Endocrinology Flashcards
Genetic Syndromes of hypokalaemia
Barters, Gitelman, Liddles
Which genetic syndrome of hypokalaemia is associated with High Blood Pressure
Liddles - rare autosomal dominant, gain-of-function mutation in ENaC leads to hereditary hypokalemia and hypertension, mimicking the syndrome of mineralocorticoid excess.
Which genetic syndrome of hypokalaemia mimics the action of loop diuretics?
Barter Syndrome
Which genetic causes of hypokalaemia lead to a metabolic alkalosis
Barter and Gitelman Syndrome
Features of Primary Hyperaldonstoeronism (Conn’s Syndrome)
Triad of Hypertension, Hypokalaemia and Metabolic Alkalosis. Excess Hyperaldosterone –> Excess excretion of Potassium (Sodium potassium exchanger in the distal convoluted tubule), metabolic alkalosis and hypertension.
Diagnosis in suspected Primary Hyperaldosteronism
Plasma Aldosterone Concentration/Plasma Renin Concentration. If significantly elevated ratio then tends to suggest Primary Aldosteronism
What are the four factors that increase the likelihood of underlying osteomyelitis in the context of ulcers
1) Grossly visible bone or ability to probe to bone
2) Ulcer size >2cm squared
3) Ulcer duration longer that one to two weeks
4) ESR >70
Which finding is specific for Grave’s Disease
Pre-tibial Myxodema
Best investigations for Grave’s Disease
1) Thyroid Antibodies - TSH receptor antibody
2) Tc 99 scan where there will be symmetrical homogenous uptake
Three treatment modalities for Graves Disease
1) Thionamides: Carbimazole/PTU
2) Radioactive Iodine
3) Thyroidectomy
Side effects of Thionamides
Itch Rash Agranulocytosis (Neutropenia) Hepatotoxicity pANCA vasculitis
Which Thionamide should be used in the first trimester of pregnancy
PTU
Which thionamide should be used after the first trimester of pregnancy
Carbimazole
Addison’s Disease metabolic changes
Reduced production of mineralocorticoid therefore hyperkalaemia, hyponatraemia and hypoglycaemia
Maintenance therapy in primary adrenal insufficiency
Glucocorticoids: Can use Hydrocort 15-25 (10mg/m squared) BD/TDS dosing or prednisone 3-5mg
Mineralocorticoid: Fludrocortisone: 100 units per day
Cardinal Features of Autoimmune Polyglandular Syndrome Type 1
Occurs in children, Addison’s disease associated with mucocutaneous candidiasis and hypoparathyroidism. Autosomal Recessive
Cardinal Features of Autoimmune Polyglandular Syndrome Type 2
Addison’s Disease
Type 1 diabetes
Thyroid Disease
Gold standard test for Primary Adrenal Insufficiency
Insulin Tolerance Test
Investigation of Primary Adrenal Insufficiency
Morning cortisol
Short Synacthen Test
Insulin Tolerance Test
Most common deficiency if Congenital Adrenal Hyperplasia
21 hydroxylase which leads to an increase in 17 hydroxylase (the precursor)
When should you investigate for Adrenoleukodystrophy? What is the screening test
Young males with adrenal insufficiency. Very long chain fatty acids (elevated = diagnosis)
What is gold standard diagnostic test for differentiating between a pituitary or ectopic cause of ACTH dependent Cushing’s syndrome
Bilateral Inferior Petrosus Sinus Sampling. Central step up ratio of ACTH central to perisperhal of >2 is diagnostic of pituitary cause
Triad of symptoms associated with phaechromocytoma
Episodic
Tachycardia
Diaphoresis
Headache
Genetic Syndromes associated with Phaechromocytoma
In order
MEN 2
VHL
NF1
Main Adverse Effect of GLP-1 receptor agonist (Exenatide or Dulaglutide)
- Nausea + Vomitting - normally transient and improves after 1-2 weeks
Contraindications & precautions with Exenatide/Dulaglutide
- Gastroparesis (delays gastric emptying)
- History of Pancreatitis with GLP-1 analogue
- Treatment with oral sulfonylurea or insulin (increases risk of hypo)
- Gallbladder disease (increase risk of needing a cholecystectomy)
Indication for Exenatide/Dulaglutide
HBA1c >7% with dual or triple oral therapy/insulin
PBS criteria for commencing anti-osteoperotic therapy in patients on sertoids
1) >7.5 of pred
2) 3 months
3) T score <1.5
Bisphosphonates mechanism of action
Binds to surface of bones –> Inhibition of osteoclast activity (loss of ruffled border and induced apoptosis)
Targets farnesyl pyrophosphate
“paints bone then leads to osteoclast apoptosis)
SERM mechanism of action
Selective Estrogen Receptor Modulator - binds to oestrogen receptors
Prevents vertebral factures (only)
Also decreases the risk of breast cancer
Zoledronic Acid adverse effects
Flu like reaction (paracetamol and NSAID’s)
? Atrial Fibrillation
Denosumab MOA
Monoclonal antibody that binds RANK ligand preventing osteoclast activation
Nb discontinuation or missing of doss –> rapid reduction of bone density (rapid bone resorption). Do not commence in someone who may be non-compliant.
