Endocrine Flashcards
1
Q
Define endocrinology
A
Study of hormones and their glands or origin, receptors, intracellular signalling pathways and associated diseases
2
Q
Define endocrine
A
Glands pouring secretions directly into bloodstream without ducts
3
Q
Define exocrine
A
Glands pour secretions through a duct to the site of action
4
Q
Where do endocrine secretions act?
A
Blood borne- act at distant sites
5
Q
Where do paracrine secretions act?
A
Nearby adjacent cells
6
Q
Where do autocrine secretions act?
A
Feedback excerted on same cell that secretes the hormone
7
Q
What are the features of water soluble hormones?
A
Unbound
Bind to surface receptors
Short half life
Fast clearance
8
Q
What are the features of fat soluble hormones?
A
Protein bound
Diffuse into cell
Long half life
Slow clearance
9
Q
What is an example of a peptide hormone?
A
Insulin
10
Q
Outline peptide hormone synthesis, packaging and storage+secretions
A
Synthesis: prehormone -> prohormone
Packaging: prohormone -> hormone stored in vesicle
Storage and secretion: hormone released
11
Q
What are 3 amine hormones?
A
Dopamine
Adrenaline
Noradrenaline
12
Q
How are peptide hormones released?
A
Pulses/ bursts
13
Q
What are adrenaline and noradrenaline broken down by?
A
COMT
14
Q
What is adrenaline broken down into?
A
Metanephrine
15
Q
What is noradrenaline broken down into?
A
Normetanephrine
16
Q
What occurs when adrenaline binds to alpha receptors?
A
Vasoconstriction
Bowel contraction
Sweating and anxiety
17
Q
What occurs when adrenaline binds to beta receptors?
A
Vasodilation
Increased heart rate and contractility
Relaxation of bronchi
18
Q
What are 2 examples of iodothyronines?
A
T3: triiodothyronine
T4: thyroxine
19
Q
What are T3 and T4 bound to?
A
TBG: thyroid binding globulin
20
Q
Is T3 or T4 more active?
A
T3 more active but T4 more numerous
21
Q
Where is most T3 derived from?
A
Breakdown of T4
22
Q
What are 4 cholesterol derived hormones?
A
Cortisol
Aldosterone
Testosterone
Oestrogen
23
Q
How do steroids activate mRNA production?
A
Fat soluble so diffuses into cell
Receptor hormone complex enters nucleus
Binds to GRE
Binding initiates mRNA transcription
24
Q
What are 4 hormone receptor locations?
A
- Cell membrane
- Cytoplasm
- Nucleus
- Cytoplasm/nucleus
25
Where are peptide hormone receptors located?
Cell membrane
26
Where are steroid hormone receptors located?
Cytoplasm
27
Where are thyroid hormone receptors located?
Nucleus
28
What are 4 hormone secretion patterns?
1. Continuous release
2. Pulsatile
3. Circadian rhythm
4. Release inhibiting patterns
29
What is a hormone that is continuously released?
Prolactin
30
What is a hormone that is released in a Pulsatile pattern?
Insulin
31
What is a hormone that is released in a circadian rhythm?
Cortisol
GH
ACTH
32
What is a hormone that is controlled by release inhibiting factors?
Somatostatin and GH
33
Define synergism
Combined effects of 2 hormones amplified
34
Define antagonism (in term of hormones)
One hormone opposes the other hormone
35
Define diabetes mellitus
syndrome of chronic hyperglycaemia due to relative insulin deficiency, resistance, or both
36
Describe DMT1
When the pancreas doesn’t make any/insufficient insulin
37
What are normal blood glucose levels?
3.5-8 mmol/L
38
What are the functions of insulin?
Decreases glycogenolysis and gluconeogenesis
Increases glucose uptake in tissues
Suppresses lipolysis and ketogenesis
39
What are the 2 phases of insulin release?
1. B cells detect rising glucose and rapidly release insulin
2. If levels remain high, more is synthesised and released
40
What are the functions of glucagon?
Increases glycogenolysis and gluconeogenesis
Reduces peripheral glucose uptake
Stimulates peripheral release of gluconeogenic precursors
Stimulates lipolysis and ketogenesis
41
What is the precursor of insulin?
Proinsulin`
42
How is synthetic insulin detected?
Lack of C peptide
-C peptide is present when natural glucose is cleaved
43
What is the function of insulin in the fasting state?
Regulate glucose release by liver
44
What is the function of insulin in the post-prandial state?
Promote glucose uptake by fat and muscle
45
How is glucose transported into cells?
GLUT proteins
46
What is the function of GLUT-1 receptors?
Enables basal non-insulin stimulated glucose uptake
47
What is the function of GLUT-2 receptors?
In beta cells- transport in glucose enabling sensing of glucose levels and release insulin in response to high glucose
48
Where are GLUT-2 receptors found?
Beta cells mainly
-Renal tubules
-hepatocytes
49
What is the function of GLUT-3 receptors?
Enables non-insulin mediated glucose uptake in neurones and placenta
50
What is the function of GLUT-4 receptors?
Mediates peripheral insulin action- how glucose is taken into muscle and adipose tissue
51
What happens when glucose binds to a glucose receptor?
1. Activation of tyrosine kinase
2. Initiates cascade response
3. Migration of GLUT-4 to cell surface
4. Glucose uptake
52
What are some conditions that diabetes may be secondary to?
Pancreas issues eg. Pancreatitis
Endocrine disease eg. Acromegaly or Cushings
Drugs
MODY
53
Who is DMT1 most common in?
Children and young people
- Northern Europeans and especially Finnish people
54
What is LADA?
Latent autoimmune diabetes in adults
- DMT1 with slower progression to insulin deficiency
55
Outline the aetiology of DMT1
Autoimmune response destroys the beta cells of the pancreas
56
What are the risk factors of DMT1?
Northern European
Family history
Autoimmune disease- Addisons, pernicious anaemia, thyroid issues, coeliac
Dietary factors
Enteroviruses
Vitamin D deficiency
57
Outline the pathophysiology of DMT1
1. Destruction of beta cells via autoantibodies
2. Decreased insulin secretion
3. Breakdown of glycogen
58
Is C peptide found in patients with DMT1?
No- complete beta cell destruction
59
What is the main antibody in the circulation of patients with DMT1?
Glutamic acid decarboxylase (GAD)
60
What are the 3 main symptoms of DMT1?
Polyuria and nocturia
Polydipsia
Weight loss
61
Why does polyuria occur in DMT1?
Glucose dries water into urine and it can not be re absorbed as the maximum capacit has been reached
62
Why does polydipsia occur in DMT1?
Loss of fluid and electrolytes from excess water and glucose in urine
63
Why does weight loss occur in DMT1?
Fluid depletion
Breakdown of fat and muscle
64
What signs of DMT1 can be seen on physical examination?
Fruity breath
Lean patient
Cuts and bruises taking a while to heal
Signs of dehydration
65
What 4 investigations are carried out to diagnose DMT1 and 2?
HbA1c test
Fasting plasma glucose
Random plasma glucose
Oral glucose tolerance tests
66
What random plasma glucose value indicates diabetes?
> 11.1 mmol/L
67
What fasting plasma glucose value indicates diabetes?
> 7mmol/L
68
When are 2 abnormal values needed to diagnose diabetes?
Asymptomatic individuals
69
What test is used for borderline diabetes diagnosis?
OGTT
70
What values of an OGTT indicate diabetes?
Fasting = > 7mmol/L
2 hours post glucose = > 11.1mmol/L
71
What value on a HbA1c test indicates diabetes?
48mmol/mol (> 6.5% normal)
72
What does a HbA1c test measure?
Glycated haemoglobin shows average blood glucose over the past 3 months
73
What is the first line treatment for DMT1?
Basal bolus insulin
74
Why may some DMT1 patients be unable to drive?
Hypoglycaemia
Retinopathy
75
What are the 3 types of insulin doses?
Short acting soluble insulin
Short acting insulin analogues
Longer acting insulin
76
When are short acting soluble insulins given?
15-30 mins before meals
Insulin pumps
IV infusion in labour
77
When are short acting insulin analogues given?
Evening meal in patients prone to nocturnal hypoglycaemia
78
How long to short acting soluble insulins take to start working and last?
Work in 30-60 mins
Last for 4-6 hours
79
How are longer acting insulins made?
Retarding agents precipitate crystals
80
What are the complications of DMT1?
Heart disease
Stroke
Feet problems
Circulatory issues
Neuropathy
Nephropathy, sight problems
81
What are the complications of insulin treatment?
