Endocrine Flashcards
1
Q
Epidemiology of type 1 DM
A
o Often starts before puberty, or <30 years
o Usually lean
o More common in Caucasian population
2
Q
Epidemiology of type 2 DM
A
o Usually older patients, >30 years
o Usually overweight
o More common in South Asian population
3
Q
Causes and risk factors for type 1 DM
A
o Autoimmune
o HLA DR3/4 affected in 90% (family history)
4
Q
Causes and risk factors for type 2 DM
A
o Decreased insulin secretion and increased insulin resistance
o RFs: obesity, older, FH, South Asian ethnicity, HTN, hyperlipidaemia, alcohol excess
o Genetic susceptibility but not HLA link
5
Q
Pathophysiology of type 1 DM
A
Autoimmune destruction of pancreatic beta cells in Islets of Langerhans, triggered by environmental antigens
6
Q
Pathophysiology of type 2 DM
A
o Polygenic – environmental factors trigger
o Beta cell mass 50% of normal
o Low insulin secretion and peripheral insulin
resistance
7
Q
Secondary causes of DM
A
o CF
o Chronic pancreatitis
o Acromegaly
o Cushing’s
8
Q
Signs and symptoms of DM (hyperglycaemia)
A
- Polyuria and polydipsia
- Unexplained weight loss
- Blurred vision
- Genital thrush
9
Q
Investigations for DM
A
- Fasting glucose (>7mmol/L) or random plasma glucose (>11.1mmol/L)
- HbA1c: >48mmol/mol
- Oral GTT (glucose tolerance test)
- C peptide goes down in type 1, persists in 2
10
Q
Type 1 DM management
A
o Glycaemic control through diet and insulin (twice daily and with meals)
o Exercise encouraged
11
Q
Type 2 DM management
A
- Lifestyle modification – diet, weight control, exercise, smoking cessation
- Monotherapy – 1st line standard release Metformin
- Dual therapy – Metformin + DPP4I (gliptins)/ glitazone/ sulphonylurea/ SGLTI
- If no change add insulin
12
Q
Metformin mechanism
A
Increases insulin sensitivity and helps weight
13
Q
Metformin SE’s and CI’s
A
SE’s: anorexia, D&V
CI’s: renal failure
14
Q
Sulfonylurea mechanism
A
Opens channels in Beta cells so more insulin is produced
15
Q
Sulfonylurea SE’s and CI’s
A
SE’s: hypoglycaemia and weight gain
CI’s: pregnancy and liver disease
16
Q
DPP-4 receptors (gliptins) mechanism
A
Prevent breakdown of GLP-1, most effective if used early
17
Q
Glitazone mechanism
A
Increases insulin sensitivity
18
Q
Glitazone SE’s
A
Hypoglycaemia, fractures, fluid retention
19
Q
Secondary prevention in DM
A
o Eye and foot screening
o BP checks and CV risk assessment – statins and BP lowering drugs if needed
o Kidney tests
20
Q
Complications of DM
A
- Diabetic nephropathy
- Diabetic neuropathy
- Diabetic retinopathy
- Arterial disease
- Diabetic ketoacidosis
21
Q
Diabetic ketoacidosis pathophysiology
A
• Hallmark of type 1 DM
• Uncontrolled hyperglycaemia and catabolic state
• Body metabolites amino acids and triglycerides ->
ketones
• Renal hypoperfusion occurs due to osmotic diuresis
-> coma and circulatory failure -> death
22
Q
Signs and symptoms of DKA
A
o Lethargy o Polyuria and polydipsia o Confusion o Abdominal pain o Ketone smell in breath (fruity)
23
Q
Investigations/diagnosis of DKA
A
o Acidaemia (pH <7.3) o Hyperglycaemia ( >11.0mmol/L) o Ketonaemia or ketouria (dipstick)
24
Q
Managament of DKA
A
o Fluid balance and rehydration
o Actrapid IV insulin
o Potassium replacement
25
Causes of hypothyroidism
o Primary hypothyroidism:
Primary atrophic hypothyroidism
Hashimoto’s thyroiditis (autoimmune)
Post-thyroidectomy/radioiodine treatment
Drug induced e.g. lithium
o Secondary hypothyroidism - hypopituitarism
26
Pathophysiology of primary hypothyroidism
Aggressive destruction of thyroid cells by various immune processes. Antibodies bind and block TSH receptors -> inadequate thyroid hormone production and secretion
27
Pathophysiology of secondary hypothyroidism
Reduced release or production of TSH -> reduced T3 and T4 release
