TOPIC 9 - endocrinology Flashcards
(182 cards)
1
Q
what are the main endocrine glands?
A
- hypothalamus
- pituitary
- thyroid
- parathyroid
- pancreas
- adrenals
- ovaries/testicles
2
Q
what does the pituitary gland control?
A
most glands in the body
3
Q
what two lobes is the pituitary gland split into?
A
anterior pituitary
posterior pituitary
4
Q
what does the anterior pituitary do?
A
produces various hormones
5
Q
what does the posterior pituitary do?
A
stores various hormones produced by hypothalamus
6
Q
what hormones does the anterior pituitary produce?
A
- GH: Growth Hormone
- ACTH: adrenocorticotrophic hormone
- Gonadotrophins: FSH/LH
- TSH: thyroid stimulating hormone/thyrotrophin
- PRL: prolactin
7
Q
what does GH do?
A
growth hormone, for skeletal growth
8
Q
what does ACTH do?
A
adrenocorticotrophic hormone, stimulates adrenals to produce steroids
9
Q
what do gonadotrophins (LH/FSH) do?
A
follicle stimulating hormone/luteinising hormone, stimulate testes/ovaries to produce sex hormones and sperm/ova
10
Q
what does TSH do?
A
thyroid stimulating hormone, stimulates thyroid to produce thyroid hormones
11
Q
what does prolactin do?
A
PRL, stimulates breast milk production
12
Q
what does ADH do?
A
antidiuretic hormone, stimulates water reabsorption by the kidneys
13
Q
what does oxytocin do?
A
helps uterine contractions during labour
14
Q
what controls the anterior pituitary gland?
A
hypothalamus
15
Q
what stimulates ACTH secretion?
A
corticotrophin releasing hormone (CRH)
16
Q
what stimulates GH secretion?
A
growth hormone releasing hormone (GHRH)
17
Q
what stimulates TSH secretion?
A
thyrotropin releasing hormone (TRH)
18
Q
what stimulates FSH and LH secretion?
A
gonadotrophin releasing hormone (GnRH)
19
Q
what stimulates prolactin secretion?
A
prolactin releasing hormone does not exist and prolactin is under the inhibitory effect of the hypothalamus
20
Q
what is the effect on prolactin if we cut the connection between the hypothalamus and pituitary gland?
A
increase levels of prolactin as we no longer have the inhibitory effect of the hypothalamus
21
Q
what switches off ACTH and CRH?
A
cortisol
22
Q
what switches off GH and GHRH?
A
growth hormone
23
Q
which hormone switches off TSH and TRH?
A
thyroid hormone
24
Q
which hormone switches off FSH/LH and GnRH?
A
sex hormones
25
what process switches hormone secretion off?
negative feedback
26
what are the 4 glands not controlled by the pituatry?
- adrenal medulla
- parathyroid
- pancreas
- gut hormones
27
what hormone does adrenal medulla produce?
adrenaline and noradrenaline
28
what does the parathyroid control?
Controls calcium levels
29
what is the thyroid gland composed of
- midline isthmus (just below the cricoid cartilage)
- right lobe
- left lobe
30
how are the thyroid cells arranged and what do they produce?
arranged in follicles and produce thyroid hormones
31
what other cell does the thyroid follicle contain and what does this produce?
C cells
produce calcitonin
(calcium metabolism only nothing to do with thyroid hormone)
•Pituitary gland does not control calcium secretion
32
how do thyroid hormones work?
interact with their receptors in various organs, thereby regulating gene expression and various aspects of organ function
33
what is calcium metabolism controlled by?
4 parathryoid glands sitting behind the thyroid
34
what other organs, other than the parathyroid are involved in calcium metabolism?
- Kidneys- Calcium excretion and production of active vitamin D
- Gut - Absorption of calcium
- Bone- Storage of calcium
- Thyroid
35
what are the adrenal glands composed of?
- adrenal cortex
| - adrenal medulla
36
what does the adrenal cortex produce
- Corticosteroids (cortisol)
- Androgens (male hormones)
- Mineralocorticoid (aldosterone)
37
is cortisol essential for life?
- yes severe deficiency can be fatal
| - inject person with cortisol when suspected even before results of test=save life
38
what do the adrenal medulla produce?
