Hyposecretion of Anterior Pituitary Hormones

Question 1

What is the tissue type of the anterior and posterior pituitary?

Answer 1

AP: glandular tissue (upward growth from buccal cavity)
PP: neural tissue (downward growth from the base of the brain)

Question 2

What are the anterior pituitary hormones and cell types?

Answer 2

FSH/LH (gonadotrophs)
PROLACTIN (lactotrophs)
GH = somatotrophin (somatotrophs)
TSH (thyrotrophs)
ACTH (corticotrophs)

Question 3

What is a secondary endocrine gland disease?

Answer 3

The problem lies within the anterior pituitary

Question 4

What is a primary endocrine gland disease?

Answer 4

The problem lies within the endocrine gland itself, e.g. thyroid, adrenal cortex, gonads…

Question 5

Hypopituitarism

Answer 5

DECREASED PRODUCTION OF ALL ANTERIOR PITUITARY HORMONES (PANHYPOPITUITARISM) OR: OF SPECIFIC HORMONES

-> CONGENITAL (rare) or ACQUIRED

Question 6

What is a decreased production of all AP hormones called?

Answer 6

Panhypopituitarism

Question 7

Congenital panhypopituitarism

Answer 7

• rare
• usually due to a mutation of TF genes needed for normal AP development
• deficient in GH and at least one other AP hormone
• short stature
• hypoplastic pituitary gland on MRI

Question 8

What is a mutation that can cause congenital panhypopituitarism?

Answer 8

PROP 1 -> the expression of PROP1 leads to ontogenesis of pituitary gonadotropes as well as somatotropes, lactotropes and caudomedial thyrotropes.

Question 9

“Ontogenesis”

Answer 9

The development of an individual organism or anatomical or behavioural feature from the earliest stage to maturity.

Question 10

Acquired Panhypopituitaruism (Causes)

Answer 10

• Tumors (hypothalamic: craniopharyngioma; pituitary: adenomas, metastases, cysts)
• Radiation (-> hypothalamic/pituitary dmagage; GH is most vulnerable, TSH is relatively resistant)
• Infection (e.g. meningitis)
• Traumatic Brain Injury
• Infiltrative diseases (-> often involve the pituitary stalk e.g. neurosarcoidosis)
• Inflammatory (hypophysitis)
• Pituitary Apoplexy (haemorrhage or less common infarction)
• Peri-partum infarction (Sheehan’s Syndrome)

Question 11

How does Panhypopituitarism present?

Answer 11

FSH/LH: Secondary hypogonadism

  - > Reduced libido
  - > Secondary amenorrhoea
  - > Erectile dysfunction

ACTH: Secondary hypoadrenalism (cortisol deficiency)
-> Fatigue

TSH : Secondary hypothyroidism
-> Fatigue

Question 12

Simmond’s disease

Answer 12

Panhypopituitarism is occasionally called this.

Question 13

What part of the pituitary is affected in Sheehan’s syndrome?

Answer 13

Only the anterior pituitary.

Question 14

Sheehan’s Syndrome

Answer 14

• Post-partum hypopituitarism secondary to hypotension. PPH (post partum haemorrhage) leads to pituitary infarction.
• less common in developed countries
• pituitary increases in size in pregnancy due to lactotroph hyperplasia

Question 15

How does Sheehan’s syndrome present?

Answer 15

• Lethargy, anorexia, weight loss – TSH/ACTH/(GH) deficiency
• Failure of lactation – PRL deficiency
• Failure to resume menses post-delivery
• Posterior pituitary usually not affected

Question 16

Pituitary Apoplexy

Answer 16

• Intra-pituitary haemorrhage or (less commonly) infarction
• Often dramatic presentation in patients with pre-existing pituitary tumours (adenomas)
• May be first presentation of a pituitary adenoma
• Can be precipitated by anti-coagulants

Question 17

Diplopia

Answer 17

Double vision

Question 18

Ptosis

Answer 18

Droopy upper eyelid

Question 19

How does pituitary apoplexy present?

Answer 19

• SEVERE sudden onset headache
• Visual field defect – compressed optic chiasm, bitemporal hemianopia
• Cavernous sinus involvement may lead to diplopia (IV, VI), ptosis (III)

Question 20

How can you diagnose hypopituitarism? (simple)

Answer 20

• biochemical tests (basal plasma levels or dynamic tests)

- radiology (pituitary MRI)

Question 21

Biochemical methods to diagnose hypopituitarism

Answer 21

1. Basal plasma concentrations of pituitary or target endocrine gland hormones;
   HOWEVER:
   
   • interpretation may be limited
   • undetectable cortisol – what time of day?)
   • T4 – circulating t1/2 6 days
   • FSH/LH – cyclical
   • GH/ACTH - pulsatile
2. Stimulated (‘Dynamic’) Pituitary Function Tests
   
