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Year 2 - BRS > 3.1 - Hypopituitarism > Flashcards

3.1 - Hypopituitarism Flashcards

1
Q

What are the hormones the anterior pituitary gland makes?

A
  • growth hormone (somatotrophin)
  • prolactin
  • thyroid stimulating hormone (TSH)
  • luteinising hormone (LH)
  • follicle stimulating hormone (FSH)
  • adrenocorticotrophic hormone (ACTH, corticotrophin)
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2
Q

How does the hypothalamus control the anterior pituitary?

A
  • hypothalamus produces hypothalamic releasing or inhibitory factors which travel in hypothalamo-pituitary portal circulation to the anterior pituitary to regulate anterior pituitary hormone production
  • portal system has leaky, fenestrated blood vessels
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3
Q

What does growth hormone release lead to?

A
  • growth
  • GHRH from hypothalamus –> GH –> IGF-1 –> growth
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4
Q

What does prolactin release lead to?

A
  • milk production
  • negatively regulated by dopamine
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5
Q

What does LH release lead to?

A
  • acts on ovary –> oestrogen and progesterone release in women
  • acts on testes –> testosterone release in men
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6
Q

What does FSH release lead to?

A
  • acts on ovary –> oestrogen and progesterone release in women
  • acts on testes –> testosterone and spermatogenesis in men
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7
Q

What does TSH release lead to?

A
  • triiodothyronine (T3) and thyroxine (T4) from thyroid gland
  • regulated by TRH
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8
Q

What does ACTH release lead to?

A
  • cortisol release from adrenal gland
  • regulated by CRH
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9
Q

What are the two types of anterior pituitary failure?

A
  • primary disease - the gland itself fails e.g. gonads, adrenal cortex, thyroid
  • secondary disease - no signals from hypothalamus or anterior pituitary
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10
Q

What happens in primary hypothyroidism and give an example?

A
  • problem with thyroid gland - T3 and T4 fall, TSH increases due to no -ve feedback
  • TRH would also be high but we do not measure it
  • e.g. autoimmune destruction of thyroid gland
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11
Q

What happens in secondary hypothyroidism and give an example?

A
  • problem with anterior pituitary or hypothalamus = TSH cannot be made
  • TSH falls –> T3 and T4 fall
  • e.g. pituitary tumour damaging thyrotrophs
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12
Q

What happens in primary hypoadrenalism and give an example?

A
  • problem with adrenal gland - cortisol falls, ACTH increases due to no -ve feedback
  • CRH would also be high but we do not measure it
  • e.g. autoimmune destruction of adrenal cortex e.g. Addison’s
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13
Q

What happens in secondary hypoadrenalism and give an example?

A
  • problem with anterior pituitary or hypothalamus so ACTH cannot be made
  • ACTH falls –> cortisol falls
  • e.g. pituitary tumour damaging corticotrophs
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14
Q

What happens in primary hypogonadism and give an example?

A
  • problem with testes/ovaries - testosterone (men) or oestrogen (women) falls, LH and FSH increase due to no -ve feedback
  • GnRH would also be high but we do not measure it
  • e.g. destruction of testes (e.g. mumps) or ovaries (e.g. chemotherapy)
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15
Q

What happens in secondary hypogonadism and give an example?

A
  • problem with anterior pituitary or hypothalamus so LH/FSH cannot be made
  • LH/FSH fall –> testosterone/oestrogen fall
  • e.g. pituitary tumour damaging gonadotrophs
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16
Q

What are the two types of causes of hypopituitarism?

A

Congenital and acquired

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17
Q

What is congenital hypopituitarism?

A
  • pituitary gland has not developed properly in utero
  • usually due to mutations of transcription factor genes needed for normal APG development
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18
Q

What are the features of congenital hypopituitarism?

A
  • deficient in GH and at least one more anterior pituitary hormone
  • short stature
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19
Q

What does an MRI show in congenital hypopituitarism?

