Endocrinology Flashcards
What is the pathophysiology of diabetes type 1?
Autoimmune destruction of pancreatic beta islet cells. Therefore insulin deficient/absent.
What is significant about the immunology of patients with type 1 diabetes?
90% Associated with HLA DR3/4 which means a high risk of other autoimmune diseases
What is the pathophysiology of diabetes type 2?
Progressive reduced relative insulin production due to high demand for insulin - From high levels of adipose tissue or prolonged exposure to high blood glucose.
Then reduced insulin insensitivity as prolonged exposure causes Insulin receptors to upregulate the threshold for response.
What are the risk factors for diabetes type 2? 3x unmodifiable and and 3x modifiable
Asian
Male
Age
Obesity
Diet - calories and sugar
Alcohol
What are the criteria for diagnosis of diabetes?
- Symptoms (polyuria, polydipsia, lethargy, weight loss, thrush, vision changes) plus 1 raised glucose (fasting over 7 and random over 11)
- 2 separate raised glucose
- Hba1c over 6.5%
What is the difference between impaired glucose tolerance and impaired fasting glucose? Which is more predictive of developing into full blown diabetes?
Both demonstrate pre diabetes.
Fasting - over 6 but not quite 7
Tolerance - (after 2hrs) over 7.8 but not quite 11
Tolerance more predictive but both useful
What are some non lifestyle causes of diabetes?
Pregnancy
Steroids
Cushings
Acromegaly
Hyperthyroidism
Pancreatitis
Pancreatic surgery
CF
Antipsychotics
Thiazides
What are the differences between type 1 and type 2 diabetes?
Cause - autoimmune versus progressive insensitivity
Age - pre-puberty versus older
Genetics - HLA d3/4 versus no HLA link
Presentation - weight loss/DKa versus complications e.g. MI
What is included in a prediabetic/metabolic syndrome care plan?
Group education programs Smoking cessation Dietary advice Statin Bp control Foot care Retinal screening
What is the treatment for type 1 diabetes?
Insulin Dafne course to help adjustment Monitor hba1c Specialist nurse Dietician Foot care Retinal screening Bp Statin Smoking cessation
What is the treatment for type 2 diabetes?
Metformin
Then add gliclazide (sulphonylurea)
Then swap one for sitagliptin (DPP-4) or exenatide (GLP analogue)
Then consider insulin
Dietician Specialist nurse Foot care Retinal screening Bp Statin Smoking cessation
What should be checked in a patient with established diabetes?
Injection sites - infection/lipohypertrophy
Vascular - pulses, diet, smoking, hypertension
Nephropathy- urine dip for microalbuminuria (-ve protein but increased albumin:creatinine)
Fundoscopy
Feet - ulcers, pulses, sensation
Episodes of hypos
What would you see on fundoscopy in progressive diabetic retinopathy?
- Micro aneurysms and hard exudates
- Pre proliferative - haemorrhages, venous beading and cotton wool spots (infarcts)
- Proliferative - haemorrhages and new vessel formation. These can can bleed and fibrose and detach the retina
What are the signs of diabetic ischaemia in the feet?
Absent dorsalis pedis and posterior tibialis pulse
Leads to punched out painless arterial ulcer (+- infection)
What are the signs of diabetic neuropathy in the feet?
Glove and stocking loss of sensation
Absent ankle jerks
Deformity - pes cavus, claw toes, loss of transverse arch, rocker bottom sole
How would you manage a diabetic foot?
Assess
- Sensation loss
- Ischaemia via pulses and Doppler
- Bony deformity- Charcot may require X-ray
- Infection- swabs
- Regular chiropodist, therapeutic shoes
- Consider surgery
- IV abx for cellulitis
What are the indications for surgery in a diabetic foot?
Abcess - drain Spreading anaerobic infection Wet Gangrene Rest pain Septic arthritis
What is the difference between wet and dry gangrene?
Gangrene is visible necrosis
Wet is caused by venous occlusion, packed with blood, oedematous, has undefined borders, full of bacteria, backs up and spreads.
Dry is caused by arterial occlusion and very little blood, shrunken, defined edges, not too much bacteria, autoamputates.
What types of neuropathy are associated with diabetes?
Autonomic - eg gastroparesis, postural hypotension, erectile dysfunction
Symmetric sensory peripheral neuropathy- glove and stocking
Mononeuritis multiplex- e.g. Single cranial nerve
Amyotrophy - wasting of quads
What is the mechanism of DKA?
Acute increase in demand for glucose by the cells leads to an acute deficiency in insulin
Cells resort to using ketones for energy. This is inefficient and produces acetone as a byproduct.
