Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

x 2nd Year Medicine > Endocrine > Flashcards

Endocrine Flashcards

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Give an example of a glycoprotein or peptide

A

Oxytocin

Insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Give an example of a steroid

A

Cortisol

Testosterone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Give an example of a Tyrosine or Tryptophan derivative

A

Adrenaline
Thyroid hormones
Melatonin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How are amines synthesised, stored and released?

A

Pre-synthesised
Stored in vesicles
Released in response to Ca2+ dependant exocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How are steroids synthesised?

A

Synthesised and secreted upon demand

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What increases steroid synthesis and secretion?

A

cellular uptake and availability of cholesterol

rate of conversion of cholesterol to pregnenolone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What type of hormone is not transported freely in plasma and relies on carrier proteins?

A

Steroids (+thyroxine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

As well as increasing the amount transported, what other effect do carrier proteins have with steroids?

A

Prevent Filtration at the kidney

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is CBG?

A

Cortisol-binding globulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is TBG?

A

Thyroxine-binding globulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is SSBG?

A

Sex steroid-binding globulin (testosterone and oestrodiol)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Name 2 general carrier proteins

A

Albumin

Transthyretin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the 3 classes of hormone receptors?

A

GPCRs
Receptor Kinases
Nuclear Receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are GPCRs activated by?

A

amines and some proteins/peptides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Give an example of a receptor kinase

A

Insulin receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What do alpha cells in pancreatic islets do?

A

secrete glucagon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What do beta cells in pancreatic islets do?

A

secrete insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What do delta cells in pancreatic islets do?

A

secrete somatostatin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What do PP cells in pancreatic islets do?

A

secrete pancreatic polypeptide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Where in the beta cells in insulin formed

A

RER

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Apart from an insulin molecule, what other 2 components make up a molecule of prepoinsulin

A

signal peptide

C-peptide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

How many phases does insulin release occur in? How long does each phase last for?

A

2
1st phase = 10-15minutes
2nd phase = 1-2 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is KATP inhibited by (drug)

A

Sulphonylureas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Give examples of sulphonylureas

A

tolbutamide

glibenclamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is KATP stimulated by

A

Diazoxide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What other function does Diazoxide do? (Other than KATP stimulation)

A

Inhibits insulin secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

A mutation in which protein of the KATP channel can lead to neonatal diabetes?

A

Kir6.2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What are the 2 proteins of the KATP channels?

A

Kir6.2 and SUR1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What does MODY stand for?

A

Maturity Onset Diabetes of the Young

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is MODY?

A

Monogenic diabetes with a genetic defect in beta cell function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

In MODY, what can a glucokinase mutation cause?

A

BG threshold for insulin increases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

MODY is not best treated with insulin in most cases, what other drug class is better indicated in MODY?

A

Sulphonylureas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Define Type 1 Diabetes

A

Loss of insulin secreting beta cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Define Type 2 diabetes

A

Initially hyperglycaemia with hyperinsulinaemia.

Decreased insulin sensitivity in the tissues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What is the insulin receptor?

A

Dimeric tyrosine kinase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What is the insulin receptor made up of?

A

2 extracellular alpha subunits
2 transmembrane beta subunits
alpha and beta subunits linked by disulphide bonds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Insulin binds to the alpha subunits of the receptor, what does this cause the beta subunits to do?

A

autophosphorylate to activate the receptors catalytic activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Name 3 biological effects of insulin

A 
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What are the causes and symptoms of Leprechaunism (Donohue Syndrome)?

A

Caused by a rare, autosomal recessive genetic trait causing mutations in the gene for the insulin receptor.
Causes severe insulin resistance and developmental abnormalities.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What is the cause and the symptoms of Rabson-Mendenhall syndrome?

A

Rare, autosomal recessive genetic trait causing severe insulin resistance, hyperglycaemia and compensatory hyperinsulinaemia, developmental abnormalities and more.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Where are ketone bodies formed?

A

Liver mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Is ketoacidosis more associated with type 1 or type 2 diabetes?

A

Type 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Define Diabetes mellitus (DM)

A

A group of metabolic diseases characterised by hyperglycaemia, resulting from defects in insulin secretion, insulin action or both.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What is the HbA1c diagnostic criteria for DM?

A

above 48mmol/mol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What is the fasting glucose diagnostic criteria for DM?

A

above 7mmol/l

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What is the random glucose diagnostic criteria for DM?

A

above 11.1mmol/l

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Give 2 tests used to descriminate between T1DM and T2DM

A

GAD/anti-islet cell antibodies (T1DM)

Ketones (T1DM)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What does LADA stand for in an endocrine setting?

A

Latent Autoimmune Diabetes of Adulthood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What is monogenic diabetes? Give 2 examples of types of diabetes in which this can occur

A

When diabetes is caused by a mutation in a single gene.

MODY and Neonatal diabetes can be monogenic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

If a mother has T2DM, what is the chance that her daughter will develop it at some point in her life? (%)

A

40%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

What percentage of T2DM patients are overweight or obese?

A

90%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

As well as being overweight, what other factor must an individual have to develop T2DM?

A

vulnerable beta cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

As well as insulin resistance and T2DM, what other factors must a person have 2 of before they are considered to have metabolic syndrome?

A

Dyslipidaemia
Hypertension
Obesity
Microalbuminuria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What is the 1st line treatment for an overweight individual with T2DM?

A

Metformin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What is the 1st line treatment for an individual of normal weight with T2DM?

A

Sulphonylureas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Give an example of a thiazolidinedione used in T2DM

A

Pioglitazone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

When is pioglitazone contraindicated?

A

Heart Failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

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?

A

Insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

What HbA1c % is aimed for to decrease risk of complications?

A

less than 7%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Monitoring of BG is not necessary in all T2DM patients. What 2 drugs indicate BG monitoring?

A

Insulin + Sulphonylureas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

What is the target BP for diabetics?

A

less than = 130/80mmHg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

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?

A

Cholesterol
Simvastatin 40mg
Atorvastatin 10mg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

What is the usual staring dose for metformin?

A

500mg od or bd

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

What are the main effects of metformin? (4 things)

A

HbA1c decreased by 15-20mmol/mol
Weight decrease
Prevention of micro and macro vascular complications
Decreased Triglycerides and LDL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Is metformin safe in pregnancy?

A

Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

What are the adverse effects of metformin?

A

GI disturbances
Anaemia - rare
Lactic acidosis - very rare
Liver failure - discontinue if this occurs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

What effect does eGFR have on the dose of metformin given?

A

less than 30ml/min = discontinue drug

30-45ml/min = half dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

Give the names of (and standard doses) of the 3 sulphonylureas which can be given in T2DM

A

Glicazide (40mg od - 160mg bd)
Glibenclamide (5mg-15mg od)
Glimepiride (1mg-6mg od)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What do sulphonylureas do on the cellular level?

A

Close the KATP channel, and stimulate insulin release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

How much do sulphonylureas generally reduce the HbA1c by?

A

15-20mmol/mol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Do sulphonylureas prevent macro or micro vascular complications?

A

Micro

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

What are the adverse effects of sulphonylureas

A

Hypoglycaemia
Weight gain
GI disturbances
Headache

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

What is the standard dose range for pioglitazone?

A

15-45mg od

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

What effects does pioglitazone have on a T2DM patient?

A

HbA1c reduced by 15-20mmol/mol
Improvement in microalbuminurea
Reduced end point mortality

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

What are the adverse effects of pioglitazone?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

What T2DM therapies work by increasing secretion of insulin?

A

SUs
GLP-1 analogues
Glinides
DPP-4 inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

What T2DM therapies work by decreasing insulin resistance and decreasing hepatic glucose output?

A

Biguanides

Thiazolidinediones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

What T2DM therapy works by slowing glucose absorption from the GI tract?

A

alpha-glucosidase inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

What T2DM therapy works by enhancing glucose excretion from the kidney?

A

SGLT2 inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

What T2DM therapies work via insulin independent actions?

A

alpha-glucosidase inhibitors and SGLT2 inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

If BG levels rise, what does GLUT2 facilitate?

A

Increased diffusion of glutamide into beta cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

What is it that stimulates insulin secretion from a cell?

A

Opening of voltage-activated Ca2+ channels, increasing the level of intracellular calcium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

What is formed by a tetramer of Kir6.2 subunits?

A

Potassium selective ion channel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

What causes the opening of the voltage activated Ca2+ channels

A

Membrane depolarisation from closed KATP channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

How do SUs interact with the KATP channels?

A

They displace ADP-Mg2+ from the SUR1 subunit, which closes the KATP channel, thus causing insulin secretion independent to BG levels.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

Give 2 examples of glinides (meglitinides)

A

Repaglinide

Nateglinide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

What drug class do glinides work similarly to? and how do they differ?

A

Work similarly to SUs, but act at a distant site to the SUR1 subunit.
They are also less likely to cause severe hypos

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

What stimulates GLP-1 secretion in an individual?

A

Ingestion of food

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

Where is GLP-1 released from?

A

Enteroendocrine cells in the small intestine (L + K cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

What effects does GLP-1 have on the pancreatic cells?

A

Enhance insulin release from beta cells

Decrease glucagon release from alpha cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

What is the main GLP-1 analogue in theraptutic use? why does it differ from the normal physiological response?

A

Exenatide

The effects last for longer thus lowering BG more steadily

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

What other beneficial effects do GLP-1 analogues have on the T2DM patient?

A

Slows gastric emptying and decreases apetite

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

What new longer acting GLP-1 analogue now exists? How is it given?

A

Liraglutide

od subcut. injection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

What terminates the effects of GLP-1?

A

DPP-4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

How do gliptins (DPP4-inhibitors) work?

A

Competitively inhibit DPP-4, prolonging the effects of GLP-1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

What is the main gliptin agent used? (And what other agents can be used?)

A

Sitagliptin - orally od

Saxigliptin and vildagliptin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

What is the alpha-glucosidase inhibitor in theraputic use?

A

Acarbose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

What is alpha-glucosidase?

A

A brush border enzyme which breaks down starch and disaccharides to absorbable glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

What does acarbose do?

A

Inhibits alpha-glucosidase thus reducing the postparandial (after meal) increase in glucose.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

When in acarbose used?

A

When lifestyle changes and other oral agents are not effective in HbA1c and BG control

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

What are the adverse effects of acarbose?

A

GI disturbances and infections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

How do biguanides (metformin) work?

A

Reduce hepatic gluconeogenesis - stimulates AMPK
Increases glucose uptake and utilisation by skeletal muscle
Decreases carbohydrate absorption
Increases fatty acid oxidation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

What are TZDs (Glitazones)

A

Exogenous agonists of PPAR-alpha which associates with RXR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

What do TZDs do?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

Give an example of a TZD

A

Pioglitazone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

What do SGLT2 inhibitors do?

