1. Hyposecretion of the Anterior Pituitary Hormones

Question 1

Hypopituitarism definition

Answer 1

Decreased production of ALL anterior pituitary hormones (PANhypopituitarim) or of specific hormones

Question 2

Classifying endocrine gland disease

Answer 2

1. Disorders of any endocrine gland results in PRIMARY endocrine gland disease
2. Disorders of the anterior pituitary results in SECONDARY endocrine gland disease
3. Disorders of the hypothalamus results in TERTIARY endocrine gland disorders

Question 3

Causes of panhypopituitarism

Answer 3

• Can be due to congenital defects
• Can be due to gene mutations (rarer) e.g PROP1 mutation- a transcription factor that allows the development of the pituitary gland to take place
• Radiotherapy on pituitary gland

Usually the disese will manifest in adults with progressive loss of pituitary secretion

Question 4

Order of loss of endocrine secretions

Answer 4

1. Gonadotrophins (LH and FSH)
2. GH
3. Thyrotrophin
4. Corticotrophin

Prolactin deficiency is uncommon/unrecognised

Question 5

Three main types of panhypopituitarism

Answer 5

1. Simmond’s disease
2. Steehan’s syndrome
3. Pituitary apoplexy

Question 6

Simmond’s disease causes and symptoms

Answer 6

INSIDIOUS onset- develops very slowly

Causes:

• infiltrative processes
• pituitary adenomas
• craniopharyngomas
• cranial injury
• following surgery

Symptoms mainly manifest due to decreased thyroidal, adrenal and gonadal function

Symptoms:

• Secondary amenorrhoea
• impotence
• loss of labido
• tiredness
• waxy skin
• hypotension

Question 7

Steehan’s syndrome

Answer 7

Specific in WOMEN

Develops acutely following post partum haemorrhage resulting in pituitary infarction- blood loss results in vasoconstrictor spasm of hypophysial arteries:

• Ischaemia of the pituitary
• Necrosis of the pituitary

Question 8

Pituitary apoplexy

Answer 8

Similari to sheehan’s syndrome but is not specific to women

Due to an intra-pituitary infarction or haemorrhage

RAPID presentation in patients with pre-existing pituitary tumours

Question 9

Diagnosis of hypopituitarism

Answer 9

We cannot measure the hypothalamic hormones so we measure the basal plasma values of the pituitary or target endocrine hormones

Most hypothalamic hormones are relesaed in PULSES- so a single measurement means nothing- must do a stimulation/ provocation test

Question 10

Examples of secondary endocrine gland failure

Answer 10

• Gonadotrophins- hypogonadism
• Thyrotrophin- Hypothyroidism
• Corticotrophin- Hypoadrenocorticalism

Question 11

Effects of lack of somatotrophin

Answer 11

In children, presents as pituitary dwarfism

effects in adults are uncertain

Question 12

Causes of GH deficiency in children

Answer 12

1. Congenital

• Deficiency of hypothalamic GHRH
• Mutations of the GH gene
• Developmental abnormalities (e.g aplasia or hypoplasia of the PG)

2. Acquired

• Tumours of the hypothalamus or pituitary
• Other intracranial tumours nearby
• Irradiation
• head injury

Question 13

Endocrine related short stature mechanism

Answer 13

GH is controlled at the hypothalamic level by GHRH and somatostatin

Most endocrine related causes of short stature are due to decreased production of GHRH

GH stimulates the production of IGF 1 (Insulin-like growth factor 1) in the LIVER- this mediates growth effects

Question 14

LARON DWARFISM

Answer 14

Due to a GH receptor defect

As a result the IGF1 levels are low due to the fact that somatotrophin isnt having its effect

Question 15

Kallmann’s syndrome

Answer 15

An example of tertiary hypopituitarism (specific hormone defect)

• Hypogonadism associated with anosmia.
• Cuased by a genetic defect where the neurones in that embryo which will go on to produce GnRH are unable to migrate to the hypothalamus
• The defect also prevents the neurones which develop to give a sense of smell from migrating

Question 16

GH provocation tests

Answer 16

This used to be conducted using IV GHRH

This is now difficult to get hold of so the new standard test is to stimulate GH production by inducing HYPOGLYCAEMIA

GOLD STANDARD: insulin-induced hypoglycaemia (IV)

Other alternatives:

• Arginine- amino acid stimulates GH release
• Glucagon- though it produces hyperglycaemia it may have a stimulatory effect on somatotrophs
• Exercise

Plasma GH must be measured before and after the test

Question 17

Hormone replacement therapy in hypopituitarism

Answer 17

Question 18

Problems with growth hormone therapy in children

Answer 18

Resistence may develop (antibody formation)- so you nee to consider when to start the therapy

Other hormones may also be affected by GH use in which case you must also replace these

Other adverse effects:

• Lipoatrophy at the site of injection
• Intracranial hypertension
• Headaches (as a result of the intracranial hypertension)
• GH is also a cell stimulation hormone so there is increased risk that you’ll stimulate tumours - increased incidence of leukaemia

Question 19

Administration of growth hormone therapy (somatotrophin)

Answer 19

• Subcutaneous or intramuscular
• tend to give DAILY or 4/5 times a week
• tend to give in the afternoon because GH varies during the day and levels tend to be highest at night
• Adjust dose to size

Question 20

Metabolism of somatotrophin

Answer 20

Hepatic/ renal

Relatively short half life- 20 mins

Question 21

Symptoms of GH deficiency in adults

Answer 21

• REduced lean mass
• Increased adiposity
• Increased waist:hip ratio
• Reduced muscle strength and bulk

Question 22

Potential benefits of GH therapy in adults

Answer 22

(Bearing in mind somatotrophin levels naturally fall with age)

• Improved body composition
• Improved muscle strength and capacity
• Normalisation of HDL-LDL balance
• Increased bone mineral content

Question 23

potential risks of GH therapy in adults

Answer 23

• Increased risk of cardiovascular events (can cause cardiomegaly)
• Increased soft tissue growth
• Increased susceptibility to cancer