Endocrinology 2 Flashcards
1
Q
Where does ingested glucose go?
A
40% to liver
60% to periphery (mostly muscle)
2
Q
What is glucagon?
A
A peptide hormone that raises the concentration of glucose and fatty acids in the bloodstream
3
Q
Which cells secrete glucagon?
A
Alpha cells of the Islets of Langerhans (in pancreas)
4
Q
Which cells secrete insulin?
A
Beta cells of the Islets of Langerhans (in pancreas)
5
Q
What is paracrine ‘crosstalk’ between alpha and beta cells?
A
When beta cells secrete insulin, there is tonic inhibition on alpha cells so that they cannot release glucagon
6
Q
What are examples of counterregulatory hormones?
A
Glucagon, adrenaline, cortisol and growth hormone
7
Q
What is type 1 diabetes?
A
Autoimmune destruction of pancreatic beta cells leading to complete insulin deficiency
8
Q
Describe the epidemiology of type 1 diabetes
A
- Usually presents between ages 5-15
- 10% of diabetes diagnoses
9
Q
Name the 3 risk factors for type 1 diabetes
A
- Family history (HLA DR3-DQ2 or HLA DR4-DQ8)
- Northern European
- Other autoimmune disease
10
Q
Describe the pathophysiology of type 1 diabetes
A
- Autoantibodies attach to beta cells
- This causes an insulin deficiency and leads to hyperglycaemia
- Insulin absence results in an increased breakdown of glycogen (hepatic gluconeogenesis)
- This decreases peripheral glucose causing glycosuria
11
Q
Name 5 symptoms of type 1 diabetes
A
- Polydipsia
- Polyuria
- Weight loss (BMI<25)
- Fatigue
- Ketosis
12
Q
What is type 2 diabetes?
A
Patient gradually becomes insulin resistant or pancreatic beta cells fail to secrete enough insulin. Progresses from impaired glucose tolerance
13
Q
Name 6 causes of type 2 diabetes
A
- Reduced insulin secretion
- Increased insulin resistance
- Gestational diabetes
- Steroids
- Cushing’s
- Chronic pancreatitis
14
Q
Name the 4 risk factors for type 2 diabetes
A
- Lifestyle (e.g. obesity, lack of exercise, excess of alcohol, diet)
- Asian men
- Age 40 and above
- Hypertension
15
Q
Name 6 symptoms of type 2 diabetes
A
- Polydipsia
- Polyuria
- Glycosuria
- Central obesity
- Blurred vision
- Fatigue
16
Q
What are the normal and diabetes levels of fasting plasma glucose?
A
Normal = <6mmol/L
Diabetes = >7mmol/L
* pre diabetes = between
17
Q
What are the normal and diabetes levels of random plasma glucose?
A
Normal = <11mmol/L
Diabetes = >11mmol/L
18
Q
What are the normal and diabetes levels of HbA1c?
A
Normal = <42mmol/L
Diabetes = >48mmol/L
* pre diabetes = between
19
Q
What does HbA1c measure?
A
Measures the amount of glucose latched onto circulating RBCs. As RBCs live for about 3 months, it tells you about glucose levels throughout the last 3 months
20
Q
What is the 1st line management for type 2 diabetes?
A
Lifestyle changes:
- Dietary advice
- Weight control
- Smoking cessation
- Decreased alcohol intake
- Encourage exercise
- Regular blood glucose and HbA1c monitoring
21
Q
What is the 2nd line management for type 2 diabetes?
A
Medications:
- Biguanides
- Dual therapy (biguanides + sulfonylureas)
- Triple therapy
- Insulin
22
Q
What are biguanides? Give an example and side effects
A
- E.g. metformin
- Cause decreased gluconeogenesis in the liver
- Increase cell sensitivity to insulin
- Side effects include GI disturbances
23
Q
What are sulfonylureas? Give an example and side effects
A
- E.g. gliclazide
- Promote insulin secretion by binding to beta cells
- Side effects include hypoglycaemia and weight gain
24
Q
What is diabetic ketoacidosis (DKA)?
A
Complete lack of insulin resulting in high ketone production (serious complication of type 1 diabetes)
25
Describe the pathophysiology of diabetic ketoacidosis
- Absence of insulin causes unrestrained gluconeogenesis --> hyperglycaemia
- Hyperglycaemia causes osmotic diuresis and dehydration
- Increase in circulating free fatty acids which are oxidised to Acetyl CoA which form ketone bodies (which are acidic --> acidosis)
26
Name 5 signs of diabetic ketoacidosis
1. Kussmaul's breathing (deep and laboured breathing)
2. Pear drop breath
3. Hypotension
4. Tachycardia
5. Reduced tissue turgor
27
Name 5 symptoms of diabetic ketoacidosis
1. Extreme diabetes symptoms
2. Nausea and vomiting
3. Confusion and reduced mental state
4. Lethargy
5. Abdominal pain
28
What are 6 investigations for patients with diabetic ketoacidosis?
