Endocrine Flashcards
Define endocrine
These glands ‘pour’ secretions directly into blood stream, without ducts
e.g. thyroid, adrenal, beta cells of pancreas
Define exocrine
These glands ‘pour’ secretions through a duct to site of action
e.g. submandibular, parotid, pancreas (amylase & lipase)
Describe the action of endocrine hormones
Blood-borne, acting on distant sites
Describe the action of paracrine hormones
Acting on nearby adjacent cells
Describe the action of autocrine hormones
Feedback on same cell that secreted hormone - acts on itself
Define Diabetes Mellitus T1
Autoimmune disease, causes the destruction of beta cells leading to insulin deficiency
∴ hyperglycaemia
Epidemiology DMT1
Usually younger < 30 years
↑ Northern Europe, esp Finland!
Incidence is increasing
22yr old woman with DMT1 is pregnant - what is the chance of her child also having DMT1?
1 in 25
(It is accepted that the child of any women below 25 years has a 1 in 25 chance of getting T2DM)
Monitoring of T2DM
HbA1c checked after 6 months
Checks for CVD, diabetic retinopathy, nephropathy, neuropathy etc done annually
What is LADA?
Latent Autoimmune diabetes in adults
‘Slow burning’ variant of DMT1 - slower progression to insulin deficiency, occurs in later life
∴ can be difficult to differentiate from DMT2
RF DMT1
Genetic susceptibility -
HLA-DR3-DQ2 or HLA-DR4-DQ8
Other autoimmune diseases
Vit D def
Enteroviruses e.g. Coxsackie B4
Why does polydipsia occur in DMT1?
Results of fluid and electrolyte loss
Why does polyuria occur in DMT1?
Result of osmotic diuresis
When blood glucose levels > renal tubular reabsorptive capacity
Why must DMT1 Px have insulin?
They are more prone to diabetic ketoacidosis
Key presentation of DMT1
2-6 week history of :
Unexplained weight loss, polyuria, polydipsia
State 1 other signs of DMT1
Breath may smell of ‘pear drops’ (KETONES)
Ix DMT1
Fasting plasma glucose (no food for 8hrs)
Random plasma glucose
Oral glucose tolerance test
Diagnostic values for DM
In symptomatic patient :
Symptoms + raised plasma glucose detected ONCE
If Asymptomatic, must show raised glucose on TWO SEPARATE occasions
–
Fasting glucose ≥ 7mmol/L (6mmol/L)
Random glucose ≥ 11.1 mmol/L
HbA1c ≥ 48 mmol/mol (41 mmol/mol)
If between normal and fasting, PRE-DIABETIC (T2)
What is the most common way children present with new T1DM?
Diabetic ketoacidosis
Tx DMT1
Patient education!!
BASAL BOLUS INSULIN
SC insulin - combo of long acting insulin (basal) od
& short acting insulin (bolus) injected 30 mins before meals
Define DMT2
Relative insulin def due to combination of insulin resistance and less severe insulin def
4 non-modifiable RF DMT2
> 40 years
Ethnicity - Black, Chinese, South Asian
FHx
Male
4 modifiable RF DMT2
Obesity
Sedentary lifestyle
High carbohydrate diet
HTN
Key presentation of DMT2
Usually asymptomatic and found incidentally on routine blood tests
Symptoms of a Px w/ severe T2DM
acanthosis nigricans
GS Ix DMT2
HbA1c test ! (tells us avg. BG for last 3 months)
State some complications of insulin treatment
Hypoglycaemia!
Lipohypertrophy (at injection site)
Insulin resistance
Weight gain - bc insulin makes people feel hungry
Tx DMT2
Lifestyle modifications first !!
- Metformin
- If HbA1c rises to 58 mmol/mol, dual therapy :
Metformin + sulphonylurea e.g. gliclazide
Metformin + DPP4 inhibitor e.g. sitagliptin
Metformin + pioglitazone
Metformin + SGLT-2i (glifazon) - If STILL remains at 58 mmol/mol, triple therapy :
Metformin + SU + DPP4 inhibitor
Metformin + SU + pioglitazone
Metformin + SU/pioglitazone + SGLT-i
–
IF symptomatic, SU or insulin until BG stable
Name some macrovascular complications of diabetes mellitus
Stroke
Ischaemic heart disease
Peripheral vascular disease
Which sex is at more risk of macrovascular complications of DM?
Neither - DM removes vascular advantage that females have
What can be given to DM patients to reduce the risk of macrovascular complications?
