FRCA Notes

Acromegaly

The relevant curriculum items are: 'Explains the anaesthetic implications of pituitary disease including endocrine effects' and 'endocrine abnormalities of significance to anaesthesia'.

Resources

  • Acromegaly is caused by a growth hormone-secreting pituitary macroadenoma
  • Onset of symptoms is insidious and patients typically present in middle age
  • Growth hormone (somatotrophin) is a 191 amino acid polypeptide
  • It plays a complex role in growth, maturation and metabolism

Synthesis

  • Manufactured by acidophilic cells called somatotrophs
    • Make up 50% of the cells of the anterior pituitary
    • 300-500μg daily release (5% of pituitary store)

Secretion

  • Secretion demonstrates a 2-hr periodicity including a nocturnal peak
  • Absolute GH levels increase throughout childhood, peaking in puberty before steadily falling and declining in old age

  • Synthesis and release is controlled by other hormones
    • Stimulate GH Inhibit GH
    GHrH Somatostatin
    Cortisol IGF-1
    Thyroid hormones Growth hormone
    Hyperglycaemia
    High circulating free fatty acids
    Beta-adrenoreceptor agonists

  • Highly protein bound
  • Half-life approximately 20mins

Downstream effectors

  • All cells express growth hormone receptors
  • Downstream effects are mediated by molecules known as somatomedins
  • These are highly protein-bound mediators which maintain fairly constant levels
  • Examples include hepatically-produced IGF-1 and IGF-2, as well as various paracrine somatomedins

Acute (2-3hrs) metabolic effects

  • Increased lipolysis and ketogenesis
  • Gluconeogenesis, glycogenolysis and increased hepatic glucose release
  • Reduced insulin sensitivity in liver and skeletal muscle → antagonises insulin with regard to carbohydrate and fat metabolism
  • Increased amino acid uptake into cells to promote protein growth → complementary to insulin with regard to protein metabolism

Anabolic effects

  • Widespread growth and protein synthesis
  • Lengthening of long bones via epiphyseal activity and bone mineralisation
  • Hypertrophy and hyperplasia
  • Enhanced salt and water retention via inhibition of ANP

Airway and Respiratory

  • A number of changes increase the likelihood of a difficult airway:
    • Enlargement of the jaw, nose, lips and ears
    • Nasal turbinate enlargement
    • Macroglossia
    • Thickened pharyngeal and laryngeal soft tissue
    • Vocal cord hypertrophy (& deepening of voice)
    • Decreased laryngeal aperture i.e. laryngeal stenosis
    • Subglottic stenosis
    • Recurrent laryngeal nerve palsy

  • Presence of OSA (up to 80%) ± reduced central respiratory drive
  • Presence of thyroid goitre (25%) ± tracheal compression

Cardiovascular

  • Hypertension (30%), which is often refractory
  • Eccentric LV hypertrophy, cardiomegaly, cardiomyopathy and myocardial fibrosis
  • Arrhythmias
  • Right heart failure, which may be secondary to OSA
  • Atherosclerotic disease

Neurological

  • Peripheral neuropathies, especially carpal tunnel syndrome which is often bilateral
  • Potential for raised ICP
  • Headaches

MSK

  • Enlargement of hands and feet
  • Kyphoscoliosis
  • Arthropathy

Gastrointestinal

  • Increased incidence of malignancy e.g. colorectal cancer

Nutritional and metabolic

  • Normally, GH release is suppressed by both IGF-1 and glucose (75g glucose load)
  • In acromegaly, there are chronically raised IGF-1 levels and glucose does not suppress GH levels
  • Type 2 diabetes mellitus (25%)

Gonadal

  • Reduced libido
  • Erectile dysfunction
  • Infertility
  • Oligomenorrhoea
  • Galactorrhoea

  • Medical therapy
    • First line: somatostatin analogues e.g. octreotide, lanreotide
    • Second line: dopamine agonists e.g. bromocriptine, cabergoline
    • Other: growth hormone receptor antagonists e.g. pegvisomant
  • Pituitary radiotherapy
  • Pituitary surgery

  • Long-term
    • Regular colonoscopy as high risk of colorectal cancer
    • Long-term follow up of IGF-1 levels

Perioperative management of the patient with acromegaly


Investigations

  • Screening for OSA
  • 12-lead ECG
  • TTE
  • Glucose and HbA1c levels

Optimisation

  • Consider preoperative somatostatin analogue therapy to reduce anaesthetic and surgical risks caused by excess GH production
  • Cardiology referral for optimisation of blood pressure ± further management of cardiac involvement
  • Diabetes team input
  • ENT; nasendoscopy to visualise larynx pre-operatively

Monitoring and access

  • AAGBI
  • Venous access may be difficult due to excessive soft tissue

  • Arterial lines may be indicated because of coalescing cardiovascular disease
  • However, ulnar collateral circulation may be poor thus relatively contraindicating radial A-lines

Airway

  • Anticipate difficult airway
  • Facemask ventilation requires larger masks and often an OPA
  • Caution with nasal airways due to enlarged turbinates
  • Use a smaller-than-anticipated ETT
  • Consider awake tracheal intubation
  • Check cuff leak prior to extubation

Care bundle

  • Meticulous positioning as at high risk of nerve entrapment
  • Intra-operative management of diabetes as appropriate

  • Consider HDU care, especially if established OSA
  • Post-operative complications:
    • Post-operative stridor
    • Difficulty with oxygenation due to the contraindication to CPAP and HFNO following trans-sphenoidal surgery
    • Endocrine abnormalities such as SIADH or diabetes insipidus