Endo top tier Flashcards
diabetes type 1 vs type 2
T1DM - insulin deficiency
T2DM - ineffective insulin + deficiency
diabetes diagnosis
fasting glucose: 7.0mmol/L
random glucose: 11.1mmol/L
OGGT: 11.1mmol/L
Hb1AC : 48mmol/mol , 6.5%normal
C peptide (down in type 1, normal in type 2) autoantibodies (present in type 1, not in type 2)
pre diabetes diagnosis
fasting glucose: 5.6-7.0
random glucose: 7.8-11.1
OGGT
Hb1AC: 42-47mmol/mol, 6-6.5%normal
fasting glucose test =
only water for 8 h
OGTT=
2 hours oral glucose tolerance test. 75g sugar drink given. blood taken 1 and 2h later
hb1ac =
proportion of haemoglobin with glucose stuck to it– measure of glucose levels over the last 2-3 months
type 1 vs type 2 diabetes symptoms
Type 1 symptom onset is acute
Type 2 symptom onset is gradual
diabetes symptoms
- Polydipsia, thirst
- Polyuria- nocturia, glycosuria, ketonuria
- Fatigue
- Dry skin
- Weight loss - lipid and muscle loss due to unrestricted gluconeogenesis
- Hunger - lack of usable energy source
- Infections
- – Recurrent thrush
- – Poor healing of wounds
- Blurred vision, esp at night (due to glucose/water in lens)
- Breath can smell of acetone smell (nail polish remover)/ pear drops (ketones- esp type 1
- Acanthosis nigricans = blackish pigmentation at the name of the neck and in the axillae – severe insulin resistance in DMT2
type 1 diabetes pathophysiology
Insulin deficiency due to autoimmune destruction of beta cells
— autoantibodies against insulin and islet cells
(high glucagon, more lipolysis, glycolysis, gluconeogensis, decreased peripheral glucose uptake, increased muscle breakdown)
so increased glucose conc, increased glucose lost in urine
Healthy at birth but damage to beta cells over time, eventually diabetes
type 1 diabetes untreated
high glucagon, high glucose
weak - muscle broken down
fat broken down (oxidised to ketone bodies)
prone to ketoacidosis
diabetes type 1 signs from investigations
dehydration
low BP
high levels of islet autoantibodies
no C peptide present (from pancreas)
diabetes type 1 risk factors
Northern european - especially finnish
Family history (HLA-DR3 , maybe other DRs?)
Associated with other autoimmune diseases (eg coeliac, graves, addison’s etc)
Vitamin D deficiency
ketoacidosis
free fatty acids and glucose levels high
these form acetyl coA
so increased ketones
ketones are strong acids so low blood pH. this impairs the ability of haemoglobin to bind to oxygen (dissoc curve shifted to the right)
+ pH dependant enzymes less effective
+ metabolic acidosis (high h+, low HCO3-)
+ breath smells of pear drops (=ketones)
causes of ketoacidosis
- Unknown, idiopathic
- Infection
- MI
- Treatment errors
- Undiagnosed diabetes (esp type 1)
Not really type 2, as even a small amount of insulin can halt breakdown of fat and muscle into ketones. So therefore, can occur in the very late stages where there is absolute insulin deficiency - Stopping insulin therapy
- Surgery
- Pancreatitis
ketoacidosis symptoms
Acute Polyuria Polydipsia , thirst May be unable to pass urine if not high water intake nausea , vomiting Weight loss Abdominal pain drowsiness/ confusion Weakness
ketoacidosis SIGNS
- Hyperventilation : Kussmaul’s respiration (deep rapid breathing)
- Dehydration: Urea and creatinine raised
- Hypotension
- Tachycardia
- Conscious disturbance, coma
- Breath smells of pear drops (ketones)
- Low body temperature
- Glycosuria, ketonuria
- Raised wbc maybe
ketoacidosis management
1 ABC (airways, breathing, circulation) 2 rehydration . no delay. In order to dilute acid and glucose 3 Insulin -- Stop new ketone production -- Stop glucose production in liver -- Lower glucose - convert to glycogen -- Monitor glucose 4 replace k+ -- Electrolytes -- K+ seems high (serum levels), but acc is in deficit because it moves out of cells to serum due to acidosis. It falls further with the rehydration (step 1) 5 Treat underlying cause
type 2 diabetes pathophysiology
- Impaired insulin secretion and insulin resistance in muscle and fat
- Beta cell mass reduces
- May have high levels of circulating insulin at the beginning, due to high levels of glucose from liver and reduced uptake– but this insulin is ineffective and inadequate at restoring hyperglycaemic state.
