Hypopituitarism

Question 1

What hormone inhibits the release of GH?

Answer 1

Somatostatin

Question 2

What hormone do each of the following anterior pituitary cells release:
Thyrotrophs 
Lactotrophs 
Somatotrophs 
Gonadotrophs 
Corticotrophs

Answer 2

TSH 
Prolactin 
GH 
LH and FSH 
ACTH

Question 3

Briefly explain the hypothalamus-pituitary circulation.

Answer 3

Hypothalamic regulatory factors are released from hypothalamic parvocellular neurones into the primary
capillary plexus within the median eminence. Exert inhibitory or stimulatory effect on endocrine cells via the secondary capillary plexus. Regulate pituitary hormone production via portal circulation.

Question 4

What will direct dysfunction of the anterior pituitary gland cause?

Answer 4

A downstream inhibition of hormone secretion from the target organs.

Question 5

What happens to T3/T4 and to TSH levels if a patient has primary hypothyroidism?

Answer 5

T3 & T4 decreases, TSH increases
(TRH is unmeasurable) – there is a loss of
negative feedback exerted onto anterior
pituitary gland and hypothalamus.

Question 6

What happens to the levels of T3/T4 and TSH in a patient with secondary hypothyroidism?

Answer 6

TSH falls

T4 and T3 fall

Question 7

Does ACTH regulate aldosterone production?

Answer 7

NO

Aldosterone production is regulated by the renin -angiotensin system

Question 8

What happens to cortisol and ACTH levels in a patient with primary hypoadrenalism?

Answer 8

Cortisol falls
ACTH increases
(we don’t measure CRH but that would also be high)

Question 9

What happens to cortisol and ACTH levels in a patient with secondary hypoadrenalism?

Answer 9

Can’t make ACTH therefore ACTH falls and cortisol falls

Question 10

What happens to a male patients testosterone, and LH and FSH levels if they have primary hypogonadism?

Answer 10

Testosterone will fall, but FSH and LH will increase (we don’t measure GnRH but that would also be high)

Question 11

What type of cause of hypopituitarism is more rare?

Answer 11

Congenital

Question 12

What is a congenital cause of hypopituitarism usually due to? (give an example)

Answer 12

Mutations of transcription factor genes needed for normal pituitary development. e.g. PROP1 mutation

Question 13

Why would being born with hypopituitarism exhibit short stature?

Answer 13

Low GH + at least one more anterior pituitary hormone - therefore don’t grow.

Question 14

What does hypoplastic mean?

Answer 14

Underdeveloped

Question 15

List the acquired causes of hypopituitarism

Answer 15

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

Question 16

What is panhypopituitarism?

Answer 16

The total loss of anterior and posterior pituitary function is panhypopituitarism.

Question 17

Hypopituitarism - nomenclature

Answer 17

May affect one axis, several or all
Often describes anterior pituitary dysfunction, but certain processes - especially inflammation (hypophysitis) or surgery - may cause posterior pituitary dysfunction too.

Question 18

Radiotherapy induced hypopituitarism

Answer 18

Pituitary and hypothalamus are both sensitive to radiation,
- Radiotherapy direct to pituitary (acromegaly)
- Indirect – nasopharyngeal carcinoma
Extent depends on the overall dose of radiotherapy delivered to the hypothalmo-pituitary axis (Gy).

Risk persists up to 10 years after radiotherapy, so there is an annual assessment.

Question 19

What 2 anterior pituitary hormones most sensitive to radiotherapy?

Answer 19

GH and gonadotrophin

Question 20

What hormone can increase after radiotherapy?

Answer 20

Prolactin due to the loss of hypothalamic dopamine

Question 21

Presentation of hypopituitarism for the following hormones:
FSH/LH
ACTH 
TSH 
GH 
PRL

Answer 21

FSH/LH: Reduced libido, secondary amenorrhoea, erectile dysfunction and reduced pubic hair.

ACTH: Fatigue, NB not a salt losing crisis (renin-angiotensin)

TSH: Fatigue

GH: Reduced quality of life, NB short stature only in children

PRL: Inability to breastfeed

Question 22

What is Sheehan’s Syndrome?

