endocrinology Flashcards
(355 cards)
1
Q
what are the anterior pituitary hormones
A
GH
FSH/LH
TSH
prolactin
ACTH
2
Q
what happens in primary hypothyroidism
A
T3 and T4 decrease
TSH increase
3
Q
what happens in secondary hypothyroidism
A
TSH decrease
T3 and T4 decrease
4
Q
what happens in primary hypoadrenalism
A
cortisol decrease
ACTH increase
5
Q
what happens in secondary hypoadrenalism
A
ACTH decrease
cortisol decrease
6
Q
suggest a cause of secondary hypoadrenalism
A
pituitary tumor damage corticotrophs, cannot make ACTH
7
Q
suggest a cause of primary hypoadrenalism
A
desrtcution fo adrenal cortex (eg autoimmune)
8
Q
suggest a cause of secondary hypothyroidism
A
pituitary tumor damage thyrotrophs
9
Q
suggest a cause of primary hypothyroidism
A
autoimmune destruction of thyroid gland
10
Q
what happens in primary hypogonadism
A
decrease oestrogen/testosterone
increase FSH and LH
11
Q
what happens in secondary hypogonadism
A
decrease FSH/LH
decrease oestrogen/testosterone
12
Q
suggest a cause of primary hypogonadism
A
destruction of testis (mumps) or ovaries (chemo)
13
Q
suggest a cause of secondary hypogonadism
A
pituitary tumor damage gonadotrophs
14
Q
congenital causes of hypopituitarism
A
mutations of transcirption factor
deficient in GH and at least 1more anterior pituitary hormone
15
Q
acquired causes of hypopituitarism
A
tumors, radiation, paituitary surgery, infection, traumatic brain injury
16
Q
what is the name of total loss f anterior and posterior pituitary function
A
panhypopituitarism
17
Q
why radiotherapy can cause radiotherapy induced hypopituitarism
A
pituitary and hypothalamus are both sensitive to radiation
18
Q
which hormones are most sensitive to radiotherapy
A
GH and gonadotrophins
19
Q
what is sheehan’s syndrome
A
post-partum hypopituitarism secondary to hypotension
may lead to pituitary infarction
20
Q
symptoms of Sheehan’s syndrome
A
lethargy, anorexia, weight loss, failure of lactation (PRL deficiency), posterior pituitary usually not affected, failure to resume menses post delivery, TSH/ ACTH/ GH deficiency
21
Q
how to radiologically visualise pituitary gland
A
MRI
22
Q
what is pituitary apoplexy
A
bleeding into pituitary
may be first presentation of pituitary adenoma
23
Q
symptoms of pituitary apoplexy
A
sudden onset headache
visual field detected
bitemporal hemianopia
diplopia (double vision)
ptosis(drop eyelid)
24
Q
what are biochemical ways to diagnosis hypopituitarism
A
9am cortisol
T4
FSH/LH
GH/ACTH
25
how to test ACTH and GH for hypopituitarism
insulin induced hypoglycaemia, cause GH and ACTH release (measure cortisol)
TRH stimulates TSH release
GnRH stimulates FSH and LH release
26
which anterior hormone cannot be replaced
PRL
27
what is the treatment for GH deficiency
daily injection (no oral option)
measure response by improvement in QoL and plasma IGF-1
28
what treatment for TSH deficiency for both primary and secondary hypopituitarism
daily T4 (levothyroxine) once
aim for fT4 above middle of reference range
cannot use this to adjust dose in secodnary hypopituitarism as TSH is low
29
what treatment for ACTH deficiency
replace cortisol rather than ACTh
prednisolone or hydrocortisone (replacement steroids)
30
which group of patients are at risk of adrenal crisis
pt with priamry adrenal failure (Addison's) or secodnary adrenal failure (ACTH defiicency)
31
features of adrenal crisis
dizzy
hypotension
vomit
weakness
collapse and death can be resulted
32
what are sick day roles for pt who take replacement steroid
steroid alert bracelet
double glucocorticoid dose if fever
unable to take tablets, inject or go A&E
33
treatment for FSH/LH deficiency in men with no fertility required
replace testosterone (as this does not restore sperm production, which is dependent on LH and FSH)
measure plasma testosterone
34
treatment for FSH/LH deficiency in men with fertility required
introduction of spermatogenesis by gonadotrophin injections
best response if secondary hypogonadism occurs after puberty
measure testosterone and semen analysis
35
treatment for FSH/LH deficiency in women with no fertility required
replace oestrogen (oral or topical)
need additional progestogen if intact
uterus to prevent endometrial hyperplasia)
36
treatment for FSH/LH deficiency in women with fertility required
induce ovulation by carefully timed gonadotrophin injections (IVF)
37
what are posterior pituitary hormones
oxytocin
AVP
38
function of AVP
stimulate water reabsorption
vasoconstrictor via V1 receptor
stimulates ACTH release from anterior pituitary
39
which receptor does AVP act on to stimulate water reabsorption
V2 receptor in kidney
40
how to visualise posterior pituitary
MRI
posterior bright spot
41
what are the 2 problems with AVP not working
AVP-D
AVP-R
42
what is AVP-D
cranial diabetes insipidus
problem with hypothalamus/posterior pituitary
unable to make AVP
43
what is AVP-R
nephrogenic diabetes insipidus
can make AVP normally but kidney/collecting duct not responding
44
what are the presentations of AVP-R or AVP-D
polyuria
nocturia
thirst
polydipsia
45
how can AVP-D / AVP-R cause death
polydipsia then dehydration then death
46
causes of AVP-D
acquired:
traumatic brain injury
pituitary surgery
pituitary tumors
inflammation of pituitary stalk eg TB
autoimmune
congenital rarer than acquired
47
causes of AVP-R
congenital:
mutation in gene encoding V2 receptor
acquired:
drugs (eg lithium)
48
