Endo Flashcards
(137 cards)
1
Q
Six hormones produced from the anterior pituitary
A
Growth hormone
Prolactin
TSH
LH
FSH
ACTH
2
Q
How does blood get from the hypothalamus to the anterior pituitary
A
Portal circulation (capillaries on both ends)
3
Q
Difference between primary and secondary failure in the thyroid, adrenal cortex and the gonads?
A
Primary: the gland itself is failing
Secondary: problem / no signals from the hypothalamus or the anterior pituitary
4
Q
How can you tell the difference between primary and secondary hypothyroidism
A
T3 and T4 would fall in both
TSH increases in primary (due to less negative feedback - no problem with the pituitary) but is low in secondary as it can’t be made
5
Q
Primary vs secondary hypoadrenalism
A
Cortisol falls in both but ACTH increases in primary hypoadrenalism but ACTH falls in secondary as it can’t be made
6
Q
Primary vs secondary hypogonadism
A
Primary : testosterone and oestrogen fall, LH & FSH INCREASE
Secondary : LH/FSH fall, testosterone and oestrogen fall
7
Q
Which hormone is affected by hypoadrenalism
A
Cortisol (regulated by ACTH)
Not aldosterone (regulated by renin-angiotensin)
8
Q
Congenital causes of Hypopituitarism
A
Rarely congenital - mostly because of mutations in anterior pituitary transcription factor genes
Hypoplastic anterior pituitary (MRI)
9
Q
Acquired causes of Hypopituitarism (7)
A
Tumours (press on pituitary, pushing it against sella turcica which stops function)
Radiation (check brain function in children with brain tumour)
Infection (meningitis)
Trauma
Pituitary surgery
Hypophysitis (pituitary inflammation) - difficult to diagnose
Pituitary apoplexy (haemorrhage) - small tumour which bleeds causes severe headache
Peri partum infarction
10
Q
Outline the Pathophysiology of Sheehans Syndrome
A
During pregnancy lactotrophs are enlarged however the blood supply to the pituitary remains the same, therefore trauma or haemorrhage during delivery would cause a drop in blood pressure meaning there is decreased blood flow to the pituitary. This causes infarction. (cell death due to hypoxia)
11
Q
What is the total loss of function from both anterior and posterior pituitary called?
A
Panhypopituitarism
12
Q
Hypopituitarism due to radiotherapy?
A
Radiotherapy (direct to pituitary or indirect to CNS tumour)
Higher does - higher risk of HPA axis damage
13
Q
Which hormone axes are most sensitive to radiotherapy?
A
GH
Gonadotrophin (therefore radiotherapy can cause infertility)
Risks persist up to 10 yrs later - annual assessments
14
Q
Presentation of reduced FSH/LH
A
Reduced libido
Secondary amenorrhoea
Erectile dysfunction
Reduced pubic hair
15
Q
Presentation of low ACTH in Hypopituitarism
A
Fatigue
16
Q
Presentation of low TSH in Hypopituitarism
A
Fatigue
Low pulse rate
17
Q
Presentation of low GH in Hypopituitarism
A
Reduced quality of life
Short stature (only in children)
18
Q
Presentation of low prolactin in Hypopituitarism
A
Inability to breastfeed
19
Q
What is lactotroph hyperplasia
A
Anterior pituitary enlargement due to pregnancy, therefore post partum haemorrhage can lead to pituitary infarction
20
Q
Symptoms of Sheehan’s Syndrome
A
Lethargy, anorexia/weight loss (all expected after pregnancy so usually ignored). Due to TSH/ACTH/GH deficiency
Failure of lactation due to prolactin deficiency (some people don’t want to so can’t therefore not a definitive sign)
Menses don’t resume post delivery
No damage to AVP as posterior pituitary is not affected
21
Q
What is pituitary apoplexy?