A

Selectively block reabsorption of glucose by SGLT2 in the proximal tubule of the kidney nephron, deliberately causing glucosuria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

What other benefit do SGLT2 inhibitors have?

A

Cause calorific loss and weight loss - glucose voided

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

What is the currently licensed SGLT2 inhibitor?

A

Dapagliflozin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

What are the highest risk HLA genotypes with development of T1DM? What percentage of T1DM patients have one of these?

A

DR3-DQ2/DR4-DQ8

95% of patients less than 30 have 1 or both

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

What autoantibodies are associated with some development in T1DM?

A

GAD (glutamic acid decarboxylase)
Insulin (IAA)
IA2 (Islet-antigen 2)
ZnT8 (Zinc transporter)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

What is the classic triad of symptoms in T1DM?

A

Polyuria
Polydipsia
Weight loss

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

What symptoms other than the classic triad can present in T1DM?

A

Fatigue
Blurry vision
Candidial infection
DKA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

Where is insulin secreted into?

A

Portal vein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
117
Q

When fasting, what is the rate of insulin secretion?

A

0.25-1.5 units per hour

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
118
Q

What type of diabetes are children <6months likely to have?

A

Monogenic (Neonatal)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
119
Q

How is LADA diagnosed?

A

Presence of increased pancreatic autoantibody levels in patients with recently diagnosed diabetes not needing immediate insulin therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
120
Q

Name 3 conditions associated with diabetes

A 
Cystic fibrosis (25% have DM)
DIDMOAD
Bardet-Biedl syndrome
Addisons disease
Thyroid disease
Coeliac disease
Pernicious anaemia
IgA deficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
121
Q

What 2 AI conditions are very strongly associated with T1DM?

A 
Thyroid disease (1:50 in normal population; 1:20 in T1DM)
Coeliac disease (1:100 in normal population; 1:20 in T1DM)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
122
Q

What is polyglandular endocrinopathy?

A

A set of multiple endocrine gland deficiences that may or may not be AI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
123
Q

What is the normal age of onset of MODY?

A

less than 25 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
124
Q

What is the best treatment for HNF1-alpha mutations?

A

Gliclazide (an SU)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
125
Q

What is the definition of neonatal diabetes?

A

Requires insulin treatment within first 3 months of life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
126
Q

What are the 2 types of neonatal diabetes and how are they defined?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
127
Q

If Permanent neonatal DM is caused by mutations in Kir6.2, what can this be treated with rather than insulin?

A

Glibenclamide (an SU)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
128
Q

What types of insulin are marketed as rapid acting? (last between 4-6 hours)

A

Humalog
Novorapid
Apidra

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
129
Q

What types of insulin are marketed as short acting? (~8 hour duration)

A

HumulinS
Actrapid
Insuman rapid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
130
Q

What types of insulin are marketed as intermediate acting? (18-20 hours duration)

A

Humulin I

Insuman basal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
131
Q

What types of insulin are considered as long-acting analogues?

A

Lantus

Levemir

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
132
Q

What are some of the rapid acting/ intermediate acting insulin mixes that are available?

A

Humalog mix 25/mix 50

NovoMix 30

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
133
Q

What are some of the short acting/ intermediate acting insulin mixes that are available?

A

Humulin M3

Insumancomb 15, 25, 50

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
134
Q

What is the advantage of a basal bolus insulin regimen?

A

Mimics normal endogenous insulin production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
135
Q

What factors can affect the absorption action of insulin?

A 
temperature
injection site
injection depth
exercise
pen accuracy
leakage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
136
Q

What should a patient with insulin always check for at the injection sites?

A

Lipohypertrophy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
137
Q

What is HbA1c?

A

Glycated haemoglobin - formed by non-enzymatic glycation of haemoglobin in exposure to glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
138
Q

What HbA1c range is diagnostic for diabetes?

A

> = 48mmol/mol (6.5%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
139
Q

What do ketone meters measure?

A

3betaOH-butyrate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
140
Q

What are some symptoms of hypoglycaemia?

A 
Shaking
Sweating
Anxiousness
Dizziness
Headache
Irritability
Hunger
Tachycardia
Impaired vision
Weakness/fatigue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
141
Q

How is severe hypoglycaemia defined as?

A

Hypoglycaemia that leads to seizures, unconsciousness or the need for external asistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
142
Q

How is hypoglycaemia treated?

A

Consuming 15-20g glucose or simple carbohydrates

Recheck BG and keep rechecking until normal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
143
Q

How would severe hypoglycaemia be treated?

A

Inject 1mg glucagon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
144
Q

What is hypoglycaemia unawareness?

A

When BG is 3.5-4mmol/l and the individual has no symptoms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
145
Q

In what groups of people is hypoglycaemic unawareness more likely to occur in?

A

Frequent low BG levels
Longstanding T1/T2DM
Intensively treated T1DM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
146
Q

In a non-diabetic what changes does the body cause when BG = 3.8mmol/l?

A

Glucagon and adrenaline kick in

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
147
Q

In a non-diabetic what changes does the body cause when BG = 3.0mmol/l?

A

Symptoms of hypoglycaemia begin to appear

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
148
Q

In a non-diabetic what changes does the body cause when BG = 2.8mmol/l?

A

Cagnitive dysfunction occurs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
149
Q

Why is hypoglycaemia more common in T1DM patients?

A

Neither insulin or glucagon is present to prevent the hypo so no corrective action can be taken by the body itself

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
150
Q

What is DKA?

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
151
Q

How does DKA cause death in adults?

A

Hypokalaemia
Aspiration pneumonia
ARDS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
152
Q

How can DKA cause death in children?

A

Cerebral oedema

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
153
Q

What are the main pathophysiological points that contribute to DKA?

A

Hyperglycaemia
Increased ketogenesis
Acidosis
Hyperosmolarity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
154
Q

What can trigger DKA?

A

Non-compliance with medication (most common)
Infections
Illicit drugs and alcohol
Newly-diagnosed diabetes (on no treatment)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
155
Q

What biochemistry results can be used to diagnose DKA?

A

Ketonaemia >3mmol/l or significant ketonuria
BG >11mmol/l or known diabetes
Bicarbinate less than 7.3 (attempt to compensate for acidosis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
156
Q

What typical symptoms are associated with DKA?

A

Thirst, polyuria, dehydration

Flushing, vomiting, abdo pain, tenderness, breathlessness, ketones (pear drops) on breath

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
157
Q

Other than ketones, what other biochemistry results may be raised?

A

Amylase + WCC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
158
Q

How is DKA treated?

A

Fluid - initially with 0.9% NaCl, then when BG falls <15, switch to 10% dextrose
Insulin
Potassium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
159
Q

What is the normal range for lactate?

A

0.6-1.2mmol/l

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
160
Q

Where does lactate come from?

A

RBCs, skeletal muscle, brain and renal medulla

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
161
Q

What causes type A lactic acidosis?

A

Tissue hypoxaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
162
Q

What causes type B lactic acidosis?

A

Liver disease
Diabetes (occurs in 10% DKA episodes)
Metformin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
163
Q

How does lactic acidosis present clinically?

A

Hyperventillation
Mental confusion
Stupor or coma if severe

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
164
Q

How does lactic acidosis appear in biochemistry results?

A

Low bicarb
Increased anion gap
Glucose often high
High phosphate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
165
Q

How is lactic acidosis treated?

A

Fluids and antibiotics

Withdrawal of any causative medications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
166
Q

How does hyperglycaemic hyperosmolar syndrome present?

A 
incresed refined carbohydrates before the event
BG very high ~60
Significant renal impairment
increased osmolarity
Less ketonaemia/acidotic than DKA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
167
Q

How is hyperglycaemic hyperosmolar syndrome different from DKA?

A 
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
168
Q

How is hyperglycaemic hyperosmolar syndrome treated differently from DKA?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
169
Q

What are the main macrovascular complications of diabetes?

A

IHD

Stroke

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
170
Q

What are the main microvascular complications of diabetes?

A

Neuropathy
Nephropathy
Retinopathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
171
Q

Other than micro/macrovascular complications, what other complications can occur in diabetes?

A

Erectile dysfunction

Psychiatric

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
172
Q

What are the different types of neuropathy which can occur in diabetes?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
173
Q

What symptoms may be associated with diabetic neuropathy?

A 
Numbness, pain, tingling
Ulcers
Muscle wasting
Indigestion, NV
Dizziness
Urination issues
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
174
Q

What increases the risks of developing diabetic neuropathy?

A 
Duration of diabetes
Poor control
T1DM
High cholesterol
Smoking/Alcohol
Genetics
Mechanical injuries
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
175
Q

What are the symptoms of a distal symmetric or sensorimotor neuropathy?

A 
Numbness
Tingling/burning
Sharp pains/cramps
Sensitivity to touch
Loss of balance/coordination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
176
Q

What complications may arise as a result of distal symmetric or sensorimotor neuropathy?

A

Infection/ulceration
Deformities (hammer toe/collapse of midfoot)
Amputations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
177
Q

How is painful neuropathy treated? (list with increasing amounts of pain)

A 
Simple analgesia
TCAs
Gabapentin
Duloxetine/Pre-gabalin
Stronger opiods  - oxycodone/tramadol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
178
Q

What topical treatment can be used for painful neuropathy?

A

Capsaicin cream

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
179
Q

How can autonomic neuropathy affect the digestive system?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
180
Q

How can autonomic neuropathy affect the sweat glands?

A

Body temp is not regulated

May sweat profusely at night or when eating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
181
Q

Autonomic neuropathy may cause hypoglycaemic unawareness, what is this?

A

Symptoms of hypos may not occur

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
182
Q

How can autonomic neuropathy affect the CVS?

A

Postural hypotension

HR may stay high despite normal body functions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
183
Q

How can autonomic neuropathy affect the eyes?

A

Pupils have decreased responsiveness to changes in light

This makes driving in the dark difficult

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
184
Q

How can neuropathy be diagnosed?

A 
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
185
Q

What types of nephropathy may occur in diabetics?

A

Kimmelsteil-Wilson syndrome
Nodular GN
Angiopathy of capillaries

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
186
Q

Between 1-5% diabetics are found to have CKD, what are the consequences of this?

A

Hypertension
Decline in renal function
Accelerated vascular disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
187
Q

What screening program exists for diabetic nephropathy?

A

All patients >12 have urinary ACR testing done once a year

Dipstick testing is also done

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
188
Q

What are the risk factors for progression on nephropathy?

A 
Hypertension
High cholesterol
Poor glycaemic control
Smoking
Albuminuria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
189
Q

What should all patients with microalbuminuria/proteinuria be commenced on and why?

