Endo Flashcards
What is Acromegaly?
A disorder of excessive growth hormone
what is the most common cause of acromegaly?
Pituitary adenoma - 95%
what is gigantism?
excessive GH secretion before epiphyseal closure, during childhood or adolescence leading to increased linear growth
what are 5 rarer causes of acromegaly?
Bronchial carcinoid tumour
Lung carcinoids
Pancreatic islet cell tumour
Phaeochromocytoma
Paraneoplastic syndrome due to ectopic growth hormone releasing hormone (GHRH) or growth hormone (GH) secretion
what 2 hormones inhibit the secretion of GH?
Dopamine
Somatostatin
what is the pathophysiology of acromegaly?
Increased GH => increased glucose release, muscles retain nitrogen causing them to grow => epiphyseal plates fused so can only grow in places where there is still growth => jaw, nose, hands, feet
5 symptoms of acromegaly?
Bigger hands, feet and face
excessive sweating
tiredness
weight gain
headache
deep voice/amenorrhoea
6 signs of acromegaly?
Bi-temporal hemianopia
spade like hands and feet
large tongue - macroglossia
Jaw protrusion - prognathism
interdental seperation
predominant forehead
what are 6 conditions related to acromegaly?
Hypertrophic heart
Hypertension
T2DM
Carpal tunnel syndrome
Colorectal cancer
what is the 1st line investigations for acromegaly?
Raised insulin like growth factor 1
What is the gold standard test for acromegaly to comfirm diagnosis after 1st line testing?
oral glucose tolerance test
- in normal patients GH suppressed to <2 with hyperglycaemia
- no suppression of GH in acromegaly
what scan can be used in acromegaly?
MRI pituitary - ?pituitary tumour
What is the 1st, 2nd and 3rd line management for acromegaly?
1st line - trans-sphenoidal surgery if pituitary adenoma
2nd line -
- Cabergoline (dopamine agonist)
- Somatostatin analogue (octreotide)
- Pegvisomant - GH receptor antagonist give SC OD
3rd line - Radiotherapy,
What are 5 complications of acromegaly?
T2DM
Arthritis and carpal tunnel
Cardiac - cardiomyopathy, heart failure, HTN
Colorectal cancer
Obstructive sleep apneoa
what visual field defect is associated with acromegaly?
Bitemporal hemianopia
what is the inheritance pattern for inherited multiple endocrine neoplasia?
autosomal dominant
what are the 3 different types of multiple endocrine neoplasia?
MEN1
MEN2A
MEN2B
what is the most common presentation of MEN1?
hypercalcaemia
what is the most common cancer associated with multiple endocrine neoplasia 1?
Pituitary adenoma - 60% of MEN1 patients
what is the cause of MEN1?
mutations in MEN1 tumour supressor gene
what is the presentation of multiple endocrine neoplasia (MEN) 1?
3Ps
Primary Hyperparathyroidism
Pancreatic neuroendocrine tumour (50%)
Pituitary Adenoma (70%)
Also adrenal and thyroid cancers
what is Addison’s disease?
Autoimmune destruction of the adrenal glands leading to reduced cortisol and aldosterone production
Most common cause of primary hypoadrenalism in UK
what are 5 causes of secondary adrenal insufficiency?
Underacting pituitary not releasing ACTH
congenital underdevelopment (hypoplasia) of pituitary
Pituitary surgery
infection
loss of blood flow to pituitary - apoplexy
Pituitary radiotherapy
what is the cause of tertiary adrenal insuficiency?
Inadequate CRH release from hypothalamus
Usually due to long term steroid use (>3 weeks) which suppresses hypothalamus
What are 3 risk factors for Addison’s?
Female
Autoimmune diseases
HIV/TB
What are 8 clinical presentations of Addison’s?
Hypotension
Metabolic acidosis
Hypoglycaemia
Hyponatraemia and Hyperkalaemia
Lethargy, weakness, anorexia
Nausea and vom
Weight loss
Salt craving
Hyperpigmentation - especially of palmar creases
is hyperpigmentation a feature of secondary or tertiary adrenal insuficiency?
NO - only primary (addisons)
why does Addison’s cause skin hyperpigmentation?
High ACTH leads to stimulation of melanocytes
what is the gold standard test for Addison’s?
ACTH stimulation test (synacthen’s test) - low
what is an alternative investigation for Addison’s disease if the gold standard is unavailable?
9am serum cortisol
> 500 - Addison’s unlikely
<100 - abnormal
100-500 - send for ACTH stimulation test
What is the management for Addison’s?
Daily -Hydrocortisone - 20-30gm per day
AND
Fludrocortisone
Emergency -
medical alert bracelets/cards
Hydrocortisone for injection
what are the sick day rules in addison’s disease?
Double glucocorticoids (hydrocortisone)
Fludrocortisone remains the same
what is the management of an Addisonian crisis?
Hydrocortisone 100mg IV/IM
1L NaCl over 30-60 mins + dextrose if hypoglycaemic
Hydrocortisone 6 hourly until stable
oral replacement after 24 hours
what are 3 complications of Addison’s?
Secondary Cushing’s syndrome (too much glucocorticoid replacement)
osteopenia/porosis
treatment related hypertension
What is Cushing’s syndrome?
features of prolonged high levels of glucocorticoids in the body
what are the 2 corticosteroid hormones?
glucocorticoids - cortisol
mineralocorticoids - aldosterone
what is Cushing’s disease?
pituitary adenoma secreting excessive adrenocorticotrophic hormone (ACTH) stimulating excessive cortisol release from adrenal
what are 6 actions of cortisol (glucocorticoids)?
Increased alertness
inhibits immune system and reduces inflammation
inhibits bone formation
Raises blood glucose
increases metabolism
Supports cardiovascular function
when in the day is cortisol the highest?
morning
what are 3 medication that act as glucocorticoids (cortisol)?
Prednisolone
Hydrocortisone
Dexamethasone
what is the action of mineralocorticoids (aldosterone)?
Increase sodium reabsorption from distal tubule
Increase potassium secretion from distal tubule
Increase hydrogen secretion from collection ducts
what medication mineralocorticoid?
fludrocortisone
Is Cushing’s more common in women or men?
women
what are 4 causes of Cushing’s syndrome?
CAPE
Cushing’s disease - pituitary adenoma releasing excessive ACTH - MOST COMMON
Adrenal adenoma - adrenal tumour secreting cortisol
Paraneoplastic syndrome
Exogenous steroids
what are 4 causes of pseudo cushings?
Alcohol excess
severe depression
obesity
pregnancy
what tumour commonly causes paraneoplastic cushing’s syndrome?
small cell lung cancer
What are 4 risk factors for Cushing’s?
Exogenous corticosteroid use
pituitary/adrenal adenoma
adrenal carcinoma
small cell lung cancer
What are 8 clinical manifestations of Cushing’s?
Moon face
Central obesity
Abdominal striae
Enlarged fat pad on back - buffalo hump
Proximal limb muscle wasting - difficulty standing from sitting
Hirsutism
Easy bruising and skin healing
Hyperpigmentation of skin
what are 6 complications of cushing’s syndrome?
Hypertension
cardiac hypertrophy
T2DM
Dyslipidaemia
Osteoporosis
Adverse mental health
what can be seen on blood gas in cushings?
hypokalaemic metabolic alkalosis
what investigation is used to diagnose cushing’s syndrome?
dexamethasone suppression test
what are the 3 different types of dexamethasone suppression test?
low dose overnight test - 1mg
low dose 48 hour test - 0.5mg every 6-8 hours
High dose 48 hour test - 2mg every 6-8 hours
what investigation can be used to differentiate between cushings and pseudo-cushings?
insulin stress testing
What is the management of Cushing’s?
1st line - treat cause - trans-sphenoidal pituitary adenectomy/ adrenalectomy/removal of small cell lung cancer
adjuncts - post surgery corticosteroid/non-corticosteroid replacement, chemo, radiotherapy on primary tumour
what is nelson’s syndrome?
development of ACTH producing pituitary tumour after the surgical removal of both adrenal glands due to lack of cortisol and negative feedback - causes skin hyperpigmentation, bitemporal hemianopia and lack of other pituitary hormones
is reoccurrence common with Cushing’s?
Yes
What is T1DM?
a metabolic autoimmune disorder characterised by hyperglycaemia due to destruction of insulin producing beta cells in the islet of langerhans in the pancreas, results in absolute insulin deficiency.
what are 3 risk factors for T1DM?
Genetics
Other autoimmune disease
Viral tiggers - coxsackie, enterovirus
what causes T1DM?
autoimmune pancreatic beta cell destruction
subclinical until 80-90% of beta cells have been destroyed
what is the blood glucose target fasting and at other times of day?
