hyposecretion of anterior pituitary hormones

Question 1

what are the anterior pituitary hormones

Answer 1

FSH LH TSH GH ACTH - tell adrenal cortex to make cortisol prolactin

Question 2

describe the hypothalamo-pituitary axis

Answer 2

hypothalamus is at the top of the control chain - secretes releasing or inhibiting hormones these cause the ant pit to produce anterior pituitary hormones these act on the endocrine gland causing it to release the primary hormone

Question 3

list the hormones in the hypathalamo-pituitary-thyroid axis

Answer 3

TRH TSH T3 T4

Question 4

what type of disease are endocrine system susceptible

Answer 4

autoimmune eg T1DM

Question 5

what does a ‘primary endocrine gland disease’ refer to *

Answer 5

disorder with the endocrine gland itself - there would be high pituitary hormones but low primary hormones

Question 6

what does a ‘secondary endocrine disease’ refer to *

Answer 6

problem with the anterior pit - so there are no anterior pituitary hormones and so no signal to the endocrine gland so it doesn’t produce primary hormones

Question 7

define the term panhypopituitarism *

Answer 7

decreased production of all anterior pituitary hormones

Question 8

what are the causes of panhypopituitarism *

Answer 8

congenital - rare, mutation of transcription factor genes needed for ant pit development eg PROP1 mutation acquired

Question 9

what happens if you have congenital panhypopituitarism *

Answer 9

deficient in GH and at least 1 other ant pit hormone short stature - because of GH deficiency hypoplastic anterior pit on MRI - tiny - not developed properly

Question 10

how can panhypopituitarism be acquired *

Answer 10

tumour - hypothalamic eg craniopharyngiomas - squash ant pit or stop hyp producing releasing hormones OR pituitary - adenomas, metastasis, cysts (squash)

radiation (hypothalamic or pituitary damage) - late effects of cancer treatment, GH most vul, TSH relatively resistant

infection - meningitis

trauma

infiltrative disease - involves the pit stalk - neurosarcoidosis

inflammatory - autoimmune of the ant pit eg hypophysitis

pituitary apoplexy from haemorrhage/ infarction - less common

peri-partum infaction - Sheehan’s syndrome

Question 11

alternative name for panhypopituitarism

Answer 11

Simmond’s syndrome

Question 12

presentation of panhypopituitarism - symptoms *

Answer 12

depends on the deficient hormones

FSH/LH - reduced libido, secondary amenorrhoea, erectile dysfunction

ACTH - cortisol deficiency = fatigue

TSH - fatigue

waxy skin, loss of body hair, hypotension

Question 13

what are the conditions called with deficiency of - FSH/LH - ACTH - TSH *

Answer 13

secondary hypogonadism secondary hypoadrenalism secondary hypothyroidism

Question 14

describe Sheehan’s syndrome - peri-partum infarction *

Answer 14

cause of hypopituitarism secondary to hypotension which was caused by post-partum haemorrhage because prolactin production increases in pregnancy there is lactotroph hyperplasia there is only a small blood supply via the stalk of the pituitary - so with the hyperplasia there is already a large demand

if there is post partum haemorrhage - the blood vol reduces causing vasoconstrcitor spasm of the arteries- meaning the BP reduces - less blood flows to the ant pit = pituitary infarction

Question 15

what is the presentation of Sheehan’s syndrome *

Answer 15

lethargy, weight loss and anorexia - because of TSH, ACTH and GH deficiency

failure to lactate - prolactin deficiency

failure to resume menses after birth - FSH/LSH deficiency

difficult to detect this because these symptoms are normal after pregnancy.

Question 16

describe pituitary apoplexy *

Answer 16

intra-pituitary haemorrhage or infarction dramatic first presentation of benign adenomas (10% pop have them) they can enlarge and haemorrhage can be precipitated by anticoagulants - cause the adenoma to bleed into the pituitary gland

cause sudden onset headache, reduction in visual acuity and/diplopia

Question 17

why does a pituitary adenoma cause a severe headache *

Answer 17

it stretches the dura

Question 18

how would you diagnose hypopituitarism biochemically

Answer 18

basal plasma conc of pituitary or target hormones - interpretation limited because hormone levels fluctuate - cortisol v low at night, FSH/LH cyclical, GH/ACTH - pulsatile, T4 t1/2 = 6 days - so level would very on the day

