Acromegaly

• Acromegaly is a condition caused by elevated levels of growth hormone (GH) over a prolonged period
• Acromegaly occurs post-epiphyseal fusion. In contrast, gigantism is a condition of childhood due to excessive growth hormone secretion prior to epiphyseal growth plate fusion.
• Normally a sporadic condition seen in middle-aged adults. Rarer familial causes include MEN1
• Acromegaly is usually caused by a growth hormone (GH)-secreting pituitary adenoma. Rarely, pituitary hyperplasia may also result in elevated GH
• IGF-1 is produced in response to GH. IGF-1 mediates the effects of GH and has a negative feedback effect to inhibit GH secretion by producing somatostatin and acting on somatotrophs
• GH is also termed somatotropin
• Growth hormone releasing hormone (GHRH) is released from the arcuate nucleus of the hypothalamus.

  It is transported via the hypophyseal portal system to the anterior pituitary. Here it stimulates the release of growth hormone.
• IGF-1 is produced and released by the liver. It has widespread growth promoting effects.

  This axis features negative feedback, in which IGF-1 and GH release leads to the inhibition of GHRH and stimulation of somatostatin release. Somatostatin is a negative regulator of growth hormone secretion.
• Other causes of acromegaly other than pituitary adenomas are very rare. They are related to excess secretion of GHRH or GH:

  • 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.
• Symptoms:

  • Headache, visual changes (bitemporal hemianopia)
  • Change in appearance
  • Weight gain
  • Fatigue
  • Joint pain
  • Voice changes
  • Snoring (OSA)
  • sweating
• Mass effect from the adenoma can cause reduction in production of other hormones e.g. menstrual cycle dysfunction or erectile dysfunction if prolactin is affected
• Clinical exam:

  • Frontal bossing (prominent forehead)
  • Macroglossia (large tongue)
  • Prognathism (protruding lower jaw)
  • Interdental separation
  • Enlarged hands and fingers
  • Skin thickening
  • Signs of carpal tunnel syndrome (bilateral)
  • Hypertension
• Bedside exam:

  • Visual field exam - bitemporal hemianopia
• Lab investigations:

  • IGF-1 will be raised
  • Oral glucose tolerance test used to confirm diagnosis - GH will not be suppressed
  • Blood glucose, calcium, phosphate and triglycerides - may be raised
  • Pituitary assessment - prolactin, cortisol, TFTs, FSH/LH and testosterone
• Serum growth hormone is not routinely used due to GH pulses throughout the day and at times of stress
• Imaging:

  • MRI pituitary to investigate for pituitary adenoma
• Surgical removal of the pituitary adenoma is usually performed via transsphenoidal surgery. This is the initial treatment for most patients and involves making an incision in the nose (sphenoid sinus) to allow access to the pituitary adenoma.

  Patients can be considered cured after surgery but will need regular follow-up.
• Medical management is normally used as adjuvant treatment or for patients where surgery is not recommended
• Medical management:

  • Somatostatin analogues e.g. octreotide - inhibit the release of GH
  • GH receptor antagonists e.g. Pegvisomant - inhibits the synthesis of IGF-1
  • Dopamine agonists e.g. Bromocriptine - supressed GH secretion. Also suppress prolactin secretion.
• Pituitary radiotherapy (most often, stereotactic gamma-knife) is used when there is a failure of surgical or medical treatment and can be used in combination with medical therapy.

  Radiotherapy carries the risk of hypopituitarism which can affect fertility.
• Disease activity monitoring includes:

  • IGF-1
  • Change in signs and symptoms
  • Pituitary hormone tests: TFT, cortisol, prolactin, oestradiol and testosterone
  • MRI pituitary: to monitor the size of the adenoma.
• Monitoring for complications may include:

  • Blood pressure measurements
  • ECG and echocardiography
  • Epworth sleepiness scale
  • OGTT
  • Colonoscopy every 10 years (due to the increased risk of colonic polyps)
• Major complication is cardiovascular disease - hypertension, CCF, stroke and CAD
• Other complications:

  • Diabetes
  • OSA
  • Colorectal cancer - increased risk of polyps
  • Thyroid cancer
  • Hypopituitarism
  • Carpal tunnel syndrome
  • Osteoarthritis