Then levels decrease due to secretory failure.
So insulin deficiency relative to increased demands causes hypersecretion by depleted beta cell mass → progresses to absolute insulin deficiency (where levels are low (not only relatively))
what is the viscous cycle of insulin resistance ? which type of diabetes
type 2
impaired glucose secretion (less insulin) and insulin resistance in muscle and fat (less effective insulin)
this causes impaired glucose tolerance, take up and clearance
this causes hyperglycaemia, this worsens glucose secretion and insulin resistance
diabetes risk factors
Modifiable:
- Obesity- high fat levels
- High cholesterol levels
- Sedentary lifestyle
- Low activity levels/ exercise
- Smoking
- High blood pressure
- medications - thiazide diuretic with beta blocker
Non–modifiable:
- Race: south asians, Chinese, middle-eastern, African-Caribbean or black African origin
- Gender (male>female)
- Genetic disposition
- Family history of diabetes
- Low birth weight
- History of gestational diabetes
gestational diabetes inc risk factors
- high blood sugar when foetus in pregnancy, usually disappears after birth
- Likely to have this if mum is overweight, south Asian, Black, African-Caribbean or Middle Eastern origin, had pregnancies with previous gestational diabetes/ large baby
- 40 yrs +
MODY=
MODY = maturity onset diabetes of youth
Dominant
type 2 risk factor
‘typical’ type 1 vs type 2 presentation
1 symptoms sudden young lean associated with other autoimmune diseases
2 symptoms sudden 30y+ overweight familial hypercholestrolemia often present hypertension alcohol family history
peptide C diabetes
from pancreas
not present in type 1
yes present in type 2
diabetes symptoms control
- control symptoms eg infections, fatigue
- control diabetes related eg gangrene feet, retinopathy
- prevent acute emergencies eg hyperglycaemia, ketoacidosis
- lifestyle changes – only for type 2
- glycaemic control medication (metformin, TZDs, sulphonylurea, incretin mimics, insulin)
if acute diabetes and you are not sure if it is type 1 or 2 what should you do?
treat with insulin – assume type 1 until you know otherwise – test for autoantibodies / peptide c
diabetes lifestyle changes
only for type 2
- smoking cessation
- sustained weight loss and exercise
- – can reverse insulin resistance! and lipotoxicity! so hyperglycaemia reduced
- – orlistat - inhibits intestinal lipase so reduces absorption of fat - weight loss and lower fat levels
- – bariatric surgery - makes stomach smaller - more satiety
- – reduce CV risk : ACEi, statins
compliance is hard
metformin
- action
- why bad/good?
1st line treatment
- decrease hepatic glucose production (gluconeogenesis)
- Decreases absorption of glucose in intestine
- Increases peripheral glucose uptake
- Improves insulin sensitivity, reduces insulin resistance
Weight gain- avoid for overweight
Less weight gain and less hypos than insulin
TZDs=
- action
- contraindications
Thiazolidinediones
Lower insulin resistance
Bad for individuals with heart failure, bone fractures, eye damage
sulphonylurea
- action
- why bad
- used when
Stimulates insulin secretion by increases B cell function
Short term is good but causes increase in stress to B cell so several years later, more B cell dysfunction Weight gain Contact DVLA (driving risk)
Used when metformin not adequate for glycemic control
incretin mimics
- what are incretins
- action of incretins
- why good
- types
Incretins are hormones produced after meals(triggered by nutrient intake), secreted by intestinal endocrine cells
- body produces more insulin,
- suppress post-prandial (post mealtime) glucagon release
- delay stomach emptying
- increase insulin sensitivity
- Promotes satiety
- Decreases gluconeogenesis?