1. Random plasma glucose >11mmol/L
2. Plasma ketones >3mmol/L
3. Blood pH <7.35 or bicarb <15mmol/L
4. Urine dipstick = glucosuria and ketonuria
5. Serum U+E = raised urea and creatine
6. Serum U=E = decreased total K+ and increased serum K+
29
What is the treatment for diabetic ketoacidosis?
- ABC management
- Replace fluid (0.9% saline IV)
- IV insulin
- Restore electrolytes
30
What is hyperosmolar hyperglycaemia state (HHS)?
Marked hyperglycaemia, hyperosmolality and mild/no ketosis (serious complication of type 2 diabetes)
31
Describe the pathophysiology of hyperosmolar hyperglycaemia state
- Low insulin causes increased gluconeogenesis --> hyperglycaemia (however there are sufficient enough levels of insulin to inhibit ketogenesis)
- Hyperglycaemia causes osmotic diuresis and dehydration
32
Name 5 symptoms of hyperosmolar hyperglycaemic state
1. Extreme diabetes symptoms
2. Confusion and reduced mental state
3. Lethargy
4. Hyperosmolality
5. No ketones in blood or urine
33
What are the investigations for patients with hyperosmolar hyperglycaemic state?
1. Random plasma glucose >11mmol/L
2. Urine dipstick = glycosuria
3. High plasma osmolality
4. U+E = decreased total K+ and increased serum K+
34
What is the treatment for hyperosmolar hyperglycaemia state?
- Replace fluid (0.9% saline IV)
- Insulin
- Restore electrolytes
- Low molecular weight heparin (to decrease risk of thromboembolism)
35
What is hypoglycaemia?
Low glucose levels
36
How is hypoglycaemia classified?
- Level 1 = plasma glucose <3.9mmol/L and no symptoms
- Level 2 = plasma glucose <3mmol/L
- Non-severe = patient has symptoms but can self treat and cognitive function is mildly impaired
- Severe = patient has impaired cognitive function sufficient to require external help tor recover
37
Name 5 autonomic symptoms of hypoglycaemia
1. Trembling
2. Palpitations
3. Sweating
4. Anxiety
5. Hunger
38
Name 6 neuroglycopenic symptoms of hypoglycaemia
1. Difficulty concentrating
2. Confusion
3. Weakness
4. Drowsiness/dizziness
5. Vision changes
6. Difficulty speaking
39
Name 2 non specific symptoms of hypoglycaemia
1. Nausea
2. Headache
40
What is the treatment for hypoglycaemia?
- Treat with 15g fast-acting carbohydrate
- Retest in 15 mins to ensure blood glucose >4mmol/L
- Eat long-acting carbohydrate
41
What is hyperthyroidism and what are the two types?
Excess thyroid hormone
Primary = abnormal increased thyroid function
Secondary = abnormal increased TSH production
42
Name 5 primary causes of hyperthyroidism
1. Grave's disease2. Nodules (multinodular goitre, toxic adenomas)3. Iodine excess4. Amiodarone5. Metastatic follicular thyroid cancer
43
Name a secondary cause of hyperthyroidism
TSH pituitary tumour
44
What is Grave's disease?
An autoimmune condition in which there is increased production of T3 and T4 due to antibodies binding to TSH receptors
45
Describe how Grave's disease works
- IgG autoantibodies (anti-TSHR-Ab) are produced which bind to and activate thyrotropin receptors
- This results in the increased production of thyroid hormones (T3 and T4)
46
What does Grave's disease cause?
- Symptoms of hyperthyroidism
- Thyroid eye disease = eyelid retraction, periorbital swelling, proptosis/exophthalmos
- Pretibial myxoedema
- Thyroid acropachy
47
What is pretibial myxoedema?
Accumulation of excess glycosaminoglycans in the dermis and subcutis of the skin
48
What does thyroid acropachy cause?
- Nail clubbing
- Painful swelling of digits/toes
- Periosteal reaction (bone growth)
49
What are the 5 risk factors for hyperthyroidism?
1. Being female (F:M = 9:1)2. Smoking3. Stress4. Genetic (HLA-DR3)5. Other autoimmune diseases
50
Describe the pathophysiology of hyperthyroidism
- Increased T3 causes an increase in metabolic rate
- This activates the sympathetic nervous system and so increases cardiac output, bone resorption etc.
51
What are the 3 signs of hyperthyroidism?
1. Periorbital swelling2. Goitre3. Tachycardia
52
What are 8 symptoms of hyperthyroidism?
1. Hot and sweaty
2. Diarrhoea
3. Weight loss
4. Anxiety/restlessness
5. Hyperphagia (increased desire to eat)
6. Oligomenorrhoea (irregular menstrual bleeding)
7. Palpitations
8. Tremor
53
What are the investigations for patients with hyperthyroidism?
- Thyroid function tests (TFTs) = high T3/T4 but low TSH (primary), high T3/T4 and high TSH (secondary)
- Thyroid autoantibodies (anti-TSHR)
- US and CT head
54
What is the treatment for hyperthyroidism?
