Hypersecretion Of Anterior Pituitary Hormones

Question 1

Hyperpituitarism

Answer 1

Symptoms associated with excess production of adenohypophysial hormones
Usually due to isolated pituitary tumours but can also be ectopic (i.e. from non-endocrine tissue) in origin
Can quite often be associated with visual field and other (e.g. cranial nerve) defects
As well as endocrine-related signs and symptoms

Question 2

Bitemporal hemianopia

Answer 2

Slide 5-6 [pic]

Question 3

Excess ACTH (corticotrophin) can result in…?

Answer 3

Cushing’s disease

Question 4

Excess TSH (thyrotrophin) can result in…?

Answer 4

Thyrotoxicosis

Question 5

Excess gonadotrophins (LH and FSH) can result in…?

Answer 5

Precocious puberty in children

Question 6

Excess prolactin can result in…?

Answer 6

Hyperprolactinaemia

Question 7

Excess GH can result in…?

Answer 7

Gigantism, acromegaly

Question 8

Hyperprolactinaemia

Answer 8

Physiological
- pregnancy
- breastfeeding
Pathological
- prolactinoma (often microadenomas < 10mm diameter)
- prolactinoma = most common functioning pituitary tumour
- high prolactin suppresses GnRH pulsatility

Question 9

Hyperprolactinaemia due to pituitary adenoma

Answer 9

In women:

 - galactorrhoea (milk production)
 - secondary amenorrhoea (or oligomenorrhoea)
 - loss of libido
 - infertility

In men:

 - galactorrhoea uncommon (since appropriate steroid background usually inadequate)
 - loss of libido
 - erectile dysfunction
- infertility

Question 10

Regulation of prolactin secretion

Answer 10

Inhibitory regulation by dopamine

Lactotrophs —> prolactin
Lactotrophs express D2 receptors
Dopamine from hypothalamic dopaminergic neurones = no prolactin released
Pharmacologically D2 recpetor agonists can be used

Slide 14 [pic]

Question 11

Treatment of hyperprolactinaemia

Answer 11

Medical treatment is 1st line
    - dopamine receptor (D2) agonists
           Decrease prolactin secretion
           Reduce tumour size
Examples:
     - Bromocriptine
     - Cabergoline
Oral administration

Question 12

Side effects of dopamine receptor agonists

Answer 12

Nausea and vomiting
Postural hypertension
Dyskinesias
Depression
Impulse control disorder (e.g. pathological gambling, hypersexuality)

Question 13

Excess growth hormone

Answer 13

In childhood = gigantism
In adulthood = acromegaly

Usually due to benign growth hormone secreting pituitary adenoma

Question 14

Acromegaly

Answer 14

Insidious in onset
Signs and symptoms progress gradually (can remain undiagnosed for many years)
Untreated, excess GH is associated with increased morbidity and mortality
Death:
- cardiovascular disease 60%
- respiratory complications 25%
- cancer 15%

Question 15

What grows in acromegaly?

Answer 15

Periosteal bone
Cartilage
Fibrous tissue
connective tissue
Internal organs (cardiomegaly, splenomegaly, hepatomegaly, etc.)

Question 16

Clinical features of acromegaly

Answer 16

Excessive sweating (hyperhidrosis)
Headache
Enlargement of supraorbital ridges, nose, hands and feet, thickening of lips and general coarseness of features
Enlarged tongue (macroglossia)
Mandible grows causing protrusion of lower jaw (prognathism)
Carpal tunnel syndrome (median nerve compression)
Barrel chest, kyphosis

Question 17

Metabolic effects of acromegaly

Answer 17

1. Excess growth hormone
2. Increased endogenous glucose production, decreased muscle glucose uptake
3. Increased insulin production = increased insulin resistance
4. Impaired glucose tolerance
5. Diabetes mellitus

Slide 26 [pic]

Question 18

Complications of acromegaly

Answer 18

Obstructive sleep apnoea
- bone and soft-tissue changes surrounding the upper airway lead to narrowing and subsequent collapse during sleep
Hypertension
- direct effects of Gh and/or IGF-1 on vascular tree
- GH mediated renal sodium reabsorption
Cardiomyopathy
- hypertension, DM, direct toxic effects of excess GH on myocardium
Increased risk of cancer
- colonic polyps, regular screening with colonoscopy

Question 19

Co-secretion of prolactin and grwoth hormone in acromegaly

Answer 19

Prolactin is often high in acromegaly - may reflect tumour secreting GH and prolactin
Hyperprolactinaemia will cause secondary hypogonadism

Question 20

Regulation of GH secretion

Answer 20

Slide 29 [pic]

Question 21

Diagnosis of acromegaly

Answer 21

GH pulsatile - so random measurement unhelpful
Elevated serum IGF-1
Failed suppression (‘paradoxical rise’) of GH following oral glucose load - oral glucose tolerance test

Question 22

Glucose-induced suppression of growht hormone secretion in acromegaly

Answer 22

Slide 31 [pic]

Question 23

Treatment of acromegaly

Answer 23

Surgery (trans-sphenoidal) - 1st line
Medical
- somatostatin analogues (e.g. octreotide)
- dopamine aggonists (GH secreting pituitary tumours frequently express D2 receptors) (e.g. cabegoline
Radiotherapy

Question 24

Somatostatin analogues

Answer 24

‘Endocrine cyanide’
Injection: sc (short acting) or monthly depot
Gi side effects common (e.g. nausea, diarrhoea, gallstones can occur)
Reduces Gh secretion and tumour size
Pre-treatment before surgery may make resection easier
Use post-operatively if not cured or whilst waiting for radiotherapy to take effect (slow)