Hypoglycaemia
Lipohypertrophy
Insulin resistance
Weight gain
82
Define DMT2
Hyperglycaemia due to insulin resistance (mainly) and insulin deficiency
83
Outline the epidemiology of DMT2
More common in black and south Asian people
Usually >30
84
Describe the aetiology of DMT2
Decreased insulin secretion
Increased insulin resistance
85
List the risk factors of DMT2
Family history
Increasing age
Obesity and lack of exercise
Low birth weight
86
Is DMT2 associated with an insulin binding problem?
No- the resistance is post receptor
87
By how much is beta cell mass reduced in DMT2?
50%
88
What is an early sign of DMT2?
Loss of normal biphasic response
89
Why are circulating insulin levels high in DMT2 patients?
-Increased glucose production from lack of gluconeogenesis suppression
- Reduced peripheral glucose uptake
90
What is shown by starling curve of the pancreas?
Insulin levels rise and decline years after diabetes progression due to secretory failure
91
Why is DKA uncommon in patients with DMT2?
Small amounts of glucose can inhibit the breakdown of ketogenesis
92
What are the symptoms of DMT2?
Polyuria
Polydipsia
Weight loss
Retinopathy
Polyneuropathy can cause tingling and numbness in feet
Erectile dysfunction
93
What signs of DMT2 can be seen on physical examination?
Retinopathy
Acanthosis nigricans - insulin resistance causing black pigmentation on base of neck
94
What is the first line of treatment for DMT2?
Lifestyle and dietary changes
95
What is the first line of oral treatments for DMT2?
Biguanide eg. METFORMIN
96
How does metformin work?
Reduces gluconeogeneis
Increases glucose sensitivity
Reduces CVS risk
97
What has replaced sulfonylureas as the second line oral treatment for DMT2?
DPP-4 inhibitors
GLP-1 analogues
SGLT-2 inhibitors
98
How do sulfonylureas work?
Promote insulin secretion by binding to beta cell receptors
99
What are the risks of sulfonylureas?
- HYPOGLYCAEMIA
- can be dangerous in people with liver problems
- Weight gain
100
How do GLP analogues work?
Insulin alternative- mimic 2 peptide hormones and promote insulin release ect
101
How do SGLT-2 inhibitors work?
Block glucose reabsorption in the kidney
102
What are the side effects of SGLT-2 inhibitors?
Thrush
Euglycaemic ketoacidosis
103
What are the risks of DMT2?
CVD
Nephropathy
Strokes
Hearing damage
Sleep apnea
104
What type of DM is diabetic ketoacidosis (DKA) usually seen in?
DMT1
105
What 3 circumstances are linked with DKA?
1. Undiagnosed diabetes
2. Interruption of insulin therapy
3. Stress of intercurrent illness
106
What are the complications of DMT2?
Diabetic retinopathy
Diabetic neuropathy- can lead to amputation
Stroke
CVD (most commmon)
HHS- hyperglycaemic hyperosmolar state
107
What is the commonest type of monogenic diabetes?
MODY
108
What type of genetic mutation is MODY?
Autosomal dominant- single gene affects beta cell function
109
Outline the epidemiology of MODY
<25
Non-obese
110
What are the risk factors for MODY?
Parent with diabetes
Evidence of non-insulin dependence
111
Describe MODY3
HNF1A mutation
112
How is MODY3 treated?
Sensitive to sulphonylurea
Insulin usually not required 80%
113
Describe MODY2
Glucokinase gene mutation
114
Describe MODY1
HNF4A mutation
115
What are the qualities of MODY1?
Macrosomia (4.4kg birthweight)
AND
Neonatal hypoglycaemia
116
Describe investigations for diagnoses of MODY
Absence of islet autoantibodies
Sensitive to sulphonlyurea
No ketones
Measurable C peptide
Good control on low insulin
117
When can DKA occur in DMT2?
Late stage when there is absolute insulin deficiency
118
What does HHS stand for?
Hyperosmolar hyperglycaemic state
119
What is HHS?
Metabolic emergency characteristic of uncontrolled DMT2
120
What is the gold standard for diagnosing DMT2?
HbA1c
121
What are the micro vascular complications of DMT2?
Retinopathy
Neuropathy
Peripheral neuropathy
122
What are the macrovascular complications of DMT2?
Stroke
Hypertension
Peripheral artery disease
Coronary artery disease
123
Outline the pathophysiology of HHS
Insulin levels are reduced but sufficient to inhibit ketogenesis but not glucose production
Hyperglycaemia -> osmotic diuresis -> raised serum osmolarity and hyper viscosity of blood
124
Outline the epidemiology of HHS
Middle or later life of previously undiagnosed diabetes
125
What are the common presentations of HHS?
Severe dehydration
Hyperglycaemia
Decreased consciousness
Hyperosmolarity
No ketones
Stupor or coma
126
What is used to diagnose HHS?
Hyperglycaemia - glucose >11mmol/L
Heavy glycosuria - urine stick test
Hypotension
Hyperosmolarity
127
How is HHS treated?
Fluid replacement 0.9% saline
Low molecular weight heparin (anticoagulant)
Restore K+ loss
Insulin if ketones and lack of glucose decrease after treatment
128
What are the complications of HHS?
Stroke
MI
PE
129
What are the risk factors for DKA?
Stopping insulin
Infection
Surgery
MI
Pancreatitis
Undiagnosed diabetes
130
What ketone level is required for ketosis?
Blood ketones >3mmol/L
131
Outline the pathophysiology of DKA
Absence of insulin -> unrestrained glucose production and decreased uptake -> hyperglycaemia-> dehydration -> lipolysis -> inc. FFA -> ketones -> ACIDOSIS
132
How does DKA present?
Pear drop breath smell
Dehydration and hypotension
Nausea and vomiting
Abdo pain
Hyperventilating
Drowsy/reduced consciousness
133
How is DKA diagnosed (4 things)?
Hyperglycaemia >11mmol/L
Increased ketones >3mmol/L
Acidaemia = >7.3
Metabolic acidosis = bicarbonate <15mmol/L
134
How is DKA treated?
1.ABC
2. 0.9% saline fluid replacement
3. Insulin
4. Restore K+ loss
5. Treat diabetes
135
What are the complications of DKA?
Cerebral oedema (if fluid increased too quickly)
Coma
Hypotension
Thromboembolism
136
What are some ways to reduce the complications associated with DM?
BP control eg. Ramapril
Cessation of smoking
Statin eg simvastatin
137
When are people most at risk of diabetic retinopathy?
Long time DM
Poor glycaemic control
Hypertension
On insulin
Pregnant
138
What are the signs of diabetic retinopathy?
Tiny red dots- micro aneurysms
Blots- haemmorages
Cotton wool spots- micro infarcts of occluded vessels
139
How is diabetic retinopathy treated?
Laser therapy stabilises deterioration and prevents progression
140
What are the risks of laser surgery for diabetic retinopathy?
-Night vision difficulty
- 1/5 lose peripheral vision
- Vitreous haemorrhage
- Temporary drop in acuity with intensive treatment
141
What is the diagnostic marker for diabetic nephropathy?
Proteinuria via albumin: creatine ratio of >3
142
How does diabetic nephropathy occur?
Thickening of basement membrane due to poor glycaemic control
143
How is diabetic nephropathy treated?
Aggressive BP control ie. ACE inhibitor
Avoid metformin
Reduce insulin dose
Late stage = ESKD -> dialysis or transplant
144
How many diabetics does neuropathy affect?
30-35%
145
What is the most common form of diabetic neuropathy?
Distal symmetrical neuropathy
146
What are the risk factors of diabetic neuropathy?
Hypertension
Smoking
High HbA1c
Long duration of diabetes
High BMI
147
What are the features of diabetic neuropathy?
Pain: allodynia, parasthesia, burning
Diarrhoea, constipation
Erectile dysfunction
Loss of sensation in feet
148
How is diabetic neuropathy treated?
Good glycaemic control
Paracetamol
Tricyclic antidepressant eg. Amitriptyline
Anticonvulsant eg. Pregabalin
Opiates eg. Tramadol
149
Define appetite
The desire to eat food
150
Define anorexia
Lack of appetite
151
Define fullness
Feeling of fullness- appetite disappearing after a meal
152
What is the function of leptin?
Switches off appetite and is immunostimulatory
153
How do leptin levels change before and after a meal?
Increase after meal
Decrease after fasting
154
What are the effects of peptide YY?
Inhibits gastric motility
Reduces appetite
155
When and where is peptide YY secreted?
Secreted from ileum, pancreas and colon in response to food
156
What are the effects of cholecystokinin?
Satiety via vagus
-delays gastric emptying
- Gall bladder contraction
- insulin release
157
Where are cholecystokinin receptors found?
Pyloric sphincter
158
What are the functions of ghrelin?
Stimulates:
Gh release
Appetite
159
What 2 mechanisms stimulate appetite?
