1. Hyposecretion of the Anterior Pituitary Hormones Flashcards
Hypopituitarism definition
Decreased production of ALL anterior pituitary hormones (PANhypopituitarim) or of specific hormones
Classifying endocrine gland disease
- Disorders of any endocrine gland results in PRIMARY endocrine gland disease
- Disorders of the anterior pituitary results in SECONDARY endocrine gland disease
- Disorders of the hypothalamus results in TERTIARY endocrine gland disorders
Causes of panhypopituitarism
- 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
Order of loss of endocrine secretions
- Gonadotrophins (LH and FSH)
- GH
- Thyrotrophin
- Corticotrophin
Prolactin deficiency is uncommon/unrecognised
Three main types of panhypopituitarism
- Simmond’s disease
- Steehan’s syndrome
- Pituitary apoplexy
Simmond’s disease causes and symptoms
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
Steehan’s syndrome
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
Pituitary apoplexy
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
Diagnosis of hypopituitarism
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
Examples of secondary endocrine gland failure
- Gonadotrophins- hypogonadism
- Thyrotrophin- Hypothyroidism
- Corticotrophin- Hypoadrenocorticalism
Effects of lack of somatotrophin
In children, presents as pituitary dwarfism
effects in adults are uncertain
Causes of GH deficiency in children
- Congenital
- Deficiency of hypothalamic GHRH
- Mutations of the GH gene
- Developmental abnormalities (e.g aplasia or hypoplasia of the PG)
- Acquired
- Tumours of the hypothalamus or pituitary
- Other intracranial tumours nearby
- Irradiation
- head injury
Endocrine related short stature mechanism
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
LARON DWARFISM
Due to a GH receptor defect
As a result the IGF1 levels are low due to the fact that somatotrophin isnt having its effect
Kallmann’s syndrome
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
GH provocation tests
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
Hormone replacement therapy in hypopituitarism


Problems with growth hormone therapy in children
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
Administration of growth hormone therapy (somatotrophin)
- 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
Metabolism of somatotrophin
Hepatic/ renal
Relatively short half life- 20 mins
Symptoms of GH deficiency in adults
- REduced lean mass
- Increased adiposity
- Increased waist:hip ratio
- Reduced muscle strength and bulk
Potential benefits of GH therapy in adults
(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
potential risks of GH therapy in adults
- Increased risk of cardiovascular events (can cause cardiomegaly)
- Increased soft tissue growth
- Increased susceptibility to cancer