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brs (phase 1b) > (endo) hypopituitarism > Flashcards

(endo) hypopituitarism Flashcards

1
Q

what is hypopituitarism?

A

diminished hormone secretion by the anterior pituitary gland

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2
Q

what is the origin of the anterior pituitary gland?

A

glandular

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3
Q

what is the origin of the posterior pituitary gland?

A

neuronal

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4
Q

what hormones does the anterior pituitary produce?

A 
growth hormone (somatotrophin)
prolactin
adrenocorticotrophic hormone (corticotrophin)
FSH & LH
thyroid stimulating hormone
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5
Q

what is growth hormone alternatively known as?

A

somatotrophin

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6
Q

what is adrenocorticotrophic hormone alternatively known as?

A

corticotrophin (or ACTH)

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7
Q

what are LH & FSH alternatively known as?

A

gonadotrophins

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8
Q

what is thyroid stimulating hormone alternatively known as?

A

thyrotrophin

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9
Q

what structure is the anterior pituitary function reliant on?

A

hypothalamus

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10
Q

how is the anterior pituitary reliant on the hypothalamus?

A

hypothalamus releases either releasing or inhibiting factors into the hypophyseal-pituitary portal circulation which carries them down to the blood vessels surrounding the APG endocrine cells stimulating hormone release

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11
Q

what is growth hormone responsible for?

A

growth

production of IGF-1 in the liver

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12
Q

what is prolactin responsible for?

A

lactation (milk production)

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13
Q

what are LH & FSH responsible for?

A

oestrogen, progesterone and testosterone production

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14
Q

what is ACTH responsible for?

A

cortisol production

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15
Q

what is TSH responsible for?

A

T3 and T4 production

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16
Q

what are the two main causes for anterior pituitary failure?

A

primary disease or secondary disease

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17
Q

differentiate between primary disease and secondary disease

A

primary disease = problem with the gland itself

secondary disease = no signals from hypothalamus or anterior pituitary to gland

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18
Q

what is primary hypothyroidism?

A

reduced thyroid gland function due to autoimmune damage

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19
Q

what would be the blood thyroid report for a patient with primary hypothyroidism?

A

reduced T3 & T4 levels

elevated TSH levels

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20
Q

why would TSH levels be elevated in primary hypothyroidism?

A

due to the negative feedback loop that responds to reduced T3 & T4 levels

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21
Q

why can’t TRH levels be measured?

A

it is a releasing factors produced in the hypothalamus and released into the hypophyseal-pituitary portal circulation which is not part of the systemic circulation

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22
Q

what is secondary hypothyroidism? (give an example of a cause)

A

reduced thyroid gland function due to reduced/underactive anterior pituitary gland function

e.g. pituitary adenoma affecting thyrotrophs

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23
Q

what would be the blood thyroid report for a patient with secondary hypothyroidism?

A

reduced T3 & T4 levels

reduced TSH levels

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24
Q

what is primary hypoadrenalism?

A

reduced adrenal cortex function due to destruction of the adrenal cortex (e.g. autoimmune)

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25
Q

what would be the blood report for a patient with primary hypoadrenalism?

A

reduced cortisol, elevated ACTH

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26
Q

why can’t CRH levels be measured?

A

it is a releasing factors produced in the hypothalamus and released into the hypophyseal-pituitary portal circulation which is not part of the systemic circulation

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27
Q

what is secondary hypoadrenalism? (give an example of a cause)

A

reduced adrenal cortex function due to underactive/reduced anterior pituitary function

e.g. pituitary adenoma affecting corticotrophs

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28
Q

what would be the blood cortisol report for a patient with secondary hypocortisolism?

A

reduced cortisol

reduced ACTH

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29
Q

what is primary hypogonadism?

A

reduced gonadal function due to damage to the ovaries (women) or the testes (men)

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30
Q

what would be the blood thyroid report for a patient with primary hypogonadism?

A

women - reduced oestrogen, elevated LH & FSH

men - reduced testosterone, elevated LH & FSH

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31
Q

what is secondary hypogonadism?

A

reduced gonadal function due to underactive/reduced anterior pituitary function

e.g. pituitary adenoma affecting gonadotrophs

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32
Q

what would be the blood thyroid report for a patient with secondary hypogonadism?

A

women - reduced oestrogen, reduced LH & FSH

men - reduced testosterone, reduced LH & FSH

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33
Q

why can’t GnRH levels be measured?

A

it is a releasing factors produced in the hypothalamus and released into the hypophyseal-pituitary portal circulation which is not part of the systemic circulation

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34
Q

what can cause destruction of the testes in primary hypogonadism?

A

mumps

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35
Q

what can cause destruction of the ovaries in primary hypogonadism?

