ENDOCRINOLOGY Flashcards
What is the normal blood glucose range for a healthy person:
- fasting
- post meal
Fasting 4 - 5.9 (or 5.4 ish)
Post meal can go up to 7.8
Think of this as approx 2 mmol range from 4 that roughly doubles post meal
What is the diagnostic blood sugar range for diabetes
Fasting >7 mmol/l
Post meal >11.1 mmol/l
7/11
What is the blood sugar range for pre-diabetes
Impaired fasting glucose: 6.1 - 7 mmol/l
Impaired glucose tolerance: 7.8 - 11 mmol/l (glucose challenge 75 mg)
Describe the pathology of Diabetes mellitus type 1
Autoimmune - autoantibodies against beta cells in islets of langerhans
Islet cell antibodies - ICA
Anti-glutamic acid decarboxylase (GAD) antibodies
Depleted beta cells = no insulin production (get down to around 10% at diagnosis)
No insulin = glucagon dominant state
=Increase gluconeogenesis (exacerbates hyperglycemia, as no insulin to clear)
=glycosuria
=Increase lipolysis, beta oxidation of fats, ketogenesis
Because there is so little insulin, you get unregulated ketogenesis
=Ketoacidosis
=Ketouria
DKA
Treatment - Insulin
Describe the pathology of type 2 diabetes
- Impaired insulin secretion (possibly bc of fat deposits in pancreas and liver)
- Insulin resistance across cells
Low insulin = glycogen dominant state
=gluconeogenesis (but glucose cant be cleared as cells resistant)
=increase lipolysis BUT bc some baseline insulin, do go into DKA, as insulin still has some regulatory effect
Insulin resistance
=Cant clear glucose
=Glycouria
NO ketouria
Treatment: Metformin, and possibly insulin if production is bad
Think of this one as being driven by physiological mechanisms that have the potential to be reversed
List some differences in the pathology of type 1 and type 2 DM
1: ketouria + glucouria; autoimmine, beta cell destruction, associated with other autoimmune diseases; HLA DR3, DR4 associated (90%)
2: glucouria only, physiological, caused by obesity, lack of exercise, calorie and alcohol excess. Reversible
What autoantibodies are associated with type 1 diabetes
Islet cell antibodies
GAD antibodies - Anti glutamic acid decarboxylase
Risk factors for type 1 diabetes
HLA DR3, DR4 positive
Other autoimmune disease - hypothyroid
Inheritance risk:
if a mother has the condition, the risk of developing it is about 2%
If a father has the condition, the risk of developing it is about 8%
if both parents have the condition, the risk of developing it is up to 30%
if a brother or sister develops the condition, the risk of developing it is 10%
(rising to 15% for a non-identical twin and 40% for an identical twin).
Risk factors for type 2 diabetes
Obesity Lack of exercise Alcohol excess High calorie intake 80% concordance in identical twins Pre-diabetes - progresses from this Gestational diabetes
Asian men
What does cortisol do to insulin
Counteracts it
This is why steroids can cause diabetes
Atypical causes of diabetes
Steroids, HIV meds, antipsychotics
Pancreatitis, pancreas surgery
Cushing’s, acromegaly, hyperthroidism, pregnancy
What is metabolic syndrome
BMI >30 or high waist circumference - central obesity Plus two of the following: BP >135/85 Triglycerides >1.7 mmol/L HDL - hyperlipidemia Pre-diabetes Diabetes
obesity + signs of cardiovascular disease (hypertension, hyperlipidemia etc) + diabetes
What are the typical symptoms of type 1 diabetes
Polyuria - osmotic diuresis Thirst - osmotically driven, not bc of fluid loss Weight loss Fatigue Blurred vision Pruritis vulvae - vaginal candidiasis Chest infections Hunger - lack of useable energy source
Signs of DKA
Drowsiness
Unexplained vomitting
Dehydration
+type 1 diabetes symptoms
Symptoms: develop over days polyuria and polydipsia nausea and vomiting weight loss weakness abdominal pain (confused with surgical abdomen) Drowsiness / confusion
Signs: hyperventilation (Kussmaul breathing) dehydration (average fluid loss 5-6 litres) hypotension Tachycardia coma
Difference in presentation of type 1 and 2 diabetes
Type 1 acute onset, may present in ketoacidosis
Type 2 insidious onset - pt may be asymptomatic at diagnosis - very rare to present in ketoacidosis, may present with complications instead of classic symptoms - eg vision changes
Type 1 - bloods will show autoantibodies, ICA, GAD; HLA D3 and D4 associated
Type 1 often starts before puberty, or younger pt
Type 2 over 30
Flags for type 1 diabetes
Short history (Weeks) of symptoms
Weight loss
Ketouria
What happens if you dont treat ketoacidosis
Absence of insulin and rising counterregulatory hormones leads to increasing hyperglycaemia and rising ketones
