Endocrinology Flashcards
Which MODY uses sulfonylurea for treatment?
MODY3
Diagnostic criteria for diabetes
Hba1c > 6.5%
Fasting glucose > 7
Random glucose > 1.1
OGTT - meeting above criteria
GDM diagnosis
OGTT 24-28 weeks
Fasting > 5
1 hour > 10
2 hour > 8.5
MoA of metformin
Suppresses hepatic gluconeogenesis
SLGT2 benefit in diabetic nephropathy - mechanism
Reduce intraglomerular pressure due to increased afferent arteriole resistance
Reduced hyperfiltration
Which SGLT2 has higher risk of amputations?
Canglifozin
Benefit of degludec vs lantus/levemir
Reduces overnight hypoglycaemia
Types of Type 1 Diabetes
Type 1A - immune.
- Usually polygenetic
- Monogenic - AIRE (Polyendocrinopathy), FOXP3 (IPEX)
Polyendocrinopathy
X linked
Enteropathy
IPEX
FOXP3 gene
HLA associated with diabetes
HLA DR3 and HLA DR4 (have both = 50%)
Pathophys of T1DM
T cell mediate process
T1DM Ab’s
GAD
Insulin
IA-2
ZnT8
Anti-CD3 reducing time of onset T1DM
Tepiluzimab
Name of principal where long term complications of diabetes occur if there is poor control early
Metabolic memory
Glargin vs detemir
Gargine - hexamers under skin, delay absoprtion
Detemir - binds albumin, prolongs half life
Meal ratio calculation
500/TDD
1 unit of insulin for how many g for of CHO
Insulin sensitivity factor
100/TDD
1 unit of insulin drops BGL by how manny mmol/L
Evidence for CGM (continuous gucose monitor)
REduction in Hba1c
Reduces hypos
Improves time in range (closed loop therapy)
Whipple’s triad
Symptoms of low BGL
Low BGL
Symptoms imrpove after correcting BGL
Lymphocytic hypophysitis
- Features
- Differentiate from Sheehan syndrome
Hypopituitarism and headaache postpartum, no PPH
Sheehan - PPH, ischaemic infarction of pituitary causing hypopituitarism
Apoplexy
Haemorrahge into pituitary adenoma
Acute headache, diplopia, hypopituitarism
GH physiology
- Period when it is highest
- Stimulator and Inhibitor
- MoA
Puberty
GHRH stimulates, somostatin inhibits
Binds to receptors on liver, causing dimerisation + phosphorylation and IGF-1 release.
Effects - CHO and fat breakdown, protein buildup
Diagnosis of Acromegaly
Elevated IGF1? - diagnoses
Equivocal
- OGTT - GH not adequately suppressed
Proceed to pituitary MRI
Treatment of acromegaly
Somostatin analogues
- Octreotide
- Pasireotide - causes new onset diabetes in 60%
Pegvisomant
- Recombinant GH molecule, prevents receptor dimerisation. Enhances insulin sensitivity
Test for GH deficiency
Serum IGF1
Equivocal, do provocation tests:
- Macromelin test (grehlin, stimulates GH release)
- GHRH test
Treatment prolactinoma
Cabergoline - ergot Da receptor agonist
A/E of cabergoline
Valvular heart disease
False positive elevated PRL, without any symptoms (galactorrhoea, amenorrhoea)
Macroprolactin - PRL bound to Ig’s
Ostoporosis agents
- Prevent breakdown
Bisphopsphonate - prevent osteoclast binding and induce apoptosis
Denosumab - RANK-L
SERM’s - inhibit osteoclasts through upregulating OPG
Bone anabolic agents
Teriparitide - increase osteoblast activity
Romosozumab -inhibits sclerostin, which inhibits osteoblast formation. Increases osteoblast activity
Physiology of FGF23
- When released
- Effects
- Klotho
Hyperphosphataemia
Decreases phosphate reabsorption
Decreases calcitriol synthesis (reducing intestinal absorption)
Suppresses PTH (suppress vit D)
Klotho is a co-receptor that enhanced FGF23. Depleted in CKD, so reduced efefct of FGF23 in CKD (on kidneys, parathyroid) –> lead to CKD MBD
Calcium sensing receptor
- Function
- Defects
Senses iCa, increases PTH release in response to low levels
Inactivation - causes familial hypocalcuric hypercalcaemia (excess PTH release as iCa not sensed)
Cincalcet - CasR sensitiser, sensitising to Ca and suppressing PTH release (in CKD-MBD)
Bone resorption markers
Urine NTX
Serum CTX
Bone formation markers
BSAP
PINP
Ca replacement when on PPI
Ca citrate
Denosumab
- Risk of not taking within 4 weeks
Spontaneous vertebral fractures
- Need to take bisphosphonate cover
Denosumab - cf with bisphosphonates
Increased eczema and infection risk
Less renal dose adjustment
Atypical femur fracture
- Presentation
- Management
Indolent groin pain whilst on bisphosphonate
Stop bisphopshonate/denosumab immediately and refer to orthopaedic centre
Bisphosphonates duration
5 years for oral, 3 years for IV
Continue in high risk (Age > 70, low T score, high risk fragility fracture)
Drug holiday for 2-3 years, recheck T score
Phentermine
- MoA
- Use
- A/E
Adrenergic agent suppresses appetite
Obesity
Adrenergic A?E
Orlistat
- MoA
- A/E
Lipase inhibitor, reduces fat absorption
Steatorrhoea, flatulence, oxalate stones
Criteria for bariatric surgery
BMI > 40
BMI >35 and failed medical therapy
Pathogenesis of thyroid eye and skin disease
TSH receptors and IGF-1 receptors on orbital fibroblasts and skin
Excess TSH stimulates receptors in eye muscles and skin
–> excess GAG secretion, fluid accumulation.
