Epidemiology

  • Incidence: 1.00 cases per 100,000 person-years
  • Peak incidence: 40-50 years
  • Sex ratio: 1:1
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Pathophysiology

In acromegaly there is excess growth hormone secondary to a pituitary adenoma in over 95% of cases. A minority of cases are caused by ectopic GHRH or GH production by tumours e.g. pancreatic.

Clinical features

Features
  • coarse facial appearance, spade-like hands, increase in shoe size
  • large tongue, prognathism, interdental spaces
  • excessive sweating and oily skin: caused by sweat gland hypertrophy
  • features of pituitary tumour: hypopituitarism, headaches, bitemporal hemianopia
  • raised prolactin in 1/3 of cases → galactorrhoea
  • 6% of patients have MEN-1

Investigations

Growth hormone (GH) levels vary during the day and are therefore not diagnostic.

Serum IGF-1 levels have now overtaken the oral glucose tolerance test (OGTT) with serial GH measurements as the first-line test. The OGTT test is recommended to confirm the diagnosis if IGF-1 levels are raised.

The Endocrine Society guidelines suggest the following:


1.1 We recommend measurement of IGF-1 levels in patients with typical clinical manifestations of acromegaly, especially those with acral and facial features.
...
1.5 In patients with elevated or equivocal serum IGF-1 levels, we recommend confirmation of the diagnosis by finding lack of suppression of GH to < 1 μg/L following documented hyperglycemia during an oral glucose load.

Serum IGF-1 may also be used to monitor disease

Oral glucose tolerance test
  • in normal patients GH is suppressed to < 2 mu/L with hyperglycaemia
  • in acromegaly there is no suppression of GH
  • may also demonstrate impaired glucose tolerance which is associated with acromegaly

A pituitary MRI may demonstrate a pituitary tumour.

Management

Trans-sphenoidal surgery is the first-line treatment for acromegaly in the majority of patients

Dopamine agonists
  • for example bromocriptine
  • the first effective medical treatment for acromegaly, however now superseded by somatostatin analogues
  • effective only in a minority of patients

Somatostatin analogue
  • directly inhibits the release of growth hormone
  • for example octreotide
  • effective in 50-70% of patients
  • may be used as an adjunct to surgery

Pegvisomant
  • GH receptor antagonist - prevents dimerization of the GH receptor
  • once daily s/c administration
  • very effective - decreases IGF-1 levels in 90% of patients to normal
  • doesn't reduce tumour volume therefore surgery still needed if mass effect

External irradiation is sometimes used for older patients or following failed surgical/medical treatment

Complications

Complications