Endocrine notes Flashcards
What are the causes of hypoK?
What are the indications for screening of Conns syndrome?
- Refractory hypertension: uncontrolled hypertension despite the use of at least 3 different classes of antihypertensives
- Young aget onset hypertension (below 40)
- Family history of associated young death
- HypoK and hypertension already has probability risk
What screening and confiramtory tests for conns syndrome?
check ABG: alkalosis (endocrine causes), acidosis (renal causes –> no time for renal compensation)
- Measure aldosterone renin ratio: >750 is confirmatory (if already 5 digits it is confirmatory of conns syndrome)
Confirmatory testing
* NS suppression test: infuse with 2L of NS, there should be suppression of aldosterone to less than 140
* Salt loading test: test for 24 hour urinary aldosterone (if still elevated = positive)
Less commonly used test: captopril suppression test, fludrocortisone suppression test
Localization test
After NS test, can do postural stimulation test to differentiate adenoma from hyperplasia
* Measure aldosterone at supine 8am than measure standing up after 4 hours
* Adenoma: ACTH stimulates production of aldosterone. ACTH is low in hte noon.
* Bilateral adrenal hyperplasia: ACE stimulates the bilateral adrenal hyperplasia when standing. Aldosterone will be will be low in the morning and high in the afternoon.
Afternoon cortisol level must be lower than morning cortisol due to ACTH.
What is the necessary diagnostics to proceed to surgery in Conns syndrome?
- NS test positive (elavated PAC despite test)
- Postural test is high
- CT imaging shows unilateral adrenal mass (if bilateral requires venous sampling to do lateralization test)
If during venous sampling the differene is 3-4x it points to lateralization and the side with more secretion can be removed. If ratio is less than 4 will not do surgery and just do medication.
If fulfill all 3 –> can proceed to surgery
How is adrenal venous sampling done for Conn syndrome?
- Using laterality index of >4 as cut off
- Administer ACTH than measure the cortisol level of IVC and adrenal vein
What are CT features that favor adrenal adenoma over malignancy?
What size is considered more likely malignant?
- Adenomas are small <3cm
- Round, or ovoid homogenous with low density and smooth borders
- Contain fat
- Non contrast imaging: <10 HFU
- Washout imaging (15 mins post contrast): >60% absolute washout, >40% relative washout
Phaeochromocytomas and hypervascular metastases such as RCC and HCC may have identical washout values. Hence if >120 HU on the portal venous phase, the washout value should be ignored, as the lesion is most likely a hypervascular metastasis (RCC/HCC) or phaeochromocytoma rather than a lipid-poor adenoma
What is treatment for thyrotoxic periodic paralysis vs hypoK periodic paralysis?
Thyrotoxic periodic paralysis:
Stabilize patient with K+ supplementation
Long term treatment:
if symptomatic should do RAI or thyroidectomy as with hypoK there is high risk of arrhythmia
Hypokalemic periodic paralysis (idiopathic)
K+ sparing diuretics (prevent urinary loss of K+): spironolactone
Acetazolamide
What Ix done for phaeochromocytoma?
- Urine catecholamines: metanephrine, normetanephrine, dopamine, and vanillylmandelic acid (VMA)
- CT scan
- MIBG scan: can be therapeutic via MIBG radionuclide therapy
- 68-Ga-DOTATE PET CT scan (phaeochromocytoma has malignant potential) which shows somatostatin receptor positive tumors: can use peptide receptor radionuclide therapy
In DM patient with thyroid associated orbitopathy, apart from eye exam what would you do?
Fundoscopy
* Choroidal flow signifies severity of thyroid eye disease
* See if DM retinopathy (impairing visual acuity)
In thyroid associated opthalmopathy patient what is the triad of signs to assess?
- Eye
- Acropachy (digital clubbing, soft tissue swelling of the hands and feet, periosteal new bone formation)
- Pretibial myxedema (dermopathy)
What are the risk factors for aggravation of graves opthalmopathy?
- Smoking: if patient has hyperthyroidism (therapeutic efficacy of PTU/methimazole will be impaired thus inducing hypothyroidism –> increasing TSH)
- Thyroid dysfunction: especially hypothyroidism (causes increased TSH: the eye has same TSHr as thyroid which causes them to bind to EOM inducing thickening and inflammation)
- Radioactive iodine: may induce chemical thyroiditis
- Trauma: prone to pretibial myxedema (myxedema can occur at any traumatic site e.g. BCG scar at arm)
What is the pathophysio of myxedema?
- Form of cutaneous and dermal edema secondary to increased deposition of connective tissue components
- Fibroblast stimulation by TSHr causes increased deposition of GAG which results in osmotic edema and fluid retention. Many cells responsible for forming connective tissue react to increases in TSH level (hence any trauma can form myxedema)
- Lymphocyte stimulation (trauma). Lymphocytes react against TSHr (present in mixed connective tissues) by inappropiately producing thyroid stimulating immunoglobulin –> tissue damage and scar tissue formation
What are the Ix done for thyroid eye disease?
