Endocrine Flashcards
1
Q
which receptor type do amines e.g. adrenaline bind to?
A
G protein coupled receptor
2
Q
what activates nuclear hormone receptors?
A
- steroid hormones
- thyroid hormones
3
Q
what receptor does growth hormone work on?
A
tyrosine kinase receptors
4
Q
What does somatostatin do?
A
-inhibits glucagon and insulin secretion
-decreases stomach acid secretion and production
-inhibits secretion of growth hormone and TSH
(basically inhibits secretion of growth and metabolic hormones)
5
Q
How is insulin secreted? (5 steps)
A
- Glucose enters B cells through GLUT2
- if enough glucose enters cell will be phosphorylated by glucokinase (Km = 5mM)
- B cell metabolises glucose to ATP
- ATP inhibits K+ channels -> cell membrane depolarises
- Ca2+ channels open, Ca2+ enters cell and stimulates release of vesicles full of insulin
6
Q
How does DKA work?
A
- no glucose is available so FA oxidised to provide energy giving Acetyl-CoA
- if no oxaloacetate available (from glycolysis) to accept Acetyl-CoA in krebs cycle then Acetyl-CoA is diverted to become ketone bodies
- accumulation of ketones -> acidosis
- insulin cannot move out of blood as no insulin so excreted in urine -> dehydration
- lack of insulin meant K+ cannot move into cells -> hyperkalaemia
7
Q
Diagnosis criteria for diabetes (type 1 or 2)
A
- HbA1C over 48m/m
- fasting glucose over 7
- 2h OGTT or random glucose over 11.1 mmom/L
8
Q
Some of more common MODY mutations
A
- mutation in glucokinase meaning its Km is 7 or 8
- mutations in GLUT-2 channels
- mutations in Kir6.2 subunit of Katp channels
9
Q
treatment for Graves/hyperthyroidism in pregnancy
A
propylthiouracil
10
Q
Hashimoto’s thyoroiditis antibodies
A
anti thyroid peroxidase (anti TPO)
11
Q
What is de quervain’s/ giant cell thyroiditis?
A
- transient presence of anti thyroid antibodies
- post viral infection
- painful goitre
- symptoms of hyper then hypo
12
Q
Genes associated with papillary thyroid cancer
how common is it?
A
- RET
- BRAF
- most common thyroid cancer
13
Q
Risk factors for papillary carcinoma
A
-exposure to ionising radiation during childhood
14
Q
histological features of papillary thyroid cancer
A
- finger-like projections of follicle cells
- Orphan Annie nuclei (empty nuclei)
- psammoma bodies (calcium deposits)
15
Q
where is papillary thyroid cancer going to metastasise to first?
A
-lymphatic vessels and lymph nodes
16
Q
genes associated with follicular carcinoma
how common is it?
A
- RAS
- deactivation of PTEN (tumour suppressor gene)
-second most common thyroid cancer
17
Q
risk factors fro follicular carcinoma
A
-low dietary iodine intake
18
Q
what does follicular carcinoma metastasise to first?
A
- breaks through thyroid fibrous capsule
- blood vessels
- liver, bone, brain
19
Q
Genes associated with medullary carcinoma
A
- RET
- MEN2a and MEN2b
20
Q
histological features of medullary carcinoma
A
- spindle shaped cells
- fibrous deposits around C cells (excessive production of calcitonin)
21
Q
Whats unusual about medullary thyroid cancer?
A
-can release ectopic hormones e.g. serotonin, VIP
22
Q
what is the most aggressive thyroid cancer?
A
-anaplastic thyroid cancer
23
Q
symptoms of thyroid cancer
A
- solitary painless nodule in thyroid gland
- usually cold i.e. it doesn’t secrete anything
- large tumours may compress other structures
24
Q
What is the Guthrie test?
A
- newborn screening test
- detects neonatal metabolic conditions
- heel prick onto blotting paper
- from this can get TSH and T4 levels (lack of indicates congenital hypothyroidism)
25
Addison's disease biochemistry
- hyponatraemia
| - hyperkalaemia
26
what does zona glomerulosa secrete
- aldosterone
| - regulated by K+ and AII
27
what does zona fasciculata secrete?
- glucocorticoids
| - regulated by ACTH
28
what does zona reticularis secrete?
-sex steroids
29
what does adrenal medulla secrete?
- adrenaline
| - noradrenaline
30
investigations for acromegaly
- comparing IGF1 values to age and sex
| - glucose tolerance test (acromegaly is confirmed if glucose does not suppress GH secretion)
31
examples of dopamine agonists used in the treatment of prolactinoma
- cabergoline
| - dostinex
32
primary aldosteronism features
- hypertension
- hyperkalaemia
- alkalosis
33
investigation for primary aldosteronism
- plasma aldosterone to renin ratio (is aldosterone proportional to renin?)
- saline suppression test
34
where do neuroblastoma most commonly occur?
- adrenal glands
| - young kids
35
10% rule of pheochromocytoma
- 10% extra adrenal
- 10% bilateral
- 10% malignant
- 10% not associated with hypertension
- 25% familial
36
medical treatment of pheochromocytoma
-phenoxybenzamine
-propanolol
(alpha then beta blockade)
37
Defective enzyme in congenital adrenal hyperplasia
-21 hydroxylase
38
investigation for congenital adrenal hyperplasia
-basal 17-OH progesterone (precursor to aldo and cortico before 21 hydroxylase action)
39
MEN1 tumours
- pituitary
- parathyroid*
- bronchial carcinoid
- enteropancreatic
40
MEN2 tumours
- nerve
- thyroid C cell (medullary)
- pheochromocytoma
41
What is McCune-Albright syndrome?