A 
ACEI
Dilates renal arteries
Lowers filtration pressure
Reduces proteinuria
Reduces GFR (upto 20%)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
190
Q

What eye pathologies can diabetics get?

A

Diabetic retinopathy
Cataract
Glaucoma
Acute hyperglycaemia (visual blurring)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
191
Q

What do cotton wool spots suggest when seen on the fundus?

A

Ischaemic areas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
192
Q

What do hard exudates suggest when seen on the fundus?

A

Lipid breakdown products

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
193
Q

What would a retinopathy of grade R0 suggest?

A

No diabetic retinopathy - rescreen in 12 months

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
194
Q

What would a retinopathy of grade R1 suggest?

A 
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
195
Q

What would a retinopathy of grade R2 suggest?

A

BDR - >=4 blot haemorrhages in 1 hemi-field only

Rescreen in 6 months

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
196
Q

What would a retinopathy of grade R3 suggest?

A

BDR with 1 of the following:
4 or more blot haemorrhages in both hemi-fields
Venous bleeding
Intra-retinal microvascular abnormalities
Refer to ophthalmology

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
197
Q

What would a retinopathy of grade R4 suggest?

A

Proliferative diabetic retinopathy:
Active new vessels
Vitreous haemorrhage
Refer to ophthalmology ASAP!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
198
Q

What would a retinopathy of grade M1 suggest?

A

Lesions within a radius of >1 but <2 disc diameters(DDs) from the fovea
Rescreen in 6 months

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
199
Q

What would a retinopathy of grade M2 suggest?

A

Lesions less than 1DD from the fovea

Refer to ophthalmology (does not need ASAP treatment but does need close surveillance)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
200
Q

What other complications can arise from diabetic retinopathy?

A

Secondary glaucoma

Retinal detachment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
201
Q

How is retinopathy treated?

A

Laser therapy
Vitrectomy
Anti-VEGF injections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
202
Q

How common is erectile dysfuction in males with diabetes?

A

affects 50% of diabetic men, and 55% of those >60y/o

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
203
Q

How can erectile dysfuction caused by diabetes be treated?

A

improve glycaemic control/lose weight/improve lipids
Lower alcohol intake
Withdrawal of causative drugs where possible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
204
Q

What oral medication can be given to men with erectile dysfunction?

A

sildenafil (viagra)
vardenafil (levitra)
tadalafil (cialis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
205
Q

What are the contraindications to taking medications for erectile dysfunction?

A

If the patient is on nitrates, nicorandil
Stroke/MI in past 3 months
Hypotension
Severe hepatic dysfunction
Hereditary degenerative retinal disorders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
206
Q

What vascular disorders does having diabetes increase the risk of?

A

Stroke
Peripheral vascular disease
Coronary artery disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
207
Q

Why does diabetes increase the risk of developing vascular disease?

A 
Dyslipidaemia
Endothelial dysfunction
Platelet aggregation
Thrombogenesis
Inflammation/increased oxidative stress
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
208
Q

What psychiatric disorders can come from diabetes?

A

Depression
Eating disorders
Bi-polar disorder
Schizophrenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
209
Q

What does the thyroid gland tissue secrete?

A

Thyroxine (T4)
Tri-iodothyronine (T3)
Calcitonin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
210
Q

What do the 4 parathyroid glands secrete?

A

PTH - parathyroid hormone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
211
Q

How does the thyroid tissue appear histologically?

A

Colloid-tyrosine containing thyroglobulin filled spheres enclosed by follicular cells
Surrounding the follicles lies the parafollicular C cells which secrete calcitonin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
212
Q

How are the thyroid hormones created and stored?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
213
Q

What is T4?

A

Thyroxine - approx 90% of thyroid hormones secreted

Converted to T3 by the liver and kidney

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
214
Q

What is T3?

A

Triiodothyronine - approx 10% of thyroid hormones secreted
4x more potent than T4
Is the major biologically active thyroid hormone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
215
Q

What does carbimazole and propythiouracil inhibit?

A

Iodine attaching to tyrosine residues to form T3 and T4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
216
Q

How and to where are T3 and T4 released?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
217
Q

What happens when T3 reaches its target cell?

A

T3 acts upon the nuclear receptors of the target cell, which then produces mRNA proteins and then a biological response.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
218
Q

T3 + T4 are hydrophobic/lipophilic so to be transported they must bind to plasma proteins. What are these plasma proteins?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
219
Q

What can caused Increased TBG levels?

A 
Pregnancy
Newborns
Oestrogen levels
Hep A/Active hepatitis
Billiary cirrhosis
Genetics
Heroin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
220
Q

What can cause decreased TBG levels?

A 
Androgens
Large doses of glucocorticoids
Acromegaly
Systemic illness
Chronic liver disease
Genetics
Pheytoin, carbamzepine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
221
Q

How do the thyroid hormones affect BMR?

A

Increased number and size of mitochondria
Increased oxygen use and rates of ATP hydrolysis
Increased synthesis of resp. chain enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
222
Q

How do the thyroid hormones affect thermogenesis?

A

approx 30% thermoregulation due to thyroid hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
223
Q

How do the thyroid hormones affect carbohydrate metabolism?

A

Raised BG - due to stimulation of glycogenolysis and gluconeogenesis
Insulin-dependent glucose uptake into cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
224
Q

How do the thyroid hormones affect lipid metabolism?

A

Mobilises fats from adipose

Fatty acid oxidation in tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
225
Q

How do the thyroid hormones affect Protein metabolism?

A

Stimulates protein synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
226
Q

How do the thyroid hormones affect growth?

A

Causes GHRH production and secretion
Glucocorticoid-induced GHRH release
GH/somatomedins
All require thyroid hormones in order to happen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
227
Q

How do the thyroid hormones affect the development of the fetal and neonatal brain?

A

Myelinogenesis and axonal growth requires thyroid hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
228
Q

How do the thyroid hormones affect normal CNS activity?

A 
Hypothyridism = slow intellectual functions
Hyperthyroidism = nervousness, hyperkinesis and emotional instability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
229
Q

How do the thyroid hormones affect permissive sympathomimmetic actions?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
230
Q

How are thyroid hormone levels regulated?

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
231
Q

What is hypothyroidism?

A

Deficiency of T3 and T4 levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
232
Q

What causes primary hypothyroidism?

A

Thyroid gland failure - may be associated with goitre

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
233
Q

What causes secondary hypothyroidism?

A

TRH or TSH abnormalities - no goitre

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
234
Q

What are the symptoms of hypothyroidism?

A 
Low BMR
Slow pulse
Fatigue, lethargy, slow response times, mental sluggishness
Cold intolerance
Put weight on easily
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
235
Q

What signs may indicate hypothyroidism in only adults?

A

Myxoedema - puffy face, hands and feet

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
236
Q

What signs may indicate hypothyroidism in only babies?

A

Cretinism - dwarfism + limited mental functioning

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
237
Q

What is the most common cause of hyperthyroidism?

A

Grave’s disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
238
Q

What is the pathology behind grave’s disease?

A

AI condition where TSI (thyroid stimulating immunoglobulin) acts like TSH but goes unchecked by T3 + T4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
239
Q

What symptoms and signs are associated with Grave’s disease?

A 
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
240
Q

What is the commonest type of thyroid cancer?

A

Papillary (76%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
241
Q

What is the second commonest type of thyroid cancer?

A

Follicular (17%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
242
Q

What varients of thyroid cancer are diffentiated?

A

Follicular and Papillary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
243
Q

How do most differentiated thyroid cancers (DTCs) act physiologically?

A

Take up iodine and secrete thyroglobulin

Are driven by TSH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
244
Q

How do DTCs present?

A

Palpable thyroid nodules

5% will have have local or disseminated metastases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
245
Q

How does Papillary TC spread?

A

via lymphatics

via blood to lungs, bone, liver and brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
246
Q

What thyroid disease is papillary TC associated with?

A

Hashimoto’s thyroiditis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
247
Q

What is the general prognosis of papillary TC?

A

10 year mortality less than 5%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
248
Q

Where is there increased incidence of follicular TC?

A

Areas where iodine deficiency is common

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
249
Q

How does follicular TC spread?

A

Via the blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
250
Q

What investigation is usually done for a neck lump suspected to be associated with the thyroid?

A

US-guided FNA

Potentially excision biopsy of the lymph nodes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
251
Q

What clinical features would suggest a thyroid lump is more likely to be malignant?

A 
New thyroid nodule in those 50
Male sex
Nodule growing
>4cm diameter
History of head/neck irradiation
Vocal cord palsy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
252
Q

What is the treatment of choice for DTC?

A

Surgery
Thyroid lobectomy with isthmusectomy
Sub-total thyroidectomy
Total thyroidectomy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
253
Q

What does the risks of surgery depend on?

A

AMES

A = age
M = metastases
E = extent of primary tumour
S = size of primary tumour
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
254
Q

What is the 20 year survival rate for those who have low AMES scores?

A

99%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
255
Q

What is the 20 year survival rate for those who have high AMES scores?

A

61% (with surgery alone)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
256
Q

When is thyroid lobectomy with isthmusectomy indicated?

A

Papillary microcarcinoma (<1cm)
Minimally invasive follicular tumour
AMES low risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
257
Q

When is sub-total/total thyroidectomy indicated?

A 
DTC with extra-thyroidal spread
Bilateral/multifocal
Distant mets
Nodal involvement
AMES high risk
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
258
Q

What is involved in the post-op care of a thyroidectomy of any sort?

A

Calcium checked within 24hours

Calcium replaced if less than 2mmol/l

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
259
Q

When is whole body iodine scanning used?

A

3-6 months post-op of a sub-total or total thyroidectomy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
260
Q

What must be done before a whole body iodine scan is performed?

A

T4 stopped 4 weeks before scan
OR
T3 stopped 2 weeks before scan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
261
Q

Why does the whole body iodine scanning take a full week?

A

Injections to raise TSH given on mon and tues
Radioactive iodine capsule administered on wed
Patient returns for the imaging process on Friday

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
262
Q

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?

A

Patient will undergo thyroid remnant ablation (TRA) the following Tues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
263
Q

What happens to the patient when receiving TRA?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
264
Q

What can Thyroglobulin (Tg) be used as?

A

A tumour marker post TRA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
265
Q

If a child has a high BG, but no ketones and is clinically well, how soon should they get a paediatric clinical review?

A

24-48hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
266
Q

If a child has high BG, ketones, but is clinically well, how soon should they see a paediatrician?

A

Within the same day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
267
Q

How is DKA treatment different in children?

A

Fluid resus is based on weight
Risk of cerebral oedema is highlighted
Insulin in commenced 1 hour after IV fluids are started

268
Q

What are the signs of early vascular disease in children?

