Endo Flashcards
What condition associated with Turners syndrome. ( XO) should be regularly screened for ?
Aortic aneurysm
What is the most common cause of thyroid cancer?
Papillary
What tumours are associated with MEN1?
3Ps - Parathyroids, pituitary, pancreas
(can also get gastrinomas - duodenum)
What is the mode of inheritance of MEN1?
AD
What is the most common tumour ( and presenting tumour) in MEN 1?
Parathyroid tumour causing hyperparathyroidism, can have multiple ( even after parathyroidectomy)
What is the most common type of pituitary adenoma in MEN 1?
Lactotroph (also most common in general)
What is VIPo,a syndrome?
VIPomas are rare tumours with unregulated secretion of vasoactive intestinal polypeptide.
Clinically - waterry diarrhoea that persists with fasting, teacoloured odorless stool in high volume, hypokalaemia, hypochlorhydria
What is Zollinger Ellison syndrome? ZES
Gastrinomas –> hypergastrinaemia that lead to multiple peptic ulvers or diarrhoea.
What is the function of gastrin?
Released by G cells in the gastric antrum and duodenum - leads to secretion of HCl, gastric motility, and mucosal growth.
Released in response to food
What is the genetic mutation in MEN 1?
MEN1 gene mutation
What is the gene mutation in MEN2?
RET - proto-oncogene
What is the inheritance of MEN2?
AD with high penetrance
What are the common tumours for MEN2?
Thyroid, parathyroid, and adrenal glands
(medullary thyroid cancer, pheochromocytoma, primary hyperparathyroidism)
What is MEN2B?
No hyperparathyroidism in this syndrome.
Tumours develop earlier and are more agressive.
Which thyroid cancer has a strong association to MEN2?
Medullary thyroid cancer, shoud suspect MEN2 if someone develops this esp at <35
What are the lab findings of primary hyper PTH?
Hypercalcaemia
Hypophosphataemia
High PTH
High ALP
High cAMP
What causes famillial hypocalciuric hypercalaemia?
Defective calcium sensing receptor in the paratyroid gland leading to overproduction of PTH –> calcium reabsorption by the kidneys
What is the main type of collagen in bone?
Type 1
what does rank-l do?
released by osteoblasts to stimulate maturation of osteoclasts
what does opg do?
released by osteoblasts to block rnk-l and prevent osteoclast maturation
what is the most common osteoporotic #?
vertebral
What are the ratios of cortical bone to trabecular bone?
Cortical - 80%, trabecular - 20%
What is the definition of osteoporosis?
T score of <-2.5 or occurence of one minimal trauma fracture
What is T score and what is Z score?
T score - compared to young mean (30-40 year old bone denisity)
Z score - compared to age matched control
What is Z score used for
Not really used - can help determine if someone has accelerated bone loss ( e.g in RA, or coeliac)
What factors are included in FRAX?
Low BMI
Age
Previous #
RA
Fam Hx
Smoking
Corticosteroid use
What are the risk cut offs that requrie treatment on FRAX score?
Hip # risk >3%
Major osteoporotic >20%
What occurs in Glucocorticoid induced osteoporosis?
Accelerated loss of cancellous bone in first year
# occurs in 30-50% of long term GC users
What is the MoA of bisphosphonates?
Prevents osteoclast breakdown of bone by loss of ruffled borderand inhibition of vesicle tracking leading to increased apoptosis of osteoclasts
What is the specific enzyme inhibited by bisphosphonates?
famesylpyrophosphate-synthase
What is the MoA of denosumab?
Binds to RANK-Linhibiting osteoclast formation/maturation
Which type of fracture does denosumab most prevent?
New vertebral #s
What happens when denosumab is stopped?
Rapid loss of vertebral bone density within 12 months and “rebound” multiple vertebral #s
What are side effects of bisphosphonates
Flu-like illness day of infusion
Osteonecrosis of the jaw
Atypical femoral fractures - these are stress fractures
Where to atypical femoral fractures occur
Below the trochanter and above the femoral condyl
What are the radiologic features of atypical femur fractures?
No communition
Transverse at the lateral cortex
medial spike
Diffuse cortical thickening
Focal lateral cortical thinning
In what population group are atypical femur #s with bisphosphonates more common?
Asian women - may need to consider other therapy for this group as number of #s prevented is close to no. AFFs
What is the management of patients who develop an atypical femur # on bisphosphonates
Stop bisphosphonate
If incomplete # with pain and lucency - prophylactic nail
Monitor contralateral hip
How do patients with atypical femur # present?
Minimal-no trauma
Thigh or groin pain on affected side
What is teriparatide and how does it work?
Same structure as PTH -
For a 2 year period Teriparatide stimulates increased bone formation and RANKL production and reduced OPG from osteoblasts. NET effect is bone formation, but this changes after 2 years where there is increased osteoclast formation
What is LRP5 and what happens when its mutated?
It is intergral in bone formation pathways in osteoblasts.
Activating Mutation prevents binding of sclerostin or DKK (inhibitory) leading to unrestrained bone formation (sclerosteosis) + high bone mineral density
What is romosozumab?
Binds to sclerostin so it cannot inhibit LPR5 allowing for increased bone formation by osteoblasts in treatment of osteoporosis