Endocrine Flashcards
1
Q
Define endocrine
A
These glands ‘pour’ secretions directly into blood stream, without ducts
e.g. thyroid, adrenal, beta cells of pancreas
2
Q
Define exocrine
A
These glands ‘pour’ secretions through a duct to site of action
e.g. submandibular, parotid, pancreas (amylase & lipase)
3
Q
Describe the action of endocrine hormones
A
Blood-borne, acting on distant sites
4
Q
Describe the action of paracrine hormones
A
Acting on nearby adjacent cells
5
Q
Describe the action of autocrine hormones
A
Feedback on same cell that secreted hormone - acts on itself
6
Q
Define Diabetes Mellitus T1
A
Autoimmune disease, causes the destruction of beta cells leading to insulin deficiency
∴ hyperglycaemia
7
Q
Epidemiology DMT1
A
Usually younger < 30 years
↑ Northern Europe, esp Finland!
Incidence is increasing
8
Q
22yr old woman with DMT1 is pregnant - what is the chance of her child also having DMT1?
A
1 in 25
(It is accepted that the child of any women below 25 years has a 1 in 25 chance of getting T2DM)
9
Q
Monitoring of T2DM
A
HbA1c checked after 6 months
Checks for CVD, diabetic retinopathy, nephropathy, neuropathy etc done annually
10
Q
What is LADA?
A
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
11
Q
RF DMT1
A
Genetic susceptibility -
HLA-DR3-DQ2 or HLA-DR4-DQ8
Other autoimmune diseases
Vit D def
Enteroviruses e.g. Coxsackie B4
12
Q
Why does polydipsia occur in DMT1?
A
Results of fluid and electrolyte loss
13
Q
Why does polyuria occur in DMT1?
A
Result of osmotic diuresis
When blood glucose levels > renal tubular reabsorptive capacity
14
Q
Why must DMT1 Px have insulin?
A
They are more prone to diabetic ketoacidosis
15
Q
Key presentation of DMT1
A
2-6 week history of :
Unexplained weight loss, polyuria, polydipsia
16
Q
State 1 other signs of DMT1
A
Breath may smell of ‘pear drops’ (KETONES)
17
Q
Ix DMT1
A
Fasting plasma glucose (no food for 8hrs)
Random plasma glucose
Oral glucose tolerance test
18
Q
Diagnostic values for DM
A
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)
19
Q
What is the most common way children present with new T1DM?
A
Diabetic ketoacidosis
20
Q
Tx DMT1
A
Patient education!!
BASAL BOLUS INSULIN
SC insulin - combo of long acting insulin (basal) od
& short acting insulin (bolus) injected 30 mins before meals
21
Q
Define DMT2
A
Relative insulin def due to combination of insulin resistance and less severe insulin def
22
Q
4 non-modifiable RF DMT2
A
> 40 years
Ethnicity - Black, Chinese, South Asian
FHx
Male
23
Q
4 modifiable RF DMT2
A
Obesity
Sedentary lifestyle
High carbohydrate diet
HTN
24
Q
Key presentation of DMT2
A
Usually asymptomatic and found incidentally on routine blood tests
25
Symptoms of a Px w/ severe T2DM
acanthosis nigricans
26
GS Ix DMT2
HbA1c test ! (tells us avg. BG for last 3 months)
27
State some complications of insulin treatment
Hypoglycaemia!
Lipohypertrophy (at injection site)
Insulin resistance
Weight gain - bc insulin makes people feel hungry
28
Tx DMT2
Lifestyle modifications first !!
1. **Metformin**
2. 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)
3. 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
29
Name some macrovascular complications of diabetes mellitus
Stroke
Ischaemic heart disease
Peripheral vascular disease
30
Which sex is at more risk of macrovascular complications of DM?
Neither - DM removes vascular advantage that females have
31
What can be given to DM patients to reduce the risk of macrovascular complications?
Statin
ACE-I
32
What are some microvascular complications of DM?
Diabetic neuropathy
Diabetic retinopathies
Diabetic nephropathy
33
Describe the pathophysiology of Diabetic neuropathy
Occlusion of vasa nervorum and accumulation of fructose and sorbitol
Disrupts structure and function of nerves
34
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
35
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!!
36
Diabetic foot ulcer management
FOOT SCREENING!
Patient education! - Check feet daily, tie laces for enough room, keep feet away from heat
37
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
38
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
39
State and describe the two types of diabetic retinopathy
1. **Non-proliferative**
new blood vessels not growing
2. **Proliferative
Damaged blood vessels close off ∴ new abnormal vessels grow, will leak
40
Ix diabetic retinopathy
Fundoscopy
Cotton wool spots and flare haemorrhages
41
Early indication of diabetic nephropathy
Microalbuminuria
42
Other types of diabetes
MODY
LADY (latent autoimmune diabetes of young)
Gestational diabetes - usually in 3rd trimester
43
Tx diabetic nephropathy
Aggressive BP control (ACE-I, angiotensin-II antagonists etc)
44
Causes of hypoglycaemia
**EXPLAIN**
**Ex**ogenous drugs - insulin, alcohol binge w/ no food
**P**ituitary insufficiency
**L**iver failure
**A**ddison's disease
**I**slet's cell tumour & **I**mmune hypoglycaemia
**N**on-pancreatic neoplasm e.g. fibrosarcoma
45
Key presentation of hypoglycaemia
Odd behaviour (aggression), sweating, tachycardia
46
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
47
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
48
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
49
What is diabetic ketoacidosis characterised by?