Statin
ACE-I
What are some microvascular complications of DM?
Diabetic neuropathy
Diabetic retinopathies
Diabetic nephropathy
Describe the pathophysiology of Diabetic neuropathy
Occlusion of vasa nervorum and accumulation of fructose and sorbitol
Disrupts structure and function of nerves
How can diabetic foot ulceration occur/get so bad?
Diabetic neuropathy increases risk of Px not noticing ulceration.
Also, causes skin dryness of foot ∴ more susceptible to cracking and ulcers
Describe some symptoms of diabetic neuropathy
Numbness, ↓ ability to feel pain/temp changes
Tingling/burning sensation
Sharp pain/cramps
Hypersensitivity
Muscle weakness
Loss of balance/coordination
diabetic foot - ulcers!!
Diabetic foot ulcer management
FOOT SCREENING!
Patient education! - Check feet daily, tie laces for enough room, keep feet away from heat
State a common consequence of childhood diabetes relating to skin and how to demonstrate this
Skin contractures
Ask Px to join hands in prayer - MCP and IP joints cannot be opposed
Describe pathophysiology of diabetic retinopathy
XS glucose in blood
∴ glucose uptake into lens and blockage of retinal blood supply
∴ eye attempts to grow new blood vessels but don’t develop properly and can leak
State and describe the two types of diabetic retinopathy
-
Non-proliferative
new blood vessels not growing - **Proliferative
Damaged blood vessels close off ∴ new abnormal vessels grow, will leak
Ix diabetic retinopathy
Fundoscopy
Cotton wool spots and flare haemorrhages
Early indication of diabetic nephropathy
Microalbuminuria
Other types of diabetes
MODY
LADY (latent autoimmune diabetes of young)
Gestational diabetes - usually in 3rd trimester
Tx diabetic nephropathy
Aggressive BP control (ACE-I, angiotensin-II antagonists etc)
Causes of hypoglycaemia
EXPLAIN
Exogenous drugs - insulin, alcohol binge w/ no food
Pituitary insufficiency
Liver failure
Addison’s disease
Islet’s cell tumour & Immune hypoglycaemia
Non-pancreatic neoplasm e.g. fibrosarcoma
Key presentation of hypoglycaemia
Odd behaviour (aggression), sweating, tachycardia
Ix Hypoglycaemia
1st - Whipple’s triad !
1. Signs/symptoms of hypoglycaemia
2. Low BG
3. Resolution of symptoms w/ correction of BG
GS 48-72 hr fast w/ serial BG
Tx hypoglycaemia
In Community -
Oral glucose (10-20g) - liquid, gel, tablet
Px might have ‘hypokit’ w/ IM or SC glucagon
In Hospital Setting
If Px alert, quick acting carb
If unconscious/unable to swallow, SC or IM glucagon
OR IV 20% glucose solution
How does the presentation of hypoglycaemia change and at what blood glucose level?
< 3.3 mol/L - sweating, shaking, hunger, anxiety, nausea
< 2.8 mol/L - weakness, vision change, confusion
What is diabetic ketoacidosis characterised by?
- Hyperglycaemia > 11 mmol/L
- ↑ Plasma ketones > 3 mmol/L
- Metabolic acidosis - pH < 7.3
Causes/RF Diabetic ketoacidosis
Untreated DMT1 or stopping insulin therapy
Undiagnosed DM
Infection/illness
MI
What is a big and preventable cause of diabetic ketoacidosis?
When patients stop/reduce insulin suddenly (bc Px is vomiting or not eating).
INSULIN SHOULD NEVER BE STOPPED IN T1DM
Pathophysiology diabetic ketoacidosis
Complete absence of insulin results in unrestrained hepatic gluconeogenesis
∴ ↑ circulating glucose
∴ osmotic diuresis
∴ dehydration
Peripheral lipolysis occurs ∴ ↑ circulating FFAs
Oxidised to Acetyl CoA ∴ ↑ ketones
∴ metabolic acidosis
Process is accelerated by “stress hormones e.g. catecholamines, glucagon, cortisol
Secreted in response to dehydration and intercurrent illness
Why is insulin def necessary for diabetic ketoacidosis?
Because even a small elevation will inhibit hepatic ketogenesis
DKA prognosis
Medical emergency!
If untreated, can be fatal!
