hyposecretion of anterior pituitary hormones

Question 1

what does hyposecretion of anterior pituitary hormones mean?

Answer 1

inadequate anterior pituitary function

Question 2

what are the 5 main anterior pituitary hormones

Answer 2

FSH/LH
prolactin 
GH
TSH 
ACTH

Question 3

define hypopituitarism

Answer 3

DECREASED PRODUCTION OF ALL ANTERIOR PITUITARY HORMONES (PANHYPOPITUITARISM) or of specific hormones

Question 4

what 2 can hypopituitarism be classified into

Answer 4

congenital defects

acquired

Question 5

classifying endocrine gland diseases into primary and secondary

Answer 5

Disorder results in
SECONDARY
endocrine gland disease= defect in the anterior pituitary gland

Disorder results in
PRIMARY endocrine
gland disease = defect in the actual gland such as the endocrine gland

Question 6

what is congenital panhypopituitarism?

Answer 6

Deficient in GH and at least 1 more anterior pituitary hormone

Question 7

what is congenital panhypopituitarism due to?

Answer 7

Rare
Usually due to mutations of transcription factor genes needed for normal anterior pituitary development
eg PROP1 mutation

Question 8

what does congenital panhypopituitarism result in?

How can it be diagnosed?

Answer 8

Short stature

Hypoplastic anterior pituitary gland on MRI

Question 9

what can lead to ACQUIRED PANHYPOPITUITARISM

Answer 9

Tumours
hypothalamic - craniopharyngiomas
pituitary – adenomas, metastases, cysts
Radiation
hypothalamic/pituitary damage
GH most vulnerable, TSH relatively resistant
Infection eg meningitis
Traumatic brain injury
Infiltrative disease – often involves pituitary stalk
eg neurosarcoidosis
Inflammatory (hypophysitis)
Pituitary apoplexy
haemorrhage (or less commonly infarction)
Peri-partum infarction (Sheehan’s syndrome)

Question 10

what are symptoms of PANHYPOPITUITARISM due to deficient hormones?
FSH/LH
ACTH
TSH

Answer 10

Occasionally called Simmond’s disease 
Symptoms due to deficient hormones 
FSH/LH= Secondary hypogonadism
Reduced libido
Secondary amenorrhoea
Erectile dysfunction
ACTH= Secondary hypoadrenalism (cortisol 			deficiency) Fatigue
TSH	 = Secondary hypothyroidism, Fatigue

Question 11

what is sheehan’s syndrome specifically?

Answer 11

SPECIFIC IN WOMEN
Specifically describes post-partum hypopituitarism secondary to hypotension (post partum haemorrhage - PPH)
Less common in developed countries
Anterior pituitary enlarges in pregnancy (lactotroph hyperplasia), so when there is a haemorrhage and great loss of blood, there is not enough blood supplying the newly enlarged pituitary gland- so it eventually dies off.
PPH leads to pituitary infarction

Question 12

what is the presentation of sheehan’s syndrome?

Answer 12

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 13

what is pituitary apoplexy?

Answer 13

Similar to sheehan’s but not specific to women.
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
Rapid presentation

Question 14

what is the presentation of pituitary apoplexy?

Answer 14

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

Question 15

biochemical diagnosis for hypopituitarism

• basal plasma conc
• what are the cons?

Answer 15

Basal plasma concentrations of pituitary or target endocrine gland hormones

	- interpretation may be limited
   		- undetectable cortisol – what time of 	day?
   		- T4 – circulating t1/2 6 days
 		- FSH/LH – cyclical
	- GH/ACTH - pulsatile

Question 16

biochemical diagnosis for hypopituitarism

-stimulated (dynamic) pituitary function tests

Answer 16

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 17

biochemical diagnosis for hypopituitarism

-radiological diagnosis

Answer 17

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

Empty sella – thin rim of pituitary tissue

Question 18

HORMONE REPLACEMENT THERAPY IN HYPOPITUITARISM

• ACTH
• TSH
• FSH/LH (f)
• FSH/LH (m)
• GH

Answer 18

• hydrocortisone
• thyroxine
• HRT
• Testosterone
• GH

Question 19

what does growth hormone (somatotrophin) deficiency lead to?
-in adults and children

Answer 19

in children results in short stature (=2 SDs < mean height for children of that age and sex)

in adults, effects less clear

Question 20

what are other causes of short stature

Answer 20

Genetic: Down’s syndrome, Turner’s syndrome, Prader Willi syndrome
Emotional Deprivation
Systemic disease: Cystic Fibrosis, Rheumatoid arthritis
Malnutrition
Malabsorption: Coeliac disease
Endocrine Disorders: Cushing’s syndrome, Hypothyroidism, GH deficiency, poorly controlled T1DM
Skeletal dysplasias: Achondroplasia, osteogenesis imperfecta

Question 21

whats the growth axis for GHRH- draw

Answer 21

SS+ GHRH
somatotrophin
(liver)
IGFII and IGFI

Question 22

what leads to prader willi syndrome?

Answer 22

GH deficiency secondary to hypothalamic dysfunction

Question 23

what leads to pituitary dwarfism?

Answer 23

childhood GH deficiency

-lack of GH produced released

Question 24

what leads to laron dwarfism

Answer 24

Mutation in GH receptor (in liver)

IGF-1 treatment in childhood can increase height

Question 25

causes of acquired GH deficiency in adults

Answer 25

TRAUMA PITUITARY TUMOUR PITUITARY SURGERY CRANIAL RADIOTHERAPY

Question 26

what can be used to diagnose GH deficiency?

Answer 26

Random GH little use – pulsatile PROVOCATIVE CHALLENGE (i.e. STIMULATION) TEST

Question 27

what are GH provocation tests?

Answer 27

GHRH + ARGININE (i.v.) (in combination more effective than each alone) INSULIN (i.v.) – via hypoglycaemia GLUCAGON (i.m.) (causing over vomiting, leading to stress) EXERCISE (e.g. 10 min step climbing; when appropriate) Measure plasma GH at specific time-points (before and after)

Question 28

why is there GH secretion in response to hypoglycaemia?

Answer 28

GH are stress hormones Hypoglycaemia leads to stress in the body So a lot of GH is released.

Question 29

examples of growth hormone therapy/treatment

Answer 29

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

Question 30

what are the signs and symptoms of GH deficiency in adults?

Answer 30

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 31

what are the potential benefits of GH therapy in adults?

Answer 31

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 32

what are the potential risks of GH therapy in adults?

Answer 32

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

Question 33

what is achondroplasia due to?

Answer 33

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