1. Drug management2. Radioiodine3. Thyroidectomy
55
Describe drug management for hyperthyroidism
1st line = carbimazole (blocks synthesis of T4)2nd line = propylthiouracil (prevents conversion of T4 into T3)Beta blockers = provide rapid symptom relief
56
What is hypothyroidism and what are the two types?
Lack of thyroid hormone
Primary = abnormal decreased thyroid function
Secondary = abnormal decreased TSH production
57
Name 5 primary causes of hypothyroidism
1. Hashimoto's2. Primary atrophic hypothyroidism3. Iodine deficiency4. Drugs5. Post thyroidectomy/radioiodine
58
Name a secondary cause of hypothyroidism
Hypopituitarism
59
What is Hashimoto's?
An autoimmune condition in which antibodies attack the thyroid causing inflammation and dysfunction, lowering T3/T4 levels
60
What are the 3 risk factors for hypothyroidism?
1. Being female (F:M = 6:1)2. Post partum3. Other autoimmune diseases
61
Describe the pathophysiology of hypothyroidism
- Decreased T3 levels mean that there is an insufficient amount for normal body functions
62
What are the 3 signs of hypothyroidism?
1. Delayed reflexes2. Goitre3. Bradycardia
63
What are the 8 symptoms of hypothyroidism?
1. Cold intolerance2. Constipation3. Weight gain4. Fatigue and lethargy5. Loss of appetite6. Menorrhagia (heavy menstrual bleeding)7. Brain fog8. Depression
64
What are the investigations for patients with hypothyroidism?
- Thyroid function tests (TFTs) = low T3/T4 but high TSH (primary), low T3/T4 and low TSH (secondary)- Autoantibodies (anti-TPO)
65
What is the treatment for hypothyroidism?
Levothyroxine (T4)
66
What are 4 other causes of thyroid disorders?
1. De Quervain's Thyroiditis2. Post-partum thyroiditis3. Amiodarone4. Lithium toxicity
67
What is De Quervain's Thyroiditis?
- Mild hyperthyroidism following a viral infection of the thyroid- Lasts for a few weeks- Pain and tenderness over thyroid gland- Flu-like symptoms- Beta blockers given to relief symptoms, no other treatment given
68
What is post-partum thyroiditis?
- Mild hyperthyroidism which develops in the first year after childbrith- Lasts for a few weeks- Often very few symptoms- Beta blockers given to relief symptoms, no other treatment given
69
What is amiodarone and how does it affect the thyroid?
- An iodine-containing drug used for the treatment of certain irregularities of heart rhythm- Can cause hyperthyroidism or hypothyroidism- Blood thyroid levels should be checked before and throughout taking the drug
70
What is lithium toxicity and how does it affect the thyroid?
- Lithium carbonate is used for depression and mania- It can cause goitres and hypothyroidism- Thyroxine is given alongside treatment
71
What are the two main types of thyroid cancer?
1. Papillary cancer - tumour contains papillae or fronds2. Follicular cancer - distinctly abnormal appearance with some structures that resemble the normal follicles of the thyroid
72
How is thyroid cancer diagnosed?
Fine needle aspiration (type of biopsy) or following surgery
73
How is papillary cancer treated?
Total thyroidectomy as there is a tendency for the cancer to occur in various places throughout the gland
74
How is follicular cancer treated?
Hemithyroidectomy as it tends to only occur in one part of the thyroid
75
What additional treatment is given following thyroidectomys?
- Radioactive iodine given to remove any remaining cancer cells- Thyroxine (T4) given to reduce TSH levels in the blood
76
Where is the pituitary gland?
Embedded in the sella turcica just below the optic chiasma
77
Describe the blood supply of the anterior pituitary gland (adenohypophysis)
- No arterial blood supply- Receives blood through a portal venous system from the hypothalamus
78
What 4 things does the pituitary gland control?
- Growth (GH)- Thyroid (TSH)- Puberty/fertility (LH, FSH)- Cortisol
79
Describe the thyroid axis
- Hypothalamus releases TRH (thyrotropin releasing hormone)- This stimulates the release of TSH (thyroid stimulating hormone) from the anterior pituitary- This stimulates the thyroid follicular cells to release T3 ad T4- T3 and T4 feedback to the hypothalamus and pituitary (negative feedback)
80
If the thyroid gland is removed, will TSH levels increase or decrease?
Increase
81
If the thyroid is overactive (thyrotoxicosis), will TSH levels increase or decrease?
Decrease
82
Describe the gonadal axis
- The hypothalamus releases GnRH (gonadotrophin-releasing hormone)- This triggers the release of LH and FSH from the anterior pituitary- LH stimulates the release of testosterone from the testis (men) and oestrogen/estradiol (women) from the ovaries to trigger ovulation- FSH triggers the production of sperm (men) and eggs (women)- Oestrogen and testosterone feedback at the pituitary and hypothalamus (negative feedback)
83
Describe what happens to LH, FSH and oestrogen levels at menopause
Ovaries fail and stop secreting oestrogen which causes LH and FSH levels to increase
84
Describe what happens to gonadotropin levels if people are taking testosterone/anabolic steroids
Gonadotropin levels will decrease
85
Describe the hypothalamus-pituitary-adrenal (HPA) axis
- Hypothalamus produced CRH (corticotrophin releasing hormone)- This stimulates the anterior pituitary to release ACTH (adrenocorticotrophic hormone)- This stimulates the release of cortisol from the adrenal glands- Cortisol feeds back to the hypothalamus and pituitary (negative feedback)
86
Describe what happens to the adrenal glands if pateints are taking steroids?
