Hyposecretion of Anterior Pituitary Hormones Flashcards
07.10.2019
What is the tissue type of the anterior and posterior pituitary?
AP: glandular tissue (upward growth from buccal cavity)
PP: neural tissue (downward growth from the base of the brain)
What are the anterior pituitary hormones and cell types?
FSH/LH (gonadotrophs) PROLACTIN (lactotrophs) GH = somatotrophin (somatotrophs) TSH (thyrotrophs) ACTH (corticotrophs)
What is a secondary endocrine gland disease?
The problem lies within the anterior pituitary
What is a primary endocrine gland disease?
The problem lies within the endocrine gland itself, e.g. thyroid, adrenal cortex, gonads…
Hypopituitarism
DECREASED PRODUCTION OF ALL ANTERIOR PITUITARY HORMONES (PANHYPOPITUITARISM) OR: OF SPECIFIC HORMONES
-> CONGENITAL (rare) or ACQUIRED
What is a decreased production of all AP hormones called?
Panhypopituitarism
Congenital panhypopituitarism
- rare
- usually due to a mutation of TF genes needed for normal AP development
- deficient in GH and at least one other AP hormone
- short stature
- hypoplastic pituitary gland on MRI
What is a mutation that can cause congenital panhypopituitarism?
PROP 1 -> the expression of PROP1 leads to ontogenesis of pituitary gonadotropes as well as somatotropes, lactotropes and caudomedial thyrotropes.
“Ontogenesis”
The development of an individual organism or anatomical or behavioural feature from the earliest stage to maturity.
Acquired Panhypopituitaruism (Causes)
- Tumors (hypothalamic: craniopharyngioma; pituitary: adenomas, metastases, cysts)
- Radiation (-> hypothalamic/pituitary dmagage; GH is most vulnerable, TSH is relatively resistant)
- Infection (e.g. meningitis)
- Traumatic Brain Injury
- Infiltrative diseases (-> often involve the pituitary stalk e.g. neurosarcoidosis)
- Inflammatory (hypophysitis)
- Pituitary Apoplexy (haemorrhage or less common infarction)
- Peri-partum infarction (Sheehan’s Syndrome)
How does Panhypopituitarism present?
FSH/LH: Secondary hypogonadism
- > Reduced libido - > Secondary amenorrhoea - > Erectile dysfunction
ACTH: Secondary hypoadrenalism (cortisol deficiency)
-> Fatigue
TSH : Secondary hypothyroidism
-> Fatigue
Simmond’s disease
Panhypopituitarism is occasionally called this.
What part of the pituitary is affected in Sheehan’s syndrome?
Only the anterior pituitary.
Sheehan’s Syndrome
- Post-partum hypopituitarism secondary to hypotension. PPH (post partum haemorrhage) leads to pituitary infarction.
- less common in developed countries
- pituitary increases in size in pregnancy due to lactotroph hyperplasia
How does Sheehan’s syndrome present?
- Lethargy, anorexia, weight loss – TSH/ACTH/(GH) deficiency
- Failure of lactation – PRL deficiency
- Failure to resume menses post-delivery
- Posterior pituitary usually not affected
Pituitary Apoplexy
- Intra-pituitary haemorrhage or (less commonly) infarction
- Often dramatic presentation in patients with pre-existing pituitary tumours (adenomas)
- May be first presentation of a pituitary adenoma
- Can be precipitated by anti-coagulants
Diplopia
Double vision
Ptosis
Droopy upper eyelid
How does pituitary apoplexy present?
- SEVERE sudden onset headache
- Visual field defect – compressed optic chiasm, bitemporal hemianopia
- Cavernous sinus involvement may lead to diplopia (IV, VI), ptosis (III)
How can you diagnose hypopituitarism? (simple)
- biochemical tests (basal plasma levels or dynamic tests)
- radiology (pituitary MRI)
Biochemical methods to diagnose hypopituitarism
- Basal plasma concentrations of pituitary or target endocrine gland hormones;
HOWEVER:- interpretation may be limited
- undetectable cortisol – what time of day?)