DKA key presentation
Dehydration, vomiting, abdominal pain, ↓ tissue turgor
DKA is rare in T2DM, more common in T1 !!
dont forget
DKA signs/symptoms
Kussmaul’s sign
‘Pear drop’ breath
Low BP
Low body temp - even in presence of infection
Sunken eyes
-
Drowsiness/confusion
DKA Ix
Usually recognised from clinical features and confirmed w/ Ix
Blood glucose measurement (BG > 11 mmol/L)
ABG ( ph < 7.3 and/or bicarbonate < 15 mmol/L)
Finger prick sample and near-patient meter (measures Beta-hydroxybutyrate) - to measure plasma ketones ( > 3 mmol/L)
–
Urine dipstick - heavy glucosuria and ketonuria
Serum U+E
DKA Tx
Immediate ABCDE management if unconscious!
Fluid replacement w/ IV 0.9% saline (NaCl)
Replace deficient insulin - IV insulin (+ glucose to prevent hypoglycaemia)
Electrolytes! K+
monitor closely and treat if necessary!
Complications of DKA & why does this occur?
Cerebral oedema
Blood is initially v conc w/ corresponding hypernatraemia.
W/ Tx, blood becomes hyponatraemic
∴ osmotic shift -> water moves from blood into tissues
In the brain, can cause swelling in enclosed space (skull). This causes rapid deterioration/coma/can be fatal.
∴ Fluid should be undertaken SLOWLY ! Over 48 hours
Describe how fluid replacement in DKA should be given
Slowly!! Over 48 hours!
Why can insulin treatment for DKA cause hypokalaemia? Why is this dangerous?
Insulin decreases K+ in blood
bc redistributes K+ into cells via ↑ Na+/K+ pump activity
∴ low serum K+
Describe the action of biguanide and give an example
Increases peripheral insulin sensitivity and hepatic glucose uptake
e.g. Metformin
Describe the action of Sulfonylurea and give an example
e.g. Gliclazide
Depolarises islet cells in pancreas ∴ ↑ insulin release
Describe the action of Thiazolidinedione and give an example
e.g. Pioglitazone
↑ Peripheral insulin sensitivity
Describe the action of SGLT-2i and give an example
e.g. Dapglifozin
↑ Urinary glucose loss
Describe the action of DPP4-i and give an example
e.g. Sitagliptin
Inhibits GLP1 breakdown
Describe the action of GLP1 analogue and give an example
e.g. Exenatide
↑ Insulin secretion and sensitivity
Describe the action of Intestinal Alpha-Glucosidase Inhibitors and give an example
e.g. Acarbose
Delays intestinal carbohydrate absorption
S/E biguanide
Lactic acidosis, GI disturbance
S/E Sulfonylurea
Hypoglycaemia, weight gain
S/E Thiazolidinediones
Fluid retention, weight gain, worsening heart failure
S/E SGLT-2i
DKA when used w/ insulin
↑ Risk of UTI
S/E DPP4-i
Hypoglycaemia, GI upset
S/E GLP1 analogues
Hypoglycaemia, GI upset
May increase risk of pancreatitis when used with DPP4-i
S/E Intestinal alpha-glucosidase inhibitors
Flatulence, GI disturbance
Define Hyperosmolar Hyperglycaemic State
Medical emergency!
Characterised by :
1. Marked hyperglycaemia
2. Hyperosmolality
3. Mild/No ketosis
Hyperosmolar hyperglycaemic state usually presents in whom?
Elderly w/ poorly controlled T2DM
Hyperosmolar hyperglycaemic state - RF
*Infection! esp pneumonia
Consumption of glucose rich fluids
Concurrent medication - thiazide diuretic or steroids
Pathophysiology of Hyperosmolar Hyperglycaemic State
↓ Endogenous insulin
Enough to inhibit hepatic ketogenesis
but not enough to inhibit hepatic glucose production
Key presentation of Hyperosmolar Hyperglycaemic State
Severe dehydration
↓ Levels of consciousness
Other signs/symptoms of Hyperosmolar Hyperglycaemic State
General : Fatigue, N+V
Neurological : Headaches, papilloedema, weakness
Haematological : Hyperviscosity - could result in MI, stroke, periph arterial thrombosis etc
Cardiovascular : dehydration, hypotension, tachycardia
Bicarbonate level in Hyperosmolar Hyperglycaemic State
NORMAL
Diagnostic values for Hyperosmolar Hyperglycaemic State
Hyperglycaemia (> 30 mmol/L)
Hypotension
Hyperosmolality (usually > 320 mosmol/kg)
Unlike DKA, NOT accompanised w/ acidosis or ketosis
Ix Hyperosmolar Hyperglycaemic State
Blood glucose
Plasma osmolality
Urine stick test
K+ levels in Hyperosmolar Hyperglycaemic State
Total body K+ is low (osmotic diuresis)
BUT serum K+ is often high bc low insulin
∴ K+ shifts out of cells
Tx of Hyperosmolar Hyperglycaemic State
Fluid replacement w/ 0.9% saline
Insulin (only if high levels of ketones/glucose don’t decrease after fluid replacement) - patients more sensitive to insulin ∴ lower rate of infusion
VTE prophylaxis (venous thromboembolism) - high risk bc severe dehydration
∴ give LMWH e.g. SC enoxaparin
Complications of Hyperosmolar Hyperglycaemic State
Cerebral oedema - from rapid lowering GB from insulin Tx (bc Px vv sensitive)
Epidemiology of Hyperthyroidism
F > M
Presents between 20 - 40 (not Graves’)
Causes of Hyperthyroidism
**Graves’ Disease
Toxic multinodular goitre (elder women)
De Quervain’s
Toxic thyroid adenoma
Drug induced - iodine, amiodarone
How does De Quervain’s usually present?
