ENDOCRINOLOGY Flashcards
what are the major endocrine constituents
pituitary gland, thyroid gland, parathyroid gland, adrenal glands, pancreas, ovaries and testes
what are the features of water soluble hormones
they are unbound, and bind to cell surface receptors. They have a short half life and clearance is fast.
what are examples of water soluble hormones
peptides
monoamines - adrenaline/noradrenaline
what are the features of fat soluble hormones
they are protein bound, and diffuse into the cell. they have a long half-life and clearance of them is slow
what are examples of fat soluble hormones
Thyroid hormones
steroids
can peptide hormones be stored
yes they can be stored in vesicles
what are the steps of peptide production from synthesis to secretion
synthesis - preprohormone into prohormone
packaging - prohormone to hormone
storage - hormone
secretion - hormone
are thyroid hormones water soluble
no they are not water soluble - 99% are protein bound
what are the features of vitamin D
it is fat soluble, it enters the cell directly to the nucleus to stimulate mRNA production. It is transported round the body by vitamin D binding protein
what are some cholesterol derivative hormones
- vitamin K
- Adrenocorticoids
- Sex hormones
what are features of adrenocortical and gonadal steroids
95% of them are protein bound and after entering the cell they pass into the nucleus to induce a response, binding to cytoplasmic receptors
what are the actions of steroid hormones
- steroid hormones diffuse through the plasma membrane and binds to receptors
- receptor - hormone complex enters the nucleus
- receptor - hormone complexes bind to the GRE
- binding initiates transcription of the gene to mRNA
- mRNA then becomes protien syntheis
how does the body control hormone secretion
- basal secretion; continuously or pulsatile
- Negative feedback; i.e dopamine inhibits prolactin
- releasing factors
how does the body control hormone secretion
- basal secretion; continuously or pulsatile
- Negative feedback; i.e dopamine inhibits prolactin
- releasing factors
how does the body control hormone action
- hormone metabolism - increased metabolism to reduce function
- hormone receptor induction - induction of LH receptors by FSH in follicle
- hormone receptor down regulation - hormone secreted in large quantities cause down regulation of its target receptors
what is synergism
it is the combined effects of two hormones amplified
what is an example of hormone synergism in the body
glucagon with adrenaline
what is antagonism
one hormone opposes another hormone
what is an example of hormone antagonism
glucagon antagonises insulin
what can cause pituitary dysfunction
- tumour mass effects
- hormone excess
- hormone deficiency
what is the hypothalamus - pituitary - thyroid axis
hypothalamus - TRH - anterior pituitary - TSH - thyroid gland - thyroid hormones
what is thyroid hormone function
- accelerates food metabolism
- increases protein synthesis
- enhances fat metabolism
- brain development during foetal life and postnatal development
- growth rate accelerated
what steroid hormones does the adrenal cortex produce
- Mineralocorticoids - aldosterone
- Glucocorticoids - cortisol androgens
- Androgens - androstenedione and DHEA
what hormones do the adrenal medulla produce
produces adrenaline and noradrenaline
what is satiety
the feeling of fullness - disappearance of appetite after a meal
what are the different BMI groupings
<18.5 - underweight
18.5-24.5 - normal
25.0-29.9 - overweight
30.0-39.9 - obese
> 40 - morbidly obese
what are risks of obesity
- type 2 diabetes
- hypertension
- coronary artery disease
- stroke
- osteoarthritis
- obstructive sleep apnoea
- carcinoma: breast, endometrium, prostate, colon
what are the reasons we eat
- internal physiological drive to eat
- feeling that prompts thought of food and motivates food consumption
- external physiological drive to eat
- sometimes even the absence of hunger
what region of the brain which has a central role in appetite regulation
the hypothalamus
what nutrients have a quick short effect on satiety
highly refined sugar
what nutrients give a prolonged satiety
high protein foods
what nutrients can stimulate and entice people to eat more
high fat
what is peptide YY
it is a protein structurally similar to NPY binding to its receptors. and reduces appetite
what areas of the body produces peptide YY
it is secreted by neuroendocrine cells in the ileum, pancreas and colon in response to food
what is the function of peptide YY
it inhibits gastric motility and reduces appetite
what is the function of cholecystokinin
it delays gastric emptying, causes gall bladder contraction and insulin release
via the vagus nerve it induces satiety
where are CCK receptors found
in the pyloric sphincter
what stimulates appetite
olfactory, gustatory, cognitive and visual stimuli increase appetite
what hormone increases hunger
ghrelin
what factors increase satiety to stop feeding
stretch receptors in the stomach
release of CCK, GLP, insulin and PYY
what are the anterior pituitary hormones
FSH and LH
ACTH
GH
TSH
Prolactin
what can pituitary tumours cause
- can press on local structures such as the optic chiasm producing bitemporal hemianopia
- Hyopituitism
- Hyperpituitism
what does the posterior pituitary release
oxytocin
vasopressin
what are the functions of cortisol
increases protein and carbohydrate breakdown
it upregulates alpha receptors on arterioles and therefore increases blood pressure.
it suppresses the immune response
it increases osteoclast activity and therefore its osteoporotic
it increases insulin resistance
what is the definition of diabetes type 1
autoimmune destruction of pancreatic beta cells leading to complete insulin deficiency
what are risk factors for type 1 diabetes
HLA DR3-DQ2 or HLA DR4-DQ8
northern european
autoimmune diseases - 90%
what is the pathophysiology of type 1 diabetes
autoantibodies attack beta cells in the islets of langerhans which causes an insulin deficiency and hyperglycaemia.
this causes continuous breakdown of glycogen from the liver due to gluconeogenesis and produces glycosuria
what are the signs and symptoms of diabetes type 1
Classic triad; polydipsia, polyuria, weight loss (BMI <25)
usually a short history of severe symptoms
may present with ketosis
how do you diagnose type 1 diabetes
In symptomatic patients you need to have a random plasma glucose of over 11mmol/L or a fasting blood glucose of over 7 mmol/L
In asymptomatic patients they must show raised glucose on 2 separate occasions
what is the treatment for type 1 diabetes
- insulin
- short - acting insulins and insulin analogues (4-6 hours)
- longer (basal) acting insulin (12-24 hours)
what is the definition of type 2 diabetes
it is non insulin dependent
patients gradually become insulin resistant/pancreatic beta cells fail to secrete enough insulin or both. it progresses from an impaired glucose tolerance to diabetes.
what are the causes of type 2 diabetes
Non modifiable - Older age, ethnicity, family history male
Modifiable - obesity, sedentary lifestyle, high carbohydrate diet, hypertension
what are risk factors for type 2 diabetes
lifestyle factors: obesity, lack of exercise, calorie and alcohol excess
higher prevalence in asian men
above the age of 40 - later onset
hypertension
what are signs and symptoms of type 2 diabetes
- polydipsia
- polyuria
- glycosuria
- central obesity
- slower onset
- blurred vision
how does someone get diagnosed with type 2 diabetes
- fasting plasma glucose: more than 7mmol/L
- random plasma glucose: more an 11 mmol/L
- HbA1c more than 48 mmol/L - GOLD STANDARD
- if someone has no symptoms - GTT 75g glucose, fasting over 7 or 2hr value over 11mmol/l which is repeated on 2 occasions
what is first line lifestyle changes for type 2 diabetes
- dietary advice; high in complex carbs and low in fat
- smoking cessation
- decrease in alcohol intake
- encourage exercise
- regular blood glucose and HbA1c monitoring
what is second line management for type 2 diabetes
Medications
1. metformin: increases insulin sensitivity - first choice for overweight patients
2. If HbA1c remains high then dual therapy with metformin:
- DPP4 inhibitor
- Sulphonylurea - increases insulin secretion
- Pioglitiazone
3. if still high then you have triple therapy
4. then insulin
what is diabetic ketoacidosis
when complete lack of insulin results in high ketone production
- medical emergency
what sort of release does insulin have
a biphasic release
what receptors does glucose bind to in the pancreas
binds to the GLUT2 receptors (B cells) stimulating insulin release
what happens when insulin binds to peripheral insulin receptors
- it activates intracellular tyrosine kinases and its cascade
- it results in increased GLUT4 channel expression on the cell surface membrane
- it increases peripheral uptake
what is given in response to unresponsive hypoglycemic patients
IM glucagon
what does oxytocin do
causes milk ejection and labour induction
what does vasopressin do
increases blood pressure
- vasoconstriction
- APO II expression in CD
- increased aldosterone
what are complications of diabetic ketoacidosis
- coma
- cerebral oedema
- thromboembolism
- aspiration pneumonia
- death
how do you manage diabetic ketoacidosis
ABC
- replace fluid loss with 0.9% saline IV
- IV insulin + glucose to prevent hypoglycaemia
- Restore electrolytes such as K+
what does post prandial mean
means after eating
how do beta and alpha cells act on each other
the beta cells keep the alpha cells in a state of tonic inhibition when there is high glucose. this is opposed with reduced glucose levels
simply how does glucose act on beta cells in the pancreas
glucose binds to GLUT2 receptors on beta cells. Through intracellular signaling it causes ADP transformation into ATP. This induces closure of potassium channels causing depolarisation of the membrane. This causes calcium channels to open and calcium moves into the cell, causing insulin secretory granules to be released from the cell
how does insulin act on peripheral receptors
insulin binds to its receptor and induces intracellular GLUT4 vesicles to be mobilised to the membrane, allowing glucose to bind and enter the cell
what does HbA1c show
it shows a trend over time - how much glucose is stuck in a red blood cell can tell you the two/three month blood sugar
what is the threshold of when glucose starts appearing in the urine
anything above 10-11mmol/L of glucose in the blood
which type of diabetes is ketoacidosis more common in
type 1 but you can get it late stage type 2
what is a hyperosmolar hyperglycaemic state
it is common in type 2 diabetes. It is where the kidneys become dehydrated (even through you are drinking a lot). The kindeys eventually go into kidney failure
what is the pathogenesis of type 1 diabetes
there is absent insulin secretion, meaning you have no fat, muscle or hepatic insulin effect. Because of this you have impaired glucose clearance and muscle fat breakdown. You also have unrestrained glucose and ketone production. More glucose enters the blood with a lack of it being taken up by peripheral tissues and you end up with hyperglycaemia and raised ketones in the blood and urine. Will eventually become ketoacidotic
what is the pathogenesis of type 2 diabetes
Repeated exposure to high levels of glucose leads to the repeated release of insulin which makes the cells in the body become resistant to the effects of insulin.