what are the plasma presentations for AVP-R / AVP-D
increased concentration as pt becomes dehydrated
increase sodium
glucose normal
49
how psychogenic polydipsia mimic AVP -D or AVP-R
also have polydipsia, polyuria, nocturia
but not problem with AVP
symptoms arise from drinking too much
50
how to distinguish between psychogenic polydipsia and AVP-R AVP-D
water deprivation test
over time measure urine vol and conc and plasma conc
51
why do we needa weigh in water deprivation test
if lose >3% body weight it is a marker for AVP-R or AVP-D
52
how to distinguish AVP-D and AVP-R
give desmopressin
(works similar to AVP)
AVP-D responses to desmopressin so urine concentrates but AVP-R no increase in urine osmolarity as kidney don't respond
53
treatment for AVP-D
replace AVP using desmopressin selective for V2 receptor
(tablets or intranasal)
54
what is syndrome of Inappropriate ADH (SIADH)
too much AVP, reduced urine output
55
presentations of SIADH
high urine osmolarity
low plasma osmolarity
low plasma sodium
56
causes of SIADH
CNS (head injury, stroke, tumor)
lung infections pneumonia)
malignancy (lung cancer small cell)
drug related (anti-depressants, anti-epileptics)
idiopathic
57
management of SIADH
fluid restrict
use vasopressin receptor antagonist (but expensive)
58
which 2 hormones increase serum calcium
PTH
Vitamin D
59
which hormone reduce serum calcium
calcitonin
60
steps for Vit D metabolism
7-dehydrocholesterol -> pre vitamin D3 -> Vit D3 -> 25(OH)cholecalciferol via 25 hydroxtlase -> 1,25(OH)2 cholecalciferol via 1 alpha hydroxylase -> calcitriol (Vit D)`
61
effect of Calcitriol
bones: increase Ca2+ and PO4 3- reabsorption
kidney: increase Ca2+ and PO4 3- reabsorption
gut: increase Ca2+ and PO4 3- absorption
62
effect of PTH
bones: binds to osteoblast to signal osteoclast to cause bone resoprtion to increase Ca2+ resorption from bone to bloodstream
kidney: increase Ca2+ reabsorption, increase PO4 3- excretion thru urine, increase 1 alpha hydroxylase activity to increase Calcitriol
gut: increase Ca2+ and PO4 3- absorption
63
effect of FGF23 to regulate serum phosphate
FGF23 inhibit phosphate transporter / reabsorption in kidney
reduce phosphate reabsorption thru gut
PTH also inhibits reabsorption of Phosphate thru blocking Na+/PO4 3- co-transporter
64
symptoms of hypocalcaemia
sensities excitable tissues
muslce cramps
tetany
tingling
paraesthesia
convulsions
arrhythmias
65
what are the 2 signs caused by hypocalcemia
chvosteks' sign (facial paresthesia, twitch infacial msucle when gently tapping on patient's cheek bone))
trousseau's sign (carpopedal spasm, contract without relaxing)
66
causes of hypocalcaemia
hypoparathyroidism - low PTH level(surgical neck surgery, auto-immune, congenital)
low Vit D (deficiency, lack UV, impaired production due to renal failure)
67
symptoms of hypercalcaemia
CNS, GI, Psych effects
reduced neuronal excitability (atonal muscle), stones, abdominal moans, psychic groans
68
causes of hypercalcaemia
hyperparathyroidism
malignancy
XS Vit D
69
what happens in primary hyperparathyroidism
Ca increase, but PTH still high, so low phosphate as well
(no negative feedback)
due to parathyroid adenoma producing too much PTH
70
treatment for primary hyperparathyroidism
parathyroidectomy
71
risks of parathyroidectomy
osteoporosis (cause reduce BMD, increase risk of fractures)
renal calculi (stones)
psychological impact(mood, mental function)
72
what happens in secondary hyperparathyroidism
normal physiological response to hypocalcaemia
low Ca, high PTH
73
causes of secondary hyperthyroidism
Vit D deficiency
renal failure -> cannot make calcitriol
74
treatment for secondary hyperparathyroidism in normal patients
Vit D replacement
- ergocalciferol
- cholecalciferol
can give as patient can convert this to calcitriol via 1 alpha hydroxylase
75
treatment for secondary hyperparathyroidism in renal failure patients
give alfacalcitriol (active Vit D) as patients hv inadequate 1 alpha hydroxylase, cannot activate 25 hydroxy Vit D preparations
76
what happens in tertiary hyperparathyroidism
initially Ca falls and PTH rises, but overtime high PTH drives enlarged parathyroid gland to increase Ca
chronic renal failure
chronic Vit D deficiency
cammot make calcitriol, PTH increases
Parathyroid gland enlarge
77
treatment for tertiary hyperparathyroidism
parathyroidectomy
78
how to diagnose hypercalcaemia
check PTH
79
what happens in hypercalcaemia malignancy
high Ca
suppressed PTH
80
how to diagnose Vit D deficiency
low calcium
high PTH (secondary to low Ca)
81
how do we measure Vit D
measure 25 (OH) cholecalciferol (as calcitriol is difficult to measure)
82
does PTH stimulate osteoblast or osteoclast
osteoblast
83
what are some osteoclast activating factor
RANKL, receptor activator of nuclear factor kappa-B ligand
84
what inhibits bone resportion in osteoclast
bisphosphonates
85
what is crytorchidism
failure of one or both testes to descend into the scrotum
most stay in inguinal canal
86
what is endometriosis
presence of functioning endometrial tissue outside of uterus
87
symptoms of endometriosis
increase menstrual pain
menstrual irregularities
deep dyspareunia (pain before/during/after sex)
infertility
88
what is fibroids
benign myometrium tumors
89
symptoms of fibroids
usually asymptomatic
increase menstrual pain
menstrual irregularities
deep dyspareunia
infertility
90
causes of endocrine male infertility in hypothalamus (3)