A 
Microalbuminaemia
CV autonomic neuropathy
Sensory nerve damage
Retinopathy
Thickened skin and limited joint mobility of hands and fingers
Skin vascular changes
269
Q

What is primary congenital thyroid disease?

A

Dysplastic gland +/- an abnormal site e.g. sublingual

270
Q

What is secondary/tertiary congenital thyroid disease?

A

Congenital pituitary disease

Usually associated with hypopituitarism

271
Q

What are the clinical symptoms of congenital thyroid disease?

A

Delayed jaundice
Poor feeding but “normal” weight gain
Hypotonia
Skin and hair changes

272
Q

How is congenital thyroid disease screened for?

A

Capillary blood spot in blotting paper at 5 days to measure TSH and/or T4 levels = Guthrie test

273
Q

If a child is found to have congenital thyroid disease when should therapy be commenced?

A

within 2 weeks of birth

2-3 month window where protected by placental thyroid hormones

274
Q

If a child with congenital thyroid disease is not treated within 3 months and thyroxine is absent, then what will happen?

A

Child will develop cretinism - permanent developmental delay

275
Q

How does hypothyroidism present in children?

A 
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
Q

How is hypothyroidism in children treated?

A

Thyroxine replacement for life

Dose is dependent on the size of the child

277
Q

How does hyperthyroidism present in children?

A 
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
Q

How is hyperthyroidism treated in children?

A

Initially = beta-blockers
Suppressant for at least first 2 years = carbimazole +/- thyroxine
Permanent cure = Radio-iodine + surgery

279
Q

What causes primary underactive adrenal disorders in children?
(low steroid production)

A

Adrenal hyperplasia
Inborn error of metabolism
CAH

280
Q

What causes secondary underactive adrenal disorders in children?

A

Pituitary disease

Suppression secondary to steroids

281
Q

What does overactive production of steroids cause in children?

A

Cushing’s disease
Primary = Adrenal cause
Secondary = Pituitary cause

282
Q

What does 21-alpha-hydroxylase deficiency lead to?

A

No aldosterone or cortisol production
High testosterone conversion
= Fetal virilisation

283
Q

What happens to the body when there is no cortisol or aldosterone?

A

“Addison crisis” - hyponatraemia, hyperkalamia and hypotension

284
Q

How is an addison crisis managed?

A

Urgent therapy with salt and cortisol

285
Q

What does virilisation in females cause?

A

ambiguous genitalia

286
Q

What does virilisation in males cause?

A

Precocious puberty

287
Q

What conditions may lead to ambiguous genitalia?

A

CAH or other steroid abnormalities
Gene and/or chromosomal abnormalities
Congenital defects

288
Q

What conditions may lead to ambiguous genitalia?

A

CAH or other steroid abnormalities
Gene and/or chromosomal abnormalities
Congenital defects

289
Q

What would the TFTs show in primary hypothyroidism?

A

TSH high

T4/T3 low

290
Q

What would the TFTs show in primary hyperthyroidism?

A

TSH low

T4/T3 high

291
Q

What would the TFTs show in secondary hypothyroidism?

A

TSH low

T3/T4 low

292
Q

What would the TFTs show in secondary hyperthyroidism?

A

TSH high

T3/T4 high

293
Q

What causes secondary hypothyroidism?

A

Pituitary gland failure

Hypothalamic problems

294
Q

What causes secondary hyperthyroidism?

A

TSHoma (rare)

295
Q

What is myxoedema?

A

Severe hypothyroidism leading to a myxoedema coma

296
Q

What is pretibial myxoedema?

A

Accumulation of hydrophilic mucopolysaccharides in the ground substance of the dermis leading to a doughy induration of the skin typically in the shins

297
Q

What thyroid disease can present with pretibial myxoedema?

A

Grave’s disease (thyrotoxicosis)

298
Q

What are the 2 main causes of goitrous, primary hypothyroidism?

A 
Chronic thyroiditis (Hashimoto's thyroiditis)
Iodine deficiency
299
Q

What is the main cause of non-goitrous, primary hypothyroidism?

A

Atrophic thyroiditis

300
Q

What are the self-limiting causes of hypothyroidism?

A

Withdrawal of thyroid suppressive therapy
Subacute thyroiditis and chronic thyroiditis with transient hypothyroidism
Post-partum thyroiditis

301
Q

What are the main causes of secondary hypothyroidism caused by the hypothalamus?

A

Congeital defects
Encephalitis
Sarcoidosis
Malignancy

302
Q

What are the main causes of secondary hypothyroidism caused by the pituitary?

A

panhypopituitarism (trauma. infection, infiltration, neoplasm)
Isolated TSH deficiency

303
Q

What are the main causes of secondary hypothyroidism caused by the pituitary?

A

panhypopituitarism (trauma. infection, infiltration, neoplasm)
Isolated TSH deficiency

304
Q

What hypothyroid disorder is also known as an AI condition?

A

Hashimoto’s thyroiditis

305
Q

What is the pathophysiology behind Hashimoto’s thyroiditis?

A

AI destruction of the thyroid gland causing decreased thyroid hormone production

306
Q

What investigtions would prove a diagnosis of Hashimoto’s thyroiditis?

A

Thyroid peroxidase antibodies in the blood

T-cell infiltrate and inflammation on microscopy

307
Q

What symptoms occur in the hair/skin in hypothyroidism?

A 
Coarse, sparse hair
Dull, expressionless face
Periorbital puffiness
Pale, cool skin that feels doughy to touch
Hypercarotenaemia? (yellow skin)
308
Q

How does hypothyroidism affect thermogenesis?

A

Become intolerant to cold

309
Q

How does hypothyroidism affect the body’s fluid status?

A

Causes pitting oedema

310
Q

What cardiac symptoms may be present in hypothyroidism?

A

Low HR
Cardiac dilatation
Pericardial effusion
Worsening of pre-existing HF

311
Q

How might hypothyroidism affect the metabolism and BMR?

A

Hyperlipidaemia
Decreased appetite
Weight gain

312
Q

What GI symptoms may present with hypothyroidism?

A

Constipation
Megacolon and intestinal obstruction (rare)
Ascites (rare)

313
Q

What resp. symptoms may present with hypothyroidism?

A

Deep hoarse voice
Macroglossia
Obstructive sleep apnoea

314
Q

What neurological/CNS symptoms may appear with hypothyroidism?

A 
Decreased intellectual and motor activities
Depression
Muscle stiffness/cramps
Peripheral neuropathy
Carpal tunnel syndrome
Decreased visual acuity
315
Q

What gynaecological/Repro symptoms may present with hypothyroidism?

A 
Menorrhagia
Hyperprolactinaemia (high TSH = high prolactin)
316
Q

What lab results will show with hypothyroidism?

A

Macrocytosis (large RBCs)
High creatinine kinase
High LDL cholesterol
Hyponatraemia - decreased renal tubular water loss

317
Q

What lab results will show with hypothyroidism?

A

Macrocytosis (large RBCs)
High creatinine kinase
High LDL cholesterol
Hyponatraemia - decreased renal tubular water loss

318
Q

What thyroid antibodies (and what percentage of people) are present in Grave’s disease?

A

Anti TPO (70-80%)
Anti-thyroglobulin (30-50%)
TSH-receptor (70-100%)

319
Q

What thyroid antibodies (and what percentage of people) are present in AI hypothyroidism?

A

Anti TPO (95%)
Anti-thyroglobulin (60%)
TSH-receptor (10-20%)

320
Q

How is hypothyroidism managed?

A

Thyroxine od before breakfast

Restoration of normal BMR gradually

321
Q

When might thyroxine levels have to be increased for a patient with hypothyroidism?

A

Pregnancy (25-50% increase in dose requirements)

322
Q

Who is most likely to be affected by myxoedema coma?

A

Elderly women with longstanding untreated/poorly treated hypothyroidism

323
Q

How does myxoedema coma present?

A

ECG - Bradycardia, low voltage complexes, heart block, T-wave inversion, prolonged QT
Type 2 resp failure: Hypoxia, hypercarbia, resp. acidosis

324
Q

How is myxoedema coma treated?

A

ABCDE
Slowly rising temp
Close monitoring of ECG, BP, BG, urine output
Fluids and electrolytes - closely monitored
Broad spectrum antibiotics

325
Q

How does amiodarone affect the thyroid function?

A

upto 50% have abnormalities

  • 2% = thyrotoxicosis
  • 13% = hypothyroidism
326
Q

What are the cardiac symptoms associated with hyperthyroidism?

A

Palpitations/AF

HF (rare)

327
Q

What are the cardiac symptoms associated with hyperthyroidism?

A

Palpitations/AF

HF (rare)

328
Q

How can hyperthyroidism affect the CNS?

A

Anxiety, nervousness, irritability, sleep disturbance

329
Q

How can hyperthyroidism affect the GI system?

A

Frequent, loose bowel movements

330
Q

How might hyperthyroidism affect the vision?

A

Lid retraction
Double vision
Proptosis

331
Q

How may hyperthyroidism affect the hair and skin?

A

Brittle, thinning hair

Rapid fingernail growth

332
Q

How can hyperthyroidism affect the repro system?

A

Menstrual cycle changes - lighter and less frequent

333
Q

How can hyperthyroidism affect the muscles?

A

Weakness esp. in thighs and upper arms

334
Q

What happens to the metabolism in hyperthyroidism?

A

Weight loss despite increased appetite

335
Q

How does hyperthyroidism affect thermogenesis?

A

Becomes intolerant to heat

336
Q

What are the causes of hyperthyroidism?

A

AI - Grave’s
Nodular thyroid - Goitre, toxic nodule (adenoma)
Thyroiditis
Iodine (rare)
Medication (rare) - Lithium, amiodarone, thyroxine

337
Q

Who is most likely to get Grave’s disease?

A

Women between 20-50 with a +ve FH and increased iodine intake.

338
Q

At 18 months what happens to those with Grave’s disease?

A

50% - burn out

50% - relapse

339
Q

What would investigations show in an individual with Grave’s disease?

A

High T3/T4
Low TSH
Antibody +ve (TRAbs)

340
Q

How would a patient with Grave’s disease present?

A 
Smooth symmetrical goitre
Lid retraction and lid lag
Swellin of conjunctivae
Proptosis
Visual loss and diplopia
341
Q

How is Grave’s disease treated?

A 
Lubricants
Decompression surgery
Radiotherapy
Corrective surgery
Smoking cessation
342
Q

What age group is more likely to get nodular thyroid disease?

A

Older patients

343
Q

How does Nodular thyroid disease differ from Grave’s?