ACTH production is switched off so the release of cortisol is decreased and the adrenal glands are suppressed
87
Describe the growth hormone (GH)/insulin-like growth factors (IGF-1) axis
- The hypothalamus releases GHRH (growth hormone releasing hormone) and SMS (somatostatin)- These stimulate the anterior pituitary to release GH (growth hormone)- This stimulates the release of ILGF-1 (insulin-like growth factor-1) from the liver- IGF-1 feeds back
88
Describe the release of prolactin
- Dopamine is secreted from the hypothalamus- This inhibits prolactin release (inhibitory hormone)- Prolactin is released from the anterior pituitary gland when dopamine levels are low
89
Describe what happens to prolactin levels when a patient has a damaged hypothalamus or is taking anti-dopaminergic drugs
Prolactin levels will increase as there is a lack of dopamine to inhibit it
90
Name 5 diseases of the pituitary
1. Benign pituitary adenoma2. Craniopharyngioma3. Trauma4. Sheehan syndrome --> apoplexy5. Sarcoidosis/TB
91
Describe the effect of benign pituitary adenomas on the pituitary
Can grow bigger and cause damage e.g. by pressing on optic nerves
92
Describe the effect of craniopharygiomas on the pituitary
Benign tumours that are epithelial in origin. Despite being benign, they can grow large and have cysts
93
Describe the effect of trauma on the pituitary
Shaking/rupture of the pituitary stalk from trauma can cause hypopituitarism
94
Describe the effect of Sheehan syndrome on the pituitary (apoplexy)
The pituitary gland may grow (particularly in pregnancy). Extreme blood loss (e.g. during childbirth/post partum bleeds) can cause injury/infarction of the pituitary causing apoplexy
95
What is apoplexy?
Unconsciousness/incapacity resulting from cerebral haemorrhage or stroke
96
Describe the effect of sarcoidosis/TB on the pituitary
Inflammatory conditions can cause inflammation of the hypothalamus and pituitary which can cause hypopituitarism
97
What 3 questions should be asked regarding pituitary tumours?
1. Is there pressure on local structures?2. Is there pressure on the normal pituitary?3. Is it a functioning tumour?
98
Why should you ask if there is pressure on local structures regarding pituitary tumours?
- Pressure on optic chiasm can cause bitemporal hemianopia (visual field defects)
- Pressure on the 4th ventricle can cause hydrocephalus/stretching of dura which can lead to headaches
- Lateral extension of tumour can cause other cranial nerve palsies
- Downward extension of tumour can cause CSF to leak through the sella turcica into the sphenoid sinus and out through the nose
99
Why should you ask if there is pressure on the normal pituitary regarding pituitary tumours?
- Can cause hypopituitarism (may need to replace hormones)
- Commonly presents in males as pale, hairless and central obesity (fat, pale, hairless male)
100
Why should you ask if it is a functioning tumour regarding pituitary tumours?
- Prolactinoma- Acromegaly/gigantism- Cushing's disease
101
What is a prolactinoma?
A non cancerous tumour of the pituitary gland causing it to produce too much prolactin
102
What does prolactin do?
- Initiates lactation and breast development- Controls osmolality and carbs/fat metabolism
103
What is a sign of a prolactinoma?
Low testosterone
104
What are 4 symptoms of a prolactinoma?
1. Amenorrhoea (absence of menstruation)2. Galactorrhoea (nipple discharge)3. Gynaecomastia (swelling of breasts in males)4. Low libido
105
What is the treatment for patients with prolactinomas?
- Surgery- Bromocriptine/cabergoline (dopamine agonists)
106
What is acromegaly?
Rapid growth of body tissues and bones due to excess production of growth hormone by pituitary tumours (gigantism in children)
107
What does growth hormone do?
- Stimulates bone and muscle growth- Increases protein synthesis and fat/glycogen breakdown- ILGF-1 also drives growth
108
What are the 3 signs of acromegaly?
1. Hypertension2. Insulin resistance3. Bitemporal hemianopia
109
What are the 5 symptoms of acromegaly?
1. Large hands2. Box jaw3. Thick skin4. Arthritis5. Sight problems
110
How is acromegaly diagnosed?
- ILGF-1 blood test- Ask about changes in ring/shoe size over time
111
How is acromegaly treated?
- Tumour surgery- Dopamine agonist (cabergoline)- Somatostatin analogue (octreotide)- GH receptor antagonist (pegvisomant)
112
What is Cushing's syndrome?
