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
What events are increased risk in patients taking romosozumab?
Increased CVD evetns - shouldn’t be used in people who have had an MI within 12 months of therapy
Should only be used for 12 months in all
What is osteomalacia?
Deficiency of mineralised bone
What are indications for treatment of pagets disease and what is treatment?
Bone pain, involvement of critical bones (spine, petrous temporal bone) HF, Involvement of skull, cosmetic change, bending of tibia or femur
Treat with bisphosphonates
What are the skeletal complications of hyperparathyroidism?
Low BMD
Increased #
Osteitis firbrosca cystica
Brown tumours
Sub periosteal resorption of phalanges
Salt and pepper skull
How do you calculate osmolarity?
(2x serum Na) + urea + glucose
What is osmolar gap?
lab osmolarity - calculated osmolarity
Where does AHD work?
ADH works by increasing permeability of the cortical and medullary collecting tubules
What is Conns syndrome?
The classic presenting signs of primary aldosteronism are hypertension and hypokalemia
What is the first investigation for suspected acromegaly?
measurement of a serum insulin-like growth factor-1 (IGF-1) concentration
What electrolyte abnormalities are assoicated with cushings?
Cushing’s syndrome is associated with cortisol excess - which leads to potassium depletion and sodium and water retention. There is a compensatory hypochloraemia and metabolis alkalosis
What is the difference between type 1 and type 2 amiodarone hyperthyroidism?
In type I, there is increased synthesis of thyroid hormone, whereas in type II, there is excess release of T4 and T3 due to a destructive thyroiditis
What is the mechanism of hyperthyroidism in type 1 amiodarone hyperthyroid?
the excess iodine from amiodarone provides increased substrate, resulting in enhanced thyroid hormone production. Usually underlying goitre or latent graves
How to differentiate amiodarone hyperthyroidism Type 1 and 2?
type 1 occurs early (3 months)
type 2 occurs late (30 months)
If it occurs after amiodarone has been stopped Type 2
No radioiodine uptake in Type 2, normal/high uptake type 1
doppler USS type I (increased vascularity) from type II (absent vascularity)
What antibodies are found in Hashimoto thyroiditis?
Anti-TPO (in 90%) and anti-thyroglobulin (80-90)
presence of thyroid antibodies correlates well with the presence of a lymphocytic infiltrate in the thyroid gland
What is on the basolateral surface of the follicular cell?
TSH-R, Na/I co transporter
Is exopsed to the blood
What is on the apical surface of the follicular cell?
TPO
Is exposed to the colloid
What factors other than genetic suseptibility can lead to Hashimotos thyroiditis
Infection, stress, sex steroids, pregnancy, iodine intake, and radiation exposure are the known possible precipitating factors for Hashimoto’s thyroiditi
Is hashimotos thyroiditis painful?
No
What antibody is present in Graves?
anti-TSHR Ab
What is another name for Hashimoto thyroiditis?
Autoimmune thyroiditis
What population of patients with graves shouldn’t have Radioiodine ablative therapy?
patients with moderate or severe orbitopathy
- Makes it worse, can cause orbitopathy in patients who didn’t have it prior
What are requirements for patients after radioiodine ablation?
- Don’t get pregnant for 6 months
- Avoid pregnant woman and children
- Don’t share a bed with an adult for 3-10 days
Why are steroids helpful in type 2 amiodarone hyperthyroidism?
Glucocorticoids inhibit peripheral T4 to T3 conversion
What does cholestyramine do?
Increases clearance of T4 + reduces bile acid resorption in the gut
What are the side effects of Thionamides? (PTU, carbimazole)
Minor side effects – Rash, hives, arthralgias, transient granulocytopenia, gastrointestinal symptoms
Major side effects – Agranulocytosis, vasculitis (lupus-like syndrome), hepatitis
Risk of fetal goiter, hypothyroidism, and congenital anomalies if pregnant
What Thionamide is best in pregnancy?
PTU for first trimester at least, then canbe carried on throughout or go back to usual one
If an adrenal mass has HU <10 what is it likely to represent?
Benign adrenal adenoma
If HU are 0 = 100% specific for adenoma
What is the benefit of weight loss in PCOS?
5-10% wt loss –> restore ovulation
Increases sex-hormone binding globulin which would bind to and reduce free testosterone
What meds are androgren blockers for PCOS?
spiro + cyproterone
What is the COC used for in PCOS?
Supressing ovarian androgen production and increasing SHBG
What is elfornithine?
Topical treatment that inhibits hair growth (for hirsutism)
What is used for fertility/ovulation induction in PCOS?
Letrozole first line - aromatase inhibitor blocks peripheral conversion of androgens to estrogen in peripheral tissue
What is Hypothalamic amennorhoea?
Dysfunction due to excess exercise, weight or nutrition or chronic illness
What tests used to diagnose primary ovarian insufficiency?