Adverse effect of prolonged anti-resorptive therapy
1) Osteonecrosis of the jaw
> 8 weeks of exposed alveolar bone after dental extraction
2) Atypical femoral fracture (prodrome with thigh pain). Risk factor is treatment with glucocorticoids.
Treatment of Atyipical femur fracture
1) Discontinue anti-resorptive
2) Incomplete - prophylactic nail fixation
3) Complete - orthropods
4) Monitor risk in contralateral hip
Potential treatment for refractory osteoporosis
PTH - Skeletal anabolic steroid
Effect of irony infusion on phsophate
Loss of phosphate though the kidneys
Findings in osteomalacia
1) High ALP
2) Bone pain/fractures
3) myopathy
What is osteomalacia caused by
1) Vitamin D Deficiency
2) Low phosphate
Risk factors for Graves disease
1) Family hx of autoimmune thyroid disease
2) Recent iodine exposure
3) Post partum
Technetium scan in Graves Disease
Uniform uptake of technetium
Mgmt Graves disease
1) Beta Blocker - symptomatic
2) Control hyperthyroidism
- Thionamide (adverse effect neutropenia/rash/pANCA vasculitis)
- Radioactive iodine (contraindicated in eye disease and can be slow onset) (adverse effect hypothyroidism
- Surgery
Pathognomic signs of graves disease
1) Pretibial myxoedema
2) Graves orbitopathy
Adverse effects of thionamides
1) Neutropenia
2) Rash
3) pANCA vasculitis
PTU: Fulminant inflammatory hepatitis
Which thionamide to use in first trimester
PTU “primary trimester”
Risk factors for graves orbitopathy
1) Smoking
2) Radioactive iodine
3) Hypothyroidism (through fluid retention)
Treatment for grave’s orbitopathy
Pulse methylprednisolone
Radiotherapy if no response
Surgical debunking in the chronic phase
Periodic paralysis associated with graves disease precipitant and electrolyte findings
1) Thyrotoxicosis due to graves disease
2) High carbohydrate meal –> insulin
3) Hypokalaemia
Below the waist paralysis
Seen in patients with Asian heritage
Dosing thyroxine in pregnancy
Increase dose by 1.3 times
Subclinical hypothyroidism in pregnancy
Give thyroxine during pregnancy
Toxic nodule on technetium scan
One major nodule with remainder of the thyroid suppressed
Treatment for toxic nodule
Radioactive iodine
trapped in overactive area
Treatment for multi nodular goitre
Radioactive iodine
Thyroidits on technetium
No uptake + neck tenderness
Treatment for thyroiditis
Propanolol for symptoms
NSAID’s/pred for pain
Amiodarone thyroiditis
1) Type 1: Iodine load
2) Type 2: Thyroiditis
Treatment for amiodarone thyroiditis
1) Thionamides
2) Steroids for thyroiditis
3) Colestyramine to decrease ? intrahepatic flow of thyroid hormones
Technetium scan in amiodarone thyroiditis
Cold as amiodarone competes with technetium for uptake.
