Hypopituitarism & Anterior Pituitary dysfunction

Question 1

what are the anterior pituitary hormones

Answer 1

Growth Hormone
Prolactin
Thyroid stimulating hormone
Lutenising hormone/Follicle stimulating hormone
Adrenocorticotrophic hormone

Question 2

where does the pituitary sit

Answer 2

Sella turcica of sphenoid bone

Question 3

what does the anterior pituitary rely on?

Answer 3

the hypothalamus (to regulate function by releasing or inhibiting factors which travel via portal circulation)

Question 4

what factors are released by the hypothalamus for the AP

Answer 4

growth hormone releasing hormone
somatostatin
thyrotrophin releasing hormone
dopamine
gonadotrophin releasing hormone
corticotrophin releasing hormone

Question 5

what is a primary endocrine disease

Answer 5

disease where the pathology originates in the gland itself e.g thyroid, adrenal cortex (cortisol), gonads

Question 6

what is a secondary endocrine disease

Answer 6

disease where the pathology originates in the signals from the hypothalamus/anterior pituitary

Question 7

what is primary hypothyroidism

Answer 7

thyroid doesn’t produce thyroxine e.g. due to autoimmune destruction of thyroid gland
Hashimotos
T3&4 fall TSH high (we don’t measure TRH but that would also be high)

Question 8

what is secondary hypothyroidism

Answer 8

eg pituitary tumour damaging thyrotrophs
Can’t make TSH
TSH falls
T3 & T4 fall (as no TSH)

Question 9

what is primary hypoadrenalism

Answer 9

Addisons disease
adrenal cortex damaged/destroyed by autoimmune
ACTH high, cortisol low (we don’t measure CRH but that would also be high)

Question 10

what is secondary hypoadrenalism

Answer 10

E.g. pituitary tumour damaging corticotrophs
adrenal cortex functioning,
but can’t make ACTH
ACTH falls, cortisol low

Question 11

what is primary hypogonadism

Answer 11

eg destruction of testes (eg mumps) or ovaries (eg chemotherapy)
Testosterone (men) or oestrogen (women) fall, LH & FSH increase (we don’t measure GnRH but that would also be high)

Question 12

what is secondary hypogonadism

Answer 12

eg pituitary tumour damaging gonadotrophs
Can’t make LH/FSH
LH/FSH fall, Testosterone/oestrogen fall

Question 13

congenital causes of hypopituitarism

Answer 13

Rare. Usually due to mutations in transcription factor genes needed for normal anterior pituitary development e.g PROP1

Question 14

what are the signs of congenital hypopituitarism

Answer 14

deficient in GH & at least one more hormone since birth
Short stature
Hypoplastic (underdeveloped) anterior pituitary on MRI

hypoplastic (underdeveloped) anterior pituitary

Question 15

acquired causes of hypopituitarism

Answer 15

Tumours (adenoma, metastases, cysts)
radiation
infection (meningitis)
traumatic brain injury
pituitary surgery
inflammation (hypophysitis)/autoimmunity
pituitary apoplexy (haemorrhage, or less commonly infarction)
Peri-parturm infarction (Sheehan’s syndrome)

Question 16

what is hypophysitis

Answer 16

inflammation of the pituitary or infundibulum

Question 17

what is pituitary apoplexy

Answer 17

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

Question 18

what is the name for complete loss of pituitary function (post. and ant.)

Answer 18

panhypopituitarism

Question 19

what are the causes of pituitary apoplexy

Answer 19

haemorrhage

less commonly infarction

Question 20

what procedures may cause radiotherapy-induced hypopituitarism
What factor is risk of HPA damage proportional to

Answer 20

Radiotherapy directly to pituitary (e.g. hormone producing pituitary tumor) or indirect (e.g. CNS tumor nearby)
Higher total radiotherapy dose (Gy)= higher risk of HPA axis damage

Question 21

what hormones are most sensitive to radioactivity

Answer 21

Growth hormone and gonadotrophins

Question 22

how long does the risk of radiotherapy persist for?

Answer 22

up to 10yrs, so annual assessment

Question 23

how does hypopituitarism affecting LH/FSH present?

Answer 23

reduced libido
secondary amenorrhoea
erectile dysfunction
reduced pubic hair

Question 24

how does hypopituitarism affecting ACTH present?

Answer 24

fatigue
Not a salt losing crisis (that’s RAAS)

Question 25

how does hypopituitarism affecting TSH present?

Answer 25

fatigue, weight gain

Question 26

how does hypopituitarism affecting GH present?

Answer 26

reduced quality of life, short stature in children

Question 27

how does hypopituitarism affecting Prolactin present?

Answer 27

inability to breastfeed

Question 28

what is sheehan's syndrome? In what regions of the world is it most common?