A

chemotherapy

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36
Q

what are the congenital causes of hypopituitarism?

A

mutation of the genes needed for normal anterior pituitary development e.g. POP1 mutation

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37
Q

what would be the blood hormone levels of a patient with congenital hypopituitarism?

A

deficent in GH + at least one more APG hormone

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38
Q

what are the symptoms of congenital hypopituitarism?

A

short stature and hypoplastic APG on an MRI

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39
Q

define hypoplastic

A

underdeveloped

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40
Q

what causes of hypopituitarism are more common: congenital or acquired?

A

acquired

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41
Q

list possible acquired causes of hypopituitarism

A

pituitary tumours (adenoma, metastases, cysts)

radiation (causes hypothalamic/APG damage)

traumatic brain injury

infection (e.g. meningitis)

pituitary surgery (accidental lesions during surgery)

inflammation (hypophysitis)

pituitary apoplexy (haemorrhage)

peri-partum infarction (Sheehan’s syndrome)

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42
Q

how can tumours cause hypopituitarism?

A

pituitary adenomas (hyperproliferation of APG cells) or metastases forming secondary tumours from other cancers

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43
Q

how can radiation cause hypopituitarism?

A

radiation directed towards APG or nearby APG can cause damage to the hypothalamus + APG

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44
Q

how can traumatic brain injury cause hypopituitarism?

A

can cause lesion of the PG = impaired pituitary function

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45
Q

how can pituitary surgery cause hypopituitarism?

A

can cause lesion of the PG or pituitary stalk = impaired pituitary function

(during tumour resection or other pituitary surgeries)

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46
Q

how can infection cause hypopituitarism?

A

meningitis impairs pituitary function

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47
Q

define hypophysitis and explain how it can cause hypopituitarism

A

inflammation of the pituitary gland or pituitary stalk = impairs pituitary function

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48
Q

how can pituitary apoplexy cause hypopituitarism?

A

haemorrhage into pituitary gland impairs function

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49
Q

how can Sheehan’s syndrome cause hypopituitarism?

A

pituitary infarcts and dies due to ischaemia as a result of hypotension in a peri-partum haemorrhage

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50
Q

which axes does hypopituitarism refer to?

A

could be one axis or several axes

51
Q

which portion of the pituitary gland is referred to in hypopituitarism?

A

most commonly the APG however if the cause is surgery or hypophysitis (inflammation), PPG can also be affected

52
Q

define panhypopituitarism

A

total loss of anterior AND posterior pituitary function

53
Q

how does radiotherapy-induced hypopituitarism occur?

A

the hypothalamo-pituitary axis is either:

  • direct target of radiation (e.g. pituitary adenoma causing acromegaly)
  • indirect target of radiation (e.g. nasopharyngeal carcinoma)
54
Q

why does radiotherapy-induced hypopituitarism occur?

A

both the hypothalamus and the APG are sensitive to radiation

55
Q

what determines the extent of radiotherapy-induced hypopituitarism?

A

the dose of radiotherapy given

56
Q

which APG cells are most sensitive to radiotherapy and what is the implication of this on hormone levels?

A

gonadotrophs and somatotrophs (so gonadotrophins and GH most likely lost)

57
Q

what happens to prolactin levels as a result of radiotherapy-induced hypopituitarism?

A

if only lactotrophs damaged + hypothalamus intact = prolactin decrease

if hypothalamus damaged = prolactin increase (due to dopamine decrease)

58
Q

why is an annual assessment important in patients who receive radiation direct at/near the pituitary gland?

A

risk of radiotherapy-induced hypopituitarism persist up to 10 years after completion of radiotherapy

59
Q

how does hypopituitarism present in terms of LH & FSH?

A 
reduced libido
reduced pubic hair
secondary amenorrhoea (females)
erectile dysfuction (males)
60
Q

what is secondary amenorrhoea?

A

absence of three or more menses in a row in a female who has had her period in the past

61
Q

what is primary amenorrhoea?

A

absence of menses at the age of 15 in the presence of normal growth and normal secondary sexual characteristics

62
Q

how does hypopituitarism present in terms of ACTH?

A

fatigue

63
Q

how does hypopituitarism present in terms of TSH?

A

fatigue

maybe changes in weight?

64
Q

how does hypopituitarism present in terms of GH?

A 
short stature (only in children)
reduced quality of life (adults)
65
Q

how does hypopituitarism present in terms of prolactin?

A

inability to breastfeed (women)

no known obvious symptoms in men

66
Q

what is the best radiological way to visualise the pituitary gland?

A

an MRI scan

67
Q

why does a deficiency in ACTH not necessarily result in an adrenal crisis?

