Acromegaly

Question 1

… is a condition caused by an excess of growth hormone (GH) most commonly related to a pituitary adenoma.

Answer 1

Acromegaly is a condition caused by an excess of growth hormone (GH) most commonly related to a pituitary adenoma.

Question 2

Growth hormone, also termed somatotropin, is a peptide hormone that is produced and released by somatotropic cells within the … …

Answer 2

Growth hormone, also termed somatotropin, is a peptide hormone that is produced and released by somatotropic cells within the anterior pituitary.

Question 3

… adenomass account for > 90% of cases of acromegaly.

Answer 3

Pituitary adenomas account for > 90% of cases of acromegaly.

Question 4

Growth hormone secreting somatotroph adenomas are the commonest cause of acromegaly. When this occurs in childhood prior to fusion of the epiphyseal growth plates pituitary … is seen.

Answer 4

Growth hormone secreting somatotroph adenomas are the commonest cause of acromegaly. When this occurs in childhood prior to fusion of the epiphyseal growth plates pituitary gigantism is seen.

Question 5

Other causes of acromegaly are very rare. They are related to excess secretion of GHRH or GH: list 3

Answer 5

Ectopic release of GH: May be seen in neuroendocrine tumours.
Ectopic release of GHRH: Related to tumours including carcinoid and small cell lung cancer.
Excess hypothalamic release of GHRH: Related to hypothalamic tumours.

Question 6

Acromegaly typically has an … onset and is often diagnosed late.

Answer 6

Acromegaly typically has an insidious onset and is often diagnosed late.

Question 7

Clinical features of acromegaly may be related to:

Answer 7

Excess growth hormone secretion

Mass effects of a pituitary adenoma

Question 8

… leads to enlargement of hands, feet, lips and nose. Examination should look for wide spaced teeth, prognathism and frontal bossing. Men may note a deepening of their voice and some patients develop carpal tunnel syndrome.

Answer 8

Acromegaly leads to enlargement of hands, feet, lips and nose. Examination should look for wide spaced teeth, prognathism and frontal bossing. Men may note a deepening of their voice and some patients develop carpal tunnel syndrome.

Question 9

Cardiovascular disease and acromegaly

Answer 9

Cardiovascular disease: There is an increased risk of cardiovascular disease and its complications. This includes hypertension, cardiomyopathy, left ventricular hypertrophy and heart failure.

Question 10

Acromegaly results in increased … … and a risk of developing type 2 diabetes.

Answer 10

Acromegaly results in increased insulin resistance and a risk of developing type 2 diabetes.

Question 11

There is an increased incidence of … in those with acromegaly.

Answer 11

There is an increased incidence of … in those with acromegaly.

Question 12

Colonic pathology in acromegaly

Answer 12

There appears to be an increased risk of colorectal cancer and diverticulosis.

Question 13

Thyroid gland in acromegaly

Answer 13

Enlargement of the thyroid gland is common and may be either a diffuse enlargement or multinodular in nature. There may be an increased incidence of thyroid cancer

Question 14

…: This may be related to mass effect from a pituitary adenoma or as a result of GH excess itself.

Answer 14

Headache: This may be related to mass effect from a pituitary adenoma or as a result of GH excess itself.

Question 15

Visual loss: Visual changes develop in up to …% of patients. Suprasellar extension of a macroadenoma can lead to direct pressure on the optic chiasm. The defect is classically bitemporal hemianopia.

Answer 15

Visual loss: Visual changes develop in up to 10% of patients. Suprasellar extension of a macroadenoma can lead to direct pressure on the optic chiasm. The defect is classically bitemporal hemianopia.

Question 16

Pituitary function in acromegaly

Answer 16

Pituitary function: A macroadenoma may impair the ability of the rest of the pituitary to function. In women menstrual dysfunction is seen, whilst men can be affected by erectile dysfunction. In up to 30% of patients concomitant hyperprolactinaemia is seen. Features of hyperprolactinaemia include galactorrhea, dysmenorrhoea, hypogonadism and infertility.

Question 17

What condition is this representing?

Answer 17

Acromegaly

Question 18

Diagnosis for acromegaly - what is required?

Answer 18

Diagnosis requires biochemical confirmation of GH excess.

