Endocrine Flashcards
(667 cards)
1
Q
What are the 3 main classes of hormones?
A
Glyoproteins and peptides (amino acid chains of variable length)
Steroids (derived from cholesterol)
Tyrosine and Tryptophan (Amine) derivatives
2
Q
Give an example of a glycoprotein or peptide
A
Oxytocin
Insulin
3
Q
Give an example of a steroid
A
Cortisol
Testosterone
4
Q
Give an example of a Tyrosine or Tryptophan derivative
A
Adrenaline
Thyroid hormones
Melatonin
5
Q
How are amines synthesised, stored and released?
A
Pre-synthesised
Stored in vesicles
Released in response to Ca2+ dependant exocytosis
6
Q
How are peptides and proteins synthesised, stored and released?
A
Pre-synthesised (usually from a longer precursor)
Stored in vesicles
Released in response to Ca2+ dependant exocytosis
7
Q
How are steroids synthesised?
A
Synthesised and secreted upon demand
8
Q
What increases steroid synthesis and secretion?
A
cellular uptake and availability of cholesterol
rate of conversion of cholesterol to pregnenolone
9
Q
What type of hormone is not transported freely in plasma and relies on carrier proteins?
A
Steroids (+thyroxine)
10
Q
As well as increasing the amount transported, what other effect do carrier proteins have with steroids?
A
Prevent Filtration at the kidney
11
Q
What is CBG?
A
Cortisol-binding globulin
12
Q
What is TBG?
A
Thyroxine-binding globulin
13
Q
What is SSBG?
A
Sex steroid-binding globulin (testosterone and oestrodiol)
14
Q
Name 2 general carrier proteins
A
Albumin
Transthyretin
15
Q
What are the 3 classes of hormone receptors?
A
GPCRs
Receptor Kinases
Nuclear Receptors
16
Q
What are GPCRs activated by?
A
amines and some proteins/peptides
17
Q
Give an example of a receptor kinase
A
Insulin receptor
18
Q
Name the 3 classes of nuclear receptor and give an example of which each can be activated by
A
Class 1 - steroid hormones
Class 2 - Lipids
Hybrid Class - T3
19
Q
What do alpha cells in pancreatic islets do?
A
secrete glucagon
20
Q
What do beta cells in pancreatic islets do?
A
secrete insulin
21
Q
What do delta cells in pancreatic islets do?
A
secrete somatostatin
22
Q
What do PP cells in pancreatic islets do?
A
secrete pancreatic polypeptide
23
Q
Where in the beta cells in insulin formed
A
RER
24
Q
Apart from an insulin molecule, what other 2 components make up a molecule of prepoinsulin
A
signal peptide
C-peptide
25
How many phases does insulin release occur in? How long does each phase last for?
2
1st phase = 10-15minutes
2nd phase = 1-2 hours
26
What is KATP inhibited by (drug)
Sulphonylureas
27
Give examples of sulphonylureas
tolbutamide
| glibenclamide
28
What is KATP stimulated by
Diazoxide
29
What other function does Diazoxide do? (Other than KATP stimulation)
Inhibits insulin secretion
30
A mutation in which protein of the KATP channel can lead to neonatal diabetes?
Kir6.2
31
What are the 2 proteins of the KATP channels?
Kir6.2 and SUR1
32
What does MODY stand for?
Maturity Onset Diabetes of the Young
33
What is MODY?
Monogenic diabetes with a genetic defect in beta cell function
34
In MODY, what can a glucokinase mutation cause?
BG threshold for insulin increases
35
MODY is not best treated with insulin in most cases, what other drug class is better indicated in MODY?
Sulphonylureas
36
Define Type 1 Diabetes
Loss of insulin secreting beta cells
37
Define Type 2 diabetes
Initially hyperglycaemia with hyperinsulinaemia.
| Decreased insulin sensitivity in the tissues.
38
What is the insulin receptor?
Dimeric tyrosine kinase
39
What is the insulin receptor made up of?
2 extracellular alpha subunits
2 transmembrane beta subunits
alpha and beta subunits linked by disulphide bonds
40
Insulin binds to the alpha subunits of the receptor, what does this cause the beta subunits to do?
autophosphorylate to activate the receptors catalytic activity
41
Name 3 biological effects of insulin
```
Amino acid uptake in muscles
DNA synthesis
Protein synthesis
glucose uptake in muscle and adipose tissue
lipogenesis in adipose tissue and the liver
glycogen synthesis in liver and muscle
gene expression
lipolysis
gluconeogenesis in the liver
```
42
What are the causes and symptoms of Leprechaunism (Donohue Syndrome)?
Caused by a rare, autosomal recessive genetic trait causing mutations in the gene for the insulin receptor.
Causes severe insulin resistance and developmental abnormalities.
43
What is the cause and the symptoms of Rabson-Mendenhall syndrome?
Rare, autosomal recessive genetic trait causing severe insulin resistance, hyperglycaemia and compensatory hyperinsulinaemia, developmental abnormalities and more.
44
Where are ketone bodies formed?
Liver mitochondria
45
Is ketoacidosis more associated with type 1 or type 2 diabetes?
Type 1
46
Define Diabetes mellitus (DM)
A group of metabolic diseases characterised by hyperglycaemia, resulting from defects in insulin secretion, insulin action or both.
47
What is the HbA1c diagnostic criteria for DM?
above 48mmol/mol
48
What is the fasting glucose diagnostic criteria for DM?
above 7mmol/l
49
What is the random glucose diagnostic criteria for DM?
above 11.1mmol/l
50
Give 2 tests used to descriminate between T1DM and T2DM
GAD/anti-islet cell antibodies (T1DM)
| Ketones (T1DM)
51
What does LADA stand for in an endocrine setting?
Latent Autoimmune Diabetes of Adulthood
52
What is monogenic diabetes? Give 2 examples of types of diabetes in which this can occur
When diabetes is caused by a mutation in a single gene.
| MODY and Neonatal diabetes can be monogenic
53
If a mother has T2DM, what is the chance that her daughter will develop it at some point in her life? (%)
40%
54
What percentage of T2DM patients are overweight or obese?
90%
55
As well as being overweight, what other factor must an individual have to develop T2DM?
vulnerable beta cells
56
As well as insulin resistance and T2DM, what other factors must a person have 2 of before they are considered to have metabolic syndrome?
Dyslipidaemia
Hypertension
Obesity
Microalbuminuria
57
What is the 1st line treatment for an overweight individual with T2DM?
Metformin
58
What is the 1st line treatment for an individual of normal weight with T2DM?
Sulphonylureas
59
Give an example of a thiazolidinedione used in T2DM
Pioglitazone
60
When is pioglitazone contraindicated?
Heart Failure
61
If oral therapy is ineffective, or if the HbA1c is deemed to high to justify adding another oral drug, what treatment is used in T2DM?
Insulin
62
What HbA1c % is aimed for to decrease risk of complications?
less than 7%
63
Monitoring of BG is not necessary in all T2DM patients. What 2 drugs indicate BG monitoring?
Insulin + Sulphonylureas
64
What is the target BP for diabetics?
less than = 130/80mmHg
65
As well as BG and BP levels, what else should be well controlled in diabetics over 40? And what should be used to control it?
Cholesterol
Simvastatin 40mg
Atorvastatin 10mg
66
What is the usual staring dose for metformin?
500mg od or bd
67
What are the main effects of metformin? (4 things)
HbA1c decreased by 15-20mmol/mol
Weight decrease
Prevention of micro and macro vascular complications
Decreased Triglycerides and LDL
68
Is metformin safe in pregnancy?
Yes
69
What are the adverse effects of metformin?
GI disturbances
Anaemia - rare
Lactic acidosis - very rare
Liver failure - discontinue if this occurs
70
What effect does eGFR have on the dose of metformin given?
less than 30ml/min = discontinue drug
| 30-45ml/min = half dose
71
Give the names of (and standard doses) of the 3 sulphonylureas which can be given in T2DM
Glicazide (40mg od - 160mg bd)
Glibenclamide (5mg-15mg od)
Glimepiride (1mg-6mg od)
72
What do sulphonylureas do on the cellular level?
Close the KATP channel, and stimulate insulin release
73
How much do sulphonylureas generally reduce the HbA1c by?
15-20mmol/mol
74
Do sulphonylureas prevent macro or micro vascular complications?
Micro
75
What are the adverse effects of sulphonylureas
Hypoglycaemia
Weight gain
GI disturbances
Headache
76
What is the standard dose range for pioglitazone?
15-45mg od
77
What effects does pioglitazone have on a T2DM patient?
HbA1c reduced by 15-20mmol/mol
Improvement in microalbuminurea
Reduced end point mortality
78
What are the adverse effects of pioglitazone?
Hypoglycaemia (unusual unless in combination with a SU)
Increase in weight
Increased risk of hospital admission with HF
Does not prevent micro or macrovascular complications
Increase hip fracture risk by 20% per year of use
79
What T2DM therapies work by increasing secretion of insulin?
SUs
GLP-1 analogues
Glinides
DPP-4 inhibitors
80
What T2DM therapies work by decreasing insulin resistance and decreasing hepatic glucose output?
Biguanides
| Thiazolidinediones
81
What T2DM therapy works by slowing glucose absorption from the GI tract?
alpha-glucosidase inhibitors
82
What T2DM therapy works by enhancing glucose excretion from the kidney?
SGLT2 inhibitors
83
What T2DM therapies work via insulin independent actions?
alpha-glucosidase inhibitors and SGLT2 inhibitors
84
If BG levels rise, what does GLUT2 facilitate?
Increased diffusion of glutamide into beta cells
85
What is it that stimulates insulin secretion from a cell?
Opening of voltage-activated Ca2+ channels, increasing the level of intracellular calcium
86
What is formed by a tetramer of Kir6.2 subunits?
Potassium selective ion channel
87
What causes the opening of the voltage activated Ca2+ channels
Membrane depolarisation from closed KATP channels
88
How do SUs interact with the KATP channels?
They displace ADP-Mg2+ from the SUR1 subunit, which closes the KATP channel, thus causing insulin secretion independent to BG levels.
89
Give 2 examples of glinides (meglitinides)
Repaglinide
| Nateglinide
90
What drug class do glinides work similarly to? and how do they differ?
Work similarly to SUs, but act at a distant site to the SUR1 subunit.
They are also less likely to cause severe hypos
91
What stimulates GLP-1 secretion in an individual?
Ingestion of food
92
Where is GLP-1 released from?
Enteroendocrine cells in the small intestine (L + K cells)
93
What effects does GLP-1 have on the pancreatic cells?
Enhance insulin release from beta cells
| Decrease glucagon release from alpha cells
94
What is the main GLP-1 analogue in theraptutic use? why does it differ from the normal physiological response?
Exenatide
| The effects last for longer thus lowering BG more steadily
95
What other beneficial effects do GLP-1 analogues have on the T2DM patient?
Slows gastric emptying and decreases apetite
96
What new longer acting GLP-1 analogue now exists? How is it given?
Liraglutide
| od subcut. injection
97
What terminates the effects of GLP-1?
DPP-4
98
How do gliptins (DPP4-inhibitors) work?
Competitively inhibit DPP-4, prolonging the effects of GLP-1
99
What is the main gliptin agent used? (And what other agents can be used?)
Sitagliptin - orally od
| Saxigliptin and vildagliptin
100
What is the alpha-glucosidase inhibitor in theraputic use?