Over time, the pancreas (specifically the beta cells) becomes fatigued and damaged by producing so much insulin and they start to produce less.
A continued onslaught of glucose on the body in light of insulin resistance and pancreatic fatigue leads to chronic hyperglycaemia.
what is the action of sulphonylureas
they depolarise the calcium channel allowing calcium channels to open and increase insulin release
what are side effects of sulphonylureas
they can cause hypoglycaemia
how do thiazolidinediones work
they bind to the nuclear receptor PPARy and activates genes which a concerned with glucose uptake and utilisation, as well as lipid metabolism
- help improve insulin sensitivity
what are side effects of thiazolidinediones
they can increase weight, increase the risk of heart failure and increase the risk of fractures
Where is GLP-1 secreted from
secreted from the L cells in the intestine
What are the modes of action of GLP-1
- stimulates insulin secretion
- supresses glucagon secretion
- slows gastric emptying
- reduces food intake
- increases beta cell mass and improves function
- improves insulin sensitivity
- enhances glucose disposal
what actions do GLP-1 agonists have
they reduce food intake while stimulating insulin secretion, it can help reduce weight and CVD independent of lowering glucose levels
- incretin mimetic which inhibits glucagon secretion
what is DPP - iv
it breaks down GLP-1 and stops its affects on the body
Also increases incretin levels which inhibits glucagon secretion
what are examples of DPP - iv inhibitors
Vildagliptin and sitagliptin
- oral agents and have a modest glucose lowering effect. they have no effect on CVD or weight
what is the action of SGLT2 inhibitors
inhibit the glucose reuptake transporters in the nephron. this means that all glucose is urinated out which will then reduce blood glucose and reduce patient symptoms
what is the action of SGLT2 inhibitors
inhibit the glucose reuptake transporters in the nephron. this means that all glucose is urinated out which will then reduce blood glucose and reduce patient symptoms
what are examples of SGLT2 inhibitors
empagliflozin, canagliflozin and dapagliflozin
what are side effects of SGLT2 inhibitors
genital thrush, UTIs and dehydration
what are benefits of SGLT2 inhibitors
they significantly reduce heart failure, heart attacks and kidney disease
what are the two types of insulin given in diabetes
long and short acting
- basal insulin is long lasting
- bolus gives a spike which can be taken before dinner
what are some examples of basal insulin
NPH insulin, insulin glargine, insulin detemir, insulin degludec
what are some examples of prandial insulins
insulin lispro, insulin glulisine, EDTA/citrate human insulin and faster-acting insulin aspart
how many people with type 2 diabetes will end up on insulin after 10 years
about 50%
what are the classifications for hypoglycaemia
Level 1 - alert value, plasma glucose below 3.9mmol/L and no symptoms
Level 2 - serious biochemical, plasma glucose <3mmol/L
Non severe vs severe symptomatic:
Non severe: patient has symptoms but self treated and cognitive
Severe: patient has impaired cognitive function and required external help to recover
what are the side effects of hypoglycaemia
brain - cognitive dysfunction, backouts, seizures, comas
musculoskeletal - falls, accidents, fractures, dislocations
heart - myocardial ischemia, arrhythmias
circulation - inflammation, blood coagulation abnormal, haemodynamic changes, endothelial dysfunction
what are common hypoglycaemic symptoms
- autonomic: trembling, sweating, palpitations, anxiety, hunger
- Neuro: confusion, weakness, dizziness, drowsiness, vision and speech difficulty, difficulty concentrating
- non-specific: nausea and headache
what happens if you have repeated episodes of hypoglycaemia
youre awareness to the adrenaline response becomes progressively blunted. you can eventually loose the awareness. this can be combatted if you can avoid hypoglycaemia for as little as 4-6 weeks
where is the glucose sensor in the brain
in the ventral medial hypothalamus
what are causes of hypoglycaemia
long duration of having diabetes
increasing age
increased physical activity
sleeping
use of drugs - prescribed or alcohol
What is MODY diabetes
maturity onset diabetes of youths
- rare T2DM presenting in young patients
what are some secondary causes of diabetes
- acromegaly and cushings
- haemochromotosis
- thiazides/corticosteroids
what is LADA diabetes
it is late onset of diabetes in adults
- the opposite of MODY; type 1 presentation in older patients
do you have a ‘pre-diabetes’ stage in type 1 diabetes
NO - no lifestyle modification will affect this disease development
what are symptoms of T1DM diabetic ketoacidosis
- kussmaul breathing - deep laboured breaths
- pear drop breath - fruity breath smell
- reduced tissue turgor, hypotension and tachycardia
how do you diagnose diabetic ketoacidosis
ketones (blood) = >3mmol/L
Hyperglycaemic > 11.1mmol/L RPG
Acidosis (met) <7.3pH or <15mmol HCO3-
what is the treatment for diabetic ketoacidosis
ABCDE
- first line is ALWAYS fluid and then insulin
what are symptoms of type 2 diabetes
- obese
- hypertensive
- older patient
- polydipsia
- polyphagia - excessive hunger
- polyuria
- glycosuria
- can get dark pigmented skin folds
what are the blood measurements for pre-diabetic diabetes
IGT = normal FPG >6mmol/L and 2hr OGTT between 7.8-11mmol/L
IFG = F.PG 6.1-6.9mmol/L and 2hr OGTT <7.8mmol/L
what are main macrovascular and microvascular complications in DM1 and 2
Macrovascular: Cardiovascular, ischemic stroke, peripheral arterial (PVD)
Microvascular: retinopathy, neuropathy (charat foot), nephropathy (nephrotic syndrome)
what are non diabetic reasons for hypoglycaemia
Oral, Liver failure and addisons disease
what spinal levels does the thyroid sit at
C5-T1
what connects the two lobes of the thymus
the Isthmus
where does the anterior pituitary receive its blood supply from
receives its blood from the portal venous circulation from the hypothalamus
describe the growth hormone/IGF-1 axis
The growth hormone/ IGF-I (insulin-like growth factor) axis begins at the hypothalamus which produces Growth Hormone Releasing Hormone (GHRH) or somatostatin (SMS), also known as growth hormone inhibiting hormone (GHIH). GHRH increases the amount of growth hormone produced by the pituitary, which then goes to the liver. GHIH decreases GH production from the pituitary so that less goes to the liver.
