Hyposecretion of Anterior Pituitary Hormones

Question 1

What are the anterior pituitary hormones?

Answer 1

LH/FSH
Ptolactin
ACTH
GH
TSH

Question 2

Describe the features of primary hypopituitarism

Answer 2

Increased TSH
Decreased T4

*problem is with the endocrine gland

Question 3

Describe the features of secondary hypopituitarism

Answer 3

Decreased TSH
decreased T4

*problem with pituitary

Question 4

What is pan hypopituitarism?

Answer 4

Decreased production of all anterior pituitary hormones

Question 5

What are some causes of acquired panhypopituitarism?

Answer 5

Tumour (hypothalamus/pituitary)
Radiation
Infiltrative disease
Inflammation
Infection e.g meningitis
Pituitary apoplexy (haemorrhage)
Traumatic brain injury
Peri-partum infarction ( Sheehan’s syndrome)

Question 6

In what order does loss of secretion happen?

Answer 6

Gonadotropin 
GH
Thyrotrophin
Corticotrophin
Prolactin

Question 7

What are the causes and and symptoms of panhypopituitarism (Simmond’s disease)?

Answer 7

Insidious onset - develops slowly
Causes : 
infiltrative process (e.g lymphocytes)
pituitary adenomas
craniopharyngiomas
cranial injury
following surgery

Symptoms :
decreased thyroidal, gonadal and adrenal function

FSH/LH Secondary hypogonadism
impotence
secondary amenorrhoea/ oligomenorrhoea
loss of libido

ACTH Secondary hypoadrenalism (cortisol deficiency)
Fatigue

TSH Secondary hypothyroidism
Fatigue

Question 8

What are the features of Sheehan’s syndrome?

Answer 8

Specific in women
During pregnancy anterior pituitary enlarges to produce more prolactin (physiological)
Sheehan’s syndrome develops acutely following postpartum haemorrhage resulting in pituitary infarction/necrosis of the pituitary

Presents as:
Lethargy (common after giving birth)
Anorexia
Weight loss
FAILURE IF LACTATION (prolactin deficiency)
Failure to resume menses post-delivery

*posterior pituitary not usually affected

Question 9

What is pituitary apoplexy?

Answer 9

Similar to Sheehan’s but not specific to women
In pre-existing pituitary adenomas- intra-pituitary haemorrhage
Precipitated by anti-coagulants

Symptoms:
Severe sudden onset headache
Bitemporal heminopia (compression on optic chiasm)
Diplopia (double vision)
Ptosais (dropping under eyelid)

Question 10

What are the two biochemical ways to diagnose hypopituitarism?

Answer 10

1. Basal plasma concentrations of pituitary or target endocrine gland hormones.
   - Cortisol is in small volumes –varies throughout the day.
   - T4/thyroxine has a long half-life (6 days) and so may take a while for it to fall.
   - FSH/LH is cyclical.
   - GH/ACTH is pulsatile.

2.Stimulated pituitary function tests.
ACTH & GH = stress hormones –stress is defined as hypoglycaemia (<2.2mM glucose).
An insulin-induced hypoglycaemia stimulates GH and ACTH (cortisol measured) release. TRH (in injection) then stimulates TSH release and GnRH stimulates FSH and LH release.

Question 11

What is the method of radiological diagnosis of hypopituitarism?

Answer 11

pituitary MRI - may reveal specific pituitary pathology e.g haemorrhage (apoplexy)/ adenoma
may show empty sella

Question 12

What are the replacement hormones for each of the anterior pituitary hormones? What do you check?

Answer 12

ACTH - hydrocortisone - serum cortisol
TSH - thyroxine - serum free T4
LH/FSH (women) - HRT (E2 plus progestagen) - symptom improvement, withdrawl bleeds
LH/FSH (men) - testosterone - symptom improvement , serum testosterone
GH - GH - IGF1, groth chart (children)

*prolactin can’t be replaced

Question 13

What is the definition of short stature?

Answer 13

Children  =  <2  SDs  from  the  mean.  
Adults  =  less  clear  definition.

Question 14

What are the causes of short stature?

Answer 14

• Genetic e.g. Down’s, Turner’s, Prader-Willi syndromes
• Emotional deprivation
• Systemic disease
• Malnutrition.
• Malabsorption e.g. coeliac disease
• Endocrine disorders e.g. Cushing’s, hypothyroidism, GH deficiency
• Skeletal dysplasia e.g. Achondroplasia, osteogenesis imperfecta

Question 15

Outline the growth axis. Where are the faults that cause PWS, Pituitary dwarfism and Laron dwarfism? What causes achondroplaisa?

Answer 15

Hypothalamus -> GHRH -> anterior pituitary -> GH -> liver (or straight to target tissue) -> IGF1/2

Achondroplasia. - mutation in Fibroblast Growth Factor Receptor 3 (FGF3) -> bnormalities in growth plate chondrocytes that impairs linear growth resulting in an average sized trunk and short arms/legs.

Pituitary Dwarfism-childhood GH deficiency.

Prader Willi syndrome -GH deficiency secondary to hypothalamic dysfunction.

Laron dwarfism–high local incidence, mutation in GH receptor treated with IGF-1 in childhood.

Question 16

What are the causes of acquired GH deficiency in adults?

Answer 16

trauma
pituitary tumour
pituitary surgery
cranial radiotherapy

Question 17

How do you diagnose GH deficiency?

Answer 17

Provocative Challenge (stimulation) test.
Cannot measure GH as it is pulsatile in nature.
Provocation tests include:
- GHRH + Arginine (IV)
- Insulin (IV), glucagon (IM)
- exercise (10mins).

Plasma GH is then measured at specific time points after

Question 18

Outline the features of growth hormone therapy

Answer 18

• Preparation -human recombinant GH
• Administration -daily, subcutaneous injection, monitor clinical responses and adjust dose to IGF-1.
• Absorption & distribution - maximal concentration in plasma in 2-6 hours
• Metabolism - hepatic/renal with a short half-life of 20 minutes
• Duration of action-lasts well beyond clearance, peak IGF1 levels at approx. 20 hours.

Question 19

What are the signs an symptoms of GH deficiency in adults?

Answer 19

reduced lean mass, increased adiposity, increased waist:hip ratio
reduced muscle strength and bulk, reduced exercise performance
decreased plasma HDL - cholsterol and raised LDL- choelsterol
impaired ‘physiological well being’ and reduced quality of life

Question 20

What are the risks of growth hormone replacement therapy?

Answer 20

increased susceptibility to cancer (no currently supported data)

expensive