Endo 1: Hyposecretion of anterior pituitary hormones Flashcards
5 hormones of AP
LH/FSH, somatotrophin, TSH, prolactin and ACTH
Differentiate primary and secondary endocrine disease
Primary, problem with the gland itself (insufficient primary hormone)
Secondary, lack of stimulation of the gland due to insufficient stimulating hormone (insufficient releasing/inhibiting hormone or anterior pituitary hormone)
TSH and T4 levels in primary and secondary hypothyroidism
Prim- TSH sky high and T4 low
Secondary- TSH low and T4 low
2 types of hypopituitarism
Panhypopituitarism (=all low)
Specific hormones
Explain congenital panhypopituitarism
Mutations of transcription factors genes needed for normal anterior pituitary development I.E. PROP1
What are the conditions for a panhypopituitarism diagnosis
Deficient in GH and one other hormone (short stature and hypoplastic anterior pituitary on MRI)
Acquired causes of panhypopituitarism
(think iri pitta)
TUMOURS- pituitary (adenoma, metastases or cyst) or hypothalamic (craniopharyngioma)
INFILTRATIVE- usually involves infundibulum e.g. neurosarcoidosis
INFLAMMATORY -neurophysitis
TRAUMA
APOPLEXY- infarction or haemorrhage leading to insufficient blood supply
PERI-PARTUM INFARCTION (Sheehan’s syndrome)
INFECTION- e.g. meningitis
RADIATION- hypothalamic or pituitary damage`
Which AP hormone is most and least vulnerable to damage from radiation
Most- GH Least- TSH
Presentation of panhypopituitarism (aka Simmond’s)
Symptoms due to deficient hormones:
FSH/LH: Secondary hypogonadism (sec. amenorrhea, loss of libido, erectile dysfunction)
TSH: Secondary hypothyroidism (fatigue)
ACTH: Secondary hypoadrenalism (cortisol deficiency) so fatigue
Effect of pregnancy on the AP
It grows lots to release lots of prolactin (lactotroph hyperpasia)
Cause of Sheehan’s syndrome (more common is less developed ountries)
Post partum infarction
Basically, mother has a huge haemorrhage during child birth, and the pituitary gland (which is now huge because of all the prolactin it is pumping out) has insufficient blood supply due to hypotension
Presentation of Sheehan’s syndrome
Lethargy, anorexia and weightloss due to TSH/ACTH and GH deficiency
Failure of lactation (despite the lactotroph hyperplasia, the pituitary gland now has impaired blood supply so prolactin deficiency)
Failure to resume menses post devliery (LH/FSH deficiency)
Post. pit not usually affected
In Sheehan’s syndrome, there is less TSH yet the patient loses weight. Why?
Because there is also deficiency of ACTH, and lack of cortisol (i.e. in hypoadrenalism) leads to weight loss
What is pituitary apoplexy
Intra-pituitary haemorrhage
Dramatic presentation in those who already have a pituitary adenoma
Can be first presentation that someone has pituitary adenoma
Can be caused by anticoagulants
Why are basal plasma concentrations of pituitary or target endocrine gland hormones (as biochemical diagnosis) not accurate
Undetectable cortisol depending on time of day
T4 has a 6 day circulating half life
FSH/LH is cyclical
GH/ACTH is pulsatile
Presentation of pituitary apoplexy
Severe sudden onset headache, visual field defect (bitemporal hemianopia), cavernous sinus involvement pay lead to diplopia (IV, VI) and ptosis (III)
What type of biochemical test can be used then, aside from basal concentrations
STIMULATED DYNAMIC PITUITARY FUNCTION TEST
ACTH/GH are stress hormones. Stimulated by hypoglycaeia (<2.2mM). So you give insulin and see if ACTH is released by measuring cortisol
TSH you give TRH
FSH and LH can give GnRH
Outline radiological diagnosis of hypopituitarism- what can it tell you
MRI of piuitary could tell you about apoplexy or adenoma or there could be an empty sella (thin rim of pituitary tissue)
Which AP hormone cannot be replaced
Prolactin
State replacement hormones for all the AP hormones than can be replaced
TSH- thyroxine Woman FSH/LH- HRT (E2 plus progestogen) Man FSH/LH- testosterone GH- GH ACTH- hydrocortisone
How do we check that the replacement hormones for AP are working
TSH- serum free T4
Woman FSH/LH- symptom improvement, withdrawal bleeds
Man- symptom improvement, serum testosterone
GH- IGF-1 child growth chart
ACTH- serum cortisol
Effect of GH deficiency in child vs adult
Child- short stature (2SDs less than mean heigh for children of that age and sex
Adult- unclear
Causes of short stature
Genetic (Down’s, Turner’s and prader willi)
Malnutrition,
Malabsorption (e.g. coeliac),
Emotional neglect,
Endocrine (cushing’s, hypothyroidism, GH deficiency, poorly controlled T1DM)
Systemic disease (CF, rheumatoid arthritis)
Skeletal Dysplasia (achondroplasia and osteogenesis imperfecta)
Think GEMMED S (d for skeletal Dysplasia)
How do pituitary dwarfism, prader willi and laron dwarfism affect the growth axis
Praderwilli- problem in hypothalamis
Pit. dwarfism- Not enough somatotrophin made at pit.
Laron dwarfism- GH receptor defect on liver so ack of IGF1/2
How does prader willi affect growth
GH deficiency secondary to hypothalamic dysfunctin
Dwarfism (i.e. NOT PITUITARY/ LARON)
Is achondroplasia- normal sized trunk but short limbs due to mutation in FGF3, abnormality in growth plate chondrocytes so impaired linear growth. Not endocrine cause
Treatment for Laron dwarfism
IGF-1 treatment in childhood can increase height
Interpret slide 29
Child in 25th decile (so bottom 25% of normal) so she’s fine, and we would expect her to stay on this line all through childhood,
But by age 5 shes fallen to 9th decile and by 11 she falls below o.4th decile, so very very short.
She had coeliac disease, but given a gluten free diet she gets back on track
Causes o acquired GH deficiency in adults
trauma
pituitary tumour
pituitary surgery
cranial radiotherapy
How can GH deficiency be diagnosed
So we mentioned, stress them
Give insulin (they become hypoglycaemic, so GH should increase above 3mcg/L)
Give glucagon
Give GHRH and arginine
Make child run up and down stairs for 10 minutes
THEN MEASURE GH AT SPECIFIC POINTS BEFORE AND AFTER
How is growth hormone therapy prepared and administered
Human recombinant GH (somatotropin)
Admin: daily, subcutanous injection, monitor clinical response and ADJUST TO IGF-1
Signs and symptoms of GH deficiency
Reduced lean mass, inreased adiposity and increased waist to hip ratio
Reduced muscle strength and bulk (worse exercise)
Decreased plasma HDL- cholesterol and raised LDL
Potential benefits of GH therapy in adults
Improved body composition, decreased waist circumference and less visceral fat
Improved muscle strength and exercise capaity
Better lipid profile (higher HDL lower LDL)
Increased bone minderal density
Improved psychological wellbeing
Risks of GH therpay in adults
Nothing to suggest increased susceptibility to cancer
Expensive 42k for lifelong treatment
