Hyposecretion of anterior pituitary hormones Flashcards
Name the 5 anterior pituitary hormones:
LH/FSH- gonadotrophins
Prolactin-lactation post-partum
TSH- stimulates thyrotrophin release from thyroid
GH- somatotrophin
ACTH- stimulates cortisol release from adrenal cortex
Outline the disorder category levels of endocrinological disease:
Primary endocrine disorder: disease affecting the endocrine gland itself eg: primary hypothyroidism (lack of T3/T4)
Secondary endocrine disorder: disease affecting the adenohypophysis eg: TSH deficiency
Tertiary endocrine disorder: disease affecting hypothalamus
What is hypopituitarism/panhypopituitarism?
What is panhypopituitarism sometime’s called?
Decreased production of ALL anterior pituitary hormones.
Can be all or be a specific one.
Causes: congenital (rare) or acquired
Simmond’s disease
Features and causes of congenital panhypopituitarism:
- RARE
- Caused by mutations in transcription factor genes needed for normal APG development eg PROP1 mutation.
- usually lack of growth hormone and one other APG hormone
- Short stature due to lack of GH
- Hypoplastic (underdeveloped) APG on MRI
What are the causes of acquired panhypopituitarism?
- COMMON
- Tumours
Hypothalamic: craniopharyngomas
Pituitary: adenomas, mestastases, cysts
•Radiation (effects from cancer treatment)
hypothalamic/pituitary damage
GH most vulnerable, TSH relatively resistant
- Infection eg meningitis
- Traumatic brain injury
- Infiltrative disease – often involves pituitary stalk
eg neurosarcoidosis
- Inflammatory (hypophysitis)= AI destruction of PG
- Pituitary apoplexy (damaged PG)
- haemorrhage (or less commonly infarction)
•Peri-partum infarction (Sheehan’s syndrome)
What does panhypopituitarism present with and why?
Symptoms are due to deficiency in hormomnes:
FSH/LH- secondary hypogonadism; secondary amennorhoea, reduced libido, ED
TSH- secondary hypothyroidism; fatigue
ACTH- secondary hypoadrenalism; signal missing from PG to make cortisol, fatigue
Explain the aetiology of Sheehan’s syndrome:
Sheehan’s syndrome describes post partum hypopituitarism secondary to post partum haemorhage.
In pregnancy APG enlarges due to lactotrophic hyperplasia, increasing the vascular demand of the APG.
During post-partum haemorrhage, hypotension occurs causing decreased blood flow to the APG, causing a pituitary infarction.
Less common in developed country due to lesser risk of PPH.
What is the presenation of Sheehan’s syndrome:
Lethargy/anorexia/weightloss:
TSH deficiency/ ACTH defiency (cortisol increases appetite)/ GH deficiency
Failure of lactation
Failure to resume menses post partum
What is pituitary apoplexy, which pituitary is it common in?
Intra-pituitary haemorrhage or (less common) infarction.
Dramatic presentation in Patients with pre-existing pituitary adenomas
- can be the first sign of a pituitary adenoma
- may be precipitated by anti-coagulants (blood thinners cause a bleed)
What are presentations and symptoms of pituitary apoplexy?
- Sudden severe onset headaches
- Visual field defects: bleeding compresses optic chiasm= bilateral hemianopia (loss of outer field vision in both eyes
- bleeding into Cavernous sinus: diplopia (double vision) and ptosis (drooping of eyelid)
Outline two types of diagnosis of hypopituitarism
BIOCHEMICAL DIAGNOSIS:
basal plasma conc of pituitary hormone/target endocrine gland hormone
Hormones fluctuate, single measurement is not a good indicator
undetectable cortisol – what time of day? Usually starts higher in the morning, decreases throughout the day.
- T4 – circulating t1/2 6 days
- FSH/LH – cyclical
- GH/ACTH - pulsatile
Stimulated/dynamic pituitary function test:
ACTH/GH stress hormones so induce stress
>2mMol/L hypoglycaemia
Insulin-induced hypoglycaemia stimulates
GH release
ACTH release (cortisol measured)
- TRH given at same time stimulates TSH release
- GnRH given at same time stimulates FSH & LH release
RADIOLOGICAL DIAGNOSIS:
PITUITARY MRI: may reveal adenoma, haemorrhage( apoplexy)
Empty sella (thin rim of tissue indicating hypopituitarism has been for a long time
Lok for posterior bright spot on MRI
Which hormone replacament therapy is used in hormone deficiencies, how is the efficacy checked?