No weight gain
- Mimic GLP1 = incretin mimics (GLP1 is an incretin)
Enhance GLP1= DDP 4 inhibitors
DDP 4 is an enzyme that inactivates incretins. Incretins have a short half life. So DDP 4 inhibitors allow the incretins to function better and extends their usage
which glycaemic medicine is injection and which isnt
injection
- insulin
- GLP1 analogues
not injection
- DDP4 inhibitor
- metformin
- sulphonylurea
- TZD
- SGLT-2 inhibitor
insulin
types - difference and when they are taken
basal insulin = long acting (mixed with retarding agents). taken during fasting . basal analogues = flatter – longer duration and lower peak
prandial/bolus insulin = rapid acting, taken pre-glucose spike of meal, adjusted according to meal’s carb content
can take separately or in mixed forms
-mixed forms = single preperation however cannot seperate doses so requires consistent meal and exercise times and amounts
type 2 diabetes - when should it be treated with insulin
there is a shift to treat it early as there is reduced complications with tighter glycaemic control
however, it can be impacted largely by lifestyle changes
and insulin causes weight increase
- this causes insulin resistance which then requires more insulin (vicious cycle)
glucose targets
- aim for what?
- special cases
aim for lowest Hb1ac balanced with hypoglycaemic risks relax targets if hypos are more dangerous: - old - complications / chronic illness - high risk of hypos - high risk of falls - cognitive impairment with these groups try to minimise chance of hyperglycaemia
hypoglycaemia
- what is it, pathophysiology
- levels (types)
- effects
- low plasma glucose
- glucagon is first defence (not present in T1/2DM)
- second line defence is adrenaline. each episode weakens response so threshold for a response increases
- impaired brain function
Level 1. Mild- 3.0-3.9
- Self treated (Unless child- child always requires 3rd party assistance)
- Mild cognitive impairment
- Many episodes are asymptomatic
Level 2. Severe- <3.0
- Require 3rd party assistance
- (as) Cognitive function significantly impaired
- can cause anxiety- fear of future hypos
- can cause accidents (driving, tree surgeon)
- increases CV risk
hypoglycaemia more common in which type of diabetes and why
type 1 because higher proportion take insulin and are on insulin for much longer time
hypoglycaemia causes
diabetics, non diabetics
diabetics:
- missed meal
- increased activity
- overdose
non diabetics : EXPLAIN
Exogenous drugs - insulin, alcohol binge with no food
Pituitary insufficiency
Liver failure
Addisons
Islet cell tumour (= insulinoma) and immune hypoglycaemia
Non-pancreatic neoplasm (eg firbosarcomas)
risk factors for severe hypos
- type 1
- type 2
type 1
- history of episodes - adrenaline response weakened
- long duration of diabetes
- less awareness
- very young/old
type2
- history of episodes - adrenaline response weakened
- long duration of insulin treatment
- cognitive impairment (forget if eaten, take insulin)
- old
- depression
+ High exercise levels
+Low HbA1C
+High daily insulin dosage
+Renal impairment – loss of glucose (less reabsorption)
hypos symptoms
Neuroglycopenia (shortage of glucose in brain)
- confusion
- weakness
- Drowzy, fatigue
- dizzy
- Difficulty concentrating
- Difficulty speaking (appears drunk sometimes)
- Visual changes
Autonomic -caused by adrenaline
- Sweat
- anxious
- trembling
- palpitation
- hunger
- — these symptoms before the neuro ones if glucose level falls slowly
Non-specific
- Nausea, malaise
- headache
- Patient had jaw clamp, cramp
- Tingling around mouth
severe = collapse, convulsion, coma
hypoglycaemia management
confirm diagnosis - fingerprick blood
fast acting carbohydrate given
retest in 15 mins and retreat if necessary
give long acting carbohydrate
whipple’s triad
for hypoglycaemia
biochemical confirmation, symptoms, symptoms relieving with treatment
prevention of hypos
Screening:
– See risk factors
Education of patients/carers eg DAFNE
- Risk factors
- Recognition
- Treatment
Cut back on treatment if previous hypos/ exercise (unless intense- as adrenaline is released)
hyperglycaemia
risk factors
not related to patient / diabetes
- Infection
- High glucose intake
- Medication
- — Thiazide diuretics
- — Steroids
hypo/hyperglycaemia relates to hypo/hyperosmolar states how?