W/ fever, neck pain, malaise
At what age does Graves’ disease present?
40-60 years
Earlier if maternal FHx
Define Thyrotoxicosis
Increase in T3 and T4 levels in circulation
Define hyperthyroidism
Increased synthesis of T3 and T4 in the thyroid gland
Signs/symptoms of hyperthyroidism
Weight loss
Heat intolerance
Palpitations
DIFFUSE GOITRE
Increased sweating
Diarrhoea
Oligomenorrhoea
Anxiety
Onycholysis
What are some Graves’ disease specific signs/symptoms?
Orbitopathy
Exophthalmos
Ophthalmoplegia
Thyroid acropachy
Pretibial myxoedema
What is thyroid acropachy?
TRIAD OF :
1. Digital clubbing
2. Soft tissue swelling of hands and feet
3. Periosteal new bone formation
RF Graves’ disease
Female - common postpartum
Genetics - HLA-B8, DR3 & DR4
E.coli & other GRAM-NEG
Stress
Amiodarone (AF), Alemtuzumab (MS)
Autoimmune diseases
Why are E.coli and other GRAM-NEG organisms a risk factor for Hyperthyroidism?
Contain TSH-binding sites
∴ molecular mimicry may occur
Key presentation of Hyperthyroidism
Weight loss
Irritability
Heat intolerance
Key presentation of Hyperthyroidism
Weight loss
Irritability
Heat intolerance
Thyroid hormone plays a major role in …
… Metabolism, growth and development
1st Ix Hyperthyroidism (Graves’)
Thyroid function tests (TFTs) - ↑ T4, ↓ TSH
In TFT, how can you differentiate between 1º and 2ºhyperthyroidism? Why is this difference shown?
1º - high T3/T4, low TSH
2º - high T3/T4, high TSH
bc in 2º, problem with pituitary ∴ TSH not suppressed
Give some examples of 2º hyperthyroidism
Pituitary resistance
Pituitary secreting adenoma
If thyroid peroxidase antibodies (TPO Abs) are found in blood, what does this indicate?
Thyroid disease due to autoimmune disorder
e.g. Graves’, Hashimoto’s
GS Ix Hyperthyroidism
TSH-receptor Ab - if pos = Graves’
TPO-Ab - to confirm Graves’
diagnosis made in addition to TFT results
Tx Hyperthyroidism
1ST LINE -
Propranolol - used at diagnosis, to rapidly treat symptoms (e.g. tremor)
–
Anti-thyroid drug - Carbimazole OR Propylthiouracil (PTU)
Radioiodine treatment - Radioactive I(131)
Surgery - thyroidectomy
What treatment should be given to patients with active moderate-severe and sight-threatening orbitopathy with Graves’ disease?
IV corticosteroids e.g. methylprednisolone
Describe the mechanism of Carbimazole in the treatment of Hyperthyroidism
Blocks thyroid peroxidase
∴ reduces thyroid levels
What is a common S/E of Carbimazole?
AGRANULOCYTOSIS
Describe the mechanism behind radioiodine treatment for Hyperthyroidism?