   • ACTH & GH = ‘stress’ hormones
     -> Hypoglycaemia (<2.2mM) = ‘stress’
     -> Insulin-induced hypoglycaemia stimulates
     
     • GH release
     • ACTH release (cortisol measured)
   • TRH stimulates TSH release
   • GnRH stimulates FSH & LH release

Question 22

Radiological methods to diagnose hypopituitarism

Answer 22

Pituitary MRI
- May reveal specific pituitary pathology (eg haemorrhage (apoplexy), adenoma)

  - Empty sella – thin rim of pituitary tissue

Question 23

How do you treat Hypopituitarism?

Answer 23

Hormone replacement and check hormone levels to make sure that the dose is right.

-> see powerpoint cards

Question 24

What does growth hormone deficiency cause?

Answer 24

Children: short stature (2SD < mean height of children that same age and sex)

Adults: effects less clear

Question 25

What are genetic causes of short stature?

Answer 25

Down Syndrome Turner syndrome Prader Willi Syndrome

Question 26

What are the causes for short stature

Answer 26

- genetic - emotional deprivation - systemic disease (CF, rheumatoid arthritis) - Malnutrition - Malabsorption (e.g. coeliac disease) - endocrine disorders (Cushing's syndrome, hypothyroidism, GH deficiency, uncontrolled T1DM) - skeletal dysplasias ( achondroplasia, osteogenesis imperfecta)

Question 27

What are some endocrine disorders that cause short stature?

Answer 27

- Cushing's syndrome - hypothyroidism - GH deficiency - poorly controlled T1DM

Question 28

Cushing's syndrome vs disease

Answer 28

S: cause unknown D: pituitary adenoma (excessive cortisol)

Question 29

skeletal dysplasia causes for short stature

Answer 29

- Achondroplasia | - Osteogenesis imperfecta

Question 30

What can cause short stature due to malabsorption?

Answer 30

Coeliac disease

Question 31

What are IGFI and IGFII?

Answer 31

Insulin like growth factors 1 and 2 When GH is secreted it acts on the liver and IGFI and IGFII are set free and act on body tissues.

Question 32

Laron Dwarfism

Answer 32

- due to GH receptor mutation - IGF-1 treatment in childhood can increase height - High incidence in a specific village in Ecuador – descendants of Spanish Sephardic Jews fleeing Spain during Inquisition

Question 33

Pituitary dwarfism

Answer 33

lack of GH

Question 34

Dwarfism (Achondroplasia)

Answer 34

- Mutation in Fibroblast Growth Factor Receptor 3 (FGF3) - Abnormality in growth plate chondrocytes - impaired linear growth) - Average size trunk - Short arms and legs

Question 35

What are causes of acquired GH deficiency in adults?

Answer 35

- TRAUMA - PITUITARY TUMOUR PITUITARY SURGERY - CRANIAL RADIOTHERAPY

Question 36

How can you diagnose GH deficiency?

Answer 36

- random blood test is of little use as the levels are pulsatile - PROVOCATION CHALLENGE (i.e. stimulation test)

Question 37

What are signs of GH deficiency?

Answer 37

- 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’ and reduced quality of life

Question 38

What are the downsides of GH therapy in adults?

Answer 38

Increased susceptibility to cancer – no data to support this currently Expensive – NICE estimated cost of lifelong GH treatment in adult = £42K - Daily injections

Question 39

Potential benefits of GH therapy in adults

Answer 39

- Improved body composition – decreased waist circumference, less visceral fat - Improved muscle strength and exercise capacity - More favourable lipid profile - higher HDL-cholesterol, lower LDL-cholesterol - Increased bone mineral density - Improved psychological well being and quality of life

Question 40

GH Therapy

Answer 40

- Preparation: Human recombinant GH (approved name: SOMATOTROPIN) - Administration: Daily, subcutaneous injection; Monitor clinical response & adjust dose to IGF-1

Question 41

Do patients with Prader Willi Syndrome respond to GH?

Answer 41

Yes they do. | The problem with Prader Willi and short stature lies within the hypothalamus.

Question 42

What are some possible GH provocation tests?

Answer 42

- GHRH and Arginine (in marmite) i.v. should increase GH - Insulin via hypoglycaemia should cause GH release - Glucagon i.m. causes GH and ACTH increase (makes you vomit, so probably through the stress of that) - exercise (done in children) -> measure GH levels before and after

Question 43

Summarise congenital panhypopituitarism

Answer 43

- rare - usually due to a mutation in a TF needed for normal AP development. - e.g. PROP1 -> deficient in GH and at least one more AP hormone - short stature and hypoplastic AP on MRI