hypoglycaemic =
hypoosmolality
hyperglycaemic = hyperosmolality
hyperglycaemia signs/ investigations
- Dehydration (osmotic diuresis, due to high glucose → water excreted (polyuria))
- — Low K+ in body but serum is high due to no insulin
- — Polydipsia, polyuria
- —Kidney failure due to lack of blood volume
Decreased consciousness. Stupor, coma
Hyperglycemia - serum and urine
Hyperosmolality
No ketones in serum/urine. Bicarbonate not lowered
hyperglycaemia treatment
Insulin
Fluid replacement (0.9% saline)
LMW Heparin -
- as blood is thick due to hyperglycemia so increased thromboses so more emboli
- reduce risk of thromboembolism/MI/stroke due to hyperosmolality
hyperglycaemia complications
acute and chronic
Acute
- Diabetic ketoacidosis
- Hyperosmolar coma
Chronic
- Tissue complications
- – Microvascular
- – Macrovascular
complications of diabetes
macrovascular
- atherosclerosis
- – CV disease
- – stroke,
- – peripheral vascular disease (claudication, rest pain, amputation)
microvascular
- diabetic retinopathy
- diabetic nephropathy
- diabetic neuropathy
- peripheral vascular disease (kinda micro, kinda macro)
diabetic retinopathy
- risk factors
Insulin Pregnant Poor glycemic control Hypertension High HbA1C
diabetic retinopathy
pathophysiology
Over years, blood vessel leakage and occlusion in the retina.
Microaneurysms cause loss of pericytes, and protein deposition
Glial cells grow in response, causing occlusion of capillaries → ischaemia / haemorrhage
diabetic retinopathy treatment
Damage cant be reversed so treatment is only to prevent progressive worsening
Laser therapy to burn vessels
Successful treatment however can damage night/peripheral vision
diabetic nephropathy/ neuropathy risk factors
Poor glycemic control
Hypertension
High HbA1C
diabetic nephopathy pathophysiology
Decrease in renal fucntion caused by hyperglycaemia
Injury to the glomerulus, basement membrane– so protein passes into the filtrate and is lost in the urine
– proteinuria (dipstick)
– albumin creatinine ratio. creatinine excreted fully whereas albumin meant to be retained (both micro and macro are above normal but macro is worse/more developed) . indicates the GFR and kidney damage
– Normal = 0-30
– Microalbuminuria = 30-300
– macroalbuminuria= 300+
diabetic nephropathy treatment
Risk factor control - BP and glucose
Diet change
diabetic neuropathy symtpoms
Sensory
- Pain, burning, tingling, loss of sensation
- Can sometimes lead to motor damage - clawing of toes and arch of foot
- Worse at night- interrupts sleep
- DPN= diabetic peripheral neuropathy. This is the lower limbs and feet
- Infection as a result of lack of sensation → ulceration → amputation
- Made worse by slower healing
Autonomic
- diarrhea/ constipation, incontinence
- Hypotension (postural)
- Erectile dysfunction
- Gastroparesis (feel sick after eating)
- Sweating cessation → dry, cracked, damaged fee
diabetic neuropathy treatment
Antidepressents (amitryptilline) Pain killers Very inadequate: most people have only moderate reduction in suffering Glycaemic control Foot screening
peripheral vascular disease diagnosis, inc signs/symptoms
Cold feet Weak pulses in feet Weak nails Thin skin No hair on feet
Pain at rest
Pain when walking builds up - calf pain (claudication)
Cold feet
so think it is arterial based on these symptoms
PVD pathophysiology
Reduced perfusion due to atherosclerosis
Ischaemia in feet/ toes → amputation
this is a complication of diabetes
PVD treatment
Atherosclerosis medication
Pain killers
Walk through pain ! effective
secondary causes of diabetes
acromegaly addisons (i'm now doubting) cushings chronic pancreatitis CF
hyperthyroidism symptoms
think pop tarts
- intolerance to heat, sweating
- facial flushing
- tachycardia, palpitations, BP rise
- weight loss
- muscle wasting
- anxiety, irritability
+
- finger clubbing
- tremors
- diarrhea
- hypogonadism (oligomenorrhea, infertility)
- graves opthalmology = bulging eyes. periorbital oedema, diplopia–> blindness, lid lag
hypothyroidism sympyoms
think opposite!