A
Bleeding (haemorrhage) into the pituitary
Normally due to existing adenoma
Can be precipitated by anticoagulants
22
Q
Symptoms of pituitary apoplexy
A
Severe headache with sudden onset
Bitemporal hemianopia
Haemorrhage May press CN III, IV, V : therefore cavernous sinus involvement can cause Diplopia (double vision) or ptosis (droopy eyelid)
23
Q
Why is biochemical diagnosis of Hypopituitarism difficult?
A
Hormone levels are pulsatile/ are higher at different times, impacting diagnosis
24
Q
How is dynamic pituitary function used in Hypopituitarism diagnosis?
A
Body is put under stress by insulin-induced hypoglycaemia which stimulates GH and ACTH release
Injected with insulin, TRH and GnRH
TRH stimulates release of TSH
GnRH stimulates FSHand LH release
25
What is used for radiological diagnosis of Hypopituitarism?
MRI
26
What is empty sella syndrome?
Small tumour which pushes pituitary along rim of sella and which later infarcts
The pituitary still works after this but sella looks empty
27
Which hormone do you not need to replace for Hypopituitarism and why?
Prolactin- controlled negatively therefore a tumour normally means there’s an increase in PRL
Function not major therefore doesn’t need replacement
28
Which hormone can’t be taken orally in Hypopituitarism treatment and why?
Growth hormone
It is a peptide hormone meaning it would be broken down by gastric acid in the stomach
Taken as an injection
29
What is the treatment for GH deficiency?
Daily injection
Measure the response by :
- improvement in QoL
-plasma IGF-1 which is constant not pulsatile therefore easier to measure
30
What is the treatment of TSH deficiency?
levothyroxine once daily
Can’t use TSH to adjust the dose of levothyroxine like in primary hypothyroidism
Therefore change dose with aim for a T4 above the middle of the reference range
31
What’s the treatment for ACTH deficiency in Hypopituitarism?
Replace cortisol not ACTH
Synthetic glucocorticoids:
Prednisolone once daily am
Hydrocortisone three times a day (short half life so 3)
Difficult to mimic cortisols diurnal pattern
32
Symptoms of adrenal crisis
Dizziness
Hypotension
Vomiting
Weakness
May result in collapse and death
Triggered by undercurrent illness in people with primary/secondary adrenal failure
33
What are sick day rules?
Wear steroid alert/pendant
Take double the glucocorticoid does if fever/ intercurrent illness (to avoid crisis)
If unable to take tablets eg vomiting, inject IM or go A&E
34
What is the treatment of FSH/LH deficiency in men?
No fertility required :
Replace testosterone-topical / intramuscular
(Measure plasma testosterone)
Does not restore sperm production
normal QoL and libido
Fertility :
Spermatogenesis induction using Gonadotrophin injections (LH and FSH twice a week)
Best response if after puberty
Measure testosterone and semen analysis to check dosage for spermatogenesis (may take 6-12 months)
35
What’s the treatment for LH/FSH deficiency in women?
No fertility required :
Replace oestrogen and (if uterus intact) progestogen (prevents endometrial hyperplasia/ cancer)
Oral or topical
Fertility:
IVF - carefully timed Gonadotrophin injections
36
How can you tell the difference between the anterior pituitary and the posterior pituitary on an MRI?
Posterior appears as a bright spot vs anterior is grey
37
What stimulates AVP release?
Increase in plasma osmolality
Detected by osmoreceptors in hypothalamus
38
How do osmoreceptors regulate AVP?
If deprived of water extracellular sodium concentration increases and so osmoreceptors release water causing them to shrink. This change in shape causes increased osmoreceptor firing. This stimulates release of AVP from hypothalamic neurones. Avoids dehydration as water is reabsorbed from the urine.
39
What are two physiological responses to water deprivation?
Thirst
Increased AVP release (reduces urine volume and increases its osmolality. Decreases plasma osmolality)
40
What are the two problems/diseases relating to vasopressin?
Arginine Vasopressin Deficiency
Arginine vasopressin resistance
41
What’s AVP-D?
