Hypopituitarism

Question 1

How is anterior pituitary hormone production regulated?

Answer 1

Hypothalamic releasing or inhibitory factors travel in the portal circulation to the anterior pituitary

Question 2

Describe the differences you would see in a TFT for Primary vs Secondary Hypothyroidism

Answer 2

Primary Hypothyroidism —> thyroid gland itself cannot produce T3/4, e.g. autoimmune destruction of gland. Fall in T3/T4 but rise in TSH due to less -ve feedback to AP thyrotrophs.
Secondary Hypothyroidism —> eg. pituitary tumour damaging thyrotrophs. Fall in TSH production causing a fall in T3/4.

Question 3

Describe the differences you would see in a blood test for Primary vs Secondary Hypoadrenalism

Answer 3

Primary Hypoadrenalism —> Destruction of adrenal cortex, e.g. autoimmune. Fall in cortisol but rise in ACTH due to less -ve feedback to the anterior pituitary corticotrophs.
Secondary Hypoadrenalism —> eg. Pituitary tumour damaging corticotrophs. Can’t make ACTH therefore cortisol low and ACTH is low.

Question 4

Is aldosterone regulated by ACTH?

Answer 4

No, it is regulated by the renin-angiotensin system therefore patient won’t experience aldosterone deficiency related symptoms.

Question 5

Describe the differences you would see in a blood test for Primary vs Secondary Hypogonadism.

Answer 5

Primary Hypogonadism —> Destruction of testes (e.g. mumps) or ovaries (eg. due to chemo). Fall in testosterone or oestrogen but rise in FSH/LH —> less -ve feedback to AP gonadotrophs.
Secondary Hypogonadism —> eg. pituitary tumour damaging gonadrotrophs. Can’t make LH/FSH —> fall in LH/FSH and a consequent fall in T and O.

Question 6

Describe the possible acquired causes for Hypopituitarism and explain what happens to cause this?

Answer 6

Tumours e.g. adenomas, metastases, cysts
Radiation (hypothalamic/pituitary damage)
Infection e.g. meningitis
Traumatic brain injury
Pituitary surgery
Inflammatory (hypophysitis)
Pituitary apoplexy - haemorrhage (or less commonly infarction)
Peri-partum infarction (Sheehan’s syndrome)

Question 7

Describe the possible congenital cause for Hypopituitarism and explain what happens to cause this?

Answer 7

• Rare
• Usually due to mutations of transcription factor genes needed for normal anterior pituitary development such as PROP1 mutation
• Deficient in GH and at least 1 more anterior pituitary hormone therefore they are short in stature
• Hypoplastic (underdeveloped) anterior pituitary gland on MRI

Question 8

What is loss of both anterior and posterior pituitary function referred to as?

Answer 8

Panhypopituitarism

Question 9

If you are going to lose anterior pituitary function because of radiotherapy then which hormones are lost first as a result of this?

Answer 9

GH and gonadotrophins are most sensitive

Question 10

If you are going to increase activity of a hormone because of radiotherapy then which hormone is affected?

Answer 10

Dopamine release reduced leading to an increase in the amount of prolactin due to decreased hypothalamic dopamine inhibition

Question 11

What are the causes of radiotherapy induced hypopituitarism?

Answer 11

• Pituitary and hypothalamus are both sensitive to radiation
• Direct: radiotherapy targeting pituitary (e.g. hormone producing pituitary tumour)
• Indirect: CNS tumour nearby
  + Higher the RT dose (measured in Gy), higher the risk of HPA axis damage

Question 12

How long does the risk of damage to the anterior pituitary last after radiotherapy?

Answer 12

• Up to 10 years so patients require an annual assessment
• Radiotherapy is a slow process so effects on pituitary/hypothalamus aren’t immediately seen

Question 13

What are the presentations of hypopituitarism due to a lack of FSH/LH?

Answer 13

Reduced libido
Secondary amenorrhoea
Erectile dysfunction
Reduced pubic hair

Question 14

How does the lack of ACTH present itself in hypopituitarism?

Answer 14

Fatigue

Note: not a salt losing crisis as aldosterone is not regulated by ACTH, only cortisol is

Question 15

What effect does the lack of TSH have in hypopituitarism?

Answer 15

Fatigue - body’s energy production requires a certain amount of thyroid hormones

Question 16

What effect does the lack of GH have in hypopituitarism?

Answer 16

Reduced quality of life (difficult to measure)

Note: short stature only seen in children

Question 17

How does the effect on prolactin in hypopituitarism present itself?