5-7 mmol/L - Fasting
4-7 mmol/L usually
5-9 mmol/L - after meals
How does insulin reduce blood glucose?
Causes cells to take up glucose
causes muscle and liver cells to store glucose as glycogen
where is glucagon produced?
Alpha cells of islets of Langerhans
How does glucagon increase blood glucose?
Breaks down glycogen in liver into glucose - glycogenolysis
Causes liver to convert fats and protein to glucose - gluconeogenesis
What are 8 clinical manifestations of T1DM?
polyuria + polydipsia + hunger
blurred vision
fatigue/tiredness
weight loss
recurrent infections
secondary enuresis
KETOACIDOSIS
what is an atypical presentation of T1DM and what additional test can be done?
> 50 year
BMI > 25
C-peptide
what 5 tests should a new type 1 diabetic get?
FBC, U+E
HbA1c
TFTs and anti-TPO
anti-TTG
Insulin antibodies, anti-GAB, islet cell antibodies
What is the management of T1DM?
1 - Basal-bolus insulin given once daily
Short acting insulin given 30 mins before carbohydrate intake
2 - fixed insulin dosing in those who cannon self-manage
What are 3 side effects of insulin?
hypoglycaemia
weight gain
lipodystrophy
what are 3 different types of long acting insulin and their brand names?
Insulin detemir - Levemir
Insulin glargine - Lantus - Abasaglar, Semglee, Toujeo
Insulin degludec - Tresiba
what is the onset on long acting insulins?
duration of action of up to 24 hours - produce steady state in 2-4 days
what are 3 examples of intermediate acting insulins?
Humalin I
Insuman basal
Insulatard
how long is the onset and action of intermediate insulins?
onset 1-2 hours with maximal effects at 3-12 hours
11-24 hour duration
what are 2 examples of short acting insulin?
Actrapid
Humulin S
what is the onset and duration of short acting insulin?
onset in 30-60 mins
up to 8 hour duration
what are 2 examples of rapid acting insulins?
Humalog - insulin lispro
Novorapid - insulin aspart
what is the onset and duration of rapid acting insulin?
Onset 15 mins
duration 2-5 hours
what is the 1st line long acting insulin choice?
Insulin detemir - levemir
when is metformin added in T1DM?
BMI >25
what is needed for a child to qualify for an insulin pump on the NHS?
> 12 years
Difficulty controlling HbA1c
what are 2 different types of insulin pumps?
tethered - replaceable infusion sets and insulin that attaches with belt around patient waist - has wires
patch - sits directly on skin without any tubing, replace entire patch when runs out
what are the sick day rules for T1DM?
Do not stop insulin
check BMs more often - every 1-2 hours
Check urine ketones
Maintain normal meal pattern if possible - replace with sugary drinks if reduced appetite
Aim to drink 3L of water
How often should T1 diabetics have their HbA1c measured?
every 3-6 months
How often should people with T1DM measure blood glucose?
4x per day Adults
5x per day children
MINIMUM
What are the 3 microvascular complications of Diabetes?
retinopathy
peripheral neuropathy
nephropathy
what are 4 macrovascular complications of diabetes?
coronary artery disease
cerebrovascular disease
peripheral artery disease
Hypertension
what are 4 infection related complications of diabetes?
UTI
Pneumonia
Skin and soft tissue infections
Fugal infections - candida
what are the legal requirements of a person on insulin or sulfonylureas?
inform DVLA of insulin use
No severe hypoglycaemia in past 12 months
Full hypoglycaemic awareness
Adequate control of condition with BM monitoring at least BD and before driving
Understand risks of hypoglycaemia
No other complication
what are 8 patients where HbA1c should not be used to diagnose DM?
<18 years
Pregnant or <2 mon PP
Symptoms <2 months
Acutely unwell
On medications that can cause hyperglycaemia
Acute pancreatic damage/surgery
End stage CKD
HIV
what are 4 people to use HbA1c with caution in?
Abnormal haemoglobin - haemoglobinopathies
anaemia
altered red cell lifespan
recent blood transfusion
what is T2DM?
A metabolic disorder of hyperglycaemia due to a combination of insulin resistance and deficiency leading to persistently high blood glucose
what are 6 risk factors for T2DM?
Non-modifiable
older age ethnicity
FHx
Modifiable
Obesity
Sedentary lifestyle
High carbohydrate diet
what is the pathophysiology of T2DM?
Repeated exposure to glucose and insulin causes cell resistance to insulin leading to more insulin needing to be produced. This fatigues the pancreas causing insulin output to be reduced
High carb diet plus insulin resistance and reduced pancreatin functioning leads to chronic hyperglycaemia and it’s micro and macovascular complications
what is the pathophysiology of T2DM?
post receptor resistance
50% of beta cell mass usually lost => greater amounts of insulin produced by fewer beta cells => hyperglycaemia and lipid excess are toxic to beta cells.
What are 7 clinical manifestations of T2DM?
polyuria, nocturia + polydypsia
Weight loss and fatigue
glycosuria
Acanthosis nigricans - black pigment on nape of neck and axillae
Opportunistic infections
slow wound healing
what is the HbA1c in pre-diabetes?
42-47 mmol/mol
what is the HbA1c target for a new diabetic?
48 mmol/mol
what is the HbA1c target for a patient requiring more than one antidiabetic?
53 mmol/mol
How often is HbA1c measured in T2DM?
3-6 monthly until stable
What is the 1st line management of T2DM?
LIFESTYLE
what is the 1st line medication in T2DM?
Metformin 500mg OD initially
Can increase up to 2g OD/1g BD
what is the 1st line medical management of T2DM if metformin is contraindicated?
with CVD - SGLT-2 inhibitor
NO CVD - DDP-4 inhibitor or pioglitazone or sulfonylurea
what additional medication should people with Diabetes AND CVD, heart failure or a Qrisk >10% be put on?
SGLT-2 inhibitor
what is the 2nd line management of T2DM?
ADD
Sulfonylurea
OR
Pioglitazone
OR
DPP-4 inhibitor
OR
SGLT-2 inhibitor
what is the 3rd line management of T2DM?
Tripple therapy - metformin + 2 others
OR
Insulin therapy
what is one option in T2DM if triple therapy fails in a patient with BMI >35?
switch one drug to GLP-1 mimetic (liraglutide)
what class is metformin?
Biguanide
what does metformin do?
increases insulin sensitivity and decreases glucose production by liver
does not cause weight gain or hypoglycaemia
what are 2 notable side effects of metformin?
GI symptoms - trial of MR formulation
Lactic acidosis - usually secondary to AKI - stop in AKI
what are 4 examples of SGLT-2 inhibitors?
empagliflozin
canagliflozin
Dapagliflozin
Ertugliflozin
what is the MOA of SGLT-2 inhibitors?
Block resorption of glucose in kidneys by sodium glucose co-transporter 2 proteins in proximal tubule
leads to reduced BMs, BP, weight loss, improves heart failure
what are 7 notable side effects of SGLT-2 inhibitors?
Normoglycaemic DKA
Glycosuria
Increased frquency and urgency
Weight loss
Genital and UTIs
lower limb amputaton
Fournier’s gangrene
what is the MOA of pioglitazone?
Thiazolidinedione that increases insulin sensitivity and decreases liver production of glucose
DOES NOT typically cause hypoglycaemia
what are 4 notable side effects of pioglitazone?
weight gain
heart failure
increased fracture risk
small increased risk of bladder cancer
how do sulfonylureas work?
stimulate insulin release from pancreas
what is the most common sulfonylurea?
gliclazide
what are 4 notable side effects of sulfonylureas?
weight gain
hypoglycaemia
SIADH
Liver dysfunction
what are 2 examples of DDP-4 inhibtors?
Sitagliptin
Alogliptin
how do DPP-4 inhibitors work?
block action of DDP-4 which allows for increased incretin (GLP-1) activity by decreasing peripheral breakdown and allowing for increased insulin secretion, inhibition of glucagon production, slower absorption from GI tract
what are 2 notable side effects of DPP-4 inhibitors?
Headaches
Acute pancreatitis
what are 2 examples of GLP-1 mimetics?
exenatide
liraglutide
what are 3 side effects of GLP-1 mimetics?
weight loss
reduced appetite
GI symptoms
what is seen as impaired fasting glucose?
fasting glucose 6.1-7.0
then >7 = diabetes
what is the inheritance of MODY (maturity onset diabetes of the young)?
Autosomal dominant
usually onset <25 years
what are the features of MODY?
Usually picked up incidentally
presents with non-ketosis hyperglycaemia and patients are often a normal weight
usually does not require treatment or can be treated with sulfonylureas or insulin
What is Grave’s disease?