Chronic excess of cortisol hormone released by the adrenal glands due to an ACTH secreting pituitary adenoma (leads to bilateral hyperplasia)
113
What can cause excess cortisol levels (besides Cushing's syndrome)?
- ACTH dependent causes (ectopic ACTH production or ACTH treatment)- ACTH independent causes (adrenal adenomas/iatrogenic)
114
How does Cushing's syndrome present clinically?
1. Central obesity2. Plethoric complexion (red)3. Moon face4. Mood change5. Proximal muscle weakness6. Purple abdominal striae7. Gastric ulcers8. Osteoporosis9. Hirsutism (excess hair growth)10. Buffalo hump
115
How is Cushing's syndrome diagnosed?
- Drug history (can be caused by oral steroids)- Screening = random plasma cortisol- High random plasma cortisol --> overnight dexamethasone suspension test- ^ positive = test plasma ACTH
116
What is the treatment for Cushing's syndrome?
- If caused by pituitary adenoma = trans sphenoidal surgical resection- If caused by adrenal adenoma = adrenalectomy
117
What is a carcinoid tumour?
Rare tumour of the neuroendocrine system that secretes serotonin
118
What is a carcinoid crisis?
- When a carcinoid tumour outgrows its blood supply or is handled too much during surgery, mediators flood out- Results in life threatening vasodilation, hypotension, tachycardia, bronchoconstriction and hyperglycaemia
119
How is a carcinoid crisis treated?
High dose octreotide and supportive measures/careful management of fluid balance
120
What is carcinoid syndrome?
Groups of symptoms due to the release of serotonin and their vasoactive peptides into the systemic circulation from a carcinoid tumour
121
What are the characteristics of carcinoid syndrome?
- Tend to express somatostatin receptors- Affects the lung, stomach and bowel- Metastasises to the liver
122
What are the 4 symptoms of carcinoid syndrome?
1. Palpitations2. Abdominal cramps3. Diarrhoea4. Flushing
123
What are the 2 signs of carcinoid syndrome?
1. Signs of right heart failure2. Bronchospasm
124
What are the investigations for patients with carcinoid syndrome?
- 24 hours 5 hydroxyindoleacetic acid increase (product of serotonin breakdown)- Metabolic panel and LFTs- Liver ultrasound to confirm metastases
125
How is carcinoid syndrome treated?
- Local = surgical resection and peri-operative octreotide infusion- Metastases = above and additional radiofrequency and ablation
126
What is octreotide?
- A somatostain analogue- Blocks the release of tumour mediators and counters peripheral effects
127
What is Conn's syndrome?
Autonomous aldosterone production that exceeds the body's requirements and is independent of the renin-angiotensin II system (primary hyperaldosteronism)
128
What are the 2 causes of Conn's syndrome?
1. Aldosterone-producing unilateral adenoma in adrenal gland (one gland)2. Bilateral adrenal hyperplasia (both glands)
129
Describe the consequences of excess aldosterone
- Causes increased K+ excretion and increased Na/water retention- = hypokalaemia --> muscle dysfunction --> heart problems
- Low renin release
130
What are the 2 signs of Conn's syndrome?
1. Hypertension (resistant)2. Hypokalemia
131
What are the 6 symptoms of Conn's syndrome?
1. Polyuria/polydipsia2. Nocturia3. Mood disturbance4. Difficulty concentrating5. Muscle weakness6. Parasthesia
132
What are the investigations for patients with Conn's syndrome?
- Aldosterone:renin ratio blood test = increased- Plasma potassium = reduced- U+E
133
What are the aims of treatment for Conn's syndrome?
- Lower blood pressure- Decrease aldosterone levels- Resolve electrolyte imbalance
134
What are the treatments for Conn's syndrome?
- If single benign adrenal tumour = laparoscopic unilateral adrenalectomy- If bilateral adrenal hyperplasia = spironolactone (aldosterone antagonist)
135
What is Addison's disease?
- Primary adrenal insufficiency- Disorder that affects the adrenal glands, causing decreased production of adrenocortical hormones (cortisol/aldosterone)
136
What are the 3 causes of Addison's disease?
- Autoimmune destruction (21-hydroxylase antibodies)- TB- Adrenal metastases
137
Describe the pathophysiology of Addison's disease
- Destruction of adrenal cortex- Decreased production of glucocorticoid (cortisol) and mineralocorticoid (aldosterone)
138
What are the 3 risk factors for Addison's disease?
1. Being female2. Adrenocortical antibodies3. Other autoimmune diseases
139
What are the 3 signs of Addison's disease?
1. Hyperpigmentation2. Postural hypotension3. Hypoglycaemia
140
What are the 3 symptoms of Addison's disease?
1. Fatigue2. Weakness3. Weight loss
141
What are the investigations for patients with Addison's disease?
- Serum electrolytes = decreased Na+ and increased K+
- U+E = hyponatraemia, hyperkalaemia and hypoglycaemia
- Short SynACTHen test (ACTH stimulation test) = low cortisol and high ACTH
- FBC = anaemia and eosinophilia
- Reduced morning serum cortisol
- Adrenal CT/MRI
- 21-hydroxylase adrenal autoantibodies
142
What is the management for Addison's disease?
