Anterior pituitary hyposecretion

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 (rarer)
Acquired

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 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
Pituitary gland physiological swells during pregnancy due to hypertrophy of lactotrophs and in case of post-partum haemorrhage vasoconstrictor spasm of hypophysial arteries causes pituitary infarction
This develops very RAPIDLY

Most obvious symptom - failure to lactate

Also presents with weight loss, fatigue (think low cortisol) and lack of menses (low LH/FSH)

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 (usually of pre-existing microadenoma) This also has a RAPID presentation

Also affects cranial nerves 2 (leading to bitemporal hemianopia) 4 and 6 (leading to diplopia) and 3 (leading to Ptosis)

Question 9

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

Answer 9

Hypothalamic hormones tend to be released in pulses or cycles

Question 10

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

Answer 10

Stimulation (dynamic)/provocation test -

Induce hypoglycaemia <2.2mM with insulin measure GH and ACTH.

Inject TRH and measure TSH

(Sometimes inject GnRH and measure LH/FSH)

Question 11

How are the releasing hormones administered in these tests?

Answer 11

Intravenous

Question 12

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

Answer 12

Children – stunted growth (pituitary dwarfism)

Adults – loss of GH effects are uncertain

Question 13

State some other causes of short stature.

Answer 13

Genetic - Down’s,Turner’s and Prader Willi syndrome

Malnutrition or Malabsorption – Coeliac disease

Emotional deprivation

Endocrine disorders - Cushing’s syndrome, Hypothyroidism, GH deficiency, poorly controlled T1DM

Skeletal - Achondroplasia, osteogenesis imperfecta

Question 14

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

Answer 14

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 15

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

Answer 15

Decreased production of GHRH

Question 16

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 16

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

Question 17

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

Answer 17

Laron Dwarfism - Low IGF I, because functioning GH receptors are necessary for GH to stimulate the production of IGF I

Question 18

Why are the Pygmies in Africa naturally short?

Answer 18

IGF I does not function properly

Question 19

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

Answer 19

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 20

State three triggers for an increase in GH release.

Answer 20

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 21

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

Answer 21

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 22

How is ACTH deficiency treated and monitored?

Answer 22

Give hydrocortisone

Monitor serum cortisol

Question 23

How is TSH deficiency treated and monitored?

Answer 23

Give thyroxine

Monitor serum T4

Question 24

How is LH/FSH deficiency treated and monitored in women?

Answer 24

Give ethinyloestradiol and medroxyprogesterone

Monitor libido and oestrogen deficiency

Question 25

How is LH/FSH deficiency treated and monitored in men?

Answer 25

Give testosterone undecanoate

Monitor libido and serum testosterone

Question 26

How is GH deficiency treated and monitored?

Answer 26

Give GH

Monitor IGF I

Question 27

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

Answer 27

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

Question 28

What is a problem with growth hormone therapy in children?

Answer 28

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

Question 29

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

Answer 29

Subcutaneous or Intramuscular

It is given daily or 4/5 times a week

Question 30

Describe the absorption, metabolism and duration of action of human recombinant GH.

Answer 30

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 31

State some adverse effects of GH therapy in children.

Answer 31

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 32

State some signs and symptoms of GH deficiency in adults.

Answer 32

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 33

How can you diagnose GH deficiency in adults?

Answer 33

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

Question 34

What are the potential benefits of GH therapy in adults?

Answer 34

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 35

What are the potential risks of GH therapy in adults?

Answer 35

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

Question 36

What replacements are given in each anterior pituitary hormone deficiency

Answer 36

Prolactin - None available : (
ACTH - Hydrocortisone
TSH - Thyroxine
LH/FSH (F) - E2 to progestagen (improves symptoms)
LH/FSH (M) - Testosterone (improves symptoms)
GH - GH