Answer 22

Post-partum hypopituitarism secondary to hypotension (post-partum haemorrhage).
Anterior pituitary enlarges in pregnancy (lactotroph hyperplasia).
PPH leads to pituitary infarction.

Question 23

In what parts of the world is Sheehan’s Syndrome most common?

Answer 23

Developing countries

Question 24

What are the symptoms of Sheehan’s syndrome?

Answer 24

Lethargy, anorexia, weight loss- TSH/ACTH/GH deficiency
Failure to lactation – PRL deficiency
Failure to resume menses post-delivery
(Posterior pituitary function maintained)

Question 25

What type of scan is the best way to look at the PG?

Answer 25

MRI

Question 26

What is apoplexy?

Answer 26

Refers to stroke symptoms occurring SUDDENLY. Such symptoms occur due to bleeding into the brain. It can also occur by a blood clot in a brain blood vessel. Conditions such as subarachnoid hemorrhage or stroke are sometimes called apoplexy.

Question 27

What is pituitary apoplexy?

Answer 27

An intra-pituitary haemorrhage or (less commonly infarction) associated with pituitary tumours (adenomas). May be the first presentation of pituitary adenoma. Can be precipitated by anti-coagulants.

Question 28

How may a patient present with pituitary apoplexy?

Answer 28

Severe sudden onset headache Visual field defect – compressed optic chiasm manifesting as bitemporal hemianopia Cavernous sinus involvement may lead to diplopia (IV, VI), ptosis (III).

Question 29

``` What should you be careful of when interpreting the basal plasma concentrations of the following hormones: Cortisol T4 FSH/LH GH/ACTH ```

Answer 29

Cortisol - highest in morning, comes down as the day goes on. T4 - long half life therefore on the first day of pituitary apoplexy T4 levels may be normal. FSH/LH - cyclical in women therefore depends at what time during the menstrual cycle it is measured. GH/ACTH - pulsatile

Question 30

What 2 pituitary hormones can be called as "stress" hormones?

Answer 30

ACTH and GH

Question 31

Explain the purpose of doing a dynamic test in the diagnosis of hypopituitarism.

Answer 31

Insulin induced hypoglycaemia stimulates the release of GH and ACTH (cortisol response). If however the patient doesn't respond by releasing GH and ACTH it means they have hypopituitarism. (TRH stimulates TSH release and GnRH stimulates FSH and LH release).

Question 32

Can you replace prolactin?

Answer 32

No

Question 33

Treatment of GH deficiency

Answer 33

Confirm GH deficiency on dynamic pituitary function test Assess quality of life using specific questionnaire Daily growth hormone injection Measure response by improvement in QoL and plasma IGF-I

Question 34

Treatment of TSH deficiency

Answer 34

Replace with levothyroxine TSH will be low in the case of secondary hypothyroidism. You should therefore aim for fT4 above the middle of the reference as an indicator that the medication is working.

Question 35

Treatment of ACTH deficiency

Answer 35

``` Replace CORTISOL Difficult to mimic diurnal variation of cortisol Prednisolone once daily AM (3mg) OR Hydrocortisone thrice daily 10mg/5mg/5mg ```

Question 36

Outline the sick day rules for patients with ACTH deficiency.

Answer 36

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/intercurrent illness Unable to take tablets (eg vomiting), inject IM or come straight to A&E

Question 37

List adrenal crisis features.

Answer 37

Dizziness, hypotension, vomiting, weakness, can result in collapse and death

Question 38

Treatment of FSH/LH deficiency (Male) - No fertility required

Answer 38

Replace testosterone – topical or intramuscular most popular Measure plasma testosterone Replacing testosterone does not restore sperm production (this is dependent on FSH)

Question 39

Treatment of FSH/LH (Male) - Fertility required

Answer 39

Induction of spermatogenesis by gonadotropin injections. Best response if secondary hypogonadism has developed after puberty. Measure testosterone and semen analysis Sperm production may take 6-12 months.

Question 40

Treatment of FSH/LH deficiency women - No fertility required

Answer 40

Replace oestrogen Oral or topical Will need additional progestogens if intact uterus to prevent endometrial hyperplasia

Question 41

Treatment of FSH/LH deficiency women - Fertility required

Answer 41

Can induce ovulation by carefully timed gonadotropin injections (IVF)