-Catecholamines (adrenaline, noradrenaline and dopamine)
39
does pituitary control the adrenal cortex?
controls part of the adrenal cortex
40
is catecholamine secretion controlled by the pituitary ?
no - related to BP
41
is mineralocorticoid (aldosterone) controlled by the pituitary?
no- related to renin-angiotensin system, which controls the blood pressure
- in low BP= increase in aldosterone secretion
42
where are the ovaries situated?
pelvis on either side of the uterus
43
what do the ovaries contain?
follicles (each containing an oocyte) at different stage of maturation during reproductive life
- limited no. of oocyte
44
what hormones control the female reproductive system?
- GnRH- which switches on and off
- FSH and LH
- Oestradiol- switches FSH off (- feedback) and LH on (+ feedback)
- Progesterone also produced by ovaries (- feedback on LH)
- Inhibin - only negative feedback
45
does the secretion of FSH and LH depend on the time of the cycle?
yes
| FSH at first part cycle, LH at second part
46
where are testes found?
the scrotum- except in a minority with testicular maldescent
47
what are testes composed of?
- intersitial/Leydig cells
- Seminiferous tubules
- Sertoli cells
48
what do the intersitial/Leydig cells do?
produce testosterone
49
what do the Seminiferous tubules do?
made up of germ cells producing sperms
50
what do the Sertoli cells do?
help in sperm production and produce inhibin
51
are FSH and LH important in male hormone production?
yes
- FSH important for sperm production
- LH important for testosterone production
52
what is a primary abnormality of a gland?
when the abnormality comes from the gland itself
53
what is a secondary abnormality of a gland?
when the abnormality is influenced by something other than the gland- eg. the pituitary
54
what are the 3 main abnormalities that affect hormones?
* Hormonal over-secretion
* Hormonal under-secretion
* Tumour/nodules in the gland without affecting hormone secretion
55
what are the 3 main tests we do for hormonal abnormalities?
- Static tests
- Stimulation tests
- Suppression tests
56
why would we take a static test?
can diagnose abnormalities of thyroid and sex glands
| -single blood sample will make diagnosis
57
in one with primary hyperthyroidism (thyroid hormone overproduction) what would we test for?
–Thyroid hormones (T3 and T4)
–TSH
-If primary hyperthyroidism (abnormality in thyroid itself independent from pituitary) is present then T3 and/or T4 is elevated with suppressed (undetectable) TSH
58
why would we take a stimulation test?
for suspected hormonal under-secretion where a static test is NOT ENOUGH (i.e. results are equivocal)
- stimulates gland to produce hormones
- If levels don’t go up drastically= person has under secretion in gland
- With mild cases can go undetectable
59
give an example of a specific stimulation test
- giving ACTH to test for adrenal insufficiency
- If an individual fails to respond to a stimulation test then gland failure is diagnosed
- Other examples: glucagon stimulation and insulin stress test for pituitary failure (tests for ACTH and GH response
60
what happens in an insulin stress test?
put person in state hyperglycaemia
so pituitary secretes hormones to raise glucose levels
this inc. ACTH
if levels fail to rise= diabetes
61
why would we use a suppression test
for some hormonal over-secretion
62
give examples of 2 suppression tests
–Giving steroids and testing for endogenous steroid production (external steroids should switch off internal steroid production)
–Giving glucose and testing GH secretion (glucose switches off GH secretion in normal individuals)
63
if both Free T4 levels are higher and TSH levels are lower than normal- what is the diagnosis ?
primary hyperthyroidism
64
if Free T4 levels are lower and TSH are higher than normal - diagnosis?
primary hyporthyroidism
| more TSH due to negative feedback- trying to increase the Free T4 levels
65
if we have too much Free T4 and TSH- diagnosis?
secondary hyperthyrodism
| problem in pitiuatry
66
what does over secretion of endocrine glands leads to?
benign tumours
67
what does under secretion of endocrine glands lead to?
gland destruction due to:
–Inflammation (including autoimmune conditions)
–Infarction
–Other
68
what is the last disease of endocrine glands?
Tumours/nodules with normal hormone production
69
how do we get prolactin oversecreation?
pituitary tumour secreting prolactin (prolactinoma)
70
what is the clinical presentation of overactive prolactin?