Drugs that can affect the thyroid
1) Amiodarone - Hypothyroidism or thyroiditis
2) Lithium - Hypothyroidism or thyroiditis
3) Immune checkpoint inhibitors
- PD-1: primary thyroiditis
- Anti-CTLA4: central and secondary hypothyroidism
4) Alemtuzumab
- Graves disease common (15% of patients)
5) Interferon alpha
6) Tyrosine kinase inhibitors
7) Bexarotene (cutaneous lymphoma)
Which drug used in MS is associated with Grave’s disease?
Alemtuzumab
Findings in subclinical hypothyroidism
Normal T3/T4 but elevated TSH
Treat young and also pregnant
Do not treat old
Findings in subclinical hypothyroidism
Normal t3/t4 but low TSH
Treat old people irrespective
Treat young people if very low TSH
Commonest type of thyroid cancer
Papillary
Thyroid scan on technetium scan
Cold
Important first test when working up thyroid nodule?
TSH - helps differentiate toxic nodule from thyroid cancer
Tumor marker in follicular derived thyroid cancer
Serum thyroglobulin
What is given to facilitate radio-iodine post surgical removal of thyroid cancer
Recombitant TSH
Treatment for radio-iodine refractory, surgery inappropriate progressive thyroid cancer
Lenvatinibi - multi targeted kinase inhibitor
Most common mutation in medullary thyroid cancer
RET mutation
MEN 2A
Phaeo
Medullary thyroid cancer
Hyperparathyroidism
What to exclude in medullary thyroid cancer
Exclude phaeo with 24 hr urinary metanephrines
Tumor marker for medullary thyroid cancer
Calcitonin
MEN 2B
Marfarnoid habitus
Medullated corneal nerves
Aerodigestive ganglioneuromas
Medullary thyroid cancer
Investigation for ACTH deficiency
Insulin tolerance test
–> hypoglycaemia –> ACTH
GH deficiency
Insulin tolerance test
Pituitary mass clinical features
1) Amenorrhea
2) Visual field defect
3) Occulomotor palsy
Most common functioning pituitary adenoma
Porlactinoma
Treatment for prolactinoma that does not require surgical intervention
Dopamine agonist: Bromacriptine/Cabergoline
What to measure on acromegaly to screen for GH secreting adenoma
IGF-1
Medical (pre-surgical) treatment for GH adenoma
Somatostatin analogues.
Treatment for Acromegaly post surgery with elevated IGF-1
1) Dopamine agonist
2) Somatostatin analogues
3) Pegvisomant
Adverse effects of somatostatin analogies –> diabetes mellitus due to suppressive effects on Beta cells
Acromegaly cancer association
1) Thyroid cancer
2) Colon cancer
- Colonoscopy from age 40 n
Pegvisomant mechanism of action (used in Acromegaly)
Pegvisomant: Blocks growth hormone receptor
ACTH excess clinical feature
Hyperpigmentation
Easy bruising
Wounds that don’t heal
Spinal osteoporosis
Next best test when elevate cortisol identified on test
Coupled cortisol and acth to determine if ACTH dependent or ACTH independent
How do you prevent Nelsons syndrome in ACTH excess with adrenalectomy?