A

Hypoplastic (underdeveloped) anterior pituitary gland

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20
Q

What are examples of acquired hypopituitarism? (8)

A
  • tumours e.g. adenomas, metastases. cysts
  • radiation (hypothalamic/pituitary damage)
  • infection e.g. meningitis
  • traumatic brain injury
  • pituitary surgery
  • inflammatory (hypophysitis)
  • pituitary apoplexy - haemorrhage/less commonly infection
  • peri-partum infarction (Sheehan’s syndrome)
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21
Q

What is the occurrence of congenital vs acquired hypopituitarism?

A

Congenital is rare, acquired is much more common

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22
Q

What does hypopituitarism usually describe?

A
  • anterior pituitary dysfunction
  • but, certain processes - especially inflammation (hypophysitis) or surgery may cause posterior pituitary dysfunction too
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23
Q

What is panhypopituitarism?

A

Total loss of anterior and posterior pituitary function

24
Q

How can radiotherapy cause radiotherapy induced hypopituitarism?

A
  • pituitary and hypothalamus are both sensitive to radiation
  • radiotherapy could be direct to pituitary (e.g. to treat acromegaly)
  • radiotherapy could be indirect to pituitary (e.g. to treat CNS tumour nearby) = pituitary innocent bystander
25
Q

What does the extent of damage to the pituitary caused by radiation depend on?

A

Total dose of radiotherapy delivered to hypothalamo-pituitary axis - higher dose = higher risk of HPA axis damage

26
Q

What happens to GH, gonadotrophins and prolactin due to radiotherapy induced hypopituitarism?

A
  • GH and gonadotrophins are most sensitive to damage
  • prolactin can increase after radiotherapy due to loss of hypothalamic dopamine
27
Q

How long does risk to pituitary persist for after radiotherapy?

A

Up to 10 years, so annual assessment needed

28
Q

How does hypopituitarism present for FSH/LH? (4)

A
  • reduced libido
  • secondary amenorrhoea
  • erectile dysfunction
  • reduced pubic hair
29
Q

How does hypopituitarism present for ACTH?

A
  • fatigue
  • NB not a salt losing crises as aldosterone dependent on renin-angiotensin axis
30
Q

How does hypopituitarism present for TSH? (3)

A
  • fatigue
  • maybe weight gain
  • bradycardia if extreme
31
Q

How does hypopituitarism present for GH?

A
  • reduced QOL
  • NB short stature only in children
32
Q

How does hypopituitarism present for prolactin?

A

Inability to breastfeed

33
Q

What is Sheehan’s syndrome?

A
  • post-partum hypopituitarism secondary to hypotension (post-partum haemorrhage - PPH)
  • PPH (blood loss) leads to pituitary infarction (loss of blood supply)
  • more common in developing countries
34
Q

How does Sheehan’s syndrome occur?

A
  • at the end of pregnancy, anterior pituitary is 2x normal size but blood supply has not increased
  • this is normal but any blood loss means blood supply to pituitary too low
  • blood supply not low enough for organ failure/death, but enough to infarct pituitary = cells die
  • (PPG not affected as downgrowth of hypothalamus so neuronal not glandular)
35
Q

What are the symptoms of Sheehan’s syndrome?

A
  • lethargy, anorexia, weight loss - TSH/ACTH/GH deficiency
  • failure of lactation (cannot breastfeed) - prolactin deficiency
  • failure to resume menses post-delivery
  • posterior pituitary usually not affected
36
Q

How is Sheehan’s disease treated?

A

Lifelong supply of pituitary hormones

37
Q

What happens to anterior pituitary during pregnancy?

A

It enlarges (lactotroph hyperplasia)

38
Q

What is pituitary apoplexy?

A
  • bleeding (haemorrhage) into the pituitary
  • often dramatic presentation in patients with pre-existing pituitary tumours (adenomas)
  • may be first presentation of pituitary adenoma
39
Q

What can the haemorrhage in pituitary apoplexy be precipitated by?

A

Anticoagulants

40
Q

What are the features of pituitary apoplexy?