- T4 – circulating t1/2 6 days
- FSH/LH – cyclical
- GH/ACTH - pulsatile
- Stimulated (‘Dynamic’) Pituitary Function Tests
- ACTH & GH = ‘stress’ hormones
-> Hypoglycaemia (<2.2mM) = ‘stress’
-> Insulin-induced hypoglycaemia stimulates- GH release
- ACTH release (cortisol measured)
- TRH stimulates TSH release
- GnRH stimulates FSH & LH release
- ACTH & GH = ‘stress’ hormones
Radiological methods to diagnose hypopituitarism
Pituitary MRI
- May reveal specific pituitary pathology (eg haemorrhage (apoplexy), adenoma)
- Empty sella – thin rim of pituitary tissue
How do you treat Hypopituitarism?
Hormone replacement and check hormone levels to make sure that the dose is right.
-> see powerpoint cards
What does growth hormone deficiency cause?
Children: short stature (2SD < mean height of children that same age and sex)
Adults: effects less clear
What are genetic causes of short stature?
Down Syndrome
Turner syndrome
Prader Willi Syndrome
What are the causes for short stature
- genetic
- emotional deprivation
- systemic disease (CF, rheumatoid arthritis)
- Malnutrition
- Malabsorption (e.g. coeliac disease)
- endocrine disorders (Cushing’s syndrome, hypothyroidism, GH deficiency, uncontrolled T1DM)
- skeletal dysplasias ( achondroplasia, osteogenesis imperfecta)
What are some endocrine disorders that cause short stature?
- Cushing’s syndrome
- hypothyroidism
- GH deficiency
- poorly controlled T1DM
Cushing’s syndrome vs disease
S: cause unknown
D: pituitary adenoma
(excessive cortisol)
skeletal dysplasia causes for short stature
- Achondroplasia
- Osteogenesis imperfecta
What can cause short stature due to malabsorption?
Coeliac disease
What are IGFI and IGFII?
Insulin like growth factors 1 and 2
When GH is secreted it acts on the liver and IGFI and IGFII are set free and act on body tissues.
Laron Dwarfism
- due to GH receptor mutation
- IGF-1 treatment in childhood can increase height
- High incidence in a specific village in Ecuador – descendants of Spanish Sephardic Jews fleeing Spain during Inquisition
Pituitary dwarfism
lack of GH
Dwarfism (Achondroplasia)
- Mutation in Fibroblast Growth Factor Receptor 3 (FGF3)
- Abnormality in growth plate chondrocytes - impaired linear growth)
- Average size trunk
- Short arms and legs
What are causes of acquired GH deficiency in adults?
- TRAUMA
- PITUITARY TUMOUR PITUITARY SURGERY
- CRANIAL RADIOTHERAPY
How can you diagnose GH deficiency?
- random blood test is of little use as the levels are pulsatile
- PROVOCATION CHALLENGE (i.e. stimulation test)
What are signs of GH deficiency?
- 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’ and reduced quality of life
What are the downsides of GH therapy in adults?
Increased susceptibility to cancer
– no data to support this currently
Expensive – NICE estimated cost of lifelong GH treatment in adult = £42K
- Daily injections
Potential benefits of GH therapy in adults
- Improved body composition – decreased waist circumference, less visceral fat
- Improved muscle strength and exercise capacity
- More favourable lipid profile - higher HDL-cholesterol, lower LDL-cholesterol
- Increased bone mineral density
- Improved psychological well being and quality of life
GH Therapy
- Preparation: Human recombinant GH (approved name: SOMATOTROPIN)
- Administration: Daily, subcutaneous injection; Monitor clinical response & adjust dose to IGF-1
Do patients with Prader Willi Syndrome respond to GH?
Yes they do.
The problem with Prader Willi and short stature lies within the hypothalamus.
What are some possible GH provocation tests?
- GHRH and Arginine (in marmite) i.v. should increase GH
- Insulin via hypoglycaemia should cause GH release
- Glucagon i.m. causes GH and ACTH increase (makes you vomit, so probably through the stress of that)
- exercise (done in children)
-> measure GH levels before and after
Summarise congenital panhypopituitarism
- rare
- usually due to a mutation in a TF needed for normal AP development.
- e.g. PROP1 -> deficient in GH and at least one more AP hormone
- short stature and hypoplastic AP on MRI