Cranial diabetes insipidus
Unable to make AVP because of a problem with the hypothalamus/ posterior pituitary
42
What’s AVP-R?
Nephrogenic diabetes insipidus
Kidney (collecting duct) unable to respond to it even though the post pituitary can make the AVP
(Resistance)
43
Outline the presentation of AVP-D/AVP-R.
AVP problem results in impaired concentration of urine in renal collecting duct. Therefore large volumes of dilute urine (hypotonic). Means increased plasma osmolality and sodium. Causes stimulation of osmoreceptors-> thirst /polydipsia .
As long as patient has access to water circulation continues normally
44
How can AVP-R / AVP-D result in death?
No access to water will result in dehydration and death
45
What is the presentation of AVP deficiency / resistance
Polydipsia
Nocturia
Polyuria
46
What are the symptoms of diabetes insipidus usually a sign of?
Diabetes Mellitus due to osmotic diuresis. Therefore if a patient normally presents they most likely have DM not DI
47
What are causes of AVP deficiency?
Mostly acquired, rarely congenital
1- traumatic brain injury
2- pituitary surgery/tumour
3- inflammation of the pituitary stalk eg TB.. therefore the AVP can’t travel down the stalk
4-autoimmune
48
What are causes of AVP resistance?
Less common than deficiency
Congenital: eg mutation in gene for V2 receptor
Acquired: drugs eg lithium (normally used for bipolar affective disorder)
49
What is the presentation of diabetes insipidus?
Large volumes of Hypo-osmolar urine
Hyper-osmolar plasma.
Patient is dehydrated
Hypernatraemia
Normal blood glucose
50
What is psychogenic polydipsia?
No problem with AVP, problem is that the patient drinks too much water so passes large volumes of dilute urine.
Sometimes in psych patients as meds cause dry mouths which leads to the polydipsia
51
What happens in psychogenic polydipsia?
Increased drinking -> drop in plasma osmolality and sodium -> less AVP secretion -> large volumes of hypotonic urine -> plasma osmolality returns to normal
52
What test is used to distinguish between DI & psychogenic polydipsia?
The water deprivation test
53
What is the water deprivation test?
No access to anything to drink for about 8 hrs
Monitor urine volumes, urine concentration, plasma concentration
Normally urine conc increases as water is reabsorbed due to the high plasma osmolality
54
What is the water deprivation test?
No access to anything to drink for about 8 hrs
Monitor urine volumes, urine concentration, plasma concentration
Normally urine conc increases as water is reabsorbed due to the high plasma osmolality
55
What does the water deprivation test of someone with psychogenic polydipsia look like?
Nothing wrong with it as AVP is produced and is able to concentrate the urine to bring the plasma osmolality down again
56
What does the water deprivation test of someone with DI look like?
Line stays flat as the patients is not able to concentrate the urine therefore would have large volumes of dilute urine with high plasma osmolality
57
What is used to distinguish AVP-D /AVP-R in a water deprivation test?
Desmopressin
58
How is desmopressin used to distinguish between AVP resistance and deficiency?
It works as AVP therefore once given desmopressin AVP-D patient would be able to concentrate their urine and respond
Patient with AVP-R would have no increase in urine osmolality as kidney can’t respond
59
Why do you monitor weight in a water deprivation test?
You stop the test if the patient loses more 3% of their body weight as this is a marker of significant dehydration (occurs in AVP-R / AVP-D)
60
What is the treatment for AVP deficiency?
Desmopressin
(Selective for V2 not V1 as V1 is for vasoconstriction)
Tablet or intranasal
61
What is the name of the condition when there is too much AVP?
Syndrome of Inappropriate Anti-diuretic Hormone (SIADH)
62
What are signs of SIADH?
Reduced urine output
Water retention
High urine osmolality
Low plasma osmolality
Low plasma sodium
63
What are causes of SIADH?
-CNS : head injury, stroke, tumour
- lung infections eg pneumonia
- malignancy eg lung cancer
-Drug related : anti-epileptics, anti-depressants
-Idiopathic
64
How is SIADH managed?
