gene mutation is associated with primary pigmented nodular adrenal disease (PPNAR)?
PPKAR1A mutation
Associated with Carney complex
Name 6 non-pharmaceutical causes of hyperprolactinaemia.
CKD
Seizure
Post-partum
PRLoma
Macroadenoma with stalk disruption
Stalk trauma
Name 3 causes for Conn’s syndrome
Aldosterone-producing adenoma
Idiopathic/bilateral hyperplasia
Adrenal Ca
How do you interpret the results of an aldosterone suppression test?
Abnormal is >240
Normal is <140
How does copeptin testing work?
Measure baseline copeptin
Give hypertonic Na to Na 150
Copeptin normally increases; if not, it is suggestive of diabetes insipidus
How do you approach a unilateral adrenal tumour based on age?
<40 - adrenalectomy
> 40 - incidentaloma is most likely - consider adrenal vein sampling
What features on CT or MRI are suggestive of a benign adrenal tumour? Name 5 features.
Smooth border
Round/ovoid shape
Homogenous border
Low intensity signal (<10 HU)
Isodense with liver MRI
Carcinoma = hyperdense vs liver, heterogeneous, microcalcification
What conditions are associated with phaeochromocytoma? Name 4
MEN2A
MEN2B
VHL
NF-1
Also genes SDBH (most important) and SDHD (assoc with head and neck tumours rather than paragangliomas, unlike the others)
Which imaging modalities can be used to assess for phaeochromocytomas? Name 3
CT
MRI
GaTATE scanning
MIBG is not used so much anymore
Which populations do multinodular goitres typically affect? Name 3.
Older adults
Women
People from iodine-deficient areas
What are the pathophysiological processes of AIT types I and II?
Type I - increased synthesis T4 due to iodine load (T4 ++ T3 -)
Type II - thyrocyte cytotoxicity
Both feature 5’ deiodinase inhibition
USS shows increased vascularity in type I but decreased in type II
Name 4 causes of subclinical hyperthyroidism.
Multinodular goitre
Grave’s disease
Over-replacement of thyroxine
Iodine exposure
How do you manage thyroid storms? 11 points.
HDU/ICU admission
Beta-blocker (propranolol or esmolol to maintain HR <100)
Rehydrate
Control fever
Avoid aspirin
PTU
Lugol’s iodine
Hydrocort/pred
Cholestyramine (clears T4)
Plasmapheresis
What clinical and diagnostic features would you expect to see with subacute thyroiditis? 5 points.
HLA-B35 in 75%
Thyrotoxicosis
High ESR/CRP/leuks
High thyroglobulin
USS - enlarged hypoechoic gland with decreased vascularity
Typically there is thyrotoxicosis, hypothyroidism then recovery.
What are the different types of thyroid cancer, in order of incidence?
Papillary
Follicular
Poorly differentiated
Anaplastic
Medullary
How is papillary thyroid cancer diagnosed?
FNA
How is follicular thyroid cancer diagnosed?
Excision biopsy or hemithyroidectomy
It may be adenoma or carcinoma hence FNA not reliable
How is follicular thyroid cancer differentiated from follicular adenomas? And what signalling pathway defects are implicated?
Capsular and vascular invasion
MEK or ERK system defects
What are negative prognostic features for follicular thyroid cancer? Name 3.
Age > 40
Tumour size > 4cm
Local extension or distant mets
Spread to lymph nodes is very common (>80%), but spread beyond the neck is <10% - generally indolent without causing death.
What is the treatment for follicular thyroid cancers?
Total thyroidectomy with remnant ablation radio-iodine
Surveillance with thyroglobulin measurement, whole body iodine scan and neck USS
TKI therapy for non-iodine avid recurrent and progressive disease
What are the indications for surgery with primary hyperparathyroidism? 6 criteria.
Serum Ca 2.9 or above
Urine Ca >10mmol/day
eGFR <60
Nephrolithiasis/calcinosis
T-score < -2.5 in spine, neck of femur, total hip or distal third radius
Age < 50
What is the pathophysiology of familial hypocalcuric hypercalcaemia?
Inactivating mutation of calcium sensing receptor in PTH glands and kidneys
What is the pathophysiology of autosomal dominant hypocalcaemia?
Activating mutation of calcium-sensing receptor in PTH glands and kidney i.e. increased sensitivity of receptors to ionised calcium
PTH therefore decreased at normal calcium levels
Which gene is implicated in vitamin D dependent rickets type 1a?
VDDR-1A gene CYP27B1
Vitamin D activation gene
Which gene is implicated in vitamin D dependent rickets type 1b?
VDDR-1A gene CYP2R1
Vitamin D activation gene
Which gene is implicated in vitamin D dependent rickets type 2?
HNRNPC - vitamin D receptor co-activator
What are the diagnostic criteria for PCOS?
2 out of 3 of…
Oligomenorrhoea/anovulation
Clinical or biochemical hypoandrogenism
Polycystic ovaries
What biochemical abnormalities would you expect to see with PCOS? 3 abnormalities.
Elevated free serum testosterone
Low SHBG
Androstenedione or DHEAS often mildly elevated
Elevated free androgen index subsequently
What 2 criteria (either/or) do you require in order to make a diagnosis of primary ovarian insufficiency?
2 x FSH >40 at least 1 month apart
Or
Decreased oestradiol and increased FSH
Then go on to clarify aetiology e.g. Fragile X (FMR1), Polyendocrine Syndrome Type 1 (AIRE) etc.
How quickly do you aim to correct Na in SIADH normally, and how quickly do you aim to correct it in severe cases?
Aim to increase Na by 4-6 mmol/L per 24 hours
If severe - aim to increase by 4-6 mmol/L per 2-3 hours (give hypertonic Na 2ml/kg over 15 mins)
