What are examples of anterior pituitary hormones?
FSH/LH Prolactin Growth Hormone TSH ACTH
What is hypopituitarism/panhypopituitarism?
Decreased production of ALL adenohypophysial hormones - can be specific however
What usually causes congenital panhypopituitarism?
Mutations of transcription factor genes needed for normal pituitary development eg PROP1 mutation
What is the outcome of congenital panhypopituitarism?
Deficiency of GH and at least 1 other pituitary hormone
What are signs of congenital panhypopituitarism?
Abnormal slowing of growth Delayed puberty Excessive thirst and excessive urination Less frequent menstrual periods Low blood sugar (hypoglycemia) Prolonged jaundice in infants Sensitivity to cold Poor appetite Weight loss or weight gain Unusually dry skin Nausea or dizziness Fatigue or drowsiness Small penis in males
What investigations would you do for congenital panhypopituitarism?
Look for a hypoplastic (underdeveloped) adenohypophysis on an MRI
In what different ways can you acquire panhypopituitarism?
Tumours (hypothalamic or pituitary)
Radiation (GH most vulnerable while TSH is relatively resistant)
Infection
Traumatic brain injury
Infiltrative disease (neurosarcoidosis)
Pituitary apoplexy
Peri-partum infaction (sheehans syndrome)
What symptoms are caused by a FSH/LH deficiency?
Reduced libido
Secondary amenorrhoea
Erectile dysfunction
What symptoms are caused by an ACTH deficiency?
weight loss, lack of appetite (anorexia), muscle weakness, nausea and vomiting, and low blood pressure (hypotension). Low blood levels of sugar and dilutional hyponatremia (low blood sodium levels) may occur
What symptoms are caused by a TSH deficiency?
fatigue, lethargy, cold intolerance, and weight gain
(brittle fingernails; coarsening and thinning hair; puffy eyes; pale, dry skin; weakness; and constipation. Hoarseness; menstrual disorders; puffy hands, face and feet; thickening of the skin; thinning of eyebrows; increased cholesterol levels; muscle and/or joint aches and stiffness; slowed speech; and decreased hearing are symptoms usually expressed later in the course of the disease)
What are the presentations of panhypopituitarism and what is it also called?
Secondary hypogonadism
Secondary hypoadrenalism
Secondary hypothyroidism
Also called Simmond’s disease
What is sheehan’s syndrome?
Post partum hypopituitarism secondary to hypotension due to post partum haemorrhage where due to the already enlarged anterior pituitary that happens in pregnancy and from the hypotension from loss of blood leads to the pituitary becoming underperfused by the small superior hypophyseal artery that supplies all the blood and then infarcts
How does Sheehan’s Syndrome present?
Hard to notice - lethargy, anorexia, weight loss (TSH, ACTH, GH deficiency)
Easy to notice - failure of lactation (prolactin deficiency), failure to resume menstrual cycles post delivery
Normally hard to see sheehans syndrome because lots of the symptoms are normal signs post pregnancy
What is a pituitary aploplexy
An intra pituitary haemorrhage/infarction
What are the symptoms of a pituitary apoplexy?
Severe sudden onset headache, bitemporal hemianopia, diplopia, pitosis
What is diplopia?
Double vision
What is ptosis?
Drooping upper eyelid
How can you biochemically diagnose hypopituitarism?
Basal plasma conc of hormones: cortisol is low, T4/tyroxine, FSH/LH, GH/ACTH
Stimulated pituitary function tests: ACTH/GH are stress hormones, insulin induced hypoglycaemia stimulates GH/ACTH release. TRH stimulates TSH release and GnRH stimulates FSH and LH release
What is stress biochemically defined as in the body?
Hypoglycaemia <2.2mM glucose
How can you radiologically diagnose hypopituitarism?
Pituitary MRI can show things like an ‘empty sella’ where there is only a thin rim of pituitary tissue
If someone is deficient in ACTH what do you treat with to replace the hormone and how do you check?
Replacement: hydrocortisone
Check: Serum cortisol
If someone is deficient in TSH what do you treat with to replace the hormone and how do you check?
Replacement: Thyroxine
Check: Serum free T4
If a woman is deficient in LH/FSH what do you treat with to replace the hormone and how do you check?
Replacement: HRT (E2 plus progestagen)
Check: Symptom improvement, withdrawal bleeds
If a man is deficient in LH/FSH what do you treat with to replace the hormone and how do you check?
Replacement: Testosterone
Check: Symptom improvement, serum testosterone
If someone is deficient in GH what do you treat with to replace the hormone and how do you check?
Replacement: GH
Check: IGF2, growth chart (children)
What are causes of growth hormone deficiency
Genetic eg prader-willi Emotional deprivation Systemic disease Malnutrition Malabsorption eg coeliac disease Endocrine disorders eg cushings, GH deficiency Skeletal dysplasia eg achondroplasia
What is the definition of short stature in children?
<2 SD from the mean
What is the definition of short stature in adults?
Less clear definition
What mutation causes achondroplasia?
Mutation on fibroblast growth factor receptor 3 (FGF3)
What abnormalities happen in achondroplasia?
Abnormalities in growth plate chondrocytes that impairs linear growth resulting in an average sized trunk and short arms/legs
What causes short stature in pituitary dwarfism?
Childhood GH deficiency
What causes short stature in prader willi syndrome?
GH deficiency secondary to hypothalamic dysfunction
What causes short stature in Laron dwarfism?
High local incidence, mutation in GH receptor treated with IGF-1 in childhood
How is short stature diagnosed?
Predicted height calculated according to parents heights and other factors, then the child’s length (later height) is mapped against its weight and followed. If they fall below the lowest line, they often need referring to a paediatrician
What are causes of acquired GH deficiency in adults?
Trauma
Pituitary tumour/surgery
Cranial radiotherapy
How can you diagnose acquired GH deficiency in adults?
Provocative challenge - a stimulation test
GHRH + Arginine (IV), Insulin (IV), glucagon (IM), exercise (10mins).
Plasma GH is then measured at specific time points after.
The NICE cut off for hormonal replacement therapy for GH ?
3mcg/L
How is growth hormone therapy prepared and administered?
Human recombinant GH is administered daily, as a subcutaneous injection that monitors clinical responses and adjusts dose to IGF-1
What is the absorption and distribution of growth hormone therapy?
Maximal concentration in plasma in 2-6 hours
What is the half life of GHRT
20 mins
What is the duration of action of GHRT?
Lasts well beyond clearance with peak IGF1 levels at approx 20 hours
What are GH deficiency symptoms
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.
What are the risks of GHRT
Increased susceptibility to cancer although no currently supported data.
Expensive.