Acetone is acidic which causes acidosis with an anion gap
Hyperglycaemia causes water to be drawn out of cells - dehydration and dilutional hyponatraemia
What are the signs of dka?
Vomiting and abdo pain Drowsy Dehydration Ketotic breath Kussmaul breathing
What might trigger a dka?
Infection Surgery MI Pancreatitis Chemo Antipsychotics Insulin non compliance
Why is there hyponatraemia in dka?
Osmolar pressure from hyperglycaemia draws water out of cells and dilutes the Na
Why is there hyperkalaemia in dka?
Acute loss of insulin relative to demand. Less k going into cells. May need to replace as insulin is given.
Give some causes of a raised wcc.
Infection Dka Allergy Steroids Leukaemia Rheumatoid arthritis UC/crohns
Which drug has a risk of lactic acidosis?
Metformin
What is the mechanism of HONK?
Hyperglycaemic osmolar non ketotic coma
Type 2 acutely high glucose (above 35)
No ketones so no acidosis, but huge dehydration and dilution of salts. Very Thrombotic state.
What are the skin manifestations of diabetes?
- Ulcers
- Necrobiosis lipoidica (shiny yellowish area on shin with telangiectasia)
- Acanthosis nigricans (pigmented thickened skin in folds eg neck axilla groin)
What are the risk factors for hypothyroidism?
High lipids
Diabetes
Addissons
Radioactive iodine for thyroid cancer
What are the risk factors for hyperthyroidism?
AF Amiodarone Lithium Downs /Turners Pregnancy
What are the symptoms of hypothyroidism?
Tired Weight gain Cold Dry skin Depression Menorrhagia Cramps
What are the signs of hypothyroidism?
Bradycardia Reflexes slow Ataxia - cerebellar Dry skin and hair Yawning Cold Ascites and non pitting oedema Round Defeated Ileus Congestive heart failure
Goitre
Pleural effusions
What are the symptoms of hyperthyroidism?
Restless Weight loss Palpitations Sweating Amenorrhea Anxious Hot
What are the signs of hyperthyroidism?
Clubbing Palmar erythema Tremor AF / tachycardia Eye signs Brisk reflexes Proximal myopathy Pretibial myxoedema
What are the eye signs of hyperthyroidism?
Photophobia
Diplopia
Exopthalmos
Proptosis
Eyelid retraction
Opthalmoplegia
What is the differential for a neck lump?
Goitre - hyper or hypothyroidism Thyroglossal cyst Branchial cyst Sebaceous cyst Lipoma Lymphadenopathy
How would you examine a neck lump?
Inspect
Swallow - goitre moves up
Stick out tongue - thyroglossal cyst moves up
Palpation
Nodular or diffuse
Fluctuance - lipoma
Feel below - if not retrosternal extension
Auscultation
Bruit - graves
What is the difference between t3 and t4?
T4 is thyroxine
Les active
Longer half life
Direct release from thyroid
T3 is mostly converted peripherally by deiodinase.
How is thyroxine synthesised?
- Iodine uptake into follicle cell by channel sensitive to tsh
- Activated and bound to tyrosine on thyroglobulin by thyroid peroxidase
- Stored as colloid in the middle of follicle
- Endocytosis back into cell
- Lysozyme release from thyroglobulin which is recycled
- Diffusion into blood
- Circulates bound to thyroid binding globulins (tbgs)
- Some is peripherally converted to t3 by deiodinase
What are the causes of a goitre?
Physiological (supply/demand) - iodine deficiency, pregnancy, puberty
Subacute viral thyroiditis (painful)
Nodular - benign or adenoma/carcinoma
Autoimmune - graves or hashimotos
What is the diagnosis if thyroid function test results are as follows?
Tsh high
T4 low
Primary hypothyroidism
The hypothalamic- pituitary is producing trh and tsh but the thyroid is not responding appropriately
What is the diagnosis if thyroid function test results are as follows?
Tsh high
T4 normal
Treated hypothyroidism
What is the diagnosis if thyroid function test results are as follows?
Tsh low
T4 high
Primary hyperthyroidism
The thyroid is producing too much, and the hypothalamus/pituitary are responding appropriately via negative feedback.
What is the diagnosis if thyroid function test results are as follows?
Tsh low
T4 normal
Subclinical hyperthyroidism
What is the diagnosis if thyroid function test results are as follows?
Tsh low
T4 low
Problem with hypothalamus/pituitary because thyroid is responding appropriately
Or sick euthyroid
Which antibodies are positive in Graves’ disease?