- intolerance to cold, shivering,
- bradycardia, low BP
- ascites, due to brady
- dry, rough, thickened skin, and brittle hair/nails, hair loss/ receeding hairline
- apathy, dull expression, low mood, lethargy
- menorrhagia (heavy)
- constipation
hypo/hyperthyroidism presentation in elderly
elderly:
hypo= cognitive impairment, looks similar to ageing
hyper= atrial fibrilation, tachy, heart failure
hypo/hyperparathyroidism in children
CHILDREN
hypo= slow growth, poor school performance
hyper = excessive growth rate/height, hyperactive
goitre=
- Different types
- present in hypo or hyperthyroidism
swelling of thyroid due to lots of TSH
diffuse goitre = while thyroid swells, smooth
nodular goitre = nodules in thyroid swell, bumpy
both!
Hypo: low t3/4 so high TSH (feedback) eg iodine deficiency
Hyper: high TSH so lots of t3/4
hyper/hypothyroid epidemiology
- ages (of graves, and hyper)
- gender
- which is more common
More women
More hypos than hypers
Graves : 40-60y
Other hyper : 20-40y
graves=
- causes what
- pathophysiology
- signs
- age
- cause of hyperthyroidism
- autoantibodies bind to TSH receptor in thyroid, this activates it lots (its attacking it which makes it overproductive)
- so t3/4 overproduced
- and hyperplasia of follicular cells (diffuse goitre)
- graves opthalmology (eyes, bulge, retro orbital inflammation). + general hyperthyroid presentation
- 40-60y
causes of hyperthyroidism that are not graves
- ingestion of excess thyroid hormone
- drugs (iodine, lithium, amiodarone)
- toxic multinodular goitre (nodules secrete too much thyroid hormones), esp elderly women
- adenoma
- De quervain’s thyroiditis (Transient hyperthyroidism due to acute inflammation of the thyroid gland, probably due to virus infection )
- preformed hormone leaks out of folicular cells
pregnancy + hyperthyroidism?
Can affect baby, autoantibodies/t3t4 cross placenta?
Especially predisposed post partum. Autoimmune activity suppressed during pregnancy to not attack the baby but increases after with vengeance!
De quervain’s thyroiditis
associated with what
treatment
- Transient hyperthyroidism due to acute inflammation of the thyroid gland, probably due to virus infection
- Usually associated with fever, malaise, neck pain
- Treat with aspirin and only give prednisolone (corticosteroid that dampens immune system ) if very symptomatic
hyperthyroidism risk factors
- Female
- Genetic
- E.coli and some other gram NEG organisms contain TSH binding sites so can initiate pathogenesis
- Smoking
- Stress
- High iodine intake (diet)
- Autoimmune disease (more likely to have Graves)
investigation of hyperthyroidism
history/symptoms
Bloods
- Levels of tsh and t3/4
- Primary: low tsh, high t3/4 (Graves is primary)
Secondary: high tsh, high t3/4
- TSHR-Ab (TSH receptor stimulating antibodies) : raised in graves (diagnostic)
- Thyroid peroxidase (TPO) and thyroglobulin antibodies
- Mild neutropenia in graves
Imaging
- CT/MRI: Eyes examined looking for graves ophthalmology
- Ultrasound thyroid - to see toxic adenoma
primary vs secondary hyper/hypothyroidism
primary = issue with thyroid
secondary = issue with hypothalamus or pituitary
hyperthyroidism treatment
radioiodine (131)
antithyroid drugs
- carbimazole (inhibits TPO thyroid peroxidase enzyme, prevents synthesis. also immunosuppressive so good for graves)
- propylthiouracil (inhibits conversion of t4–> t3 (also TPO i think))
beta blockers for symptoms eg tachy
thyroidectomy (goitre/porr response/side effects/malignancy)
how does radioiodine work as a treatment for hyperthyroidism
Thyroid readily takes up the iodine, it accumulates and results in local irradiation and tissue damage so that normally thyroid function returns
thyroidectomy =
- indications
- partial/total
- complication
For large goitre/ poor response to drugs/ drug side-effects/ suspected malignancy (toxic adenoma)/ graves
either. Partial / total (partial if function is normal)
Patients become hypothyroid
hyperthyroidism complication (one specific one)
- =?