A
  • severe sudden onset headache (due to sudden increase in intracranial pressure)
  • visual field defect - compressed optic chiasm (bitemporal hemianopia)
  • if blood enters cavernous sinus it could compress nearby cranial nerves causing eye movement problems: diplopia - double vision (IV, VI), ptosis (III)
41
Q

What is important to keep in mind when measuring basal plasma hormone concentrations to diagnose hypopituitarism?

A
  • cortisol - diurnal rhythm so time of day changes conc in blood
  • T4 - circulating half life of 6 days so may be normal on day of presentation but low a week later
  • FSH/LH - cyclical in women
  • GH/ACTH - pulsatile
42
Q

What is a dynamic pituitary function test for ACTH & GH?

A
  • ACTH & GH are stress hormones so we induce stress in patients by making them hypoglycaemic (<2.2mM) using insulin
  • look for GH increase and ACTH release (cortisol measured since ACTH is hard to measure)
  • if high levels, normal function
43
Q

What is a dynamic pituitary function test for TSH?

A

Could give TRH to see whether pituitary can make TSH

44
Q

What is a dynamic pituitary function test for FSH and LH?

A

Could give GnRH to see whether pituitary can make FSH and LH

45
Q

How would we make a radiological diagnosis of hypopituitarism?

A
  • pituitary MRI - CT not so good at delineating pituitary gland
  • may reveal specific pituitary pathology e.g. haemorrhage (apoplexy), adenoma
  • would see an empty sella - thin rim of pituitary tissue
46
Q

How do we treat GH deficiency?

A
  • NICE guidance
  • confirm GH deficiency on dynamic pituitary function test
  • assess QoL using specific questionnaire
  • daily injection (no oral option as peptide)
  • measure response by improvement in QoL and plasma IGF-1
47
Q

How do we treat prolactin deficiency?

A

Cannot treat

48
Q

How do we treat TSH deficiency?

A
  • replace with once daily levothyroxine
  • in secondary hypothyroidism, TSH is low so you cannot use this to adjust dose as you do in primary hypothyroidism
  • aim for a fT4 above the middle of the reference range
49
Q

How do we treat ACTH deficiency?

A
  • replace cortisol rather than ACTH
  • difficult to mimic diurnal variation of cortisol
  • two main options in the UK using synthetic glucocorticoids
50
Q

What are the two main options in the UK to replace cortisol using synthetic glucocorticoids?

A
  • Prednisolone - once daily AM e.g. 3mg
  • Hydrocortisone - three times per day e.g. 10mg/5mg/5mg
51
Q

Who is at risk of adrenal crisis?

A

Those with primary adrenal failure (Addison’s) or secondary adrenal failure (ACTH deficiency) at risk of adrenal crisis triggered by intercurrent illness

52
Q

What are the features of an adrenal crisis? (5)

A
  • dizziness
  • hypotension
  • vomiting
  • weakness
  • can result in collapse and death
53
Q

What are the sick day rules for patients with ACTH deficiency? (4)

A
  • patients who take replacement steroid e.g. prednisolone, hydrocortisone must be told sick day rules
  • steroid alert pendant/bracelet
  • double steroid dose (glucocorticoid not mineralocorticoid) if fever/recurrent illness
  • if unable to take tablets (e.g. vomiting), inject IM hydrocortisone or come to A&E
54
Q

How is FSH/LH deficiency treated in men when no fertility is required?

A
  • replace testosterone - topical or intramuscular
  • measure plasma testosterone
  • replacing testosterone does not restore sperm production (FSH dependent)
55
Q

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

A
  • induction of spermatogenesis by gonadotrophin injections
  • best response if secondary hypogonadism has developed after puberty
  • measure testosterone and semen analysis
  • sperm production may take 6-12 months
56
Q

How is FSH/LH deficiency treated in women when no fertility is required?

A
  • replace oestrogen
  • oral or topical
  • will need additional progestogen if intact uterus to prevent endometrial hyperplasia
57
Q

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

A

Can induce ovulation by carefully timed gonadotrophin injections (IVF)

Year 2 - BRS (84 decks)

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