Hyposecretion of Anterior Pituitary Hormones

Question 1

What is the difference between primary, secondary and tertiary endocrine gland disease?

Answer 1

Primary – problem with the endocrine gland/hormone released
Secondary – problem with the pituitary gland/hormone released
Tertiary – problem with the hypothalamus

Question 2

What is the term given to decreased secretion of all anterior pituitary hormones?

Answer 2

Panhypopituitarism

Question 3

Broadly speaking, what can panhypopituitarism be caused by?

Answer 3

Congenital defects (rare) 
Gene mutations (more rare)

Question 4

In what order does loss of secretion occur?

Answer 4

Usually develops in adults with progressive loss of pituitary secretion
Gonadotrophins  
GH
Thyrotrophin 
Corticotrophin 
Prolactin

Question 5

What are three main types of panhypopituitarism?

Answer 5

Simmond’s Disease
Sheehan’s Syndrome
Pituitary Apoplexy

Question 6

Describe the onset of Simmond’s disease and state some of its causes and symptoms.

Answer 6

Insidious (slow) onset  
Can be caused by: 
 Infiltrative diseases  
 Craniopharyngioma 
 Cranial injury 
 Pituitary adenomas  
 Following surgery 
Symptoms: (mainly due to loss of adrenal, gonadal and thyroid function) 
 Impotence  
 Loss of libido 
 Hypotension 
 Tirednesss 
 Secondary amenorrhoea or oligomenorrhoea 
 Loss of body hair  
 Waxy skin

Question 7

State the cause of Sheehan’s syndrome and describe its onset.

Answer 7

This is specific to WOMEN
It is caused by vasoconstrictor spasm of hypophysial arteries as a result of post-partum haemorrhage
This spasm causes pituitary infarction
This develops very RAPIDLY

Question 8

What is pituitary apoplexy? Describe its onset.

Answer 8

This is similar to Sheehan’s syndrome but isn’t specific to women
It is caused by intra-pituitary infarction or haemorrhage This also has a RAPID presentation

Question 9

Why is a single measurement of most hypothalamic hormones not useful?

Answer 9

Most hypothalamic hormones tend to be released in pulses

Question 10

What type of test do you do to test if someone is producing a hormone?

Answer 10

Stimulation/provocation test

Question 11

How are the releasing hormones administered in these tests?

Answer 11

Intravenous

Question 12

What is the name given to the secondary endocrine gland failure that results from a lack of corticotrophin release from the pituitary?

Answer 12

Hypoadrenocorticalism

Question 13

What are the effects of a lack of somatotrophin in children and in adults?

Answer 13

Children – stunted growth (pituitary dwarfism)

Adults – loss of GH effects are uncertain

Question 14

State some other causes of short stature.

Answer 14

Genetic
Malnutrition
Emotional deprivation
Endocrine disorders

Question 15

State some genetic and acquired causes of GH deficiency in children.

Answer 15

Genetic:
 Deficiency of hypothalamic GHRH
 Mutations of GH gene
 Developmental abnormalities (e.g. aplasia or hypoplasia of the pituitary gland)
Acquired:
 Tumours of the hypothalamus and pituitary
 Other intracranial tumours nearby (e.g. optic nerve glioma)
 Irradiation
 Head injury
 Infection or inflammation
 Severe psychosocial deprivation

Question 16

What are most endocrine-related causes of short statue due to (with reference to the HP axis)?

Answer 16

Decreased production of GHRH

Question 17

As well as being its own hormone, GH stimulates the production of other hormones. State one important hormone that is stimulated by GH, its side of production and its effects.

Answer 17

IGF I = insulin-like growth factor I
It is produced in the LIVER
It mediates growth effects

Question 18

What type of dwarfism is caused by a GH receptor defect?

Answer 18

Laron Dwarfism

Question 19

Describe the IGF I levels in people with this type of dwarfism.

Answer 19

LOW IGF I

Because functioning GH receptors are necessary for GH to stimulate the production of IGF I

Question 20

Why are the Pygmies in Africa naturally short?

Answer 20

Their IGF I doesn’t function properly

Question 21

Using GnRH as an example. State and describe two examples of tertiary hypopituitarism.

Answer 21

Kallmann’s Syndrome
 Hypogonadism + Anosmia
 Genetic defect where the neurones in the embryo that will go on to produce GnRH are unable to migrate to the hypothalamus
 So they have a hypothalamus that lacks GnRH neurones
 The defect also affects the migration of neurones involved in olfaction (which causes anosmia)
Prader-Willi Syndrome
 Hypogonadism is one of the aspects of this disorder and the problem is at the level of the hypothalamus

Question 22

What is the gold standard method of testing the ability of the pituitary to release growth hormone?

Answer 22

Insulin-induced hypoglycaemia

Hypoglycaemia is a potent stimulus for growth hormone release

Question 23

State three other triggers for an increase in GH release.

Answer 23

Arginine
Glucagon (seems odd as this increases blood glucose but it turns out that in people who have GH deficiency, glucagon is good at stimulating growth hormone release)
Exercise

Question 24

Describe how the insulin-induced hypoglycaemia test is used to test GH secretion.

Answer 24

In a normal subject, the insulin-induced hypoglycaemia will give a massive rise in GH secretion
If you have a partial deficiency of GH then your response will be reduced

Question 25

For each of the following anterior pituitary hormone deficiencies, state the replacement used and the parameter that is monitored during treatment:

a. ACTH
b. TSH
c. Women - LH/FSH
d. Men - LH/FSH
e. GH

Answer 25

a. ACTH 
Give hydrocortisone 
Monitor serum cortisol 
b. TSH 
Give thyroxine 
Monitor serum T4
c. Women – LH/FSH 
Give ethinyloestradiol and medroxyprogesterone 
Monitor libido and oestrogen deficiency
d. Men – LH/FSH 
Give testosterone undecanoate 
Monitor libido and serum testosterone 
e.GH
Give GH  
Monitor IGF I

Question 26

State some of the effects of growth hormone therapy in children.

Answer 26

Increased linear growth
Decease in body fat
Younger children respond better
Obese children respond better

Question 27

What is a problem with growth hormone therapy in children?

Answer 27

Tolerance may develop so you need to think about when to start GH therapy

Question 28

How is the human recombinant GH used in GH therapy administered and how frequently must it be given?

Answer 28

Subcutaneous or Intramuscular

It is given daily or 4/5 times a week

Question 29

Describe the absorption, metabolism and duration of action of the drug.

Answer 29

It has a maximal plasma concentration after 4-6 hours
Metabolism – renal and hepatic with a short half-life (20 mins)
Duration of action – it works on protein synthesis so it’s duration of action is going to be quite long.
IGF I levels peak after around 20 hours

Question 30

State some adverse effects of GH therapy.

Answer 30

Lipoatrophy at the site of administration Intracranial hypertension
Headaches (due to intracranial hypertension)
GH is also a cell stimulation hormone so there is an increased risk of tumours

Question 31

State some signs and symptoms of GH deficiency in adults.

Answer 31

Decreased muscle mass  
Increased adiposity  
Increased waist: hip ratio  
Decrease HDL and increased LDL 
Reduced muscle strength and bulk 
Impaired psychological wellbeing and quality of life

Question 32

How can you diagnose GH deficiency in adults?

Answer 32

Lack of response to GH stimulation test (e.g. insulin-induced hypoglycaemia)
Low plasma IGF I
Low plasma IGF-BP3

Question 33

What are the potential benefits of GH therapy in adults?

Answer 33

Improved body composition
Improved muscle strength and exercise capacity Normalisation of HDL-LDL
Increased bone mineral content
Improved psychological and mental wellbeing and quality of life

Question 34

What are the potential risks of GH therapy in adults?

Answer 34

Increased risk of cardiovascular accidents
Increased growth of soft tissue e.g. cardiomegaly
Increased susceptibility to cancer