Acarbose
101
What is alpha-glucosidase?
A brush border enzyme which breaks down starch and disaccharides to absorbable glucose
102
What does acarbose do?
Inhibits alpha-glucosidase thus reducing the postparandial (after meal) increase in glucose.
103
When in acarbose used?
When lifestyle changes and other oral agents are not effective in HbA1c and BG control
104
What are the adverse effects of acarbose?
GI disturbances and infections
105
How do biguanides (metformin) work?
Reduce hepatic gluconeogenesis - stimulates AMPK
Increases glucose uptake and utilisation by skeletal muscle
Decreases carbohydrate absorption
Increases fatty acid oxidation
106
What are TZDs (Glitazones)
Exogenous agonists of PPAR-alpha which associates with RXR
107
What do TZDs do?
Enhance the action of insulin at target tissues (decrease the amount of insulin needed to maintain a given BG)
Promote fatty acid uptake and storage in adipocytes rather than skeletal muscle and the liver
Decreases the hepatic glucose output
108
Give an example of a TZD
Pioglitazone
109
What do SGLT2 inhibitors do?
Selectively block reabsorption of glucose by SGLT2 in the proximal tubule of the kidney nephron, deliberately causing glucosuria
110
What other benefit do SGLT2 inhibitors have?
Cause calorific loss and weight loss - glucose voided
111
What is the currently licensed SGLT2 inhibitor?
Dapagliflozin
112
What are the highest risk HLA genotypes with development of T1DM? What percentage of T1DM patients have one of these?
DR3-DQ2/DR4-DQ8
| 95% of patients less than 30 have 1 or both
113
What autoantibodies are associated with some development in T1DM?
GAD (glutamic acid decarboxylase)
Insulin (IAA)
IA2 (Islet-antigen 2)
ZnT8 (Zinc transporter)
114
What is the classic triad of symptoms in T1DM?
Polyuria
Polydipsia
Weight loss
115
What symptoms other than the classic triad can present in T1DM?
Fatigue
Blurry vision
Candidial infection
DKA
116
Where is insulin secreted into?
Portal vein
117
When fasting, what is the rate of insulin secretion?
0.25-1.5 units per hour
118
What type of diabetes are children <6months likely to have?
Monogenic (Neonatal)
119
How is LADA diagnosed?
Presence of increased pancreatic autoantibody levels in patients with recently diagnosed diabetes not needing immediate insulin therapy
120
Name 3 conditions associated with diabetes
```
Cystic fibrosis (25% have DM)
DIDMOAD
Bardet-Biedl syndrome
Addisons disease
Thyroid disease
Coeliac disease
Pernicious anaemia
IgA deficiency
```
121
What 2 AI conditions are very strongly associated with T1DM?
```
Thyroid disease (1:50 in normal population; 1:20 in T1DM)
Coeliac disease (1:100 in normal population; 1:20 in T1DM)
```
122
What is polyglandular endocrinopathy?
A set of multiple endocrine gland deficiences that may or may not be AI
123
What is the normal age of onset of MODY?
less than 25 years
124
What is the best treatment for HNF1-alpha mutations?
Gliclazide (an SU)
125
What is the definition of neonatal diabetes?
Requires insulin treatment within first 3 months of life
126
What are the 2 types of neonatal diabetes and how are they defined?
Transient - diagnosed less than 1 week and resolves within 12 weeks when insulin can be stopped
Permanent - Diagnosed 0-6 weeks and requires lifelong treatment
127
If Permanent neonatal DM is caused by mutations in Kir6.2, what can this be treated with rather than insulin?
Glibenclamide (an SU)
128
What types of insulin are marketed as rapid acting? (last between 4-6 hours)
Humalog
Novorapid
Apidra
129
What types of insulin are marketed as short acting? (~8 hour duration)
HumulinS
Actrapid
Insuman rapid
130
What types of insulin are marketed as intermediate acting? (18-20 hours duration)
Humulin I
| Insuman basal
131
What types of insulin are considered as long-acting analogues?
Lantus
| Levemir
132
What are some of the rapid acting/ intermediate acting insulin mixes that are available?
Humalog mix 25/mix 50
| NovoMix 30
133
What are some of the short acting/ intermediate acting insulin mixes that are available?
Humulin M3
| Insumancomb 15, 25, 50
134
What is the advantage of a basal bolus insulin regimen?
Mimics normal endogenous insulin production
135
What factors can affect the absorption action of insulin?
```
temperature
injection site
injection depth
exercise
pen accuracy
leakage
```
136
What should a patient with insulin always check for at the injection sites?
Lipohypertrophy
137
What is HbA1c?
Glycated haemoglobin - formed by non-enzymatic glycation of haemoglobin in exposure to glucose
138
What HbA1c range is diagnostic for diabetes?
>= 48mmol/mol (6.5%)
139
What do ketone meters measure?
3betaOH-butyrate
140
What are some symptoms of hypoglycaemia?
```
Shaking
Sweating
Anxiousness
Dizziness
Headache
Irritability
Hunger
Tachycardia
Impaired vision
Weakness/fatigue
```
141
How is severe hypoglycaemia defined as?
Hypoglycaemia that leads to seizures, unconsciousness or the need for external asistance
142
How is hypoglycaemia treated?
Consuming 15-20g glucose or simple carbohydrates
| Recheck BG and keep rechecking until normal
143
How would severe hypoglycaemia be treated?
Inject 1mg glucagon
144
What is hypoglycaemia unawareness?
When BG is 3.5-4mmol/l and the individual has no symptoms
145
In what groups of people is hypoglycaemic unawareness more likely to occur in?
Frequent low BG levels
Longstanding T1/T2DM
Intensively treated T1DM
146
In a non-diabetic what changes does the body cause when BG = 3.8mmol/l?
Glucagon and adrenaline kick in
147
In a non-diabetic what changes does the body cause when BG = 3.0mmol/l?
Symptoms of hypoglycaemia begin to appear
148
In a non-diabetic what changes does the body cause when BG = 2.8mmol/l?
Cagnitive dysfunction occurs
149
Why is hypoglycaemia more common in T1DM patients?
Neither insulin or glucagon is present to prevent the hypo so no corrective action can be taken by the body itself
150
What is DKA?
A disordered metabolic state, usually occurring in absolute or relative insulin deficiency accompanied by an increase of counter-regulatory mechanisms e.g glucagon, adrenaline, cortisol + GH.
151
How does DKA cause death in adults?
Hypokalaemia
Aspiration pneumonia
ARDS
152
How can DKA cause death in children?
Cerebral oedema
153
What are the main pathophysiological points that contribute to DKA?
Hyperglycaemia
Increased ketogenesis
Acidosis
Hyperosmolarity
154
What can trigger DKA?
Non-compliance with medication (most common)
Infections
Illicit drugs and alcohol
Newly-diagnosed diabetes (on no treatment)
155
What biochemistry results can be used to diagnose DKA?
Ketonaemia >3mmol/l or significant ketonuria
BG >11mmol/l or known diabetes
Bicarbinate less than 7.3 (attempt to compensate for acidosis)
156
What typical symptoms are associated with DKA?
Thirst, polyuria, dehydration
| Flushing, vomiting, abdo pain, tenderness, breathlessness, ketones (pear drops) on breath
157
Other than ketones, what other biochemistry results may be raised?
Amylase + WCC
158
How is DKA treated?
Fluid - initially with 0.9% NaCl, then when BG falls <15, switch to 10% dextrose
Insulin
Potassium
159
What is the normal range for lactate?
0.6-1.2mmol/l
160
Where does lactate come from?
RBCs, skeletal muscle, brain and renal medulla
161
What causes type A lactic acidosis?
Tissue hypoxaemia
162
What causes type B lactic acidosis?
Liver disease
Diabetes (occurs in 10% DKA episodes)
Metformin
163
How does lactic acidosis present clinically?
Hyperventillation
Mental confusion
Stupor or coma if severe
164
How does lactic acidosis appear in biochemistry results?
Low bicarb
Increased anion gap
Glucose often high
High phosphate
165
How is lactic acidosis treated?
Fluids and antibiotics
| Withdrawal of any causative medications
166
How does hyperglycaemic hyperosmolar syndrome present?
```
incresed refined carbohydrates before the event
BG very high ~60
Significant renal impairment
increased osmolarity
Less ketonaemia/acidotic than DKA
```
167
How is hyperglycaemic hyperosmolar syndrome different from DKA?
```
More common in older T2DM patients
Caused by undiagnosed DM, diuretics, steroids, fizzy drinks
Often a infection predisposing event
Much higher mortality
More liklely to have comorbidities
```
168
How is hyperglycaemic hyperosmolar syndrome treated differently from DKA?
Fluids are given slower due to higher risk of cerebral oedema
Insulin given slower
Avoidance of rapid sodium fluctuations, may need to use 0.45% saline
LMWH
169
What are the main macrovascular complications of diabetes?
IHD
| Stroke
170
What are the main microvascular complications of diabetes?
Neuropathy
Nephropathy
Retinopathy
171
Other than micro/macrovascular complications, what other complications can occur in diabetes?
Erectile dysfunction
| Psychiatric
172
What are the different types of neuropathy which can occur in diabetes?
Peripheral - pain/loss of feeling in feet/hands
Autonomic - bowel/bladder function changes, hypoglycaemic unawareness
Proximal - pain in thighs, hips or buttocks
Focal - Sudden weakness in one nerve causing muscle weakness and/or pain
173
What symptoms may be associated with diabetic neuropathy?
```
Numbness, pain, tingling
Ulcers
Muscle wasting
Indigestion, NV
Dizziness
Urination issues
```
174
What increases the risks of developing diabetic neuropathy?
```
Duration of diabetes
Poor control
T1DM
High cholesterol
Smoking/Alcohol
Genetics
Mechanical injuries
```
175
What are the symptoms of a distal symmetric or sensorimotor neuropathy?
```
Numbness
Tingling/burning
Sharp pains/cramps
Sensitivity to touch
Loss of balance/coordination
```
176
What complications may arise as a result of distal symmetric or sensorimotor neuropathy?
Infection/ulceration
Deformities (hammer toe/collapse of midfoot)
Amputations
177
How is painful neuropathy treated? (list with increasing amounts of pain)
```
Simple analgesia
TCAs
Gabapentin
Duloxetine/Pre-gabalin
Stronger opiods - oxycodone/tramadol
```
178
What topical treatment can be used for painful neuropathy?
Capsaicin cream
179
How can autonomic neuropathy affect the digestive system?
Gastric slowing - constipation
Gastroparesis (slow stomach emptying) - N+V, bloating and loss of appetite
Can make BG levels fluctuate greatly
Oesophageal nerve damage - swallowing is difficult
180
How can autonomic neuropathy affect the sweat glands?
Body temp is not regulated
| May sweat profusely at night or when eating
181
Autonomic neuropathy may cause hypoglycaemic unawareness, what is this?
Symptoms of hypos may not occur
182
How can autonomic neuropathy affect the CVS?
Postural hypotension
| HR may stay high despite normal body functions
183
How can autonomic neuropathy affect the eyes?
Pupils have decreased responsiveness to changes in light
| This makes driving in the dark difficult
184
How can neuropathy be diagnosed?
```
Nerve conduction studies/EMG
HR variability in response to changes to BP, stance and breathing etc.