28
Symptoms of hypothyroidism
```
o Hoarse voice
o Constipation
o Cold intolerance
o Weight gain
o Menorrhagia
o Weakness and tiredness
o Dementia
```
29
Signs of hypothyroidism
```
o Bradycardia
o Reflexes relax slowly
o Dry thin hair/skin
o Yawning/drowsiness/coma
o Cold hands
o Round, puffy face
o Menorrhagia
```
30
Investigations for hypothyroidism
o Primary:
- Increased TSH and decreased T4
- TPO antibodies in Hashimoto’s
o Secondary - decreased TSH and T4
31
Management of hypothyroidism
o Levothyroxine (T4 replacement) – smaller does if
elderly as risk of angina or MI
o Primary – resect obstructive goitre
o Secondary – treat underlying cause
32
Conditions associated with hypothyroidism
```
o Autoimmune (T1DM, Addison’s, pernicious anaemia)
o Inherited (Turner’s Down’s, CF)
```
33
Definition of hypothyroidism (thyrotoxicosis)
Lack of thyroid hormone
34
Definition of hyperthyroidism
Excess thyroid hormone, usually from gland hyperfunction
35
Causes of hyperthyroidism
```
o Grave’s disease
o Toxic multinodular goitre - elderly, iodine defficient
o Toxic adenoma
o Ectopic thyroid tissue
o Exogenous (iodine/T4 excess)
```
36
Symptoms of hyperthyroidism
o Palpitations
o Sweats, heat intolerance
o Weight loss, appetite increase
o Diarrhoea
37
Signs of hyperthyroidism
```
o Palmar erythema, moist, warm skin
o Tachycardia
o Thin hair
o Goitre
o Hyperreflexia
o Amenhorrea
```
38
Investigations for hyperthyroidism
```
o Decreased TSH, increased T3/4
o FBC (normocytic anaemia)
o Raised ESR, Ca2+ and LFT
o Autoantibodies
o Visual fields, acuity, movements (thyroid eye)
```
39
Management of hyperthyroidism
o Beta-blockers (propranolol)
o Anti-thyroid medication (carbimazole)
o Radioiodine, thyroidectomy – SE: hypothyroidism,
CI: pregnancy
40
Carbimazole SE
Agranulocytosis
41
Graves's disease pathophysiology
Thyroid stimulating Ig’s bind to TSH receptors -> stimulate T4 and T3 -> T4 receptors in pituitary gland activated by excess hormone -> reduce TSH release
42
Grave's disease signs and symptoms
```
o Tachycardia
o Tremor
o Diffuse palpable goitre with audible bruit
o Eye problems
o Swelling of hands and fingers)
```
43
Investigations for Grave's Disease
Bloods - high T4, low TSH
44
Definition of Cushing's Syndrome
Chronic cortisol excess
45
ACTH dependant causes of Cushing's Syndrome
o Cushing’s disease – ACTH-secreting pituitary adenoma
| o Ectopic ACTH production – tumour
46
ACTH independent causes of Cushing's syndrome (negative feedback causes low ACTH)
o Iatrogenic – steroids (common)
o Adrenal adenoma/cancer
o Adrenal nodular hyperplasia
47
What can cause pseudo-Cushing's
Excessive alcohol
48
Symptoms of Cushing's syndrome
* Weight gain
* Mood change
* Proximal weakness
* Gonadal dysfunction
* Recurrent Achilles injury
49
Signs of Cushing's syndrome
* Fat distribution (central obesity, buffalo hump)
* Skin changes (bruises, stretch marks)
* Osteoporosis
* Muscle atrophy
50
Investigations for Cushing's syndrome
o Overnight dexamethasone supression test - no
suppression in Cushing's syndrome
o Plasma and urine ACTH
51
Management of Cushing's syndrome
• Iatrogenic – stop steroids
• Cushing’s disease/adenoma/carcinoma – trans-
sphenoid surgery
• Ectopic ACTH – surgery + cortisol-inhibiting drugs
52
Complications of Cushing's disease
* HTN
* Obesity
* Death
53
Acromegaly definition
Overall growth of all organ systems due to excess growth hormone
54
Causes of acromegaly
Pituitary tumour or hyperplasia
55
Pathophysiology of acromegaly
* GH stimulates bone and soft tissue growth through increased secretion of insulin-like growth factor-1
* If occurs before fusion of epiphyseal plates (children) -> gigantism
56
Symptoms of acromegaly
* Acroparaesthesia
* Amenorrhea and decreased libido