A

More gradual onset

Gland may feel nodular and asymmetrical

344
Q

What would investigations show in an individual with Nodular thyroid disease?

A

High T3/T4
Low TSH
Antibody -ve (TRAbs)

345
Q

What would investigations show in an individual with Nodular thyroid disease?

A

High T3/T4
Low TSH
Antibody -ve (TRAbs)

346
Q

What is sub-acute thyroiditis/De Quervains?

A

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
Q

What do the TFTs show in sub-acute thyroiditis/De Quervains?

A

T4 =high in early stage, low in late, then normal

TSH = low in early stage, high in late, then normal

348
Q

What is a thyroid storm?

A

A medical emergency with severe hyperthyroidism, resp and cardiac collapse, exaggerated reflexes and hyperthermia

349
Q

How is a thyroid storm treated?

A

Lugols iodine, glucocorticoids, PTU, beta-blockers, fluids, and very close monitoring

350
Q

How is hyperthyroidism treated?

A

Carbimazole
Propylthiouracil (PTU) (used in pregnancy)
Beta blockers
Radioiodine or surgery

351
Q

What is the composition of the thryroid?

A

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
Q

How would a thyroid adenoma present?

A

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
Q

How would a thyroid adenoma present?

A

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
Q

What HLA groups is Hashimoto’s thyroiditis associated with?

A

HLA-DR3

HLA-DR5

355
Q

What are the genetic features associated with Papillary thyroid carcinomas?

A

activate the MAPK pathways
rearrangements of RET ot NTKR1
Activating point mutation in BRAF

356
Q

How does a papillary thyroid carcinoma present?

A

Usually a solitary nodule in the thyroid sometimes with lymph node mets

357
Q

What are the genetic features associated with a follicular thyroid carcinoma?

A

Mutations in P13K/AKT pathway

358
Q

How does follicular thyroid carcinoma usually present?

A

Single nodule which slowly enlarges is painless and non-functional
Rarely has lymphatic spread but may have haematogenous spread to bones/lungs/liver

359
Q

What genetic factors are associated with Medullary Thyroid carcinoma (MTC)?

A

MEN2 - germline RET mutations

360
Q

What is MTC derived from?

A

C-cells (neuroendocrine) and may secrete calcitonin

361
Q

What does a MTC contain?

A

Spindle or polygonal cells arranged in nests, trabeculae or follicles

362
Q

What may the cause of a MTC be?

A

Sporadic (70%)
Associated with multiple endocrine neoplasia (MEN)
Familial

363
Q

Amyloid deposition may be associated with a MTC, why?

A

Amyloid represents deposition of an abnormally folded protein - in this case calcitonin

364
Q

How does MTC usually present?

A

Neck mass with local effects

Paraneoplastic symdrome - diarrhoea, Cushings

365
Q

How does MTC usually present?

A

Neck mass with local effects

Paraneoplastic symdrome - diarrhoea, Cushings

366
Q

What is anaplastic thyroid carcinoma?

A

An undifferentiated, aggressive tumour usually found in older patients

367
Q

What genetic factors are associated with anaplastic thyroid carcinoma?

A

Features of both papillary and follicular carcinomas + p53 and beta-catenin mutations

368
Q

In thyroid cytology what would a specimen with Thy1 results be?

A

Insufficient/uninterpretable results

369
Q

In thyroid cytology what would a specimen with Thy2 results be?

A

Benign

370
Q

In thyroid cytology what would a specimen with Thy3 results be?

A

Atypia/probably benign/equivocal

371
Q

In thyroid cytology what would a specimen with Thy4 results be?

A

atypia suspicious of malignancy

372
Q

In thyroid cytology what would a specimen with Thy5 results be?

A

Malignant

373
Q

How many parathyroid glands does an individual have?

A

usually 4

10% populus have 2/3

374
Q

What do chief cells which make up the parathyroid glands do?

A

secrete PTH

act on Ca homeostasis

375
Q

What do chief cells look like histologically?

A

Round cells with moderate cytoplasm and bland, round central nuclei

376
Q

What do oxyphil cells do?

A

Support the chief cells in the parathyroid glands

377
Q

What do the oxyphil cells look like on histology?

A

Slightly larger than chief cells

Acidophilic cytoplasm

378
Q

What are most cases of hyperparathyroidism caused by?

A

small adenomas on 1 parathyroid gland

379
Q

What is hyperplasia of the parathyroid glands associated with?

A

MENI and MENIIa

380
Q

If one parathyroid gland contains an adenoma, what happens to the other parathyroid glands?

A

They become atrophic

381
Q

How does a parathyroid adenoma present microscopically?

A

Resembles normal parathyroid but may see a fibrous connective tissue capsule with adjacent rim of compressed parathyroid tissue

382
Q

How does a parathyroid adenoma present microscopically?

A

Resembles normal parathyroid but may see a fibrous connective tissue capsule with adjacent rim of compressed parathyroid tissue

383
Q

In hyperplasia of the parathyroid glands how many glands are typically affected?

A

Usually all of them

384
Q

What is secondary hyperparathyroidism?

A

Chronic hypocalcaemia causes compensatory overactivity of the parathyroid glands

385
Q

What can secondary hyperparathyroidism cause?

A 
Renal failure (low Ca intake, Vit D deficiency)
Hyperplasia of parathyroid tissue
386
Q

What is tertiary hyperparathyroidism?

A

Parathyrid activity becomes autonomous

Associated with hypercalcaemia

387
Q

What are the signs and symptoms of hyperparathyroidism?

A

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
Q

Hypoparathyroidism is very rare, but what can cause it?

A

Post-op of thyroid
congential absence - DiGeorge
familial - associated with primary adrenal insuffiency and mucocutaneous candidiasis

389
Q

What can hypoparathyroidism cause?

A

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
Q

What hormone does the ovum produce?

A

oestradiol

391
Q

What hormone is detected on a pregnancy test if fertilisation of the ovum occurs?

A

hCG

392
Q

What hormones does the placenta produce?

A

Human placental lactogen (hPL)
placental progesterone
placental oestrogens

393
Q

Progesterones + hPL in an insulin resistant mother leads to what?

A

Increased BG and gestational diabetes

394
Q

What complications may occur in pregnancy as a result of poor diabetic glycaemic control?

A 
Congenital malformation
Prematurity
Intra-uterine growth retardation
Large birth weight
Polyhydramnous (too much fluid around baby)
Intrauterine death
395
Q

What complications may occur in the baby if a diabetic mother has poorly controlled BG levels?

A 
Resp distress due to immature lungs
Hypoglycaemia and/or hyperglycaemia = fits
Anencephaly + spina bifida
caudal regression syndrome 
ureteric dulplication
396
Q

What percentage of people who suffered from gestational diabetes will go on to develop T2DM in 10 or so years?

A

50%

More in obese individuals

397
Q

What effect does thyroid disease have on pregnancy?

A

Hyper or hypo thyroidism may cause anovulation

Increased demand on thyroid during pregnancy (thyroxine dose needs to increase)

398
Q

What effect does hCG have on TFTs in pregnancy?

A

9% have low TSH

14% have high ft4

399
Q

What effect does hCG have on TFTs in pregnancy?

A

9% have low TSH

14% have high ft4

400
Q

What should be done for pregnant women with pre-existing hypothyroidism?

A

Increase medication dose

TFTs monthly until 20 weeks, then 2 monthly until term

401
Q

What are the risks of untreated hypothyroidism during pregnancy?

A 
Increased spontaneous abortion risk
Pre-eclampsia
Pstpartum haemorrhage
Perterm labour
Foetal neuropsychological dvelopment (lower IQ)
402
Q

What can cause thyrotoxicosis in pregnancy?

A

Grave’s disease
TMNG, toxicadenoma
Thyroiditis
Gestational hCG-associated thyrotoxicosis (resolves by 20 weeks)

403
Q

What are the risks in pregnancy in a woman with pre-existing hyperthyroidism?

A 
Infertility
Spontaneous miscarriage
stillbirth
thyroid crisis in labour
transient neonatal thyrotoxicosis
404
Q

How is hyperthyroidism managed in pregnancy?

A

Supportive management for symptoms
Beta blockers in early pregnancy
Low dose antithyroid drugs

405
Q

What is postpartum thyroiditis?

A

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
Q

What is the physiology of the posterior pituitary lobe?

A

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
Q

What does ADH act on?

A

Urine collection channels in the kidneys

408
Q

What does oxytocin act on?

A

Mammary glands and smooth muscles above the uterus

409
Q

What is the physiology of the posterior pituitary lobe?

A

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
Q

What does oxytocin act on?

A

Mammary glands and smooth muscles above the uterus

411
Q

What happens in the anterior lobe of the pituitary?

A

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
Q

What does ACTH act on?

A

Adrenals

413
Q

What does TSH act on?

A

Thyroid

414
Q

What does FSH and LH act on?

A

reproductive organs

415
Q

What does PRL act on?

A

mammary glands

416
Q

What does STH act on?

A

Muscle

417
Q

What happens in the hypothalamo-pituitary testicular axis?

A
  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
Q

What is the role of ABG in males?

A

Binds to testosterone and keeps it in the seminiferous tubules

419
Q

What is the role of inhibin in males?

A

Supports spermatogensis and inhibits production of FSH, LH and GnRH

420
Q

What does CRH release from the hypothalamus cause to happen in the pituitary gland?

A

stimulates ACTH release

421
Q

What does ACTH release cause to happen in the adrenal gland?

A

Cortisol release

422
Q

What does ACTH release cause to happen in the adrenal gland?

A

Cortisol release

423
Q

What effects does cortisol have on the body?

A

Regulates glucose levels
Increases body fat
Defends body against infection
Helps body respond to stress

424
Q

What dynamic tests can be done to identify whether or not too much or too little hormone is being produces?

A

Too much hormone = do tests to suppress the hormone

Too little hormone = do tests to stimulate the hormone

425
Q

What hormone stimulation tests exist to test hormone function?

A

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
Q

What are the 2 different types of pituitary adenoma?

A

Microadenoma less than or = 1cm

Macroadenoma >1cm

427
Q

What effects can a non-functioning pituitary adenoma have on the body?

A 
Compression of optic chiasm
Compression of cranial nerves
Hypoadrenalism
Hypothyroidism
Hypogonadism
DI
GH deficiency
428
Q

What effects can a non-functioning pituitary adenoma have on the body?

A 
Compression of optic chiasm
Compression of cranial nerves
Hypoadrenalism
Hypothyroidism
Hypogonadism
DI
GH deficiency
429
Q

What are the physiological causes of increased prolactin levels in the body?

A

Breast feeding
Pregnancy
Stress
Sleep

430
Q

What drugs can caused increased body prolactin levels?