congenital hypogonadotrophic hypogonadism
acquired hypogonadotrophic hypogonadism
hyperlactinaemia
91
what happens in hypogonadotrophic hypogonadism in hypothalamus
decrease GnRH
decrease LH & FSH
decrease T / E2
92
causes of endocrine male infertility in pituitary
hypopituitarism (tumor, infiltration, apoplexy, surgery, radiation)
93
what happens in hypogonadotrophic hypogonadism in anterior pituitary gland
decrease LH & FSH
decrease T / E2
94
causes of endocrine male infertility in gonads
congenital pituitary hypogonadism
(Klinefelters)
acquired pituitary hypogonadism (cryptorchidism, trauma, chemo,radiation)
95
what happens in hypergonadotrophic hypogonadism in gonads
increase LH &FSH
decrease T / E2
96
what is Kallmann Syndrome
failure of migration of GnRH neurons with olfactory fibres, accompanied with failure of puberty and infertility
97
how hyperprolactinaemia affect HPA
prolactin binds to prolactin receptors on kisspeptin neurones
inhibit kisspeptin release
decrease GnRH, LH, FSH, Tor O
inferitility, oligo, amenorrjea
98
symptoms of klinefelters syndrome
tall stature
decrease facial hair
breast development
small penis and testes
mildly impaired IQ
narrow shoulders
reduced chest hair
wide hips
low bone density
infertility
99
what are the key hx for male infetility
duration
previous children
pubertal milestones
associated symptoms
100
what are the key examination of male infertility
BMI
sexual characteristics
testicular vol
anosmia
101
key investigations of male infertility
semen analysis
blood tests
imaging
102
treatment for male infertility
dopamine agonist for hyperPRL
gonadotrophin treatment for fertility
testosterone
surgery
optimise BMI
smoking cessation
alcohol reduction/cessation
103
what pattern will u see in premature ovarian insufficiency for FSH LH and oestradiol
increase FSH & LH
decrease oestradiol
104
causes of premature ovarian insufficiency
autoimme
turner's syndrome (genetic)
cancer therapy
105
what pattern will u see in anorexia nervosa induced amenorrhea for FSH LH and oestradiol
all decrease
106
what is PCOS
irregular periods
XS androgen in female
polycystic ovaries enlarged with lots of fluid filled sac surrounding egg
107
PCOS treatment for infertility
ovulation induction (IVF)
108
PCOS treatment for irregular menses/amenorrhoea
oral contraceptive pill
metformin
109
PCOS treatment for increase insulin resistance
metformin
diet/lfiestyle changes
110
PCOS treatment for endometrial cancer risk
progesterone courses
111
PCOS treatment for hirsutism
anti-androgens
creams, laser, waxing
112
Symptoms of Turners Syndrome
short stature
low hairline
shield chest
wide spaced nipples
coarctation of aorta
poor breast development
amenorrhoea
underdeveloped reproductive tract
small fingernails
113
female infertility key hx
duration, previous children, pubertal milestones, menstrual hx, medications
114
female infertility key exams
BMI
sexual characteristics
hyperandrogenism signs
anosmia
115
key investigations for female infertility
blood test
pregnancy test
imaging
116
why in testosterone replacement need at least 2 fasting measurements of serum testosterone in morning
food can decrease testosterone temporarily
117
what are some testosterone replacement safety monitorings
increased Hct (as testosterone increase blood cells)
risk of hyperviscosity and stroke
prostate (prostate specific antigen level)
118
what is secondary hypogonadism
deficiency of gonadotrophins (LH/FSH) --> hypogonadotrophic hypogonadism
119
importance of gonadotrophins (LH, FSH)
induce spermatogenesis
120
function of LH in sperm induction
LH stimualtes leydig cells to increase intratesticular testosterone levels
121
function of FSH in sperm induction
stimulates seminiferous tubule development and spermatogenesis
122
why we should not give testosterone to men desiring fertility
testosterone can further reduce LH/FSH and worsen spermatogenesis
123
what are some treatments for inducing spermatogenesis
hcG injections (act on LH receptors to increase LH)
if no response then FSH injections
124
how letrozole triggers ovulation
letrozole acts on aromatase, cause low oestradiol, decreased -ve feedback , cause higher GnRH and hence increase FSH/LH to induce ovulation
125
where does clomiphene act on to induce ovulation
oestrogen receptor to reduce negative feedback of oestradiol
126
how does oral contraceptive pills work on HPG axis
contains and aim to increase oestrogen and progesterone
1. reduce ovulation in ovaries
2. progesterone cause thickening of cervical mucus
3. cause thinning of endometrial lining to reduce implantation
127
what are some non contraceptive uses for combined oral contraceptive pills
1. make periods lighter and less painful
2. regular withdrawal bleeds or no bleeds
3. reduce LH and hyperandrogenism (acne/hirsutism)
128
what are some long acting reversible contraceptives
1. coils
2. intra-uterine device (copper coil)
3. itranuterine systems to secrete progesterone
progesterone - only injectable contraceptives or subdermal implants
129
what are some emergency contraceptives
copper intrauterine device (IUD)
ulipristal acetate (stops progesterone and prevent ovulation)
levonorgestrel (prevents ovulation)
130
benefits of HRT (menopause hormone treatment)
1. relief symptoms due to low oestrogen (low mood, flushing, disturbed sleep etc)
2. reduction in osteoporosis related fractures
3. transdermal reduce risk of VTE and stroke