–Galactorrhoea (breast milk production)
–Menstural problems in women
–Amenorrhoea (no period) in women and sexual dysfunction in men
–Causes irregular periods
–Headaches and visual field problems in large tumours
71
how do we diagnose prolactin?
* Static test is enough- prolatictin test
| * Pituitary MRI- to see if they have tumour
72
with what kind of tumours do we get defects in visual fields?
pituitary gland tumour
73
why do we get visual fields defects with pituitary tumours?
the tumour puts pressure on the optic chiasm (which receives signals from right and left side) = half of visual field is taken away
74
what are the reasons for mildly raised prolactin?
* Sexual intercourse
* Nipple stimulation
* Stress
* Large number of drugs (including antipsychotics and antidepressants)- always advice check prolactin before the drugs and only test prolactin if we have to
* Non-functioning pituitary tumour (compressing the hypothalamus and interfering with the inhibitory effect on prolactin secretion)
75
how do we treat prolactinomas?
usually over-secreting pituitary tumours that can be treated medically dopamine agonists
surgical intervention
If its due to stalk compression
76
GH oversecreation in childhood or adolescents leads to....
–Excessive growth spurt and increased size of feet and hands
| –If left untreated growth hormone excess leads to gigantism
77
GH oversecreation in adults leads to.....
–Acromegalic face
–Wide and large hands/feet
–Increased sweating (common complaint)
- visual defects in tumour compressing optical chiasm
78
diagnosis of GH oversecreation
* Suppression tests are necessary
* Glucose is given followed by GH measurements at different time points (in healthy individuals, glucose suppresses GH production and hence plasma levels of the hormones fall but not in those with over-secretion)
* Imaging is necessary to confirm the presence of pituitary tumour
79
treatment of overactive GH
* Surgical removal of the tumour
| * Radiotherapy and medical therapy may also be needed as surgery does not always remove the whole tumour
80
what are the main causes of cushing's syndrome
–Pituitary secreting ACTH tumour (Cushing’s disease)
–Adrenal tumours secreting cortisol
–Cancers producing ACTH (such as lung cancers= lots of ACTH= too much coritsol)
81
what is the clinical presentation of cushing's syndrome
```
•Growth arrest in children
•Typical facial appearance
– Round (moon-like) face
– Acne
– Hirsuitism
•Fat redistribution
– Truncal obesity
– Thin extremities
•Skin abnormalities
– Thin skin and easy bruising
– Striae on abdomen
•Complications
– Hypertension
– Diabetes mellitus
– High risk of infections
– Poor wound healing
```
82
tests for cushing's syndrome?
* Static tests are not enough and suppression tests are required.
* Dexamethasone suppression test is used to confirm the failure to suppress endogenous cortisol production.
83
How do you differentiate between adrenal and pituitary Cushing’s?
meausre ACTH
84
what are steroid hormones derived from?
cholesterol
85
what are thyroid hormones derived from?
tyrosine residues within the protein thyroglobulin
86
what property do both steriod and thyroid hormones have in common?
Both classes of hormone are hydrophobic- so both can diffuse across plasma membrane into cytosol
87
what class of hormones are sex hormones
androgens and eostrogens are steroid hormones
88
do androgens have an aromatic ring?
no
89
which sex hormone has an aromatic ring?
oestrogen's such as oestrdiol have aromatic ring introduced by enzyme aromatase
90
how do steroid hormones effect transcription- whats the process?
1- steriod hormones cross the cell membrane
2- the hormone binds to an intracellular receptor present in either nucleus or cytosol
3- if free receptor was in cytosol the hormone- receptor complex moves into nucleus (whether in cytosol or nucleus we always end up in nucleus)
4- the hormone receptor complex acts as a transcription factor
5- mRNA is transcribed and protein is produced
91
where are promoter elements located on genes?
some very close to the transcription start site
| other elements- eg.yellow boxes- several kB away
92
how many domains do nuclear hormone receptors have?
4 domains
93
what is the name of the domain that specifically recognises hormone?
hormone binding domain at carboxyl terminus which makes them specific
94
what is the name of the domain that pairs up?