A 
Dopamine antagonists
Antipsychotics
Antidepressants
Oestrogens
Coccaine
431
Q

What pathological conditions can cause increased prolactin production?

A

Hpothyroidism
Stalk lesions
Prolactinomas

432
Q

What symptoms and signs occur in females with increased prolactin levels?

A 
EARLY presentation
Galactorrhoea
Menstrual irregulartiy
Ammenorrhoea
Infertility
433
Q

What symptoms and signs occur in males with increased prolactin levels?

A 
LATE presentation
Galactorrhoea in less than 30%
Visual field abnormalities
Headache
Impotence
Anterior pituitary dysfunction
434
Q

What investigations can be done when suspicions of prolactinoma arise?

A

Prolactin conc.
MRI pituitary
Visual field testing
Pituitary function tests

435
Q

How is excess prolactin (prolactinoma) treated?

A

Dopamine agonists:

  • Bromocriptine
  • Quinagolide
  • Cabergoline
436
Q

How effective is treatment for prolactin excess?

A

Prolactin is normalised in 96%
Menstruation regained in 94%
Pregnancy rate 91%
Tumour shrinkage

437
Q

What causes acromegaly?

A

GH excess

438
Q

What re the signs and symptoms of acromegaly?

A 
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
Q

How is acromegaly diagnosed?

A

IGF1 levels - age and sex matches

GTT - GH unchanged after glucose >1microgram/l

440
Q

How is a glucose tolerance test (GTT) performed?

A

75g oral glucose bolus is given
GH is checked at 0, 30, 60, 90 and 120 mins
In normal cases GH suppresses to

441
Q

How is a glucose tolerance test (GTT) performed?

A

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
Q

What is the treatment for acromegaly?

A

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
Q

What are the effects of somatostatin analogues in acromegaly?

A

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
Q

What are the side effects of somatostatin analogues?

A

Local stinging
Flatulence, diarrhoea, abdo pains
Gastritis in 50-60%
Gallstones in 60%

445
Q

What drugs are somatostain analogues?

A

Octerotide
Sandostatin
Lanreotide autogel

446
Q

What dopamine agonists is used in acromegaly?

A

Cabergoline upto 3g weekly

Reduces GH to less than 2 in 15% cases

447
Q

What drug is a GH anatgonist and used in acromegaly?

A

Peguisomant

448
Q

What doe GH antaginists do?

A

Bind to the GH receptor and block GH activity
Has an 85% response rate
IGF-1 decreases

449
Q

What is included in the follow-up and long term management of acromegaly?

A 
Achieve clinically safe levels (less than 1)
Check for other pituitary disorders
Cancer surveillance
Manage CVD risk factors
Manage sleep apnoea
450
Q

What is the main cause of Cushing’s syndrome?

A

Excess cortosol

451
Q

What are the symptoms of protein loss in Cushing’s

A

Myopathy
Osteoporosis
Thin skin

452
Q

What are the symptoms of mineralocorticoid excess in Cushing’s?

A

Hypertension

Oedema

453
Q

What are the symtoms of excess androgen in Cushing’s?

A

Virilism
Hirsutism
Acne
Oligo/amenorrhoea

454
Q

What does altered carbohydrate/lipid metabolism in Cushing’s cause?

A

DM

Obesity

455
Q

What does an altered psyche is Cushing’s cause?

A

Psychosis

Depression

456
Q

What does an altered psyche is Cushing’s cause?

A

Psychosis

Depression

457
Q

What is the most common clinical presentation of Cushing’s syndrome?

A 
Thin skin
Proximal myopathy
Frontal balding in women
Conjunctical oedema
Osteoporosis
'moon face'
458
Q

What screening tests are available for Cushing’s syndrome?

A

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
Q

What definitive test exists for Cushing’s syndrome?

A

2 day 2mg/day dexamethosone suppression test

A cortisol less than 50nmol/l 6h after the last dose is -ve for Cushing’s

460
Q

What are the causes of Cushing’s syndrome?

A

Pituitary >80%
Adrenal adenoma - beign/cancerous
Ectopic - thymus, lung, pancreas
Psuedo - Alcohol and depression, steroid medication

461
Q

How is Cushing’s caused by a pituitary disease treated?

A

Hypophysectomy (pituitary removal) and external radiotherapy if recurrance

462
Q

How is Cushing’s disease caused by adrneal adenoma treated?

A

Adrenalectomy

463
Q

How is Cushing’s disease caused by an ectopic cause treated?

A

Remove source OR bilateral adrenalectomy

464
Q

What drug treatment is available for Cushing’s syndrome?

A

Metyrapone - if other treatments fail or while waiting for radiotherapy to work
Ketoconazole
Pasireotide

465
Q

What drug treatment is available for Cushing’s syndrome?

A

Metyrapone - if other treatments fail or while waiting for radiotherapy to work
Ketoconazole
Pasireotide

466
Q

What does pan hypopituitarism cause in the anterior pituitary?

A

Growth failure
Hypothyroidism
Hypogonadism
Hypoadrenal

467
Q

What does pan hypopituitarism cause in the posterior pituitary?

A

Diabetes insipidus (DI)

468
Q

What causes pan hypopituitarism?

A 
Pituitary tumours
Secondary mets from lungs and breast
Local brain tumours
Granulomatous diseases
Vascular diseases
Trauma
Hypothalamic diseases
Iatrogenic
AI
Infection
469
Q

What are the signs and symptoms of pan hypopituitarism ?

A 
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
Q

What tests should be done when suspecting pan hypopituitarism in an individual?

A

fT4, TSH
Oestradiol/testosterone, LH + FSH
GH, IGF-1
Prolactin

471
Q

How is pan hypopituitarism treated?

A 
Thyroxine
Hydrocortisone
ADH
GH
Sex steroids
472
Q

How do GH injections affect adults?

A 
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
Q

How do GH injections affect adults?

A 
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
Q

What are the risks of artificial testosterone replacement?

A

Prostate enlargement
Polycthaemia (increased RBCs)
Hepatitis

475
Q

What are the causes of DI?

A 
Familial = DIDMOAD
Acquired = trauma, idiopathic, RTAs, surgery, skull fracture
Rare = Tumour, sarcoid, external irradiation, meningitis
476
Q

How is DI treated?

A

Desmospray

Desmopressin oral tablets/sublingual tablets/injection

477
Q

What is the most important thing to remember when thinking about sodium and water balance?

A

WATER FOLLOWS SODIUM EVERYWHERE

478
Q

How are sodium levels in the body controlled?

A

Mineralocorticoid activity - sodium retention in exchange for potassium and/or H+

479
Q

What steroids have a mineralocorticoid activity?

A

Aldosterone (main)

Cortisol

480
Q

What are the effects of too much and too little mineralocorticoid activity?

A

Too much = sodium retention (+ water)

Too little = sodium loss (+water)

481
Q

What process brings back sodium and water into the system?

A

Low BP activating the RAAS system - aldosterone is produced (high BP has the opposite effect)

482
Q

How are water levels controlled in the body?

A

By ADH

483
Q

What does ADH cause to occur in the renal tubules?

A

Water reabsorption

Antidiuretic effect

484
Q

What does ADH cause to occur in the renal tubules?

A

Water reabsorption

Antidiuretic effect

485
Q

If urine osmolarity is high, what does this do to the urine?

A

Concentrated urine

486
Q

What causes increased ADH secretion and hence concentrated urine?

A

Increased sodium levels in the blood (low sodium causes the opposite)

487
Q

What causes Decreased sodium concentration in the blood?

A

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
Q

What causes Increased sodium concentration in the blood?

A

Too little water - Increased water loss (DI) or Decreased water intake
Too much sodium - RARE, some IV drugs, near-drowning in the sea.

489
Q

What is the basis behind Addison’s disease?

A

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
Q

What are the common presenting features of Addison’s disease?

A

Dizziness and hypotension from reduced ECF

Excess pigmentation thus tanned skin from excess ACTH production

491
Q

What complication of Addison’s disease is associated with Na loss?

A

K retention and thus hyperkalaemia

492
Q

What is the basis behind SIAD?

A

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
Q

How is SIAD diagnosed?

A

Decreased sodium found on U&Es.

494
Q

How is SIAD diagnosed?

A

Decreased sodium found on U&Es.

495
Q

What is the basis behind DI?

A

Disruption of pituitary or pituitary stalk thus no ADH secreted. Lots of (pure) water lost in urine and sodium conc is high.

496
Q

When should abnormalities of sodium levels be considered serious?

A

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
Q

What is the basic make-up of the anterior pituitary?

A

Adenohypophysis
Derived from Rathke’s pouch
Secretes trophic (TSH, ACTH, FSH, LH) and non-trophic (GH, prolactin) hormones

498
Q

What is the basic make-up of the posterior pituitary?

A

Neurohypophysis
Extension of neural tissue consists of modified glial cells and axonal processes
Secretes ADH (vasopressin) and oxytocin

499
Q

What is the basic histology of the anterior pituitary gland?

A

Islands, cords of cells
Acidophils
Basophils
Chromophobe

500
Q

What is the basic histology of the anterior pituitary gland?

A

Islands, cords of cells
Acidophils - Somatotrophs (GH), Mammotrophs (PRL)
Basophils - Corticotrophs (ACTH), Thyrotrophs (TSH), Gondaotrophs (FSH/LH)
Chromophobe

501
Q

What is the basic histology of the posterior pituitary gland?

A

Non-myelinated axons of neurosecretory cells

502
Q

What pathologies affect the anterior pituitary gland?

A 
Hyperfunction = adenoma/carcinoma
Hypofunction = surgery/radiation, sudden haemorrhage, ischaemic necrosis, tumours extending into sella, inflammatory conditions
503
Q

What pathologies affect the posterior pituitary gland?

A

DI

SIADH

504
Q

What are pituitary adenomas?

A

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
Q

What symptoms may large adenomas present with?

A

Visual field defects
Pressure atrophy of surrounding tissue
Infarction can lead to panhypopituitarism

506
Q

What symptoms may large adenomas present with?

A

Visual field defects
Pressure atrophy of surrounding tissue
Infarction can lead to panhypopituitarism

507
Q

What is a prolactinoma?

A

The most common type of functional pituitary adenoma

Causes infertility, lack of libido and ammenorrhoea

508
Q

What is a GH-secreting adenoma?

A

2nd most common type of functional pituitary adenoma

May cause gigantism or acromegaly

509
Q

What can an ACTH secreting adenoma cause?

A

Cushing’s

510
Q

What causes pituitary hypofunction?

A 
Primary or metastatic tumours
Traumatic brain injury
Subarachnoid haemorrhage
Surgery or radiation
Granulomatous inflammation
Infarction
Hypothalamis lesions
511
Q

What is a craniopharyngioma?