Olfactory, gustatory, cognitive and visual stimuli
Ghrelin secretion
160
What are 4 mechanisms that decrease appetite?
1. Oral receptors alter pleasantness and food intake
2. Stretch receptors in stomach increase satiety
3. CCK,GLP, Insulin, PYY increase satiety
4. Leptin, nutrients and temperature regulates satiety
161
What is the most common endocrine emergency?
Hypoglycaemia
162
What value indicates serious biochemical hypoglycaemia?
Plasma glucose <3 mmol/L
163
What value indicates alert level hypoglycaemia?
Plasma glucose < 3.9 mmol/L
164
What are the most common causes of hypoglycaemia in diabetics?
Insulin
Sulphonylurea
- Ie. Increased activity, missing meals, overdose
165
What are the non-diabetic causes of hypoglycaemia?
EXPLAIN:
EX-Exogenous drugs
P- Pituitary insufficiency
L- Liver failure
A- Addison’s disease
I- islets cell tumour and immune hypoglycaemia
N- Non-pancreatic neoplasm
166
What are the common symptoms of hypoglycaemia?
Autonomic: trembling, palpitations, sweating, anxiety and hunger
Neuroglycopenic: confusion, weakness, dizziness, vision changes
Nausea
Headache
167
How is hypoglycaemia diagnosed?
-Finger prick blood- low glucose < 3.9 mmol/L
-Elevated HbA1c can have symptoms > 3.9mmol/L
Also:
- drug history and exclude liver failure
- bloods: glucose, insulin, C-peptide, ketones
168
How is hypoglycaemia treated?
1. Oral sugar and long-acting starch
2. 50% IV glucose if unable to swallow, IM if not possible
169
What is goitre?
Swelling of the thyroid which causes a lump to form in the neck
170
What causes goitre?
TSH receptor stimulation which causes the thyroid to grow in size
171
How does hyperthyroidism cause goitre?
Excessive stimulation of TSH receptor = more hormone = growth
172
How does hypothyroidism cause goitre?
Pituitary detects low thyroid levels = more TSH production = stimulates TSH receptors
173
Define thyrotoxicosis
Excess thyroid hormones in blood
174
Define hyperthyroidism
Overproduction of thyroid hormone
-Increase synthesis of T3 and T4 in the thyroid gland
175
What is the most common cause of hyperthyroidism?
Most common- Graves’ disease
Toxic multinodular goitre
Toxic adenoma
Thyroiditis
Excess iodine
176
Describe the epidemiology of hyperthyroidism
Females
Genetic defects
177
Describe the risk factors of hyperthyroidism
Smoking
Stress
High iodine
Autoimmune disease- vitiligo, Addison’s, MG
178
Outline the pathophysiology of hyperthyroidism
1. IgG antibodies (in graves) bind to TSH receptors
2. T3 and T4 production stimulated
3. Low TSH levels
4. Effects metabolism, growth, and development
179
How is hyperthyroidism diagnosed?
1st line: thyroid function tests (TFTs)
- Serum TSH low
- High T4 and sometimes T3
TPO and thyroglobulin antibodies present
180
How is hyperthyroidism treated?
Thioamides (carbimazole) and propylthiouracil (PTU)
Propanolol: (ie beta blocker) to control symptoms
Radioactive iodine
Surgery
181
How does propylthiouracil (PTU) work?
Stops conversion of T4 to T3
182
How does oral carbimazole work?
Blocks thyroid hormone biosynthesis and has immunosuppressive effects
183
What type of drug is carbimazole?
Thioamide
184
What are the 2 strategies of thioadmide administration?
1. Titration: 4 weeks and then reduce doses according to thyroid function test
2. Block and replace therapy: carbimazole + thyroxine
185
What are the most common side effects of thiodmides?
RASH- most common
Hepatitis
Neuritis
Vasculitis
186
What side effects of thioamides mean the drug has to be stopped?
Sore throat
Mouth ulcers
Fever
187
What is the most serious side effect of thionamides?
Agranulocytosis: decrease in WBCs
- Must warn patients
- Stop if symptoms develop and check FBC
188
What is given for radioactive iodine treatment?
Radioactive I(131)
189
When is radioactive iodine contraindicated?
Pregnancy and breastfeeding
190
How does radioactive iodine work?
Iodine taken up by thyroid
Accumulates and results in local irradiation and tissue damage
Returns to normal thyroid function over 4-12 weeks
191
What are the side effects of radioactive iodine?
Necrosis follicular cells
Vascular occlusion
Atrophy and fibrosis
Chronic inflammation
Late hypothyroidism
192
When is surgery needed in hyperthyroidism?
Large goitre
Poor response to drugs
Side effects of drugs
193
What are the 2 methods of surgery for hyperthyroidism?
Subtotal thyroidectomy
Total thyroidectomy (for large goitre, graves, or malignancy)
194
What are the complications of thyroid surgery?
Thyroidectomy = hypothyroid
Tracheal compression
Laryngeal nerve palsy
Transient hypocalcaemia
195
What is thyroid crisis/ thyroid storm?
Rare, life threatening condition where there is rapid deterioration of thyrotoxicosis (rapid T4 increase)
196
What are the features of thyroid crisis?
Hyperpyrexia
Tachycardia
Delirium
Coma
Death
197
What are the causes of thyroid crisis?
Stress
Infection
Surgery
Radioactive iodine therapy
198
How is thyroid crisis treated?
Large doses of:
- Oral Carbimazole
- Oral propranolol
- Oral potassium iodide
- IV hydrocortisone
199
What is hypothyroidism?
Under activity of thyroid gland due to thyroid disease (primary) or secondary causes
200
Outline the risk factors of hypothyroidism
More common in females
Incidence increases in age
Autoimmune disease
201
What are the causes of hypothyroidism?
Primary:
Iodine deficiency, Hashimoto’s thyroiditis, drugs, thyroidectomy
Secondary: pituitary and hypothalamic disease, genetic disorders
202
What drugs can cause hypothyroidism?
Carbimazole
Lithium
Amiodarone
203
Outline the pathology of autoimmune/atrophied hypothyroidism
Antithyroid antibodies lead to lymphoid infiltration causing atrophy and fibrosis
204
What are the features of post-partum thyroiditis?
Transient condition in pregnancy
Autoimmune modifications causing hypo/hyperthyroidism
Can be misdiagnosed as postpartum depression
205
What are the symptoms of hypothyroidism?
Hoarse voice
Goitre (iodine deficiency)
Weight gain
Cold intolerance
Dry, rough skin
Constipation
206
What are the symptoms of hyperthyroidism?
Weight loss
Tachycardia
Heat intolerance
Anxiety
Tremor
Diarrhoea
207
What are the signs of hypothyroidism?
BRADYCARDIC
B- bradycardia
R- reflexes relax slowly
A- Ataxia
D- dry hair and skin
Y- yawning/ drowsy
C- cold hands
A- ascites
R- round puffy face
D- defeated demeanour
I- immobile
C- congestive heart failure
208
How is hypothyroidism diagnosed?
TFT- thyroid function test
-low T4 and high TSH
-secondary hypothyroidism = low TSH too
-thyroid antibodies eg TPO in Hashimotos
209
Outline the pathophysiology of primary hypothyroidism
T3/T4 not produces
High compensatory TSH
210
Outline the pathophysiology of secondary hypothyroidism
Low TSH levels cause low T3 and T4
211
How is hypothyroidism treated?
Oral levothyroxine (T4)
- dose titrated in primary hypothyroidism
- start lower in IHD patient
212
What are the complications of hypothyroidism?
Myxedema coma (severe deficiency of thyroid hormones)
- hypothermia, heart failure, hypo ventilation ect
213
How is myxedema treated?
IV/oral T3 and glucose infusion
214
Describe Graves’ disease
Autoimmune disease caused by excess production of thyroid hormone (TSH receptor antibodies)
215
Outline the epidemiology of Graves’ disease
Most common cause of hyperthyroidism (2/3)
Females more commonly affected
Typically presents at 40-60 years
216
What are the risk factors of Graves’ disease?
Female
E. coli
Autoimmune disease- Vitiligo, Addisons, pernicious anaemia, MG
Alemtuzmab (MS drug)
217
Describe the pathophysiology of Graves’ disease
Serum IgG antibodies called TSHR-Ab bind to TSH receptors
stimulate thyroid production (behave like TSH)
Cause excess secretion of thyroid hormones -> diffuse goitre
218
What are the clinical presentations of Graves’ disease?
-Graves ophthalmology- exophthalmos (protruding eyes) an ophthalmoplegia (paralysis of eye muscles)
- diffuse goitre
-pretibial myxoedema- raised purple skin lesions over thighs
- thyroid acropachy- clubbing, swollen fingers, periosteal bone formation
219
How is Graves’ diagnosed?