A

with ACTH deficiency in anterior pituitary failure = cortisol production impaires BUT aldosterone production intact due to functional renin-angiotensin system

(nb - blood pressure controlled by both cortisol and aldosterone)

68
Q

what is Sheehan’s syndrome?

A

a post-partum condition wherein a peri-partum haemorrhage causes hypotension which leads to an infarction of the pituitary gland causing post-partum hypopituitarism

69
Q

where is Sheehan’s syndrome most commonly seen?

A

most common in developing countries

70
Q

explain the pathophysiology of Sheehan’s syndrome

A

during pregnancy, APG enlarges due to imminent increase in prolactin demand (increased need to breastfeed) = lactotroph hyperplasia

enlarged APG requires a richer, more significant blood supply

during childbirth, increased blood loss (haemorrhage) causes peri-partum hypotension

episode of hypotension enables a small window of time for a pituitary infarction to take place (as enlarged pituitary gland is extremely sensitive)

pituitary infarcts and dies = impaired production of endocrine hormones = secondary domino effects

71
Q

why does lactotroph hyperplasia normally occur during pregnancy?

A

in preparation for a huge increase in prolactin demand (for lactation)

72
Q

why is the anterior pituitary affected most by the the peri-partum hypotension?

A

enlarged in pregnancy (lactotroph hyperplasia) and therefore, more sensitive to changes in blood pressure

73
Q

what are the common symptoms of Sheehan’s syndrome?

A

lethargy, anorexia, weight loss, failure to lactate, failure to resume menses post-delivery

74
Q

what causes lethargy, anorexia and weight loss in Sheehan’s syndrome?

A

deficiency of TSH/GH/ACTH

75
Q

what causes failure of lactation in Sheehan’s syndrome?

A

deficiency of prolactin

76
Q

what causes failure of menses returning post delivery?

A

deficiency of LH/FSH

77
Q

what is pituitary apoplexy?

A

intra-pituitary haemorrhage (or less commonly, infarction)

i.e. uncontrolled bleeding into PG/impaired blood supply to PG

78
Q

what is an infarction?

A

obstruction of blood supply to tissue causing local death of tissue (due to thrombus/embolus)

79
Q

how does pituitary apoplexy relate to pituitary adenomas?

A

dramatic presentation of apoplexy in individuals with pituitary adenomas

(often first presentation of adenoma too)

80
Q

what can pituitary apoplexy be precipitated by?

A

use of anti-coagulants or blood thinners (e.g. warfarn) = increase likelihood of haemorrhage (into pre-existing pituitary adenoma)

81
Q

what are the main symptoms of pituitary apoplexy?

A

sudden onset headache

bitemporal hemianopia

ptosis/diplopia (problems with eye movement)

82
Q

how does pituitary apoplexy cause bitemporal hemianopia?

A

visual field defect due to compressed optic chiasm = blocks sensory information transmission from temporal visual fields to the primary visual cortex

83
Q

how does pituitary apoplexy cause problems with eye movements?

A

due to compression of the blood vessels and nerves passing through the cavernous sinus (e.g. impaired CN III causes ptosis OR impaired CN IV/VI causes diplopia)

84
Q

what does compression of CN III in pituitary apoplexy cause?

A

ptosis (drooping eyelid)

85
Q

what does compression of CN IV or CN VI in pituitary apoplexy cause?

A

diplopia (double vision)

86
Q

what precautions need to be taken before interpreting basal plasma hormone concentrations?

A

cortisol - diurnal rhythm, peaks during AM

T4 - has a half life of six days

FSH/LH - cyclical in women

GH/ACTH - pulsatile

87
Q

what precautions need to be taken before interpreting basal plasma cortisol concentrations?

A

diurnal rhythm, peaks during AM

88
Q

what precautions need to be taken before interpreting basal plasma T4 concentrations?

A

circulating half life of T4 is six days

89
Q

what precautions need to be taken before interpreting basal plasma FSH/LH concentrations?

A

cyclical in women

90
Q

what precautions need to be taken before interpreting basal plasma GH/ACTH concentrations?

A

pulsatile rhythm

91
Q

besides a blood test, how can ACTH and GH levels be measured?

A

using insulin-induced hypoglycaemia - DYNAMIC PITUITARY FUNCTION TEST

by injecting insulin to stimulate a blood glucose level of <2.2mM (inducing stress)

this in turn will stimulate GH and ACTH release (latter used to measure cortisol)

92
Q

besides a blood test, how can TSH levels be measured?

A

by injecting TRH to stimulate a TSH release - DYNAMIC PITUITARY FUNCTION TEST

93
Q

besides a blood test, how can FSH and LH levels be measured?

A

by injecting GnRH to stimulate LH and FSH release - DYNAMIC PITUITARY FUNCTION TEST

94
Q

why do we not do random hormone measurements as opposed to inducing hormone release?

what is it better to do instead?