–> Extraocular muscle swelling, proptosis, pretibial myxoedema
Specific and non-specific features of Grave’s disease
Specific - periorbital oedema, proptosis, conjunctival inflammation
Non-specific - lid lag, stare
Treatment of Grave’s eye disease
- Everyone
- Mod/severe
Treat hyperthyroid, stop smoking, conservative with drops
Severe
- steroids
- Teprotumumab - IGF-R inhibitor
Thyroid storm
- Features
Hyperthyroid
Fever
Tachycardia
CNS - psychosis, seizure, coma
Heart failure
Hepatic dysfuncton
MoA of PTU in thyroid storm
Blocks T3/T4 synthesis
Blocks peripheral T4 –> T3
MoA of Lugol’s iodine in thyroid storm
Remember it is iodine solution
Blocks T3/T4 release
MoA of Dex in thyroid storm
Blocks T4 –> T3 peripherally
When to treat hyperthyroidism in pregnancy
Graves - TSHRAb positive, as this can cross placenta
- PTU 1st trimester
- Carbimazole other times
Do not treat gestational
Episodes muscle weakness
Low K
Cause?
Differentiate from?
Hypokalaemia periodic paralysis
Exclude thyroid disease
Exclude Anderson syndrome (ECG for long QT)
Test for primary hyperaldosteronism
Plasma aldosterone high, plasma renin low. If K low, confirms
Confirmatory tests
- Oral Na load
- Saline suppression
- Fludrocort suppression
Phaeo management
- Imaging
- Genetic testing
- Medical
MRI/CT ABdo - look for unilateral or b/l
Genetic - vHL, MEN2, can have bilateral
Medical - ALWAYS alpha blocker first
AIRE
Autoimmune polyendocrine syndrome 1
- adrenal insufficiency
Diabetic
Collapse of midfoot/arch
Acute hot, red swollen foot
?cause
?other considerations
Charcot’s (diabetic) neuroarthropathy
Charcot’s think midfoot/arch.
Exlude osteomyelitis, gout
Management of charcot’s
Contact casting/podiatry to offload foot
Function of kisspeptin
Stimulates GnRH release (remember pulsatile fashion)
Requirements for functional GnRH secretion
GnRH neurons must migrate appropriately (through olfactor bulb) - error = Kallmans’ syndrome
Must secrete in pulsatile manner - continuous (GnRH agonists) = suppression
Pathophys of PCOS
Functional ovarian hyperandrogenism -increased sensitivity to LH
Functional adrenal hyperandrogenism
Selective insulin resistance - insulin acts on theca cells to increase androgen synthesis
Diagnosis of PCOS
Amenorrhoea/oligomenorrhoa
> 20 follicles U/S
High testosterone
- Clinical - hirsuitism
-Elevated testosterone
Test for CAH
21 a hydroxylase deficiency
Check 17 OH levels - high indicates 21a hydroxylase deficiency
Fertility management for PCOS
Metformin/weight loss - by 10% can improve fertility
Ovulation induction
- Letrozole, aromatase inhibitor increased ovarian oestrogen
Clomiphene - oestrogen receptor antagonist, increases FSH production
Diagnosis of relative energy deficiency (functional hypothalamic amenorrhoae
Amenorrhoea
Low FSH, LH and oestradiol
Diagnosis of relative energy deficiency (functional hypothalamic amenorrhoae
Amenorrhoea
Low FSH, LH and oestradiol
Trigger - eating disorder, excercise, stress
Mullerian ducts/structures
Uterus
Fallopian tubes
Superior part of vagina
Female external genitalia
Male sex development from embroy
XY - Y has SRY gene which causes gonad to become testes
Testis produce 3:
- AMH - regress Mullerian ducts
- 5a DHT - male sex characteristics
- testosterone - wollfian ducts
Female characteristic development
XX - default ovaries produced
Mullerian ducts form –> female sex characteristics
Lack of SRY, or lack of AMH from testis (gonadal dysgenesis) cause female characteristics
Female sex characteristics
Normal pubarche, adrenarche
Streak gonads
46XY gonadal dysgenesis
Amenorrhoea
Female characteristics, absence of hair, adrenarche
46XY
Androgen insensitivity syndrome
Evaluation of possible primary ovarian insufficiency
TSH and PRL - ensure normal
Check FSH, LH, E2 and AMH
- E2 low, FSH and LH high –> likely POI
AMH low also supports diminshed ovarian reserve
2 most common causes POI
Idiopathic
Autoimmune -APS1 (AIRE)
When to use transdermal ostrogen rather than oral
Hypertriglyceridaemia
Imapired Liver
Migraine with aura
Woman with uterus - formulation for HRT?