- dimerization domain
- pair up so they are facing opposite directions =C terminus of one next to N terminus of another
- the two hormone receptors bind to make dimer
95
what is the name of the domain that binds to the DNA helix?
the DNA binding domain
| -with 'zinc fingers' - what bind to DNA helix
96
what are zinc fingers?
- projections in protein sequence that insert themselves into grooves of DNA helix
- loops of protein that contain Zn2+ atom
- in the case of steriod hormone receptors: coordinated with 4 cysteine residues
97
why are cystine residues in zinc fingers of importance?
cystine residues have SH groups that coordinate with zinc to hold it in position
98
what domain do nuclear hormone receptors have at the amino terminus?
transcription regulation domain
| interacts with other proteins that regulate transcription
99
what is vitellogenin?
a protein made by egg laying insects, molluscs, fish, reptiles, birds and monotremes (egg-laying mammals)
100
what is the process which vitellogenin ends up in egg yolks?
- vitellogenin synthesised in liver of female fish reptiles and birds
- released into blood stream into oocyte
- cleaved by proteases into functional fragments
- incorporated into egg-yolk as these smaller proteins
101
what hormone regulates the production of vitellogenin?
oestrogens
102
what animal synthesised a large amount of vitellogenin?
frogs and toads
103
what kind of sequence is the oestrogen response element in vitellogenin?
a palindrome
| sequence reads same forwards and backwards
104
how does the oestrogen receptor bind to the palindrome of vitellogenin?
one pair of the dimers recognises of one the palindromes and the other dimer recognises the other strand
- as the 2 nuclear factors face opposite directions = can interact with the two elements of the palindrome which face in different directions
105
where in vitellogenin is the palindrome located?
300bp upstream of the transcription site
| lies next to other sequences that are thought to promote vitellogenin transcription
106
what are the 2 closely related oestrogen receptors?
ERa
| ERb
107
do healthy tissues express more ERb or ERa?
ERb
108
what type of oestrogen receptor is strongly expressed in some breast cancers?
ERa
109
what hormone promotes rapid division of ERa+ in breast cancer cells?
oestrogen
110
how can ERa+ breast cancers be detected?
by staining sections of tumour biopsies with antibodies against the oestrogen receptor on thin slices of tissues . (ERα positive cells are stained brown).
111
how can the growth and spread of these breast cancers be inhibited?
administering anti-oestrogen drugs such as tamoxifen- block action of oestrogen = strop rapid dividing of cells .
112
what kind of drug is tamoxifen
pro drug
| gets converted to an active form within body
113
what is the usual process of oestrogen binding to an oestrogen receptor?
- once oestrogen bound to receptor = acquires changed shape
| - eostrogen receptor can then bind to coactivators
114
how does tamoxifen work?
- tamoxifen molecule binds to oestrogen receptor
- receptor does not acquire changed shape
- receptor cannot bind to coactivators
- transcription pathway unactivated = oestrogen action blocked = tumour cannot proliferate in same way
115
what has X-ray crystallography determined?
exact shape of oestrogen receptor with hormone molecule bound and with tamoxifen bound
116
what is T4 and where is it synthesied?
tetra-iodothyronine/thyroxine
| synthesised in thyroid gland
117
what other protein is made in the thyroid?
thryroglobin
118
what is the process by which we form thyroxine molecule
1- aromatic ring on a couple of tyrosine molecules on protein thyroglobulin are iodinated
2- iodotyrosine molecules in thyroglobulin are cross-linked
3- One of the thyrosine aromatic rings loses its original position in the protein molecule = so we get thyroxine being made
4- thyroxine molecule is cut out of thyroglobulin.
119
how do we get the active form of hormone T3(tri-iodothyronine) formed?
produced in the peripheral tissues through deiodination of T4- one of iodine atoms taken off T4
120
how many genes are there for thyroid hormone receptors?
2 separate genes
121
how many receptors are there for each thyroid and oestrogen
both have 2 receptors
| two receptors have slightly different actions to one another
122
what is the recognition sequence in the promoter region of the thyroid hormone?