A

not reliable/robust enough due to diurnal/cyclical/pulsatile rhythms etc

somehow decrease hypoglycaemia

95
Q

why are ACTH and GH released during insulin-induced hypoglycaemia?

A

in response to stress and as part of the adrenergic response

96
Q

how can hypopituitarism be radiologically diagnosed?

A

using a pituitary MRI

97
Q

how is GH deficiency treated in adults?

A

assess GH deficiency using a dynamic pituitary function test

assess quality of life (QoL) using a specific questionnaire

if results suggest deficiency,, then daily GH injection

98
Q

why is GH deficiency a problem in adults?

A

growth hormone is believed to be essential for psychological wellbeing

99
Q

what is a dynamic pituitary function test?

A

stimulating or suppressing a particular hormonal axis and observing the appropriate hormonal response

e.g. insulin-induced hypoglycaemia to measure ACTH/GH levels

100
Q

how is the efficacy of daily GH injections monitored in GH deficient patients?

A

measure response by assessing improvement in QoL or measuring plasma IGF-1 levels

101
Q

why is plasma IGF-1 measured in GH deficient patients receiving treatment?

A

when GH is released, it acts on liver to stimulate IGF-1 production

102
Q

why is the posterior pituitary unaffected in Sheehan’s syndrome?

A

the PPG is neuronal in origin and so lacks a blood supply = so no haemorrhage can occur

103
Q

can lactotroph hyperplasia lead to bitemporal hemianopia?

A

not unless there is a pre-existing pituitary adenoma that is pushed further up by lactotroph hyperplasia, causing compression of the optic chiasm

104
Q

how is ACTH deficiency treated?

A

replace missing cortisol rather than missing ACTH

105
Q

how is the diurnal variation of cortisol maintained in ACTH deficiency treatment?

A

difficult to maintain diurnal variation BUT either of two synthetic glucocorticoids are given:

  • hydrocortisone (thrice a day in 10mg, 5mg, 5mg)
  • prednisolone (once a day AM e.g. 3mg)
106
Q

what are hydrocortisone and prednisolone and what are they used for?

A

synthetic glucocorticoids used to replace missing cortisol in ACTH deficiency

107
Q

why would prednisolone be preferentially given rather than hydrocortisone in ACTH deficiency?

A

prednisolone (synthetic) is more potent and much longer-lasting compared to hydrocortisone

108
Q

what is the hydrocortisone dose given in ACTH deficiency?

A

thrice a day (10mg, 5mg and 5mg)

109
Q

what are patients with ACTH deficiency at a higher risk of?

A

greater risk of adrenal crisis

110
Q

what is ACTH deficiency alternatively known as?

A

secondary adrenal failure

as pituitary doesn’t make enough ACTH to stimulate cortisol production in the adrenal glands - primary site

111
Q

what are the features of an adrenal crisis?

A

hypotension, dizziness, vomiting, weakness

112
Q

what can adrenal crisis lead to?

A

collapse and death

113
Q

what must patients with ACTH deficiency that take replacement steroids be told?

A

‘sick day rules’

114
Q

what is primary adrenal failure also known as?

A

Addison’s disease

115
Q

what are the ‘sick day rules’ that a patient with ACTH deficiency should know?

A

steroid alert pendant/bracelet

double steroid dose required of glucocorticoid, not mineralocorticoid (!) if fever/intercurrent illness

if unable to take tablets (i.e. vomiting), inject IM hydrocortisone/A&E

116
Q

how is FSH/LH deficiency treated in men when fertility is NOT required?

A

replace testosterone (orally ot topically) and then measure plasma testosterone

117
Q

would replacing testosterone in LH/FSH deficient men restore sperm production and why?

A

no, as sperm production depends on FSH levels not testosterone

118
Q

how is FSH/LH deficiency treated in men when fertility is required?

A

induce spermatogenesis using gonadotrophin (LH/FSH) injections and then measure testosterone and do a sperm analysis

119
Q

how long may sperm production take after gonadotropin injections have been given to LH/FSH deficient men?

A

may be between 6-12 months

120
Q

how is FSH/LH deficiency treated in women when fertility is NOT required?

A

replace oestrogen (orally or topically)

121
Q

how is FSH/LH deficiency treated in women when fertility is required?

A

can induce ovulation using carefully timed LH/FSH injections (IVF)

122
Q

what is the difference between progesterone and progestogen?

A

progesterone = pro-gestational steroid hormone

progestogen = synthetic progesterone

123
Q

what must also be prescribed if oestrogen is taken to treat LH/FSH deficiency in women and why?

A

progestogen (only if uterus is intact) to prevent endometrial hyperplasia

brs (phase 1b) (71 decks)

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