Common cause of prolonged hospital stay
Fluids restriction
Vasopressin receptor antagonist - vaptan (binds to V2 receptor)
65
What 2 factors increase/ control serum calcium levels?
-Vitamin D (synthesised in skin, diet)
-Parathyroid hormone
66
What can be secreted by thyroid parafollicular cells to decrease serum calcium?
Calcitonin (reduce acutely, no negative effect of these cells are removed)
67
What do you measure to check vitamin D status in body?
25-OH Vitamin D (not calcitriol)
68
What is secreted from the kidney to activate vitamin D / convert 25(OH)cholecalciferol into calcitriol?
1 alpha hydroxylase
69
What are the effects of calcitriol on the body? (4)
1) Increased calcium and phosphate reabsorption from the kidneys
2) increased phosphate absorption from the gut
3) increase calcium absorption from the gut
4) calcium and phosphate reabsorption from the bone
70
What are the effects of PTH on the body? (5)
1)Increased calcium reabsorption from the kidney
2. Increased phosphate excretion from the kidney
3) increased activity o f1 alpha hydroxylase (increased vitamin D synthesis)
4)increased calcium resorption from the bone
5) vitamin D causes increased calcium and phosphate absorption from the gut
71
What is the overall effect of parathyroid hormone on calcium and phosphate osmolality?
Reduces overall phosphate in bloodstream
Increases calcium concentration
72
How does PTH cause increased excretion of phosphate from the kidney?
PTH inhibits the sodium/phosphate co-transporter promoting phosphate excretion through urine
73
What is the function of FGF-23?
Reduces phosphate in the body by:
1) inhibition of the sodium phosphate contransporter, oncreasing phosphate excretion
2) inhibits calcitriol - less phosphate reabsorption from the gut
74
What are signs of hypocalcaemia?
Paraesthesia (tingling/numbness)
Convulsions
Arrhythmias
Tetany (muscles contract and can’t relax)
Chvosteks sogn
Trousseau’s sign
75
What is chvosteks’ sign?
Facial paraesthesia (tap on the zygomatic arch causes it)
Seen in hypocalcaemia
76
What is Trousseau’s sign?
Carpopedal spasm -inducing tetany by inflating bp cuff
Seen in hypocalcaemia
77
What are causes of hypocalcaemia?
Hypoparathyroidism - low PTH
-surgical
-autoimmune
Congenital (agenesis)
Low vitamin D
—deficiency -poor diet, lack of UV, impaired production eg renal failure
78
What are signs of Hypercalcaemia?
Stones (renal effects)
-nephrocalcinosis (calcium passes through kidney and is deposited)
-GI effects - anorexia, nausea, dyspepsia (heart burn), constipation, pancreatitis
- CNS effects -fatigue, depression, impaired concentration
79
What are causes of Hypercalcaemia?
-Primary hyperparathyroidism- too much PTH (parathyroid adenoma). No negative feedback so both OTH and calcium high
-malignancy
-vitamin D excess
80
How can malignancy cause Hypercalcaemia?
Some cancers (eg squamous cell carcinoma) secrete PTH related peptide which acts at PTH receptors. (Can’t be detected by a PTH assay)
81
What happens in primary hyperparathyroidism?
Eg a parathyroid adenoma
Producing too much PTH
calcium increases but no -ve feedback because of autonomous secretion of PTH
(High calcium, low phosphate, high PTH)
82
How is primary hyperparathyroidism treated?
Parathyroidectomy
83
What are the risks of untreated primary hyperparathyroidism?
Osteoporosis (weak because of extent of calcium resorption)
Renal calculi (stones)
Psych impact -mental function / mood
84
What is secondary hyperparathyroidism?
Normal physiological response to hypocalcaemia
Calcium is low causing the PTH to be high to increase its reabsorption
Normally caused by vitamin D deficiency
85
What are possible causes of vitamin D deficiency causing secondary hyperparathyroidism?