A

A tumour derived from the remnants of Rathke’s pouch

A slow-growing, often cystic tumour which may calcify

512
Q

What symptoms does a craniopharyngioma cause?

A

Headaches and visual disturbances

513
Q

What are the adrenal glands?

A

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
Q

What are the 3 zones of the adrenal cortex?

A

Zona glomerulosum - mineralocorticoids and aldosterone

Zona fasciculata - glucocorticoids and cortisol

Zona reticularis - sex steroids and glucocorticoids

515
Q

What are the 3 zones of the adrenal cortex?

A

Zona glomerulosum - mineralocorticoids and aldosterone

Zona fasciculata - glucocorticoids and cortisol

Zona reticularis - sex steroids and glucocorticoids

516
Q

What cells lie in the adrenal medulla?

A

Neuroendocrine (chromaffin) cells which secrete catecholamines

517
Q

What is congenital adrenocorical hyperplasia?

A

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
Q

What is acquired adrenocortical hyperplasia?

A

Endogenous ACTH production

Bilateral adrenal enlargement

519
Q

How do adrenocortical tumours present?

A

Incidental finding
Hormonal effects
Mass lesion
Carcinomas with necrosis leads to fever

520
Q

What features of a tumour indicate an adrenocortical carcinoma?

A

Large size >50g or >20cm
Haemorrhage and necrosis
Frequent mets
Lack of clear cells

521
Q

What are the typical features of an adrenocortical adenoma?

A

Well circumscribed, encapsulated lesions
Small
Yellow-brown cut surface
Well-differentiated, small nuclei

522
Q

What is primary aldosteronism also known as?

A

Conn’s syndrome

523
Q

What is Conn’s syndrome ususally associated with?

A

Diffuse or nodular hyperplasia of both adrenal glands

524
Q

What happens in and what causes secondary hyperaldosteronism?

A

Increased Rennin

Decreased renal perfusion, hypovolaemia, pregnancy

525
Q

What happens in and what causes secondary hyperaldosteronism?

A

Increased Rennin

Decreased renal perfusion, hypovolaemia, pregnancy

526
Q

What is hypercortisolism also known as?

A

Cushing’s disease

527
Q

What are the ACTH dependent causes of hypercortisolism?

A

ACTH secreting pituitary tumour

Ectopic ACTH - small cell lung cancer

528
Q

What are the ACTH independent causes of hypercortisolism?

A

Adrenal adenoma or carcinoma

Non-lesional adrenal gland atrophies

529
Q

What can cause primary adrenocortical hypofunction?

A

May be acute or chronic

Many causes and associations

530
Q

What can cause secondary adrenocortical hypofunction?

A

Failure to stimulate adrenal cortex

Suppression of the adrenal cortex

531
Q

What causes acute primary adrenocortical insufficiency?

A

Rapid steroid withdrawal
Crisis in patients with chronic adrenocortical sufficiency
Massive adrenal haemorrhage

532
Q

What causes chronic primary adrenocortical insufficiency?

A 
Addison's
AI adrenalitis
Infections
Unusual causes
Signs and symptoms occur when >90% gland is destroyed
533
Q

What causes chronic primary adrenocortical insufficiency?

A 
Addison's
AI adrenalitis
Infections
Unusual causes
Signs and symptoms occur when >90% gland is destroyed
534
Q

What are the symptoms of Addison’s disease?

A 
weakness
fatigue
anorexia
N+V
weight loss
diarrhoea
pigmentation
535
Q

What happens to the body when mineralocorticoid levels fall?

A

K+ retention
Na+ loss
Volume depletion and hypotension

536
Q

What happens to the body when glucocorticoid levels fall?

A

Hypoglycaemia

537
Q

What can cause an Addisonian crisis?

A

Stress, Infection, Trauma, Surgery

538
Q

What are the symptoms of an Addisonian crisis?

A 
Vomiting
abdo pain
hypotension
shock
death
539
Q

How common are neuroblastomas?

A

1 in 7000 live births

540
Q

What percentage of neuroblastomas arise from the adrenal medulla?

A

40% - the rest arise along the sympathetic chain

541
Q

What is a neuroblastoma composed of?

A

Primative appearing cells but may show maturation and differentiation

542
Q

What is a phaeochromocytoma?

A

A neoplasm derived from chromaffin cells in the adrenal medulla which secretes catecholamines
A rare cause of secondary hypertension

543
Q

What complications can arise as a result of a phaeochromocytoma?

A

HF
Infarction
arrhythmias
CVA

544
Q

How are phaeochromocytomas diagnosed?

A

Detection of urinary catecholamines and metabolites

545
Q

Why are phaeochromocytomas known as the 10% tumour?

A 
10% are extra-adrenal
10% are bilateral
10% are biologically malignant
10% NOT associated with hypertension
25% familial
546
Q

How do phaeochromocytomas appear macroscopically?

A

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
Q

How do phaeochromocytomas appear macroscopically?

A

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
Q

Where do phaeochromocytomas typically metastatise to?

A

Skeletal muscle
Regional lymph nodes
Liver
Lung

549
Q

What condition is phaeochromocytoma a small part of?

A

MEN (IIA or IIB)

550
Q

What is MENIIA?

A

Phaeochromocytoma (40-50%)
Medullary thyroid cancer (100%)
Parathyroid hyperplasia (10-20%)
Phaeochromocytoma may be bilateral and occur at extra-adrenal sites

551
Q

What genetic mutation is MENIIA linked to?

A

Germline gain of function mutation in RET oncogene on Ch10

552
Q

What is MENIIB?

A

Phaeochromocytoma, medullary thyroid carcinoma, neuromas or ganglioneuromas
Marfinoid habitus

553
Q

What genetic mutation is MENIIB linked to?

A

Germline in RET oncogene - distinct from IIA mutations, almost always activating point mutation in the catalytic domain of the encoded enzyme.

554
Q

What genetic mutation is MENIIB linked to?

A

Germline in RET oncogene - distinct from IIA mutations, almost always activating point mutation in the catalytic domain of the encoded enzyme.

555
Q

What regulates functions of the zona glomerulosa?

A

Angiotensin II and K+

556
Q

What regulates the zona fasiculata?

A

ACTH

557
Q

What regulates the functions of the Zona reticularis?

A

ACTH + other unknown factors

558
Q

What lies in the adrenal medulla?

A

Chromaffin cells
Medullary veins
Splanchnic nerves

559
Q

How does RAAS regulate aldosterone?

A

Activated in response to low BP

Produces angiotensin II which causes direct vasoconstriction and indirect (via aldosterone) methods of BP elevation

560
Q

What is the mechanism of corticosteroids?

A

Bind intracellular receptors

Receptor/ligand complex binds DNA to affect transcription

561
Q

What are the 6 classes of steroid receptor?

A 
Glucocorticoid
Mineralocorticoid
Progestin
Oestrogen
Androgen
Vit D
562
Q

How do glucocorticoids (cortisol) affect the CNS?

A

Mood lability
Euphoria/psychosis
Decreased libido

563
Q

How do glucocorticoids (cortisol) affect the Bone/connective tissue?

A

Accelarates osteoporosis
Decreased serum calcium
Decreased collagen formation
Slower wound healing

564
Q

How do glucocorticoids (cortisol) affect the Immunological system?

A

Decreased:

  • capillary dilataion/permeability
  • leucocyte migration
  • macrophage activity
  • inflammatory cytokine production
565
Q

How do glucocorticoids (cortisol) affect the Metabolic system?

A

Increased:

  • BG
  • Lipolysis
  • Proteolysis
566
Q

How do glucocorticoids (cortisol) affect the Circulatory/renal system?

A

Increased:

  • CO
  • BP
  • Renal blood flow and GFR
567
Q

In general what does too much cortisol cause?

A

AI disease

568
Q

What are the clinical roles of corticosteroids?

A

Suppress inflammation
Suppress immune system
Replace treatment

569
Q

What are the effects of aldosterone via mineralocorticoid receptors?

A

Sodium/Potassium balance
BP regulation
ECFV regulation

570
Q

Where are mineralocorticoid receptors (MRs) found?

A

Kidneys
Salivary glands
Gut
Sweat glands

571
Q

Where are mineralocorticoid receptors (MRs) found?

A

Kidneys
Salivary glands
Gut
Sweat glands

572
Q

What conditions show primary insufficiency of the adrenal glands?

A

Addison’s
CAH
Adrenal TB/malignancy

573
Q

What conditions show secondary insufficiency of the adrenal glands?

A

lack of ACTH stimulation
Iatrogenic - excess exogenous steroid
Pituitary/hypothalamic disorders

574
Q

How can adrenal insufficiency be tested for?

A 
Low Na or High K levels
Hypoglycaemia
Short synACTHen test
v. high ACTH levels
v. high rennin and low aldosterone levels
Adrenal autoantibodies
575
Q

How is a Shory synacthen test performed?

A

Plasma cortisol is measured before and 30mins after IV ACTH
Normal =
-Baseline >250nmol/l
-postACTH >480nmol/l

576
Q

How is adrenal insufficiency treated?

A

Hydrocortisone to replace cortisol
Fludrocortisone to replace aldosterone
Education

577
Q

What is Addison’s disease?

A

An AI disease causing destruction of the adrenal cortex thus leading to primary adrenal insufficiency

578
Q

What other AI conditions is Addison’s associated with?

A

T1DM
Grave’s disease
Pernicious anaemia

579
Q

What are the clinical features of Addison’s disease?

A 
Anorexia and weight loss
Ammenorrhoea
Fatigue/lethargy
Dizziness and low BP
Abdo pain
Vomiting
Diarrhoea
580
Q

What causes the skin pigmentation seen in Addison’s disease?

A

v. high ACTH levels

581
Q

What is the commonest cause of secondary adrenal insufficiency?

A

Exogenous steroid use

Further lowers CRH and aCTH

582
Q

How does secondary adrenal insufficiency present?

A

Same as Addison’s
EXCEPT
Skin pale/normal (no excess ACTH)
Aldosterone production is intact

583
Q

How is secondary adrenal insufficiency treated?

A

Hydrocortisone (fludrocortisone is unnecessary as aldosterone is normal)

584
Q

How is secondary adrenal insufficiency treated?

A

Hydrocortisone (fludrocortisone is unnecessary as aldosterone is normal)

585
Q

What is iatrogenic Cushing’s syndrome?

A

Commonest cause of cortisol excess due to prolonged high dose steroid therapy
Causes chronic suppression of ACTH production and adrenal atrophy

586
Q

What are the implications of an individual having iatrogenic Cushing’s syndrome?

A

Unable to respond to stress
Needs extra doses of steroid when ill or prior to surgery
Cannot stop treatment suddenly

587
Q

How is iatrogenic cushing’s syndrome treated?

