Hypopituitarism

 

• Background

  Deficiency in any pituitary hormone.

  Causes

  Congenital:

  • Genetic, including midline defect syndromes.
  • Traumatic: birth trauma or asphyxia.

  Tumour:

  • Non-functional adenoma.
  • Functional adenoma compressing stalk.
  • Craniopharyngioma
  • Neighbouring tumour.
  • Mets

  Vascular:

  • Pituitary apoplexy: bleeding or infarction that affects the pituitary.
  • Sheehan syndrome: pituitary ischaemia following obstetric haemorrhage.

  Inflammatory or toxic:

  • Haemochromatosis
  • Lymphocytic hypophysitis.
  • Sarcoidosis
  • TB

  Iatrogenic:

  • Post-surgery
  • Cranial radiotherapy.

  If it's due to a secondary mass effect, it usually affects less important hormones first – e.g. an isolated deficit in GH or LH/FSH – before the more vital hormones (ACTH, TSH, AVP).

  Secondary endocrine effects of hypopituitarism

  Many endocrine glands are controlled by the pituitary, which in turn is controlled by the hypothalamus. For such glands, a problem in the gland itself is 'primary', a problem in the pituitary is 'secondary', and in the hypothalamus is 'secondary' or 'tertiary'.

  Lab findings:

  • Primary: low hormone levels lead to feedback on functioning pituitary → ↓hormone and ↑pituitary hormone.
  • Secondary: low hormone levels but ineffective feedback on non-functioning pituitary → ↓hormone and ↓pituitary hormone, or pituitary hormone is inappropriately normal.
  • For disorders of excess hormone, primary is ↑hormone and ↓pituitary hormone, while secondary is ↑hormone and ↑/normal pituitary hormone.

• Signs and symptoms

  Children:

  • Hypoglycaemia (due to ↓GH and ↓ACTH).
  • Early jaundice.
  • Growth failure and/or delayed puberty.

  Adults:

  • Secondary endocrine deficiencies: hypogonadism, ↓thyroid, ↓adrenal hormones.
  • Tumour mass effect: headache, mild ↑prolactin due to suppression of stalk and hence reduction in inhibitory dopamine (very high PRL, however, suggests prolactinoma).
  • Sudden retro-orbital headache in pituitary apoplexy.
  • CVD (↓GH).
  • DI (↓AVP)

• Investigations

  Insulin tolerance test:

  • IV insulin should lead to ↓glucose, followed by a rebound in glucose due to cortisol and GH effects.
  • Deficiency in cortisol and GH in hypopituitarism will lead to reduced rebound.
  • Contraindications: IHD, seizures.

  Hormone levels:

  • Some should be done at 8am: ↓cortisol, ↓ACTH, ↓testosterone/FSH/LH (in men).
  • ↓E2/FSH/LH (in women): test can be done any time of day.
  • ↓IGF-1
  • ↓T4, ↓TSH
  • ↑Prolactin

  ACTH stimulation:

  • Blunted rise in adrenal hormones in established hypopituitarism, though this is also seen in primary adrenal disease.
  • Therefore, ACTH levels are needed to differentiate.

• Management

  Incremental hormone replacement e.g. testosterone, T4, GH, and/or corticosteroids.