4. lower risk of CVD in ypunger
131
risks of HRT
1. venous thrombo embolism
2. pulmonary embolism
3. Hormone sensitive cancer (breast, ovarian)
4. endometrial cancer (must prescribe progesterone in women with endometrium)
5. CVD, stroke
oral will increase clotting factor
transdermal oestrgens are safer for VTE than oral
132
what is precurosr of steroid
cholesterol
133
which part secretes corticosteroids
adrenal cortex
134
example of corticosteroids
mineralcorticoids (aldosterone)
glucocorticoids (cortisol)
sex steroids (androgens, oestrogens)
135
effect of angiotensin ll on adrenals
activate metabolic enzymes to increase corticosteroids production
136
effect of aldosterone
controls BP and sodium
lowers potassium
137
activation of enzymes ti form aldosterone
side chain cleavage
3 hydrosteroid dehydrogenase, 21,11,18 hydroxylase
138
activation of enzymes to form cortisol
3,17,21,11
139
what rhythm does cortisol have
diurnal
140
what is Addison's disease
primary adrenal failure
autoimmune, immune system destroys adrenal cortex
141
what happens in Addison's
pituitary secretes lots of ACTh hence MSH , so skin has hyperpigmentation
142
symptoms of Addison's
hyperpigmentation in skin
low BP
weakness
weight loss
vitiligo
n+v
diarrhea
constipation
abdominal pain
143
what is pro-opio-melanocortin (POMC)
POMC is large precursor of protein cleaved to form smaller peptides eg ACTH, MSH, endorphines
high levels of ACTh become tanned in pt
144
causes of adrenocorticoid failure
adrenal glands destroyed
missing enzymes in steroid synthetic pathway
tuberculosis addison's disease
autoimmune addison's disaese
congential adrenal hyperplasia
145
consequecnes of adrenocorticoid failure
BP fall
loss salt in urine, low NA in plasma (hyponatraemia)
increased plasma potassium(less potassium excreted in urine)
low glucose due to glucocorticoid deficiency
high ACTH cause increased pigmentation
death due to severe hypotension
146
tests of addison's
9am cortisol
clincial:fatigue
blood tests: biochem (low Na, high K)
high ACTH
short synACTHen test
147
primary adrenocorticoid failure treatments
repalce cortisol and aldosterone
no need to replace adrenal sex steroids (gonads)
148
why use fludrocortisone than aldosterone for primary adrenocortical failure
half life of aldosterone too short for safe once daily administration, fludrocortisone longer acting
149
what is congenital adrenal
hyperplasia
21-hydroxylase deficiency
(can be complete or partial)
150
which hormone will be totoally absent in complete 21-hydroxylase deficiency
aldsterone and cortisol
151
how long can babies survive in complete 21-hydroxylase deficiency
babies present within 1-3 weeks with a salt losing crisis
152
which hormones will be in excess in complete 21-hydroxylase deficiency
sex steroids (androgens, estrogens and progestogens.)
and testosterone
153
which hormones will be in deficient in partial 21-hydroxylase deficiency
cortisol and aldosterone
154
which hormones will be in excess in partial 21-hydroxylase deficiency
sex steroids and testosterone
155
main problem in girls in partial 21-hydroxylase deficiency
hirsutism
virilisation
156
what happens in 11 hydroxylase deficiency
accumulate of 11-deoxycorticosteroe
not enough cortisol to inhibit ACTH
chronic adrenal overactivity
157
which hormone does 11 deoxycorticosterone behave like
mineralocorticoid
158
what happens to excess aldosterone / 11 deoxycorticosterone
hypertension
hypokalaemia
159
which hormones will be in deficient in 11-hydroxylase deficiency
cortisol
aldosterone
160
which hormones will be in excess in 11-hydroxylase deficiency
sex steroids
testosterone
11-deoxycorticosterone
161
what problems are in 11-hydroxylase deficiency
virilisation
hypertension
hypokalaemia
162
which hormones will be in deficient in 17-hydroxylase deficiency
cortisol
sex steroids
163
which hormones will be in excess in 17-hydroxylase deficiency
aldosterone
11 deoxycorticosterone
164
what problems are in 17-hydroxylase deficiency
hypertension
hypokalaemia
sex steroids deficiency
cortisold deficiency
165
clinical features of Cushing's
centripetal obesity
moon face
buffalo hump
proximal myopathy
hypertension
hypokaelemia
red striae
thin skin
bruising
osteroporosis
diabetes
166
role of 11B-hydroxysteroid dehydrogenase
stops cortisol from activating aldosterone receptors
turns cortisol to cortisone (inactive form)
167
causes of Cushing's
take too many steroids
pituitary dependent (cause Cushing's disease)
ectopic ACTH from lung cancer
adrenal adenoma secretes cortisol
168
tests to determine cause of Cushinhg's syndrome
24hr urine collection for urinary free cortisol
blood diurnal cortisol levels (highest at 9am and lowest at midnight if asleep)
low dose dexamethasone suppresion test
169
what happens to the rhythm of cortisol in cushings
high all the time
170
what is dexamethasone
artificial glucocorticoid (steroid)
171
how healthy people and Cushing's pt respond to dexamethasone
healthy: suppress cortisol to 0
Cushing's : fail to suppress cortisol
172
what are some pharmaclogical manipiulation of steroids
enzyme inhibitors
receptor blockign drugs
173
what is metyrapone
inhibit steroid biosynthesis
11B-hydroxylase inhibitor
174
what is the mechanism of metyrapone
inhibit 11B-hydroxylase
arrest steroid synthesis in zona fasciculata and reticularis at 11-deoxycortisol stage
11-deoxycortisol has no negtaive feedback on hypothalamus and pituitary gland
175