An autoimmune thyroid condition associated with hyperthyroidism and over production of thyroid hormones
are thyroid disorders and cancers more common in men or women?
women
what causes Grave’s disease?
thyroid hormone overproduction stimulated by TSH receptor antibodies
can be genetic
What are 4 risk factors for Grave’s disease?
FHx
Autoimmune disease
Stress
High Iodine intake
What is the pathophysiology for Grave’s disease?
TSH receptor autoantibodies cause thyroid hormone hyperproduction as well as thyroid hypertrophy and hyperplasia of thyroid follicular cells resulting in the clinical manifestations of hyperthyroidism and diffuse goiter.
What are 6 clinical presentations of Grave’s disease?
Thyroid acropachy - clubbing, and hand swelling
Thyroid bruit
Pretibial myxoedema
Diffuse goitre
Thyroid eye disease
Hyperthyroidism signs - heat intolerance, sweating, tremor
What is the diagnostic test for Grave’s disease?
serum TSH receptor antibodies - present
what are 4 differential diagnoses for Grave’s disease?
toxic nodular goitre
post-natal thyroiditis
TSH producing pituitary adenoma
Excessive thyroxine
What is the management of Grave’s disease?
1 - Carbimazole 15-40mg OD for 4-8 weeks then reduce gradually over 12-18 months
2 - Propylthiouracil 200-400mg OD till euthyroid then reduce over time
3 - radioactive iodine treatment, thyroidectomy
Beta blockers - propranolol 10-40mg T/QDS - for symptom control
what are 2 adverse effects of carbimazole?
Acute pancreatitis
Agranulocytosis (also propylthiouracil)
what are 6 complications of graves disease?
AF
Pregnancy related issues - miscarriage, prem, thyroid dysfunction of foetus
Sight threatening orbitopathy
Osteoporosis
Congestive heart failure
Thyroid storm
what is thyroid storm?
rare but life threatening sudden significant rise in thyroid hormone levels resulting in fever, profuse sweating, diarrhoea, vomiting, delerium, profound weakness, seizure, jaundice, raised HR, BP and temp and eventually coma
what are 4 complications of Grave’s disease?
bone mineral loss
AF/congestive heart failure
sight threatening complications
elephantiasis dermopathy
what is Hashimoto’s thyroiditis?
an autoimmune-mediated lymphocytic inflammation of the thyroid gland resulting in a destructive thyroiditis with release of thyroid hormone causing transient hyperthyroidism (for 2/3 months) then permanent hypothyroidism
what are 3 risk factors for Hashimoto’s thyroiditis?
Female
Autoimmune disease
genetics - Turner’s/Down’s
what antibodies cause Hashimoto’s thyroiditis and what do they do?
ant-Thyroid peroxidase antibodies
attack thyroid cells causing fibrosis and the release of stored thyroid hormone causing transient hyperthyroidism for a few months before stores run out and permanent hypothyroidism ensues
what are 3 features of hashimoto’s thyroiditis?
Hypothyroidism features
firm non-tender goitre
anti-TPO antibodies
what is the gold standard test for Hashimoto’s thyroiditis?
serum ant-Thyroid peroxidase antibodies
what is the management of Hashimoto’s?
levothyroxine
what are 3 complications of Hashimoto’s?
Atrial fibrillation
IHD/CHF
low risk of developing Grave’s disease
what is the prognosis for Hashimoto’s thyroiditis?
Permanent hypothyroidism and treatment with levothyroxine
What is defined as the normal range for serum potassium?
3.5-5.3 mmol/L
what is seen as mild hyperkalaemia?
5.4-5.9 mmol/L
what is seen as moderate hyperkalaemia?
6-6.4 mmol/L
what is seen as severe hyperkalaemia?
> 6.5 mmol/L
what are 7 causes of hyperkalaemia?
AKI
CKD - stage 4/5
Rhabdomyolysis
Adrenal insufficiency - Addison’s disease
Tumour lysis syndrome
Massive blood transfusion
Medications
what are 6 medications that can cause hyperkalaemia?
Aldosterone antagonists - spironolactone, eplerenone
ACEi
ARBs
NSAIDs
Ciclosporin - calcineurin inhibitors
heparin
what are 4 clinical manifestations of hyperkalaemia?
Muscle cramps/ weakness
ECG changes
Paraesthesia
Palpitations
what 5 ECG changes are present in hyperkalaemia?
Tall peaked (tented) T waves
Long PR (>200ms)
Loss of P waves
Broad QRS (>100ms)
Sinusoidal wave pattern
Can cause ventricular fibrilation
what are the 2 indications for emergency treatment of hyperkalaemia?
ECG changes
Potassium >6.5 mmol/L
what is given in a hyperkalaemic emergency?
IV calcium gluconate/chloride 10ml 10% - stabilise cardiac membrane (does not lower K+)
Insulin/glucose infusion - 10 units insulin and 25g glucose - given over 15-30 mins
Nebulised salbutamol
Haemodialysis
what is a complication of hyperkalaemia?
life threatening arrhythmias and cardiac arrest
what can be given in hyperkalaemia to bind potassium?
Sodium ziconium cyclosilicate 30mg PR
Patiromer calcium
No longer recommended -Calcium polystyrene sulfonate (resonium) - enema or oral - enema more effective
What is the pathophysiology of Hyperosmolar Hyperglycaemic state?
Hyperglycaemia drives osmotic diuresis leading to fluid and electrolyte loss
Due to small amounts of insulin present lipolysis does not occur hence no ketoacidosis
what are 5 key features of HHS?
Hyperglycaemia
Hyperosmolality (>320 mosmol/Kg)
Dehydration
Electrolyte abnormalities
WITHOUT Ketoacidosis
what are 3 risk factors for HHS?
Infection
MI
Poor medication compliance
what are 5 clinical manifestations for HHS?
Weakness and leg cramps
Reduced GCS, confusion, lethargy, headache, seizure
polyuria/oliguria + polydipsia
Nausea, Vom ,abdo pain
Dehydration - tachy, hypotension, dry
what are the four 1st line investigations for HHS
Serum/urine glucose
U+Es
ABG
Blood/urinary ketones
what is the gold standard test for HHS?
serum osmolality - raised
How can serum osmolarity be calculated?
2(Na+) + Glucose + Urea
what is the diagnostic criteria for HHS?
Hyperglycaemia >30 mmol/L
Hyperosmolality >320 mOsmol/Kg
Hypovolaemia
NO hyperketonaemia
NO acidosis (pH >7.3, Bicarb >15)
what is the management for HHS?
1st line - fluid replacement (0.9% saline), potassium replacement if low
adjuncts - LMWH, restore electrolyte loss, insulin if needed
when should insulin be given in HHS?
only IF blood glucose stops falling with IV fluids alone
How slowly should plasma sodium fall in HHS?
no quicker than 10 mmol/24 hours
How quickly should plasma glucose fall in HHS?
4-6 mmol/hour
what are 4 complications of HHS?
CV - VTE, arrythmias, MI
Neuro - stroke, seizure
Renal - AKI
Iatrogenic - cerebral oedema/cerebral pontine myelinolysis
what are 5 causes of hyperthyroidism?
Grave’s disease (most common)
Toxic multinodular goitre
Thyroiditis
Thyroid cancer
subacute thyroiditis (granulomatous or De Quervain’s)
what are 8 risk factors for hyperthyroidism?
female
post-partum
60+
FHx
autoimmune diseases
radiation
lithium therapy
smoking
What are 5 symptoms of hyperthyroidism?
Heat intolerance/sweating
palpitations/tremor
irritability
menstrual irregularities/sexual dysfunction
Goitre
what are 5 signs of hyperthyroidism?
orbitopathy (Grave’s)
cardiac flow murmur (thyroid bruit)
scalp hair loss
acropachy (Grave’s)
weight loss
what is the gold standard investigation for hyperthyroidism?
serum free total T3/4
what are 3 investigations for hyperthyroidism?
TSH - high/low
TSH receptor antibodies - present in Graves
Serum free/total T3/T4 - high
what are 6 causes of primary hyperthyroidism?
Graves - most common
Toxic multinodular goitre
Toxic adenoma
Subclinical hyperthyroidism
Thyroiditis - de quervains, hashimotos, post partum
Drugs - amiodarone, lithium
what is toxic multinodular goitre?
Several autonomously functioning thyroid gland nodules resulting in hyperthyroidism - often benign but can be malignant
what are 3 causes of secondary hyperthyroidism?
Pituitary adenoma - secreting TSH
Ectopic tumour - hCG secreting tumour (choriocarcinoma)
Hypothalamic tumour
what is hypokalaemia?
serum potassium <3.5 mol/L
what is mild hypokalaemia?
3.0-3.5 mmol/L
what is moderate hypokalaemia?