1. Hyperglycaemia > 11 mmol/L
2. ↑ Plasma ketones > 3 mmol/L
3. Metabolic acidosis - pH < 7.3
50
Causes/RF Diabetic ketoacidosis
Untreated DMT1 or stopping insulin therapy
Undiagnosed DM
Infection/illness
MI
51
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
52
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
53
Why is insulin def necessary for diabetic ketoacidosis?
Because even a small elevation will inhibit hepatic ketogenesis
54
DKA prognosis
Medical emergency!
If untreated, can be fatal!
55
DKA key presentation
Dehydration, vomiting, abdominal pain, ↓ tissue turgor
56
DKA is rare in T2DM, more common in T1 !!
dont forget
57
DKA signs/symptoms
Kussmaul's sign
'Pear drop' breath
Low BP
Low body temp - even in presence of infection
Sunken eyes
-
Drowsiness/confusion
58
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
59
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!
60
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
61
Describe how fluid replacement in DKA should be given
Slowly!! Over 48 hours!
62
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+
63
Describe the action of biguanide and give an example
Increases peripheral insulin sensitivity and hepatic glucose uptake
e.g. Metformin
64
Describe the action of Sulfonylurea and give an example
e.g. Gliclazide
Depolarises islet cells in pancreas ∴ ↑ insulin release
65
Describe the action of Thiazolidinedione and give an example
e.g. Pioglitazone
↑ Peripheral insulin sensitivity
66
Describe the action of SGLT-2i and give an example
e.g. Dapglifozin
↑ Urinary glucose loss
67
Describe the action of DPP4-i and give an example
e.g. Sitagliptin
Inhibits GLP1 breakdown
68
Describe the action of GLP1 analogue and give an example
e.g. Exenatide
↑ Insulin secretion and sensitivity
69
Describe the action of Intestinal Alpha-Glucosidase Inhibitors and give an example
e.g. Acarbose
Delays intestinal carbohydrate absorption
70
S/E biguanide
Lactic acidosis, GI disturbance
71
S/E Sulfonylurea
Hypoglycaemia, weight gain
72
S/E Thiazolidinediones
Fluid retention, weight gain, worsening heart failure
73
S/E SGLT-2i
DKA when used w/ insulin
↑ Risk of UTI
74
S/E DPP4-i
Hypoglycaemia, GI upset
75
S/E GLP1 analogues
Hypoglycaemia, GI upset
May increase risk of pancreatitis when used with DPP4-i
76
S/E Intestinal alpha-glucosidase inhibitors
Flatulence, GI disturbance
77
Define Hyperosmolar Hyperglycaemic State
Medical emergency!
Characterised by :
1. Marked hyperglycaemia
2. Hyperosmolality
3. Mild/No ketosis
78
Hyperosmolar hyperglycaemic state usually presents in whom?
Elderly w/ poorly controlled T2DM
79
Hyperosmolar hyperglycaemic state - RF
*Infection! esp pneumonia
Consumption of glucose rich fluids
Concurrent medication - thiazide diuretic or steroids
80
Pathophysiology of Hyperosmolar Hyperglycaemic State
↓ Endogenous insulin
Enough to inhibit hepatic ketogenesis
but not enough to inhibit hepatic glucose production
81
Key presentation of Hyperosmolar Hyperglycaemic State
Severe dehydration
↓ Levels of consciousness
82
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
83
Bicarbonate level in Hyperosmolar Hyperglycaemic State
NORMAL
84
Diagnostic values for Hyperosmolar Hyperglycaemic State
Hyperglycaemia (> 30 mmol/L)
Hypotension
Hyperosmolality (usually > 320 mosmol/kg)
Unlike DKA, NOT accompanised w/ acidosis or ketosis
85
Ix Hyperosmolar Hyperglycaemic State
Blood glucose
Plasma osmolality
Urine stick test
86
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
87
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
88
Complications of Hyperosmolar Hyperglycaemic State
Cerebral oedema - from rapid lowering GB from insulin Tx (bc Px vv sensitive)
89
Epidemiology of Hyperthyroidism
F > M
Presents between 20 - 40 (not Graves')
90
Causes of Hyperthyroidism
****Graves' Disease**
Toxic multinodular goitre (elder women)
De Quervain's
Toxic thyroid adenoma
Drug induced - iodine, amiodarone
91
How does De Quervain's usually present?
W/ fever, neck pain, malaise
92
At what age does Graves' disease present?
