Disorders of the hypothalamus and pituitary

Question 1

Outline the physiology of the pituitary gland

Answer 1

Anterior pituitary:

• Gonadotrophin axis
• Growth axis
• Prolactin
• Thyroid axis
• Adrenal axis

Posterior pituitary:

• ADH
• Vasopressin

Question 2

What is the commonest cause of pituitary disease?

Answer 2

Pituitary tumours, typically benign pituitary adenomas

Pathological effects caused by

• Mass effect of tumour
• Excess hormone secretion
• Inadequate production of hormone

Question 3

Define functioning and non-functioning pituitary tumours

Answer 3

Functioning tumours secrete pituitary hormones and cause clinical syndromes.

Non-functioning tumours do not secrete pituitary hormones, therefore do not cause clinical syndromes.

Question 4

List the types of functional pituitary tumours

Answer 4

GH ➔ Gigantism and Acromegaly
ACTH ➔ Cushing’s disease and Nelson’s syndrome
PRL ➔ Hyperprolactinaemia or Prolactinoma
TSH (very rare) ➔ Hyperthyroidism

Question 5

How can non-functioning pituitary tumours present?

Answer 5

Optic chasm ➔ Visual field defects and visual loss
Bony structure and meninges ➔ Headaches
Cavernous sinus ➔ CN III, IV, VI (extraocular muscles)
Hypothalamus ➔ Altered appetite, obesity, thirst, wakefulness, precocious puberty
Ventricles ➔ Hydrocephalus
Sphenoid sinus ➔ CSF rhinorrhoea
Hypopituitarism

Question 6

What investigations should be done for pituitary tumours?

Answer 6

MRI of the pituitary

Visual fields

Question 7

Outline the treatment of pituitary tumours

Answer 7

Trans-sphenoidal resection*
Transcranial resection
Radiotherapy

Medical: Dopamine agonist (prolactinomas), Somatostatin analogue (acromegaly), GH antagonists (acromegaly)

Question 8

Describe the pathophysiology of hypopituitarism

Answer 8

Deficiency of hypothalamic releasing hormones or of pituitary trophic hormones can be selective or multiple. These include deficiencies of GH, LH/FSH, ACTH, TSH and ADH.

Multiple usually result from tumour growth or destructive lesions. There is a general progressive loss of anterior pituitary function.

Question 9

Name 5 causes of hypopituitarism

Answer 9

Neoplastic: Pituitary or hypothalamic tumours, meningiomas, gliomas, lymphoma
Iatrogenic: Surgery, radiotherapy, chemotherapy
Vascular: Pituitary apoplexy, Sheehan’s syndrome, Carotid artery aneurysm
Infection: Basal meningitis, encephalitis, syphilis
Trauma: Basal skull fracture
Autoimmune
Infiltrations: Sarcoidosis, hereditary haemochromatosis
Congenital: Kallmann’s syndrome

Question 10

How is hypopituitarism investigated?

Answer 10

Basal hormone levels:

• LH/FSH ➔ Oestradiol
• LH/FSH ➔ Testosterone
• IGF-1
• PRL
• TSH ➔ T3/T4
• Cortisol
• Plasma/urine osmolality

Dynamic tests:

• Growth: Insulin tolerance test, Glucagon test
• Adrenal: Insulin tolerance test, Synacthen test
• Water deprivation test

Question 11

Describe the indications, process, results of an insulin tolerance test

Answer 11

Diagnosis or exclusion of ACTH and GH deficiency

Patient fasts overnight
Insulin at time 0 to induce hypoglycaemia and stress
Bloods for glucose, cortisol, GH at 0, 30, 45, 60, 90, 120

Normal response:
Cortisol >550 nmol/L
GH >7 ng/L
Glucose must be <2.2 mmol/L

Question 12

How is hypopituitarism treated?

Answer 12

Hormonal replacement for any deficits. Especially steroid and thyroid hormones.

HCG or GnRH to improve fertility

Question 13

Describe the indications, process, results of a Synacthen test

Answer 13

Diagnosis or exclusion of adrenal insufficiency

Basal sample of cortisol
Give 250mcg Synacthen IV/IM
Sample for cortisol at time 30 and 60

Normal response:
Basal cortisol >170nmol/L
Cortisol increase to at least 580 nmol/L