The liver produces IGF-I which reduces the production of GHRH.
what is IGF-1
it is insulin like growth factor 1 and is produced by the liver
what stimulates growth hormone release from the pituitary
Growth hormone releasing hormone
- somatostatin inhibits
what stimulates LH and FSH release from the anterior pituitary
GnRH
what stimulates ACTH release from the anterior pituitary
CRH
What stimulates TSH release from the anterior pituitary
TRH
What pituitary diseases can cause pituitary dysfunction
- Benign pituitary adenoma
- Craniopharyngioma
- Trauma
- Apoplexy/Sheehans - excessive blood loss
- Sarcoid/TB
what are the three vital signs of presentation for diagnosing pituitary tumours
- Pressure on local structure (optic nerves) - bitemporal hemianopia
- Pressure on normal pituitary - hypopituitarism
- Functioning tumour: prolactinoma, Acromegaly, Cushings
how would someone present with a prolactinoma
galactorrhoea, amenorrhoea and infertility
loss of libido
visual field defects
low testosterone
erectile dysfunction
reduced facial hair
is a prolactinoma more common in men or women
more common in women
how do you treat a prolactinoma
treat with a dopamine agonist first
what is acromegaly
Acromegaly is a rare condition where the body produces too much growth hormone, causing body tissues and bones to grow more quickly. Over time, this leads to abnormally large hands and feet, and a wide range of other symptoms.
what are co-morbidities often related to acromegaly
hypertension and heart disease
cerebrovascular events and headache
arthritis
sleep apnoea
insulin - resistant diabetes
what are presenting clinical features of acromegaly
- acral enlargement
- arthralgias
- amenorrhoea
- bi-temporal hemianopia
- maxillofacial changes
- excessive sweating
- headache
- hypogonadal symptoms
- can have visual field defects
- lower pitch of voice
- obstructive sleep apnoea
what are the diagnosis steps for acromegaly
- acromegaly is excluded if GH <0.4ng/ml and normal IGF-1
- if either is abnormal then do 75gm glucose tolerance test
- acromegaly excluded if IGF-1 normal and GTT <1ng/ml
the gold standard of test is the oral glucose tolerance test - normally serum GH will decrease when given glucose but this wont happen in acromegaly
what are treatment options for acromegaly
- pituitary surgery
- Medicine - dopamine agonists: cabergoline, somatostatin analogues: octreotide, GH receptor antagonists; Pegvisomant
- Radiotherapy
what is an example of a dopamine agonist used for acromegaly
cabergoline
what is the definition of a prolactinoma
lactotroph cell tumour of the pituitary
what are clinical features of a prolactinoma
local effects - headache, visual field defects, CSF leak
effect of prolactin - menstrual irregularity/amenorrhoea, infertility, galactorrhoea, low libido, low testosterone in men
what is the management of a prolactinoma
medical rather than surgery, use dopamine agonists such as cabergoline.
what is a cardinal rhythm
physical, mental and behavioral changes that follow a daily cycle
what is adrenal insufficiency
a condition in which the adrenal glands do not produce adequate amounts of steroid hormone (mainly cortisol)
what are examples of primary, secondary and tertiary adrenal insufficiency
Primary - issue with gland itself - Addison’s disease
Secondary - Hypopituitarism
Tertiary - Suppression of HPA
how do you diagnose an adrenal insufficiency
Symptoms: fatigue, weight loss, poor recovery from illness, adrenal crisis, headache, vitiligo, hypoglycaemia
Past history: TB, post partum bleed, cancer
Family history: Autoimmunity, congenital disease
Gold standard is a Short synacthen
what is the treatment of adrenal insufficiency
steroids
what are the symptoms of an adrenal crisis
- hypotension and cardiovascular collapse
- fatigue
- fever
- hypoglycaemia
- hyponatraemia and hyperkalaemia
whats somethings to think of when someone is presenting with adrenal insufficiency
recent steroid use
what is the definition of hyperthyroidism
clinical effect of excess thyroid hormone.
primary - abnormal increased thyroid function
secondary - abnormal increased TSH production
what can cause hyperthyroidism
smoking
stress
HLA-DR3
other autoimmune conditions: T1DM, addisons and diabetes
Graves disease
Toxic multinodular goitre
iodine excess
De Quervains thyroiditis
Drug induced - iodine or amiodarone `
what is the pathophysiology of hyperthyroidism
there is an increased T3 and T4 production, thus increasing the metabolic rate, cardiac output, bone resorption and activates the sympathetic nervous system
- feedback to pituitary and causes low TSH levels
what are the different things that can cause hyperthyroidism
Graves disease - 65-75% of cases
autoimmune problems
toxic multinodular goitre
toxic adenoma
metastatic follicular thyroid cancer
iodine excess
secondary causes such as a TSH secreting pituitary tumour
who is more likely to have hyperthyroidism
young women - 20-24yrs
what are the signs and symptoms of hyperthyroidism
everything goes fast
hot and sweaty
diarrhoea
hyperphagia
weight loss
palpitations
tremor
irritability
anxiety
oligomenorrhoea
goitre
what investigations are done to diagnose hyperthyroidism
- TFTs look at T3 and 4 and if it is increased, as well as if TSH is decreased (primary)
- look for thyroid antibodies
- Ultrasound and CT head
what treatment is given for hyperthyroidism
- Drug management; beta blockers provide rapid symptom relief. 1st line carbimazole which blocks T4 synthesis, second like propylthiouracil which prevents T4 to T3 conversion
- radioiodine
- thyroidectomy (surgery)
what will TSH levels be like in secondary hyperthyroidism
they will be increased - problem with the pituitary
what hyperthyroid treatment shouldnt be given to pregnant women
carbimazole shouldnt be given
what is the pathophysiology of graves disease
it is where IgG antibodies (anti-TSHR-Ab) bind to TSH receptors to increase T4/3 production
- also react with orbital autoantigens
what are symptoms other than hyperthyroidism which are associated with graves disease
- Thyroid eye disease (25-50%); eyelid retraction, periorbital swelling and proptosis/exophthalmos
- pretibial myxoedema (leg swelling and discolouration)
- thyroid acropachy
what is the definition of hypothyroidism
is is the clinical effect of a lack of thyroid hormone
- primary is a abnormal reduction in thyroid function
- secondary is an abnormal reduction in TSH production
what is the epidemiology surrounding hypothyroidism
- about 4/1000 per year and it is mostly in over 40s. it is also seen more commonly in women to men (6:1)
what are causes of hypothyroidism
Autoimmune causes - Hashimoto’s, primary atrophic hypothyroidism, De Quervans thyroiditis
Other primary causes - iodine deficiency drugs (antithyroid drugs, iodine, lithium), post thyroidectomy or radioiodine
secondary - hypopituitarism
what are signs and symptoms of hypothyroidism
everything goes slow
- fatigue
- weight gain
- loss of appetite
- cold
- lethargy
- constipation
- low mood and depression
- menorrhagia
- goitre
what investigations are done to diagnose hypothyroidism
TFT - low T3 and T4 with an increased TSH
in secondary there will be a low TSH
also do blood test for autoantibodies
what is the treatment for hypothyroidism
Levothyroxine - artificial T4
What is Cushing’s syndrome
long term exposure to excessive cortisol hormone which is released by the adrenals
what are causes of cushings syndrome
ACTH Dependent
- Cushings disease - ACTH secreting from pituitary adenoma
- Ectopic ACTH production from small cell lung cancer
ACTH Independent
- Iatrogenic - steroid use
- adrenal adenoma
what are the signs and symptoms of cushings syndrome
- moon face
- central obesity
- Buffalo hump
- Acne
- Hypertension
- Striae - stretch marks
- Hirsutism
- weight gain
what investigations are done to determine if someone has Cushings syndrome
- random plasma cortisol (would be raised)
- Overnight dexamethasone suppression test - cortisol wont be suppressed in cushings
- Urinary free cortisol (24hr)
- Plasma ACTH
what are the treatment options for cushings syndrome
Dependent on the underlying cause
1. Latrogenic; stop medications if possible
2. Cushings disease - removal of the adenoma
3 Adrenal adenoma - adrenalectomy
4 Cortisol synthesis inhibition
what drugs are used to inhibit cortisol synthesis
metyrapone and ketoconazole
what are causes of acromegaly
pituitary tumour (adenoma) - most common 99%
secondary to a malignancy that secretes ectopic GH such as a lung cancer
what can be some complications of acromegaly
erectile dysfunction, diabetes mellitus
what is the pathophysiology of acromegaly
the overproduction of growth hormone acts directs on tissues such as the liver, muscle bone or fat and causes overgrowth of certain things like the hands and jaw, as well as causing other clinical features. GHRH is released from the hypothalamus and stimulates the release of GH from the anterior pituitary.
The excess growth hormone (GH) from the anterior pituitary results in excessive production of insulin like growth factor (IGF-1) which is responsible for inappropriate growth. This stimulates bone and soft tissue growth.
other than a prolactin producing tumour what are other reasons someone may develop hyperprolatinaemia
- non functioning pituitary tumour compresses on the pituitary stalk and therefore there is no dopamine inhibition of prolactin release
- antidopaminergic drugs
what are the two types of prolactinomas
- microtumours - less than 10mm in diameter (90%)
- macro - more than 10mm
what investigations are done to diagnose a prolactinoma
blood test to see prolactin and a CT of the head
what is Conn’s syndrome
it is primary hyperaldosteronism due to an aldosterone producing adenoma
what is the pathophysiology of Conn’s syndrome
there is an excess production of aldosterone, independent of the RAA system
- there is high sodium and water retention
- there is increased potassium secretion
- there is low renin release
what are signs and symptoms of Conn’s syndrome
hypertension
hypokalaemia
nocturia
polyuria
mood disturbance
difficulty concentrating
what investigations are done to diagnose conn’s syndrome
- aldosterone-renin ratio blood test: increased
- plasma potassium: reduced
- U+E
- Selective adrenal venous sampling (GOLD STANDARD)
what is the treatment for Conn’s syndrome
1st line: Spironolactone (pre-op controls BP and K+ levels)
Gold standard is laparoscopic adrenalectomy if its an adenoma
what is the blood supply to the thyroid
the inferior and superior thyroid artery
- inferior from the thyrocervical trunk (subclavian)
- superior from the external carotid (ECA)
how is T3 and T4 made
iodine becomes trapped and diffuses into the colloid of the thyroid gland. This then binds to tyrosine residues on thyroglobulin using the TPO enzyme to form T1 or T2.