2 x FSH elevated above 40u/l at least one month apart in addition to low oestradiol and in the context of amenorrhoea, and menopausal symptoms.
In the evaluation of amenorrhoe what is the likely abnormality if High FSH and Low estrogen?
Primary ovarian insufficiency
In eval of Amenorrhoea what is the dx if LOW FSH and LOW estrogen?
Central amenorrhoea
- functional hypotholamic
- GnRH deficiency
In eval of amonorrhoea what is ddx if normal FSH, normal-low Estrogen?
Outflow tract obstruction VS
Hyperandrogenism (PCOS, CAH< Cushings, Adrogen tumour)
What hormones peak in the normal menstrual cycle before ovulation?
Estrogen, LH, FSH
What hormone peaks after ovulation in the luteal phase?
Progesterone
What happens during the hormone surge mid-cycle?
switch from negative feedback control of luteinizing hormone (LH) secretion by ovarian hormones (such as estradiol and progesterone) to a sudden positive feedback effect, resulting in a 10-fold increase in serum LH concentrations and a smaller rise in serum follicle-stimulating hormone (FSH) concentration
In fetal development what hormone regulates prostate and male external genitalia?
Dihydrotestosterone, formed by 5-alpha-reduction of testosterone, regulates development of the prostate and male external genitalia during embryogenesis
What is the role of testosterone in fetal sex development?
stimulates wolffian duct differentiation into epididymides, vasa deferentia, seminal vesicles, and ejaculatory ducts (internal genitalia)
What is the inheritance of 5-alpha-reductase 2 deficiency?
AR
What manifestations of 5-alpha reductase deficiency do XY males have?
5-a-reductase needed to convert testosterone to dihydrotestosterone. with no DHT there is no/altered development of the external male genitalia leading to female external genitalia
What is the pattern of inheritance with androgen receptor mutations?
X-linked
What is complete androgen insensitivity syndrome?
characterized by an external female phenotype in a 46,XY individual with absent or sparse genital hair, absent uterus, serum testosterone concentrations that are higher than or within the usual male range, and the ability to synthesize testosterone and Sertoli cell markers, such as inhibin B and anti-müllerian hormon
What is Conns syndrome and how does it present?
Hypertension, hypokalaemia, metabolic acidosis
Primary hyperaldosteronism
What are the aldosterone and renin findings in someone with primary hyperaldosteronism?
plasma aldosterone concentration high and PRA: plasma renin activity low. This + hypokalaemia = diagnostic for primary hyperaldost
What meds interfere with plasma aldosterone concentration and plasma renin acitivity testing?
Mineralocorticoid receptor antagonists, ACE, ARB, renin inhibitors,
What does both the PRA (or PRC) and PAC increased and the PAC/PRA ratio is <10 indicate?
Secondary hyperaldosteronism (eg, renovascular disease)
What confirmatory tests are done in primary hyperaldosteronism?
Sodium should increase BP and supress aldosterone secretion so
24 hour urine aldosterone after high sodium diet ( if high >12) then confirmatory
IV isotonic saline infusion and aldosterone level following - same, should be supressed, if not, then confirmatory
What part of the adrenal produces aldosterone?
Zona glomerulosa - adrenal cortex
What part of the adrenal produces glucocorticoids (cortisol)
Zona fasciculata
What part of the adrenal produces androgens?
Zona reticulata
What part of the adrenal produces adrenaline?
adrenal medulla ( most important in the middle)
In the investigation of primary aldosteronism when do you do adrenal vein sampling?
For patients who would like to pursue surgical management (unilateral adrenalectomy) of their primary aldosteronism
If people are already on ACEi and Spiro, what duration do they need to stop before a saline supression test?
BP meds for 2 weeks prior to the best, and 4 weeks for spironolactone.
How do you know if there is unilateral disease after adrenal vein sampling?
Check the ratio of aldosterone to cortisol on both sides both with the central sampling and peripheral sampling. If one ratio is much higher than the others, then that points to unilateral hyperaldosteronism
At what age should they definitely have adrenal vein sampling to check for unilateral disease in aldosteronism?
> 35-40
What is Congenital adrenal hyperplasia?
disorders where one or more steroid precurser enzymes are deficient leading to steroid decifiency. . 21hydroxylate the most common ( CYP 21)
Which normally converts 17-OH progresteronee to cortisol, if absent you get reduced of complete blockage of cortisol and shunting of this to androgen
What increases plasma cortisol binding protein?
Pregnancy, estrogen, hyperthyroidism
Autoimmune polyglandular syndrome is secondary to what mutation?
AIRE mutation - normally in thymus T cells that recognise self are removed, not done if there is AIRE mutation
What HIV medication can precipitate cushings syndrome ?
Ritonivir - CYP inhibitor - means that steroids are around longer and can cauyse steroid excess