US
Gastric emptying studies
Foot screening once per year
```
185
What types of nephropathy may occur in diabetics?
Kimmelsteil-Wilson syndrome
Nodular GN
Angiopathy of capillaries
186
Between 1-5% diabetics are found to have CKD, what are the consequences of this?
Hypertension
Decline in renal function
Accelerated vascular disease
187
What screening program exists for diabetic nephropathy?
All patients >12 have urinary ACR testing done once a year
| Dipstick testing is also done
188
What are the risk factors for progression on nephropathy?
```
Hypertension
High cholesterol
Poor glycaemic control
Smoking
Albuminuria
```
189
What should all patients with microalbuminuria/proteinuria be commenced on and why?
```
ACEI
Dilates renal arteries
Lowers filtration pressure
Reduces proteinuria
Reduces GFR (upto 20%)
```
190
What eye pathologies can diabetics get?
Diabetic retinopathy
Cataract
Glaucoma
Acute hyperglycaemia (visual blurring)
191
What do cotton wool spots suggest when seen on the fundus?
Ischaemic areas
192
What do hard exudates suggest when seen on the fundus?
Lipid breakdown products
193
What would a retinopathy of grade R0 suggest?
No diabetic retinopathy - rescreen in 12 months
194
What would a retinopathy of grade R1 suggest?
```
Background diabetic retinopathy (BDR) - rescreen in 12 months
At least 1 of the following anywhere:
Dot haemorrhages
Microaneurysms
Hard exudates >2DD
Cotton wool spots
Superficial/flame shaped haemorrhages
```
195
What would a retinopathy of grade R2 suggest?
BDR - >=4 blot haemorrhages in 1 hemi-field only
| Rescreen in 6 months
196
What would a retinopathy of grade R3 suggest?
BDR with 1 of the following:
4 or more blot haemorrhages in both hemi-fields
Venous bleeding
Intra-retinal microvascular abnormalities
Refer to ophthalmology
197
What would a retinopathy of grade R4 suggest?
Proliferative diabetic retinopathy:
Active new vessels
Vitreous haemorrhage
Refer to ophthalmology ASAP!
198
What would a retinopathy of grade M1 suggest?
Lesions within a radius of >1 but <2 disc diameters(DDs) from the fovea
Rescreen in 6 months
199
What would a retinopathy of grade M2 suggest?
Lesions less than 1DD from the fovea
| Refer to ophthalmology (does not need ASAP treatment but does need close surveillance)
200
What other complications can arise from diabetic retinopathy?
Secondary glaucoma
| Retinal detachment
201
How is retinopathy treated?
Laser therapy
Vitrectomy
Anti-VEGF injections
202
How common is erectile dysfuction in males with diabetes?
affects 50% of diabetic men, and 55% of those >60y/o
203
How can erectile dysfuction caused by diabetes be treated?
improve glycaemic control/lose weight/improve lipids
Lower alcohol intake
Withdrawal of causative drugs where possible
204
What oral medication can be given to men with erectile dysfunction?
sildenafil (viagra)
vardenafil (levitra)
tadalafil (cialis)
205
What are the contraindications to taking medications for erectile dysfunction?
If the patient is on nitrates, nicorandil
Stroke/MI in past 3 months
Hypotension
Severe hepatic dysfunction
Hereditary degenerative retinal disorders
206
What vascular disorders does having diabetes increase the risk of?
Stroke
Peripheral vascular disease
Coronary artery disease
207
Why does diabetes increase the risk of developing vascular disease?
```
Dyslipidaemia
Endothelial dysfunction
Platelet aggregation
Thrombogenesis
Inflammation/increased oxidative stress
```
208
What psychiatric disorders can come from diabetes?
Depression
Eating disorders
Bi-polar disorder
Schizophrenia
209
What does the thyroid gland tissue secrete?
Thyroxine (T4)
Tri-iodothyronine (T3)
Calcitonin
210
What do the 4 parathyroid glands secrete?
PTH - parathyroid hormone
211
How does the thyroid tissue appear histologically?
Colloid-tyrosine containing thyroglobulin filled spheres enclosed by follicular cells
Surrounding the follicles lies the parafollicular C cells which secrete calcitonin
212
How are the thyroid hormones created and stored?
Iodine is taken up into follicle cells where it is attached to tyrosine residues on thyroglobulin to form MIT (monoiodotyrosine) and DIT (Di-iodotyrosine)
```
MIT+DIT = T3
2*DIT = T4
```
T3 and T4 are then stored in colloid thyroglobulin until required
213
What is T4?
Thyroxine - approx 90% of thyroid hormones secreted
| Converted to T3 by the liver and kidney
214
What is T3?
Triiodothyronine - approx 10% of thyroid hormones secreted
4x more potent than T4
Is the major biologically active thyroid hormone
215
What does carbimazole and propythiouracil inhibit?
Iodine attaching to tyrosine residues to form T3 and T4
216
How and to where are T3 and T4 released?
TSH acts upon the follicular cell and T3T4 are secreted from the colloid, through the follicular cells, and into the blood, where T3 is turned into T4
217
What happens when T3 reaches its target cell?
T3 acts upon the nuclear receptors of the target cell, which then produces mRNA proteins and then a biological response.
218
T3 + T4 are hydrophobic/lipophilic so to be transported they must bind to plasma proteins. What are these plasma proteins?
Thyroxine binding globulin (TBG) = 70%
Thyroxine binding prealbumin (TBPA) = 20%
Albumin (5%)
T3 and T4 are only biologically active when UNBOUND from these plasma proteins
219
What can caused Increased TBG levels?
```
Pregnancy
Newborns
Oestrogen levels
Hep A/Active hepatitis
Billiary cirrhosis
Genetics
Heroin
```
220
What can cause decreased TBG levels?
```
Androgens
Large doses of glucocorticoids
Acromegaly
Systemic illness
Chronic liver disease
Genetics
Pheytoin, carbamzepine
```
221
How do the thyroid hormones affect BMR?
Increased number and size of mitochondria
Increased oxygen use and rates of ATP hydrolysis
Increased synthesis of resp. chain enzymes
222
How do the thyroid hormones affect thermogenesis?
approx 30% thermoregulation due to thyroid hormones
223
How do the thyroid hormones affect carbohydrate metabolism?
Raised BG - due to stimulation of glycogenolysis and gluconeogenesis
Insulin-dependent glucose uptake into cells
224
How do the thyroid hormones affect lipid metabolism?
Mobilises fats from adipose
| Fatty acid oxidation in tissue
225
How do the thyroid hormones affect Protein metabolism?
Stimulates protein synthesis
226
How do the thyroid hormones affect growth?
Causes GHRH production and secretion
Glucocorticoid-induced GHRH release
GH/somatomedins
All require thyroid hormones in order to happen
227
How do the thyroid hormones affect the development of the fetal and neonatal brain?
Myelinogenesis and axonal growth requires thyroid hormones
228
How do the thyroid hormones affect normal CNS activity?
```
Hypothyridism = slow intellectual functions
Hyperthyroidism = nervousness, hyperkinesis and emotional instability
```
229
How do the thyroid hormones affect permissive sympathomimmetic actions?
Increased responsiveness to adrenaline and NA
CV responsiveness also increased (increased force and rate of contraction of the heart)
Beta-blockers are initially used in hyperthyroidism to prevent this
230
How are thyroid hormone levels regulated?
Thyrotrophin releasing hormone (TRH) stimulates TSH.
T3 + T4 exert a -ve feedback control of TRH and TSH
Low temps causes TRH release in young children and babies
Stress inhibits TRH and TSH release
Thyroid hormones are higher at night and lower in the morning.
231
What is hypothyroidism?
Deficiency of T3 and T4 levels
232
What causes primary hypothyroidism?
Thyroid gland failure - may be associated with goitre
233
What causes secondary hypothyroidism?
TRH or TSH abnormalities - no goitre
234
What are the symptoms of hypothyroidism?
```
Low BMR
Slow pulse
Fatigue, lethargy, slow response times, mental sluggishness
Cold intolerance
Put weight on easily
```
235
What signs may indicate hypothyroidism in only adults?
Myxoedema - puffy face, hands and feet
236
What signs may indicate hypothyroidism in only babies?
Cretinism - dwarfism + limited mental functioning
237
What is the most common cause of hyperthyroidism?
Grave's disease
238
What is the pathology behind grave's disease?
AI condition where TSI (thyroid stimulating immunoglobulin) acts like TSH but goes unchecked by T3 + T4
239
What symptoms and signs are associated with Grave's disease?
```
Exopthalmos - water retaining carbohydrate build up behind eyes
Goitre
High BMR
V. fast pulse
Nervousness and emotional instability
Insomnia
Sweating and heat intolerance
Tendency to lose weight easily
```
240
What is the commonest type of thyroid cancer?
Papillary (76%)
241
What is the second commonest type of thyroid cancer?
Follicular (17%)
242
What varients of thyroid cancer are diffentiated?
Follicular and Papillary
243
How do most differentiated thyroid cancers (DTCs) act physiologically?
Take up iodine and secrete thyroglobulin
| Are driven by TSH
244
How do DTCs present?
Palpable thyroid nodules
| 5% will have have local or disseminated metastases
245
How does Papillary TC spread?
via lymphatics
| via blood to lungs, bone, liver and brain
246
What thyroid disease is papillary TC associated with?
Hashimoto's thyroiditis
247
What is the general prognosis of papillary TC?
10 year mortality less than 5%
248
Where is there increased incidence of follicular TC?
Areas where iodine deficiency is common
249
How does follicular TC spread?
Via the blood
250
What investigation is usually done for a neck lump suspected to be associated with the thyroid?
US-guided FNA
| Potentially excision biopsy of the lymph nodes
251
What clinical features would suggest a thyroid lump is more likely to be malignant?
```
New thyroid nodule in those 50
Male sex
Nodule growing
>4cm diameter
History of head/neck irradiation
Vocal cord palsy
```
252
What is the treatment of choice for DTC?
Surgery
Thyroid lobectomy with isthmusectomy
Sub-total thyroidectomy
Total thyroidectomy
253
What does the risks of surgery depend on?
AMES
```
A = age
M = metastases
E = extent of primary tumour
S = size of primary tumour
```
254
What is the 20 year survival rate for those who have low AMES scores?
99%
255
What is the 20 year survival rate for those who have high AMES scores?
61% (with surgery alone)
256
When is thyroid lobectomy with isthmusectomy indicated?
Papillary microcarcinoma (<1cm)
Minimally invasive follicular tumour
AMES low risk
257
When is sub-total/total thyroidectomy indicated?
```
DTC with extra-thyroidal spread
Bilateral/multifocal
Distant mets
Nodal involvement
AMES high risk
```
258
What is involved in the post-op care of a thyroidectomy of any sort?
Calcium checked within 24hours
| Calcium replaced if less than 2mmol/l
259
When is whole body iodine scanning used?
3-6 months post-op of a sub-total or total thyroidectomy
260
What must be done before a whole body iodine scan is performed?
T4 stopped 4 weeks before scan
OR
T3 stopped 2 weeks before scan
261
Why does the whole body iodine scanning take a full week?
Injections to raise TSH given on mon and tues
Radioactive iodine capsule administered on wed
Patient returns for the imaging process on Friday
262
What happens if following a whole body iodine uptake scan the uptake in the thyroid bed is found to be >0.1% of the ingested activity?