Glucose and ketones escape in the urine but lead to an osmotic diuresis and falling circulating blood volume
Ketones (weak organic acids) cause anorexia and vomiting
Vicious circle of increasing dehydration, hyperglycaemia and increasing acidosis eventually lead to circulatory collapse and death
What are the diagnostic features of DKA
Hyperglycaemia (plasma glucose usually <50 mmol/l)
Raised plasma ketones (urine ketones > 2+)
Metabolic acidosis – plasma bicarbonate < 15 mmol/l
Hyperglycaemia
Ketones
Acidosis
NB - K+ will be high on presentation as K+ leaves cell to counteract acidity, but will fall when treat with insulin so need to treat this
What is the treatment of DKA
rehydration (3L first 3 hrs) insulin (inhibits lipolysis, ketogenesis, acidosis, reduces hepatic glucose production, increase tissue glucose uptake) replacement of electrolytes (K+) treat underlying cause Treatment must be started without delay Follow DKA protocol in hospital
List some of the complications of DKA
cerebral oedema (deterioration in conscious level) children more at risk
adult respiratory distress syndrome
thromboembolism – venous and arterial
aspiration pneumonia (in drowsy/comatose patients)
death
What is the normal range for HbA1c
<42
Outline the treatment for type 1 diabetes
Basal-bolus insulin regime
Basal long-acting insulin at night to cover hypoglycemia through the night
x3 short-acting insulin pre or post meal during the day
Benefits:
Its flexible to the patients life as they can control they insulin dose based on their meal (carb content) and when they eat, or alter according to exercise
Disadvantages:
It is arduous - pt has to actively manage their blood sugars and cannot miss any injections
They also need to match their dose to their carb load - requires checking carbohydrate content and matching
Risk of weight gain
Must still have plan for hypo
Outline the treatment for type 2 diabetes
- Diet, exercise, weight loss (aim is to improve insulin sensitivity)
- Metformin on its own (inhibits glyconeogenesis from liver, to reduce glucose load - improves insulin sensitivity)
- Metformin + second line drug to improve insulin sensitivity/ secretion
DPP4 inhibitors - Gliptin (inhibit the breakdown of incretin)
Sulphaylurea
Pioglitazone - Triple therapy: Metformin + 2 others
- Insulin therapy
Outline insulin therapy for type 2 diabetes
- May take a bolus at night to cover risk of hypo + maintain oral therapies - metformin etc
- Biphasic regime: bolus + 2 short acting
- QDS - basal-bolus regime - same as that used by type 1s
- Mixed insulin - 70/30 mix of long and short - covers you for the whole day but you cant change routine/ when you have meals as wont be covered by insulin
What are the different types of insulin for diabetics
Short acting
Intermediate
Long acting
Mixed - 70/30 long to short
What advice would you give to a patient on how to prevent a hypo
Educate them on risk factors - eg. insulin dose that is not matched to the carb load of their meal, exercise
Educate them on identifying when a hypo is starting - palpitations, dizziness, sweating, anxiety, hunger, tremor
Advice them to carry fast acting carbs with them, eg jelly babies so that they can treat the hypo immediately
Advice them to discuss with friends and family, so that they also know signs and can help
Advice then on what to do if they do not have anything to treat the hypo and are along - call for an ambulance
List some factors that make it difficult for people with diabetes to maintain self management
Risk of hypoglycaemia Too arduous a treatment Risk of weight gain Interference with lifestyle Lack of sufficient training from diabetes teams
*Have to balance risk of hyperglycemia and the associated complications against the risk of having a hypo
What blood marker predicts the likelihood of microvascular complications of diabetes
HbA1C
What are the risk factors for macrovascular complications of diabetes
Hypertension
Hyperlipidemia
Stroke
MI
Hence, diabetics are put on statins and ACE inhibitors to lower this risk
What are the microvascular complications of diabetes and their signs
Retinopathy - haemorrhage, cotton-wool spots (areas of ischemia), lipid deposits (hard exudate - leaky vessel), micro aneurysm
Peripheral neuropathy - glove and stocking distribution, paraesthesia, loss of pain sensation, absent ankle reflexes, infection
Ischemia signs - absent foot pulse, do doppler measuremens
Nephropathy - nephrotic - raised urine albumin:creatinine ration, microalbuminuria - when urine negative for protein but the albumin:creatinine ratio is raised
Outline the treatment of a hypo
