Hypopituitarism

Question 1

What hormones are released by the anterior pituitary gland (6)?

Answer 1

• Growth hormone
• Prolactin
• Thyroid stimulating hormone (TSH)
• Luteinising hormone (LH) & Follicle stimulating hormone (FSH)
• Adrencorticotrophic hormone (ACTH)

Question 2

Which glands can fail resulting in endocrine hormone deficiencies (4)? Differentiate between primary (1) and secondary (3) pituitary failure.

Answer 2

• Primary pituitary failure:
• Pituitary gland
• Secondary pituitary failure:
• Thyroid gland
• Adrenal cortex
• Gonads

Question 3

Define panhypopituitarism.

Answer 3

Total loss of anterior & posterior pituitary function

Question 4

What are the hormone levels in primary hypothyroidisim (destruction of thyroid gland)?

Answer 4

• T3 & T4 deficiency
• TSH increase

Question 5

What are the hormone levels in secondary hypothyroidism (destruction of thyrotrophs)?

Answer 5

• TSH deficiency
• T3 & T4 deficiency

Question 6

What are the hormone levels in primary hypoadrenalism (destruction of adrenal cortex)?

Answer 6

• Cortisol deficiency
• ACTH increase

Question 7

What are the hormone levels in secondary hypoadrenalism (destruction of corticotrophs)?

Answer 7

• Cortisol deficiency
• ACTH deficiency

Question 8

What are the hormone levels in primary hypogonadism (destruction of testes or ovaries)?

Answer 8

• Testosterone deficiency
• LH & FSH increase

Question 9

What are the hormone levels in secondary hypogonadism (destruction of gonadotrophs)?

Answer 9

• Testosterone deficiency
• LH & FSH deficiency

Question 10

What are the causes of hypopituitarism divided into?

Answer 10

• Congenital
• Acquired

Question 11

Which mutation is concerned with congenital hypopituitarism?

Answer 11

• PROP1 mutation (transcription factor required for anterior pituitary development)
• IGF1 mutation (GH reception mutation)

Question 12

What are the causes of acquired hypopituitarism (1 / Infection 3 / Trauma 3 / Vascular 2)?

Answer 12

• Tumour: any brain tumour can squashe the pituitary (i.e. adenoma, metastases, cysts)
• Infection and inflammation: Meningitis / Encephalitis / Autoimmune
• Trauma: Radiotherapy (Hypothalamic/pituitary damage) / Traumatic brain injury / Pituitary surgery
• Vascular: Pituitary apoplexy (infarcted pituitary tumour) / Sheehan’s syndrome (Post-partum haemorrhage -> infarction of pituitary gland)

Question 13

What is the relation between radiotherapy and the risk of HPA axis damage?

Answer 13

• Higher total radiotherapy dose (Gy), higher risk of HPA axis damage

Question 14

What are the symptoms of congenital hypopituitarism?

Answer 14

• GH deficiency→ Short stature

Question 15

What are the symptoms of acquired hypopituitarism (4 FSH/LH / 1 ACTH & TSH / 1 GH / 1 PRL)?

Answer 15

• FSH/LH : Reduced libido / Secondary amenorrhoea / Erectile dysfunction / Reduced pubic hair
• ACTH & TSH: Fatigue
• GH: Reduced quality of life
• PRL: Inability to breastfeed

Question 16

What is the non dynamic investigation used to diagnose hypopituitarism?

Answer 16

• Serum hormone level

Question 17

What are the dynamic tests used to diagnose hypopituitarism (3)?

Answer 17

• Insulin induced hypoglycaemia to stimulate stress → GH & ACTH release
• TRH to stimulate TSH release
• GnRH stimulates FSH & LH release

Question 18

Which hormones are released by the anterior pituitary gland in response to hypoglycaemia (<2.2mM) (2)?

Answer 18

• GH
• ACThH

Question 19

What are the radiological tests used to diagnose hypopituitarism?

Answer 19

• Congenital: Hypoplastic (underdeveloped) anterior pituitary gland on MRI
• Acquired: Empty sella on MRI thin rim of pituitary tissue

Question 20

What is the treatment of primary hypopituitarism?

Answer 20

• Replace missing hormones

Question 21

What is the treatment of GH deficiency in hypopituitarism? How is the response measured (2)?

Answer 21

• Daily injections of GH
• Response measure: improvement in QoL / Plasma IGF-1

Question 22

What is the treatment of TSH deficiency in hypopituitarism? How is the response measured?

Answer 22

• Daily tablet of levothyroxine
• Response measure: Aim for a fT4 above the middle of the reference range

Question 23

What are the treatments of ACTH deficiency in hypopituitarism (2)?

Answer 23

• Prednisolone once daily AM eg 3mg
• Hydrocortisone three times per day eg 10mg/5mg/5mg

Question 24

What is the treatment of FSH/LH deficiency in hypopituitarism (men with no fertility required)? How is the response measured?

Answer 24

• Topical or intramuscular testosterone
• Response measure: Measure plasma testosterone

Question 25

What is the treatment of FSH/LH deficiency in hypopituitarism (men with fertility required)? How is the response measured?

Answer 25

* **Gonadotropin injections** (Best response if secondary hypogonadism has developed after puberty) * Response measure: **Measure testosterone** / **Semen analysis** (Sperm production may take 6-12 months)

Question 26

What is the treatment of FSH/LH deficiency in hypopituitarism (female with no fertility required) (2)?

Answer 26

* **Oral / Topical oestrogen** * **Additional progestogen** (if intact uterus) to prevent endometrial hyperplasia

Question 27

What is the treatment of FSH/LH deficiency in hypopituitarism (female with fertility required)?

Answer 27

* Induce ovulation by carefully timed **gonadotropin injections** (IVF)

Question 28

What are the sick day rules for patients with ACTH deficiency (2)?

Answer 28

* **Steroid alert** pendant/bracelet * **Double steroid dose** (glucocorticoid not mineralocorticoid) if fever/intercurrent illness

Question 29

What causes post-partum hypopituitarism (Sheehan's Syndrome)?

Answer 29

* Anterior pituitary enlarges in pregnancy (**lactotroph hyperplasia**) * **Post-partum haemorrhage** leads to hypotension * **Pituitary infarction** (obstruction to blood supply to pituitary tissue)

Question 30

What are the symptoms of Sheehan's syndrome (TSH, ACTH, GH 3 / PRL 1 / LH,FSH 1)?

Answer 30

* TSH / ACTH / GH deficiency: **Lethargy** / **Anorexia** / **Weight loss** * Prolactin deficiency: **Failure of lactation** * LH/FSH deficiency: **Failure to resume menses post delivery**

Question 31

What causes pituitary apoplexy?

Answer 31

* **Bleeding** (haemorrhage) into the pituitary or loss of blood flow (infarction) to the pituitary, usually due to pre-existing adenoma

Question 32

What are the symptoms of a pituitary apoplexy (3)?

Answer 32

* Sudden severe onset **headache** * **Visual field defect** (compressed optic chiasm / bitemporal hemianopia) * May have **diplopia** (CNIV / CNVI compression and/or **ptosis** (CNIII compression))