Answer 28

post-partum haemorrhage—> postpartum hypotension—>pituitary infarction—> postpartum hypopituitarism Most common in developing countries

Question 29

what are the signs/ effects of sheehans syndrome

Answer 29

lethargy, anorexia, weight loss ((bc loss of GH, ACTH, TSH)), failure of lactation, failure to resume menses Posterior pituitary not usually affected

Question 30

what happens to the pituitary during pregnancy

Answer 30

enlargement (lactotroph hyperplasia)

Question 31

what is the onset of pituitary apoplexy? What is it often precipitated by

Answer 31

dramatic and sudden often precipitated by anti-coagulants

Question 32

what are the signs of pituitary apoplexy

Answer 32

severe sudden onset headache visual field defect - bitemporal hemianopia (optic chiasm compression) Cavernous sinus involvement leads to possible diplopia (IV, VI) and ptosis (III)

Question 33

what methods can be used to diagnose hypopituitarism

Answer 33

blood tests (biochemical diagnosis), dynamic pituitary function tests (stress test), pituitary MRI (radiology)

Question 34

what hormone dysfunction cannot be treated

Answer 34

prolactin

Question 35

what is the NICE guidance for treating hypopituitarism affecting GH?

Answer 35

Confirm GH deficiency on dynamic pituitary function test Assess Quality of Life using specific questionnaire daily injection of GHmeasure response by improvement in quality of life and plasma IGF-1

Question 36

how to confirm GH treatment is working

Answer 36

assess quality of life and measure response/improvement to this Measure serum IGF-1

Question 37

what is the guidance for treating hypopituitarism affecting TSH

Answer 37

once daily levothyroxine TSH will be low so you can’t use this to adjust dose as you would with primary hypothyroidism Aim for fT4 above the middle of the reference range

Question 38

what is the guidance for treating hypopituitarism affecting ACTH? What is the difficulty in this?

Answer 38

Replace cortisol rather than ACTH: prednisolone once daily AM (e.g. 3mg) or hydrocortisone 3x daily (10mg/5mg/5mg) Difficult to mimic diurnal variation of cortisol

Question 39

what is an adrenal crisis

Answer 39

Patients with primary adrenal failure (Addison’s) or secondary adrenal disease (ACTH deficiency) are at risk of dizziness, hypotension, vomiting, weakness triggered by intercurrent illness can collapse and die

Question 40

what should patients taking replacement steroids be advised to do?

Answer 40

“Sick day rules” keep steroid alert pendant/ bracelet double steroid dose if fever/intercurrent illness if unable to take tablets (e.g. vomiting), inject IM or come to A&E

Question 41

what are the guidelines for hypopituitarism affecting LH/FSH in men?

Answer 41

If no fertility is required- replace testosterone topically or IM, measure plasma testosterone. This doesn’t restore sperm production (dependent on FSH) If fertility is required- induce spermatogenesis by gonadotropin injections Measure testosterone and semen analysis Sperm production may take 6-12 months

Question 42

when is fertility in men best conserved?

Answer 42

if secondary hypogonadism developed after puberty (gonads are right size/development)

Question 43

what are the guidelines for hypopituitarism affecting LH/FSH in women?

Answer 43

oral or topical oestrogen addition of progesterone if uterus is intact to prevent endometrial hyperplasia- could increase risk of endometrial cancer if fertility is required, carefully timed and gonadotrophin injections can induce ovulation (IVF)

Question 44

Does the term hypopituitarism refer to anterior or posterior pituitary dysfunction Give examples of processes that can cause both anterior and posterior pituitary dysfunction

Answer 44

Generally refers to anterior pituitary dysfunction Inflammation (hypophysitis) or surgery may cause posterior pituitary dysfunction too

Question 45

Why should you be cautious when interpreting basal plasma hormone concentrations?

Answer 45

Cortisol – what time of day? T4 – circulating t1/2 6 days (so might take several days to have low T4 on test) FSH/LH – cyclical in women GH/ACTH - pulsatile

Question 46

What dynamic pituitary function tests are used in the diagnosis of hypopituitarism

Answer 46

ACTH/GH = ‘stress’ hormones Hypoglycaemia (<2.2mM) = ‘stress’ Insulin-induced hypoglycaemia stimulates GH release ACTH release (cortisol measured) TRH stimulates TSH release GnRH stimulates FSH & LH release

Question 47

Radiological diagnosis of hypopituitarism

Answer 47

Pituitary MRI (CT not so good at delineating pituitary gland) Posterior bright spot- posterior pituitary May reveal specific pituitary pathology eg haemorrhage (apoplexy), adenoma Empty sella – thin rim of pituitary tissue

Question 47

Radiological diagnosis of hypopituitarism

Answer 47

Pituitary MRI (CT not so good at delineating pituitary gland) Posterior bright spot- posterior pituitary May reveal specific pituitary pathology eg haemorrhage (apoplexy), adenoma Empty sella – thin rim of pituitary tissue