Combined oestrogen and progesterone
Absolute contraindications to HRT
ABCD
Acute liver disease
Bleeding - undiagnosed vaginal bleeding
Cancer (rbeast/uterine), Cardiovascular disease
DVT( or thrombophilia)
Low test
Low FSH/LH
Anosmia
Kallman’s syndrome
Failure of migration of GnRH neurons through olfactory bulb with olfacotry neurons
When to treat euvolemic HypoNa with Hypertonic saline
Na < 120
Cerebral symptoms - decreased GCS, seizure, headache
Inhibitors of growth hormone
IGF1
Leptin
Somostain (GHIH)
Hyperglycaemia
LISH
High TSH
High T4
Heterophile antibody - can interfere with assay
Hyperthyroid
No uptake on nuclear scan
TPO positive
DDx?
Silent thyroditis - spectrum with Hashimoto’s (progresses to Hashimoto’s with alter hypothyroid)
Postpartum - within 12 months of birth/miscarriage
Dequarvain’s thyroiditis Rx
NSAIDs first line
Pred 2nd line
BB for symptoms
Hypercalcaemia
AKI
Metabolic alkalosis
Milk Alkali syndrome
Activating mutation of TSH receptor causes?
Thyroid adenoma or toxic multinodular goitre
Treatment of hypercalcaemia
IV fluids ALWAYS 1st line
2nd line - IV bisphosphonate
Aldosterone levels in primary vs secondary adrenal insufficiency
2nd - usually preserved aldosterone
Which fracture site is at greatest risk with steroid osteoporosis?
Vertebral
High oestrogen, low LH, normal testosterone.
YOung male, gynaecomastia.
Next ix?
Suggests aromatisation of testosterone. Can be done by HCG from teste tumour
Testicular U/S
Factor greatest effect on peak bone mass?
Genetics
Osteoporosis men with hypogonadism
Treat with testosterone
Testosterone changes in obesity
Low SBG - inhibition of liver. Causes decrease total testosterone
Increase peripheral conversion by aromatase from testosterone to oestrogen
ACTH dependant Cushing’s, no lesion on MRI
Next step?
Petrosal sinus sampling - confirm if from pituitary.
Sometimes MRI won’t pick up pituitary adenoma
Mechanism of steroid induced osteoporosis
Decreased production of OPG
Low BSL
Insulin high
C peptide normal
Insulinoma
MoA of GLP-1 agonists
Stimulate glucose dependant secretion of insulin by beta cells
Delay gastric emptying
Most specific sign of Cushing’s
Most specific sign in already obese person that points to Cushings
Abdominal striae
Proximal myopathy
Drug taken with bisphopshonates that reduces absorption
CaCO3
REsponse to hypogylcaemia in order
1) Glucagon
2) Adrenaline
3) Cortisol and GH
2nd cause hyperipidaemia most assocaited with increased LDL
Hypothyroid
Therapy for proliferative diabetes
- First line
- 2nd line
1st line - panretinal photocoagulation - best to prevent vision loss
VEGF in short term (until photocoagulation)
2nd line - vitrectomy
Therapy for macular oedema
Anti-VEGF agents
Changes in T2DM
1) Impaired glucose tolerance - impaired post prandial
2) Beta cells increase insulin secretion. Can’t keep up
- Increased hepatic GNG causing fasting hyperglycaemia
Mechanism of insulin translocating GLUT4 transporter to cell surgace
Activating tyrosine kinase receptor on cell surface
Steroid induced osteoporosis
- Acute mechanism
- Long term mechanism
Acute - decreased OPG, increase RANK-L , increase bone resorption
Long term - decrease bone formation
Cushing’s
- Agents that target adrenal
KM
Ketoconazole - inhibit androgen synthesis
Metarypone - Stops GC synthesis (inhibit 11b hydroxylase)
Cushing’s disease (pituitary)
- Agents that target ACTH
- Agents that target GC receptor
PM
ACTH - pasireotide, inhibit ACTH formation
GC receptor - mifepristone
Monitor treatment in 2nd hypothyroidism
Free T4
Causes of increased CBG? (and hence elevated total cortisol)
Oestrogen - pregnancy, COCP
Insulin resistance
Why take alendronate BEFORE meals
Taken with dairy/food, can form mineral complexes
Gynacomastia and testicular cancer - cause?
bHCG production and direct effect on testicular tissue
Bisphosponate associated with impaired bone mineralisation
Etidronate
Thyroid and PRL
- What causes elevated PRL
Hypothyroid
TSH receptor AB
- when can treatment for Grave’s be stopped?
When TSH r AB low
Test to confirm primary adrenal insufficiency
Short synacthen (ACTH) test
Test to confirm secondary adrenal insufficiency
ACTH and cortisol
AND
Synacthen test
Sick Euthyroid
- Circumstances
- Labs findings
In critically ill patients, functional central hypothyroid to prevent catabolic state
Low T4, low T3, low normal TSH