Emits beta particules
∴ ionisation of thyroid cell
S/E of radioiodine treatment for Hyperthyroidism
May exacerbate thyroid eye disease
Describe the 4 phases of De Quervain’s thyroiditis
Phase 1 - last 3-6 weeks
hyperthyroidism, painful goitre, ↑ ESR
Phase 2 - lasts 1-3 weeks
Normal thyroid function
Phase 3 - weeks-months
Hypothyroidism
Phase 4 -
Thyroid structure and function goes back to normal
Key presentation of De Quervain’s thyroiditis
Neck pain (which may move to jaw and ears)
Difficulty eating
Tender, firm, enlarged thyroid
Fever
Palpitations
When is radioiodine treatment contraindicated when treating Hyperthyroidism?
Pregnancy
Breast-feeding
Describe the process of thyroidectomy in reference to treating hyperthyroidism
Removal of thyroid gland, leaving small part
so thyroid function maintained
Conditions of thyroidectomy when treating hyperthyroidism
Anti-thyroid drugs stopped 10-14 days prior
Replaced w/ oral potassium iodide
Complications of thyroidectomy when treating hyperthyroidism
Hypocalcaemia
Hypothyroidism
Hypoparathyroidism
Recurrent laryngeal palsy (laceration)
Recurrent hyperthyroidism
Key presentation of Thyroid Crisis (Thyroid Storm)
Hyperpyrexia
Tachycardia
Extreme restlessness
Maybe delirium, coma, death
What is Thyroid Storm precipitated by?
Infection
Stress
Surgery
Radioactive iodine therapy
Tx Thyroid Storm
Large doses of carbimazole
Propanolol
Potassium iodide
Hydrocortisone
How does potassium iodide help to manage thyroid storm?
Blocks release of thyroid hormone from gland
What does hydrocortisone do when used to treat Thyroid storm?
Inhibits peripheral conversion of T4 to T3
What is Thyroid Crisis/Thyroid Storm?
Rare, life-threatening disease!!
Rapid deterioration of thyrotoxicosis
Tx De Quervain’s
If hyperthyroidism phase - NSAIDs and corticosteroids (for pain)
If hypothyroidism phase - Normally no Tx but if severe, small dose of levothyroxine
What can pituitary adenomas cause?
Cushing’s Syndrome/Disease
Acromegaly
Prolactinoma
Define Cushing’s syndrome
What differentiates it from Cushing’s Disease?
XS CORTISTOL
(chronic, free circulating)
Cushing’s disease - results from pituitary adenoma
Causes of Cushing’s
ACTH independent : ACTH = normal, cortisol = high
Oral steroid use !! e.g. prednisolone - most common!!
Adrenal adenoma/carcinoma
ACTH dependent ACTH and cortisol = high
*Cushing’s disease (ant. pituitary adenoma)
Ectopic ACTH production e.g. SCLC producing ACTH
Key presentation of Cushing’s syndrome
*Round moon face
*Truncal obesity
*Thin skin/bruising
Buffalo hump - fatty hump on upper back
Acne
Hirsutism
Osteoporosis
CUSHING
Cataracts
Ulcers
Striae
HTN and Hyperglycaemia
Increased risk of infection
Necrosis
Glucosuria
What gland secretes ACTH?
Pituitary
What gland secretes cortisol?
Adrenal gland
Describe the relationship between ACTH and cortisol
ACTH stimulates adrenal gland to produce cortisol
∴ ↑ ACTH = ↑ Cortisol
Ix Cushing’s
1st line - raised plasma cortisol
GS : DEXAMETHASONE SUPPRESSION TEST
Low dose - 1mg
Failure to suppress over 24 hrs
OTHER :
24 hr urinary free cortisol - alternative to GS but doesn’t indicate underlying cause
MRI brain - pituitary adenoma
Chest CT - SCLC
Adbo CT - adrenal tumour
Tx Cushing’s
Treat underlying cause :
Iatrogenic - stop steroids !!!
Adrenal adenoma - adrenalectomy
Cushing’s disease - trans-sphenoidal surgery to remove pituitary adenoma
Ectopic ACTH production - surgery to remove neoplasm if can be located and hasn’t metastasised
If cannot surgically remove cause, remove both adrenal glands and give Px replacement steroids - lifelong
Describe the Dexamethasone Suppression Test
Given at night (10pm), measured in morning (9am)
Low dose test :
1mg dexamethasone
Results :
if low cortisol = normal
if high/normal = cushing’s syndrome (POS)
–
High dose test
8mg dexamethasone
Results :
if low cortisol = Cushing’s disease
If high/normal w LOW ACTH - Adrenal adenoma
if high/normal w HIGH ACTH - Ectopic ACTH
What inhibits the release of GH?
Somatostatin
High levels of glucose
Dopamine (not as potent as Somatostatin)