Patient will undergo thyroid remnant ablation (TRA) the following Tues
263
What happens to the patient when receiving TRA?
Admitted to a lead lined room with mains sewarage
Given 2/3GBq capsule of radioactive iodine
Patient uses disposable utensils for the duration of stay
Discharged when count rate <500cps at 1m. on T4
264
What can Thyroglobulin (Tg) be used as?
A tumour marker post TRA
265
If a child has a high BG, but no ketones and is clinically well, how soon should they get a paediatric clinical review?
24-48hours
266
If a child has high BG, ketones, but is clinically well, how soon should they see a paediatrician?
Within the same day
267
How is DKA treatment different in children?
Fluid resus is based on weight
Risk of cerebral oedema is highlighted
Insulin in commenced 1 hour after IV fluids are started
268
What are the signs of early vascular disease in children?
```
Microalbuminaemia
CV autonomic neuropathy
Sensory nerve damage
Retinopathy
Thickened skin and limited joint mobility of hands and fingers
Skin vascular changes
```
269
What is primary congenital thyroid disease?
Dysplastic gland +/- an abnormal site e.g. sublingual
270
What is secondary/tertiary congenital thyroid disease?
Congenital pituitary disease
| Usually associated with hypopituitarism
271
What are the clinical symptoms of congenital thyroid disease?
Delayed jaundice
Poor feeding but "normal" weight gain
Hypotonia
Skin and hair changes
272
How is congenital thyroid disease screened for?
Capillary blood spot in blotting paper at 5 days to measure TSH and/or T4 levels = Guthrie test
273
If a child is found to have congenital thyroid disease when should therapy be commenced?
within 2 weeks of birth
| 2-3 month window where protected by placental thyroid hormones
274
If a child with congenital thyroid disease is not treated within 3 months and thyroxine is absent, then what will happen?
Child will develop cretinism - permanent developmental delay
275
How does hypothyroidism present in children?
```
slow progress
Growth retardation and delayed puberty
poor general health
educational difficulties
Goitre
TFTs = high TSH and low free T3/T4
High thyroid cell antibody titres
```
276
How is hypothyroidism in children treated?
Thyroxine replacement for life
| Dose is dependent on the size of the child
277
How does hyperthyroidism present in children?
```
Behavioural problems, sleep disturbance, eating difficulties
Goitre, high PR
Precocious puberty
TFTs = low TSH and high Free T3/T4
High thyroid cell antibody titres
```
278
How is hyperthyroidism treated in children?
Initially = beta-blockers
Suppressant for at least first 2 years = carbimazole +/- thyroxine
Permanent cure = Radio-iodine + surgery
279
What causes primary underactive adrenal disorders in children?
(low steroid production)
Adrenal hyperplasia
Inborn error of metabolism
CAH
280
What causes secondary underactive adrenal disorders in children?
Pituitary disease
| Suppression secondary to steroids
281
What does overactive production of steroids cause in children?
Cushing's disease
Primary = Adrenal cause
Secondary = Pituitary cause
282
What does 21-alpha-hydroxylase deficiency lead to?
No aldosterone or cortisol production
High testosterone conversion
= Fetal virilisation
283
What happens to the body when there is no cortisol or aldosterone?
"Addison crisis" - hyponatraemia, hyperkalamia and hypotension
284
How is an addison crisis managed?
Urgent therapy with salt and cortisol
285
What does virilisation in females cause?
ambiguous genitalia
286
What does virilisation in males cause?
Precocious puberty
287
What conditions may lead to ambiguous genitalia?
CAH or other steroid abnormalities
Gene and/or chromosomal abnormalities
Congenital defects
288
What conditions may lead to ambiguous genitalia?
CAH or other steroid abnormalities
Gene and/or chromosomal abnormalities
Congenital defects
289
What would the TFTs show in primary hypothyroidism?
TSH high
| T4/T3 low
290
What would the TFTs show in primary hyperthyroidism?
TSH low
| T4/T3 high
291
What would the TFTs show in secondary hypothyroidism?
TSH low
| T3/T4 low
292
What would the TFTs show in secondary hyperthyroidism?
TSH high
| T3/T4 high
293
What causes secondary hypothyroidism?
Pituitary gland failure
| Hypothalamic problems
294
What causes secondary hyperthyroidism?
TSHoma (rare)
295
What is myxoedema?
Severe hypothyroidism leading to a myxoedema coma
296
What is pretibial myxoedema?
Accumulation of hydrophilic mucopolysaccharides in the ground substance of the dermis leading to a doughy induration of the skin typically in the shins
297
What thyroid disease can present with pretibial myxoedema?
Grave's disease (thyrotoxicosis)
298
What are the 2 main causes of goitrous, primary hypothyroidism?
```
Chronic thyroiditis (Hashimoto's thyroiditis)
Iodine deficiency
```
299
What is the main cause of non-goitrous, primary hypothyroidism?
Atrophic thyroiditis
300
What are the self-limiting causes of hypothyroidism?
Withdrawal of thyroid suppressive therapy
Subacute thyroiditis and chronic thyroiditis with transient hypothyroidism
Post-partum thyroiditis
301
What are the main causes of secondary hypothyroidism caused by the hypothalamus?
Congeital defects
Encephalitis
Sarcoidosis
Malignancy
302
What are the main causes of secondary hypothyroidism caused by the pituitary?
panhypopituitarism (trauma. infection, infiltration, neoplasm)
Isolated TSH deficiency
303
What are the main causes of secondary hypothyroidism caused by the pituitary?
panhypopituitarism (trauma. infection, infiltration, neoplasm)
Isolated TSH deficiency
304
What hypothyroid disorder is also known as an AI condition?
Hashimoto's thyroiditis
305
What is the pathophysiology behind Hashimoto's thyroiditis?
AI destruction of the thyroid gland causing decreased thyroid hormone production
306
What investigtions would prove a diagnosis of Hashimoto's thyroiditis?
Thyroid peroxidase antibodies in the blood
| T-cell infiltrate and inflammation on microscopy
307
What symptoms occur in the hair/skin in hypothyroidism?
```
Coarse, sparse hair
Dull, expressionless face
Periorbital puffiness
Pale, cool skin that feels doughy to touch
Hypercarotenaemia? (yellow skin)
```
308
How does hypothyroidism affect thermogenesis?
Become intolerant to cold
309
How does hypothyroidism affect the body's fluid status?
Causes pitting oedema
310
What cardiac symptoms may be present in hypothyroidism?
Low HR
Cardiac dilatation
Pericardial effusion
Worsening of pre-existing HF
311
How might hypothyroidism affect the metabolism and BMR?
Hyperlipidaemia
Decreased appetite
Weight gain
312
What GI symptoms may present with hypothyroidism?
Constipation
Megacolon and intestinal obstruction (rare)
Ascites (rare)
313
What resp. symptoms may present with hypothyroidism?
Deep hoarse voice
Macroglossia
Obstructive sleep apnoea
314
What neurological/CNS symptoms may appear with hypothyroidism?
```
Decreased intellectual and motor activities
Depression
Muscle stiffness/cramps
Peripheral neuropathy
Carpal tunnel syndrome
Decreased visual acuity
```
315
What gynaecological/Repro symptoms may present with hypothyroidism?
```
Menorrhagia
Hyperprolactinaemia (high TSH = high prolactin)
```
316
What lab results will show with hypothyroidism?
Macrocytosis (large RBCs)
High creatinine kinase
High LDL cholesterol
Hyponatraemia - decreased renal tubular water loss
317
What lab results will show with hypothyroidism?
Macrocytosis (large RBCs)
High creatinine kinase
High LDL cholesterol
Hyponatraemia - decreased renal tubular water loss
318
What thyroid antibodies (and what percentage of people) are present in Grave's disease?
Anti TPO (70-80%)
Anti-thyroglobulin (30-50%)
TSH-receptor (70-100%)
319
What thyroid antibodies (and what percentage of people) are present in AI hypothyroidism?
Anti TPO (95%)
Anti-thyroglobulin (60%)
TSH-receptor (10-20%)
320
How is hypothyroidism managed?
Thyroxine od before breakfast
| Restoration of normal BMR gradually
321
When might thyroxine levels have to be increased for a patient with hypothyroidism?
Pregnancy (25-50% increase in dose requirements)
322
Who is most likely to be affected by myxoedema coma?
Elderly women with longstanding untreated/poorly treated hypothyroidism
323
How does myxoedema coma present?
ECG - Bradycardia, low voltage complexes, heart block, T-wave inversion, prolonged QT
Type 2 resp failure: Hypoxia, hypercarbia, resp. acidosis
324
How is myxoedema coma treated?
ABCDE
Slowly rising temp
Close monitoring of ECG, BP, BG, urine output
Fluids and electrolytes - closely monitored
Broad spectrum antibiotics
325
How does amiodarone affect the thyroid function?
upto 50% have abnormalities
- 2% = thyrotoxicosis
- 13% = hypothyroidism
326
What are the cardiac symptoms associated with hyperthyroidism?
Palpitations/AF
| HF (rare)
327
What are the cardiac symptoms associated with hyperthyroidism?
Palpitations/AF
| HF (rare)
328
How can hyperthyroidism affect the CNS?
Anxiety, nervousness, irritability, sleep disturbance
329
How can hyperthyroidism affect the GI system?
Frequent, loose bowel movements
330
How might hyperthyroidism affect the vision?
Lid retraction
Double vision
Proptosis
331
How may hyperthyroidism affect the hair and skin?
Brittle, thinning hair
| Rapid fingernail growth
332
How can hyperthyroidism affect the repro system?
Menstrual cycle changes - lighter and less frequent
333
How can hyperthyroidism affect the muscles?
Weakness esp. in thighs and upper arms
334
What happens to the metabolism in hyperthyroidism?
Weight loss despite increased appetite
335
How does hyperthyroidism affect thermogenesis?
Becomes intolerant to heat
336
What are the causes of hyperthyroidism?
AI - Grave's
Nodular thyroid - Goitre, toxic nodule (adenoma)
Thyroiditis
Iodine (rare)
Medication (rare) - Lithium, amiodarone, thyroxine
337
Who is most likely to get Grave's disease?
Women between 20-50 with a +ve FH and increased iodine intake.
338
At 18 months what happens to those with Grave's disease?
50% - burn out
| 50% - relapse
339
What would investigations show in an individual with Grave's disease?
High T3/T4
Low TSH
Antibody +ve (TRAbs)
340
How would a patient with Grave's disease present?
```
Smooth symmetrical goitre
Lid retraction and lid lag
Swellin of conjunctivae
Proptosis
Visual loss and diplopia
```
341
How is Grave's disease treated?
```
Lubricants
Decompression surgery
Radiotherapy
Corrective surgery
Smoking cessation
```
342
What age group is more likely to get nodular thyroid disease?
Older patients
343
How does Nodular thyroid disease differ from Grave's?
More gradual onset
| Gland may feel nodular and asymmetrical
344
What would investigations show in an individual with Nodular thyroid disease?
High T3/T4
Low TSH
Antibody -ve (TRAbs)
345
What would investigations show in an individual with Nodular thyroid disease?
High T3/T4
Low TSH
Antibody -ve (TRAbs)
346
What is sub-acute thyroiditis/De Quervains?
A potentially virally triggered thyroiditis which affects females between 20-50.