Diet / reduced sunlight
Less common - renal failure so can’t make 1 alpha hydroxylase - can’t make calcitriol
86
What is the treatment of secondary hyperparathyroidism? (In patients with normal renal function)
Vitamin D replacement
Give it in the form of 25 hydroxy vitamin D
It is converted to calcitriol
-ergocalciferol (25 hydroxy vitamin D2)
-cholecalciferol (25 hydroxy vitamin D3)
87
What is the treatment of secondary hyperparathyroidism in a patient with renal failure?
Inadequate 1alpha hydroxylase so can’t activate the 25 hydroxy vitamin D
Give Alfacalcidol (active vitamin D)
88
What is tertiary hyperparathyroidism?
Occurs in chronic renal failure or chronic gut D deficiency
Can’t make calcitriol
High PTH because it is initially like secondary hyperparathyroidism due to low calcium
Causes parathyroid gland to enlarge (hyperplasia)
Autonomous PTH secretion causes Hypercalcaemia
89
What is the treatment of tertiary hyperparathyroidism?
Parathyroidectomy
90
What should you always also check if patient presents with Hypercalcaemia?
PTH
91
If Hypercalcaemia and the PTH is low/normal what is the likely cause of the Hypercalcaemia?
Malignancy
92
How do you manage Hypercalcaemia of malignancy?
Bisphosphonates
93
What is the function of bisphosphonates?
Inhibit osteoclasts and stop them from absorbing bone
Lowers calcium so less bony pain
94
What is infertility?
Failure to achieve a clinical pregnancy after more than 12 months of regular unprotected sex.
95
What is primary infertility?
Not had a live birth previously
96
What is secondary infertility?
Have had a life birth more than 12 months previously
97
What is the impact of infertility in couples?
Psychological distress
98
What is the cost of infertility to society?
Less births
Less tax income
Investigation and treatment costs
99
What are pre-testicular causes of infertility?
Congenital and acquired endocrinopathies eg klinefelters
100
What are testicular causes of infertility?
Congenital
Cryptochordism
Infection
Immunological
Vascular
Trauma / surgery
Toxins
101
What are post testicular causes of infertility?
Congenital - absence of vas deferens
Obstructive azoospermia
Erectile dysfunction (retrograde ejaculation, mechanical impairment, psychological)
Latrogenic eg vasectomy
102
What is cryptochordism?
Normal path for the testis is descent through inguinal canal
In cryptochordism - undescended testis
103
What is endometriosis?
Presence of functioning endometrial tissue outside of the uterus therefore responds to oestrogen
104
What are symptoms of endometriosis?
Increased menstrual pain
Menstrual irregularities
Deep dyspareunia
Infertility
105
How do fibroids cause infertility?
Fibroids - benign tumour of the myometrium. Responds to oestrogen
Can get big and block the uterus
106
What would happen to LH, FSH and Testosterone levels in hyperprolactinaemia?
All drop
107
What happens to LH, FSH and testosterone levels in Primary Testicular Failure (Klinefelters)?
Increase in LH and FSH
Drop in testosterone
108
What is Kallmann syndrome?
Congenital hypogonadotrophic hypogonadism.
The failure of migration of the GnRH neurones with the olfactory fibres.
(Normally the GnRH neurones start off at the olfactory bulb and migrate to the hypothalamus during embryologicql development
109
What are symptoms of Kallmann syndrome?
Anosmia (because of failure of migration, olfactory fibres form migrate either)
Failure of puberty
Infertility
110
What does prolactin bind to in the hypothalamus?
Kisspeptin neurones
111
How does hyperprolactinaemia cause infertility?
Prolactin binds to receptors on kisspeptin neurone. Inhibits it’s release
Decreases downstream GnRH, LH, FSH T, Oest
112
What’s a treatment for hyperprolactinaemia?
Dopamine agonists .
Or surgery
113
What’s an example of a dopamine agonist and what’s a side effect of it?
Cabergoline
Can cause impulse control disorder therefore makes people very impulsive.
