Hypersecretion of Anterior Pituitary Hormones

Question 1

What is the usual cause of hypersecretion of anterior pituitary hormones?

Answer 1

Pituitary adenoma but can be ectopic (i.e. from non-endocrine tissue)

Question 2

What visual defect is associated with pituitary adenoma?

Answer 2

Bitemporal hemianopia

Question 3

What is the cause of bilateral hemianopia? How is it assessed?

Answer 3

• At the optic chiasm, fibres from the nasal retinae cross.
• Light from outer (temporal) aspects of visual field strikes the nasal aspect of the retina
• Compression of these crossing fibres at the optic chiasm means that there is loss of vision from the outer temporal visual fields.

Assessment: Diagram below is constructed from a visual fields test. Every time the patient sees a flash they have to press a button. Shows a loss of temporal field.

Question 4

State the disease resulting from hypersecretion of:

• a. Corticotrophin
• b. Thyrotrophin
• c. Gonadotrophin
• d. Prolactin
• e. Somatotrophin

Answer 4

a. Cortictrophin - Cushing’s disease
b. Thyrotrophin - Thyrotoxicosis
c. Gonadotrophins - Precocious puberty in children
d. Prolactin - Hyperprolactinaemia
e. Somatotrophin - Gigantism/Acromegaly

Question 5

State two physiological causes of hyperprolactinaemia.

Answer 5

Pregnancy

Breast feeding

Question 6

What is the usual pathological cause of hyperprolactinaemia?

Answer 6

Prolactinoma (most commonly microadenomas (< 10 mm)) = most common functioning pituitary tumrour.

Question 7

What is the effect of high prolactin on GnRH?

Answer 7

GnRH pusatility is suppressed by high prolactin

Question 8

State the symptoms of hyperprolactinaemia in men and women.

Answer 8

• Loss of libido (in both)
• Infertility (in both)
• Galactorrhoea (rarely occurs in males since appropriate steroid background usually inadequate)
• Oligomenorrhoea/amenorrhoea (in women)
• Impotence (in men)
• Erectile dysfunction (in men)

Question 9

How is prolactin secretion regulated? How can we expolid this pharamceutically?

Answer 9

• Release of prolactin from anterior pituitary lactotrophs can be regulated by dopamine
• Dopamine from hypothalamic dopaminergic neurons binds to D2 receptors on the lactotrophs
• This stops the release of prolactin

D2 receptor agonsists can be used in hyperprolactinaemia to:

• decrease prolactin secretion
• reduce tumour size

Question 10

What is used to treat hyperprolactinaemia? What is the ROA?

Answer 10

Dopamine (D2) agonists – bromocriptine and cabergoline

ROA: oral administration

Question 11

Describe the side-effects of dopamine receptor agonists.

Answer 11

• Nausea/vomiting
• Postural hypotension
• Dyskinesias
• Depression - must tell patients about this as it could otherwise result in a lawsuit
• Pathological gambling - doctors ask patients to tell a friend to inform their doctor of any strange behaviour

Question 12

What does excess growth hormone cause in children and in adults? What is the USUAL cause?

Answer 12

Children – gigantism

Adults – acromegaly

CAUSE: benign growth hormone secreting pituitary adenoma

Question 13

What are the most common causes of death in excess GH?

Answer 13

Excess GH –> increased morbidity and mortality:

• Cardiovascular problems (60%)
• Respiratory problems (25%)
• Cancer (15%)

Question 14

What grows in acromegaly?

Answer 14

• periosteal bone
• cartilage
• fibrous tissue
• connective tissue
• internal organs (cardiomegaly, splenomegaly, hepatomegaly, etc.)

Question 15

State some common clinical features of acromegaly.

Answer 15

• Hyperhydrosis - excessive sweating
• Headache
• Enlargement of supraorbital ridges, nose, hands and feet, thickening of lips and general coarseness of features
• Macroglossia - enlarged tongue
• Proganthism - mandible grows causing protrusion of lower jaw
• Carpal tunnel syndrome - due to median nerve compression
• Barrel chest, kyphosis

Question 16

Describe the onset of acromegaly.

Answer 16

Insidious in onset - signs and symptoms progress gradually. Patients can bring old photos to help diagnose.

Question 17

What are the metabolic effects of acromegaly?

Answer 17

Excess GH –>

Increased endogenous glucose production, decreased muscle glucose uptake –>

increased insulin production=increased insulin resistance –>

impaired glucose tolerance –> diabetes mellitus (in 10%)

Question 18

What are the complications in 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 &/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

What type of cancer is more common in acromegaly?

What systemic disease are people with acromegaly likely to have?

Answer 19

Colonic cancer - polyps

Hypertension

Question 20

What type of test is used to diagnose a hyperpituitary disorder?

Answer 20

Suppression test

Question 21

What test is used to diagnose acromegaly and how are the results interpreted?

Answer 21

Glucose-induced suppression of growth hormone secretion

• Giving glucose should cause a decrease in growth hormone release in a normal individual
• In someone with acromegaly, giving glucose will cause a paradoxical rise in growth hormone release

Serum IGF-1 - elevated

Serum GH - unhelpful because pulsatile

Question 22

Apart from GH, what would be elevated in the serum in acromegaly?

Answer 22

IGF-1

Question 23

What is the FIRST line treatment of acomegaly?

Answer 23

Trans-sphenoidal surgey

Question 24

State some of the treatments for acromegaly.