Pituitary irradiation
Drugs that can be used in Cushing’s disease
not complete
1) Ketoconazole
2) Metyrapone
Causes of ectopic ACTH
Small cell lung cancer
Lung Carcinoid
Characteristic biochemistry of TSH-oma
Elevated T4/T3
Normal or elevated TSH
Ddx: resistant to thyroid hormone
Most common presenting symptom of pituitary apoplexy
Headache (between the eyes and acute onset)
Most common deficiency in lymphocytic hypophysitis? (two)
ACTH
ADH
Measurement for ADH
Copeptin
Diabetes insipidus (central - under production of ADH) NOT COMPLETE
Central
- Head injury
- Hypohpysitis
- Infiltrating lesions
Nephrogenic
MEN1 associated diseases
P’s
1) Parathyroid
2) Pancreas (neurological-endocrine)
3) Pituitary
Pituitary Apoplexy treatment
1) Give steroids -dex
2) Check prolactin/cortisol and other hormones
3) If prolactinaemia then give bromocriptine
4) Surgery
HLA -Associated disease in DR4-DQ8 or DR3-DQ2
1) T1DM
2) Autoimmune thyrpoids (screen annually)
3) Coeliac Disease
4) Pernicious Anaemia
Other: Addisons disease, ITP, Polyglandular autoimmune syndrome type 2, RA, vitiligo and autoimmune hepatitis
Markers of Beta cell autoimmunity - Autoantibodies in T1DM
Pro-insulin - beta cell specific
GAD
IA-2
Zinc Transporter 8 - beta cell specific
Benefits of insulin glargine
1) Improvements in HBA1c
2) Less nocturnal hypoglycaemia
Nb: Toujeo is associated with reduced severe hypoglycaemia
Diagnostic criteria for LADA
1) Diabetes
2) Adult
3) Evidence of islet cell autoimmunity: GAD antibodies > 5 units
4) Quick progression to insulin after initial period of insulin independence
Potential clinical features of LADA
Age <50 Acute symptoms at onset BMI <25 Personal autoimmune history Family autoimmune history
Diagnostic criteria in T2DM in asymptomatic patients
1) HbA1c ≥6.5% (48 mmol/mol) on two separate occasions
or
2) FBG ≥7.0 mmol/L or random blood glucose ≥11.1 mmol/L confirmed by a second abnormal FBG on a separate day
or
3) OGTT before (fasting) and two hours after an oral 75 g glucose load is taken. Diabetes is diagnosed as FBG ≥7.0 mmol/L or two-hour post-challenge blood glucose ≥11.1 mmol/L
Indication to commence GLP-1 agonist (exenatide/dulalgutide/semaglutide)
1) HBA1c > 7%
2) Dual or triple oral therapy or insulin
Weight loss
? Cardiovascular improvement in outcomes
DPP-4 inhibitors (Gliptins)
Adverse effect: ?Pancreatitis (Cannot use if previous pancreatitis)
Weight neutral
Best gliptin to use in renal failure
Linaglipitin
SGLT2 site of action
Proximal tubule
Contraindication for SGLT2
1) Renal impairment GFR <45
2) Hepatic impairment
3) ? Elderly
Interactions of SGLT2
Loop diuretics
Adverse effects of SGLT2
1) Polyuria
2) Genital infection - 5%
3) Hypoglycaemia (only in combo with insulin/OS)
4) Euglycaemia DKA (precipitants surgery - w/h 72 hours prior, fasting and ketogenic diets, sever intercurrent illness with reduction in oral intake, underlying autoimmune diabetes)
Most sensitive test for early peripheral neuropathy in DM?
128 Hz tuning fork
Predictor of cardiovascular death in diabetics
Microalbuminuria (Commence on RAAS agent if found)
Which of the incretin drugs is associated with weight loss?
GLP-1 Analogues
Main adverse effect of Glitazones
MOA: PPAR agonists
A/E: Heart failure
Obesity associated malignancy
1) Endometrial
2) Oesophageal
3) Gall bladder
4) Renal
5) Colon
6) Breast
Most prevalent gene associated with human obesity
MC4-R (dominant)
Stimulatory signal to the hypothalamus to eat
Ghrelin
ILP-5
Is leptin inhibitory or stimulatory?
Inhibitory
Medications that can be used for weight loss
1) Phentermine: Sympathomimetic amine
2) Topiramate: Off label
3) Orlistat: Intestinal lipase inhibitor
4) Liragluatide: GLP-1 agonist.
5) Buproprine/Naltrexone: Combined NA/DO reuptake inhibitors and nicotinic receptor antagonist + opined receptor antagonist
6) Lorcaserin: Selective 5HT receptor agonist n
Indications for bariatric surgery
1) BMI > 40 with no major comorbidities or 2) BMI > 35 or 3) BMI 30-35 with metabolic syndrome, or uncontrollable T2DM