114
What are symptoms of klinefelters syndrome?
Tall stature
Less facial hair
Breast development
Female type pubic hair pattern
Small penis and testes
Infertility
Mildly impaired IQ
Narrow shoulders
Reduced chest hair
Wide hips
Low bone density
115
What are key history questions to ask a male with infertility?
Duration of symptoms
Previous children
Pubertal milestones
Other associated symptoms
Drugs or meds
116
What examinations would you do for a patient presenting with male infertility?
BMI
sexual characteristics
Testicular volume
Anosmia
117
What are key investigations for a male presenting with infertility?
Semen analysis conc should be 15mill sperm/ml
Azospermia vs oligospermia
Motility 40%
Blood test (LH, FSH, PRL)
Morning fasting testosterone
Karyotyping
Imaging : scrotal US, MRI pituitary
118
Why a morning fasting testosterone?
Morning: testosterone follows a diurnal rhythm
Fasting: food can suppress testosterone by 20%
119
How can you treat male infertility with general lifestyle?
Optimise BMI
Smoking cessation
Alcohol reduction / cessation
120
What are specific treatments for male infertility?
Dopamine agonist for hyperPRL
Gonadotrophin treatment
Testosterone (for symptoms if no fertility required)
Surgery (Micro Testicular Sperm Extraction)
121
What pattern in LH, FSH and E2 are seen in premature ovarian insufficiency.
LH, FSH: Up
E2 : down
122
What are symptoms of POI?
Same as Menopause
123
What are causes of POI?
Autoimmune
Genetic eg Turners Syndrome
Cancer therapy (radio/chemo)
124
What pattern in LH, FSH and E2 would you see in anorexia nervosa induced amenorrhoea?
All are down
125
Why does anorexia cause infertility?
Leptin = produced by fat cells
Kisspeptin neurones need leptin therefore without it axis shuts down
126
What are signs of PCOS?
Oligo / anovulation
Clinical/biochemical hyperandrogenism. Clinical: acne, hirsutism, alopecia
Biochemical:raised testosterone
Polycystic ovaries
127
What are other risks of PCOS?
Infertility (irregular menses- endometrial cancer - lack of shedding)
Impaired glucose homeostasis (increased insulin resistance)
Hirsutism
128
What are other risks of PCOS?
Infertility (irregular menses- endometrial cancer - lack of shedding)
Impaired glucose homeostasis (increased insulin resistance)
Hirsutism
129
What are treatments for PCOS?
Metformin (for insulin resistance and amenorrhoea)
Oral contraceptive pill (amenorrhoea)
Ovulation induction (for infertility)
Anti-androgens / creams waxing and laser (hirsutism)
Progesterone course (for endometrial cancer risk)
130
What is Turner’s syndrome?
Female with only 1 X chromosome
131
What are symptoms of Turner’s syndrome?
Short stature
Low hairline
Shield chest
Wide spaced nipples
Short 4th metacarpal
Small fingernails
Brown nevi
Characteristic fancies
Webbed neck
Coarctation of aorta
Poor breast development
Elbow deformity
Underdeveloped reproductive tract
Amenorrhoea
132
What are key questions to ask in a history for a female presenting with infertility?
Duration
Previous children
Pubertal milestones
Menstrual history
Medication / drugs
133
What are key questions to ask in a history for a female presenting with infertility?
Duration
Previous children
Pubertal milestones
Menstrual history
Medication / drugs
134
What are key examinations for a female presenting with infertility?
BMI
Sexual characteristics
Hyperandrogenism signs
Anosmia
135
What key investigations to do for a female presenting with infertility?
Blood tests
Pregnancy test
Imaging
136
What blood tests should be done for a female with infertility?
LH, FSH ,PRL
oestradiol, androgens
Mid luteal progesterone (day 21 test for prog)
Karyotyping
137
What type of imaging should be used to check for female infertility?
US (transvaginal)
Hysterosalpingogram
MRI pituitary