2.5-3.0 mmol/L
what is severe hypokalaemia?
<2.5 mmol/L
what can cause hypokalaemia? (7)
Excessive losses - D+V, high output stoma, dialysis, burns
Reduced intake
Malabsorption
Diuretics - loop and thiazide diuretics
Insulin
Salbutamol
Metabolic alkalosis - increased pH causes increased activity of H+/K+ antiporter operating to correct alkalosis
what are 5 risk factors for hypokalaemia?
older age
Medications - salbutamol, loop and thiazide diuretics, insulin
Co-morbidities - diabetes, renal disorders
poor dietary intake
Cushing’s syndrome
what are 7 clinical manifestations of hypokalaemia?
Muscle weakness, cramps and pain
Hypotonia
Fatigue
Palpitations
Constipation - due to reduced peristalsis
Reduced deep tendon reflexes
what is seen in ECG in Hypokalaemia/
U waves - extra wave after T wave
Small/absent/inverted T waves
Prolonged PR interval
ST depression
long QT
U have no Pot and no T but a long PR and a long QT
what is one important medication side effect in hypokalaemia?
Increases risk of digoxin toxicity - take care with diuretics
does hypokalaemia tend to be associated with acidosis or alkalosis?
Alkalosis - low potassium causes influx of H+ ions into cells to allow K+ to leave cells and enter serum
what are 4 causes of hypokalaemia with alkalosis?
Vomiting
thiazide and loop diuretics
Cushing’s syndrome
Primary hyperaldosteronism
what are 3 causes of hypokalaemia with acidosis?
diarrhoea
renal tubular acidosis
acetazolamide
Partially treated DKA
what other electrolyte deficiency is associated with hypokalaemia?
hypomagnesaemia
what is the management of hypokalaemia?
Mild-moderate (>2.5) - Oral potassium replacement - Sando-K
Severe (<2.5) - IV potassium - 20-40mmol K+ in 0.9% NaCl
what is the fastest you can replace potassium peripherally IV?
10 mmol per hour
e.g 40 mmol in 1L of saline bag ran over 4 hours fastest
what can cause hypoparathyroidism?
post-surgery
genetic and autoimmune conditions - (di george syndrome)
iron and copper overload (haemochromatosis or Wilson’s disease)
idiopathic
Prolonged hypomagnesaemia can suppress PTH
what are 3 risk factors for hypoparathyroidism?
thyroid/parathyroid surgery, hypomagnesianism, transfusional iron overload (in thalassaemia)
what does parathyroid hormone do? (3)
Acts to increase serum calcium:
Increase renal calcium absorption and phosphate excretion
Increased production of 1,25-dihydroxyvitamin D in kidney
Increase bone calcium resorption
what is normal serum calcium?
2.2-2.6 mmol/L
what is the physiology of the parathyroid gland?
Chief call produce parathyroid hormone and store it in secretory granules
Serum calcium is detected by calcium sensing receptors on the cell surface which control the release of PTH
Higher serum calcium inhibits PTH release and low calcium leads to more PTH release
what is the physiology of PTH in bone?
increases activity and number of osteoclasts leading to calcium and phosphate release from the bone
What is the physiology of parathyroid action on the kidney? 3
1 - Stimulates calcium reabsorption in distal CT and collecting duct
2 - Decreases phosphate reabsorption in proximal CT
3 - stimulates conversion of 25-hydroxyvitamin D into the active for 1,25-dihydroxyvitamin D (CALCITRIOL)
what is the activation pathway of vitamin D?
Dietary vitamin D
Converted to 25-hydroxyvitamin D by liver 25-hydroxylase enzyme
Converted to 1,25-dihydroxyvitamin D in kidney by 1-hydroxylase enzyme
what is the name of the active form of vitamin D?
1,25-dihydroxyvitamin D
CALCITRIOL
How does active vitamin D (calcitriol) affect calcium, phosphate and parathyroid? 3
Increases calcium and phosphate absorption in small intestine
Increases calcium and phosphate reabsorption in kidneys
Inhibits PTH release through negative feedback
what is calcitonin?
a hormone excreted by thyroid parafollicular (C-cells) that acts opposite to PTH
Inhibits osteoclast activity in bone
inhibits calcium reabsorption in kidneys
How does high phosphate affect calcium?
Phosphate ions bind to calcium ions to become calcium phosphate which reduces the amount of free calcium in the blood
Lower phosphate leads to higher serum calcium
What are 3 GI presentations of hypoparathyroidism?
malnutrition
malabsorption
diarrhoea
what are 6 presentations of hypoparathyroidism?
muscle twitches/spasms
parasthesia, numbness and tingling
convulsions
irregular heartbeat
tachycardia
Trousseau’s and Chvostek’s signs
what are the two examination signs for hypocalcaemia?
Trousseau’s sign – involuntary wrist spasm causing adduction of thumb, flexion of MCP joints and extension of interphalangeal joints with wrist flexion (Italian hand) when inflating BP cuff
Chvostek’s sign – twitching of facial muscle due to tapping over facial nerve (parotid)
What are 3 differentials for hypoparathyroidism?
hypovitaminosis D
hypomagnaesaemia
renal failure/CKD
a deficiency of what mineral exacerbates hypocalcaemia?
magnesium
what are 3 complications of hypoparathyroidism?
Renal stones
Ectopic calcifications
Renal failure
Cataracts
arrythmia, cardiac arrest, tetany, death
What are 5 investigations for hypoparathyroidism?
PTH
Calcium
phosphate
magnesium
Vitamin d
ECG - Long QT
what are the 2 forms of thyroid hormone?
Triiodothyronine - T3
Thyroxine - T4
what is the physiology of the thyroid gland?
Hypothalamus produces TRH
TRH stimulates anterior pituitary to secrete TSH
Thyroid gland produces T4+T3 in response to TSH by oxidising iodide to iodine and adding it onto tyrosine residues on thryroglobulin using thyroid peroxidase (TPO)
Most T3/4 is bound to thyroglobulin, only free T3/4 is active
Free thyroid hormones act on hypothalamus as -ve feedback
which thyroid hormone is produced more?
T4 > T3
Free T4 more reliable indicator of thyroid function on testing
what is the half life of T4?
1 week - need to wait a few weeks before retesting T4
what is primary hypothyroidism?
due to pathology affecting the thyroid gland (hashimotos) OR iodine deficiency
what is secondary hypothyroidism?
due to pathology affecting the pituitary - pituitary apoplexy or tumour - OR hypothalamic disorders and drugs
What are 6 causes of primary hypothyroidism?
Hashimotos (most common cause in developed world)
iodine deficiency
De Quervain’s thyoiditis
Post-partum thyroiditis
Riedel’s thyroiditis
Thyroidextomy/radiation
Drugs - amiodarone, lithium, antithyroid drugs (carbimazole)
what is De Quervain’s thyroiditis?
Subacute thyroiditis occurring after viral infection
Phase 1 - 3-6 weeks of hyperthyroidism, painful goitre, raised ESR
phase 2 - 1-3 weeks euthyroid
phase 3 - weeks to month - hypothyroidism
phase 4 - back to normal
what is seen on thyroid scintigraphy in de Quervain’s thyroiditis?
globally reduced uptake of iodine-131
what are 5 causes of secondary hypothyroidism?
Tumours - pituitary adenoma
Surgery to pituitary
radiotherapy
Sheehan syndrome - major PPH causes avascular necrosis of pituitary
Trauma
what are 3 drugs that can inhibit TSH secretion?
Cocaine
Steroids
Dopamine
what are 7 risk factors for hypothyroidism?
Female
Middle age
Post-partum
radiotherapy
Autoimmune conditions - T1DM, coeliac
Genetic disorders - turners, downs
FHx
What are 8 presentations of hypothyroidism?
lethargy
constipation
weight gain
dry/coarse skin and hair
bradycardia
Goitre
cold sensitivity
Menorrhagia, oligomenorrhoea and amenorrhoea
what are 3 initial investigations for hypothyroidism?
Thyroid function tests - TSH increased and T3/4 low in primary, both low in secondary
Antibody tests - Anti-TPO in hashimotos
Inflammatory markers - raised in De Quervain’s thyroiditis
what is the first line management of hypothyroidism?
levothyroxine 50-100mcg OD starting dose
Review every 3 months initially then annually once stable
start on 25 mcg OD in >64 or Hx of IHD
What 2 drugs reduce absorption of levothyroxine?
Iron
alcium carbonate
should take >4 hours apart
what happens to thyroxine demand in pregnancy?
Higher demand => dose usually increased 25-50 mcg
what are 5 complications of hypothyroidism?
CVD - hypercholesterolaemia
Neruo - carpal tunel, peripheral neuropathy
Myxoedema coma - confusion, hypothermia, hypoglycaemia, hypoventilation, hypotension
Increased risk of lymphoma
what is subclinical hypothyroidism?