May be associated with a sore throat/fever
Usually self-limiting (few months)
347
What do the TFTs show in sub-acute thyroiditis/De Quervains?
T4 =high in early stage, low in late, then normal
| TSH = low in early stage, high in late, then normal
348
What is a thyroid storm?
A medical emergency with severe hyperthyroidism, resp and cardiac collapse, exaggerated reflexes and hyperthermia
349
How is a thyroid storm treated?
Lugols iodine, glucocorticoids, PTU, beta-blockers, fluids, and very close monitoring
350
How is hyperthyroidism treated?
Carbimazole
Propylthiouracil (PTU) (used in pregnancy)
Beta blockers
Radioiodine or surgery
351
What is the composition of the thryroid?
Multiple follicles surrounded by flat to cuboidal follicular epithelial cells.
In the centre of each follicle is a dense amorphic pink material containing thyroglobulin
There are scattered C (parafollicular) cells which are slightly larger with a clear cytoplasm, and secrete calcitonin.
352
How would a thyroid adenoma present?
A discrete solitary mass encapsulated by a collagen cuff.
Composed of neoplastic thyroid follicles
Usually non-functional but may secrete thyroid hormones leading to thyrotoxicosis
353
How would a thyroid adenoma present?
A discrete solitary mass encapsulated by a collagen cuff.
Composed of neoplastic thyroid follicles
Usually non-functional but may secrete thyroid hormones leading to thyrotoxicosis
354
What HLA groups is Hashimoto's thyroiditis associated with?
HLA-DR3
| HLA-DR5
355
What are the genetic features associated with Papillary thyroid carcinomas?
activate the MAPK pathways
rearrangements of RET ot NTKR1
Activating point mutation in BRAF
356
How does a papillary thyroid carcinoma present?
Usually a solitary nodule in the thyroid sometimes with lymph node mets
357
What are the genetic features associated with a follicular thyroid carcinoma?
Mutations in P13K/AKT pathway
358
How does follicular thyroid carcinoma usually present?
Single nodule which slowly enlarges is painless and non-functional
Rarely has lymphatic spread but may have haematogenous spread to bones/lungs/liver
359
What genetic factors are associated with Medullary Thyroid carcinoma (MTC)?
MEN2 - germline RET mutations
360
What is MTC derived from?
C-cells (neuroendocrine) and may secrete calcitonin
361
What does a MTC contain?
Spindle or polygonal cells arranged in nests, trabeculae or follicles
362
What may the cause of a MTC be?
Sporadic (70%)
Associated with multiple endocrine neoplasia (MEN)
Familial
363
Amyloid deposition may be associated with a MTC, why?
Amyloid represents deposition of an abnormally folded protein - in this case calcitonin
364
How does MTC usually present?
Neck mass with local effects
| Paraneoplastic symdrome - diarrhoea, Cushings
365
How does MTC usually present?
Neck mass with local effects
| Paraneoplastic symdrome - diarrhoea, Cushings
366
What is anaplastic thyroid carcinoma?
An undifferentiated, aggressive tumour usually found in older patients
367
What genetic factors are associated with anaplastic thyroid carcinoma?
Features of both papillary and follicular carcinomas + p53 and beta-catenin mutations
368
In thyroid cytology what would a specimen with Thy1 results be?
Insufficient/uninterpretable results
369
In thyroid cytology what would a specimen with Thy2 results be?
Benign
370
In thyroid cytology what would a specimen with Thy3 results be?
Atypia/probably benign/equivocal
371
In thyroid cytology what would a specimen with Thy4 results be?
atypia suspicious of malignancy
372
In thyroid cytology what would a specimen with Thy5 results be?
Malignant
373
How many parathyroid glands does an individual have?
usually 4
| 10% populus have 2/3
374
What do chief cells which make up the parathyroid glands do?
secrete PTH
| act on Ca homeostasis
375
What do chief cells look like histologically?
Round cells with moderate cytoplasm and bland, round central nuclei
376
What do oxyphil cells do?
Support the chief cells in the parathyroid glands
377
What do the oxyphil cells look like on histology?
Slightly larger than chief cells
| Acidophilic cytoplasm
378
What are most cases of hyperparathyroidism caused by?
small adenomas on 1 parathyroid gland
379
What is hyperplasia of the parathyroid glands associated with?
MENI and MENIIa
380
If one parathyroid gland contains an adenoma, what happens to the other parathyroid glands?
They become atrophic
381
How does a parathyroid adenoma present microscopically?
Resembles normal parathyroid but may see a fibrous connective tissue capsule with adjacent rim of compressed parathyroid tissue
382
How does a parathyroid adenoma present microscopically?
Resembles normal parathyroid but may see a fibrous connective tissue capsule with adjacent rim of compressed parathyroid tissue
383
In hyperplasia of the parathyroid glands how many glands are typically affected?
Usually all of them
384
What is secondary hyperparathyroidism?
Chronic hypocalcaemia causes compensatory overactivity of the parathyroid glands
385
What can secondary hyperparathyroidism cause?
```
Renal failure (low Ca intake, Vit D deficiency)
Hyperplasia of parathyroid tissue
```
386
What is tertiary hyperparathyroidism?
Parathyrid activity becomes autonomous
| Associated with hypercalcaemia
387
What are the signs and symptoms of hyperparathyroidism?
Bone disease - pain, fracture, osteoporosis
Nephrolithiasis - renal stones
GI complications - constipation, gallstones, nausea
CNS - depression, lethargy, seizures
Neuromuscular - weakness and fatigue
CVS - calcification of aortic and mitral valves
388
Hypoparathyroidism is very rare, but what can cause it?
Post-op of thyroid
congential absence - DiGeorge
familial - associated with primary adrenal insuffiency and mucocutaneous candidiasis
389
What can hypoparathyroidism cause?
Tetany
Altered mental state
Basal ganlia calcification, Parkinsonian, Raised ICP
Calcification of lens + cataract
Prolonged QT interval on ECG
Dental abnormalities - if during development
390
What hormone does the ovum produce?
oestradiol
391
What hormone is detected on a pregnancy test if fertilisation of the ovum occurs?
hCG
392
What hormones does the placenta produce?
Human placental lactogen (hPL)
placental progesterone
placental oestrogens
393
Progesterones + hPL in an insulin resistant mother leads to what?
Increased BG and gestational diabetes
394
What complications may occur in pregnancy as a result of poor diabetic glycaemic control?
```
Congenital malformation
Prematurity
Intra-uterine growth retardation
Large birth weight
Polyhydramnous (too much fluid around baby)
Intrauterine death
```
395
What complications may occur in the baby if a diabetic mother has poorly controlled BG levels?
```
Resp distress due to immature lungs
Hypoglycaemia and/or hyperglycaemia = fits
Anencephaly + spina bifida
caudal regression syndrome
ureteric dulplication
```
396
What percentage of people who suffered from gestational diabetes will go on to develop T2DM in 10 or so years?
50%
| More in obese individuals
397
What effect does thyroid disease have on pregnancy?
Hyper or hypo thyroidism may cause anovulation
| Increased demand on thyroid during pregnancy (thyroxine dose needs to increase)
398
What effect does hCG have on TFTs in pregnancy?
9% have low TSH
| 14% have high ft4
399
What effect does hCG have on TFTs in pregnancy?
9% have low TSH
| 14% have high ft4
400
What should be done for pregnant women with pre-existing hypothyroidism?
Increase medication dose
| TFTs monthly until 20 weeks, then 2 monthly until term
401
What are the risks of untreated hypothyroidism during pregnancy?
```
Increased spontaneous abortion risk
Pre-eclampsia
Pstpartum haemorrhage
Perterm labour
Foetal neuropsychological dvelopment (lower IQ)
```
402
What can cause thyrotoxicosis in pregnancy?
Grave's disease
TMNG, toxicadenoma
Thyroiditis
Gestational hCG-associated thyrotoxicosis (resolves by 20 weeks)
403
What are the risks in pregnancy in a woman with pre-existing hyperthyroidism?
```
Infertility
Spontaneous miscarriage
stillbirth
thyroid crisis in labour
transient neonatal thyrotoxicosis
```
404
How is hyperthyroidism managed in pregnancy?
Supportive management for symptoms
Beta blockers in early pregnancy
Low dose antithyroid drugs
405
What is postpartum thyroiditis?
Occurs in 5% of postpartum women (more in T1DMs)
Can occur upto 1 year postpartum but usually 1-4 months
May have a small, diffuse, non-tender goitre
Transiently thyrotoxic -> hypothyroid
406
What is the physiology of the posterior pituitary lobe?
ADH and oxytocin are synthesised in the body of the nerve cells within the hypothalamus
The neuron that secretes ADH and oxytocin moves downwards from the axon and gathers at the axon tips
Hormones enter the blood stream from a vessel joining the pituitary and ECF level rises
407
What does ADH act on?
Urine collection channels in the kidneys
408
What does oxytocin act on?
Mammary glands and smooth muscles above the uterus
409
What is the physiology of the posterior pituitary lobe?
ADH and oxytocin are synthesised in the body of the nerve cells within the hypothalamus
The neuron that secretes ADH and oxytocin moves downwards from the axon and gathers at the axon tips where the hormones enter the blood
Hormones exit the pituitary from a vessel joining the pituitary and ECF level rises
410
What does oxytocin act on?
Mammary glands and smooth muscles above the uterus
411
What happens in the anterior lobe of the pituitary?
Stimulator and inhibitor hormones are released from the body of the nerve cells in the hypothalamus which are 1st absorbed by capillaries in the hypothalamus base
Blood is then transported to the 2nd capillary network in the anterior pituitary lobe where they can then affect the anterior pituitary cells which secrete hormones.
Hormones leave though small vessels connected to the general bloodstream
412
What does ACTH act on?
Adrenals
413
What does TSH act on?
Thyroid
414
What does FSH and LH act on?
reproductive organs
415
What does PRL act on?
mammary glands
416
What does STH act on?
Muscle
417
What happens in the hypothalamo-pituitary testicular axis?
1. Hypothalamus secreted GnRH
2. GnRH travels to anterior pituitary
3. Pituitary releases LH and FSH in response
4. LH and FSH travel to testicles
5. LH stimulates Leydig cells in the testicles to produce testosterone
6. FSH stimulates sertoli cells to produge ABG and inhibin
7. Increased levels of testosterone and inhibin negatively feeback to pituitary and hypothalamus
8. Resulting in decreased LH and FSH production
9. Testosterone and inhibin levels also decrease
418
What is the role of ABG in males?
Binds to testosterone and keeps it in the seminiferous tubules
419
What is the role of inhibin in males?
Supports spermatogensis and inhibits production of FSH, LH and GnRH
420
What does CRH release from the hypothalamus cause to happen in the pituitary gland?
stimulates ACTH release
421
What does ACTH release cause to happen in the adrenal gland?
Cortisol release
422
What does ACTH release cause to happen in the adrenal gland?
Cortisol release
423
What effects does cortisol have on the body?
Regulates glucose levels
Increases body fat
Defends body against infection
Helps body respond to stress
424
What dynamic tests can be done to identify whether or not too much or too little hormone is being produces?
Too much hormone = do tests to suppress the hormone
| Too little hormone = do tests to stimulate the hormone
425
What hormone stimulation tests exist to test hormone function?