A

Gradual withdrawal of steroid therapy

588
Q

What CVD may be brought on by primary aldosteronism?

A

LVH
atheroma
Increased BP

589
Q

What are the common clinical features of primary aldosteronism?

A

Significant hypertension
Hypokalaemia
Alkalosis

590
Q

What re the rare causes of primary aldosteronism?

A

Genetic mutations
Unilateral hyperplasia
K+ channel mutations producing adenomas and hereditary hypertension

591
Q

What is the 1st step in diagnosis of primary aldosteronism?

A

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
Q

What is the 2nd step in diagnosing primary aldosteronism?

A

Confirm subtype

593
Q

What is the 2nd step in diagnosing primary aldosteronism?

A

Confirm subtype

Adrenal CT or adrenal vein sampling to demonstrate adenoma or adrenal hyperplasia

594
Q

What is the 2nd step in diagnosing primary aldosteronism?

A

Confirm subtype

Adrenal CT or adrenal vein sampling to demonstrate adenoma or adrenal hyperplasia

595
Q

What is the surgical management of primary aldosteronism?

A

Unilateral laproscopic adrenalectomy
Cures hypokalaemia
Cures hypertension in a good number of cases

596
Q

What is the medical management of primary hypoaldosteronism?

A

MR antagonists

  • spironolactone
  • eplerenone
597
Q

What is CAH?

A

Rare condition associated with enzyme defects in the steroid pathway

598
Q

What is the commonest CAH?

A

21-alpha-hydroxylase deficiency

599
Q

What are the 2 variants of 21-alpha-hydroxylase deficiency?

A 
Classical = salt-wasting, simple virilising
Non-classical = hyperandrogenaemia
600
Q

How is 21-alpha-hydroxylase deficiency diagnosed?

A

Basal 17-OH progesterone

genetic mutation analysis

601
Q

What does a 21-alpha-hydroxylase deficiency mean for the body?

A

Cortisol and aldosterone are not produced

Androstenedione and testosterone are produced in excess

602
Q

How does classical 21-alpha-hydroxylase deficiency present in males?

A

Adrenal insufficiency
Poor weight gain
Biochemical pattern similar to Addison’s

603
Q

How does classical 21-alpha-hydroxylase deficiency present in females?

A

Genital ambiguity

604
Q

How does non-classical 21-alpha-hydroxylase deficiency present?

A 
Hirsutism
Acne
Oligomenorrhoea
Precocious puberty
Infertility/sub-fertility
605
Q

How is 21-alpha-hydroxylase deficiency treated in children?

A 
Early recognition
glucocorticoid replacement
mineralocorticoid replacement
surgical correction
achieve maximal growth potential
606
Q

How is 21-alpha-hydroxylase deficiency treated in adults?

A

Control androgen excess
Restore fertility
Avoid over-replacement of steroids

607
Q

What is the clinical triad of phaeochromocytoma?

A

Hypertension
Headache
Sweating

608
Q

What other symptoms does phaeochromocytoma present with?

A 
Palpitations
breathlessness
constipation
anxiety
flushing
weight loss
609
Q

If a phaeochromocytoma is found extra-adrenally what is it known as?

A

Paraganglioma

610
Q

If a phaeochromocytoma is found extra-adrenally what is it known as?

A

Paraganglioma

611
Q

What are the clinical signs associated with phaeochromocytoma?

A 
hypertension
pallor
bradycardia and tachycardia
pyrexia
LVF
myocardial necrosis
stroke
shock
paralytic ileus of bowel
612
Q

What biochemical abnormalities may present in phaeochromocytoma?

A

hyperglycaemia
low K+
Increased haematocrit
Lactic acidosis

613
Q

What imaging is used to diagnose a phaeochromocytoma?

A

MRI

PETscan

614
Q

How are phaeochromocytomas treated?

A 
Full alpha and beta blockade
-phenoxymethylbenzamine
-atenolol or metoprolol
Fluid and/or blood replacement
Surgical
-total excision wherever possible
Chemo if mallignant
615
Q

What is Von-Hippel-Lindau syndrome?

A

Mutation in HIF1-alpha
AD
Range of vascular tumours across the body
Associated with phaeochromocytomas.

616
Q

Other than phaeochromocytomas, what other condition can caused raised catecholamines?

A

HF

617
Q

What defines the anterior triangle of the neck?

A

Bounded by the mandible superiorly
Midline medially
Anterior border of the sternocleidomastoid laterally

618
Q

What defines the posterior triangle of the neck?

A

Posterior border of SCM anteriorly
Anterior border of trapezius laterally
Clavicle inferiorly

619
Q

What defines the posterior triangle of the neck?

A

Posterior border of SCM anteriorly
Anterior border of trapezius laterally
Clavicle inferiorly

620
Q

What can cause superficial swellings on the neck?

A

Sebaceous cysts
Lipomas
Neurofibromas

621
Q

What can cause midline neck swellings?

A

Thyroid
Thyroglossal cyst
Dermoid cyst

622
Q

What can cause swellings in the anterior triangle of the neck?

A

Lymph nodes
Salivary glands
Branchial cyst
Carotid body tumour

623
Q

What can cause swellings in the posterior triangle of the neck?

A

Lymph nodes

Cystic hygroma

624
Q

What is a cystic hygroma?

A

Forms when lymph vessels fail to form correctly during foetal development

625
Q

What is a branchial cyst?

A

Congenital failure to obliterate 2nd branchial cleft

626
Q

What is a dermoid cyst?

A

A cyst containing an array of developmentally mature solid tissues

627
Q

What is a lipoma?

A

A small fatty lump that grows beneath the skin

628
Q

What is a Neurofibroma?

A

A benign nerve sheath tumour

629
Q

What symptoms are associated with cervical lymphadenopathy?

A 
Fever
weight loss
sweats
hoarseness
cough
dyspnoea
630
Q

What would a brancial cyst show on FNA?

A

cholesterol crystals

631
Q

What would a brancial cyst show on FNA?

A

cholesterol crystals

632
Q

What is osteoporosis?

A

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
Q

What are the 2 types of bone making up the human skeleton?

A

20% trabecular (porous sponge-like)

80% cortical (dense material that provides stiffness and strength

634
Q

How does bone remodelling occur?

A

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
Q

What happens with bone remodelling in osteoporosis?

A

There is an increase in resorption over formation leading to increased bone loss

636
Q

What contributes to an adults peak bone mass?

A 
Genetics - major part
Sex hormones
Exercise
Increased body weight
Diet
637
Q

What factors may contribute to bone loss?

A 
Sex hormone deficiency
Genetics
Immobility
Low body weight
Diet
Disease
Drugs - glucocorticoids + aromatase inhibitors
638
Q

What endocrine conditions can predispose an individual to osteoporosis?

A

Hyperthyroidism
Hyperparathyroidism
Cushing’s disease
T1DM

639
Q

What GI conditions can predispose an individual to osteoporosis?

A

Coeliac disease
IBD
Chronic liver disease
Chronic pancreatitis

640
Q

What respiratory conditions can predispose an individual to osteoporosis?

A

CF

COPD

641
Q

What direct effects do corticosteroids have on the bone?

A

Decreased osteoblast activity and lifespan
Suppression of replication of osteoblast precursors
Decrease in calcium absorption

642
Q

What indirect effects do corticosteroids have on bone?

A

Inhibition of gonadal and adrenal steroid production causing Increased PTH and decreased bone mass

643
Q

What indirect effects do corticosteroids have on bone?

A

Inhibition of gonadal and adrenal steroid production causing Increased PTH and decreased bone mass

644
Q

What do DEXA scans measure?

A

BMD (Bone mineral density) against a population mean - predicts fracture risk independently of other risk factors

645
Q

What is the T-score in DEXA scans?

A

Young adults female population mean

646
Q

What is the Z-score in DEXA scans?

A

Age-matched female population mean

647
Q

What is normal BMD in DEXA scanning?

A

BMD is withing 1SD of the young adult reference means

648
Q

What is osteopenia on DEXA scanning?

A

BMD more than 1SD but less than 2.5SD below the young adult mean reference

649
Q

What is osteoporosis on DEXA scanning?

A

BMD >= 2.5SD below the young adult mean

650
Q

What is severe osteoporosis on DEXA scanning?

A

BMD >= 2.5SD below the young adult mean with a fragility fracture

651
Q

What lifestyle advice is given to patients with osteoporosis?

A

High intensity strength training
Low impact weight-bearing exercises
Avoidance of excess alcohol and smoking
Fall prevention

652
Q

What dietary advice is given to patients with osteoorosis?

A

2-3 portions from milk and dairy for calcium

653
Q

When should antiresorptive therapy be considered in patients with osteoporosis?

A

T less than or equal to -2.5

If on steroids or fracture of vertebrae has occured, start at T-1.5

654
Q

What drug treatments are recommended in osteoporosis?

A

Calcium for post-menopausal women who do not get enough dietary intake
Vit D supplements for housebound under 60s or anybody over 65

655
Q

What supplementary treatments are recommended in osteoporosis?

A

Calcium for post-menopausal women who do not get enough dietary intake
Vit D supplements for housebound under 60s or anybody over 65

656
Q

What are bisphosphonates?

A

Analogues of pyrophosphate that adsorb onto bone within the matrix
Anti-resorptive agents used in osteoporosis

657
Q

How do bisphosphonates work?

A

Ingested by osteoclasts, leading to cell death, thereby inhibiting bone resorption

658
Q

How effective are bisphosphonates?

A

Increases BMD by 5-8%

Reduces fragility fracture by around 50%

659
Q

How is zoledronic acid used to treat osteoporosis

A

Once yearly infusion for 3 years
~70% reduction in vertebral fracture risk
~40% reduction in hip fracture risk

660
Q

What is denosumab?

A

Fully human monoclonal antibody that targets and binds with high affinity and specificity to RANKL

661
Q

How does denosumab prevent fractures in osteoporosis?

A

Prevents RANK, inhibiting development and activity of osteoclasts, reducing bone resorption and increasing bone density

662
Q

What are the side effects of denosumab?

A

Eczema

Cellulitis

663
Q

What are the side effects of denosumab?

A

Eczema

Cellulitis

664
Q

What is strontium ranelate?

A

An anti-resorptive agent which is third line for osteoporosis

665
Q

What are the contraindications for using strontium ranelate?

A

history of thomboembolic disease
IHD
Peripheral arterial disease
Uncontrolled hypertension

666
Q

What is teriparatide?

A

A recombinant parathyroid hormone which stimulates bone growth

667
Q

What are the symptoms of acute hypercalcaemia?

A

Thirst
Dehydration
Confusion
Polyuria

x 2nd Year Medicine (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions