Hyposecretion of anterior pituitary hormones

Question 1

What are examples of anterior pituitary hormones?

Answer 1

FSH/LH
Prolactin
Growth Hormone
TSH
ACTH

Question 2

What is hypopituitarism/panhypopituitarism?

Answer 2

Decreased production of ALL adenohypophysial hormones - can be specific however

Question 3

What usually causes congenital panhypopituitarism?

Answer 3

Mutations of transcription factor genes needed for normal pituitary development eg PROP1 mutation

Question 4

What is the outcome of congenital panhypopituitarism?

Answer 4

Deficiency of GH and at least 1 other pituitary hormone

Question 5

What are signs of congenital panhypopituitarism?

Answer 5

Abnormal slowing of growth
Delayed puberty
Excessive thirst and excessive urination
Less frequent menstrual periods
Low blood sugar (hypoglycemia)
Prolonged jaundice in infants
Sensitivity to cold
Poor appetite
Weight loss or weight gain
Unusually dry skin
Nausea or dizziness Fatigue or drowsiness
Small penis in males

Question 6

What investigations would you do for congenital panhypopituitarism?

Answer 6

Look for a hypoplastic (underdeveloped) adenohypophysis on an MRI

Question 7

In what different ways can you acquire panhypopituitarism?

Answer 7

Tumours (hypothalamic or pituitary)
Radiation (GH most vulnerable while TSH is relatively resistant)
Infection
Traumatic brain injury
Infiltrative disease (neurosarcoidosis)
Pituitary apoplexy
Peri-partum infaction (sheehans syndrome)

Question 8

What symptoms are caused by a FSH/LH deficiency?

Answer 8

Reduced libido
Secondary amenorrhoea
Erectile dysfunction

Question 9

What symptoms are caused by an ACTH deficiency?

Answer 9

weight loss, lack of appetite (anorexia), muscle weakness, nausea and vomiting, and low blood pressure (hypotension). Low blood levels of sugar and dilutional hyponatremia (low blood sodium levels) may occur

Question 10

What symptoms are caused by a TSH deficiency?

Answer 10

fatigue, lethargy, cold intolerance, and weight gain
(brittle fingernails; coarsening and thinning hair; puffy eyes; pale, dry skin; weakness; and constipation. Hoarseness; menstrual disorders; puffy hands, face and feet; thickening of the skin; thinning of eyebrows; increased cholesterol levels; muscle and/or joint aches and stiffness; slowed speech; and decreased hearing are symptoms usually expressed later in the course of the disease)

Question 11

What are the presentations of panhypopituitarism and what is it also called?

Answer 11

Secondary hypogonadism
Secondary hypoadrenalism
Secondary hypothyroidism
Also called Simmond’s disease

Question 12

What is sheehan’s syndrome?

Answer 12

Post partum hypopituitarism secondary to hypotension due to post partum haemorrhage where due to the already enlarged anterior pituitary that happens in pregnancy and from the hypotension from loss of blood leads to the pituitary becoming underperfused by the small superior hypophyseal artery that supplies all the blood and then infarcts

Question 13

How does Sheehan’s Syndrome present?

Answer 13

Hard to notice - lethargy, anorexia, weight loss (TSH, ACTH, GH deficiency)
Easy to notice - failure of lactation (prolactin deficiency), failure to resume menstrual cycles post delivery
Normally hard to see sheehans syndrome because lots of the symptoms are normal signs post pregnancy

Question 14

What is a pituitary aploplexy

Answer 14

An intra pituitary haemorrhage/infarction

Question 15

What are the symptoms of a pituitary apoplexy?

Answer 15

Severe sudden onset headache, bitemporal hemianopia, diplopia, pitosis

Question 16

What is diplopia?

Answer 16

Double vision

Question 17

What is ptosis?

Answer 17

Drooping upper eyelid

Question 18

How can you biochemically diagnose hypopituitarism?

Answer 18

Basal plasma conc of hormones: cortisol is low, T4/tyroxine, FSH/LH, GH/ACTH
Stimulated pituitary function tests: ACTH/GH are stress hormones, insulin induced hypoglycaemia stimulates GH/ACTH release. TRH stimulates TSH release and GnRH stimulates FSH and LH release

Question 19

What is stress biochemically defined as in the body?

Answer 19

Hypoglycaemia <2.2mM glucose

Question 20

How can you radiologically diagnose hypopituitarism?

Answer 20

Pituitary MRI can show things like an ‘empty sella’ where there is only a thin rim of pituitary tissue

Question 21

If someone is deficient in ACTH what do you treat with to replace the hormone and how do you check?

Answer 21

Replacement: hydrocortisone
Check: Serum cortisol

Question 22

If someone is deficient in TSH what do you treat with to replace the hormone and how do you check?

Answer 22

Replacement: Thyroxine
Check: Serum free T4

Question 23

If a woman is deficient in LH/FSH what do you treat with to replace the hormone and how do you check?

Answer 23

Replacement: HRT (E2 plus progestagen)
Check: Symptom improvement, withdrawal bleeds

Question 24

If a man is deficient in LH/FSH what do you treat with to replace the hormone and how do you check?

Answer 24

Replacement: Testosterone
Check: Symptom improvement, serum testosterone

Question 25

If someone is deficient in GH what do you treat with to replace the hormone and how do you check?

Answer 25

Replacement: GH Check: IGF2, growth chart (children)

Question 26

What are causes of growth hormone deficiency

Answer 26

``` Genetic eg prader-willi Emotional deprivation Systemic disease Malnutrition Malabsorption eg coeliac disease Endocrine disorders eg cushings, GH deficiency Skeletal dysplasia eg achondroplasia ```

Question 27

What is the definition of short stature in children?

Answer 27

<2 SD from the mean

Question 28

What is the definition of short stature in adults?

Answer 28

Less clear definition

Question 29

What mutation causes achondroplasia?

Answer 29

Mutation on fibroblast growth factor receptor 3 (FGF3)

Question 30

What abnormalities happen in achondroplasia?

Answer 30

Abnormalities in growth plate chondrocytes that impairs linear growth resulting in an average sized trunk and short arms/legs

Question 31

What causes short stature in pituitary dwarfism?

Answer 31

Childhood GH deficiency

Question 32

What causes short stature in prader willi syndrome?

Answer 32

GH deficiency secondary to hypothalamic dysfunction

Question 33

What causes short stature in Laron dwarfism?

Answer 33

High local incidence, mutation in GH receptor treated with IGF-1 in childhood

Question 34

How is short stature diagnosed?

Answer 34

Predicted height calculated according to parents heights and other factors, then the child's length (later height) is mapped against its weight and followed. If they fall below the lowest line, they often need referring to a paediatrician

Question 35

What are causes of acquired GH deficiency in adults?

Answer 35

Trauma Pituitary tumour/surgery Cranial radiotherapy

Question 36

How can you diagnose acquired GH deficiency in adults?

Answer 36

Provocative challenge - a stimulation test GHRH + Arginine (IV), Insulin (IV), glucagon (IM), exercise (10mins). Plasma GH is then measured at specific time points after.

Question 37

The NICE cut off for hormonal replacement therapy for GH ?

Answer 37

3mcg/L

Question 38

How is growth hormone therapy prepared and administered?

Answer 38

Human recombinant GH is administered daily, as a subcutaneous injection that monitors clinical responses and adjusts dose to IGF-1

Question 39

What is the absorption and distribution of growth hormone therapy?

Answer 39

Maximal concentration in plasma in 2-6 hours

Question 40

What is the half life of GHRT

Answer 40

20 mins

Question 41

What is the duration of action of GHRT?

Answer 41

Lasts well beyond clearance with peak IGF1 levels at approx 20 hours

Question 42

What are GH deficiency symptoms

Answer 42

Reduced lean mass. Increased adiposity Increased waist: hip ratio. Reduced muscle strength/bulk. Reduced exercise performance. Decreased plasma HDL-cholesterol. Raised LDL-cholesterol. Impaired psychological well-being.

Question 43

What are the risks of GHRT

Answer 43

Increased susceptibility to cancer although no currently supported data. Expensive.