- symptoms
- triggers
- treatment
Thyroid crisis = thyroid storm
- Medical emergency
- Rapid T4 increase
- Fever, tachycardia, restless, ness, delirium, coma, death
- Precipitated by stress, infection, surgery, radioactive iodine therapy
- treatment= large doses of
- —Carbimazole
- —Propranolol
hypothyroidism causes
Primary (absence/ dysfunction of thyroid gland)
- Hashimotos
- Other autoimmune causes
- — Antithyroid antibodies → atrophy (so no goitre) and fibrosis
- Postpartum thyroiditis. (Transient– normally self limiting, but can transfer to permanent. autoimmune)
- hyperthyroidism treatment (131 iodine therapy, thyroid surgery, lithium, amiodarone, interferon
- Iodine deficiency (commonest cause worldwide)
Secondary
- Pituitary dysfunction (less TSH)
Tertiary
- Hypothalamus dysfunction (less TRH)
hashimotos =
- what
- symptoms
- gender
- age
- triggers
- autoimmune damage to thyroid. cause of hypothyroidism. TPO antibodies
- goitre due to plasma and wbc infiltration + hypothyroidism
- function = hypo/euthyroid
- f>m-
- middle aged (and women aged 60-70)
- triggers : iodine, smoking, stress, infection
commonest cause of hypothyroidism worldwide
then
- what is the function of the thyroid
- where in world
- is goitre present?
iodine insufficiency
function= hypo/euthyroid
Netherlands, western pacidic, india, SE asia, russia
goitre present
hypothyroidism risk factors
Female Conditions -- Turner’s (X rather than XX), -- Down’s, -- cystic fibrosis, -- ovarian hyperstimulation -- Primary billiary cirrhosis -- Autoimmune disorder -- Hyperthyroid and on treatment Low iron diet Age
hypothyroidism investigations
Blood
- Test TSH and T3/4
- – Primary: high TSH, low T3/4
- – secondary : low TSH, low T3/4
- – Serum T4= diagnostic for hypothyroid
- TPO-Ab (hashimotos )-thyroid antibodies
- Anaemia (dif diagnosis)
- High cholesterol
- Low Na (due to increase in ADH )
hypothyroid treatment
Levothyroxine (L thyroxine)
- Long half life
- Lifelong
Surgery on goitre if obstructive
types of thyroid cancer
- which is most/least common
papillary = most follicular anaplastic medullary lymphoma = least
papillary thyroid cancer
- differentiation
- age
- prognosis
- where
Most common Well differentiated Young people Good prognosis From thyroid epithelium
follicular thyroid cancer
- differentiation
- age
- prognosis
- where
- spread
Middle age Spread to lung/bone Good prognosis Well differentiated From thyroid epithelium
medullary thyroid cancer
- differentation
- where
- prognosis
Very undifferentiated (poorly)
From thyroid epithelium
Aggressive- local spread
Poor prognosis
anaplastic thyroid cancer
- where
from calcitonin c cells
thyroid cancer
- risk factors
- gender
- how common
radiation
f>m
rare
presentation of thyroid cancer
- Thyroid nodule
- Lymphadenopathy (disease of lymph nodes)
- May metastasis to lung, cerebral, hepatic, bone
- Thyroid increase in size, irregular shape, hard texture
- Hoarse voice
- Dysphagia
- Due to compression on oesophagus/laryngeal nerve
thyroid cancer investigations
needle biopsy - benign or malignant
blood test
- TSH
- T3/4
- hypo/hyperthyroid. treat this before surgery
ultrasound thyroid - benign or malignant and exact location
thyroid cancer treatment
Iodine radiation
- Thyroid takes up readily. This then irradiates and destroys locally (little radiation to surrounding structures)
- Anaplastic carcinomas and lymphomas do not respond to it
Levothyroxine
- Keeps TSH inhibited - TSH is a growth factor for the cancer!