TSHR-Ab raised
TFT- high T4 and low TSH
220
How is Graves’ disease treated?
-Ophthalmology issues treated with IV methylprednisolone (corticosteroid) and surgical decompression
- Anti thyroid drugs
221
What is Hashimoto’s hypothyroiditis?
Autoimmune disease where the thyroid is attacked by antibodies and other cells
222
Outline the epidemiology of Hashimoto’s hypothyroiditis
Females more affected
Middle aged and 60-70 years old
223
Outline the pathophysiology of Hashimoto’s hyperthyroiditis
1. Formation of antithyroid antibodes
2. Low T4 and high TSH causes progressive fibrosis
224
What are the presentations of Hashimoto’s thyroiditis?
Goitre formation
Same as hypothyroidism
Loss of hair at lateral 1/3 eyebrows
225
What investigations are carried out for Hashimoto’s thyroiditis?
TFT- low T4 and high TSH
Anti thyroid peroxidase antibodies are positive
226
What is the treatment for Hashimoto’s thyroiditis?
Levothyroxine
227
What is de Quervain’s thyroiditis?
Subacute granulomatous thyroiditis causing inflammation
-Results in pain and discomfort due to rapid swelling
228
What are the causes/risk factors of De Quervain’s thyroiditis?
Viral infection
229
What are thee 4 phases of De Quervain’s thyroiditis?
Phase 1: goitre, hyperthyroidism
Phase 2: euthyroid (Normal)
Phase 3: weeks to months hypothyroidism
Phase 4: normal
230
How does De Quervain’s thyroiditis present?
Neck pain
Difficulty eating
Tender goitre- PAINFUL
Fever
Palpitations
231
What investigations are carried out for diagnosis of De Quervains thyroiditis?
elevated:
T4, T3, CRP, Free thyroxine uptake
232
What are the treatments of De Quervains thyroiditis?
Hyperthyroid phase: NSAIDs and corticosteroids
Hypothyroid phase: usually fine to be untreated but can give small amount of levothyroxine
233
What are the complications of De Quervains thyroiditis?
Thyroid storm
Long term hypothyroidism
234
What do TSH receptor antibodies help differentiate?
Thyroiditis from graves
Positive = Graves
235
What are TPO antibodies useful?
Identify autoimmune problems
236
What are the 4 most common types of thyroid cancer (in order)?
Papillary (70%)
Follicular (20%)
Anaplastic (<5%)
Lymphoma (2%)
237
Outline the epidemiology of thyroid carcinoma
Affects women more
400 deaths a year in UK
238
What are the risk factors for thyroid carcinomas?
Radiation
239
What are the features of papillary thyroid cancer?
Affects young people
Local spread
Good prognosis
240
What are the features of follicular thyroid cancer?
Middle age
Spread to lung/bone
Usually good prognosis
241
What are the features of anaplastic thyroid cancers?
Very undifferentiated
Aggressive local spread
Poor prognosis
242
How do thyroid carcinomas present?
In 90% present as nodules
- Hard and irregular in shape
Can have dysphagia or hoarseness
243
How is thyroid carcinoma diagnosed?
Fine needle aspiration biopsy
TFT blood test
Ultrasound
244
How are thyroid carcinomas treated?
Thyroidectomy
Levothyroxine to repress TSH which acts as a growth factor
Radioactive iodine (anaplastic does not respond)
245
where are GLUT1 receptors found?
erythrocyte membrane
246
What are the 3 layers of the adrenal cortex?
Zona glomerulosa
Zona fasiculata
Zona reticularis
247
What is produced by the zona glomerulosa?
Mineralocorticoids
-eg aldosterone
248
What is produced by the zona fasiculata?
Glucocorticoids
-eg. Cortisol
249
What is produced by the zona reticularis?
Androgens
- Must be converted to testosterone and dihydrotestosterone to be active
250
What is produced by the adrenal medulla?
Cathecholamines
-Eg. Adrenaline and noradrenaline
-under sympathetic control
251
Describe how cortisol and androgen production is stimulated
CRH from hypothalamus stimulates..
ACTH from pituitary
ACTH stimulates the production of cortisol and androgens
252
What controls the zona glomerulosa secretion?
NOT HPA AXIS
Renin release from juxtaglomelular cells of afferent arterioles in kidneys
253
Define Cushing’s syndrome
General term referring to excess cortisol whatever the cause
254
Define Cushing’s **disease**
Cortisol excess due to pituitary ACTH secreting tumour
255
Where do thyroid tumours metastasise to?
Lung (50%)
Bone (30%)
Liver (10%)
Brain (5%)
256
What can mimic Cushing’s syndrome?
Alcohol excess
257
What are the causes of Cushings syndrome?
-Oral steroids (glucocorticoids) most common
-80% due to increased ACTH- can be due to Cushings disease
258
What are the ACTH dependent causes of Cushings?
-Cushings disease (most common)
-Ectopic ACTH production (ACTH producing tumour elsewhere in the body)
-ACH treatment (eg for asthma)
259
What are the ACTH independent causes of Cushings?
Adrenal adenoma (causes cortisol release)
Iatrogenic eg glucocorticoid administration
260
What is the difference in ACTH levels between ACTH dependent and independent causes of Cushings?
ACTH dependent: Increased ACTH
ACTH independent: Decreased ACTH due to negative feedback from raised cortisol
261
Outline the pathophysiologies of Cushing’s syndrome
1.Excess ACTH stimulates excess cortisol release
2. Neoplasms in adrenals stimulate zona reticularis
3. Ingesting excess glucocorticoids
262
What is an example of a glucocorticoid drug?
Prednisolone
263
Describe the signs of Cushing’s syndrome
Obese- especially centrally
Plethoric moon face
Proximal weakness
Thin skin, purple striae on stomach
Buffalo hump
264
What are the symptoms of Cushing’s syndrome?
Increased BP
Personality changes- irritable, tired, depressed
Gonadal dysfunction- ED, irregular periods
Osteoporosis
265
What investigations are carried out to diagnose Cushing’s syndrome?
1st line: raised late night salivary cortisol levels
Gold standard: dexamethasone suppression test (1mg)
-24 hour urinary free cortisol
266
What results from an overnight low dose dexamethasone suppression test indicates Cushings?
Serum cortisol at 8am should be suppressed <50nmol/L
- Will NOT be suppressed in Cushings
267
How is adrenal tumour detected?
Plasma ACTH is undetectable
-CT and MRI then done
268
What is the next step of diagnosis if cortisol is not suppressed in Cushings?
High dose given (8mg)
269
What results of a high dose dexamethasone test indicate a pituitary adenoma (Cushings disease)?
Suppressed cortisol and ACTH
270
What results of a high dose dexamethasone test indicate an adrenal adenoma?
Cortisol not suppressed
ACTH suppressed
271
What results of a high dose dexamethasone test indicate an ectopic ACTH tumour?
Cortisol not suppressed
ACTH not suppressed
272
How is ectopic ACTH treated?
Surgery for tumour
Drugs that inhibit cortisone synthesis
273
What is a drug that inhibits cortisone synthesis?
Metyrapone
274
What is an adrenolytic drug?
Mitotane
275
How is iatrogenic Cushings treated?
Stop steroids!
276
How is Cushings disease treated?
Surgical removal of pituitary adenoma
If fails….
-Bilateral adrenalectomy
- Radiotherapy
277
How is adrenal adenoma treated?
Adrenalectomy- doesn’t cure cancer though
- Radiotherapy
- Adrenolytic drugs eg. Mitotane
278
How is ectopic ACTH treated?
Surgery if not spread
Drugs that inhibit cortisone synthesis eg. Metyrapone
279
What are the complications of Cushing’s syndrome?
Hypertension
Osteoporosis
CVD
DMT2
280
What stimulates and inhibits growth hormone (GH)?
Stimulates: GHRH (also ghrelin)
Inhibits: somatostatin (SST) and high glucose
281
Define gigantism
Excessive GH production in children before fusion of the epiphyses of the long bones
282
Define acromegaly
Excess GH in adults due to a pituitary secreting tumour (usually)
283
Describe the epidemiology of acromegaly
Rare- 3 per million
Equally as common between males and females
Mean diagnosis at 48
284
Describe the aetiology of acromegaly
benign GH producing tumour- most common
Rare: ectopic GHRH from carcinoid tumour
285
Outline the pathophysiology of acromegaly
1. Increased GH secreted
2. Travels to tissue eg. Liver
3. Binds to receptors causing increased IGF-1
4. Stimulates skeletal and soft tissue growth leading to giant like appearance
286
What are the symptoms of acromegaly?
Headaches
Acral enlargement (hands and feet)
Sweating
Vision problems
Wonky bite
Backache
Acroparaestheisa - tingling and numbness in extremities
287
What are the signs of acromegaly?