- mutation in gene needed for G protein signalling (GNAS1)
- autonomous hyper secretion from endocrine glands
- cafe au lait patches
42
What is Kallman's syndrome
- hypogonadotrophic hypogonadism
- failure of production of gonadotrophin releasing hormone
- no puberty, infertility and no sense of smell
43
how do parathyroid hormones work?
- stimulate osteoblast proliferation and expression of RANK ligand
- RANK ligand on osteoblasts can stimulate pre-osteoclasts to mature
- active osteoclasts can then release enzymes which break down bone and release Ca2+
- PTC also increase reabsorption of Ca2+ in distal convoluted tubule
44
what does calcidiol do?
| active vitamin D
-increase G.I tract Ca2+ absorption
45
causes of hypocalcamia
- increased phosphate levels e.g. CKD
- hypoparathyroidism e.g. post thyroidectomy, digeorge syndrome
- vitamin D deficiency e.g. osteomalacia/rickets
- drugs e.g. calcitonin, biphosphonates
- hypomagnasemia
46
why does hypomagnesemia cause hypocalcaemia
- magnesium is needed for cells to release calcium
- if Mg2+ low then intracellular calcium is too high
- also inhibits PTH -> hypocalcaemia
47
symptoms of hypocalceamia
- parasthesia -finger, toes, perioral
- muscle cramps, weakness tetony
- fatigue
- bronchospasm
- QT prolongation
48
Acute hypocalcaemia treatment
EMERGENCY!
- IV calcium gluconate 10ml
- IV infusate (+/- magnesium)
49
what is a normal bone mineral density?
BMD within 1 SD of young adult mean
50
osteopenia definition
BMD greater than 1SD below the adult mean
51
osteoporosis definition
BMD greater than 2.5 SD deviations below the adult mean
52
What is pagets disease
abnormal osteoclastic activity followed by increase osteoblastic activity
53
which cells produce testosterone?
leydig cells
54
what do sertoli cells do?
- take up most of testosterone in body
| - nourishes developing sperm cells
55
what stimulates testosterone production?
LH
56
what stimulates spermatogenesis
FSH
57
how long is the follicular phase and what happens in it?
- days 1-14 after menstruation (but variable)
- growth/increase in ovarian follicles, oestrogen release
- mediated by FSH
58
how long is luteal phase and what happens in it?
- days 14-28 after menstruation
- ovulation (day 14), corpus luteum formation and progesterone secretion
- mediated by LH
59
high frequency of GnRH pulses stimulates what?
LH release
60
low frequency of GnRH pulses stimulates what?
FSH release
61
- Low GnRh
- low FSH and LH
- oestrogen deficiency
hypothalamic pituitary failure (group 1)
| e.g. v low BMI
62
- normal GnRH?
- normal FSH, raised or normal LH
- normal oestrogen
hypothalamic pituitary dysfunction (type 2)
| e.g. PCOS
63
- normal/increase GnRH?
- normal/raised FSH and LH
- oestrogen deficiency
```
ovarian failure (group 3)
e.g. menopause
```
64
first line for patient with PCOS seeking fertility treatment
clomifine citrate (increase FSH and LH secretion)
65
what is a progesterone challenge test?
- give patient progesterone then stop giving it
- this should induce a withdrawal bleed
- no withdrawal bleed suggests low oestrogen as no lining thickening occurring e.g. in hypothalamic hypogonadism
66
what is hydrosalpinx?
when fallowing tube becomes blocked and fills with serous fluid
67
mechanism of metformin
- decreases hepatic gluconeogenesis
- increases peripheral glucose uptake (up-regulates insulin signalling)
- reduces carbohydrate absorption
- increases fatty acid oxidation
68
examples of sulphonylureas
- gliclazide (long acting)
| - tolbutamide (short acting)
69
mechanism of sulphonylureas
- displace ADP-Mg2+ from SUR1 subunit of KATP channel
- KATP channel closes which allows beta cell to depolarise
- depolarisation stimulates insulin release
70
example of Thiazolidinediones (TZDs)
-piaglitazone
| glitazones
71
Mechanism of TZDs
- activates PPAR gamma
- PPAR gamma is an transcription factor for insulin signalling and lipid metabolism proteins
- so enhances action of insulin
72
when are TZDs used?
why might they not be so helpful?
-add on to metformin in T2DM
- weight gain!
- hepatotoxicity
- fluid retention (don't use in those with poor renal function)
- increased fracture risk
73
Examples of SGLT2 inhibitors
- dapagliflzin
- canagliflozin
- empagliflozin
74
where do SGLT2 inhibitors act on kidney?
- sodium glucose transport protein 2
| - proximal tubule
75
examples of DPP-4 inhibitors
-sitagliptin
| gliptins
76
mechanism of DPP-4 inhibitors
- after meal GLP1 and GLP2 released to stimulate release of insulin
- DDP-4 inhibitors stop GLP proteins being broken down so they have prolonged action
77
examples of GLP-1 receptor agonists
- extenatide
- liraglutide
note: must be given sub cut
78
GLP-1 receptor agonists mechanism
- mimic action of GLP1
- GLP1 stimulates insulin secretion
- longer lasting than endogenous GLP1 as resistant to DPP-4 enzyme
79
Which diabetic meds cause weight gain?
- sulphonylureas
- pioglitazone
- insulin
80
which diabetic meds cause weight loss
- metformin (only sometimes)
| - SGLT2 inhibitors