Elevated TSH but normal T4 levels - can cause or not cause symptoms
requires regular monitoring
TSH >10 + T4 normal - consider thyroxine
TSH 5.5-10 and T4 normal - consider 6 month trial of thyroxine in <65 years
what are 4 side effects of thyroxine?
Hyperthyroidism
AF
Osteoporosis
Angina
What is phaeochromocytoma?
A tumour arising from catecholamine-producing chromaffin cells of the adrenal medulla which produces catecholamines (ADRENALIN)
what are 3 genetic disorders which increase risk of Phaeochromocytoma?
Multiple endocrine neoplasia 2 (MEN2)
Neurofibromatosis 1
Von Hippel-Lindau disease
what % of Phaeochromocytomas are bilateral, cancerous and outside the adrenal gland?
10% of each
are extra-adrenal phaeochromacytomas more common in children or adults and are they more likely to be malignant or not?
Children
more likely to be malignant
what are 6 key presentations of phaeochromacytomas?
Episodic
Anxiety
Palpitations + tachycardia
Hypertension
Diaphoresis
Tremor
Headache
What are 2 initial investigations for phaeochromacytomas?
24h urinary metanephrines
Plasma free metanephrines
what are 4 differentials of phaeochromacytomas?
anxiety and panic attacks
essential hypertension
hyperthyroidism
cardiac arrhythmias
what is the management of phaeochromacytomas?
Medical stabalisation THEN surgery
Alpha blockers - phenoxybenzamine or doxazosin
Beta blockers - only AFTER alpha blockers
Surgical removal of tumour - adrenalectomy
what is 1 complication of phaeochromacytoma?
hypertensive crisis - if beta blockers started before alpha
what are 3 risk factors for pituitary adenomas?
MEN-1
familial associated pituitary adenoma
Carney complex
What are 4 key presentations of pituitary adenomas?
compressive effects - headache, bitemporal hemianopia, cranial nerve palsy, DI
Cushing’s
Acromegaly
Prolactinoma - galactorrhea, lack of libido, erectile dysfunction
what is the most common type of pituitary adenoma?
prolactimona
what is classed as a micro pituitary adenoma vs a macro pituitary adenoma?
micro <1cm
macro >1cm
What are 3 investigations that can be done in pituitary adenomas?
Non-contrast MRI head
Visual field testing
Pituitary blood profile - GH, Prolactin, ACTH, FSH, LSH, TFTs
what are 4 differentials for pituitary adenomas?
pituitary hyperplasia
craniopharyngioma
meningioma
brain mets
what is the management of pituitary adenomas?
Medical
- Prolactinoma - cabergoline
- GH secreting - somatostatin analogues, GH receptor antagonists
transphenoidal surgery
radiotherapy
what are 6 causes of raised prolactin?
6Ps
Pregnancy
Prolactinoma
Physiological - stress, ecercise, sleep
PCOS
Primary Hypothyroidism
Phenothiazines, metoclopramide, domperidone
what are features of excessive prolactin in men and women?
Men - impotence, loss of libido, galactorrhoea
Women - amenorrhoea, galactorrhea, infertility, osteoporosis
what are 3 complications of pituitary adenomas?
meningitis
Diabetes insipidus
hypopituitarism
What is pituitary apoplexy?
sudden enlargement of pituitary tumour (usually non-functioning macroadenoma) secondary to haemorrhage or infarction
what are 4 precipitating factors for pituitary apoplexy?
Hypertension
pregnancy
trauma
anticoagulation
what are 6 features of pituitary apoplexy?
sudden onset headache
vomiting
neck stiffness
visual field defects - bitemporal superior quadrantic defect
extraocular nerve palsies
pituitary insufficiency
what is the 1st line investigation of pituitary apoplexy?
MRI head
what is the management of pituitary apoplexy?
Steroid replacement - due to loss of ACTH
Fluid balance
Surgery
what is primary hyperparathyroidism?
Excess secretion of PTH leading to hypercalcaemia
usually due to a parathyroid adenoma
what causes primary hyperparathyroidism?
80% due to benign parathyroid adenoma
Genetics -
MEN1/2A/4 , hyperparathyroidism jaw tumour syndrome, familial isolated primary hyperparathyroidism
<1% due to parathyroid malignancy
what are 4 risk factors for primary hyperparathyroidism?
female
Older age - >50-60
FHx
MEN 1/2A/4
what is the pathophysiology of primary hyperparathyroidism?
PTH is inappropriately not suppressed in normal or high calcium levels leading to over stimulation of bone resorption, kidney absorption and vitamin D conversion causing calcium levels to rise
What are the 4 clinical presentations of primary hyperparathyroidism?
Most commonly asymptomatic
Symptoms of hypercalcaemia - bones, stones, moans, groans
Polyuria, parasthesia, muscle cramps
what are 3 investigations of primary hyperparathyroidism?
Serum calcium
Serum PTH
Kidney function tests - CKD can lead to secondary/tertiary hyperparathyroidism
Vitamin D
US neck
Sestamibi scan
4D CT neck
what are 4 differentials for primary hyperparathyroidism?
secondary/tertiary hyperparathyroidism
familial hypocalciuric hypercalcaemia
Malignancy - multiple myeloma
medications - thiazides
what is the management of primary hyperparathyroidism?
1 - parathyroidectomy, monitoring
Calcitonin
Cinacalcet - mimics calcium to cause negative feedback
Desunomab
Bisphosphonates
what are 4 complications of primary hyperparathyroidism?
Osteoporosis + fractures
Kidney stones and injury
Hypertension and CVD
GI disorders - peptic ulcers, pancreatitis, gall stones
what are 4 indications for parathyroidectomy in primary hyperparathyroidism?
Symptomatic disease - hypercalcaemia, osteoporosis, renal stones
>50 years
serum calcium >2.85
eGFR <60
what is secondary adrenal insufficiency?
decreased cortisol production as a result of negative feedback on the hypothalamic-pituitary-adrenal axis, caused by excess glucocorticoids
what kind of patients is secondary adrenal insufficiency common in?
those treated with glucocorticoids - asthma, COPD, arthritis
what 3 causes of secondary adrenal insufficiency?
exogenous glucocorticoids
glucocorticoid secreting adrenal adenomas
hypothalamic pituitary disease
what are 2 risk factors for secondary adrenal insufficiency?
glucocorticoids
medroxyprogesterone use
what is the pathophysiology of secondary adrenal insufficiency?
Exposure to excess glucocorticoids => negative feedback to hypothalamus-pituitary-adrenal axis => patients may have Cushing’s symptoms due to excess glucocorticoids
What are 5 clinical presentations of secondary adrenal insufficiency?
tachycardia
hypotension
Cushingoid examination features
shock - fatigue, abdo pain, weakness, vomiting, hypotension
What are 5 investigations for secondary adrenal insufficiency?
serum chemistry panel - electrolyte abnormalities
serum a.m cortisol - low
salivary am cortisol - low
FBC - WBCs may be elevated
thyroid function test - possible elevated free thyroxine
what is the gold standard test for secondary adrenal insufficiency?
ACTH stimulation test - cortisol levels won’t rise enough in secondary adrenal insufficiency
what are 4 differentials for secondary adrenal insufficiency?
primary adrenal insufficiency
pituitary compression
tumour
head trauma
what is the treatment for primary adrenal insufficiency ?
hydrocortisone - in crisis
double dose corticosteroid in minor crisis
corticosteroid taper in stable patients
supportive measures
what are 2 complications of primary adrenal insufficiency?
corticosteroid dependence
permanent recurrence of adrenal crisis
What is syndrome of inappropriate ADH?
Continues secretion of ADH despite plasma being very dilute leading to retention of water, excess blood volume and hyponatraemia
what is the most common electrolyte disorder?
hyponatraemia
what is syndrome of inappropriate antidiuretic hormone?
Increased release of ADH from the posterior pituitary leading to increased water reabsorption from urine causing diluted blood and hyponatraemia
what is the pathophysiology of SIADH?
either increased secretion of ADH by posterior pituitary or ectopic ADH secretion commonly from small cell lung cancer
increased ADH leads to increased water reabsorption in collecting ducts which leads to euvolaemic hyponatraemia and concentrated urine with a high osmolality
What are 7 causes of SIADH?
Post operative
Malignancy - Small cell lung cancer
lung infection - atypical pneumonia, lung abscesses
Brain pathologies - head injury, stroke, IC haemorrhage, meningitis
Medication - SSRIs, carbamazepine
HIV
what are 6 risk factors for SIADH?
50+
pulmonary conditions
malignancy
Drugs
what are 6 clinical manifestations of SIADH?