When TSH-R binding occurs it stimulates T1 or T2 release
- T1+T2=T3
- T2+T2=T4
what is the Graves triad
- ophthalmopathy
- dermopathy
- acropachy - rash
what are complications of hyperthyroidism
a thyroid storm - rapid deterioration of thyrotoxicosis and a mass increase in T4. causes systemic decompensation: AF, coma
what is treatment for a thyroid storm
propylthioruracil and KI
why do you need to be careful of when prescribing levothyroxine
not overprescribing, as the dose can often cause iatrogenic hyperthyroidism
what is a complication of hypothyroidism
myxedema coma - often infection precipitated. There is a rapid reduction in T4 which causes hypothermia, loss of consciousness and heart failure
how do you treat a myxedema coma
levothyroxine, ABx and hydrocortisone (until adrenal insufficiency has been ruled out)
what are the different types of thyroid carcinoma
papillary, follicular and anaplastic (worst prognosis), lymphoma and medullary cell
what can a thyroid carcinoma mostly present as
they can present as thyroid nodules, and they may compress locally leading to a horse voice
how would you diagnose a thyroid carcinoma
a fine needle aspiration biopsy - TFTs and ultrasound the thyroid
what is the treatment for thyroid carcinoma
if its papillary and follicular = thyroidectomy, radioiodine
anaplastic = palliative mostly
what is the difference between cushing disease and cushing syndrome
Cushing’s DISEASE = pituitary oedema secreting excess ACTH
Cushing’s SYNDROME = hypercortisolemia of any cause
what blood tests are done when diagnosing Cushing’s
a random serum cortisol, if it is high then a second test is done measured at 12am. Cortisol is normally at its lowest here therefore if its high then its very abnormal
what is the dexamethasone suppression test
- measure a patients cortisol and then give dexamethasone.
- measure cortisol levels 8hrs later
- non-cushings = suppression of cortisol (>50nmol/L)
- cushings - little to now suppression
what is the dexamethasone suppression test looking at
dexamethasone is essentially cortisol, and therefore in a healthy patient there should be negative feedback when it is given, and reduce cortisol levels in the body
what are complications of Cushing’s
osteoperosis
secondary diabetes mellitus
Hypertension
Cardiovascular disease
what are the main causes of adrenal insufficiency
primary
developed world = autoantibody adrenal destruction (addison’s)
developing world = TB and sarcoidosis
Secondary
Iatrogenic - suppression of the HPG axis - steroids
other causes can be adrenal mets (liver, lung, breast) and adrenal haemorrhage
what is the short synacthen test
it tests the adrenal reserve:
1. measure basal cortisol at 9am (normally highest here)
2. Administer synacthen
3. sample cortisol again after 30 minutes
if plasma cortisol is above 580nmol/L after 30 minutes then exclude Addison’s
what is an adrenal crisis
a severe adrenal insufficiency especially hypocortisolemia, with nausea and vomiting, renal failure, LOC
what is the treatment for adrenal crisis
immediate hydrocortisone and IV solute and dextrose if they are hypoglycaemic
what is the gold standard test for acromegaly
an impaired glucose tolerance
what are complications of acromegaly
type 2 diabetes malitis and sleep apnoea
what are the two types of diabetes insipidus
cranial (reduced ADH secretion) and nephrogenic (reduced kidney response to ADH)
what are examples of pituitary mass lesions
-non functioning pituitary adenomas
-endocrine active pituitary adenomas
-malignant pituitary tumours; functional and non functional pituitary carcinomas
-metastases in the pituitary (breast, lung, stomach, kidney)
-pituitary cysts; Rathke’s cleft cyst
what is a craniopharyngioma
arises from squamous epithelial remnants of Rathke’s pouch
- tumour infiltrates the surrounding structures and can cause visual disturbance, growth failure, and pituitary hormone deficiency.
what is Rathkes pouch
it is an evagination at the roof of the developing mouth in front of the buccopharyngeal membrane which gives rise to the anterior pituitary.
what is a Rathke’s cyst
it is derived from the remnants of the pouch and is mostly asymptomatic and small. However it can present with headache and amenorrhoea, hypopituitarism and hydrocephalus
what is a meningioma
it is a tumour of the meninges and can often be caused by radiotherapy
- causes loss of visual acuity, endocrine dysfunction and visual field defects
What are the symptoms of a non functioning pituitary adenoma
if its large it can cause signs of aggressiveness, and mood changes, with 50% causing visual disturbance and 50% causing headaches
how do you treat a non functional tumour
you would do a trans-sphenoidal surgery if its threatening the patients eyesite, or if its increasing in size
what is a non functioning pituitary adenoma
They are pituitary tumour masses which don’t produce and hormones - account for about 10-15% of primary intracranial tumours
how would you test pituitary function
- test hormone function: GH, LH/FSH, ACTH, TSH, ADH
- look at circadian rhythms and pulsatile release of hormones
- look at how the peripheral target organ is working
what are consequences of growth hormone deficiency
short stature
abnormal body composition
reduced muscle mass
poor quality of life
what are consequences of LH/FSH deficiency
hypogonadism
reduced sperm count
infertility
menstruations problems
how do you treat LH/FSH disorders
testosterone in males
oestradiol and progesterone in females
what are consequences of TSH deficiency
hypothyroidism
how do you treat TSH disorders
levothyroxine
what are consequences of ACTH deficiency
adrenal failure
decreased pigment
how do you treat ACTH deficiency
Give corticosteroids such as hydrocortisone
What are consequences of ADH deficiency
diabetes insipidus, decreased water absorption in the kidney resulting in polyuria and polydipsia
how do you treat ADH deficiency
DDAVP - desmopressin
how much water is in the extracellular fluid
1/3 of total body water - 14L
how much water is found in the
a. intravascular fluid
b. interstitial fluid
a. 3.5L (1/4 of ECF)
b. 10.5L (3/4 ECF)
how much water is in the intracellular fluid
28L - 2/3 of total body water
what occurs physiologically when youre in water excess
there is a decrease in plasma osmolality causing an increase in cellular hydration. There is a reduction in thirst, and therefore reduced water intake. You also have a reduction in vasopressin secretion, causing an increase in urine water excretion by the kidney. this and the lack of thirst will reduce total body water
what occurs physiologically when you are in water deficit
water loss causes an increase in plasma osmolality and therefore a decrease in cellular hydration. This will activate the thirst reflex to increase water intake, as well as increasing vasopressin secretion thus reducing water excretion by the kidney. These two things will increase total body water
what is the release of vasopressin controlled by
- osmoreceptors
- baroreceptors
where are osmoreceptors found
in the hypothalamus
where are baroreceptors found
found in the brainstem and in the great vessels
what is the osmolality
concentration per kilo
what are some of the causes of cranial diabetes insipidus
things that cause a lack of vasopressin
- idiopathic
- trauma
- tumours
- genetic
- vascular - aneurysms or infarction
how do you manage cranial diabetes insipidus
you would treat any underlying condition
use desmopressin
when is someone hyponatraemic
when their serum sodium is less than 135mmol/L
what is the normal serum sodium range
137-144mmol/L
what are the signs and symptoms of hyponatraemia
headache
lethargy
anorexia
abdominal pain
weakness
confusion and hallucinations
what tests would someone get done when suspected to be hyponatraemic
plasma osmolality
urine osmolality
plasma glucose
urine sodium
cortisol
what is the indicator of the start of puberty in
a. men
b. women
a. first ejaculation - often nocturnal
b. menarche - first period
what causes development in secondary sexual characteristics in women
ovarian oestogens regulate the growth of breast and female genitalia. Ovarian and adrenal androgens control puberty and axillary hair
what causes development of secondary sex characteristics in males
testicular androgens cause external genitalia and pubic hair growth and enlargement of the larynx and laryngeal muscles (voice deepening)
what are the tanner stages
it is a scale that defines physical measurements of development based on external primary and secondary sexual characteristics
what is thelarche
it is breast development - first visible change of puberty
what is thelarche induced by
oestrogen increase
how long does it take to complete thelarche
completed in about 3 years
what are the effects of oestrogen on the breast
- ductal proliferation