* Headache
* Excessive sweating
* Snoring
57
Signs of acromegaly
* Growth of hands, jaw and feet
* Coarsening face, wide nose
* Macroglossia (big tongue)
* Puffy lips, skin and eyelids
* Obstructive sleep apnoea
* Carpal tunnel
58
Investigations and diagnosis of acromegaly
* Raised glucose, calcium and phosphate
* Raised IGF-I and oral GTT (gold standard)
* MRI of pituitary fossa (pituitary adenoma)
* Look at old photos
* Visual acuity
59
Management of acromegaly
1. Trans-sphenoidal resection surgery
2. Radiotherapy or actreotide
3. GH receptor antagonists (pegvisomant)
60
Complications of acromegaly
* HTN and heart disease
* Sleep apnoea
* Arthritis
* Type 2 diabetes
* Cerebrovascular events and headaches
* Blindness
61
Conn's syndrome definition
Excess production of aldosterone independent of RASS
62
Conn's syndrome pathophysiology
• Increased aldosterone -> increased reabsorption of
water and sodium + increased excretion of potassium
• Aldosterone also inhibits renin release
63
Signs and symptoms of Conn's syndrome
• Often asymptomatic or signs of hypokalaemia
(weakness, cramps, polyuria, polydipsia)
• Sometimes raised BP
64
Causes of Conn's syndrome
* Conn’s disease – solitary aldosterone producing adenoma
| * Bilateral adrenal hyperplasia
65
Investigations for Conn's syndrome
• Bloods – low renin, high aldosterone, U+E (high
sodium, low potassium)
• Don't rely on low K+
• MRI scan
66
Management of Conn's disease
o Laparoscopic adrenalectomy
| o Spironolactone pre-op
67
Management of Conn's syndrome caused by hyperplasia
Spironolactone (aldosterone antagonist)
68
Definition of Addison's disease
Adrenocorticoid insufficiency due to destruction of the adrenal cortex
69
Pathophysiology of hyperpigmentation in Addison's
destruction of adrenal cortex -> less cortical products -> excess ACTH stimulates melanocytes -> hyperpigmentation
70
Definition of secondary adrenal insufficiency
Lack of ACTH (and therefore cortisol)
71
Pathophysiology of secondary adrenal insufficiency
Inadequate pituitary of hypothalamic stimulation of the adrenal glands
72
Causes of Addison's disease
o Autoimmune
o TB
o Lymphoma
o Opportunistic infections in HIV
73
Causes of secondary adrenal insufficiency
o Iatrogenic – steroids
| o Hypothalamic-pituitary disease
74
Symptoms of adrenal insufficiency
* Nausea/vomiting, abdominal pain, constipation, weight loss
* Tanned skin
* Weakness, confusion, syncope
75
Signs of adrenal insufficiency
* Hyperpigmentation – Addison's only
* Postural hypotension
* Dehydration, general wasting, alopecia
76
Investigations for adrenal insufficiency
o Bloods - low Na+ and high K+ (Addison's), low
glucose
o ACTH stimulation test:
- give synthetic ACTH
- measure cortisol and aldosterone produced
o ACTH raised in primary, low in secondary
77
Management of adrenal insufficiency
• Replace steroids with hydrocortisone
• Fludrocortisone to replace mineralocorticoids –
Addison’s only
78
SE of hydrocortisone
Insomnia if taken late
79
Causes of hyperkalaemia
```
Drugs - ACE-i, K+ sparing diuretics
Renal failure
Endocrine - Addison's
Artefacts
DKA
```
80
Pathophysiology of hyperkalaemia
Renal impairment can lead to retention of potassium in the nephron, can also occur with K+ sparing diuretic
81
Signs and symptoms of hyperkalaemia
o Fast irregular pulse, palpitations
o Chest pain
o Weakness, light-headedness
82
Investigations for hyperkalaemia
```
o ECG:
Tall T waves
Wide QRS complex
Ventricular fibrillation
o Bloods - Potassium >5.5 (consider artefact)
```
83
Management of hyperkalaemia
o IV insulin with glucose
o salbutamol (CI tachycardic)
o review meds
o dialysis if severe
84
Complications of hyperkalaemia
MI -> death
85
Causes of hypokalaemia
o Diuretics
o Hyperaldosteronism/Conn's
o D&V
o Cushing’s