Skin darkening
Coarsening face with wide nose
Big supraorbital ridge
Deep voice
Rings are tight
Carpal tunnel
Large tongue
288
What are the complications of acromegaly?
Impaired glucose tolerance
Sleep apnoea
Hypertension
CVD
Colon cancer
Stroke and cardiovascular events
289
Why is a random growth hormone test not just used for acromegaly diagnosis?
Secretion is pulsatile
290
What is the first line test for acromegaly?
IGF-1 and plasma GH levels
291
What levels of GH and IGF-1 exclude acromegaly?
Random GH undetectable OR GH < 0.4 ng/ml
Normal IGF-1
292
What is the gold standard diagnostic test for acromegaly?
Glucose tolerance test (GTT)
293
What results on a OGTT would exclude acromegaly?
GH <1ng/ml
-normally GH would be suppressed, but this does not occur in people with acromegaly
294
What other tests can be done to diagnose acromegaly?
Visual field examination
MRI of pituitary fossa
Pituitary function test
ECH and ECHO to look for cardiomyopathy
295
What is the first line treatment for acromegaly?
Trans-sphenoid also surgery to remove the tumour from the pituitary gland
296
What is the second line treatment for acromegaly?
Somatostatin analogues to suppress GH release
297
What are 2 somatostatin analogues?
IM octrotide
IM lanreotide
298
What are some 3rd line treatments for acromegaly?
GH receptor agonists
Or
Dopamine agonist
299
What is a GH receptor antagonist?
Pegvisomant
300
What are 2 dopamine agonists?
Oral cabergoline
Oral bromocriptine
301
What does raise prolactin lead to?
Lactation
Inhibition of GNRH -> decreased LH/FSH -> decreased testosterone or oestrogen
302
Define prolactinoma
Benign prolactin producing tumours of lactotropth cells in anterior pituitary
303
What are the risk factors of prolactinoma?
Female sex
Peak incidence in childbearing age
304
Are most prolactinomas microprolactinomas or macroprolactinomas?
Micro = 90%
Macro = 10%
305
How big are micro and macroprolactinomas?
Micro = <1cm diameter
Macro = _>1cm diameter
306
Outline the pathophysiology of prolactinoma
1. Hyper secretion of prolactin inhibits GNRH
2. Causes secondary hypergonadism
307
How do females with prolactinoma present?
Amenorrhoea
Oliomenorrhoea
Infertility (inhibits ovulation)
Galactorrhoea (spontaneous flow of milk)
Low libido
Visual field defect
308
How does prolactinoma present in males?
Low testosterone
Erectile dysfunction
Reduces facial hair
Low libido
Galactorrhoea
Visual field defects
309
What are the investigations for prolactinoma?
1st line: basal prolactin level- will be RAISED
2nd line: pituitary MRI to detect adenoma
310
How is prolactinoma treated?
1st line: dopamine agonists- inhibit prolactin release causing a decrease in size of tumour
2nd line: HRT
311
What are the 4 effects of aldosterone?
1. Increases Na+ reabsorption from distal tubule
2. Increases K+ excretion from distal tubule
3. Increase H+ secretion from collecting ducts
4. Increase H2O reabsorption
312
Define primary hyperadosteronism
Excess production of aldosterone independent from the RAAS system
- By renal glands
313
What are the causes of primary hyperaldosteronism?
Bilateral adrenal hypoplasia (70%)
Conn’s syndrome: adrenal adenoma secreting aldosterone
314
Define Conn’s syndrome
An adrenal adenoma secreting aldosterone
315
Define secondary hyperaldosteronism
Excessive renin stimulates the adrenal glands to produce more aldosterone
316
Describe renin levels in primary and secondary hyperaldosteronism
Primary: serum renin low as it is suppressed by high BP
Secondary: serum renin is high
317
What are the causes of secondary hyperaldosteronism?
Renal artery stenosis (reduced arterial supply to kidney)
Renal artery obstruction
Heart failure
318
What is the most common secondary cause of hypertension?
Conn’s
319
Describe the pathophysiology of hyperaldosteronism
High aldosterone -> high Na and H2O
-> low K
Hypertension
320
Describe the pathophysiology of Conn’s syndrome
Aldosterone producing carcinoma causes effects of hyperaldosteronism
321
Describe the presentation of Conn’s syndrome
Often asymptomatic
Hypertension
Hypokalaemia
Weakness
Polyuria and polydipsia
Headaches
322
What is the differential diagnosis of Conn’s?
Secondary hyperaldosteronism
-measure renin levels
323
What investigations are carried out for Conn’s diagnosis?
1st line: aldosterone: renin ratio
GS: IV saline- aldosterone would remain high
Hypokalemic ECG
FBC, U&E, LFT
- Low K= primary
324
How is Conn’s and hyperaldosteronism treated?
Adrenalectomy
Aldosterone agonist
325
Where is aldosterone secreted from?
Adrenal glands
326
What are 2 aldosterone antagonists/potassium sparing diuretics?
Spironolactone
Amiloride
327
What are the complications of Conn’s?
Heart failure
MI
Stroke
Renal damage
328
What would indicate hypokalaemia on an ECG?
Flat T wave
ST suppression
Long QT
329
Define adrenal insufficiency
Adrenal glands do not produce enough hormones, particularly aldosterone and cortisol
330
Define Addison’s disease
Destruction of entire renal cortex resulting in deficiency of:
Mineralocorticoids- aldosterone
Glucocorticoids- cortisol
Sex steroids- androgens (sex hormone precursors)
331
Describe the epidemiology of Addison’s disease
Very rare- 0.8 per 100,000
Marked female preponderance
332
Describe primary adrenal insufficiency
AKA Addison’s disease
- Adrenal glands have been damaged
333
What are the causes of Addison’s disease?
1. Autoimmune adrenalitis- most common
- Adrenal glands destroyed by antibodies eg. 21- hydroxylase
2. TB- most common cause worldwide
334
Describe secondary adrenal insufficiency
Caused by inadequate ACTH, causing low cortisol levels
335
What are the causes of secondary adrenal insufficiency?
Loss/damage of pituitary gland
Benign pituitary tumour
336
Describe tertiary adrenal insufficiency
Inadequate CRH release by hypothalamus
Pituitary can not be stimulated so no ACTH
337
What is the most common cause of tertiary adrenal insufficiency?
Stopping corticosteroids after a long time of taking them
338
What are the symptoms of adrenal insufficiency/Addisons disease?
Fatigue and weakness
Anorexia
Nausea
Weight loss
Headaches
Abdominal pain
Poor illness recovery
339
What are the signs of Addison’s disease/ adrenal insufficiency?
Bronze pigmentation and pallor
Changes in body hair distribution
Hypotension
Weight loss
Vitiligo
340
What are cortisol levels like in Addisons?
Low
<140 mmol/L
341
What are Na and K levels like in Addison’s?
Low Na
High K
- due to decrease in aldosterone
342
What will the FBC show in Addison’s disease?
Anaemia
Eosinophilia- due to reduced cortisol
343
What are renin and aldosterone levels like in Addison’s disease?
High renin
Low aldosterone
344
What 4 tests are used to diagnose Addisons/ adrenal insufficiency?
GS: synacthen test (ACTH injection)
2. 9:00 cortisol and ACTH
3. Renin/ aldosterone
4. 21 hydroxylase test in autoimmune adrenal insufficiency
345
What results of a synacthen test indicate adrenal insufficiency?
Cortisol low
Primary ACTH = increased
Secondary ACTH = decreased
346
How is Addisons treated?
Hydrocortisone 15-25mg 2-3x daily to replace cortisol
Fludrocortisone to replace Mineralocorticoids (Aldosterone)
347
How are hypotensive Addison’s patients treated?
IV hydrocortisone
IV 0.9% saline
Glucose infusion in hypoglycaemia
348
What are the symptoms of adrenal crisis?
Nausea
Vomiting
Muscle cramps
Abdominal pain
Confusion
Hypotension
349
What are the causes of adrenal crisis?
Abrupt steroids withdrawal- MC
Adrenal damage
Pituitary injury
350
What are the treatments for adrenal crisis?
Immediate hydrocortisone 100mg
Hydrocortisone 50-100mg IV 6 hourly
Fluid resuscitation 1L/hour
351
How is secondary adrenal insufficiency differentiated from Addisons?
Low ACTH
Mineralocorticoid levels intact
352
What is the most common adrenal insufficiency?
Tertiary adrenal insufficiency
353
How is vasopressin/ADH secretion stimulated by the body?
1. Large falls in BP or volume detected by osmoreceptors or baroreceptors
2. Secretion determined by plasma osmolality
Stimulates ADH release from hypothalamus
354
Where does ADH/ vasopressin act?