- Give glucocorticoid (cortisol - hydrocortisone) and mineralocorticoid (aldosterone - fludrocortisone)- Treat underlying cause
143
What is secondary adrenal insufficiency?
- Decreased ACTH levels which leads to adrenal failure- Occurs in patients with pituitary or hypothalamic involvement
144
What is the most common cause of secondary adrenal insufficiency?
Iatrogenic due to long term steroid therapy (can cause suppression of the pituitary adrenal axis). Only becomes apparent upon withdrawal of steroids
145
Describe the pathophysiology of secondary adrenal insufficiency
- Pituitary gland does not produce enough ACTH (adrenocorticotropic hormone)- ACTH therefore cannot act on the adrenal cortex to release cortisol, aldosterone and androgens
146
What is SIADH?
- Syndrome of inappropriate ADH- Inappropriately large amounts of ADH (antidiuretic hormone) secretion causing water to be reabsorbed in the collecting duct
147
Name 6 causes of SIADH
1. Lung Disease (Small cell lung cancer)2. Infection3. Abscess or cancer4. Drugs 5. Head/brain injury6. Hypothyroidism
148
What are the 4 signs of SIADH?
1. Severe hyponatraemia2. Raised jugular venous pressure (JVP)3. Oedema4. Ascites (fluid in abdomen)
149
What are the 5 symptoms of SIADH?
1. Headache2. Nausea/vomiting3. Fatigue/lethargy4. Muscle cramps/weakness5. Confusion
150
What are the investigations for patients with SIADH?
- Diagnosis of exclusion- U+E = hyponatraemia (low Na+, normal K+ - need to exclude causes of hyponatraemia)- High urine Na+- High urine osmolality
151
How is SIADH treated?
- Treat underlying cause- Stop causative medicine- Fluid restriction - Tolvaptan (ADH receptor blocker to increase osmolarity)
152
What is diabetes insipidus?
The passage of large volumes (>3L/day) of dilute urine due to impaired water resorption by the kidney due to lack of ADH
153
What are the 5 cranial causes of diabetes insipidus?
1. Idiopathic2. Congenital3. Tumour4. Trauma5. Infection
154
What are the 4 nephrogenic causes of diabetes insipidus?
1. Inherited2. Metabolism (low K+, high Ca2+)3. Drugs (lithium)4. Chronic renal disease
155
Describe the pathophysiology of diabetes insipidus (cranial)
- Reduced ADH secretion from the posterior pituitary so large volumes of dilute urine
- Impaired water retention from the kidneys
156
Describe the pathophysiology of diabetes insipidus (nephrogenic)
- Impaired response of kidneys to ADH so large volumes of dilute urine
- Impaired water retention from the kidneys
157
Diabetes insipidus is an important cause of...?
Hyponatraemia
158
What are the 3 signs of diabetes insipidus?
1. Dry mucosa2. Sunken eyes3. Changes to skin turgidity
159
What are the 2 symptoms of diabetes insipidus?
1. Polyuria2. Polydipsia
160
What are the treatments for patients with diabetes insipidus?
- Treat underlying cause - Rehydration- Cranial = desmopressin (synthetic ADH)- Nephrogenic = bendroflumethiazide (thiazide diuretics)
161
What is hyperparathyroidism?
Excessive secretion of parathyroid hormone (PTH)
162
Describe the types of hyperparathyroidism
Primary - 1 parathyroid gland produces excess PTH
Secondary - increased secretion of PTH to compensate hypocalcaemia
Tertiary - autonomous secretion of PTH even after correction of calcium deficiency due to chronic kidney disease (CKD)
163
What are the 2 causes of primary hyperparathyroidism?
1. Adenomas (80%)2. Hyperplasia of all glands (20%)
164
What are the 2 causes of secondary hyperparathyroidism?
1. CKD2. Low vitamin D
165
What is the cause of tertiary hyperparathyroidism?
Develops from prolonger secondary hyperparathyroidism
166
Describe the pathophysiology of hyperparathyroidism
PTH increases Ca2+ levels through increased bone resorption, gut absorption, renal re absorption and activating vitamin D
167
What is the main sign of hyperparathyroidism?
Hypercalcaemia
168
What are the 4 symptoms of hyperparathyroidism?
1. Bones (bone pain)2. Stones (renal calculi)3. Moans (psychic moans/depression)4. Groans (abdominal problems - constipation, indigestion, nausea, vomiting)
169
What are the investigations for patients with hyperparathyroidism?
- PTH/bone profile = high PTH, high Ca2+, low phosphates (low serum Ca2+ in secondary)- DEXA scan- X ray = salt and pepper degradation of bone- Ultrasound for stones
170
How is primary hyperparathyroidism treated?
- Surgical removal of adenoma- Give bisphosphonates
171
How is secondary hyperparathyroidism treated?
- Calcium correction- Treat underlying cause
172
How is tertiary hyperparathyroidism treated?