what are the uses of metyrapone
control cushing's syndrome prior to surgery
improve pt symptoms and promote better post-op recovery
control cushing's symptoms after radiotherapy
176
unwanted side effects on metyrapone
hypertension on long term administration
hirsutism
177
mechanism of ketoconazole
inhibit 17-hydroxylase
use as antifungal agent
at higher conc inhibits steroidogenesis
178
uses of ketoconazole
treatment and control cushing's symptoms prior surgery
orally active
179
unwanted side effects of ketoconazole
liver damage
180
mechanism of osilidrostat
inhibit 11&17 hydroxylase
block several enzyme in steroid synthetic pathway
181
what are some surgical treatment of cushing's
pituitary surgery
bilateral adrenalectomy
unilateral adrenalectomy for adrenal mass (for single adrenal tumor)
182
medical treatment for cushing's
metyrapone
ketoconazole
osilidrostat
183
what is conn's syndrome
benign adrenal cortical tumor
aldosterone in XS
hypertension and hypokalaemia
184
what are the action of aldosterone
increase renal sodium and potassium reabsorption
increase BP (sodium and water retention)
185
how to diagnose Conn's syndrome
primary hyperaldosteronism
RA system should be suppressed
186
what are medixal treatments for Conn's Syndrome
Mineralocorticoid antagonist
spironolactone
eplerenone
187
mechanism of spironolactone
competitive antagonist of mineralocorticoid receptor
blocks Na+ reabsorption and K+ excretion in kidney tubules
188
unwanted side effects of spironolactone
gynaecomastia (androgenr eceptor)
189
mechanism of epleronone
MR antagonist
similar affinity to MR compared to spironolactone
less binding to androgen and receptors compared to spironolactone, better tolerated
190
what are phaeochromocytomas
adrenal tumors in medulla to secrete catecholamines
191
clinical features of phaeochromocytomas
hypertension in young ppl
episodic severe hypertension, cause stroke or MI
more common in certain inherited conditions
high adrenaline may cause ventricular fibrillation and death
192
treatment of phaeochromocytomas
alpha blocker
pt may need IV fluid as alpha blockade commences
beta blockade to prevent tachycardia
193
what are the anterior pituitary cells and their respective hormones (5)
somatotrophs-- GH
lactotrophs -- prolactin
Thyrotrophs -- TSH
gonadotrophs -- FSH/LH
corticotrophs -- Adrenocorticotrophic hormone (ACTH, corticotrophin)
194
what are the anterior pituitary tumors (5)
somatotrophs -- acromegaly
lactotrophs -- prolactinoma
thyrotrophs -- TSHoma
Gonadotrophs -- gonadotrophinoma
corticotrophs -- cushing's disease (corticotroph adenoma)
195
how to classify pituitary tumor (3)
radiological (MRI)
function
benign or malignant
196
how to classify pituitary tumor in terms of radiological MRI
size (microadenoma < 1cm and macroadenoma)
sellar or suprasellar
compress optic chiasm or not
invade cavernous sinus or not
197
how to classify pituitary tumor in terms of function
excess secretion of specific pituitary hormone or not
if no excretion -- non functioning adenoma
198
what is the most common functioning pituitary adenoma
prolactinoma
serum of prolactinoma con proportional to tumor size
199
presentations of prolactinoma
menstrual disturbance
erectile dysfunction
reduced libido
galactorrhoea
subfertility
200
physiological causes of elevated prolactin
pregnancy
breastfeeding
streess
venepuncture
nipple stimulation
201
pathological causes of elevated prolactin
primary hypothyroidism
PCOS
chronic renal failure
202
iatrogenic causes of elevated prolactin
antypsychotics
SSRIs
anti emetics
high dose oestrogen
opiates
203
treatment of prolactinoma
first line: medical
doopamine receptor agonists
cabergoline
204
how does dopamine receptor agonists work
dopamine from hypothalamic dopaminergic neurones/ D2 receptor agonists bind to D2 receptors on anterior pituitary lactotrophs
inhibit release of prolactin
205
mechanisms of GH action
somatotrophs release GH--> stimulate body tissues / stimulate liver to release IGF-1 and IGF-2 to stimulate body tissues --> stimualte growth and development
206
how to diagnose acromegaly
elevated serum IGF-1
oral glucose tolerance test -- failed suppression of GH following oral glucose load
once confirmed GH XS, use MRI to confirm pituitary tumor
207
what risk is associated with untreated acromegaly
cardiovascular risk
208
treatment for acromegaly
first line: surgical (trans-sphenoidal pitutiary surgery)
use medical (somatostatin analogues, dopamine agonists) prior to surgery to shrink tumor or if surgical resection incomplete
209
what is pattern of GH secretion
pulsatile -- random measurement unhelpful to diagnose acromegaly
210
Cushing's syndrome symptoms
osteoporosis
red cheeks
moon face
impaired glucose tolerance
proximal myopathy
easy bruising\thin skin
mental changes
211
what is ACTH dependent Cushing's disease
pituitry corticotroph adenoma
212
what is ACTH independent Cushing's syndrome
taking steroids by mouth
adrenal adenoma or carcinoma
213
what are non functioning pituitary adenomas
don't secrete any specific hormone
214
which symptom is often present in non functioning pituitary adenomas
visual disturbance
bitemporal hemianopia
215
why serum prolactin will raise in non functioning pituitary adenomas
dopamine cannot travel down pituitary stalk from hypothalamus
216
in primary hypothyroidism, what is the level of TSH
high, because lack thyroxine to suppress
217
what is Graves' Disease