Principal cells on collecting duct of kidney
355
How does ADH/ vasopressin stimulate increased water absorption?
1. Binds to V2R receptors in kidneys
2. Kinase actions causes insertion of aquaporin channel into apical membrane of collecting duct
3. Increases water permeability of collecting duct increasing water absorption and concentration of urine
356
What is another affect of vasopressin that causes a restoration in BP?
Causes widespread arteriolar vasoconstriction
357
Describe the relationship between blood osmolality and vasopressin
Linear- as blood gets more concentrated vasopressin and water reabsorption increases
358
What does SIADH stand for?
Syndrome of inappropriate secretion of ADH
359
Define SIADH
Excessive secretion of ADH despite plasma being dilute independent of RAAS
360
What are the effects of SIADH?
Hyponaetremia
High urine osmolality
Euvolemic state (normal fluid levels)
361
What are the causes of SIADH(tumours)?
Small cell lung carcinoma
Prostate tumour
Pancreas tumour
Lymphoma
Thymus tumour
362
What are the respiratory causes of SIADH?
SCLC
Pneumonia
TB
Lung abscess
Asthma
CF
363
What are the CNS causes of SIADH?
Meningitis
Tumours
Head trauma
Subdural haematoma
364
What drugs can cause SIADH?
Chlorpropamide (sulfonylurea)
Carbamazepine (anti convulsant)
Cyclophosphamide (immunosuppressant)
Chemo
SSRIs
365
Describe the pathophysiology of SIADH
Excess ADH = insertion of aquaporin 2 channels
= excess water retention = dilute plasma = hyponatraemia
366
What are the signs of SIADH?
Absence of hypo/hypervolaemia
Normal thyroid an adrenals
Low osmolaity
High urine Na and low plasma Na
Highly concentrated urine
367
What are the symptoms of SIADH?
Headache
Nausea+ vomiting
Fatigue
Cramps and aches
Confusion
Severe hyponatraemia = seizures + coma
368
What would urine tests show in SIADH?
High sodium >20mmol/L
High osmolality >100mosmol/L
369
What will plasma tests show in SIADH?
Low sodium <125mmol/L
Low osmolality <260mmol/L
370
What factors will be absent in SIADH?
Hypo/hypervolaemia
Oedema
Diuretics
371
How are the other causes hyponatraemia excluded in SIADH?
Synacthen test (adrenal insufficiency)
No diuretic history
No vomiting burns ect
No excessive water intake
No kidney issues
372
Where is ADH/vasopressin secreted from and produced?
Produced: hypothalamus
Secreted: posterior pituitary
373
How is SIADH differentiated from Na and H2o depletion?
1-2L 0.9% saline
- SIADH will not respond
374
What are the main methods of managing SIADH?
Fluid restriction (500mls-1L a day)
Treat underlying cause
375
What drugs are used to control SIADH?
Vasopressin receptor antagonists/ ADH inhibitors
Salt loop diuretics if severe
376
What is an example of a vasopressin receptor antagonist?
Tolvaptan
377
What is an example of a loop diuretic?
Furosemide
378
What is the main complication of SIADH?
Central pontine myelinolysis
379
What causes central pontine myelinolysis?
Rapidly corrected low sodium -> osmotic demyelination
- as Na+ falls, water moves into brain by osmosis causing swelling
380
What are the 2 phases of central pontine myelinolysis?
1: encephalopathic: confused and headaches
2. Demyelination of neurons days after rapid sodium correction: spastic quadriparesis and cognitive changes
381
What are the risk factors of central pontine myelinolysis?
Alcohol
Malnutrition
K+ depletion
Hepatic failure
382
Where does vasopressin bind to V1a receptors?
Vasculature- arteries
- Maintains BP
383
Where does vasopressin bind to V2 receptors?
Renal collecting tubule principal cellls
384
Where does vasopressin bind to V1b receptors?
Anterior pituitary
-Fire and release of ACTH
385
What 2 things control vasopressin release?
Normally: osmoreceptors in hypothalamus
Emergency: baroreceptors in brain stem and great vessels
386
What are the new names for diabetes insipidus?
Cranial = AVP DEFICIENCY
Nephrogenic = AVP RESISTANCE
387
Is AVP deficiency or AVP resistance more common?
AVP deficiency
388
Define AVP deficiency
Decreased secretion of ADH from posterior pituitary
389
Define AVP resistance
Insensitivity to ADH
390
What are the effects of AVP deficiency/ resistance?
Prevents urine concentration due to impaired water reabsorption leading to polyuria and polydipsia
3L+ urine daily
391
What diseases are also associated with autoimmune adrenalitis?
DMT1
Pernicious anaemia
Hypo/hyperthyroidism
392
What are the causes of AVP deficiency?
Idiopathic
Trauma
Tumours
Infection
Sarcoidosis
Inflammation
Pituitary surgery
393
What are the causes of AVP resistance?
Lithium
Osmotic diuresis
Renal impairment and infiltration
Hypercalcaemia an hypokalaemia
Pregnancy
394
What congenital defects can cause AVP resistance?
AVP2 receptor mutation
AQP2 mutation
Wolfram
395
Outline the pathophysiology of AVP resistance/ deficiency
Reduced secretion/impairment -> significant water loss -> dilute urine
396
What are the signs and symptoms of AVP deficiency/ resistance?
Polyuria and nocturia
Polydipsia
NO glycosuria
Hypernnatraemia
Lithium history
397
What are the differential diagnosis of AVP resistance/ deficiency?
Primary polydipsia (drinks too much water)
DM
Cushings
Hypercalcaemia
Hyperkalaemia
398
What is the gold standard for AVP deficiency/resistance diagnosis?
Water deprivation test - deprive water for 8 hours
- Diagnosis= high osmolality and inappropriately dilute urine
399
What tests can be used to differentiate AVP deficiency/resistance?
1. AVP stimulation test- 2mcg desmopressin IM
-AVP resistant: no response
- AVP deficiency: responds
2. Hypertonic saline infusion with measurement of copetin
400
What other tests are used to diagnose AVP resistance/ deficiency?
Measure polyuria (unlikely if urine is <3L)
Renal function tests
Serum calcium
Urine dipstick to exclude DM
401
How is AVP deficiency treated?
Treat underlying condition
Desmopressin V2 analog
Manage hypernatraemia
402
How is AVP resistance treated?
Thiazide diuretics (work in DCT)
NSAID- lowers urine and plasma Na+
403
How do thiazide diuretics work?
Work on DCT
Induce mild hypovolaemia -> more Na+ and water uptake in DCT -> offsets water loss
404
What is an example of a thiazide diuretic?
Oral bendroflumethiazide
indapamide
405
How is serum calcium controlled?
PTH (parathyroid hormone)
Vitamin D
406
Is hypercalcaemia or hypocalceamia more common?
Hypercalcaemia more common but hypo more common in hospital
407
Where is PTH secreted from?
Chief cells in parathyroid glands in response to decreased levels of Ca2+ plasma concentrations
408
How is a decrease of serum Ca2+ detected?
G-coupled calcium sensing receptors on the parathyroid glands
409
How does PTH increase plasma Ca2+?
Increases osteoclastic resorption of bone
Increases intestinal Ca2+ absorption
Activation of calcitrol in kidney
Increases renal tubular reabsorption of Ca2+
Increases phosphate excretion
410
What stimulates calcitriol release?
Low plasma Ca2+
Low plasma phosphate
PTH
411
What are thee 4 roles of calcitrol?
1. Increased Ca2+ and phosphate absorption in gut
2. Inhibits PTH release
3. Increases osteoclasts -> enhanced bone turnover
4. Increased Ca2+ and phosphate reabsorption in kidneys
412
Where is calcitonin made?
C-cells of thyroid
413
What are the effects of calcitonin?
Causes a decrease in plasma Ca2+ and phosphate
414
Define hyperparathyroidism
Excessive secretion of parathyroid hormone (PTH)
415
Describe the epidemiology of hyperparathyroidism
Elderly women most affected
416
What is the most common type of hyperparathyroidism?
Primary
417
Describe the pathophysiology of primary hyperparathyroidism
1. Tumour/hyperplasia of thyroid glands causes extra secretive tissue
2. Causes excess PTH production -> hypercalacemia
418
What are the causes of primary hyperparathyroidism?
80% due to solitary adenoma
20% due to gland hyperplasia
~ small amount due to parathyroid cancer
419
Outline the pathophysiology of secondary hyperparathyroidism
1. Insufficient vitamin D or chronic renal failure causes low Ca2+ absorption
2. Causes hypocalcaemia
3. Hypocalcaemia causes more PTH and hyperplasia = MORE PTH
420
Outline the pathophysiology of tertiary hyperparathyroidim
Occurs after prolonged secondary hyperparathyroidism
- Glands continue to secrete PTH after the hypocalcaemia cause has be treated
421
What is the most common cause of tertiary hyperparathyroidism?