- Cinacalcet (calcium mimetic)- Total/partial parathyroidectomy
173
What is a phaeochromocytoma?
Adrenal medullary tumour that secretes catecholamines (VERY RARE)
174
Phaeochromocytomas occur in certain familial syndromes including...?
1. Multiple endocrine neoplasia (MEN syndrome)2. Neurofibromatosis3. Von-Hippel Lindau Disease
175
What are the 5 signs of phaeochromocytoma?
1. Hypertension2. Postural hypotension3. Tremor4. Hypertensive retinopathy5. Pallor
176
What are the 4 symptoms of phaeochromocytoma?
1. Headache2. Profuse sweating3. Palpitations4. Tremor
177
What are the investigations for patients with phaeochromocytoma?
- Plasma metanephrines and normetanephrines- 24 hour urinary total catecholamines- CT for tumour
178
What are the treatments for phaeochromocytoma?
- Without HTN crisis (hypertensive crisis) = alpha blockers (phenoxybenzamine) and removal of tumour- With HTN crisis = antihypertensive agents (phentolamine)
179
What is the action of PTH on the kidneys?
- Increased Ca2+ reabsorption- Decreased phosphate reabsorption- Increased 1 alpha-hydroxylation (activation) of 25-OH vitamin D
180
What is the action of PTH on bone?
- Increased bone remodelling- Bone resorption > bone formation
181
What is the action of PTH on the GI tract?
- No direct effect- Increased Ca2+ absorption due to increased 1,25(OH)2 vitamin D
182
What is the set point of serum ionised calcium?
1.1mmol/L
183
Explain the parathyroid response to low serum calcium
- PTH increases- Increased Ca2+ reabsorption at the kidneys- Increased bone resorption- Urinary phosphate excretion increases so serum phosphate decreases- 1,25-(OH)2 vitamin D increases therefore increased Ca2+ absorption in the GI tract
184
What is hypocalcaemia?
Low calcium
185
What can cause patients to appear as if they have hypocalcaemia but don't?
Low serum albumin can cause low total serum calcium but not a low ionised calcium
186
What are the 4 symptoms of hypocalcaemia?
CATs go numb1. Convulsions2. Arrhythmias3. Tetany4. Numbness/parasthesia in hands, feet, around mouth/lips
187
What are the 2 signs of hypocalcaemia?
1. Chevosteks (contraction of facial muscle when light tapping of facial nerve in front of ear)2. Trousseaus (spasm of hand/wrist when BP cuff inflated)
188
How do you calculate corrected calcium?
Total serum calcium + (0.02 x (40 - serum albumin))
189
How does hypocalcaemia affect an ECG?
Long QT interval
190
Describe what happens to calcium, phosphate and PTH levels in patients with a vitamin D deficiency
- Calcium levels decrease as there is reduced absorption in the GI tract- PTH levels increase in order to increase calcium levels- Phosphate levels decrease due to increased PTH
191
Describe what happens to calcium, phosphate and PTH levels in patients with hypoparathyroidism
- PTH levels decrease due to underactive parathyroid glands- Calcium levels therefore decrease as there is decreased renal reabsorption and increased excretion- Phosphate levels increase due to increased renal reabsorption
192
What is pseudohypoparathyroidism?
Resistance to PTH (parathyroid hormone)
193
Describe what happens to calcium, phosphate and PTH levels in patients with pseudohypoparathyroidism
- Calcium levels decrease as PTH is ineffective- PTH levels increase as there are continuously low calcium levels- Phosphate levels increase
194
What is hypercalcaemia?
High calcium
195
What can cause patients to appear as if they have hypercalcaemia but don't?
- Tourniquet being on for too long- Old/haemolysed sampled being used
196
Name 3 causes of hypercalcaemia
1. Malignancy (bone mets, myeloma, lymphoma)2. Primary hyperparathyroidism3. Thiazides
197
What are the 4 symptoms of hypercalcaemia?
1. Bones (bone pain)2. Stones (renal calculi)3. Moans (psychic moans/depression)4. Groans (abdominal problems - constipation, indigestion, nausea, vomiting)
198
What are the 2 signs of hypercalcaemia?
1. Kidney stones2. Short QT interval
199
Describe what happens to calcium and PTH levels in patients with hypercalcaemia of malignancy
- Calcium levels will be high- Therefore PTH levels will decrease as there is less Ca2+ reabsorption required
200
Describe what happens to calcium, phosphate and PTH levels in patients with primary hyperparathyroidism
- PTH levels increase due to overactive parathyroid glands- Calcium levels therefore increase as there is increased renal reabsorption- Phosphate levels decrease due to decreased renal reabsorption
201
What is hyperkalaemia?
Higher than normal potassium levels in the blood (>5.5mmol/L)
202
What are the 3 general causes of hyperkalaemia?
1. Impaired excretion2. Increased intake3. Shift to extracellular
203
What are the 4 impaired excretion causes of hyperkalaemia?