Headache
fatigue
muscle aches and cramps
confusion
seizures
what are 5 investigations for SIADH?
Serum sodium - low
Serum osmolality - low
serum urea - usually low
urine osmolality - high
urine sodium - high
what is the plasma osmolality equation?
plasma osmolality = 2 (Na+) + 2(K+) + glucose + urea (all in mol/L)
what is the management for SIADH?
Fluid restriction - 540-1000ml per day
Vasopression receptor antagonist - tolvaptan - causes rapid rise in sodium
what is a complication of SIADH?
central pontine myelinolysis
what can cause central pontine myelonolysis?
rapid sodium serum correction >12mEq/L/Day
what is the most common endocrine malignancy?
thyroid cancer
when is thyroid cancer most common?
early adulthood - 30s-40s
what are the 4 most common thyroid cancers?
papillary
follicular
anapaestic
medullary
what are 3 risk factors for thyroid cancer?
head and neck irradiation
female
FHx
What are 6 presentations of thyroid cancer?
palpable thyroid nodule
hoarse voice
dyspnoea (SOB)
dysphagia
rapid neck enlargement
tracheal deviation
what are 4 investigations for thyroid cancer?
Thyroid function test
Neck ultrasound - nodules
fine needle biopsy
larangoscopy
what are 2 differentials for thyroid cancer?
benign thyroid nodule
goitre
what is the management of thyroid cancer?
surgery - lobectomy
radioactive iodine ablation
TSH suppression
chemo
thyroid replacement after
what are 4 complications of thyroid cancer?
hypocalcaemia (parathyroid injury)
airway obstruction
recurrent laryngeal nerve injury
secondary tumours
where is erythropoietin produced and what does it do?
kidneys (peritubular cells)
stimulates maturation of erythrocytes
What is the blood supply to the adrenal glands?
superior adrenal artery - from inferior phrenic
middle adrenal artery - from abdominal aorta
inferior adrenal artery - from renal artery
what does the zone glomerulosa produce?
Mineralocorticoids - ALDOSERONE
what does the zona fasiculata produce?
Glucocorticoids - CORTISOL
what does the zona reticularis produce?
ANDROGENS
what are corticosteroids?
mineralocorticoids + glucocorticoids (aldosterone + cortisol)
what do mineralocorticoids do?
regulate body electrolytes
aldosterone - maintain salt balance, BP, RAAS
what triggers the secretion of aldosterone?
release of renin by juxtaglomerular cells in afferent arterioles of kidneys
what is the function of cortisol?
suppresses immune system
inhibits bone formation
increases metabolism - protein catabolism & lipolysis, gluconeogenesis, increases alertness.
what triggers secretion of cortisol?
stress => hypothalamus => corticotrophin releasing hormone (CRH) => anterior pituitary => adrenocorticotropic releasing hormone (ACTH) => cortisol release from adrenal cortex
what does adrenaline release stimulate?
gluconeogenesis
lipolysis
tachycardia
redistribution of circulating volume
vasoconstriction
vasodilation (due to less noradrenaline)
what vertebral level is the thyroid located at?
C5-T1
what is the connection called in the thyroid?
isthmus
what arteries supply the thyroid?
superior and inferior thyroid arteries
what week in utero does thyroxine begin to be releases?
18-20 weeks
what is produced in the parafolicular cells/ C cells?
calcitonin
what is produced in the follicular cells of the thyroid?
T3 and T4
what does the follicle of the thyroid contain?
thyroglobulin - iodine store
what embryological tissue is the anterior pituitary formed from?
Ectoderm - Rathke’s pouch
what embryological tissue if the posterior pituitary formed from?
floor of the 3rd ventricle
what 6 hormones are released by the hypothalamus?
corticotropin releasing hormone - CRH
GHRH
thyrotropin releasing hormone - TRH
Gonadatrophin releasing hormone - GnRH
Dopamine
what 6 hormones are released by the anterior pituitary?
FSH - follicle stimulating hormone
LH - luteinizing hormone
Adrenocorticotrophic hormone - ACTH
TSH - thyroid stimulating hormone
Prolactin
Growth Hormone
FLAT PG
What 2 hormones are released from the posterior pituitary?
Anti-diuretic hormone
Oxytocin
Where in the brain is the ADH release stimulated from in the brain?
supraoptic nucleus
Where in the brain is the oxytocin release stimulated from in the brain?
paraventricular nucleus
what do delta cells in the pancreas release?
somatostatin
What is thyroid storm?
A rare but life threatening condition of untreated thyrotoxicosis (hyperthyroidism) causing irritability, high systolic and low diastolic BP, tachycardia, nausea, vomiting and diarrhoea
what is the most common cause of Primary hyperaldosteronism ?
Idiopathic adrenal hyperplasia
what does the RAAS system regulate?
BP
Electrolyte balance
Blood vessel and cardiac remodelling
where is renin secreted from?
Juxtaglomerular cells at afferent arterioles
Sense BP and increase renin production when BP is low
where is angiotensin produced?
liver
where is angiotensin I converted to angiotensin II?
Lungs by ACE
what are 3 effects of angiotensin II?
Vasoconstriction
Hypertrophy and remodelling of heart and blood vessels if chronically high
Stimulates aldosterone release by adrenals
what is the action of aldosterone?
Increases sodium reabsorption in distal tubule
Increases potassium secretion in distal tubule
Increases H+ secretion from collecting ducts
Leads to increased fluid retention, increased BP, hypernatremia and hypokalaemia
what is the synthetic form of aldosterone?
Fludrocortisone
what are 3 features of Primary hyperaldosteronism ?
Hypertension
Hypokalaemia
Metabolic alkalosis - due to H+ excretion
what is the 1st line investigation for Primary hyperaldosteronism?
Plasma aldosterone/renin ratio
High aldosterone, low renin
what imaging is used in Primary hyperaldosteronism ?
high resolution CT abdo
If normal also Adrenal venous sampling
what is the management of Primary hyperaldosteronism?
Aldosterone antagonist - spironolactone or eplerenone
What is Conn’s syndrome?
Primary hyperaldosteronism due to adrenal adenocarcinoma secreting aldosterone
Causes excessive sodium reabsorption leading to hypertension and suppression of renin and angiotensin II
What is the pathophysiology of Conn’s syndrome?
Aldosterone producing adenoma => Excessive aldosterone production => increased sodium absorption from distal tubule => if severe hypokalaemia and metabolic acidosis
what is the management of Conn syndrome?
Laparoscopic adrenalectomy (to remove adrenal adenoma)
what organ is the major consumer of glucose in the body?
the brain
what are 3 hormones that increase glucose production in liver and reduce utilisation in fat and muscle?
cortisol
adrenaline
GH
what chromosome codes for insulin?
11
what peptide isn’t present in synthetic insulin?
C peptide
what transported proteins allow beta cells to sense glucose levels in the blood?
GLUT 2
what is a diagnostic random blood glucose value for diabetes?
> 11 mmol/L
what is a diagnostic fasting blood glucose level for diabetes?
> 7 mmol/L
what is a diagnostic oral glucose tolerance test level for diabetes?
> 11 mmol/L
what is the leading cause of death in diabetic patients?
CVD
what vertebral levels are the thyroid glands located between?
C5-T1
what is the connection between the 2 lobes of the thyroid gland called?
isthmus
what 3 disease have diffuse goitres?
Grave’s
Hashimotos
De Quervain’s
What 3 conditions have nodular goitres?
Multi-nodular
Adenomas/cysts
Carcinomas
what is the most common type of thyroid carcinoma?
papillary
what is thyrotoxicosis?
clinical manifestation of excess thyroid hormone action at the tissue level due to high circulating thyroid hormone concentrations.
what is the antibody is grave’s disease?
Anti TSH antibody
what is the treatment of a thyroid storm?
IV fluids
antithyroid drugs - Propylthiouracil/carbimazole
IV hydrocortisone
B Blockers
what thyroid disorder has raised inflammatory markers?
De Quervain’s
what 3 things does ACTH stimulate the release of from the adrenals?
mineralocorticoids
glucocorticoids
gonadocorticoids
what does the zone glomerulosa respond to?
RAAS system
what is the action of aldosterone?
works on kidney to increase blood volume, increase BP. May also cause hypernatraemia.
what is the action of cortisol?
suppresses immune system, inhibits bone formation, increases metabolism - protein catabolism & lipolysis, gluconeogenesis, increases alertness.
what is the action of gonadocorticoids?
production of oestrogen and testosterone. Main role is controlling libido.
when are cortisol levels at their highest?
7-9 am
what hormone inhibits GH secretion?
somatostatin
what hormone stimulates the release of GH?