Answer 24

Transsphenoidal hypophysectomy

Radiotherapy

Chemotherapy:

• Octreotide (somatostatin analogue)
• Cabergoline (dopamine receptor agonists)

Question 25

What other hormone is often high in acromegaly? What does this show?

Answer 25

Prolactin - often high in acromegaly; may reflect the tumour secreting GH and prolactin.

Question 26

What are the secondary effects of hyperprolactinaemia?

Answer 26

Hyperprolactinaemia will cause secondary hypogonadism (NB: prolactin is co-secreted with GH in acromegaly)

Question 27

Why are dopamine antagonists useful in the treatment of acromegaly?

Answer 27

GH secreting pituitary tumours frequently express D2 receptors

Question 28

Name a somatostatin analogue used in the treatment of acromegaly. What are they sometimes called?

Answer 28

Octreotide "Endocrine cyanide"

Question 29

What are the clinical uses of somatostatin analogues e.g. octreotide?

Answer 29

* 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)

Question 30

Describe the administration and DOA of somatostatin analogues.

Answer 30

Administered by injection SC (short acting) or monthly depot

Question 31

State some of the side effects of somatostatin analogues.

Answer 31

GI side effect are common (because somatostatin is produced by the small intestine as well) e.g. * Nausea * Diarrhoea * Rarely gallstones (due to less CCK)

Question 32

Summarise briefly the regulation of GH secretion.

Answer 32

GHRH --\> GH --\> liver --\> somatomedin production e.g. IGF-1 ## Footnote *SS = somatostatin aka growth hormone inhibiting hormone*

Question 33

Polypeptide/protein hormones...? a) include growth hormone b) are well absorbed when given orally c) normally have a duration of action of more than 24h d) show no species variation e) act on membrane-bound receptors

Answer 33

Polypeptide/protein hormones: include growth hormone = True are well absorbed when given orally = False normally have a duration of action of more than 24h = False show no species variation = False act on membrane-bound receptors = True

Question 34

A tumour in the pituitary: a) most commonly presents with thyroid hormone deficiency b) can be associated with the loss of peripheral vision (bitemporal hemianopia) c) is usually a microadenoma d) may be associated with the symptoms of diabetes mellitus e) is often a cause of hypertension

Answer 34

* A tumour in the pituitary: most commonly presents with thyroid hormone deficiency = False * can be associated with the loss of peripheral vision (bitemporal hemianopia) = True * is usually a microadenoma = True * may be associated with the symptoms of diabetes mellitus = True * is often a cause of hypertension = False

Question 35

Panhypopituitarism: a. is a condition which develops following a prolonged raised circulating cortisol concentration b. is usually caused by a hypothalamic tumour c. can be a consequence of post-partum haemorrhage d. is treated with replacement hypothalamic releasing hormone therapy e. is naturally associated with the aging process

Answer 35

* Panhypopituitarism: is a condition which develops following a prolonged raised circulating cortisol concentration = False * is usually caused by a hypothalamic tumour = False * can be a consequence of post-partum haemorrhage = True * is treated with replacement hypothalamic releasing hormone therapy =False * is naturally associated with the aging process = False

Question 36

The lack of circulating growth hormone (somatotrophin): a. in children is a cause of short stature b. can result in symptoms associated with diabetes mellitus c. is associated with raised circulating IGF levels d. generally requires replacement therapy in adults e. can be successfully treated with a somatostatin agonist

Answer 36

* The lack of circulating growth hormone (somatotrophin): in children is a cause of short stature =True * can result in symptoms associated with diabetes mellitus =False * is associated with raised circulating IGF levels = False * generally requires replacement therapy in adults =False * can be successfully treated with a somatostatin agonist =False

Question 37

Prolactinomas: a. are described as macroadenomas if they are less than 1 cm in diameter b. may cause infertility c. may cause galactorrhoea in men d. are sometimes diagnosed following initial presentation with visual defects e. can be treated with cabergoline

Answer 37

* Prolactinomas: are described as macroadenomas if they are less than 1 cm in diameter = False * may cause infertility = True * may cause galactorrhoea in men =True * are sometimes diagnosed following initial presentation with visual defects =True * can be treated with cabergoline = True

Question 38

Excess production of growth hormone (somatotrophin) in adults: 1. is usually associated with a pituitary tumour 2. can be diagnosed using an oral glucose tolerance test 3. is often indicated by an increase in linear growth 4. can be the cause of hypoglycaemic episodes 5. can be treated with a somatostatin analogue

Answer 38

* Excess production of growth hormone (somatotrophin) in adults: is usually associated with a pituitary tumour = True * can be diagnosed using an oral glucose tolerance test = True * is often indicated by an increase in linear growth = False * can be the cause of hypoglycaemic episodes =False * can be treated with a somatostatin analogue = True

Question 39

Dopamine receptor agonists: a. are the drugs of choice in the treatment of acromegaly b. inhibit prolactin secretion c. are normally polypeptides d. induce nausea e. cause Parkinson-like movement disorders

Answer 39

* Dopamine receptor agonists: are the drugs of choice in the treatment of acromegaly = False * inhibit prolactin secretion = True * are normally polypeptides =False * induce nausea = True * cause Parkinson-like movement disorders = False

Question 40

Irregular periods, galactorrhoea, very high prolactin =?

Answer 40

Small tumour producing prolactin

Question 41

What is the difference between prolactinoma and non functioning adenoma?

Answer 41

Dopamine supresses prolactin Pituitary tumours = harmless, very common....