86
Pathophysiology of hypokalaemia
o Excessive loss of potassium in the kidneys in response to aldosterone or diuretics
o GI fluid loss -> less chloride -> ↑aldosterone -> ↓ potassium reabsorption
87
Signs and symptoms of hypokalaemia
o Muscle weakness, hyporeflexia
o Palpitations, light-headedness (arrythmias)
o Constipation
88
Investigations for hypokalaemia
```
o ECG:
Small T-waves
Prominent U-waves (after T wave)
Long PR interval
Depressed ST segments
o Bloods – low potassium (<3.5)
```
89
Management of hypokalaemia
```
o Mild:
Oral K+ supplement
Change thiazide diuretic to K+ sparing
o Severe - IV potassium cautiously
o Treat underlying cause
```
90
Complications of hypokalaemia
Cardiac arrhythmia and sudden death
91
Definition of SIADH
Continued ADH secretion despite normal plasma volume
92
Pathophysiology of SIADH
Ectopic production increases ADH above mechanisms of control -> retention of water and hyponatraemia
93
Causes of SIADH
* Neurological - CNS disorders, trauma, meningitis
* Chest disease – TB, pneumonia
* Drugs – opiates, SSRI, anti-epileptics
94
Signs and symptoms of SIADH
* Nausea
* Headache
* Confusion
* Fits and coma (hyponatraemia)
95
Investigations for SIADH
• Bloods:
- Dilutional hyponatraemia
- Low plasma osmolality
96
Management of SIADH
* Treat cause and restrict fluid
* Vasopressin receptor antagonist (VRA)
* Demeclocycline (ADH inhibitor)
97
SE of demeclocycline
DI
98
Physiology of central DI
Reduced ADH secretion from posterior pituitary
99
Physiology of nephrogenic DI
Impaired response of kidney to ADH
100
Causes of central DI
```
o Idiopathic
o Congenital
o Tumour
o Neurosurgery
o Autoimmune
```
101
Causes of nephrogenic DI
o Inherited
o Metabolic – hypokalaemia, hypercalcaemia
o Drugs – lithium
o Chronic renal disease
102
Symptoms of DI
* Polyuria
* Polydipsia
* Dehydration
* Symptoms of hypernatraemia
103
Investigations for DI
```
• Water deprivation test:
- monitor urine output
- high and dilute in DI
- desmopressin response = central DI
• MRI of hypothalamus
```
104
Management of DI
```
• Central - desmopressin
• Nephrogenic:
o treat cause
o thiazides
o NSAIDs
```
105
Causes of hypocalcaemia
o Vitamin D deficiency (actual or functional)
o Hypoalbuminaemia (artefact of)
o Hypoparathyroidism
o CKD
106
Pathophysiology of hypocalcaemia caused by CKD
CKD -> increased serum phosphate -> microprecipitation of calcium phosphate in tissues -> low serum calcium
107
Symptoms of hypocalcaemia
Increased excitability of muscles and nerves (numbness around mouth/extremities, spasms, cramps, tetany)
108
Signs of hypocalcaemia
o Trousseau’s (facial nerve) and Chvostek’s (hand) signs
109
Investigations for hypocalcaemia
o ECG – prolonged QT
o eGFR to check for CKD
o PTH high, vitamin D usually low (CKD)
110
Management of hypocalcaemia
o Mild – calcium PO
o Acute/severe – IV calcium gluconate
o Persistent – Vit D supplement if deficient
o If CKD or hypoparathyroidism – alfacalcidol
111
Causes of hypercalcaemia
o Malignancy
| o Primary hyperparathyroidism
112
Symptoms of hypercalcaemia
o Bones – pain
o Stones – kidney stones
o Groans – abdominal pain, nausea, constipation
o Moans – depression
113
Signs of hypercalcaemia
o Polydipsia
| o Polyuria
114
Investigations for hypercalcaemia
o Bloods – raised calcium, raised PTH is hyperparathyroidism
o ECG – shortened QT
115
Management of hypercalcaemia
o IV saline - for dehydration
o Bisphosphates - prevent bone resorption
o Loop diuretic - return calcium to normal
o Treat underlying cause
116
Definition of hypoparathyroidism
Low levels of PTH
117
Causes of hypoparathyroidism
o Parathyroidectomy
o Congenital – Di George syndrome
o Autoimmune
o Hypomagnesaemia
118
Why does hypoparathyroidism cause hypocalcaemia and hyperphosphataemia?
