Hyposecretion Of Anterior Pituitary Hormones Flashcards
Anterior pituitary hormones
FSH/LH (gonadotrophins) Prolactin GH TSH ACTH
Anterior pituitary action
Hypothalamus makes releasing/inhibiting hormone
Anterior pituitary hormone releases hormone
Endocrine gland (thyroid, gonads, adrenal cortex) produces primary hormone
Disorder in the endocrine gland results in
Primary endocrine gland disease
Disorder in the anterior pituitary results in
Secondary endocrine gland disease
Panhypopituitarism
Decreased production of all anterior pituitary hormones
NOTE: congenital is rare, mostly acquired
Congenital panhypopituitarism
Rare
Usually due to mutations of transcription factor genes needed for normal anterior pituitary development
- e.g. PROP1 mutation
Deficient in GH and at least 1 more anterior pituitary hormone
Short stature
Hypoplastic anterior pituitary gland on MRI
Acquired panhypopituitarism (causes)
Tumours
- hypothalamic - craniopharyngiomas
- pituitary - adenomas, metastases, cysts
Radiation
- hypothalamic/pituitary damage
- GH most vulnerable, TSH relatively resistant
Infection (e.g. meningitis)
Traumatic brain injury
Infiltrative disease - often involves pituitary stalk (e.g. neurosarcoidosis)
Inflammatory (hypophysitis)
Pituitary apoplexy
- haemorrhage (or less commonly infarction)
Peri-partum infarction (SHeehan’s syndrome)
Presentation of panhypopituitarism
Occassionally called Simmond’s disease
Symptoms due to deficient hormones:
FSH/LH:
- secondary hypogonadism
- reduced libido
- secondary amenorrhoea
- erectile dysfunction
ACTH:
- secondary hypoadrenalism (cortisoldeficiency)
- fatigue
TSH:
- secondary hypothyroidism
- fatigueSheehan’s syndrome
Specifically describes post-partum hypopituitarism secondary to hypotension (post partum haemorrhage - PPH)
Less common in developed countries
Anterior pituitary enlarges in pregnancy (lactotroph hyperplasia - to make lots of prolactin )
PPH leads to pituitary infarction
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Presentation of Sheehan’s syndrome
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
Bleed into pituitary gland:
- severe sudden onset headache
- visual field defect - compressed optic chiasm, bitemporal hemianopia
Cavernous sinus involvement may lead to diplopia (IV, VI), ptosis (III)
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Diagnosis of hypopituitarism - biochemical
- Basal plasma concentrations of pituitary or target endocrine gland hormones
- interpretation may be limited
- undetectable cortisol - what time of day?
- T4 - circulating t(1/2) 6 days
- FSH/LH - cyclical
- GH/ACTH - pulsatile
- Stimulated (‘dynamic’) pituitary function tests
- ACTH and GH = ‘stress’ hormones
- hypoglycaemia (<2.2mM) = stress
- inuslin-induced hypoglycamia stimulates:
GH release
ACTH release (cortisol measured) - TRH stimulates TSH release
- GnRH stimulates FSH and LH release
Hypopituitarism diagnosis - radiological
Pituitary MRI
May reveal specific pituitary pathology e.g. haemorrhage (apoplexy), adenoma
Empty sella - thin rim of pituitary tissue
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Hormone replacement therapy in hypopituitarism
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Growth hormone (somatotrophin) deficiency
In children = short stature (=2 SDs < mean height for children of that age and sex)
In adults = effects less clear
Causes of short stature
Genetic
- Down’s syndrome, Turner’s syndrome, Prader Willi syndrome
Emotional deprivation
Systemic disease
- cystic fibrosis, rheumatoid arthritis
Malnutrition
Malabsorption
- Coeliac disease
Endocrine disorders
- Cushing’s syndrome, hypothyroidism, GH deficiency, poorly controlled T1DM
Skeletal dysplasias
- Achondroplasia, osteogenesis imperfecta
The growth axis
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The growth axis - causes of short stature in children
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Prader Willi syndrome
GH deficiency secondary to hypothalamic dysfunction
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
Pituitary dwarfism
Childhood GH deficiency
Laron dwarfism
High incidence in a specific village in Ecuador - descendants of Spanish Sephardic Jews fleeing Spain during Inquisition
Mutation in GH receptor
IGF-1 treatment in childhood can increase height
Diagnosis of short stature
Mid parental height
A predicted adult height - based on father’s and mother’s height
Causes of acquired Gh deficiency in adults
Trauma Pituitary tumour pituitary surgery Cranial Radiotherapy
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Diagnosis of GH deficiency
RandomGh little use - pulsatile Provocative challenge (i.e. stimulation) test
GH provocation tests
GHRH + arginine (i.v.) (in combination more effective than each alone)
Insulin (i.v.) - via hypoglycaemia
Glucagon (i.m.)
Exercise (e.g. 10 minute step climbing; when appropriate)
Measure plasma GH at specific time - points (before and after)
Growth hormone secretion in response to hypoglycaemia
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Growth hormone therapy
Preparation:
- human recombinant GH (approved name = somatotrophin)
Administration:
- daily, subcutaneous injection
- monitor clinical response and adjust dose to IGF-1
GH deficiency in adults: signs and symptoms
Reduced lean mass, ncreased adiposity, increased waist:hip ratio
Reduced muscle strength and bulk —> reduced exercise performance
Decreased plasma HDL-cholesterol and raised LDL-cholesterol
Impaired ‘psychological well being’ and redued quality of life
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
Potential risks 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