Long-standing kidney disease
422
What are the risk factors of hyperparathyroidism?
Elderly women who have been through menopause
Prolonged severe Ca2+ or vitamin D deficiency
423
What are the lab results in primary hyperparathyroidism?
PTH = high
Ca2+ = high
Phosphate = low
424
What are the lab results in secondary hyperparathyroidism?
PTH = high
Ca2+ = low/normal
Phosphate = high(ish)
425
What are the lab results in tertiary hyperparathyroidism?
PTH = high
Ca2+ = high
Phosphate = high
426
Describe the presentation of hyperparathyroidism
Bones, stones, groans and psychiatric moans
——————————————————————
- bone pain, fractures, osteoporosis
- biliary and renal stones
-groans due to malaise, abdo pain, constipation, nausea
- moans = fatigue, depression and psychosis
427
What is alkaline phosphate like in hyperparathyroidism?
High
428
How is hyperparathyroidism investigated?
Measure PTH, Ca2+ and phosphate levels
- bone scan to differentiate from oestoporosis
- ultrasound for kidney stones
- abdomen X-ray
- detect adenomas
429
How is acute severe hypercalcaemia treated?
EMERGENCY
-IV 0.9% saline - prevents stones (1ST LINE)
-Biphosphonates - prevent bone reabsorption
- serum U&E daily and Ca2+ 48 hrs post treatment
-glucocorticoid steroids on myeloma, excess vit D, sarcoidosis
430
What is an example of a biphosponate?
Alendronate
IV pamidronate
431
How is primary hyperparathyroidism treated?
Surgical removal of tumour
432
How is secondary hyperparathyroidism treated?
Treat vitamin D deficiency
Cincalcet
Kidney transplant for CKD
433
How is tertiary hyperparathydroidism treated?
Total or partial parathyroidectomy
Calcimimetic
434
What is the function of calcimimetics?
Increases sensitivity of parathyroid cells to Ca2+ -> less PTH secretion
435
What is an example of a calcimimetic?
Cinacalet
436
Define hypercalcaemia
Decreased PTH and increased Ca2+
437
What are the causes of hypercalcaemia?
CHIMPANZEES - on drugs
C-calcium supplements
H- hyperparathydroidism
I-iatrogenic
M-multiple myeloma
P-parathyroid hyperplasia
A- alcohol
N- neoplasms
Z- Zollinger-Ellison syndrome
E- Excess vit D
E- excess vit A
S- sarcoidosis
438
What drugs can cause hypercalcaemia?
Thiazide diuretics
Vitamin D analogues
Lithium
439
Describe the presentation of hypercalcaemia
Bones, stones, groans and psychiatric moans
ECG abnormalities- short QT interval
440
What investigations are carried out for hypercalcaemia diagnosis?
Fasting serum Ca2+ and phosphate
Elevated PTH and Ca2+
Ultrasound if indications of hyperparathyroidism
24 hour urinary calcium to exclude hypocalciuric hypercalcaemia
441
How is familial hypocalciuric hypercalcaemia differentiated?
24 hour urinary calcium
442
How is hypercalcaemia treated?
Rehydration with saline
Biphosphonates
Loop diuretics sometimes
443
What could hypocalcaemia be an artefact of?
Hypoalbuminaemia
444
How common is hypocalcaemia?
Very common in hospitalised patients- up to 88% of ICU patients
445
Describe the pathophysiology of primary hypoparathyroidism
Low PTH due to parathyroid gland failure
446
What are the causes of hypoparathyroidism?
Autoimmune DiGeorge syndrome
Idiopathic hypoparathyroidism
447
What is autoimmune DiGeorge syndrome?
Congenital familial condition in which the parathyroid glands fail to develop
448
What is idiopathic hypoparathyroidism?
Rare autoimmune condition caused by parathyroid antibodies
449
What is the most common hypoparathyroidism?
Secondary hypoparathyroidism
450
What causes secondary hypoparathyroidism?
After secondary parathyroid/thyroidectomy
Radiation
Hypomagnasaemia
451
What is pseudohypoparathyroidism?
Failure of target cell response to PTH
452
What causes pseudohypoparathyroidism?
Syndrome of end-organ resistance to PTH causing a mutation in the GNAS1 protein which is coupled with the PTH receptor
453
What are the presentations associated with pseudohypoparathyroidism?
Short stature
Short metacarpals (especially pinky and next one)
Subcutaneous calcification
Sometimes intellectual impairment
454
What drugs can cause hypoparathyroidism?
Calcitonin
Bisphosphonates
455
What are calcium, PTH and phosphate levels like in primary hypoparathyroidism?
Ca2+ is low
Low PTH
Phosphate is high
456
What are phosphate, PTH and Ca2+ levels like in pseudohypoparathyroidism?
High phosphate
Low Ca2+
High PTH
457
When may hypoparathyroidism occur when phosphate is normal or reduced?
Acute pancreatitis
Osteomalacia
458
What are the presentations of hypoparathyroidism?
Symptoms of hypocalcaemia
459
What are the causes of hypocalcaemia?
Chronic kidney disease (MC)
Severe vitamin D deficiency
-Reduced UV exposure, malabsorption ect
Sclerosis
Secondary hyperparathydroidism
460
What are the symptoms of hypocalcaemia and hypoparathyroidism?
SPASMODIC
S-spasms ie Trousseaus sign
P-perioral parasthesia
A- anxious ect
S- seizures
M- muscle tone increase
O- orientation impaired
D- dermatitis
I- impetigo herpetiformis
C- Chvostek’s sign, cataracts and cardiomyopathy
461
What effect does hypocalcaemia have on an ECG?
Prolonged QT
462
What is Chvostek’s sign?
Tapping over facial nerve on parotid gland region causes twitching of ipsilateral facial muscles
463
What is Trousseau’s sign?
Carpopedal spasm induced by inflating BP cuff above systolic BP
-downturned pinching gesture
464
What investigation results indicate hypocalcaemia?
Low PTH (apart from pseudoHP)
High phosphate
Low albumin
Low serum calcium
465
What are the differential diagnoses of hypocalcaemia?
CKD
Vitamin D deficiency
466
What are the complications of hypoparathyroidism?
CKD
Kidney stones
Cataracts
Basal ganglia calcification
Laryngospasm
467
How is hypoparathyroidism treated?
Oral or IV calcium
Calcitrol (activ vitamin D)
Thiazide diuretics (reduce hypercalcureia)
468
How is hypocalcaemia treated?
IV calcium gluconate if severe
Vitamin D supplements
469
What level of hyperkalaemia is an emergency?
>6.5mmol/L
470
What are the causes of hyperkalaemia?
Self limiting occurs after vigorous exercise
MC: renal impairment and drugs interfering with K+ excretion
Drugs
Addisons
DKA
471
What drugs can cause hyperkalaemia?
K+ sparing diuretics
ACE inhibitors
NSAIDs
Ciclosporin
Heparin
472
Outline the pathophysiology of hyperkalaemia
K+ level rise causes a reduction in the action potential between inside and outside the cardiac myocyte
= abnormal heart rhythms -> VF and cardiac arrest
473
What would an ECG look like in hyperkalaemia?
Tall T wave
Small P wav
Wide QRS
U wave
474
What investigations are carried out for hyperkalaemia diagnosis?
Serum K+ test
ECG
475
How do patients with hyperkalaemia present?
Irregular pulse
Chest pain
Weakness and fatigue
Lightheadedness
476
How is hyperkalaemia primarily treated?
Treat underlying factors
477
How is hyperkalaemia treated if ECG changes after initial treatment?
Stabilise cardiac membrane with IV calcium gluconate/chloride
- doesn’t lower serum K+
478
How is hyperkalaemia treated if ECG doesn’t change after initial treatment?
Move K+ into cells
Use combined INSULIN/DEXTROSE infusion with nebulised salbutamol
479
How can K+ be removed from the body?
Calcium resonium
Loop diuretics
Dialysis
480
How is severe hyperkalaemia treated?
IV calcium gluconate
Insulin/dextrose infusion
481
What levels indicate severe hypokalaemia?
<2.5 mmol/L serum K+
482
What are the causes of hypokalaemia with alkalosis?
Vomiting
Diuretics
Cushings
Conn’s
483
What are the causes of hypokalaemia with acidosis?
Diarrhoea
RTA
Partially treated DKA
Acetazolamide
484
What are the presentations of hypokalaemia?
Muscle weakness
Hypotonia
Hyporeflexia
Tetany
Palpitations
485
What results on an ECG indicate hypokalaemia?
Small or inverted T waves
Long PR interval
Depressed ST segment
Prominent U wave
486
How is mild hypokalaemia treated?