o PTH stimulates activation of vit D -> intestinal calcium absorption, renal calcium absorption, calcium release from bone, inhibits phosphate reabsorption
o Low PTH levels -> hypocalcaemia + hyperphosphataemia
119
Symptoms of hypoparathyroidism
o Increased excitability of muscles and nerves – spasms, paraesthesia around mouth/extremities, cramps, tetany, increased reflexes
120
Signs of hypoparathyroidism
o Chvostek – corner of mouth twitches when facial nerve tapped over parotid
o Trousseau – when BP cuff inflated hand spasms
121
Investigations for hypoparathyroidism
o Bloods – calcium and PTH low, phosphate high
| o ECG – prolonged QT
122
Management of hypoparathyroidism
o IV calcium – acute
o Vit D analogue – supplement if deficient
o Alfacalcidol if persistent
123
Definition of hyperparathyroidism
High levels of PTH
124
Causes of primary hyperparathyroidism
Solitary adenoma or hyperplasia
125
Signs and symptoms of hyperparathyroidism
o Often asymptomatic
| o Bones, stones, groans and moans
126
Investigations for primary hyperparathyroidism
Bloods: hypercalcaemia, low phosphate, high PTH, phosphatase high
127
Mangement of primary hyperparathyroidism
Surgical removal of adenoma
128
Complications of parathyroid surgery
o Hypoparathyroidism
| o Recurrent laryngeal nerve damage -> hoarse voice
129
Causes of secondary hyperparathyroidism
o CKD
o Low vit D
o Malabsorption
o Any condition with hypocalcaemia
130
Pathology of secondary hyperparathyroidism
Parathyroid gland becomes hyperplastic in response to chronic hypocalcaemia
131
Investigations for secondary hyperparathyroidism
Bloods: low calcium, high PTH, high phosphate (renal disease)
132
Management of secondary hyperparathyroidism
Correct causes and calcium correction
133
Pathology of tertiary hyperparathyroidism
Glands become autonomous so produce excess PTH even after calcium correction
134
Cause of tertiary hyperparathyroidism
CKD
135
Investigations for tertiary hyperparathyroidism
Bloods: high PTH, high calcium, high phosphate (renal failure)
136
Management of tertiary hyperparathyroidism
o Calcium mimetic (cinacalcet)
| o Parathyroidectomy
137
Causes of hyperprolactinaemia
o Prolactinoma
o Compression of the pituitary stalk, reducing local dopamine levels
o Dopamine antagonists
138
Symptoms of hyperprolactinaemia
o Menstrual irregularity/amenorrhoea/infertility
o Galactorrhoea
o Low libido
o Low testosterone in men – decreased facial hair, erectile dysfunction
o Pressure effects from tumour
139
Investigations for hyperprolactinaemia
o Test prolactin – CI antidopaminergic drugs
| o Do pregnancy test
140
Management of hyperprolactinaemia
o Dopamine agonists (first line) – cabergoline
| o Trans-sphenoidal pituitary resection
141
Definition of pheochromocytoma
Catecholamine (adrenaline) secreting tumour
142
Signs and symptoms of pheochromocytoma
o Headaches
o Sweating
o Tremor
o Tachycardia
143
Definition of carcinoid tumour
Serotonin secreting tumour (usually in gut, sometimes lungs)
144
Causes of carcinoid tumour
MEN1 and MEN2 increase incidence
145
Pathology of carcinoid syndrome
o Derived from enterochromaffin cells
o Secrete serotonin and Kallikrein -> increased
bradykinin if liver mets
146
Signs and symptoms of carcinoid syndrome
o Bronchospasm (wheezing)
o Diarrhoea
o Skin flushing and
o Right sided heart lesions
147
Investigations for carcinoid tumours
o Urine: high 5-hydroxyindoleacetic acid (serotonin
breakdown product)
o Liver US
o Octreoscan
148
Management of carcinoid tumours
o Somatostatin analogue (octreotide)
| o Surgical resection
149
What is diabetes insipidus?
Secretion or response to ADH is impaired