autoimmune, hyperthyroidism
Ab binds and stimulate TSH receptor
cause goitre
218
what symptoms seen in Graves' Disease
goitre
exophthalmos cuz other Ab bind to muscles behind the eyes
pretibial myxoedema
219
why goitre in Graves' Disease
Ab binds to and stimulate TSH receptor in thyroid
220
is toxic nodular thyroid disease autoimmune
No
221
what is toxic nodular thyroid disease
single / mulyiple toxic nodules (multinodular goitre)
benign adenomas overactive at making thyroxine
222
what are the symptoms difference in Graves' and toxic nodular thyroid disease
in toxic nodular thyroid disease there is no pretibial myxoedema and no exophthalmos
223
what are the effects of thyroxine on SNS
Sympathetic activation -- sensities beta adrenoceptors to ambient levels of adrenaline and Noradrenaline
tachycardia
palpitations
tremor in hands, lid lag
224
symptoms of hyperthyroidism
weight loss despite increased appetite
breathlessness
palpitations
tachycardia
sweating
heat intolerance
diarrhoea
lid lag
225
what is thyroid storm
when someone with hyperthyroidism has more than 2 below features
hyperpyrexia (> 41 degrees celcius)
accelerated tachycardia
arrhythima
cardiac failure
delirium
frank psychosis
hepatocellular dysfunction
jaundice
226
treatment options for hyperthyroidism
surgery (thyroidectomy)
drugs
radioiodine
227
what are the drug classes for treatment in hyperthyroidism
thionamides (anti thyroid drugs)
potassium iodide
radioiodine
B-blockers (help w symptoms)
228
mechanism of thionamides
inhibit thyroid peroxidase and hence reduce T3/T4 synthesis and secretion
229
unwanted effects of thionamides
agranulocytosis
rashes
230
follow up actions after using thionamides
aim to stop anti thyroid drug after 18 months
need review periodically including thyroid function tests for remission or relapse
231
what is the role of B blockers in thyrotoxicosis
reduce tremor, slower HR, less anxiety
232
mechanism of KI in hyperthyroidism
inhibits iodination of thyroglobulin
inhibits peroxide generation and thyoperoxidase
233
problems with thyroidectomy
risk of voice change (recurret laryngeal nerve)
risk of losing parathyroid glands
scar
anaesthetic
234
examples of Beta blockers for hyperthyroidism
propranolol
235
examples of anti thyroid drug
carbimazole
propylthiouracil
236
what is viral (de Quervain's) thyroiditis
painful dysphagia
hyperthyroidism
pyrexia (fever)
thyroid inflammation
237
pathology of viral thyroiditis
virus attack thyroid gland
causing pain and tenderness
thyroid stops making thyroxine and makes virus instead
thus no iodine uptake
causing stored thyroxine released
4 weeks later stored thyroxine exhausted
hypothyroid
238
what is T1DM
autoimmune
partial or complete deficiency of insulin production
239
which type of DM can present in later life
autoimmune diabetes
latent autoimmune diabetes
240
which type of DM can present in childhood
T2DM
241
why T1DM may present later
orig may hv fully functioning B cells to secrete insulin until autoimmune attack
--> ketoacidosis
242
what is C-peptide
product when proinsulin cleaved to insulin
243
symptoms of diabetes
polyuria
nocturia
polydypsia
blurring of vision
recurrent infections
weight loss
fatigue
244
signs of diabetes
dehydration
hyperventilation
smell of ketones
glycosuria
ketonuria
245
what are the effects of insulin deficiency metabolically
proteinolysis
increase hepatic glucose output
lipolysis to increase glycerol and NEFA
246
acute complication of hyperglycaemia
diabetic ketoacidosis
247
chronic complication of hyperglycaemia
microvascular (retinopathy, neuropathy, nephropathy)
macrovascular (ischaemia heart disease, cerebrovascular disease, peripheral vascular disease)
248
management of T1DM
insulin
dietary support
educations
technologies
transplantation
249
why insulin level never drops to 0
need insulin to prevent cascade of breaking down fat, to prevent ketoacidosis
250
what are types of short acting insulin
human insulin (exact molecular replicate of human insulin)
insulin analogue
251
what are types of long acting insulin
bound to zinc or protamine
insulin analogue
252
253
relationship between cortisol and insulin
cortisol levels become elevated and you become insulin resistant
254
what are transplantation options of T1DM
islet cell transplants
simultaneous pancreas and kidney transplants
(both requires life-long immunosuppression)
255
what is HbA1c
glycated Hb
256
what can HbA1c reflect
reflect last 3 months of glycaemia
biased to the 30 days preceding measurement
irreversible reaction
257
acute complication from T1DM
diabetic ketoacidosis
uncontrolled hyperglycaemia
hypoglycaemia (from treatment)
258
is diabetic ketoacidosis a life threatening complication
yes
259
risks of hypoglycaemia
seizure
coma
death
impacts on day to day function, cognition and driving
260
risk factors of hypoglycaemia
exercise
missed meals
inappropriate insulin regime
alcohol intake
lower HbA1c
lack training ard dose adjustment for meals
261
how to support problematic hypoglycaemia
insulin pump therapy
try diff insulin analogues
education
transplantation
262
acute management for hypoglycaemia for alert and orientated patients
oral carbs
rapid acting (eg juice, sweet)
longer acting (sandwich)
263
acute management for hypoglycaemia for drowsy/confused but swallow intact patients
buccal glucose
glucogel
comple carbs
264
acute management for hypoglycaemia for unconscious or concerned abt swallow patients
