Lecture 6.2 - Pituitary disorders

Diabetes Insipidus

• Diabetes insipidus is caused by ADH resistance, where the kidneys do not respond to ADH in the normal way.
• It should not be confused with diabetes mellitus.

Prolactinoma

• Prolactinoma is a prolactin-secreting pituitary tumor.
• Macro-adenoma refers to a large tumor (>1cm), while micro-adenoma refers to a small tumor (<1cm).
• The larger the prolactinoma, the higher the prolactin levels.
• Prolactinomas are typically treated with tablets, even in cases where the tumor is large and causes visual problems.
• Prolactin is under tonic inhibitory control by dopamine, so anything blocking the pituitary stalk will lead to prolactin disinhibition.
• If prolactin levels are <5000 miU/L, it may be due to disinhibition rather than active prolactin secretion.
• If prolactin levels are >5000 miU/L, it is likely due to active prolactin secretion (prolactinoma).

Symptoms of Hyperprolactinaemia in Women

• Galactorrhoea (unexplained milk production - milky discharge from breasts)
• Menstrual disturbance

Growth Hormone Deficiency

• Growth hormone (GH) deficiency has little effect on fetal growth.
• Severe prenatal deficiency can result in hypoglycaemia and jaundice.
• From ~1 year of age until mid-teens, GH deficiency results in poor growth and short stature (treatment: human recombinant GH).

Gonadotropin Deficiency

• Gonadotropin deficiency in adults can result in:
  • Loss of secondary sexual characteristics
  • Lack of libido, infertility, and oligomenorrhea or amenorrhea in women of reproductive age
  • Decreased libido and impotence in men
• In children, gonadotropin deficiency can result in delayed puberty.

TSH and ACTH Deficiency

• TSH deficiency can result in:
  • Low thyroid hormones (low T4)
  • Non-elevated TSH
  • Symptoms: feeling cold, weight gain, tiredness, slow pulse
• ACTH deficiency can result in:
  • Low cortisol
  • Symptoms: feeling tired, dizzy, low blood pressure (low sodium)
  • HPA axis integrity is vital, so ACTH deficiency can be life-threatening.

ADH Deficiency (Diabetes Insipidus)

• ADH deficiency may result from a hypothalamic tumour or a pituitary tumour that has extended up into the hypothalamus.
• Other causes of ADH deficiency: cranial radiotherapy, pituitary surgery, autoimmune infiltration, and infections such as meningitis.
• Insufficient release of ADH from the posterior pituitary leads to:
  • Excess excretion of dilute urine
  • Dehydration
  • Increased sensation of thirst (polydipsia)

Pituitary Gland

• The pituitary gland sits below the brain in the sella turcica (a pocket of the sphenoid bone).

Pituitary Disorders

• Pituitary disorders are relatively rare (~70,000 patients in the UK).
• They manifest as either OVER or UNDER secretion of pituitary hormones.
• The most common cause is a benign tumour (adenoma).

Clinical Presentation of Pituitary Tumours

• Most pituitary tumours are "non-functioning" (the tumour cells do not produce any hormone).
• Mass effect of tumour on local structures:
  • Visual loss
  • Headache
• Abnormal pituitary function:
  • Hypo-secretion of pituitary hormones
  • Hyper-secretion of pituitary hormones
• Mass effect of pituitary tumour on local structures:
  • Optic chiasm (vision loss)
  • III, IV (eye movement)
  • Va,b (pain)
  • Internal carotid artery (blood supply)
  • VI nerve (lateral eye movement)

Investigation of a Suspected Pituitary Tumour

• Imaging: size and topographical location of the pituitary or parapituitary mass (usually by MRI scan).
• Assessment of visual field defects.
• Assessment of endocrine function to determine whether there is a hormonal excess or deficiency.
• Measuring the levels of relevant hormones in the blood (where possible staining sections from a biopsy of the tumour with antibodies for the relevant hormone).

Hypopituitarism

• Hypopituitarism is insufficient production of pituitary hormones.
• Most commonly a result of a pituitary adenoma (rarer causes include radiation therapy, inflammatory disease, and head injury).
• Loss of pituitary hormone secretion is usually secondary to a mass effect of the adenoma.
• Typically progressive loss of anterior pituitary function (GH and LH/FSH are usually the first hormones to be affected).
• Pan-hypopituitarism: deficiency for ALL anterior pituitary hormones.
• Secretion of antidiuretic hormone (ADH) and oxytocin from the posterior pituitary is usually affected significantly only if the tumour affects the hypothalamic function or if an inflammatory process is involved.