Synacthen test (synthetic ACTH) - measure cortisol at 0, 30 and 60 minutes
Insulin stress tests - measure cortisol and GH response every 30 mins for 2-3hours
Water deprivation test - check serum and urine osmolarities for 8 hours and then 4 hours after giving desmopressin (tests for diabetes insipidus)
426
What are the 2 different types of pituitary adenoma?
Microadenoma less than or = 1cm
| Macroadenoma >1cm
427
What effects can a non-functioning pituitary adenoma have on the body?
```
Compression of optic chiasm
Compression of cranial nerves
Hypoadrenalism
Hypothyroidism
Hypogonadism
DI
GH deficiency
```
428
What effects can a non-functioning pituitary adenoma have on the body?
```
Compression of optic chiasm
Compression of cranial nerves
Hypoadrenalism
Hypothyroidism
Hypogonadism
DI
GH deficiency
```
429
What are the physiological causes of increased prolactin levels in the body?
Breast feeding
Pregnancy
Stress
Sleep
430
What drugs can caused increased body prolactin levels?
```
Dopamine antagonists
Antipsychotics
Antidepressants
Oestrogens
Coccaine
```
431
What pathological conditions can cause increased prolactin production?
Hpothyroidism
Stalk lesions
Prolactinomas
432
What symptoms and signs occur in females with increased prolactin levels?
```
EARLY presentation
Galactorrhoea
Menstrual irregulartiy
Ammenorrhoea
Infertility
```
433
What symptoms and signs occur in males with increased prolactin levels?
```
LATE presentation
Galactorrhoea in less than 30%
Visual field abnormalities
Headache
Impotence
Anterior pituitary dysfunction
```
434
What investigations can be done when suspicions of prolactinoma arise?
Prolactin conc.
MRI pituitary
Visual field testing
Pituitary function tests
435
How is excess prolactin (prolactinoma) treated?
Dopamine agonists:
- Bromocriptine
- Quinagolide
- Cabergoline
436
How effective is treatment for prolactin excess?
Prolactin is normalised in 96%
Menstruation regained in 94%
Pregnancy rate 91%
Tumour shrinkage
437
What causes acromegaly?
GH excess
438
What re the signs and symptoms of acromegaly?
```
Thickened soft tissues - skin, large jaw and hands, excessive sweating
Hypertension and HF
Headaches
Snoring/sleep apnoea
DM
Visual field defects
Hypopituitarism
Early CV death
```
439
How is acromegaly diagnosed?
IGF1 levels - age and sex matches
| GTT - GH unchanged after glucose >1microgram/l
440
How is a glucose tolerance test (GTT) performed?
75g oral glucose bolus is given
GH is checked at 0, 30, 60, 90 and 120 mins
In normal cases GH suppresses to
441
How is a glucose tolerance test (GTT) performed?
75g oral glucose bolus is given
GH is checked at 0, 30, 60, 90 and 120 mins
In normal cases GH suppresses to less than 0.4micrograms/l after glucose
442
What is the treatment for acromegaly?
Pituitary surgery
External radiotherapy to the pituitary fossa
Retest GTT - if normal stop here, if still >1 then drug therapy is required:
-cabergoline
-octerotide
-peguisomant
443
What are the effects of somatostatin analogues in acromegaly?
Reduced GH in most patients
reduces tumour size by 30-50%
useful pre-op to relieve headache in 1 hour and gives an improved op outcome
444
What are the side effects of somatostatin analogues?
Local stinging
Flatulence, diarrhoea, abdo pains
Gastritis in 50-60%
Gallstones in 60%
445
What drugs are somatostain analogues?
Octerotide
Sandostatin
Lanreotide autogel
446
What dopamine agonists is used in acromegaly?
Cabergoline upto 3g weekly
| Reduces GH to less than 2 in 15% cases
447
What drug is a GH anatgonist and used in acromegaly?
Peguisomant
448
What doe GH antaginists do?
Bind to the GH receptor and block GH activity
Has an 85% response rate
IGF-1 decreases
449
What is included in the follow-up and long term management of acromegaly?
```
Achieve clinically safe levels (less than 1)
Check for other pituitary disorders
Cancer surveillance
Manage CVD risk factors
Manage sleep apnoea
```
450
What is the main cause of Cushing's syndrome?
Excess cortosol
451
What are the symptoms of protein loss in Cushing's
Myopathy
Osteoporosis
Thin skin
452
What are the symptoms of mineralocorticoid excess in Cushing's?
Hypertension
| Oedema
453
What are the symtoms of excess androgen in Cushing's?
Virilism
Hirsutism
Acne
Oligo/amenorrhoea
454
What does altered carbohydrate/lipid metabolism in Cushing's cause?
DM
| Obesity
455
What does an altered psyche is Cushing's cause?
Psychosis
| Depression
456
What does an altered psyche is Cushing's cause?
Psychosis
| Depression
457
What is the most common clinical presentation of Cushing's syndrome?
```
Thin skin
Proximal myopathy
Frontal balding in women
Conjunctical oedema
Osteoporosis
'moon face'
```
458
What screening tests are available for Cushing's syndrome?
Overnight 1mg dexamethasone suppression test:
- cortisol less than 50nmol/l next morning = normal
- cortisol >100nmol/l = abnormal
Urine free cortisol (24h urine collection)
- total less than 250 is normal
- Cortisol/creatinine ratio of less than 25 is normal
Diurnal cortisol variation
459
What definitive test exists for Cushing's syndrome?
2 day 2mg/day dexamethosone suppression test
| A cortisol less than 50nmol/l 6h after the last dose is -ve for Cushing's
460
What are the causes of Cushing's syndrome?
Pituitary >80%
Adrenal adenoma - beign/cancerous
Ectopic - thymus, lung, pancreas
Psuedo - Alcohol and depression, steroid medication
461
How is Cushing's caused by a pituitary disease treated?
Hypophysectomy (pituitary removal) and external radiotherapy if recurrance
462
How is Cushing's disease caused by adrneal adenoma treated?
Adrenalectomy
463
How is Cushing's disease caused by an ectopic cause treated?
Remove source OR bilateral adrenalectomy
464
What drug treatment is available for Cushing's syndrome?
Metyrapone - if other treatments fail or while waiting for radiotherapy to work
Ketoconazole
Pasireotide
465
What drug treatment is available for Cushing's syndrome?
Metyrapone - if other treatments fail or while waiting for radiotherapy to work
Ketoconazole
Pasireotide
466
What does pan hypopituitarism cause in the anterior pituitary?
Growth failure
Hypothyroidism
Hypogonadism
Hypoadrenal
467
What does pan hypopituitarism cause in the posterior pituitary?
Diabetes insipidus (DI)
468
What causes pan hypopituitarism?
```
Pituitary tumours
Secondary mets from lungs and breast
Local brain tumours
Granulomatous diseases
Vascular diseases
Trauma
Hypothalamic diseases
Iatrogenic
AI
Infection
```
469
What are the signs and symptoms of pan hypopituitarism ?
```
Mestrual irregularities (F)
Infertility, impotence
Gynaecomastia (M)
Abdo obesity
Loss of facial hair (M)
Loss of axillary and pubic hair
Dry skin and hair
Hypothyroid faces
Growth retardation (children)
```
470
What tests should be done when suspecting pan hypopituitarism in an individual?
fT4, TSH
Oestradiol/testosterone, LH + FSH
GH, IGF-1
Prolactin
471
How is pan hypopituitarism treated?
```
Thyroxine
Hydrocortisone
ADH
GH
Sex steroids
```
472
How do GH injections affect adults?
```
Improves well-being and QOL
Decreased abdo fat
Increases muscle mass, strength, exercise capacity and stamina
Improves cardiac function
Lowers cholesterol and increases LDL
Increases bone density
```
473
How do GH injections affect adults?
```
Improves well-being and QOL
Decreased abdo fat
Increases muscle mass, strength, exercise capacity and stamina
Improves cardiac function
Lowers cholesterol and increases LDL
Increases bone density
```
474
What are the risks of artificial testosterone replacement?
Prostate enlargement
Polycthaemia (increased RBCs)
Hepatitis
475
What are the causes of DI?
```
Familial = DIDMOAD
Acquired = trauma, idiopathic, RTAs, surgery, skull fracture
Rare = Tumour, sarcoid, external irradiation, meningitis
```
476
How is DI treated?
Desmospray
| Desmopressin oral tablets/sublingual tablets/injection
477
What is the most important thing to remember when thinking about sodium and water balance?
WATER FOLLOWS SODIUM EVERYWHERE
478
How are sodium levels in the body controlled?
Mineralocorticoid activity - sodium retention in exchange for potassium and/or H+
479
What steroids have a mineralocorticoid activity?
Aldosterone (main)
| Cortisol
480
What are the effects of too much and too little mineralocorticoid activity?
Too much = sodium retention (+ water)
| Too little = sodium loss (+water)
481
What process brings back sodium and water into the system?
Low BP activating the RAAS system - aldosterone is produced (high BP has the opposite effect)
482
How are water levels controlled in the body?
By ADH
483
What does ADH cause to occur in the renal tubules?
Water reabsorption
| Antidiuretic effect
484
What does ADH cause to occur in the renal tubules?
Water reabsorption
| Antidiuretic effect
485
If urine osmolarity is high, what does this do to the urine?
Concentrated urine
486
What causes increased ADH secretion and hence concentrated urine?
Increased sodium levels in the blood (low sodium causes the opposite)
487
What causes Decreased sodium concentration in the blood?
Too much water - Decreased excretion (SIAD) or increased intake
Too little sodium - increased sodium loss (kidneys-Addison's, gut, skin) or decreased sodium intake (v. rare)
488
What causes Increased sodium concentration in the blood?
Too little water - Increased water loss (DI) or Decreased water intake
Too much sodium - RARE, some IV drugs, near-drowning in the sea.
489
What is the basis behind Addison's disease?
Too little sodium due to adrenal insuffieciency
Not enough steroid synthesis and thus sodium not retained in the kidneys so sodium and water are lost from ECF leading to clinical dehydration
490
What are the common presenting features of Addison's disease?
Dizziness and hypotension from reduced ECF
| Excess pigmentation thus tanned skin from excess ACTH production
491
What complication of Addison's disease is associated with Na loss?
K retention and thus hyperkalaemia
492
What is the basis behind SIAD?
ADH is secreted in response to a non-osmotic stimulus (hypovolaemia/hypotension, pain, N+V), thus causing a slowly-progressing fluid retention (asymptomatic usually)
493
How is SIAD diagnosed?
Decreased sodium found on U&Es.
494
How is SIAD diagnosed?
Decreased sodium found on U&Es.
495
What is the basis behind DI?
Disruption of pituitary or pituitary stalk thus no ADH secreted. Lots of (pure) water lost in urine and sodium conc is high.
496
When should abnormalities of sodium levels be considered serious?
If {Na} is less than 120mmol/l or >155mmol/l
If patient has altered consciousness, confusion or nausea accompanying sodium disturbance
If {Na} levels have risen or fallen rapidly to reach their current level
497
What is the basic make-up of the anterior pituitary?
Adenohypophysis
Derived from Rathke's pouch
Secretes trophic (TSH, ACTH, FSH, LH) and non-trophic (GH, prolactin) hormones
498
What is the basic make-up of the posterior pituitary?