40-60 years
Earlier if maternal FHx
93
Define Thyrotoxicosis
Increase in T3 and T4 levels in circulation
94
Define hyperthyroidism
Increased synthesis of T3 and T4 in the thyroid gland
95
Signs/symptoms of hyperthyroidism
Weight loss
Heat intolerance
Palpitations
DIFFUSE GOITRE
Increased sweating
Diarrhoea
Oligomenorrhoea
Anxiety
Onycholysis
96
What are some Graves' disease specific signs/symptoms?
Orbitopathy
Exophthalmos
Ophthalmoplegia
Thyroid acropachy
Pretibial myxoedema
97
What is thyroid acropachy?
TRIAD OF :
1. Digital clubbing
2. Soft tissue swelling of hands and feet
3. Periosteal new bone formation
98
RF Graves' disease
Female - common postpartum
Genetics - HLA-B8, DR3 & DR4
E.coli & other GRAM-NEG
Stress
Amiodarone (AF), Alemtuzumab (MS)
Autoimmune diseases
99
Why are E.coli and other GRAM-NEG organisms a risk factor for Hyperthyroidism?
Contain TSH-binding sites
∴ molecular mimicry may occur
100
Key presentation of Hyperthyroidism
Weight loss
Irritability
Heat intolerance
101
Key presentation of Hyperthyroidism
Weight loss
Irritability
Heat intolerance
102
Thyroid hormone plays a major role in ...
... Metabolism, growth and development
103
1st Ix Hyperthyroidism (Graves')
Thyroid function tests (TFTs) - ↑ T4, ↓ TSH
104
In TFT, how can you differentiate between 1º and 2º hyperthyroidism? 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
105
Give some examples of 2º hyperthyroidism
Pituitary resistance
Pituitary secreting adenoma
106
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
107
GS Ix Hyperthyroidism
TSH-receptor Ab - if pos = Graves'
TPO-Ab - to confirm Graves'
diagnosis made in addition to TFT results
108
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
109
What treatment should be given to patients with active moderate-severe and sight-threatening orbitopathy with Graves' disease?
IV corticosteroids e.g. methylprednisolone
110
Describe the mechanism of Carbimazole in the treatment of Hyperthyroidism
Blocks thyroid peroxidase
∴ reduces thyroid levels
111
What is a common S/E of Carbimazole?
AGRANULOCYTOSIS
112
Describe the mechanism behind radioiodine treatment for Hyperthyroidism?
Emits beta particules
∴ ionisation of thyroid cell
113
S/E of radioiodine treatment for Hyperthyroidism
May exacerbate thyroid eye disease
114
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
115
Key presentation of De Quervain's thyroiditis
Neck pain (which may move to jaw and ears)
Difficulty eating
Tender, firm, enlarged thyroid
Fever
Palpitations
116
When is radioiodine treatment contraindicated when treating Hyperthyroidism?
Pregnancy
Breast-feeding
117
Describe the process of thyroidectomy in reference to treating hyperthyroidism
Removal of thyroid gland, leaving small part
so thyroid function maintained
118
Conditions of thyroidectomy when treating hyperthyroidism
Anti-thyroid drugs stopped 10-14 days prior
Replaced w/ oral potassium iodide
119
Complications of thyroidectomy when treating hyperthyroidism
Hypocalcaemia
Hypothyroidism
Hypoparathyroidism
Recurrent laryngeal palsy (laceration)
Recurrent hyperthyroidism
120
Key presentation of Thyroid Crisis (Thyroid Storm)
Hyperpyrexia
Tachycardia
Extreme restlessness
Maybe delirium, coma, death
121
What is Thyroid Storm precipitated by?
Infection
Stress
Surgery
Radioactive iodine therapy
122
Tx Thyroid Storm
Large doses of carbimazole
Propanolol
Potassium iodide
Hydrocortisone
123
How does potassium iodide help to manage thyroid storm?
Blocks release of thyroid hormone from gland
124
What does hydrocortisone do when used to treat Thyroid storm?
Inhibits peripheral conversion of T4 to T3
125
What is Thyroid Crisis/Thyroid Storm?
Rare, life-threatening disease!!
Rapid deterioration of thyrotoxicosis
126
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
127
What can pituitary adenomas cause?
Cushing's Syndrome/Disease
Acromegaly
Prolactinoma
128
Define Cushing's syndrome
What differentiates it from Cushing's Disease?
XS CORTISTOL
(chronic, free circulating)
Cushing's _disease_ - results from pituitary adenoma
129
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
130
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**
**C**ataracts
**U**lcers
**S**triae
**H**TN and Hyperglycaemia
**I**ncreased risk of infection
**N**ecrosis
**G**lucosuria
131
What gland secretes ACTH?
Pituitary
132
What gland secretes cortisol?
Adrenal gland
133
Describe the relationship between ACTH and cortisol
ACTH stimulates adrenal gland to produce cortisol
∴ ↑ ACTH = ↑ Cortisol
134
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
135
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
136
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
137
What inhibits the release of GH?
Somatostatin
High levels of glucose
Dopamine (not as potent as Somatostatin)