- site specific adipose deposition
- enlargement of the areola and nipple
what other hormones are involved in breast development
prolactin, glucocorticoids and insulin
what is precocious puberty
it is early onset of secondary sexual characteristics, before 8 years in girls and before 9 in boys
what can menarche before 9 lead to
short stature
what is delayed puberty
the absence of secondary sexual characteristics by 14 years (girls) and 16 years (boys)
what does delayed puberty lead to
can lead to reduced peak bone mass and osteoperosis
what is adrenarche
it is the maturational process of the adrenal gland which causes a mild advance in bone age, axillary hair, oily skin, mild ache and body odour
what is pubarche
it is the most pronounced clinical result of adrenarche
in girls what calls for investigations of delayed puberty
- lack of breast development
- over five years between breast development and menarche
- lack of pubic hair by aged 14yrs
- absent menarche by age 15-16yrs
in boys what calls for investigations of delayed puberty
- lack of testicular enlargement by age 14yrs
- lack of pubic hair by age 15
- more than 5 years to complete genital enlargement
what lab investigations are done when delayed puberty is suspected
- complete red blood count
- U+E, renal, LFT
- LH and FSH
- testosterone/oestradiol
- thyroid function
- prolactin
what may be some functional causes as to why someone has delayed puberty
- chronic renal disease
- chronic lung disease
- anorexia nervosa
- psychological/stress related problems
- drugs
what is primary hypogonadism
when there is a problem at the ovary or testis which causes a reduction or complete absence in hormone secretion from the glands
what is secondary hypogonadism
this is where the issue is at the pituitary or hypothalamus, aka, no LH/FSH or GnRH
what happens in primary female hypogonadism
oestrogen decreases which causes a lack of negative feedback, this causes a rise in LH and FSH (seen on blood)
what happens in secondary female hypogonadism
there is low/no LH or FSH release meaning there is no response to feedback. Therefore oestrogen decreases
what happens in primary male hypogonadism
testosterone release is low or not there. therefore there is lack of feedback. Therefore there is LH and FSH increase
what happens in secondary male hypogonadism
LH and FSH are low/not made and therefore there is no response to feedback meaning testosterone also decreases
what is turners syndrome
45 X0 in girls
what are symptoms of turners syndrome
- renal malformations; horseshoe kidney (fusion)
- short stature
- cardiovascular malformations: aortic arch, spontaneous rupture
how common is turner syndrome
occurs in 1 in 2000 girls
what are different causes of thyroid autoimmunity
- postpartum thyroiditis
- autoimmune thyroiditis
- autoimmune hypothyroidism
- graves disease
what is found in almost all patients with autoimmune hypothyroidism
thyroglobulin and thyroid peroxidase (TPO) antibodies
what can predispose you to hypothyroidism
- genetic and environmental factors in varying proportion
- being female
- environmental factors; stress, high iodine intake, smoking
what is a goitre
it is a palpable and visible thyroid enlargement
where are goitres endemic
in iodine deficient areas
what is the definition of hyperthyroidism
an excess of thyroid hormone in the blood
what are the three main mechanisms for increased levels of thyroid hormone in the body
- overproduction of thyroid hormone
- leakage of preformed hormone from the thyroid
- ingestion of excess thyroid hormone
what are causes of hyperthyroidism
- graves disease
- toxic multinodular goitre
- toxic adenoma
- congenital hyperthyroidism
- thyroiditis
- iodine induced
what are the clinical features of hyperthyroidism
What is an adenoma specific symptom for hyperthyroidism
a solitary nodule
what is a MNG specific symptom for hyperthyroidism
multinodular goitre
what investigations are done to diagnose hyperthyroidism
- thyroid function tests to confirm biochemical hyperthyroidism
- diagnosis of the underlying cause cause its important to treat
- clinical history, physical signs
- supporting investigations, such as thyroid antibodies
what are the three tyes of hypothyroidism
primary, secondary, tertiary
- primary is 99% of cases where there is absence or dysfunction to the thyroid gland
what is a common cause of primary hypothyroidism
hashimotos thyroiditis
what are causes of hypothyroidism in a child
- neonatal hypothyroidism
- resistance to thyroid hormone
- isolated TSH deficiency
what drugs can cause hypothyroidism
iodine, lithium and thionamides
what are the actions of the parathyroid hormone
- increases calcium reabsorption in the kidney
- increases 1 alpha hydroxylation of 25-OH vitamin D in the kidney
- decreases phosphate reabsorption in the kidney
- increases bone remodeling (bone resorption greater than formation)
- indirectly increases calcium reabsorption in the intestine
what is hypocalcaemia
low total serum calcium
what are the consequences of hypocalcaemia
paraethesia - burning or prickling sensation in hands, legs, arms and feet
muscle spasm
seizures
basal ganglia calcification
cataracts
ECG abnormalities
Osteomalacia - vitamin D deficiency
what is the calculation for working out the corrected calcium
the total serum calcium + 0.02
what is Chvostek’s sign
when you tap over the facial nerve and look for spasm of the facial muscles
what is hypoparathyroidism
it is the underproduction of the parathyroid hormone
what are causes of hypoparathyroidism
- genetics
- autoimmune - isolated, polyglandular
- infiltration of the parathyroid glands by iron overload (haemochromotosis)
- surgery - parathyroidectomy
what is pseudohypoparathyroidism
resistance to parathyroid hormone
what would the bloodwork show in someone who had pseudohypoparathyroidism
low serum calcium and high phosphate, but appropriate PTH levels for the low calcium levels
what are the consequences of pseudohypothyroidism
short stature
obesity
round faces
mild learning difficulties
short fourth metacarpals
other hormone resistance
what is hypercalcaemia
high calcium levels in the blood serum - >2.66 mmol/L
leaving what on for too long can cause hypercalcaemia
leaving a tourniquet on for too long
what are some symptoms of hypercalcaemia
thirst
polyuria
nausea
constipation
confusion
can lead to coma
painful bones
renal stones
GI symptoms
Psychosis
vomiting
cardiac arrest
what can hypercalcaemia be a consequence of
Calcium supplementation
Hyperparathyroidism
Iatrogenic drugs – thiazides
Milk alkali syndrome
Paget’s disease of bone
Acromegaly and Addison’s
Zolinger-Ellison Syndrome – MEN type I
Excess vitamin D
Excess vitamin A
Sarcoidosis
what is primary hyperparathyroisism
it is increased PTH levels due to a problem with the parathyroid glands - often a tumour
- 80% solitary adenoma
- 20% hyperplasia of glands
what are consequences of primary pyerparathyroidism
bones - osteitis fibrosa cystica, osteoperosis
kidney stones
psychic groans - confusion
abdominal moans - constipation and acute pancreatitis
what happens to PTH, calcium and phosphate levels in vitamine D deficiency
PTH - High
Calcium - Low
Phosphate - Low
Is the response of phosphate in vitamin D deficiency appropriate or not
it is appropriate
what happens to PHT, calcium and phosphate levels in hypoparathyroidism
PTH - low - inappropriate
Calcium - Low
Phosphate - high
what happens to PTH, calcium and phosphate in pseudohypoparathyroidism
PTH - High - appropriate
Calcium - low
Phosphate - high
what happens to PTH, calcium and phosphate during hypercalcaemia of malignancy
PTH - low - appropriate
calcium - high
Phosphate - unpredictable, depends on underlying cause
What is SIADH
syndrome of inappropriate ADH: large amounts secreted causing water to be reabsorbed in the collecting duct
what are causes of SIADH
- post operative from major surgery
- infection (atypical pneumonia and lung abscess)
- head injury
- medication (thiazide diuretics, carbamazepine, antipsychotics, SSRIs, NSAIDs)
what are signs and symptoms of SIADH
headache
nausea
fatigue
muscle cramps
confusion
severe hyponatraemia
what investigations need to be done with SIADH
is a diagnosis of exclusion
- look for U and E - hyponatraemia
- Urine sodium is high
- urine osmolality is high
what causes of hyponatraemia need to be excluded
do a negative short synACTHen test - exclusive adrenal insufficiency
no diarrhoea and vomiting
no history of diuretic use
no AKI/CKD
how do you manage SIADH
treat the underlying cause:
stop the causative medicine
fluid restriction
Tolvaptan (ADH receptor blocker)
when is someone considered hyperkalaemic
when their level is above 5.5mmol/L
what are the symptoms of hyperkalaemia
fatigue and light headedness
weakness
chest pain
palpitations
what are the symptoms of hyperkalaemia