Question 19

IGF-1 Levels: Whilst GH shows a great deal of variation depending on the time of day and various stressors, IGF-1 has remarkably constant levels. The vast majority of patients with acromegaly will have raised serum IGF-1 that reflects periods of excess GH. Levels guide further investigations:
High =
Equivocal =
Normal =

Answer 19

High: Essentially confirms diagnosis - can move on to imaging investigations.
Equivocal: Carry out oral glucose tolerance test.
Normal: Acromegaly unlikely.

Question 20

Oral glucose tolerance test: This is a highly specific diagnostic test. The patient is given 100g of glucose orally. Serum GH can be measured before and after glucose stimulation. In healthy individuals, GH release is suppressed following the administration of exogenous glucose. In patients with …, GH levels are unsuppressed.

Answer 20

Oral glucose tolerance test: This is a highly specific diagnostic test. The patient is given 100g of glucose orally. Serum GH can be measured before and after glucose stimulation. In healthy individuals, GH release is suppressed following the administration of exogenous glucose. In patients with acromegaly, GH levels are unsuppressed.

Question 21

In patients with suspected extra-pituitary causes a number of investigations may be arranged:

Answer 21

GHRH levels: Elevated levels indicate excess production from a hypothalamus tumour or ectopic source.

CT chest, abdomen and pelvis: Used to look for evidence of tumours that may lead to acromegaly through GH or GHRH production (e.g. small cell lung cancer, carcinoid).

Octreoscan & DOTATATE PET: Further scans that can be used to locate tumours that may produce GH/GHRH.

Question 22

The management of GH secreting pituitary adenomas may involve a number of modalities; surgical, medical and radiotherapy.

Answer 22

The management of GH secreting pituitary adenomas may involve a number of modalities; surgical, medical and radiotherapy.

Question 23

What surgery is typically first-line therapy for acromegaly?

Answer 23

Transsphenoidal surgery is typically first-line therapy. Success rates are variable, dependent on both the size and location of the adenoma. Microadenomas tend to have better results than macroadenomas.

Early cure is seen in around 80-90% of microadenomas but may be below 50% for macroadenomas.

Question 24

Medical treatments may be used in patients with acromegaly who are not operative candidates or where surgery fails to achieve biochemical cure.

The options include:

Answer 24

Somatostatin analogs (e.g. Octreotide): given as a monthly injection it reduces the release of GH and may cause shrinkage of tumours.
Growth hormone antagonists (e.g. Pegvisomant): given as daily injection, lowers IGF-1 levels.
Dopamine agonists (e.g. Bromocriptine): can reduce the release of GH, though they are only effective for a small proportion. Advantage is they can be given as a tablet.

Question 25

Radiotherapy indications in acromegaly…

Answer 25

Radiotherapy is generally reserved for cases where surgery and medical management fails. It is rarely used as a primary therapy. The biochemical response to radiotherapy can be slow, taking years.

Risks include the development hypopituitarism; therefore, it is generally avoided in those of reproductive age.

Question 26

Patients with acromegaly appear to be at increased risk of … cancer and may have an increased risk of thyroid cancer.

Answer 26

Patients with acromegaly appear to be at increased risk of colorectal cancer and may have an increased risk of thyroid cancer.

Question 27

Why may patients with acromegaly be offered a colonoscopy at an earlier age?

Answer 27

Patients may be offered colonoscopy and regular screening from the age of 40. The ongoing frequency of colonoscopy is determined by the findings at index exam and the ongoing acromegaly disease activity

Due to increased risk of colorectal cancer

Question 28

What other cancer apart from colorectal cancer are people with acromegaly at increased risk of?

Answer 28

Routine screening for thyroid cancer is not generally advised. It is unclear if the risk of thyroid cancer is increased or if as a result of the increase in benign nodular disease in acromegaly more cancers are picked up.

Patient presenting with palpable nodularities should be referred for triple assessment (see our Thyroid lumps notes for more details) on an urgent two-week wait basis.

Question 29

Acromegaly appears to be associated with an increased mortality - why?

Answer 29

Much of this risk is related to the obstructive sleep apnea and cardiovascular complications. Studies have reported average survival reduction of up to 10 years in patients with acromegaly.

Evidence suggests that this risk is significantly reduced in patients who demonstrate biochemical cure following surgical management.