1. Hyposecretion of AP

Question 1

List the AP hormones

Answer 1

Gonadotrophs (FSH/LH)
ACTH
Prolactin
TSH
GH

Question 2

Causes/diagnosis of congenital panhypopituitarism

Answer 2

Usually due to mutation of transcription factors needed for normal AP development

GH def. -> SHORT STATURE
+ 1 more AP hormone deficient

Diagnosis: Hypoplastic AP on MRI

Question 3

Causes of acquired panhypopituitarism

Answer 3

Hypothalamic/pituitary tumours
Radiation
Infection (meningitis)
Trauma
Infiltrative disease (neurosarcoidosis)
Inflammatory
Pituitary apoplexy
Sheehan's syndrome

Question 4

Presentation of panhypopituitarism

Answer 4

Secondary hypogonadism -> Reduced libido, secondary amenorrhoea, erectile dysfunction

Secondary hypoadrenalism -> Fatigue

Secondary hypothyroidism -> Fatigue

Question 5

Causes/presentation of Sheehan’s syndrome

Answer 5

Post-partum hypopituitarism, secondary to post-partum haemorrhage

AP englarges during pregnancy (lactotroph hyperplasia)
This compresses the pituitary stalk and limits blood supply
If you also get haemorrhage you get pituitary infarction

TSH/ACTH/(GH) def. = Lethargy, weight loss, anorexia
Prolactin def. = Failure of lactation
Failure to resume menses post-delivery

Question 6

What is pituitary apoplexy? Presentation

Answer 6

Intra-pituitary haemorrhage/infarction

SEVERE sudden onset headache
Bitemporal hemianopia (compressed optic chiasm)

Often the FIRST presentation of pituitary adenoma

Question 7

Diagnosis of hypopituitarism?

Answer 7

‘Dynamic’ pituitary function tests

Insulin-induced hypoglycaemia (<2.2mM) should cause release of ‘stress hormones’ GH and ACTH (measure cortisol)
OR
Inject TRH -> TSH release
Inject GnRH -> FSH/LH release

Radiological diagnosis
Pituitary MRI may reveal pathology (e.g. apoplexy, adenoma) or empty pituitary sella

Question 8

Hormone replacement therapy - list the replacements

Answer 8

ACTH -> Hydrocortisone (check serum cortisol)
TSH -> Thyroxine (check serum free T4)
Women FSH/LH -> HRT (E2 + progestagen)
Men FSH/LH -> Testosterone 
GH -> GH (check IGF1, growth chart)

Question 9

Describe the growth axis

Answer 9

Hypothalamus -> AP -> GHRH/somatostatin -> GH

GH goes to liver -> IGF1/IGF2 -> Tissues
GH can also have direct effects on tissues

Question 10

Prader Willi syndrome

Answer 10

Chromosome 15 mutation
Hypothalamic dysfunction
Results in GH deficiency -> Short stature

Question 11

Achondroplasia (dwarfism)

Answer 11

Mutation in FGFR3 (Fibroblast Growth Factor receptor 3)
Abnormality in growth plate chondrocytes
Average trunk, short arms/legs

Question 12

Laron dwarfism

Answer 12

Mutation in GH receptor

IGF-1 treatment during childhood

Question 13

Pituitary dwarfism

Answer 13

Childhood GH deficiency -> Short stature

Lack of GH produced by AP

Question 14

Diagnosis of GH deficiency

Answer 14

GH is pulsatile, so random GH sample wont work

GH + Arginine (IV)
Insulin-induced hypoglycaemia
Glucagon (im)
Exercise

Measure plasma GH at specific time points (before + after)

Question 15

Causes of short stature?

Answer 15

Prader Willi
Achondroplasia
Laron Dwarfism
Pituitary dwarfism

Also Down’s syndrome

Question 16

Causes of tall stature?

Answer 16

Marfan’s syndrome (FBN1 gene, autosomal dominant, affects connective tissue)
Klinefelter’s Syndrome (XXY)