Ghrelin
what is an adrenal crisis?
acute insufficiency of adrenocortical hormones usually caused by infection or MI causing hypotension, shock and coma
what is the management for an adrenal crisis?
IV fluids
Corticosteroids - hydrocortisone IV
treat underlying cause
what is diabetes insipidus?
a metabolic disorder characterised by an absolute or relative inability to concentrate urine, resulting in the production of large quantities of dilute urine due to either a lack of production or response to ADH
where is ADH produced and secreted from?
produced - hypothalamus
secreted - posterior pituitary
what are 5 nephrogenic causes of diabetes insipidus?
Medications - lithium
Genetics - ADH receptor gene mutations
Hypercalcaemia
Hypokalaemia
Kidney disease - polycystic kidney disease
what is the inheritance pattern of ADH receptor gene mutations?
X-linked recessive
what are 7 cranial causes of diabetes insipidus?
Brain tumours
Brain injury
Brain surgery
Brain infections
Genetic mutations in ADH gene
Wolfram syndrome - genetic condition causing optic atrophy, deafness, DM + DI
Infiltration - sarcoidosis, hystiocytosis
what is the inheritance pattern of mutations in ADH gene leading to diabetes insipidus?
Autosomal dominant
what are 4 manifestations of diabetes insipidus?
Polyuria - >3L urine/day
Polydipsia
Dehydration
Postural hypotension
what are 4 investigations for diabetes insipidus?
Urine osmolality - Low
Serum osmolality - high/normal - due to increased intake
>3L in 24 hour collection
Water deprivation test
what is the gold standard investigation for diabetes insipidus?
water deprivation (desmopressin suppression) test
what is the water deprivation test?
no water for 8 hours - measure urine osmolality
If low - give desmopressin and measure urine osmolality again 2-3 hours
If cranial cause - after desmopressin given osmolality will be high as kidneys can still respond to synthetic ADH
If nephrogenic cause - after desmopressin given urine osmolality will still be low as kidneys cannot respond
what are 2 management options for DI?
Tx cause
Cranial - Desmopressin
Nephrogenic -
ensure acess to pleanty of water
High dose desmopressin
thiazide diuretics - paradoxically decreases urine output
NSAIDs
what is one risk associated with desmopressin?
Hyponatraemia
what are the 2 most common causes of hypercalcaemia?
Primary hyperparathyroidism - most common
Malignancy
what are 3 reasons malignancy can cause hypercalcaemia?
PTH related hormone released from tumours - small cell lung cancer, breast, renal
Bony mets
Multiple Myeloma - due to increased osteoclastic bone resorption
what are 7 other causes of hypercalcaemia?
Sarcoidosis (also other granulomas)
Vitamin d intoxication
acromegaly
thyrotoxicosis
Drugs - thiazides, calcium containing antacids
Dehydration
Addison’s disease
what are 5 manifestations of hypercalcaemia?
Bones, Stones, Groans Moans
Bone pain
Renal stones
GI groans - nausea, vom, constipation, anorexia
Psychic moans - confusion, lethargy, coma
also HTN, short QT and cardiac arrhythmias
what may be seen o/e in hypercalcaemia?
Dehydration
Hypertonia or hyporeflexia
Bone tenderness/deformity
Abdo pain/tenderness
Psychiatric abnormalities
what is a differential for hypercalcaemia?
hyperalbuminaemia - 40% of calcium is bound to albumin and therefore inactive
Look at corrected calcium
what are the 3 classifications of hyperparathyroidism?
Primary - due to hyperparathyroidism or malignancy usually - due to excessive PTH release leading to increased calcium reabsorption
Secondary - occurs in response to hypocalcaemia usually due to CKD, leads to parathyroid hyperplasia
Tertiary - parathyroid glands become autonomous and secrete PTH despite normal/high calcium due to persistent parathyroid hyperplasia
what is the management for hypercalcaemia?
Rehydration - 3-4L normal saline/day
THEN
Bisphosphonates
Corticosteroids - if due to granulomatous disease or lymphomas
Calcitonin
Loop diuretics - furosemide
Dialysis
what are 4 causes of hypocalcaemia with hyperphosphataemia?
CKD
hypoparathyroididsm
pseudohypoparathyroidism
acute rhabdomyolysis
what are 4 causes of hypocalcaemia with normal phosphate?
vitamin D deficiency
osteomalacia
acute pancreatitis
over hydration
what are 8 manifestations of hypocalcaemia?
SPASMODIC
Spasms - troussau’s
Paraesthesia
anxious
seizures
Muscle tone increase
Orientation impaired
Dermatitis
Impetigo herpetiformis
Chvosteks sign - facial muscle twitches after facial nerve tapped
what are the ECG signs of hypocalcaemia?
prolonged QT
ST
arrhythmia
torsade de pointes
AF
what is the management for hypocalcaemia?
IV calcium suplements - calcium gluconate
10ml in 100ml NaCl over 10-20 mins
Then slow IV 10% 50ml/hour
vitamin D supplements - alfacalcidol
what are 5 manifestations of neuroendocrine tumours?
diarrhoea
SOB
flushing
itching
RUQ pain - hepatic metastases
Worsened by ALCOHOL
how is insulin secreted?
hyperglycaemia leads to increased glucose uptake by cells/. Glucose metabolism leads to increased levels of ATP within the cell which causes K+ channels to close leading to the depolarisation of the cell membrane. Ca2+ channels open and calcium enters the cell. Increased calcium leads to exocytosis of insulin containing vesicles so insulin is released from the pancreatic beta cells into the blood stream.
What part of the adrenal glands are the different adrenal hormones secreted from?
GFR Makes Good Sex
Zona Glomerulosa - Mineralocorticoids - Aldosterone
Zona Fasiculata - Glucocorticoids - Cortisol
Zona Reticularis - Androgens - testosterone, dihydrotestosterone
what is used for the diagnosis of toxic multinodular goitre?
Clinical features
TFTs - low TSH, raised T3/4
Radioisotope scan - multiple hot and cold areas
what is the management of toxic multinodular goitre?
1 - Radioactive iodine
2 - Thyroidectomy
what are 4 contraindications and 3 cautions with radioactive iodine treatment?
Contraindication
- pregnancy
- <16 years
- breastfeeding
- established eye disease
Caution
- no close contact with pregnant women and children for 3 weeks
- Avoid pregnancy for 6 months
- Avoid fathering children for 4 months
what are toxic thyroid nodules?
AKA toxic thyroid adenoma
a singular benign autonomously functioning thyroid nodule
what is the main risk factor for toxic thyroid nodule?
iodine deficiency
how are toxic thyroid nodules investigated?
TFTs
TSH receptor and TPO antibodies
1 - Thyroid US
2 - Radioisotope scanning
fine needle biopsy may be needed
what is the management of toxic thyroid nodule?
Radioactive iodine therapy
Thyroidectomy
what are 3 complications of thyroidectomy?
Recurrent laryngeal nerve injury
Transient hypocalcaemia
Hypothyroidism
what are 4 benign causes of thyroid nodules?
Multinodular goitre
Thyroid adenoma
Hashimoto’s
Cysts
what are 5 malignant causes of thyroid nodules?
Papillary carcinoma - most common
Follicular carcinoma
Medullary carcinoma
Anaplastic carcinoma
Lymphoma
what is the 1st line investigation of thyroid nodules?
Ultrasound
what investigations can be done of thyroid nodules?
US
Radiolabelled iodine uptake scan
Fine needle aspiration
core needle biopsy
TFTs
what is classed as hypoglycaemia?
BG <4.0 mmol/L
what are 6 causes of hypoglycaemia?
Self administration of insulin/sulphonylures
Liver failure
Addison’s disease
Alcohol - causes exaggerated insulin secretion
Insulinoma
Nesidioblastosis
what is the physiological response to hypoglycaemia?
Decreased insulin secretion
Increased glucagon release
Increased GH and cortisol release
Increased adrenergic and cholinergic neurotransmission in peripheral autonomic nervous system and CN system
what is the usual presentation of mild-moderate hypoglycaemia (2.8-3.3)?
Sweating
Shaking
Hunger
Anxiety
Nausea
what is the presentation of severe hypoglycaemia (usually <2.8)?
Weakness
Vision changes
Confusion
Dizziness
Convulsions
Coma
what is C-peptide a marker of?
Endogenous insulin production - released from pancreas in same molar amounts as insulin
what are 2 potential causes of high insulin, high c-peptide hypoglycaemia?
Endogenous insulin production
Insulinoma
Sulfonylureas
what is the cause of high insulin, low c-peptide hypoglycaemia?
Exogenous insulin - overdose or factitious disorder
what are 5 causes of low insulin, low c-peptide hypoglycaemia?
Alcohol induced
Critical illness - sepsis
Adrenal insufficiency
Growth hormone deficiency
Fasting/starvation
what is the initial management of hypoglycaemia in an awake patient?