Answer 17

Inability to breastfeed

Question 18

Briefly describe the pathophysiology behind Sheehan’s syndrome

Answer 18

• Anterior pituitary enlarges in pregnancy due to lactotroph hyperplasia
• Post-partum haemorrhage leads to hypotension (drop in BP) which leads to a pituitary infarction (tissue death - lack of blood and oxygen) in the enlarged anterior pituitary
• This leads to Post-Partum Hypopituitarism (PPH)

Question 19

What are some of the symptoms of Sheehan’s syndrome?

Answer 19

• Lethargy, anorexia and weight loss are due to a TSH, ACTH and GH deficiency
• Failure to lactate - prolactin deficiency
• Failure to resume menses post-delivery

Question 20

Is the posterior pituitary usually affected in Sheehan’s syndrome and if so, how?

Answer 20

No, it is not. It is neural tissue not glandular (continuous with hypothalamus)

Question 21

Outline the pathophysiology of pituitary apoplexy

Answer 21

Bleeding (haemorrhage) into the pituitary or loss of blood flow (infarction) to the pituitary
Often dramatic presentation in patients with pre-existing pituitary tumours (adenomas)
May be first presentation of a pituitary adenoma
Can be precipitated by anti-coagulants (blood thinners)

Question 22

What are the symptoms of a pituitary apoplexy?

Answer 22

Severe sudden onset headache
Visual field defect – compressed optic chiasm, bitemporal hemianopia
Cavernous sinus involvement may lead to diplopia (IV, VI) - double vision, ptosis (III) - drooping of eyelid

Question 23

What must you consider when making a biochemical diagnosis of hypopituitarism?

Answer 23

Cortisol – what time of day?
T4 – circulating t(1/2) - 6 days - long half life (takes time for levels to drop)
FSH/LH – cyclical in women
GH/ACTH - pulsatile

Question 24

Outline how a dynamic pituitary function test works

Answer 24

• Insulin injected to induce hypoglycaemia (<2.2mM glucose)
• ACTH and GH are stress hormones - secreted in response to hypoglycaemia
• Measure multiple blood samples from tap - measure cortisol, not ACTH
• Measure GH, TSH, FSH/LH

However, hormone levels do fluctuate based on different factors so tests can’t be considered in isolation

Question 25

What technique is used for a radiological diagnosis of hypopituitarism?

Answer 25

Pituitary MRI

Question 26

How do you treat prolactin deficiency in hypopituitarism?

Answer 26

Can’t give prolactin back
However not much effect - no known prolactin deficiency syndrome

Question 27

How do you confirm and treat GH deficiency in hypopituitarism?

Answer 27

According to NICE Guidance
Dynamic pituitary function test
Assess Quality of Life (QoL) using specific questionnaire
Daily injection

Measure response by
- improvement in QoL
- plasma IGF-1

Question 28

How do you treat TSH deficiency?

Answer 28

Replace once daily with levothyroxine

Question 29

How is TSH deficiency treated differently in secondary hypothyroidism than in primary hypothyroidism?

Answer 29

In SH, TSH will be low, so you can’t use this to adjust dose as you do in primary hypothyroidism, according to TSH levels
Aim for a fT4 above the middle of the reference range

Question 30

How do you treat ACTH deficiency?

Answer 30

Replace cortisol rather than ACTH
Difficult to mimic diurnal variation of cortisol
Synthetic glucocorticoids:
Prednisolone once daily AM eg 3mg
Hydrocortisone three times per day eg 10mg/5mg/5mg

Question 31

Who is at risk of an adrenal crisis and what are the symptoms?

Answer 31

Patients with primary adrenal failure (Addison’s) or secondary adrenal failure (ACTH deficiency) at risk
Triggered by intercurrent illness
Symptoms: dizziness, hypotension, vomiting, weakness - can result in collapse and death

Question 32

What are the sick day rules?

Answer 32

Patients who take replacement steroid must be told sick day rules
Wear steroid alert pendant/bracelet
Double steroid dose (glucocorticoid not mineralocorticoid) if fever/intercurrent illness
Unable to take tablets (eg vomiting), inject IM or come straight to A & E

Question 33

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

Answer 33

Replace testosterone (topical or intramuscular most popular)
Measure plasma testosterone

Question 34

Does replacing testosterone restore spermicide production?

Answer 34

No, replacing testosterone does not restore sperm production as this is dependent on FSH

Question 35

How is LH/FSH deficiency treated in men when fertility is required and is sperm production instant?

Answer 35

Induction of spermatogenesis by gonadotropin injections
Best response if secondary hypogonadism has developed after puberty
Measure testosterone and semen analysis

No, sperm production may take 6-12 months

Question 36

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

Answer 36

Replace oestrogen
Oral or topical
Will need additional progestogen if intact uterus - prevents endometrial hyperplasia

Question 37

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

Answer 37

Ovulation induced by carefully timed gonadotropin injections (IVF)