1. AKI (acute kidney injury) or CKD (chronic kidney disease)2. Drug affect (ACE inhibitors, NSAIDs, beta blockers)3. Renal tubular acidosis4. Addison's disease
204
What are the 2 increased intake causes of hyperkalaemia?
1. IV K+ therapy2. Increased dietary intake
205
What are the 4 shift to extracellular causes of hyperkalaemia?
1. Metabolic acidosis2. Rhabdomyolysis3. Decreased insulin4. Tumour lysis syndrome
206
What are the 3 signs of hyperkalaemia?
1. Arrhythmia
2. Reduced power and reflexes
3. Flaccid paralysis
207
What are the 4 symptoms of hyperkalaemia?
1. Fatigue and light headedness2. Weakness3. Chest pain4. Palpitations
208
What are the investigations for patients with hyperkalaemia?
- ECG
- FBC and U+E
- Urine osmolality and electrolytes
209
How does hyperkalaemia affect an ECG?
- Small/absent P waves
- Prolonged PR interval (>200ms)
- Wide QRS interval (>120ms)
- Tall tented T waves
210
What is the treatment for hyperkalaemia?
- ABC- Cardiac monitoring- Calcium gluconate (to protect myocardium)- Insulin + Dextrose or nebulised salbutamol (to drive K+ intracellularly)- Treat underlying cause
211
What is hypokalaemia?
Lower than normal potassium levels in the blood (<3.5mmol/L)
212
What are the 3 general causes of hypokalaemia?
1. Increased excretion2. Decreased intake3. Shift to intracellular
213
What are the 4 increased excretion causes of hypokalaemia?
1. Renal disease2. Drug effect (thiazide, loop diuretics, laxatives)3. GI loss (diarrhoea and vomiting)4. Conn's syndrome
214
What are the 2 decreased intake causes of hypokalaemia?
1. Dietary deficiency or fasting2. Liquorice abuse
215
What are the 2 shift to intracellular causes of hypokalaemia?
1. Metabolic alkalosis2. Drug effects (insulin, B2 agonists (SABAs e.g. salbutamol and LABAs)
216
What are the 3 signs of hypokalaemia?
1. Arrhythmia2. Muscle paralysis3. Rhabdomyolysis
217
What are 4 symptoms of hypokalaemia?
Asymptomatic
1. Fatigue
2. Generalised weakness
3. Muscle cramps and pain
4. Palpitations
218
What are the investigations for patients with hypokalaemia?
- ECG- FBC and U+E- Urine osmolality and electrolytes
219
How does hypokalaemia affect an ECG?
- Prolonged PR interval
- ST depression
- Flat T waves
- Prominent U waves
220
What is the treatment for hypokalaemia?
- Potassium (PO/IV)- Other electrolytes- Treat underlying cause
221
What is hyponatraemia?
Lower than average sodium levels in the blood
222
What is hypernatraemia?
Higher than average sodium levels in the blood
223
What is hypoparathyroidism?
Insufficient secretion of parathyroid hormone (PTH)
224
What are the 2 causes of primary hypoparathyroidism?
1. Autoimmune2. Congenital
225
Describe the pathophysiology of hypoparathyroidism
Lack of PTH decreases Ca2+ levels through decreased bone resorption, gut absorption, renal re absorption and no activation of vitamin D
226
What are the 3 signs of hypoparathyroidism?
1. Hypocalcaemia
2. Chevosteks (contraction of facial muscle when light tapping of facial nerve in front of ear)
3. Trousseaus (spasm of hand/wrist when BP cuff inflated)
227
What are the 4 symptoms of hypoparathyroidism?
CATs go numb1. Convulsions2. Arrhythmias3. Tetany4. Numbess/parasthesia in hands, feet, around the mouth/lips
228
What are the investigations for patients with hypoparathyroidism?
- PTH/bone profile = low PTH, low Ca2+, normal/high phosphates
229
How is hypoparathyroidism treated?
- IV calcium
- adcalD3
230
What is a complication of hypoparathyroidism?
Cardiac arrest
231
What is adrenal hyperplasia?
Defective enzymes mediating the production of adrenal cortex products
232
How does adrenal hyperplasia present in females?
1. Salt loss2. Ambiguous genitalia with common urogenital sinus
233
How does adrenal hyperplasia present in males?
1. Salt loss2. No/very few signs at birth3. Subtle hyperpigmentation 4. Possible penile enlargement
234
Describe the pathophysiology of adrenal hyperplasia
- Defective 21-hydroxylase disrupts cortisol biosynthesis- Causes cortisol deficiency with or without aldosterone deficiency and androgen excess
235
Describe the aetiology of adrenal hyperplasia
Genetic 21-hydroxylase deficiency causes about 95% of cases
236
What are the investigations in patients with adrenal hyperplasia?
Serum 17-hydroxyprogesterone (precursor to cortisol) levels - high
237
What is the treatment for adrenal hyperplasia?
- Glucocorticoids (cortisol) - hydrocortisone- Mineralocorticoid (aldosterone) - to control electrolytes- Sodium chloride supplement if salt loss