TRE (thyroid hormone response element)
123
where is the TRE?
upstream of various genes of energy metabolism and heart function that are switched on by thyroid hormones
124
do thyroid hormones act similar to steroid hormones?
yes both bind to nuclear hormone receptors that promote transcription
- some differences
- eg. thyroid hormone receptor always bound to DNA wether thyroid present or not
125
in the nucleus what do thyroid hormones receptors (TR)bind to
bound to thyroid hormone response elements (TRE) in the DNA both in the presence or absence of hormone.
126
in the absence of thyroid hormone what binds to TR instead
the hormone receptors bind repressor molecules that switch off transcription.
127
describe process of thyroid hormone binding to TR
1- in the presence of hormone - co-repressor leaves
| 2- coactivator bonds to receptor and transcription starts
128
is the second nuclear receptor molecule which TR pairs with another TR or a different nuclear receptor?
might be another TR- homodimer
often a different nuclear receptor - heterodimer
= v complicated transcription process
129
how many essential genes does the genome of a reterovirus contain?
3 essential genes with repeat sequences at the end
130
can a reterovirus combine with host DNA?
yes every so often
| they can still generate infectious viruses and be carried into the next cell they infect
131
what is v-erbA
- a highly mutated version of thyroid hormone receptor that has been found in transforming reteroviruses
- occurred naturally
132
what does v-erbA cause?
erythroblastosis and leukaemia in chickens
133
how does transcription usually happen with T3?
1- T3 binds and a number of genes are transcribed
2- Proteins A,B,C are made in response
3- one or more of these proteins is a tumour supressor gene which protects against cancer development
134
what happens to transcription with T3 when V-erbA binds?
1-V-erbA binds to TRE but cannot activate transcription and inhibits/prevents efficient binding of TR and hence blocks thyroid hormone action.
= dominant negative effect
2- proteins A,B,C not made to sufficient level = protection against development of cancer is lost
135
mutations in THR in humans have been linked to which cancers?
- liver
- kidney
- breast
- pitutary
- thyroid
136
what is the dominant negative effect?
Mutation only to be in one of the (thyroid) gene to cause malfunction
137
what is thyroid hormone overprodution due to?
–Primary hyperthyroidism: Very common
| –Secondary hyperthyroidism (pituitary TSH secretion): Rare
138
id thyroid overproduction more common in men or women?
women
139
causes of hyperthyroidism
- graves disease (80%)
- toxic nodule or MBG (15%)
- thyroiditis (1%)
- drug induced (amiodarone) - used for cardiac arthymias
- rarities
140
what is graves disease?
body producing antibodies that mimic action of TSH – attach to TSH receptor= thyroid overactive = organ specific (only effects one organ)
autoimmune condition
141
what is thyroiditis?
- inflammation of thyroid gland= destruction of thyroid cells = increase in thyroid hormones
- cells then go under active as thyroid cells try to recover- if too severe = under active thyroid persists
142
clinical presentation of hyperthyroidism
* Hyperactivity, irritability, insomnia
* Heat intolerance(feel warm all the time) and increased sweating
* Palpitations
* Weight loss despite overeating
* Menstrual problems
143
examination for hyperthyroidism
```
•Signs of thyrotoxicosis
–Hand tremor
–Increased sweating
–Fast pulse
•Inspection of the thyroid
•Enlarged (usually)
•Smooth: Graves’ disease
•Nodular: toxic nodule(s)
•Tender: thyroid inflammation
```
144
how can you tell if a pateint has a large goitre?
thyroid moves up when you swallow
| NB- in a massive goiture Goitre was so big compressing windpipe and effecting swallowing
145
Extrathyroidal signs thyroid eye disease
- inflamtion in muscles around eyes and fat tissue around eyes
•Swelling around the eyes
•Protrusion of the eye ball (proptosis)- eyes pushed out
•Paralysis of eye muscles- too much inflammation = people get double vision
•Periorbital swelling – swelling around eyes
146
how to test for overactive thyroid
•Thyroid blood test:
–Raised thyroid hormone
–Suppressed TSH
static test is enough
147
treatment for overactive thyroid
• Anti-thyroid drugs: disease remission in 50% of patients after treatment for 6-18 months can suppress white cell production (very rare)
•Radioactive iodine- can use in graves, TMN and TN
–Destroys the thyroid gland
• Surgery
148
do anti-thyroid drugs treat all overactive thyroid diseases?