arrhythmias - potential for cardiac arrest
reduced power and reflexes
flaccid paralysis
signs of underlying cause
what are the different causes of hyperkalaemia
Due to excessive consumption at a fast rate - IV fluids
Low levels of aldosterone in kidneys – adrenal insufficiency (addisons disease)
Drugs - ACE inhibitors, Spironolactone – potassium-sparing diuretic
NSAIDs, Ciclosporin, Heparin
Acute kidney injury – decreased filtration rate so more K+ is maintained in blood
what will happen on a ECG when someone is hyperkalaemic
there will be a small of even absent P wave. There will be prolonged PR intervals and a wide QRS interval (over 0.12s) . There will also be Tall tented T waves
- may not all be present
what investigations will be done if someone is suspected of having hyperkalaemia
- ECG
- Bloods - FBC and U+E
- Urine osmolality and electrolytes
how do you treat hyperkalaemia
ABC - Urgent care
Cardiac monitoring
Calcium gluconate - to protect myocardium
Insulin and dextrose or nebulised salbutamol to drive up potassium intracellularly
treat the underlying cause
when is someone hypokalaemic
when they have less than 3.5mmol/L in the blood
what are symptoms of hypokalamia
- can be asymptomatic
- fatigue and lightheadedness
- weakness
- cramps
- palpitations
- constipation
what are signs of hypokalaemia
- arrhythmia
- hypotonia
- hyporeflexia
- muscle paralysis
- rhabdomyolysis
- constipation
what are reasons why someone would get hypokalaemia
increased excretion - renal disease, drug effect (thiazides, loop diuretics, laxatives), GI loss (D+V), Conns syndrome, Cushings
decreased intake; Dietary deficiency or fasting, liquorice abuse
shift to intracellular; metabolic alkalosis, drug effects (insulin, B2 agonists)
GI losses - vomiting, severe diarrhoea and laxative abuse
what would you see on an EGC in hypokalaemia
a prolonged PR interval, ST depression, flat T waves, long QT, and prominent U waves
what investigations are done when someone is suspected of having hypokalaemia
- ECG
- Bloods - FBC and U+E
- urine osmolality and electrolytes
what treatments would you give someone with hypokalaemia
potassium - PO/IV
other electrolytes as requires
treat underlying cause
MILD: Usually asymptomatic (3.0-3.4mmol/L)
Oral replacement- consider IV
SEVERE: <2.5mmol/L
- IV replacement 40mmol KCL in 1L 0.9 NaCl
what are the two types of diabetes insipidus
cranial and nephrogenic
what is the pathophysiology of diabetes insipidus
- impaired water resorption
- large volumes of dilute urine
what are the reasons for cranial diabetes insipidus
idiopathic
congenital
tumour
trauma
infection
what are nephrogenic causes of diabetes insipidus
inherited
metabolic - low potassium and high calcium
drugs - lithium
- chronic renal disease
what is the gold standard test for diabetes insipidus
the 8 hour water deprivation test
how do you treat
a. nephrogenic
b. cranial diabetes insipidus
a. if it persists give bendroflumethiazide
b. desmopressin
what are the causes of a. primary, b. secondary and c. tertiary causes of hyperparathyroidism
a. parathyroid gland produces excess PTH
b. increased secretion of PTH to compensate hypocalacemia
c. autonomous secretion even after correction of calcium deficiency due to chronic kidney disease
what investigations are done for hyperparathyroidism
PTH/bone profile: high PTH, high calcium and low phosphates
primary: raised calcium
secondary: low serum calcium, high PTH
tertiary: raised calcium and raised PTH
DEXA scan, X ray, ultrasound for stones
how do you manage hyperparathyroidism
primary; sergical removal or adenoma, give bisphosphonates
secondary; calcium correction, treat underlying cause
tertiary; cinacelcet (calcium mimetic) and total/part parathyroidectomy
what can cause a. primary and b. secondary hypoparathyroidism
a. primary - gland failure - autoimmune destruction, congenital (DiGeorge syndrome)
b. Secondary - surgical removal, decreased magnesium (needed for PTH secretion)
what is Trousseaus’s sign
it is where BP cuff causes wrist flexion and the fingers to pull together
what investigations are done in hypoparathyroidism
bloods - bone profile, decreased calcium, increased or normal phosphate, decreased PTH
ECG - prolonged QT +ST segments
how do you treat hypoparathyroidism
IV calcium
AdCal D3 - calcitriol
synthetic PTH if they require it
what age does type 1 diabetes mellitus usually begin
usually between the ages of 5-15
what is the pathophysiology of type 1 diabetes mellitus
- autoimmune destruction of beta cells in the islets of langerhans by autoantibodies
- insulin deficiency and continued breakdown of liver glycogen
- hyperglycaemia and glycosuria
what is the pathophysiology of diabetic ketoacidosis
- complete absence of insulin leads to unrestrained increased hepatic gluconeogenesis and decreased peripheral glucose uptake
- this leads to hyperglycaemia and therefore osmotic diuresis and dehydration
- there is peripheral lipolysis to gain more glucose and free fatty acids increase and are oxidies into ketones causing a build up and leading to acidosis
what factors increase the risk of type 2 diabetes
increases with age
male over female
ethnicity; African-carribean, black African and south Asian
obesity
hypertension
what is the mechanism of action of metformin
it decreases gluconeogenesis in the liver and increases cell sensitivity to insulin
what is the mode of action of sulfonylureas
promotes insulin secretion from the beta cels
what investigations are done to diagnose Conns syndrome
plasma potassium - low
aldosterone/renin ratio - high
what is a phaeochromocytoma
an adrenal medullary tumour that secretes catecholamines
what are signs symptoms of phaeochromocytomas
Signs; hypertension, postural hypotension, tremor, hypertensive retinopathy, pallor
symptoms; headache, sweating, palpitations, tremor
what investigations are done for phaeochromocytomas
plasma metanephrines and normetanephrines
24 hour urinary total catecholamines
CT
what is the treatment for phaeochromocytomas
1st line; alpha blockers; phenoxybenzamine
without a HTN crisis
1st line; Antihypertensive agents; phentolamine
with HTN crisis
what is carcinoid syndrome
a group of syndromes due to the release of serotonin and other vasoactive peptides into the systemic circulation from a tumour.
what are the signs and symptoms of carcinoid syndrome
signs; palpitations, abdominal cramps, signs of right sided heart failure, bronchospasm
symptoms; diarrhoea and flushing
what investigations are done to diagnose carcinoid syndrome
high volume of 5 hydroxyindoleactic acid (breakdown product)
metabolic panel and LFTs
liver ultrasound
what is the treatment for carcinoid syndrome
- local disease: surgical resection and peri-operative octreotide infusion
- metastasis; above plus additional radio ablation
what does Conn’s syndrome refer to
PRIMARY aldosterone producing adenoma
what are causes of Conn’s syndrome
2/3 cases; solitary aldosterone producing adrenal adenoma
1/3 cases; bilateral adrenocortical hyperplasia (technically not conns)
what is the pathology of conns syndrome
excess production of aldosterone, independent of RAAS
- increases K+ loss, Na+ and water retention causing a raised BP
- decreased renin release
- Hypokalaemia
what are symptoms of Conns syndrome
it is usually asymptomatic
- constipation
- muscle weakness and cramps
- polyuria and polydipsia
- paraesthesia
unusual symptoms - sweating attacks
what are signs of conns syndrome
hypertension due to increased blood volume
increased risk of cardiac arrhythmias, particularly in patients with cardiac disease
what are differential diagnosis of conns disease
secondary hyperaldosteronism - excess renin
what does hypokalemia look like on an ECG
slightly peaked P waves
Slightly prolonged PR interval
ST depression
Shallow T wave
Prominent U wave
what are investigations done for conns syndrome
U&Es - decreased renin and increased aldosterone
EGC
Adrenal CT/MRI - aldosterone producing adenoma
What is the pathology of SIADH
Excess ADH causes an increase in AQP2 insertion, and therefore increased water retention and dilution of plasma (hyponatraemia)
BUT ALSO
Excess ADH causes increased insertion of AQP2 increasing water retention and therefore preventing RAAS release. Therefore there is secretion of Na+ and excess water removed with the Na+ so you are euvolaemic but HYPONATEAEMIC
what are malignant causes of SIADH
disordered hypothalamic pituitary secretion or ectopic production
malignancy - small cell lung carcinoma, prostate, thymus, pancreas
what are drug causes of SIADH
Drugs - opiates, chlorpropamide, carbamazepine, vincristine
what are brain causes of SIADH
brain - meningitis, cerebral abscess, head injury, tumour
what are lung causes of SIADH
lung - pneumonia, TB, abscesses, asthma, CF
what are metabolic causes of SIADH
Metabolic - porphyria and alcohol withdrawal
