Endo 1: Hyposecretion of anterior pituitary hormones

Question 1

5 hormones of AP

Answer 1

LH/FSH, somatotrophin, TSH, prolactin and ACTH

Question 2

Differentiate primary and secondary endocrine disease

Answer 2

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)

Question 3

TSH and T4 levels in primary and secondary hypothyroidism

Answer 3

Prim- TSH sky high and T4 low

Secondary- TSH low and T4 low

Question 4

2 types of hypopituitarism

Answer 4

Panhypopituitarism (=all low)

Specific hormones

Question 5

Explain congenital panhypopituitarism

Answer 5

Mutations of transcription factors genes needed for normal anterior pituitary development I.E. PROP1

Question 6

What are the conditions for a panhypopituitarism diagnosis

Answer 6

Deficient in GH and one other hormone (short stature and hypoplastic anterior pituitary on MRI)

Question 7

Acquired causes of panhypopituitarism

Answer 7

(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`

Question 8

Which AP hormone is most and least vulnerable to damage from radiation

Answer 8

Most- GH Least- TSH

Question 9

Presentation of panhypopituitarism (aka Simmond’s)

Answer 9

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

Question 10

Effect of pregnancy on the AP

Answer 10

It grows lots to release lots of prolactin (lactotroph hyperpasia)

Question 11

Cause of Sheehan’s syndrome (more common is less developed ountries)

Answer 11

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

Question 12

Presentation of Sheehan’s syndrome

Answer 12

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

Question 13

In Sheehan’s syndrome, there is less TSH yet the patient loses weight. Why?

Answer 13

Because there is also deficiency of ACTH, and lack of cortisol (i.e. in hypoadrenalism) leads to weight loss

Question 14

What is pituitary apoplexy

Answer 14

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

Question 15

Why are basal plasma concentrations of pituitary or target endocrine gland hormones (as biochemical diagnosis) not accurate

Answer 15

Undetectable cortisol depending on time of day
T4 has a 6 day circulating half life
FSH/LH is cyclical
GH/ACTH is pulsatile

Question 16

Presentation of pituitary apoplexy

Answer 16

Severe sudden onset headache, visual field defect (bitemporal hemianopia), cavernous sinus involvement pay lead to diplopia (IV, VI) and ptosis (III)

Question 17

What type of biochemical test can be used then, aside from basal concentrations

Answer 17

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

Question 18

Outline radiological diagnosis of hypopituitarism- what can it tell you

Answer 18

MRI of piuitary could tell you about apoplexy or adenoma or there could be an empty sella (thin rim of pituitary tissue)

Question 19

Which AP hormone cannot be replaced

Answer 19

Prolactin

Question 20

State replacement hormones for all the AP hormones than can be replaced

Answer 20

TSH- thyroxine 
Woman FSH/LH- HRT (E2 plus progestogen)
Man FSH/LH- testosterone
GH- GH
ACTH- hydrocortisone

Question 21

How do we check that the replacement hormones for AP are working

Answer 21

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

Question 22

Effect of GH deficiency in child vs adult

Answer 22

Child- short stature (2SDs less than mean heigh for children of that age and sex
Adult- unclear

Question 23

Causes of short stature

Answer 23

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)

Question 24

How do pituitary dwarfism, prader willi and laron dwarfism affect the growth axis

Answer 24

Praderwilli- problem in hypothalamis
Pit. dwarfism- Not enough somatotrophin made at pit.
Laron dwarfism- GH receptor defect on liver so ack of IGF1/2

Question 25

How does prader willi affect growth

Answer 25

GH deficiency secondary to hypothalamic dysfunctin

Question 26

Dwarfism (i.e. NOT PITUITARY/ LARON)

Answer 26

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

Question 27

Treatment for Laron dwarfism

Answer 27

IGF-1 treatment in childhood can increase height

Question 28

Interpret slide 29

Answer 28

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

Question 29

Causes o acquired GH deficiency in adults

Answer 29

trauma
pituitary tumour
pituitary surgery
cranial radiotherapy

Question 30

How can GH deficiency be diagnosed

Answer 30

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

Question 31

How is growth hormone therapy prepared and administered

Answer 31

Human recombinant GH (somatotropin)

Admin: daily, subcutanous injection, monitor clinical response and ADJUST TO IGF-1

Question 32

Signs and symptoms of GH deficiency

Answer 32

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

Question 33

Potential benefits of GH therapy in adults

Answer 33

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

Question 34

Risks of GH therpay in adults

Answer 34

Nothing to suggest increased susceptibility to cancer

Expensive 42k for lifelong treatment