- CBC
- TFT
- Anti TSHr (correlates with activity, used for monitoring response to drug treatment. If anti TSHr is still high after a year, cannot stop the antithyroid drug due to high risk of relapse)
- CT orbit
- MRI orbit for better delineation of periorbital EOM edema
What is the treatment for thyroid eye disease?
Aim for euthyroid status
* Eye lubricant (symptomatic relief)
* Selenium (mild eye disease): QoL and symptomatic relief
* IV pulse steroids (12 week regimen): 500mg 1x weekly for 6 weeks followed by 250mg 1x weekly for 6 weeks. Pulse steroids has better efficacy than oral steroids + less chance of cushingoid features
* MMF: synergistic effect combined with steroids –> eye prognosis better
* Tocilizumab
* Statin: atorvastatin (useful in moderate to severe eye disease): 2mg daily
- Orbital RT: has better efficacy when combined with IV pulse steroids –> helps improve diplopia (if no diplopia not done)
Contraindications - Young people <30 years (has carcinogenic effect)
- Diabetic retinopathy, hypertensive retinopathy
When steroids not successful
* Surgical decompression
* Rehabilitative surgery (1-2 years later in the fibrotic stage, not done in inflammatory stage. Tighten the muscles, improve the diplopia)
In thyroid eye disease short case how would you approach PE?
- Look at eye signs
- After I would like to look for clubbing (acropachy) and pretibial myxedema
- Than assess the thyroid status (e.g. AF, hand tremor)
If patient has thyroidectomy with graves ophtalmopathy, non drug compliance and high TSH with poor vision what should you suspect?
- Blindess due to compressive optic neuropathy
- Excess TSH due to hypothyroidism (no thyroxine taken) binds to TSHr in the eye causing compression
If there is unilateral eye opthalmoplegia what must you suspect apart from Graves opthalmopathy?
Euthryoid Graves disease is rare (+presents unilaterally). 95% of cases will present with bilateral proptosis.
Single eye involvement suspect other potential ddx
* Eye lymphoma
* Pseudotumor
* IgG4 related disease
Patient with ocular MG and graves opthalmopathy, how would you manage?
Stabilize the MG first
* Start on IVIG
* Followed by IV infusion pyridostigmine and pulse methylprednisolone (administered once a week for 6 weeks)
If given steroid first there is extremely high chance of inducing myasthenia crisis (bulbar symptoms and respiratory arrest). Hence given IVIG to protect.
In thyrotoxicosis and thyroid eye disease can you do thyroidectomy?
No as it will exacerbate the thyroid eye disease. Thyroidectomy is not a treatment for thyroid eye disease (only for after stabilizing eye for maintenance)
How to calculate thyroid hormone replacement?
If find that t4 is elevated after a long stable period what could this mean?
1.6kg x body weight
If there is full thyroxine replacement that means there is no remaining thyroid.
If there is a sudden rise in T4: the patient can may have reduced in weight.
How to ensure proper consumption of thyroxine replacement?
- Taken at empty stomach
- Can eat only 30 mins after
- See if taking any iron or calcium (will interfere with absorbance): can only be taken 3 hours before or after T4 consumption
TZD example and side effect/contraindications
eg. pioglitazone, rosiglitazone
Improve insulin sensitivity by activation of PPARgamma
AE
* Fluid retention (Edema) and congestive heart failure
* Bladder cancer
* Diabetic macular edema
* Fluid retention (Weight gain)
* Fractures
* Hepatotoxicity
* Increased ovulation and teratogenic effects
Contraindications for bisphosphonates
- Renal failure
- Esophageal erosions: GERD, benign strictures
- Hypocalcemia (will exacerbate as this is anti-resorptive agent)
Contraindications to use of teriparatide?
Anabolic agent: PTH analogue
- Hypercalcemia
- Pagets disease
- Osteogenic sarcoma
- Previous irradiation to the skeleton
- Pregnancy or breast feeding
- Bone cancer to metastatic cancer to bone
DM drugs that reduce weight
- SLGT2i (dapagloflozin)
- DPP4 inhibitor (sitagliptin)
- GLP1 agonist (liraglutide)
What are the Ix for suspected diabetic ketoacidosis?
What parameters need to be monitored?
Ix
* Urine (fast) and blood glucose
* Urine (fast) +/- plasma ketones or BAHA
* Electrolytes (Na, K, PO4 +/-Mg), anion gap
* Urea, creatinine, Hb
* ABG
If indicated (Ix to detect underlying infections which are exacerbating condition –> easy to manage)
* CXR, ECG
* Blood and urine culture and sensitivity
* Urine and serum osmolality
* PT, aPTT
Parameters to monitor
* Clinical status for dehyderation: BP, pulse. respiratory rate, consious level, I/O charting
* Hourly urine and blood glucose
* Na, K, urea, AG (till blood glucose <14mmol/L
* Repeat ABG (if patient is in ketoacidosis: may just be hyperglycemic)
What are the ancillary measures for diabetic ketoacidosis?