what are symptoms of SIADH
reduction in GCS and confusion with drowsiness
irritability
headaches
anorexia
nausea
what is the treatment for SIADH
treat the underlying cause
Restrict fluid - to increase Na+ concentration
Demeclocycline - inhibits action of vasopressin on the kidney
Vasopressin receptor antagonists
Tolvaptan - promotes water excretion with no loss of electrolytes
furosemide (oral)
what is Kussmaul’s respiration
low, deep, sighing/laboured inspiration
What is the pathology of hyperkalaemia
When K+ levels in blood rise, this reduces the different in electrical potential between cardiac myocytes and outside of the cells. this causes the threshold for action potentials to be significantly decreased and therefore abnormal action potentials occur, causing arrhythmia and cardiac arrest
what is the pathology of hypokalaemia
low serum potassium causes a cater concentration gradient out of the cell. This increases leakage from the intracellular fluid causing hyperpolarisation of the myocyte membrane and decreasing myocyte excitability
what happens on an ECG when calcium is too high
the QT interval gets shorter
what happens on an ECG when calcium is low
the QT interval gets longer
what are the causes of hypocalcaemia
vitamin D deficiency - presents with low phosphate
hypoparathyroidism - presents with high phosphate
acute pancreatitis - presents with low phosphate
osteomalacia - presents with low phosphate
chronic kidney disease - presents with high phosphate
pseudohypoparathyroidism
drugs - calcitonin and bisphosphonates
what is osteomalacia
soft bones due to low serum calcium and vitamin D deficiency
- serum calcium low as calcium cant be absorbed from the blood, parathyroid responds to this and makes PTH to suck calcium from kidneys and resorb bone
what is chvosteks sign used for
testing low serum calcium
what is trousseaus sign used for
testing low serum calcium
what is the treatment for hypocalcaemia
Mild – Adcal supplement (calcium carbonate) or cholecalciferol
Severe – Calcium gluconate
Vitamin D supplementation in persistent hypocalcaemia
what are investigations done for hypercalcaemia
ECG - short QT
CXR - rule out myeloma and lymphoma
24 hour urinary calcium
bloods - calcium and PTH
X-ray and protein electrophoresis
DEXA bone scan
high resolution CT
TSH to exclude hyperthyroidism
Tetracosactide to exclude Addisons
what is the treatment for hypercalcaemia
Lowering calcium levels and treatment of underlying cause
Primary hyperparathyroidism – surgical removal of symptomatic parathyroid adenoma
IV saline – helps to dilute levels of calcium in blood
Bisphosphonates – encourage osteoclasts to undergo apoptosis so there is less bone breakdown
what inhibits the release of growth hormone
Somatostatin
High levels of glucose
Dopamine (not as potent as somatostatin)
what is the definition of diabetes mellitus
a group of chronic disorders characterised by the bodies impaired ability to produce or respond to insulin resulting in abnormal glucose metabolism leading to hyperglycaemia
A three year old boy with a history of type 1 diabetes presents to A&E with vomiting and lethargy. On examination he is dehydrated. Bloods gas and ketones are done and its confirmed he has moderate diabetic ketoacidosis. What treatment should be commenced first?
IV 0.9% sodium chloride
what is the presentation of diabetic ketoacidosis
Nausea and vomiting
Dehydration (hypotension)
Acetone smelling breath
Abdominal pain
Drowsy or confused which can progress to coma
reduced consciousness
Hyperventilation (Kussmaul breathing)
What is the gold standard test for diagnosing type 2 diabetes
the HbA1c test - tells you average blood glucose over three months
what does some ones HbA1c test have to be for them to be diagnosed with pre-diabetes
42-47mmol/L
what are the microvascular complications of diabetes mellitus
nephropathy
retinopathy
peripheral neuropathy
what are the macrovascular complications of diabetes mellitus
stroke
hypertension
coronary artery disease
peripheral artery disease
what are the main side effects of metformin
Gastrointestinal upset
lactic acidosis
what are the main side effects of sulfonylureas
hypoglycaemia
weight gain
hyponatraemia
what are side effects of DPP-4 inhibitors
generally well tolerated but increased risk of pancreatitis
what are the main side effects of GLP-1 agonists
Nausea and vomiting
pancreatitis
what drug class is metformin a part of
Biguanides
what is the pathophysiology of hyperosmolar hyperglycemic state
decreased insulin levels are sufficient to inhibit hepatic ketogenesis (because its not absolute insulin deficiency) but insufficient to inhibit hepatic glucose production. This leads to hyperglycaemia and therefore osmotic diuresis with loss of sodium and potassium
how does hyperosmolar hyperglycemic state present
General: Fatigue, lethargy, nausea and vomiting
Neurological: altered level of consciousness with headaches, papilloedema and weakness
Haematological: hyperviscosity
Cardiovascular: dehydration, hypertension, tachycardia
how do you diagnose hyperosmolar hyperglycemic state
severe hyperglycaemia (>30mmol/L)
hypotension
hyperosmolality
(no significant acidosis or ketosis)
what is the treatment of hyperosmolar hyperglycemic state
Fluid replacement with 0.9% saline
VTE prophylaxis - these patients are high risk due to dehydration
Give insulin - only if glucose doesn’t decrease after fluid replacement
what are complications o hyperosmolar hyperglycemic state
Stroke
MI
PE
Insulin related hypoglycaemia
treatment related hypokalaemia
A 56-year-old diabetic female is admitted to hospital in order to have intravenous antibiotics for community acquired pneumonia. On day 4 of admission, she becomes confused and drowsy after which she has a short seizure which spontaneously resolves. Her capillary glucose is noted at 2.6mmol/L and she is unconscious.
What is the most appropriate immediate management of this patient?
IV glucose
what is the definition of hypoglycaemia
hypoglycaemia occurs when glucose concentration falls below the normal fasting glucose level, generally this is defined as glucose below 3mmol/L
what is the normal body response to hypoglycaemia
Blood glucose taken up by cells, levels of glucose within blood drop.
Stimulates alpha islet cells 🡪 produce glucagon and reduce production of insulin from beta cells.
Glucagon acts to increase liver gluconeogenesis and glycogenolysis.
↓ Blood glucose 🡪 increased production of adrenaline, GH and cortisol levels
All these mechanism act to increase blood glucose rapidly.
how does hypoglycaemia present when the patient has blood glucose of less than 3.3mmol/L
Sweating
shaking
hunger
anxiety
nausea
How does hypoglycaemia present when the patient has a blood glucose of less than 2.3mmol/L
weakness
vision changes
confusion
dizziness
What is the pathophysiology behind primary hypothyroidism
Problem at the thyroid level causing low T3/4 being produced
There will be compensatory high TSH levels but due to thyroid dysfunction it doesnt increase T3/4 levels
what is the pathophysiology behind secondary hypothyroidism
Pituitary disorders cause low levels of TSH and therefore low T3/4
what other tests are done for hypothyroidism (other than TFT and antibody test)
Fasting blood glucose - recommended in assessment in patients with non specific fatigue and weight gain (primary hypothyroidism is associated with type 1 diabetes)
what is Hashimoto’s thyroiditis
An autoimmune disease causing the thyroid to be attached by an immune mediated processes
what is the pathophysiology of hashimotos
The pathophysiology of Hashimoto thyroiditis involves the formation of antithyroid antibodies that attack the thyroid tissue, causing progressive fibrosis. (Low T4 and High TSH).
Associated with type 1 diabetes mellitus, Addison’s or pernicious anaemia and may cause transient thyrotoxicosis in the acute phase
what investigations are done for hashimotos
1ST LINE = Thyroid function tests(TFTs)- Primarily look at TSH ad T4 levels (Low T4 and High TSH)
GS = Antithyroid peroxidase antibodies- POSITIVE
what is the treatment for hashimotos
same as in hypothyroidism - levothyroxine
what investigations are done to diagnose graves
Thyroid function tests(TFTs)- Primarily look at TSH ad T4 levels (High T4 and low TSH)
TPO-Ab, Isotope scan, MRI, CT, Ultrasound
what is the treatment for graves disease
Anti-Thyroid drugs- block thyroid hormone synthesis, carbimazole, thiamazole
Radioactive iodine therapy-
Surgery
Patients with active moderate to severe and sight-threatening orbitopathy first-line treatment is intravenous corticosteroid (e.g., methylprednisolone)
What is De Quervain’s thyroiditis
De Quervain’s (subacute) thyroiditis is a painful swelling of the thyroid gland thought to be triggered by a viral infection, such as mumps or flu.