Only with graves disease does the drug work – in toxic nodule or toxic multiple nodule goitre the drug only controls not treat
149
what symptoms does GH deficiency cause in children
Failure of growth
150
what symptoms does GH deficiency cause in adults
– Nothing
– Tiredness
Depression
151
how do you test for GH deficiency
Stimulation test
•Glucagon stimulation test
•Insulin stress test (lowers blood glucose, stressing the body and forcing growth hormone secretion)- failure of GH to rise= GH deficiency
• Insulin stress test= can be very stressful for people
152
treatment for GH deficiency
•Growth hormone replacement
–Injections
–Expensive (choose adult patients carefully)- don’t want to give to people asympotomatic
153
what is steroid under secretion due to?
–Adrenal failure (1’ adrenal failure )
| –Pituitary failure(2’ failure)
154
what is the clinical presentation of steroid undersecretion
–Failure to grow in children
–Severe tiredness
–Dizziness due to low blood pressure
–Abdominal pain, vomiting an diarrhoea
155
tests for steroid under secretion
•Stimulation test:
–Synacthen test (giving ACTH) if primary adrenal failure is suspected
–GST or IST if secondary adrenal insufficiency is suspected: as both GH and ACTH go up
156
treatment for steroid undersecreation
Replace the missing hormone
• Tablets
• Cheap
Failing to diagnose this may result in death. In case this diagnosis is suspected, cortisol should be given even before results of investigations
157
what is primary hypothyroidism
thyroid failure and inability to produce thyroid hormones (common).
–Usually autoimmune in nature-n destruction of thyroid gland
–Can be drug induced
158
what is secondary hypothyroidism
failure to produce TSH (rare).
| –Usually part of complete pituitary failure
159
Symptoms of hypothyroidism
```
Weakness and dry skin
Sensation of cold and decreased sweating
Impaired memory
Constipation
Weight gain
Hair loss
```
160
diagnosis of hypothyroidism
static test of thyroid function- low T4 and high TSH
161
treatment if hypothyroidism
Thyroid hormone replacement (tablets, cheap)
162
what is primary sex hormone deficiency
–Males: testicular failure
| –Females: ovarian failure
163
what is secondary sex hormone deficiency
–Pituitary failure
164
what is the presentation of sex hormone deficiency in males
–Erectile dysfunction
| –Reduced libido/sexual desire
165
what is the presentation of sex hormone deficiency in females
–Menstrual abnormalities (amenorrhoea
166
what is amenorrhoea and what can be its causes
```
•Very common presentation
NO PERIOD
•Can be due to:
– Uterine problems
– Ovarian problems
– Pituitary problems
– Hypothalamic problem
```
167
diagnosis of sex hormone deficiency
–Static tests are enough:
• Testosterone (males), oestradiol (females)
• FSH/LH
168
treatment of sex hormone deficiency
–Hormone replacement therapy (testosterone for males; oestradiol/progesterone for females)
–Pituitary hormone replacement
169
what is pituitary failure due to?
- large tumour
- infarction
- other rare causes
170
how do we test for pituitary failure
It usually involves multiple hormones and therefore a combination of static and stimulatory tests are required to make the diagnosis
- for suspected tumour= MRI
171
what might an increase in parathyroid hormone production be due to
–Primary hyperparathyroidism
–Cancers
–Drugs
Other
172
what are the clinical presentation of hypercalcemia
Hypercalcaemia causes:
•Thirst and passing too much urine (osmotic symptoms)
•Constipation
Abdominal pain
173
if Ca levels are high and PTH are high what is diagnosis?
hyperparathryroidism
174
is family history important in hyperthyroidism?
yes: history of autoimmune disorders- eg. diabetes type 1, excema
175
what are the complications for surgery of hyperthyroidism
- hoarse voice= nerve damage
| - hypocalceamia = damage to parathyroid glands
176
where is the hypothalamus located?
head
177
where is the pituitary gland located?
head
178
where is the thyroid gland loacted?
neck
179
where is the parathyroid gland located?
neck (behind thyroid)
180
where is the pancreas located?
abdomen
181
where are the adrenals located?
abdomen
182
what is the function of the pancreas?
control sugar levels