Chemotherapy
- Reduce risk of spread
- Treats micro-metastases - these may be unaffected
Surgery
- Thyroidectomy
- Lymph node removal
cushings syndrome gender
cushings disease gender
cushings disease age
cushings syndrome - m>f
cushings disease - m=f, 30-50y
cushings disease vs cushings syndrome
cushings syndrome = too much cortisol
cushings disease = hormone secreting tumour in pituitary - too much ACTH
Causes of cushings syndrome
ACTH dependant
- cushings disease (benign adenoma)
- pituitary trauma/ infection / haemorrhage bleed
- ectopic tumour (elsewhere eg lungs, produced ACTH
- ACTH treatment (eg for asthma)
ACTH independant
- tumour of adrenal gland (benign adenoma releases too much cortisol)
- oral steroids (most common)
psuedocushings syndrome
alcohol excess
resolves few weeks after alcohol cessation
other causes of high cortisol (non-cushings)
depression
obesity
pregnancy
high alcohol (psuedo -cushings syndrome)
effect of too much cortisol (cushings syndrome)
Lipid and glycogen deposition
Muscle and carb catabolism
Na retention
signs and symptoms of cushings syndrome
- Decreased glucose tolerance → diabetes, hyperglycaemia
- Sodium retention → hypertension
- Osteoperosis
- Red (=ruddy)
- Obese:
- –Fat on trunk, visceral fat
- –Buffalo hump (neck)
- –Round face , swollen(moon face)
- –Around tummy
- protein catabolism -
- –Muscle wasting- proximal weakness
- –Thin skin - bruising,
- –purple striae stretch marks
- Slow healing - eg recurrent ulcers (immunosuppression)
- Depression, low mood, psychosis mood swings,
- lethargy, irritability
- Malaise
- Short children
- Acne
- Decrease in gonadal function (a/oligomennorhea, , libido)
cushings syndrome investigations
- plasma/urine/saliva cortisol (take multiple measures as time, illness and stress influence it)
- drug history - steroids
- Overnight dexamethasone suppression test (1st line test)
- –This corticosteroid injected at night, blood cortisol measured in the morning
- –Normally- ACTH suppression and thus cortisol suppression (neg feedback)
- –No suppression in cushings syndrome
- 48 h dexamethasone suppression test (2nd line test- if no suppression)
- –Take dexamethasone 4/day for 2days
- –Measure blood cortisol at 0h and 48h
- –Cuhsings’s syndrome = no suppression (Same as above)
- to distinguish whether ACTH in/dependant - measure plasma ACTH.
— none = adrenal tumour likely (CT/MRI to see mass / sample)
— detectable = cushings disease or ecoptic tumour. then…
CRH given:
cushings disease = cortisol rises. ectopic = no rise as CRH doesnt act on ectopic tumour
CXR/MRI, CT to look for ectopic tumour/pituitary one
cushing syndrome management
- if iatrogenic, stop steroids
- if tumour cause, surgical removal , radiotherapy
- medication to control excessive production
ketoconazole, mitotane, metyrapone
– used pre-op or awaiting effects of radiation
when would an adrenalectomy be used to treat cushings syndrome
if adrenal tumour (ACTH independant) is the cause (no dexamethasone suppression and serum ACTH not detected) and you are
1) unable to locate the tumour
2) it is recurrent
how common is acromegaly
rare
causes of acromegaly
Growth hormone secreting tumour
- Benign pituitary adenoma (main)
- Craniopharnygioma (a type)
- Hypothalamus tumour
- Certain Lung cancer - ectopic carcinoid tumour
Trauma
Infection
Bleed from haemorrhage (“apoplexy”)
acromegaly. =
effects
too much growth hormone
- increases IGF1 from liver
- stimulates gluconeogenesis, lipolysis (this leads to insulin resistance - increased risk of diabetes) with no neg feedback from glucose
- skeletal and soft tissue growth
signs of acromegaly
Increase risk of diabetes Increased BP Hyperglycemia Enlarged organs Carpal tunnel syndrome (pain, tingling, numbness)
symptoms of aacromegaly
- Increased height, if before spinal fusion and fusion of epiphysis of long bones (children) - gigantism
- abnormal enlargement
- –large extremities (shoes and rings no longer fit)
- –Large chin /jaw
- –Prognathism - think movement like overbite to underbite
- –Wonky bite = malocclusion
- –Wide nose
- –Large tongue = macroglossia
- –Large supraorbital redge
- –Weight gain
- Sweating
- Headache - v common
- Deep voice