IV access
20% glucose IV
265
what is T2DM
combination of insulin resistance and beta cell failure
266
when can T2DM present
young / young adult
267
what is the normal bgl in fasting state
4-5.9, under 7.8
268
what is the normal bgl in 2hrs of eating
4-7.8
269
what is the normal bgl in random
below 6.9
270
what is relative deficiency of insulin in T2DM
insulin produced by pancreatic beta cells but not enough to overcome insulin resistance
271
when does ketones form
when there's no insulin
272
why there is no ketosis in T2DM
there's still insulin, but may still hv DKA when unwell eg infection/sepsis
273
what happens in long duration of T2DM
beta cell failure progress to complete insulin deficiency
274
why in T2DM there is high bgl (2 reasons metabolically)
1. reduced insulin action causes less uptake of glucose into skeletal muscle
2. increase Hepatic glucose production as there is reduced insulin action and increase in glucagon action
275
consequences of insulin resistance in liver
increase hepatic glucose output
276
consequences of insulin resistance in myocytes
less glucose uptake by muscle
277
consequences of insulin resistance in adipocytes
increase fatty acid uptake from gut
increase fatty acid production
triglyceride from unhealthy types of lipid
278
what is a major risk for T2DM
obesity
279
T2DM presentations
hyperglycaemia
overweight
dyslipidaemia
fewer osmotic symptoms
insulin resistance
later insulin deficiency
280
risk factors for T2DM
age
BMI
PCOS
family Hx
inactivity
ethnicity
281
association with T2DM and gut microbiota
bacterial lipopolysaccharides fermentation to short chain FA, bacterial modulation bile acids
inflammation, signalling metabolic pathways
282
first line diagnosis of T2DM
HbA1c+1 symotoms
or with 2 x HbA1c >/= 48mmol/mol
283
acute presentation of complication of T2DM
hyperosmolar hyperglycaemic state
284
chronic presentation of complication of T2DM
ischaemic heart disease
retinopathy
285
what is hyperosmolar hyperglycaemic state
presents commonly with renal failure
insufficient insulin for prevention of hyperglycaemia but sufficient insulin for suppression of lipolysis and ketogenesis
286
management for hyperosmolar hyperglycaemic state
give gluids slowly
287
risk of hyperosmolar hyperglycaemic state
slowly get very hyperglycaemic
super dehydrated
288
management of T1DM
exogenous insulin
self monitoring of glucose
education
289
management of T2Dm
diet
oral meds
education
may need insulin later
290
prevention diabetes - related complications and their risk factor
retinopathy
neuropathy
nephropathy
cardiovascular
291
what are prinicples of T2DM consultation
HbA1c
weight
cholesterol level
BP
screen for complications (foot check, retinal screening)
292
which drug helps to address XS hepatic glucose production
(and the drug's strategy)
metformin
helps reduce hepatic glucose production
293
which drug helps to address resistance to action of circulating insulin
(and the drug's strategy)
metformin
Thiozolidinediones
(improve insulin sensitivity)
294
which drug helps to address inadequate insulin production for extent of insulin resistance
(and the drug's strategy)
Sulphonylureas
DPPG4-inhibitors
GLP-1 agonsits
(boost insulin secretion)
295
which drug helps to addressXS glucose in circultion
(and the drug's strategy)
alpha glucosidase inhibitor
SGLT-2 inhibitor
(inhibit carbohydrate gut absorption and renal glucose resorption)
296
what is metformin's mechanism of action
insulin sensitiser, oral
reduce insulin resistance
reduce HGO
increase peripheral glucose disposal
297
side effects of metformin
GI side effects
contraindicated in severe liver, cardiac or renal failure
298
what is sulphonylureas' mechanism of action
bind to ATP sensitive potassium channel and close it
boost insulin production of B-cells
independent of glucose or ATP which both are needed for normal insulin production
299
what is pioglitazone's mechanism of action
insulin sensitiser mainly peripheral
300
side effects of pioglitazone
HF
hepatitis
301
GLP-1 mechanism of action
stimulates insulin
suppress glucagon
increase satiety
302
what is GLP-1, where is it secreted
gut hormone
secreted in response to nutrients in gut
transcription product of pro-glucagon gene mostly from L-cell
303
example of GLP-1 agonist
liraglutide
semaglutide
304
function of GLP-1 agonist
decrease conc of glucagon and glucose
weight loss
305
example of DPPG-4 inhibitor
gliptins
306
function of DPPG-4 inhibitor
increase half life of exogenous GLP-1
increase conc of GLP-1
decrease conc of glucagon and glucose
neutral on weight
307
mechanism of SGLT-2 inibitor
inhibits Na-Glu transporter
increase glycosuria
lower HbA1c
308
what are some microvascular complications for DM
retinopathy
nephropathy
neuropathy
309
what are some macrovascular complications for DM
cerebrovascular disease
ischaemic heart disease
peripheral vascular disease
310
which complication is associated with HbA1c and BP
microvascular
positive correlation
311
factors related to microvascular complications
duration of diabetes
smoking ( endothelia dysfunction)
genetics
hyperlipidaemia
hyperglycaemic memory (inadquate glucose control earlier can result in higher risk)
312
what are the mechanism leading to microvascular complication
activation of inflammatory pathways --> damage endothelium --> leaky capillaries, ischaemia
313
what are the 4 types of retinopathy and maculopathy