Oral replacement
Switch from thiazide to K+ sparing diuretic
487
How is severe hypokalaemia treated?
IV replacement 40mmol KCl
488
What are the complications of hypokalaemia?
Chronic heart failure
Acute MI
Muscle weakness
Depression of tendon weakness
489
When is TSH high and T4 low?
Hypothyroidism- Hashimoto’s
490
When is TSH low and T4 high
Hyperthyroidism - Graves
491
When is:
PTH high
Calcium low
Phosphate high
Secondary hyperparathydroidism
492
When is:
PTH high
Calcium high
Phosphate high
Tertiary hyperparathydroidism
493
Where do carcinoid tumours originate from?
Enterochromaffin cells
494
What hormone is produced in carcinoid syndrome?
Serotonin 5HT
495
What are the effects of serotonin?
Bowel function
Mood
Clotting
Nausea
Bone density
Vasoconstriction
Inotropic and chronotropic
496
Where do carcinoid tumours originate from?
GI tract
Lungs
Liver
Ovaries
Thymus
497
Where is the most common site of metastasis of carcinoid tumours?
Liver
498
What is carcinoid syndrome?
Hepatic involvement ie. Hepatic metastasis
499
What are the symptoms of carcinoid syndrome?
Diarrhoea
Upper right quadrant pain
Flushing
Tricuspid incompetence
500
What is the main complication of carcinoid tumours/syndrome?
Carcinoid crisis
501
What is carcinoid crisis?
A tumour outgrows its blood supply or handled too much in surgery, causing mediators to flow out
502
What are the effects of carcinoid crisis?
Vasodilation- bradykinin
Hypotension - ACTH-> cortisol
Tachycardia - bradykinin
Hyperglycaemia- glucagon and ACTH
503
How is carcinoid crisis treated?
High dose somatostatin analogue
504
How is carcinoid syndrome/tumour diagnosed?
1st line: 5-hydroxyindoeacetic acid (metabolite of serotonin)
Chest and pelvis CXR
Ultrasound of liver
505
What will 5-hydroxyindoeacetic acid levels be like in carcinoid syndrome?
High
506
How is carcinoid syndrome/tumour treated?
Somatostatin analogues to block the effects of tumour hormones
Surgical resection
507
What is phaeochromocytoma?
Adrenal medullary tumour that secretes catecholamines (adrenaline)
508
What are the causes of pheochromocytoma?
Usually inherited
Associated with:
Multiple endocrine neoplasia 2a and 2b
Neurofibromatosis
509
What are the symptoms of pheochromocytoma?
Hypertension
Pallor
Sweaty
Tachycardia
510
How is pheochromocytoma diagnosed?
Increased plasma metanephrines and normetanephrine
CT chest abdo and pelvis
511
How is phaeochromocytoma treated?
Alpha beta blocker (phenoxybenzamine)+ beta blocker
Surgery to remove tumour
512
What is the main complication of pheochromocytoma?
Hypertension crisis (>180/120)
513
How is hypertension crisis treated?
Alpha blocker
514
What are the 5 Tanner stages of female development?
Stage 1: no pubic hair and elevated papilla
Stage 2: sparse hair, palpable breast bud
Stage 3: darker coarse hair, breast and areole enlarge
Stage 4: projection of areole and papilla -> secondary mound
Stage 5: hair on medial thighs
515
What are the 5 Tanner stages of male development?
Stage 1: no pubic hair, childhood size penis
Stage 2: sparse hair, testes and penis enlarge
Stage 3: dark, curlier hair, penis and testes enlarge
Stage 4: enlargement, darkening of scrotum
Stage 5: hair on medial thighs, adult shape and size
516
Define thelarche
Beginning of breast development
517
What is pubarche?
First appearance of pubic hair
518
When is adrenarche?
Maturation of adrenal gland
519
What is menarche?
First menstruation
520
Define precocious puberty
Early puberty
GnRH dependent
521
Describe the epidemiology of precocious puberty
90% girls
1 in 5-10k
522
Describe the aetiology of precocious puberty
Idiopathic
CNS tumours
CNS disorders
Secondary central precocious puberty
Psychosocial
523
What are the risk factors of precocious puberty?
Obesity
Genetics
Surgery/radiotherapy on brain
524
Outline the pathology of precocious puberty
GnRH secretion activated -> LH and FSH -> sex hormone actions
525
What are the symptoms of precocious puberty?
Advanced bone age
Testes >4ml
Thelarche
Pubarche
526
What 3 investigations are carried out for precocious puberty?
Bone age assessment
HIGH basal FSH and LH
GnRH test: LH:FSH >1
527
What do high FSH and LH levels indicate?
Precocious puberty
528
What does a LH:FSH ratio >1 indicate?
Precocious puberty
529
How is precocious puberty treated?
GnRH super-agonist
Surgery
Gonsider GH
530
Define precocious pseudopuberty
Early puberty
GnRH independent
531
Describe the aetiology of precocious pseudopuberty
Increased androgen secretion
Gonadotropin or oestrogen secreting hormones
McCune-Albright syndrome
Ovarian cyst
Hypothyroidism
532
Describe the epidemiology of delayed puberty
Mainly boys
Genetics
533
Describe the aetiology of delayed puberty
Idiopathic: delayed activation of hypothalamic pulse generator
Hypogonadotrophic hypogonadism
Hypergonadotrophic hypogonadism
534
What is hypogonadotrophic hypogonadism?
Sexual infantilism related to gonadotrophin deficiency
535
What are the 2 types of hypogonadotrophic hypogonadism?
Secondary: pituitary = low LH/FSH
Tertiary: hypothalamus = low GnRH
536
What is hypergonadotrophic hypogonadism?
Primary gonad problems
- high GnRH/FSH/LH but low gonadotrophins
537
What are the effects of delayed puberty?
Delay in acquisition of secondary sex characteristics
Psychological defects
Reduced bone mass
538
What are the signs of delayed puberty in girls?
Age 13: lack of breast development
Age 14: lack of pubic hair
Age 15-16: absent menarche
539
What are the signs of delayed puberty in boys?
Age 14: lack of testicular enlargement
Age 15: lack of pubic hair
540
What are the reversible causes of delayed puberty?
Anorexia nervosa
ADHD medication
Extreme exercise
Hypothyroidism
Cushings
541
What investigations are carried out for delayed puberty?
RBC count
U&E
LH, FSH, sex hormones
Thyroid function karotyping
542
How is delayed puberty managed?
Most don’t need treatment
- short course of sex hormones
-low exogenous sex steroid dose
- girls can have progesterone therapy
543
What is Kallman syndrome?
Hypogonadotrophic hypogonadism
- failure of episodic GnRH secretion -> delayed puberty
544
Describe the epidemiology of Kallman syndrome
1 in 10k
M:F = 4:1
545
Outline the aetiology of Kallman syndrome
X-linked
Mutations in Kal-1, FG receptor 1, prokinectin
546
What are the symptoms of kallman syndrome?
Anosmia (no smell/taste)
Cleft palate
Only one kidney
Short digits (4th finger)
Absent/ delayed puberty
Short stature
547
What is unilateral renal agenesis?
Only 1 kidney
548
What investigations are carried out for Kallman syndrome?
Low testosterone or oestrogen, LH ect
Men with congenital and severe GnRH deficiency have low serum inhibin B
549
How is Kallman syndrome treated?
Testosterone enanthate IM
Transdermal testosterone
550
How is Kallman syndrome treated in females?
Ethinyloestradiol or Oestrogen
-gradually increase dose until adult dose reached
Progesterone when full dose reached
551
What are the 2 types of hypergonadotrophic hypogonadism?
Turner syndrome (females)
Klinefelter syndrome (males)
552
Describe the aetiology of Turner syndrome
Part or all of X chromosome missing
553
What are the symptoms of Turner syndrome?
Recurrent otitis media
Broad chest
Short 4th finger
Short stature and scoliosis
Prominent ears
554
How is Turner syndrome treated?
Oestrogen treatment gradually increased
Progesterone added when full dose reached
GH for short stature
555
What is Klinefelter syndrome?
Hypergonadotrophic hypogonadism
47 XXY chromosome defect
556
What are the symptoms of Klinefelter syndrome?
Small testicular volume <5ml
Tall stature
Reduced IQ 40%
Reduced pubic hair
Gynaecomastia
557
What is gynaecomastia?
Male breasts
558
What are the complications of Klinefelter syndrome?
DMT2
Osteoporosis
Malignancies
559
How is Klinefelter syndrome treated in males?
Testosterone enanthate IM
Increasing use of transdermal testosterone
560
What is the marker of Rhabdomyolosis?
Creatine kinase high
561
Define adrenal crisis
Medical emergency caused by lack of cortisol