Oral glucose 10-20g liquid, gel or tablet
Other quick acting carbohydrate
Recheck BMs in 10-15 mins
Repeat up to 3 times!
What is the management of hypoglycaemia in an unresponsive patient?
IM glucagon
IV 20% dextrose - 75-100ml
what should be given after acute management of hypoglycaemia when BMs return to >4?
Long acting carbohydrate - biscuits, bread, milk, normal carbohydrate containing meal
what is Whipple’s triad of hypoglycaemia?
Symptoms of hypoglycaemia
low serum glucose
resolution of symptoms with administration of glucose
what is 1 caution to IV glucose administration?
Thiamine deficiency - IV glucose can precipitate wernike’s encephalopathy
Administer with B1 (thiamine)/pabrinex
what tool is used for 10 year risk of cardiovascular disease?
QRISK3
at what Qrisk should a statin be offered and at what dose?
10%
20mg Atorvastatin at night
what counts as high blood pressure in clinic?
> 140/90 mmHg
what counts as hypertension in ambulatory monotoring?
> 135/85 mmHg
what 4 tests can be done for end organ damage in HTN diagnosis?
Urine sample for estimated albumin:creatinine ratio and haematuria
Bloods - HbA1c, electrolytes, eGFR, creatinine, cholesterol
Fundoscopy - for retinopathy
ECG
what is the first line intervention for HTN?
LIFESTYLE ADVICE
Low salt diet <6g per day
reduce caffeine intake
Stop smoking
reduce drinking
what is the first line medication for HTN in those <55 and of non-African family origin or anyone with T2DM or CKD?
ACEi (ramipril) or ARB (candestartan)
what can ACEi cause in CKD?
Worse renal function
up to 25% rise in eGFR or 30% rise in creatinine is acceptable
what is the first line medication for HTN in someone >55 or of African family origin?
Calcium channel blockers - amlodipine
what can be used for HTN if a calcium channel blocker isn’t tolerated or as 3rd line medication?
thiazide-like diuretic (indapamide, bendroflumethiazide)
what is the management of HTN uncontrolled by one agent?
ADD CCB/ACEi
OR Thiazide-like diuretic
what is the management of HTN uncontrolled by two agents?
CCB + ACEi AND Thiazide-like diuretic (1 - indapamide)
what is the management of HTN not controlled by three agents?
Consider Spironolactone (If K+ <4.5)
Consider Beta blocker/Alpha blocker (if K+ >4.5)
what is classed as severe hypertension?
180/120 mmHg
what is stage 1 HTN?
Clinical - 140/80 mmHg to 159/99mmHg
Home - 135/85 - 149/94
what is stage 2 HTN?
Clinical - 160/100 - 180/120
Home - 155/95 - 175/115
what is stage 3 HTN?
180/120 +
what is the white coat effect?
discrepancy of 20/10mmHg between clinical and home BP
what are 5 general causes of hypertension?
ROPED
Renal disease
Obesity
Pregnancy and Pre-eclampsia
Endocrine
Drugs - alcohol, steroids, NSAIDs, oestrogen, liquorice
what are 5 renal causes of secondary HTN?
CKD
Chronic pyelonephritis
Diabetic nephropathy
Glomerulonephritis
Polycystic kidney disease
what are 2 vascular causes of secondary HTN?
coarctation of aorta
rental artery stenosis
what is one cause of treatment resistant hypertension?
renal artery stenosis
what are 5 endocrine causes of HTN?
Primary hyperaldosteronism (Conn syndrome)
Phaeochromocytoma
Cushings syndrome
Acromegaly
Liddle syndrome
what are 5 drugs that can cause HTN?
alcohol + other substances
COCP/Oestrogens
Monoamine oxidase inhibitors
corticosteroids
NSAIDs
what are 4 side effects of NSAIDs?
GI - gastritis, ulcers
renal - AKI (acute tubular necrosis), CKD
CV - HTN, heart failure, MI, stroke
exacerbation of asthma
how do NSAIDs cause HTN?
block prostaglandins which cause vasodilation => use with caution in HTN
what are 4 medications used to treat hypertensive emergency?
Sodium nitroprusside
Labetalol
Glyceryl trinitrate
Nicardipine
what is the lower limit of normal BP?
90/60
who are ACEi contraindicated in?
Pregnant women
what are 3 side effects of ACEi?
Cough
Angioedema
Hyperkalaemia
what are 3 side effects of CCB?
Flushing
Ankle swelling
headache
what are 3 side effects of thiazide diuretics?
Hyponatraemia
Hypokalaemia
Dehydration
what is the most common cause of secondary hypertension?
Primary hyperaldosteronism
BMI =
weight/height squared
what are 2 measures of obesity?
BMI
Waist to height ratio
what are 6 medical conditions that can cause obesity?
Prader-willi
Hypothalamic damage
PCOS
Growth hormone deficiency
Cushing’s syndrome
Hypothyroidism
what are 9 medications that increase risk of obestiy?
Pizotifen
beta-blockers
corticosteroids
lithium
antipsychotics
anticonvulsants
antidepressants
insulin in T2DM
oral hypoglycaemics
what is the medical management of obesity?
orlistat
liraglutide
when is orlistat used in obesity?
BMI >28 with 2+ risk factors
BMI >30
with continued weight loss of 5% at 3 months
use for <1 year
how does orlistat work?
pancreatic lipase inhibitor
How does liraglutide work in relation to obesity?
glucagon-like peptide mimetic used in T2DM given OD SC injection
when is liraglutide used in obesity?
BMI > 35 kg/m²
prediabetic hyperglycaemia (e.g. HbA1c 42 - 47 mmol/mol)
who should be referred for bariatric surgery?
BMI >40
what are 5 options for bariatric surgery?
Laparoscopic adjustable gastric banding
Sleeve gastrectomy
Intragastric balloon
Biliopancreatic diverstion with duodenal switch
Roux-en Y gastric bypass surgery
what is an insulinoma?
the most common pancreatic endocrine tumour deriving mainly from pancreatic islets of langerhans
10% are malignant
Associated with multiple endocrine neoplasia-1 (MEN1)
what are 4 features of insulinoma?
Hypoglycaemia
rapid weight gain
high insulin and raised proinsulin:insulin ratio
high c-peptide
what is used to diagnose insulinoma?
supervised prolonged fasting
CT pancreas
what is the management of insulinomas?
Surgery
Diazoxide and soamtostatin analogues (Octreotide) if not surgical candidates
what are 4 risk factors for insulinoma?
female
40-60 years
MEN-1
Neurofibromatosis 1
Von Hippen-Lindau syndrome
what is a carcinoid tumour?
slow growing neuroendocrine tumour that grows in lungs, intrabdominally, in the breast, testes or ovaries and releases excessive hormones mainly SEROTONIN
when is a carcinoid tumour problematic?
when metastasises to liver
if tumour is in lungs
what are 3 risk factors for carcinoid tumours?
Age 50-60
MEN1
Smoking
what are 7 features of carcinoid syndrome?
skin flushing
diarrhoea
SOB
abdo pain
wheeze
pansystolic murmur loudest over 4th intercostal - tricuspid regurgitation
Telangiectasia
what are 2 investigations for carcinoid tumours?
urinary 5-HIAA -24h collection
Serum chromogranin A - tumour marker
what is the management of carcinoid tumours?
surgey if localised tumour
somatostatin analogues - octreotide or lanreotide
what are 4 complications of carcinoid tumours?
carinoid heart disease
bowel obstruction
metastasis
cushings - if tumour secretes ACTH
what is the inheritance pattern of multiple endocrine neoplasia?
autosomal dominant
what are 3 tumours that MEN-1 is a risk factor for?
3Ps
Parathyroid - 95%
Pituitary - 70%
Pancreas - insulinoma, gastrinoma
what is the most common presentation of MEN1?
hypercalcaemia
what are 3 tumours that MENIIa makes more likely?
2Ps and 1M
Medullary thyroid cancer
Parathyroid
Phaeochromocytoma
what are 3 tumours MENIIb makes more common?
1P and 2Ms
Medually thyroid cancer
Marfanoid habitus and mucosal neuromas
Phaeochromocytoma
what 2 hormones are secreted by small cell lung cencers?
ADH
Adrenocorticotrophic hormone (ACTH)
what are 4 paraneoplastic features associated with squamous cell lung cancer?
parathyroid hormone-related protein release causing hypercalcsemia
clubbing
hypertrophic pulmonary osteoarthropathy
Hyperthyroidism due to ectopic TSH release
what are 2 paraneoplastic features of adenocarcinoma of the lung?
gynaecomastia
hypertrophic pulmonary osteoarthropathy