Anti tsh receptor stimulating antibodies
gRaveS - anti TRS
Which antibodies are positive in hashimotos?
Anti thyroid peroxidase antibodies
hashimOtos - anti TPO
How does thyroxine act on cells?
Increases cell metabolism at the nuclear receptors
Increases effects of catecholamines
Which nerve might be damaged during thyroid surgery?
Recurrent laryngeal
Which hormones are produced by the anterior pituitary?
TSH
ACTH
GH
FSH AND LH
Which hormones are produced by the posterior pituitary?
ADH
Oxytocin
Name the layers of the adrenal glands and the hormones produced there
Zona glomerulosa - aldosterone
Zona fasiculata - cortisol
Zona reticularis - androgens
Medulla - catecholamines
What are the metabolic functions of cortisol?
Insulin resistance
Gluconeogenesis
Protein catabolism
Increased bone turnover
What are the cvs functions of cortisol?
Increase bp
Fluid retention
Increase Na
What are the cns functions of cortisol?
Increase appetite
Increase gastric acid
What is the action of cortisol on skin?
Decrease collagen
What tests would you order if you suspected Cushings disease? What results would you expect for true cushings disease?
True cushings is a pituitary adenoma secreting excess ACTH.
Blood cortisol at 11pm - high
ACTH - high (ACTH dependent)
Dexamethasone suppression - suppressed
What would be the diagnosis if -
Blood cortisol high even at 11pm
ACTH high
Dexamethasone suppression- not suppressed
Ectopic ACTH secreting adenoma
What would be the diagnosis if -
Blood cortisol high even at 11pm
ACTH high
Dexamethasone suppression- suppressed
Pituitary adenoma secreting ACTH
Cushings disease
What would be the diagnosis if -
Blood cortisol high even at 11pm
ACTH low
ACTH independent cushings
So adrenal adenoma or steroids.
What are the causes of pseudo cushings? What would the blood cortisol result be?
Alcohol
Depression
Obesity
Steroids
Equivocal blood cortisol
What tests would you order if you suspected addisons disease? What results would you expect?
Primary adrenal failure
Blood cortisol - low even at 8am
U and e - low Na high k (mineralocorticoid aldosterone from zona glomerulosa also effected)
Glucose - low
Short synacthen - cortisol doesn’t rise after 30 mins.
How would you treat a dka?
0.9% saline
Then insulin 0.1u/kg/hr until
Blood glucose , bicarbonate , ph and anion gap are back to normal.
What are the targets for hba1c on 1) Metformin 2) sulphonylurea
When would you add a second drug?
1) 6.5%
2) 7%
Add a second drug if they hit 7.5%
What is the first line hypertension drug in diabetes?
ACE inhibitor
What are the side effects of Metformin?
GI disturbance
Lactic acidosis
What are the side effects of sulphonylureas?
Risk of hypo
Weight gain
SIADH
liver damage
What are the side effects of pioglitazone?
Fluid retention- contraindicated in heart failure
Weight gain
Liver damage
Bladder cancer
What are the side effects of SGLT 2 inhibitors?
Uti
Thrush
What might cause a painful goitre?
De quervains subacute thyroiditis
What might cause sick euthyroid syndrome?
Low everything
General illness/infection/surgery.
Goes away on its own
What is the genetic profile of MODY?
Autosomal dominant
Hnf alpha Or glucokinase genes
What is the main criteria for prescribing exenatide?
BMI over 35
What is the blood pressure target for :
- Primary hypertension
- Diabetic no organ damage
- Diabetic with evidence of end organ damage
- 140/90
- 140/80
- 130/80
What is Sheehans syndrome?
Hypopituitary after blood loss inbirth
What are the signs of an addissonian crisis? What causes it?
Shock Low Na High k Low glucose High ca Acidosis
Caused by sudden stop of steroids
What is the first line treatment for diabetic neuropathy?
Duloxetine/amytriptilline
Gastroparesis - metoclopramide, domperidone
What is the mechanism of action of carbimazole?
blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production
What are the side effects of carbimazole?
Rash and pruritis - treat with antihistamine
Agranulocytosis and neutropenia
Crosses the placenta, but may be used in low doses during pregnancy
What is the test for acromegaly?
Oral glucose tolerance test with GH measurement
Why does a goitre move up with a swallow?
Thyroid is attached to the larynx by the pretracheal fascia.
(Thyroglossal cyst will also move up)
What are the options for management of hyperthyroidism?
Carbimazole (Block and replace)
Propylthiouracil
Radioiodine
Thyroidectomy