- Aspirate stomach if patient unconsious or vomiting (protect airway with cuffed endotracheal tube if necessary)
- Catheterize bladder and set CVP as indicated
- Give antibiotics if evidence of infection
- Treat hypotension and circulatory failre
How to Mx diabetic ketoacidosis?
- Hydration with 1-2L 0.9% NS in the initial hour. 1L/hour or 2 hours as appropriate. If serum Na>150mmol/L use 0.45% NS. Fluid in first 12 hours should not exceed 10% BW, watch for fluid overload. When blood glucose <14mmol/L, change to D5
- Regular human insulin 0.15U/kg as IV bolus, followed by infusion. Aim at decreasing plasma glucose by 3-4mmol/L per hour, double insulin dose to achieve this rate of decrease in blood glucose if necessary. When BG <14mmol/L change to D5 and decrease dose of insulin to 0.05-0.1U/kg/hour
- K: 10-20mmol/hour in initial hour. Continue 10-20mmol/hour, change if K<3mmol/L, increase to 40mmol/hour. Aim at maintaining serum K between 4-5mmol/L. Must add K+ regardless if normal as insulin causes intracellular shift of K+.
- NaHCO3- if pH lower than 7. If pH between 6.9-7: give 50mmol in NaHCO3- in 1 hour. If pH <6.9 give 100mmol NaHCO3- in 2 hours. Recheck ABG after infusion, repeat every 2 hours until pH>7. Monitor serum K when giving NaHCO3-.
Normal saline will cause intravascular expansion and correct the hyperosmolar hypovolemic hyponatremia as it contains Na+.
What is a possible insulin regimen?
Basal to mimic and control the fasting glucose. Bolus is to control the meals glucose. If the patient is smart: patient can titrate their own prandial insulin. If large meal: more insulin. If no meal can skip insulin. Can do carbohydrate counting.
* Tresiba (insulin degludec: basal) 9 units SC AM
* Apidra (glulisine): 6U in the morning, 5 in afternoon, 3 in night
In DM what is the importance of assessing when hypoglycemia occurs in insulin replacement?
Will be able to know what insulin dosage to titrate
* If fasting hypoglycemia in the morning –> adjust basal insulin
* If happens before lunch –> adjust breakfast prandial dose
Find underlying cause: having extra dose, excessive excercise (without snack), eating half amount of food
How to confirm dx of DM with patient presenting with hyperglycemia?
- Fasting glucose (for quickest results)
- HbA1c (most accurate)
- Random glucose is not that good but done 1st line, haemstix
HyperPTH patient with high ALP, what would you suspect?
Osteitis fibrosa cystica
How to differentiate DKA vs HHS (hyperosmolar hyperglycemic state)?
Why would a T2DM patient be on insulin injection?
On presentation
* symptomatic
* Presenting with features of insulin deficiency e.g. DKA
* Very high glucose (fasting >13mmol/L, random >16.7mmol/L)
Poor glycemic control despite 2 OHAs
* Persistent symptoms
* HbA1c ?9%
How to make dx of DM?
Random glucose ≥ 11.1 + Symptoms of hyperglycemia
Fasting glucose ≥ 7.0 on two occasions in asymptomatic individuals
2 hour OGTT ≥ 11.1 during 75g OGTT
HbA1c ≥ 6.5%
Name the types of insulin
Insulin can be human insulin or insulin analog.
Inulin can be:
Ultrashort acting: Lispro, Aspart
Short acting: regular human insulin
Intermediate acting: neutral protamine hagedorn (NPH), lente
Long acting: ultralente, Detemir, Glargine, Degludec
Different preparations of premixed insulin
NPH insulin + Lispro insulin
NPH insulin + Aspart insulin
NPH insulin + regular insulin
When is HbA1c not reliable?
Falsely high - ↑ Glycation (chronic renal failure) + ↓ Erythropoiesis (iron def.) + Assay issues (↑ bilirubin).
Falsely low - ↓ RBC lifespan (blood loss, haemolysis, hypersplenism) + Blood transfusion
How to ix thyroid disorder?
- measure TSH
- Autoantibodies: anti TSH receptor Ab (TRAb), antithyroglobulin Ab, antimicrosomal Ab
- Radioactive iodine scan (diffuse uptake in graves)
- ECG
- For diplopia: MRI orbit
How to manage patient if thyrotoxic and opthalmopathy?
- Rapid control of thyroid dysfunction to euthyroid
- Immunosuppressants for infiltrative opthalmopathy –> steroids (IV pulse), cyclosporin A, plasmapharesis, Ig
- Teprotoumumab
- Orbital irradiation
- Surgery: orbital decompression or EOM surgery
NO RAI: release thyroid antigens and auto Ab –> increase risk of opthalmopathy
What is Whipple’s triad?
hyperthyroid, what is sign
Thyroid acropachy: clubbing, periosteal new bone formation in metacarpals/phalanges
PE in HT and heart failure?
Thrusting apex due to LVH, late stage = displaced
S3 gallop associated with left atrial pressure >20mmHg and increased LV end diastolic pressure
Late stage = S4