Neurohypophysis
Extension of neural tissue consists of modified glial cells and axonal processes
Secretes ADH (vasopressin) and oxytocin
499
What is the basic histology of the anterior pituitary gland?
Islands, cords of cells
Acidophils
Basophils
Chromophobe
500
What is the basic histology of the anterior pituitary gland?
Islands, cords of cells
Acidophils - Somatotrophs (GH), Mammotrophs (PRL)
Basophils - Corticotrophs (ACTH), Thyrotrophs (TSH), Gondaotrophs (FSH/LH)
Chromophobe
501
What is the basic histology of the posterior pituitary gland?
Non-myelinated axons of neurosecretory cells
502
What pathologies affect the anterior pituitary gland?
```
Hyperfunction = adenoma/carcinoma
Hypofunction = surgery/radiation, sudden haemorrhage, ischaemic necrosis, tumours extending into sella, inflammatory conditions
```
503
What pathologies affect the posterior pituitary gland?
DI
| SIADH
504
What are pituitary adenomas?
Derived from anterior pituitary cells
Sporadic or associated with MEN1
Micro or macro
Classified by the cell type or type of hormone(s) they produce
505
What symptoms may large adenomas present with?
Visual field defects
Pressure atrophy of surrounding tissue
Infarction can lead to panhypopituitarism
506
What symptoms may large adenomas present with?
Visual field defects
Pressure atrophy of surrounding tissue
Infarction can lead to panhypopituitarism
507
What is a prolactinoma?
The most common type of functional pituitary adenoma
| Causes infertility, lack of libido and ammenorrhoea
508
What is a GH-secreting adenoma?
2nd most common type of functional pituitary adenoma
| May cause gigantism or acromegaly
509
What can an ACTH secreting adenoma cause?
Cushing's
510
What causes pituitary hypofunction?
```
Primary or metastatic tumours
Traumatic brain injury
Subarachnoid haemorrhage
Surgery or radiation
Granulomatous inflammation
Infarction
Hypothalamis lesions
```
511
What is a craniopharyngioma?
A tumour derived from the remnants of Rathke's pouch
| A slow-growing, often cystic tumour which may calcify
512
What symptoms does a craniopharyngioma cause?
Headaches and visual disturbances
513
What are the adrenal glands?
Bilateral glands around 4-5g each
Sit superior and medial to the upper pole of the kidneys
Composed of an outer cortex and an inner medulla
514
What are the 3 zones of the adrenal cortex?
Zona glomerulosum - mineralocorticoids and aldosterone
Zona fasciculata - glucocorticoids and cortisol
Zona reticularis - sex steroids and glucocorticoids
515
What are the 3 zones of the adrenal cortex?
Zona glomerulosum - mineralocorticoids and aldosterone
Zona fasciculata - glucocorticoids and cortisol
Zona reticularis - sex steroids and glucocorticoids
516
What cells lie in the adrenal medulla?
Neuroendocrine (chromaffin) cells which secrete catecholamines
517
What is congenital adrenocorical hyperplasia?
A group of AR disorders which have a deficiency of the enzyme required for biosynthesis
Altered biosynthesis leads to increased andrigen production
Decreased cortisol stimulates ACTH release
518
What is acquired adrenocortical hyperplasia?
Endogenous ACTH production
| Bilateral adrenal enlargement
519
How do adrenocortical tumours present?
Incidental finding
Hormonal effects
Mass lesion
Carcinomas with necrosis leads to fever
520
What features of a tumour indicate an adrenocortical carcinoma?
Large size >50g or >20cm
Haemorrhage and necrosis
Frequent mets
Lack of clear cells
521
What are the typical features of an adrenocortical adenoma?
Well circumscribed, encapsulated lesions
Small
Yellow-brown cut surface
Well-differentiated, small nuclei
522
What is primary aldosteronism also known as?
Conn's syndrome
523
What is Conn's syndrome ususally associated with?
Diffuse or nodular hyperplasia of both adrenal glands
524
What happens in and what causes secondary hyperaldosteronism?
Increased Rennin
| Decreased renal perfusion, hypovolaemia, pregnancy
525
What happens in and what causes secondary hyperaldosteronism?
Increased Rennin
| Decreased renal perfusion, hypovolaemia, pregnancy
526
What is hypercortisolism also known as?
Cushing's disease
527
What are the ACTH dependent causes of hypercortisolism?
ACTH secreting pituitary tumour
| Ectopic ACTH - small cell lung cancer
528
What are the ACTH independent causes of hypercortisolism?
Adrenal adenoma or carcinoma
| Non-lesional adrenal gland atrophies
529
What can cause primary adrenocortical hypofunction?
May be acute or chronic
| Many causes and associations
530
What can cause secondary adrenocortical hypofunction?
Failure to stimulate adrenal cortex
| Suppression of the adrenal cortex
531
What causes acute primary adrenocortical insufficiency?
Rapid steroid withdrawal
Crisis in patients with chronic adrenocortical sufficiency
Massive adrenal haemorrhage
532
What causes chronic primary adrenocortical insufficiency?
```
Addison's
AI adrenalitis
Infections
Unusual causes
Signs and symptoms occur when >90% gland is destroyed
```
533
What causes chronic primary adrenocortical insufficiency?
```
Addison's
AI adrenalitis
Infections
Unusual causes
Signs and symptoms occur when >90% gland is destroyed
```
534
What are the symptoms of Addison's disease?
```
weakness
fatigue
anorexia
N+V
weight loss
diarrhoea
pigmentation
```
535
What happens to the body when mineralocorticoid levels fall?
K+ retention
Na+ loss
Volume depletion and hypotension
536
What happens to the body when glucocorticoid levels fall?
Hypoglycaemia
537
What can cause an Addisonian crisis?
Stress, Infection, Trauma, Surgery
538
What are the symptoms of an Addisonian crisis?
```
Vomiting
abdo pain
hypotension
shock
death
```
539
How common are neuroblastomas?
1 in 7000 live births
540
What percentage of neuroblastomas arise from the adrenal medulla?
40% - the rest arise along the sympathetic chain
541
What is a neuroblastoma composed of?
Primative appearing cells but may show maturation and differentiation
542
What is a phaeochromocytoma?
A neoplasm derived from chromaffin cells in the adrenal medulla which secretes catecholamines
A rare cause of secondary hypertension
543
What complications can arise as a result of a phaeochromocytoma?
HF
Infarction
arrhythmias
CVA
544
How are phaeochromocytomas diagnosed?
Detection of urinary catecholamines and metabolites
545
Why are phaeochromocytomas known as the 10% tumour?
```
10% are extra-adrenal
10% are bilateral
10% are biologically malignant
10% NOT associated with hypertension
25% familial
```
546
How do phaeochromocytomas appear macroscopically?
Small to v. large necrotic tumour masses
May see surface adrenal remnants
Yellow, red/brown to to haemorrhagic nature
Potassium dichromate will turn tumour dark brown due to oxidation of catecholamines.
547
How do phaeochromocytomas appear macroscopically?
Small to v. large necrotic tumour masses
May see surface adrenal remnants
Yellow, red/brown to to haemorrhagic nature
Potassium dichromate will turn tumour dark brown due to oxidation of catecholamines.
548
Where do phaeochromocytomas typically metastatise to?
Skeletal muscle
Regional lymph nodes
Liver
Lung
549
What condition is phaeochromocytoma a small part of?
MEN (IIA or IIB)
550
What is MENIIA?
Phaeochromocytoma (40-50%)
Medullary thyroid cancer (100%)
Parathyroid hyperplasia (10-20%)
Phaeochromocytoma may be bilateral and occur at extra-adrenal sites
551
What genetic mutation is MENIIA linked to?
Germline gain of function mutation in RET oncogene on Ch10
552
What is MENIIB?
Phaeochromocytoma, medullary thyroid carcinoma, neuromas or ganglioneuromas
Marfinoid habitus
553
What genetic mutation is MENIIB linked to?
Germline in RET oncogene - distinct from IIA mutations, almost always activating point mutation in the catalytic domain of the encoded enzyme.
554
What genetic mutation is MENIIB linked to?
Germline in RET oncogene - distinct from IIA mutations, almost always activating point mutation in the catalytic domain of the encoded enzyme.
555
What regulates functions of the zona glomerulosa?
Angiotensin II and K+
556
What regulates the zona fasiculata?
ACTH
557
What regulates the functions of the Zona reticularis?
ACTH + other unknown factors
558
What lies in the adrenal medulla?
Chromaffin cells
Medullary veins
Splanchnic nerves
559
How does RAAS regulate aldosterone?
Activated in response to low BP
| Produces angiotensin II which causes direct vasoconstriction and indirect (via aldosterone) methods of BP elevation
560
What is the mechanism of corticosteroids?
Bind intracellular receptors
| Receptor/ligand complex binds DNA to affect transcription
561
What are the 6 classes of steroid receptor?
```
Glucocorticoid
Mineralocorticoid
Progestin
Oestrogen
Androgen
Vit D
```
562
How do glucocorticoids (cortisol) affect the CNS?
Mood lability
Euphoria/psychosis
Decreased libido
563
How do glucocorticoids (cortisol) affect the Bone/connective tissue?
Accelarates osteoporosis
Decreased serum calcium
Decreased collagen formation
Slower wound healing
564
How do glucocorticoids (cortisol) affect the Immunological system?
Decreased:
- capillary dilataion/permeability
- leucocyte migration
- macrophage activity
- inflammatory cytokine production
565
How do glucocorticoids (cortisol) affect the Metabolic system?
Increased:
- BG
- Lipolysis
- Proteolysis
566
How do glucocorticoids (cortisol) affect the Circulatory/renal system?
Increased:
- CO
- BP
- Renal blood flow and GFR
567
In general what does too much cortisol cause?
AI disease
568
What are the clinical roles of corticosteroids?
Suppress inflammation
Suppress immune system
Replace treatment
569
What are the effects of aldosterone via mineralocorticoid receptors?
Sodium/Potassium balance
BP regulation
ECFV regulation
570
Where are mineralocorticoid receptors (MRs) found?
Kidneys
Salivary glands
Gut
Sweat glands
571
Where are mineralocorticoid receptors (MRs) found?
Kidneys
Salivary glands
Gut
Sweat glands
572
What conditions show primary insufficiency of the adrenal glands?
Addison's
CAH
Adrenal TB/malignancy
573
What conditions show secondary insufficiency of the adrenal glands?
lack of ACTH stimulation
Iatrogenic - excess exogenous steroid
Pituitary/hypothalamic disorders
574
How can adrenal insufficiency be tested for?
```
Low Na or High K levels
Hypoglycaemia
Short synACTHen test
v. high ACTH levels
v. high rennin and low aldosterone levels
Adrenal autoantibodies
```
575
How is a Shory synacthen test performed?
Plasma cortisol is measured before and 30mins after IV ACTH
Normal =
-Baseline >250nmol/l
-postACTH >480nmol/l
576
How is adrenal insufficiency treated?
Hydrocortisone to replace cortisol
Fludrocortisone to replace aldosterone
Education
577
What is Addison's disease?
An AI disease causing destruction of the adrenal cortex thus leading to primary adrenal insufficiency
578
What other AI conditions is Addison's associated with?
T1DM
Grave's disease
Pernicious anaemia
579
What are the clinical features of Addison's disease?