OR stimulated ‘dynamic’ pituitary function tests - ACTH and GH are stress hormones - go up in times of stress, so do insulin induced hypoglycaemia (glucose <2.2mM) - stim GH release, ACTH release (measure cortisol). at same time give TRH and GnRH to get TSH and FSH LH

Question 19

how can you diagnose hypopituitarism radiologically

Answer 19

pit MRI may reveal - apoplexy, adenoma or an empty sella - thin rim of pituitary tissue (pit gland sits in the sella turcica)

Question 20

image showing empty sella

Answer 20

Question 21

how do you treat deficient ACTH *

Answer 21

replace hydrocortisone, given throughout day - lot in morning to mimic the biologic cycle - can never do this perfectly so never have 100% QOL not ACTH because it is spikey, pulsatile check serum cortisol

Question 22

how do you treat deficient TSH *

Answer 22

give thyroxine check serum free T4 - this is then converted to T3 by deiodination enzymes

Question 23

how do you treat deficient LH/FSH in men *

Answer 23

give testosterone as a patch or gel or injection check for symptom improvement and serum testosterone

Question 24

how do you treat deficient LH/FSH in women *

Answer 24

HRT - oestrogen plus progesterone - need both so that they bleed every month because they have an intact uterus otherwise they would get endometrial cancer check -symptom improvement and withdrawal bleeds

Question 25

how do you treat deficient GH *

Answer 25

replace GH - daily subcutaneous injection check IGF1 and growth chart in children

Question 26

what does GH deficiency cause *

Answer 26

children- short stature adult - effects less clear

Question 27

non-endocrine causes of short stature *

Answer 27

genetic - Down’s, Turner’s, Prader Willi

emotional deprivation - childhood trauma shut down stress axis

systemic disease - CF, rheumatoid arthritis

malnutrition

malabsorption - coeliac disease

skeletal dysplasias - achondroplasia, osteogenesis imperfecta

Question 28

what primary hormones does the liver produce

Answer 28

IGF1 IGFII - mainly embryonic

Question 29

how does prader willi syndrome affect stature *

Answer 29

effects hypothalamus of axis GHRH -> nothing to stimulate GH also have learning difficulty and food seeking behaviours

Question 30

how does pituitary dwarfism cause short stature *

Answer 30

not enough GH - problem with anterior pit childhood GH deficiency

Question 31

how does laron dwarfism cause short stature *

Answer 31

GH receptor defect on liver - don’t make IGF1 - growth need IGF1 and GH IGF1 treatment in childhood can increase height

Question 32

describe dwarfism from achondroplasia *

Answer 32

mutation in fibroblast growth factor 3 abnormality in the growth plate chondrocytes - impaired linear growth average size trunk short arms and legs

Question 33

endocrine causes of short stature *

Answer 33

cushings hypothyroidism GH deficiency - pituitary dwarfism poorly controlled T1DM

Question 34

describe the diagnosis of short stature *

Answer 34

look at the height centiles the child is 2SDs less than mean height for children of that age and sex or they drop off their trajectory

Question 35

graph of centiles for a person of low stature, but was treated at 11

Answer 35

Question 36

describe the diagnosis of GH deficiency *

Answer 36

random GH - not useful - pulsatile

instead use provocative challenge ie stimulation test: give GHRH, arginine (AA stimulate GH production), insulin (force hypoglycaemia), glucagon - stimulate ACTH and GH causes vomiting which causes the stress response, exercise - more in children

measure GH over time it should increase in normal people if does not raise above 3mcg/L - NICE cut off - allowed hormone therapy - expensive

Question 37

describe GH therapy *

Answer 37

prep - human recombinant GH - somatotrophin admin - daily subcutaneous injection, monitor clinical dose and adjust to IGF1

Question 38

GH deficiency in adults signs and symptoms

Answer 38

reduced lean mass, increased adiposity, increased waist:hips ratio

relaxed muscle strength and bulk - reduced exercise performance

decreased plasma HDL cholesterol and high LDL cholesterol

impaired physiological well being and reduced QOL - don’t feel well in self

Question 39

potential benefits of GH therapy in adults *

Answer 39

improved body composition, decreased waist circumference, less visceral fat - good for CV health

improved muscle strength and exercise capacity more favourable lipid profile - higher HDL, less LDL

increased bone mineral density

improved physiological well being and QOL

Question 40

potential risks of GH therapy in adults *

Answer 40

expensive increased susceptibility to cancer - no data to support this

Question 41

treatment of panhypopituitarism *

Answer 41

hormone replacement therapy as required