background retinopathy
pre-proliferative retinopathy
proliferative retinopathy
diabetic maculopathy
314
what happens in background retinopathy
hard exudates (yellow spots)
microaneurysm
blot haemorrhages
315
what happens in pre-polferative retinopathy
cotton wool spots / soft exudates
represent retinal ischaemia
316
what happens in proliferative retinopathy
visible new vessels on disc or elsewhere in retina
these new vessels will bleed v. early, lead to haemorrhage
317
what happens in maculopathy
hard exudates / oedema near macula
same as background retinopathy but nearer to macula
can threaten vision
318
treatment for background retinopathy
continue annual surveillance
319
treatment for pre-proliferative retinopathy
early panretinal photocoagulation
320
treatment for proliferative retinopathy
panretinal photocoagulation
321
treatment for maculopathy
if oedema: anti-VEGF injections directly into eye
frid photocoagulation
322
what are we looking at when doing annual urine sample for diabetics
albumin:creatinine ration (ACR)
323
what false positives may hv in urine ACR
fever
urine infection
324
mechanism of diabetic nephropathy
diabetes --> hyperglycaemia and hypertension --> glomerular hypertension increase --> proteinuria -> glomerular ad intestinal fibrosis -> glomerular filtration rate decline -> renal failure
325
mechanism of renin angiotensin system
liver release angiotensinogen - renin from kidney change angiotensinogen to angiotensin l -> ACE change it to angiotensin ll
326
effects of angiotensin ll
vasoconstrictor
stimulate aldosterone to release in adrenal cortex
lead to hypertension
327
how to block RAS to reduce BP and progression of diabetic nephropathy
block with ACE inhibitor or angiotensin 2 receptor blocker
328
management of diabetic nephropathy
optimise glycaemic control and BP (HbA1c and BP)
start SGLT-2 inhibitor if T2DM
stop smoking
329
what happens in diabetic neuropathy
small vessels supplyign nerves are called vasa nervorum
vasa nervorum blocked -> lower limb amputation
330
why diabetic neropathy more common in feet
longest nerve supply feet
peripheral neuropathy (gloves and stocking distribution)
can be painful
but patients may not sense an injury to the foot
331
risk of diabetic foot ulceration
reduced sensation to feet (peripheral neuropathy)
foot deformity
poor vascular supply to feet (peripheral vascular disease)
332
management for peripheral neuropathy
regular inspection of foot
good footwear
avoid barefoot walking
333
management for peripheral neuropathy with ulceration
offloading
revascularisation if concomitant PVD
orthotic footwear
Antibiotics if infected
334
what is mononeuropathy
sudden motor loss (wrist drop or foot drop)
cranial nerve palsy (double vision due to oculomotor nerve palsy)
335
what is autonomic neuropathy
damage to SNS and PNS nerves (innervating GI tract, bladderm cardiovascualr system)
336
symptoms of autonomic neuropathy
GI: delayed gastric emptying, nausea, vomiting, constipation, nocturnal diarrhoea
cardiovascular: postural hypotension, collapsing on standing, sudden cardiac death
337
how to treat obesity
diet
338
what happens in leptin deficiency
infertility
stunted linear growth
decreased body temp
decreased energy expenditure
decreased immune function
339
importance of leptin
help reduce appetite
control metabolism and energy homeostasis
regulate synthesis of thyroid hormones
decrease glucose-stimulated insulin secretion
increase HR
regulate bone mass and menstrual cycle
activation of immune cells
340
how leptin administration help leptin deficiency children
restore LH pulsatility
increase LH FSH
can go thru normal puberty and reproductive cycle
341
what happens in leptin resistance
fail to signal CNS that we have sufficient fat reserves for normal functioning
342
drugs to treat obesity
orlistat
liraglutide/ Saxenda
343
side effects of orlistat
fatty n oily stool
faecal urgency
faecal incontinence
344
function of GLP-1
reduce appetite and increase satiety
increase insulin reduce glucagon
reduce liver fat and inflammation
reduce insulin resistance
increase NA excretion and diuresis
increase endothelial function
reduce arterial stiffness and inflammation
increase myocardial contractility ad ishcaemic preconditioning
reduce glucose uptake
345
where is GLP-1 from
released from GI tract
a gut hormone
346
what is liraglutide / saxenda
long acting GLP-1 receptor agonist
347
how to administer liraglutide / saxenda
daily injection
double dose for T2DM
348
when to consider bariatric surgery for obese pt
BMI > 40
BMI 35-40 + other comobidities
BMI 30-34.9 for newly diagnosed T2DM
349
what are the common types of bariatric surgery (3)
gastric bypass (top of stomach joined to small intestine, can feel fuller sooner and don't absorb that much calories from food)
gastric band (band placed ard stomach, so don't eat much to feel full)
sleeve gastrectomy (part of stomach removed, cannot eat as much as u could)
350
what is semaglutide and how it works
long acting GLP-1 receptor agonist
cause weight loss
351
what is tirzepatide and how it works
long acting GLP-1 receptor and glucose dependent insulinotropic polypeptide (GIP) receptor co-agonist
352
what is cagrilintide and how it works
long acting amylin analogue
given in combo with semaglutide
353
what is retaturtide and how it works
triple agonist of GIP, GLP-1 and glucagon receptors
354
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