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Acromegaly 

Study guide:

Definition:  

Acromegaly is broadening of the skeleton that occurs as a result of hypersecretion of the pituitary growth hormone (GH).It produces Gigantism (if acquired before epiphyseal closure) in children, and acromegaly (if acquired after epiphyseal closure) in adults. 

 

​​​Pathopyhsiology:

  • Excess growth hormone stimulates the proliferation of bones, cartilages, tissues leading to organomegaly. 

  • In normal situations, GH acts as a catabolic hormone to increase blood glucose levels, in cases of excess GH, there is loss of hypoglycemic stimulation and glucose suppression.

  • Insulin resistance and impaired glucose tolerance. 

 

Etiology:

  • Acromegaly usually occurs sporadically, although gene mutations can rarely give rise to familial acromegaly, typically the AIP gene in familial isolated pituitary adenoma.

  • Commonly, it is cause by a GH-secreting pituitary adenoma (10% of pituitary adenomas)

  • Other causes are:carcinoidor pancreatic islet tumourssecretingectopic GHRH resulting in excess GH.

Diagnosis:

  • Elevated serum insulin like growth factor-1(IGF-1, also known as somatomedin C) — is the first line diagnostic test.

  • Oral glucose suppression test (most specific) — 75 g of glucose PO suppress GH levels in healthy individuals but not in patients with acromegaly.

  • MRI of the pituitary— to look for tumors.

  • CT, MRI, or skull X-raysmay show cortical thickening, enlargement of the frontal sinuses, and enlargement and erosion of the Sella turcica.  

  • Visual field examination: defects are common (bitemporal hemianopsia)

  • Pituitary function:partial or complete anterior hypopituitarism is common.

  • Prolactin: mild to moderate hyperprolactinemia occurs in 30% of patients.​

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Management:

  • Untreated acromegaly results in reduced survival. 

  • Most deaths occur from heart failure, coronary artery disease and hypertension-related causes. 

  • When present, hypopituitarism should be corrected and concurrent diabetes and/or hypertension should be treated conventionally; both usually improve with treatment of the acromegaly.

  • The aim of therapy is to achieve a mean growth hormone level below 2.5 μg/L.

  • Surgery:Trans-sphenoidal surgery is the appropriate first-line therapy.

  • Pituitary radiotherapy: if IGF-1 levels stay elevated after surgery.

  • Medical therapy: There are three receptor targets to suppress GH secretion for the treatment of acromegaly:

  • Somatostatin receptor agonists: Octreotide and lanreotide

  • Dopamine agonists:bromocriptinean cabergoline— can be given to shrink tumours prior to definitive therapy or to control symptoms and persisting GH secretion.

  • Growth hormone antagonists: Pegvisomant 

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References:

  • Kumar and Clark’s Clinical Medicine, 8th ed.

  • Step Up to Medicine 4th Edition.

  • Toronto Notes 2017

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First author:    Fai Alhoshan


Format Editor:  Adel Yasky 

                          Bayan Alzomaili

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