- Hypogonadal symptoms
- Aches and pains in joints = Arthralgia. Back aches
- Greasy skin
- Darkened skin
- Coarse face
- Snoring
- Fatigue
- Visual disorientation
- Acroparesthesia = tingling and numbness of extremeties
- Polyuria
acromegaly investigations
blood
- IGF1 levels high (diagnostic)
- GH levels raised (not diagnostic - secretion is puslatileand influences by many physiological factors so could be based on time of test)
- high calcium, high phosphate
- visual field examination (pit= bitemp hemi)
- pituitatary function test
- MRI for pituitary mass
- old photos - see face shape change etc
- echo/ECG - heart myopathy (complication)
acromegaly treatment
Surgery
- Trans-sphenoidal surgery:remove tumour, correct/prevent compression
- Rapid improvement, decompression, cost effective
radiotherapy
- Damage DNA, kill cells in tumour
- Conventional = small fractions daily
- Stereotactic = single fraction (less radiation to surrounding tissues, more selective)
- Gamma knife kills specific area
Medicine - alongside radiotherapy
- Dopamine agonist - CABERGOLINE→ decreases GH and IGF1 (not massively effective)
- Somatostatin analogue (OCTREOTIDE) → inhibits GH release (s/e: GI cramps, flatulence, loose stools)
- GH receptor antagonist - PEGVISOMANT (expensive)- if intolerance to somatostatin analogue → attaches to GH receptors, suppresses IGF1
complications of acromegaly
- Diabetes (imparied glucose tolerance)
- Hypertension (and so LV hypertrophy, stroke, arrhythmias etc)
- CV disease
- Sleep apnea
- Arthritis
- Colon cancer
- Cerebrovascular events eg headaches
conns =
pathophysiology
primary hyperaldosteronism
too much aldosterone produced from adrenal glands, independant of RAAS (otherwise would be secondary)
increases action of aldosterone - so high Na reabsorption, and so high water retention and high K excretion in distal renal tubule (and decreased renin release)
- High blood pressure
- Low K + - hypokalemia
conns epidemiology
- gender
- how common
- age
Most common in 30-50 y
Women
Rare
causes of conns
Adrenal adenoma, secreting aldosterone = conn’s, a cause of primary hyperaldosteronism (⅔)
Bilateral adrenocortical hyperplasia = cause of primary hyperaldosteronism (not conn’s) (⅓)
differential diagnosis of conns
secondary hyperaldosteronism (conns= primary
- Here there is excess renin -and so more angiotensin 2
- So more aldosterone release
- This is due to reduced renal perfusion
- Causes:
- –Accelerated hypertension
- –Renal artery stenosis
- –Diuretics
- –Congestive heart failure
- –Hepatic failure
signs of conns
Hypertension
Hypokalemia
Possibly low urine output
High blood pH - metabolic acidosis
when should you think of conn’s with a hypertensive patient
- With no family history
- Young (under 35)
- Hypokalemia before diuretics
- Resistant to conventional anti-hypertensive therapy (3+drugs)
- Unusual symptoms (sweating attacks, weakness)
Then think primary hyperaldosteronism/ conns
as the cause for secondary hypertension
conns symptoms
Symptoms variable/ absent Polyuria Polydipsia Muscle cramping / weakness Sweating attacks) Tingling Temporary paralysis headaches
conns investigation
- High serum aldosterone
- –Not suppressed with saline infusion or mineralocorticoid
- –This is diagnostic
Low serum renin (high aldosterone:renin ratio (ARR)) - rules out secondary hyperaldosteronism!
Low serum K - hypokalemia (not always)
CT/ MRI to locate tumours in adrenals
ECG shows hypokalemia - flat T waves, ST depression, long QT
conns treatment
spironolactone = blocks aldosterone action (aldosterone antagonist)
- resolve electrolyte imbalance
- 4 weeks pre-op
- idiopathic patients!
K+ electrolytes given if acute
surgery - remove tumour/ whole adrenal
antihypertensives
hyperthyroidism – affect on calcium? (perhaps just if extreme)
hypercalcaemia
hyperthyroidism – affect on bones?
osteoperosis
- due to increased secretion of calcium and phosphate - loss of bone mineral
first line treatment for T2DM
then what
metformin AND lifestyle changes
then add sulphonylurea, then add insulin
first line investigation for suspected acromegaly?
second line
IGF1 blood test
then OGTT
(serum GH unreliable due to pulsatile secretions)