```
Anorexia and weight loss
Ammenorrhoea
Fatigue/lethargy
Dizziness and low BP
Abdo pain
Vomiting
Diarrhoea
```
580
What causes the skin pigmentation seen in Addison's disease?
v. high ACTH levels
581
What is the commonest cause of secondary adrenal insufficiency?
Exogenous steroid use
| Further lowers CRH and aCTH
582
How does secondary adrenal insufficiency present?
Same as Addison's
EXCEPT
Skin pale/normal (no excess ACTH)
Aldosterone production is intact
583
How is secondary adrenal insufficiency treated?
Hydrocortisone (fludrocortisone is unnecessary as aldosterone is normal)
584
How is secondary adrenal insufficiency treated?
Hydrocortisone (fludrocortisone is unnecessary as aldosterone is normal)
585
What is iatrogenic Cushing's syndrome?
Commonest cause of cortisol excess due to prolonged high dose steroid therapy
Causes chronic suppression of ACTH production and adrenal atrophy
586
What are the implications of an individual having iatrogenic Cushing's syndrome?
Unable to respond to stress
Needs extra doses of steroid when ill or prior to surgery
Cannot stop treatment suddenly
587
How is iatrogenic cushing's syndrome treated?
Gradual withdrawal of steroid therapy
588
What CVD may be brought on by primary aldosteronism?
LVH
atheroma
Increased BP
589
What are the common clinical features of primary aldosteronism?
Significant hypertension
Hypokalaemia
Alkalosis
590
What re the rare causes of primary aldosteronism?
Genetic mutations
Unilateral hyperplasia
K+ channel mutations producing adenomas and hereditary hypertension
591
What is the 1st step in diagnosis of primary aldosteronism?
Measurement of plasma aldosterone and rennin and express as a ratio(ARR)
If >750 then investigate with the saline suppression tests
Failure of plasma aldosterone to suppress by >50% with 2l normal saline confirms PA
592
What is the 2nd step in diagnosing primary aldosteronism?
Confirm subtype
593
What is the 2nd step in diagnosing primary aldosteronism?
Confirm subtype
| Adrenal CT or adrenal vein sampling to demonstrate adenoma or adrenal hyperplasia
594
What is the 2nd step in diagnosing primary aldosteronism?
Confirm subtype
| Adrenal CT or adrenal vein sampling to demonstrate adenoma or adrenal hyperplasia
595
What is the surgical management of primary aldosteronism?
Unilateral laproscopic adrenalectomy
Cures hypokalaemia
Cures hypertension in a good number of cases
596
What is the medical management of primary hypoaldosteronism?
MR antagonists
- spironolactone
- eplerenone
597
What is CAH?
Rare condition associated with enzyme defects in the steroid pathway
598
What is the commonest CAH?
21-alpha-hydroxylase deficiency
599
What are the 2 variants of 21-alpha-hydroxylase deficiency?
```
Classical = salt-wasting, simple virilising
Non-classical = hyperandrogenaemia
```
600
How is 21-alpha-hydroxylase deficiency diagnosed?
Basal 17-OH progesterone
| genetic mutation analysis
601
What does a 21-alpha-hydroxylase deficiency mean for the body?
Cortisol and aldosterone are not produced
| Androstenedione and testosterone are produced in excess
602
How does classical 21-alpha-hydroxylase deficiency present in males?
Adrenal insufficiency
Poor weight gain
Biochemical pattern similar to Addison's
603
How does classical 21-alpha-hydroxylase deficiency present in females?
Genital ambiguity
604
How does non-classical 21-alpha-hydroxylase deficiency present?
```
Hirsutism
Acne
Oligomenorrhoea
Precocious puberty
Infertility/sub-fertility
```
605
How is 21-alpha-hydroxylase deficiency treated in children?
```
Early recognition
glucocorticoid replacement
mineralocorticoid replacement
surgical correction
achieve maximal growth potential
```
606
How is 21-alpha-hydroxylase deficiency treated in adults?
Control androgen excess
Restore fertility
Avoid over-replacement of steroids
607
What is the clinical triad of phaeochromocytoma?
Hypertension
Headache
Sweating
608
What other symptoms does phaeochromocytoma present with?
```
Palpitations
breathlessness
constipation
anxiety
flushing
weight loss
```
609
If a phaeochromocytoma is found extra-adrenally what is it known as?
Paraganglioma
610
If a phaeochromocytoma is found extra-adrenally what is it known as?
Paraganglioma
611
What are the clinical signs associated with phaeochromocytoma?
```
hypertension
pallor
bradycardia and tachycardia
pyrexia
LVF
myocardial necrosis
stroke
shock
paralytic ileus of bowel
```
612
What biochemical abnormalities may present in phaeochromocytoma?
hyperglycaemia
low K+
Increased haematocrit
Lactic acidosis
613
What imaging is used to diagnose a phaeochromocytoma?
MRI
| PETscan
614
How are phaeochromocytomas treated?
```
Full alpha and beta blockade
-phenoxymethylbenzamine
-atenolol or metoprolol
Fluid and/or blood replacement
Surgical
-total excision wherever possible
Chemo if mallignant
```
615
What is Von-Hippel-Lindau syndrome?
Mutation in HIF1-alpha
AD
Range of vascular tumours across the body
Associated with phaeochromocytomas.
616
Other than phaeochromocytomas, what other condition can caused raised catecholamines?
HF
617
What defines the anterior triangle of the neck?
Bounded by the mandible superiorly
Midline medially
Anterior border of the sternocleidomastoid laterally
618
What defines the posterior triangle of the neck?
Posterior border of SCM anteriorly
Anterior border of trapezius laterally
Clavicle inferiorly
619
What defines the posterior triangle of the neck?
Posterior border of SCM anteriorly
Anterior border of trapezius laterally
Clavicle inferiorly
620
What can cause superficial swellings on the neck?
Sebaceous cysts
Lipomas
Neurofibromas
621
What can cause midline neck swellings?
Thyroid
Thyroglossal cyst
Dermoid cyst
622
What can cause swellings in the anterior triangle of the neck?
Lymph nodes
Salivary glands
Branchial cyst
Carotid body tumour
623
What can cause swellings in the posterior triangle of the neck?
Lymph nodes
| Cystic hygroma
624
What is a cystic hygroma?
Forms when lymph vessels fail to form correctly during foetal development
625
What is a branchial cyst?
Congenital failure to obliterate 2nd branchial cleft
626
What is a dermoid cyst?
A cyst containing an array of developmentally mature solid tissues
627
What is a lipoma?
A small fatty lump that grows beneath the skin
628
What is a Neurofibroma?
A benign nerve sheath tumour
629
What symptoms are associated with cervical lymphadenopathy?
```
Fever
weight loss
sweats
hoarseness
cough
dyspnoea
```
630
What would a brancial cyst show on FNA?
cholesterol crystals
631
What would a brancial cyst show on FNA?
cholesterol crystals
632
What is osteoporosis?
A progressive systemic skeletal disease characterised by low bone mass and microarchitechtural deterioration of bone tissue, with a consequent increased in bone fragility and susceptibility to fracture
633
What are the 2 types of bone making up the human skeleton?
20% trabecular (porous sponge-like)
| 80% cortical (dense material that provides stiffness and strength
634
How does bone remodelling occur?
Osteoclasts appear on a previously inactive surface and begin to resorb (gradually breakdown) the bone
Osteoblasts then fill the cavity by putting down osteoid that is mineralised to form new bone.
635
What happens with bone remodelling in osteoporosis?
There is an increase in resorption over formation leading to increased bone loss
636
What contributes to an adults peak bone mass?
```
Genetics - major part
Sex hormones
Exercise
Increased body weight
Diet
```
637
What factors may contribute to bone loss?
```
Sex hormone deficiency
Genetics
Immobility
Low body weight
Diet
Disease
Drugs - glucocorticoids + aromatase inhibitors
```
638
What endocrine conditions can predispose an individual to osteoporosis?
Hyperthyroidism
Hyperparathyroidism
Cushing's disease
T1DM
639
What GI conditions can predispose an individual to osteoporosis?
Coeliac disease
IBD
Chronic liver disease
Chronic pancreatitis
640
What respiratory conditions can predispose an individual to osteoporosis?
CF
| COPD
641
What direct effects do corticosteroids have on the bone?
Decreased osteoblast activity and lifespan
Suppression of replication of osteoblast precursors
Decrease in calcium absorption
642
What indirect effects do corticosteroids have on bone?
Inhibition of gonadal and adrenal steroid production causing Increased PTH and decreased bone mass
643
What indirect effects do corticosteroids have on bone?
Inhibition of gonadal and adrenal steroid production causing Increased PTH and decreased bone mass
644
What do DEXA scans measure?
BMD (Bone mineral density) against a population mean - predicts fracture risk independently of other risk factors
645
What is the T-score in DEXA scans?
Young adults female population mean
646
What is the Z-score in DEXA scans?
Age-matched female population mean
647
What is normal BMD in DEXA scanning?
BMD is withing 1SD of the young adult reference means
648
What is osteopenia on DEXA scanning?
BMD more than 1SD but less than 2.5SD below the young adult mean reference
649
What is osteoporosis on DEXA scanning?
BMD >= 2.5SD below the young adult mean
650
What is severe osteoporosis on DEXA scanning?
BMD >= 2.5SD below the young adult mean with a fragility fracture
651
What lifestyle advice is given to patients with osteoporosis?
High intensity strength training
Low impact weight-bearing exercises
Avoidance of excess alcohol and smoking
Fall prevention
652
What dietary advice is given to patients with osteoorosis?
2-3 portions from milk and dairy for calcium
653
When should antiresorptive therapy be considered in patients with osteoporosis?
T less than or equal to -2.5
| If on steroids or fracture of vertebrae has occured, start at T-1.5
654
What drug treatments are recommended in osteoporosis?
Calcium for post-menopausal women who do not get enough dietary intake
Vit D supplements for housebound under 60s or anybody over 65
655
What supplementary treatments are recommended in osteoporosis?
Calcium for post-menopausal women who do not get enough dietary intake
Vit D supplements for housebound under 60s or anybody over 65
656
What are bisphosphonates?
Analogues of pyrophosphate that adsorb onto bone within the matrix
Anti-resorptive agents used in osteoporosis
657
How do bisphosphonates work?
Ingested by osteoclasts, leading to cell death, thereby inhibiting bone resorption
658
How effective are bisphosphonates?
Increases BMD by 5-8%
| Reduces fragility fracture by around 50%
659
How is zoledronic acid used to treat osteoporosis
Once yearly infusion for 3 years
~70% reduction in vertebral fracture risk
~40% reduction in hip fracture risk
660
What is denosumab?
Fully human monoclonal antibody that targets and binds with high affinity and specificity to RANKL
661
How does denosumab prevent fractures in osteoporosis?
Prevents RANK, inhibiting development and activity of osteoclasts, reducing bone resorption and increasing bone density
662
What are the side effects of denosumab?
Eczema
| Cellulitis
663
What are the side effects of denosumab?
Eczema
| Cellulitis
664
What is strontium ranelate?
An anti-resorptive agent which is third line for osteoporosis
665
What are the contraindications for using strontium ranelate?
history of thomboembolic disease
IHD
Peripheral arterial disease
Uncontrolled hypertension
666
What is teriparatide?
A recombinant parathyroid hormone which stimulates bone growth
667
What are the symptoms of acute hypercalcaemia?
Thirst
Dehydration
Confusion
Polyuria