Recognise - sweating, palpations, hunger, dizzy, anxiety, tremor Confirm - blood sugar <3.9 Treat - fast acting carb 15g Retest - after 15 minutes Eat - long acting carb meal
What are the risk factors for Graves’s disease
Female
HLA DR3 - other autoimmune linked disease
Smoking
Stress
What would you request as part of the bloods for a pt with suspected graves, and what would expect the results to show
Thyroid function tests
Thyroid autoantibody
Thyroid stimulating antibody
Results: Raised T3 Low TSH TSA positive HLA DR3 positive Thyroid autoantibody positive - eg Antithyroid peroxidase ATP, Antithyroglobulin
List the symptoms of graves disease
Weight loss Increased appetite Diarrhoea Anxiety Palpitations Sweating Oligomenorrhoea
List the signs of graves disease
Eye disease: exopthalmos, increased tear production, change in visual acuity
Pretibial Myxoedema
Diffuse goitre
Outline the treatment options for Graves disease
1.Thionamides
Carbimazole (cant use in preg), propylthiouracil (PTU), methimazole (decrease synthesis of new thyroid hormone, T3 and T4)
Regime choice:
-Titrate to normal level - risk of hypo
-Block & replace - block all T3/4 production, replace with levothyroxine
Do this for 12-18 months, take off, 50% relpase
May then want radioiodine or surgery as alternative
2.Radio iodine therapy
3. Surgical resection of the thyroid
What are the complications of graves
Heart
Bones
Heart failure
Angina
Atrial fibrillation
Osteoperosis
Thyrotoxicosis - psychosis, panic, chorea, infertility
What is the pathology of graves disease
Autoimmune condition where have antibody that cross reacts with thyroid stimulating hormone receptor
Get overproducation of thyroid hormone
Hyperplasia of thyroid follicular cells
Drug causes of thyroid disfunction
Amioderone
List the commonest causes of Cushings disease
Steroids
Pituitary tumour
(the majority)
Rarer:
small cell lung cancer
What is IGF-1
Insulin like growth factor - 1
Which functional pituitary tumour does not usually require surgery
Prolactinoma
Use - bromocriptine to shrink, + cabergoline
Outline the treatment of acromegaly
Surgery
Medical - somatostatin inhibitors; GH antagonists; DA agonists - cabergoline; pegvisomat
Outline the treatment of hyperprolactinaemia
Not surgery
Medical management only
Use dopamine agonists - cabergoline
Bromocriptine for shrinking
What are the signs and symptoms of cushings
Face - moon, hair, acne, skin infections Mood - depressed, irritable, lethargy Body - central obesity, striae, weight gain Gonads - amenorrhea Polyuria, polydipsia
What are the signs and symptoms of acromegaly
Acroparaesthsia Facial changes - enlarged jaw, supraorbital arch, puffy lips (and eyelids?) Enlarged hands and feet Arthralgia Carpal tunnel Weight gain Decreased libido
What are the signs and symptoms of prolactinoma
Galactorrhoea Decreased libido Infertility Dry vagina Erectile dysfunction Amenorrhoea Weight gain
What is the name of the commonest basal insulin and what is the peak time
Isophane - NPH
2-4 hours
Which long acting basal insulin does not peak
Glargine
List some common fast acting insulins and the time it takes for the drug to get into the blood (onset) and peak
Aspart - 10-20 mins, peak 30 mins
Lispro same as above
Symptoms of hyperkalaemia
Chest pain, lightheaded, palpitations, SOB
Signs: short QT, arrhythmias
Tests of hyponatraemia
Plasma osmolality • Urine osmolality • Plasma Glucose • Urine sodium • Urine diptest for protein • TSH • Cortisol • Short synacthen if cortisol <500 nmol/l • Consider Alcohol
List some of the causes of hyponatraemia
Fluid overload, HF etc
Normovolemic - SIADH
Dehydrated - diabetes etc
What is the normal range for Na+ and normal plasma osmolality
137-144
<135 - hyponataemia
osmolality - normally 275–295
How would you investigate diabetes insipidus
Water deprivation test + desmopressin
Works out if kidney V2 receptors are sensitive -
if respond to desmopressin - cranial cause
if dont respond - kidney cause
What is the upper limit of fluid osmolality you can use when treating chronic hyponataemia
chronic hyponatraemia - CNS adapts
- correction must be slow - <8mmol/24hr
Treat with 0.9% saline if symptomatic
Asymptomatic, fluid restrict (750-1000ml/24 hours)
List some signs of SIADH
Hyponatraemia
No odema
Normal circulating volume (no fluid overload)
What would be the urine results of someone with SIADH
High urine osmolality (tf low plasma osmolality)
High urine Na (tf low plasma Na)
Causes of SIADH
Head injury - basically any neuro condition that changes pituitary, menigitis, encephalitis, brain tumour
Respiratory, pneumonia, TB, asthma
Drugs - carbamazepine, MAO inhibitors, thiazides
Tumours