What is the effect of GH deficiency in adults vs children?
- in children results in short stature (=2 SDs < mean height for children of that age and sex)
- in adults, effects less clear
Pathological short stature- if GH deficiency proved then GH injections given
What are the different causes of short stature?
Genetic
Emotional deproivation -stress shuts down growth axis
endocrine deficiency: Cushings, hypothyroidism, GH deficiency
Systemic disease eg CF
malnutrition
malabsorption- eg coeliac disease
skeletal dysplasias: OI, achondroplasia
Describe the growth axis:
Adenohypophysis is under hypothalamic control.
Hypothalamic signal GHRH is released, stimulating somatotrophs to secrete GH.
This travels to target tissues: muscle and liver
In the liver: stimulated to make somatomedins (IGF1 (metabolic) and IGF2 (fetal development) which also have effects on the target tissues
Outline the causes of short stature in children with refernece to the growth axis:
Hypothalamic cause: Prader-Wili Syndrome- GHRH deficiency secondary to hypothalamic dysfuction
Pituitary cause- PITUITARY DWARFISM- GH deficiency= short stature
GH receptor deficiency= LARON DWARFISM= no somatomedins produced
Compare and contrast different types of dwarfism, outlining causes and symptoms:
PWS: GH deficiency secondary to ypothalamic dysfunction.
Learning difficulties, food seeking tendencies
Achondraplasia: mutation in FGR3 (fibroblast growth factor receptor 3) causing mutation in growth plate chondrocytes.
Average size trunk, short limbs
Pituitary dwarfism:
childhood GH deficiency, patient falls off growth chart.
Laron dwarfism:
mutation in GHR- they make GH but no IGF1, so IGF1 injections given
How would you diagnose short stature in children?
MID PARENTAL HEIGHT
A predicted adult height –
based on father’s & mother’s height
GROWTH CHART MONITORING (see image)
9th centile at aged 5y, started to fall down the curves – a drop of more than 2 centiles is flagged, by aged 11y, below the 0.4th centile – diagnosis of coeliac disease made, gluten free diet – starts to grow as predicted
At 11, diagnosed with coeliac disease: malabsorption.
Diet improves: back on trajectory
What are the causes of acquired GH deficiency in adults?
TRauma, pituitary tumour, pituitary surgery, cranial, radiotherapy
How to diagnose GH deficiency in adults?
Random GH measurement is useless- GH is pulsaltile
use provocation tests:
GHRH + ARGININE (i.v.) (in combination more effective than each alone)- arginine given in the form of marmite. mechanism unknown but may inhibit SS relase, and stimulate GHRH.
INSULIN (i.v.) – via hypoglycaemia- GH spurt. If GH defiency= no spurt (see image) NICE cut off =3mcg/L so if less than 3= deficient.
GLUCAGON (i.m.)
EXERCISE (e.g. 10 min step climbing; when appropriate)
Measure plasma GH at specific time-points (before and after)
What is the treatment of GH deficiency and adminstration?
•Preparation:
–Human recombinant GH
- (approved name: SOMATOTROPIN)
- Administration:
–Daily, subcutaneous injection
–Monitor clinical response &
adjust dose to IGF-1
GH DEFICIENCY IN ADULTS:
SIGNS AND SYMPTOMS
- Reduced lean mass, increased adiposity, increased waist:hip ratio
- Reduced muscle strength & bulk à reduced exercise performance
- Decreased plasma HDL-cholesterol & raised LDL-cholesterol ( bad lipid profile)
- Impaired ‘psychological well being’ and reduced quality of life
What are the potential benefits and risks of GH therapy in adults:
Benefits:
- Improved body composition – decreased waist circumference, less visceral fat- decrease CVS risk
- 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
Risks:
Increased susceptibility to cancer
– no data to support this currently
Expensive – NICE estimated cost of lifelong GH treatment in adult = £42K