- rapid swelling or the thyroid
what is the pathophysiology of De Quervains’s thyroiditis
There are typically 4 phases:
Phase 1- lasts 3-6 weeks: hyperthyroidism, painful goitre, Raised ESR
Phase 2- Lats 1-3 weeks: Euthyroid (normal function)
Phase 3- weeks to months: Hypothyroidism
Phase 4- Thyroid structure and function goes back to normal
how does De Quervains thyroiditis present
Neck pain, difficulty eating, tender, firm, enlarged thyroid, fever, palpitations
what is diagnosis/investigations done for De Quervains thyroiditis
Total T4, 3 levels
T3 resin uptake
free thyroxine index
all elevated
what is the treatment of De quervains
Hyperthyroid phase - NSAIDS and corticosteroids can be used for pain
Hypothyroid phase - No treatment normally but can give small dose of levothyroxine in severe cases.
what are complications of de quervains thyroiditis
thyroid storm, long term hypothyroiditis
what are the four types of thyroid cancer
papillary, follicular, anaplastic, medullary
what are causes for thyroid cancer
genetic alteration and mutations
head and neck irradiation
female sex
how does thyroid cancer present
palpable thyroid nodule
who do you diagnose thyroid cancer
US neck - fine needle biopsy
laryngoscopy
how do you treat thyroid cancer
thyroidectomy followed by radioactive iodine ablation and suppression of TSH
what are complications of thyroid cancer
Complications of total thyroidectomy include an increased risk of recurrent laryngeal nerve damage or hypoparathyroidism
what is the definition of a thyroid storm
Thyroid storm (also known as thyroid or thyrotoxic crisis) represents the severe end of the spectrum of thyrotoxicosis and is characterized by compromised organ function (Rare)
what are causes of thyroid storm
Graves disease, Post thyroidectomy, Infection, Trauma, MI, DKA, Pregnancy etc, Exogenous iodine, Abrupt cessation/Lack of adherence with Antithyroid drugs
what is the presentation of a thyroid storm
Fever, cardiovascular dysfunction, profuse sweating, tachyarrhythmias, nausea and vomiting
what is the pathophysiology of acromegaly
GHRH is released from the hypothalamus and stimulates the release of GH from the anterior pituitary.
The excess growth hormone (GH) from the anterior pituitary results in excessive production of insulin like growth factor (IGF-1) which is responsible for inappropriate growth. This stimulates bone and soft tissue growth.
how do you treat acromegaly
Trans-sphenoidal surgery of the pituitary tumour is gold standard tx for acromegaly secondary to pituitary adenomas.
Surgical removal of cancer is tx for acromegaly secondary to cancer.
If the above don’t work there are medication that can be used to block GH.
2nd line-Somatostatin analogues to block GH release (e.g. octreotide)
3rd line- Pegvisomant (GH antagonist given subcutaneously and daily) OR
Dopamine agonists to block GH release (e.g. bromocriptine)
what are complications of acromegaly
Type 2 diabetes - due to constant high glucose levels
Heart disease- due to possible hypertrophy of the heart due to increased GH
Hypertension
Arthritis - due to overgrowth of cartilage
Carpal tunnel - as muscle growth compresses nerves
Visual fields defect- Bitemporal Hemianopia
what is prolactin
It is a hormone made by lactotrophs in the anterior pituitary and causes breasts to grow and milk made during pregnancy
what is the pathophysiology of a prolactinoma
Hypersecretion of prolactin causes secondary hypogonadism (hypogonadism caused by a problem in the pituitary or hypothalamus) this is due its inhibitory effects on gonadotrophin-releasing hormone.
Hypogonadism is when sex glands called gonads produce little, if any, sex hormones.
what are complications of prolactinomas
Infertility, sight loss, raised intracranial pressure due to adenoma growth in the brain.
what type of corticoid is aldosterone
a mineralcorticoid
where does aldosterone act in the kidney
Distal tubule to increase sodium absorption and potassium secretion
What is secondary hyperaldosteronism
Secondary hyperaldosteronism is where excessive renin stimulating the adrenal glands to produce more aldosterone. Serum renin will be high.
what is the presentation of adrenal insufficiency
Non specific symptoms- Fatigue, Weight loss, Nausea, Vomiting, Hypotension, Abdominal pain
Key symptom- Hyperpigmentation especially in the palmar creases for Addison’s
what is the gold standard test for adrenal insufficiency
GOLD STANDARD- Short synacthen
Ideally performed in the morning when the adrenal glands are the most “fresh”.
Give patient synacthen (synthetic ACTH).
Blood cortisol is measured at baseline, 30 and 60 minutes after administration.
In healthy patients should stimulate adrenal glands to produce cortisol.
The cortisol level should at least double in response to synacthen.
A failure of cortisol to rise (less than double the baseline) indicates primary adrenal insufficiency
what is the pathophysiology of SIADH
ADH is produced in the hypothalamus and secreted by the posterior pituitary gland. It stimulates water reabsorption from the collecting ducts in the kidneys.
Excessive ADH results in excessive water reabsorption in the collecting ducts. This water dilutes the sodium in the blood so you end up with a low sodium concentration (hyponatraemia). The water reabsorption is not usually significant enough to cause a fluid overload, therefore you end up with a “euvolaemic hyponatraemia”. The urine becomes more concentrated as less water is excreted by the kidneys therefore patients with SIADH have a “high urine osmolality” and “high urine sodium”.
what is cranial diabetes insipidus
hypothalamus doesnt produce ADH
what is nephrogenic diabetes insipidus
the collecting ducts of the kidneys dont respond to ADH
what is secondary hyperparathyroidism
insufficient vitamin D or chronic renal failure leads to low absorption of calcium from the intestines, kidneys and bones causing hypocalcaemia. This causes the Parathyroid gland to release more PTH and becomes hyperplastic to further increase excess PTH secretion.
what is tertiary hyperparathyroidism
Usually occurs after prolonged secondary hyperparathyroidism
The glands become autonomous, producing excessive PTH even after the cause of hypocalcaemia has been corrected. Don’t respond to negative feedback.
Long-standing kidney disease is the most common cause.
what are risk factors for hyperparathyroidism
Elderly women
prolonged, severe calcium or vitamin D deficiency
in primary hyperparathyroidism what are the levels of
1. PTH
2. Calcium
3. Phosphate
- high
- high
- low
in secondary hyperparathyroidism what are the levels of
1. PTH
2. Calcium
3. Phosphate
- High
- Low/normal
- depends on underlying cause
in tertiary hyperparathyroidism what are the levels of
1. PTH
2. Calcium
3. Phosphate
- High
- High
- High
how does hyperparathyroidism present
It is worth remembering the “renal stones, painful bones, abdominal groans and psychiatric moans” mnemonic for the symptoms of hypercalcaemia:
Painful bones
Renal stones
Abdominal groans refers to symptoms of constipation, nausea and vomiting
Psychiatric moans refers to symptoms of fatigue, depression and psychosis
what is the treatment for hyperparathyroidism
primary - remove the tumour
secondary - treat Vitamin D deficiency or kidney transplant
tertiary - total or subtotal parathyroidectomy
Calcimimetic - increases sensitivity of parathyroid cells to calcium
what are complications of hypocalcaemia
Seizure, cardiac arrest (decreases heart rate and contractility)- a medical emergency! Long QT syndrome
what are complications of Hypokalaemia
Cardiovascular- Chronic heart failure, Acute MI, arrythmias,
Muscle – weakness, depression of deep tendon reflexes, Rhabdomyolysis
what is the pathophysiology of carcinoid syndrome
Neuroendocrine tumours normally secrete serotonin into the circulation.
With GI tract tumours, hormones secreted> enters enterohepatic circulation> liver inactivates hormones> therefore no symptoms
However, when liver metastases are present (liver tumour)> hormone secretion> released into circulation + liver dysfunction> symptoms.
what hormone is released in carcinoid syndrome
serotonin
what is carcinoid syndrome usually caused by
neuroendocrine tumour in the GIT
state two symptoms of carcinoid syndrome
flushing, diarrhoea, abdominal cramps, bronchospasm, fibrosis
what is the definitive treatment for carcinoid syndrome
resection of the tumour
what is the most common cause of hyperthyroidism and hypothyroidism
- graves disease
- hashimotos disease
what is the first line treatment for hypothyroidism
levothyroxine
what is the antibody most associated with hyperthyroidism
Anti TSH receptor
A 57-year-old male presents to his GP following several hypoglycaemic episodes. He has a history of type 2 diabetes and heart failure. He is currently being treated with Metformin and Gliclazide
what is the most likely cause of his hypoglycaemic state
Gliclazide
A 36-year-old female presents to her GP with heat intolerance, sweating and palpitations. She is 10 weeks pregnant but has no other medical history. Bloods tests reveal raised free thyroxine and depressed TSH.
What is the most appropriate initial step to treat this patient’s condition?
Lithium
Carbimazole
Propylthiouracil
Thyroidectomy
Propylthiouracil - better in first trimester as its safer for fetus than carbimazole
A 50-year-old female presents to her general practitioner with ‘pins and needles’ around her mouth and frequent muscle cramps. On examination, she appears well, however when taking her blood pressure reading, her wrist and fingers began to cramp and flex.
What is the most likely diagnosis?
Hyperkalaemia
Hypocalcaemia
Hypernatraemia
Hypomagnesaemia
Hypocalcaemia
