Hypothalamic/pituitary axis dysfunction

Question 1

What are the uses of growth hormone releasing hormone?

Answer 1

IV injection of the synthetic analogue, sermorelin, was used as a diagnostic test for GH secretion in the UK
Other analogues e.g. hexarelin suggested to be useful in short-stature children with low GH levels but effects wear off rapidly so not worth developing as drugs

Question 2

What are the uses of somatostatin?

Answer 2

Stable analogues octreotide and lanreotide are given SC, IM or IV for short term treatment of acromegaly and neuroendocrine tumours, particularly carcinoid tumours and hypersecretory endocrine tumours; Pasireotide used for Cushing’s disease

Question 3

What are the main characteristics of growth hormone?

Answer 3

Released from anterior pituitary into the blood stream
Linear growth of bone through effects on cartilage (long bones), growth of visceral organs, adipose and connective tissue, endocrine glands and skeletal muscle
Direct effects stimulated by glucocorticoids
Indirect effects mediated by IGF-1, made in the liver, major mediator of GH effects
Effects of IGF-1 attenuated by glucocorticoids

Question 4

Hyposecretion of growth hormone leads to:

Answer 4

In children results in impairment of growth or dwarfism
Laron-type or idiopathic dwarfism, rare, familial, deficiency in GH receptors/ GH binding proteins leads to reduced IGF-1 production
Short stature, obesity, hypoglycaemia, reduced life expectancy
African pygmies- low IGF-1 levels, normal GH levels
Dwarfism often not due to problems with GH
Can use insulin tolerance test which should increase H levels to identify type of dwarfism

Question 5

What is the treatment for dwarfism?

Answer 5

Most cases treated with GH replacement therapy
Unresponsive Laron-type children treated with SC recombinant human IGF-1 (mecasermin) for several years
GH treatment follows May 2010 NICE guidelines for children and August 2003 guidelines for adults

Question 6

What are the causes of hypersecretion of GH?

Answer 6

Benign pituitary adenoma, rarely other endocrine tumours

Question 7

What are the symptoms of hypersecretion of GH in children?

Answer 7

Gigantism, excessive growth of long bones, physical weakness

Question 8

What are the symptoms of hypersecretion of GH in adults?

Answer 8

Abnormal bone and soft tissue growth- acromegaly
Coarse facial features- prominent brow, large nose, protruding jaw, enlarged lips and tongue
Enlarged fleshy spade-like hands and feet
Enlarged internal organs- heart and kidney, sometimes diabetes
Headaches and visual field disturbances, elevated plasma IGF-1
Untreated cases shortens life expectancy

Question 9

How is hypersecretion of GH diagnosed?

Answer 9

Glucose suppression test with a high dose of glucose which should decrease GH levels

Question 10

With what conditions are children treated for dwarfism?

Answer 10

Growth-hormone deficiency
Short children considered small at birth
Turner’s syndrome
Prader-Willi syndrome
Chronic renal insufficiency before puberty
Short stature homeobox-containing gene (SHOX) deficiency

Question 11

What 3 conditions do adults need to fulfil to get treatment for dwarfism?

Answer 11

Severe growth hormone deficiency
Impaired quality of life
Already being treated fro another pituitary hormone deficiency

Question 12

What is the treatment for acromegaly?

Answer 12

Removal of tumour and/or radiotherapy
Octreotide and lanreotide to reduce GH secretion and tumour size prior to surgery or for longer term treatment
Highly selective growth hormone receptor antagonist given, only in patients with poor responses
Mild cases treated with dopamine agonist for life

Question 13

What are the main characteristics of vasopressin?

Answer 13

Produced by the supraoptic nucleus and released from the posterior pituitary into the blood stream
Regulates body fluid volume
Acts on the distal convoluted tubules and collecting ducts
Main action to decrease urine volume and increase body fluid
Release controlled by plasma osmolarity and blood volume/arterial pressure

Question 14

What are the causes of hyposecretion of vasopressin?

Answer 14

Caused by damage, tumours or diabetes insipidus

Question 15

What is the treatment for hyposecretion of vasopressin?

Answer 15

Treated with vasopressin SC or IM injection, vasopressin analogue desmopressin oral, sublingual, intranasal or SC, IM or IV injection
Dose aims to provide mild diuresis to avoid water intoxication
Vasopressin and desmopressin only used for pituitary diabetes insipidus not nephrogenic
Thiazide diuretics e.g. chlortalidone can be useful in nephrogenic and partial pituitary diabetes insipidus
Carbamazepine sometimes used in partial pituitary diabetes insipidus

Question 16

What are the causes of hypersecretion of vasopressin?

Answer 16

Ectopic tumour, pulmonary disorders, brain lesions, antidepressant/ antipsychotic drug treatment, diuretics

Question 17

What are the symptoms of hypersecretion of vasopressin?

Answer 17

Rare, Schwartz-Bartter syndrome, excessive water retention, hyponatraemia and high urine osmolarity, weakness, lethargy, weight gain, anorexia, cerebral oedema can lead to confusion, convulsions, coma and death

Question 18

What is the treatment for hypersecretion of vasopressin?

Answer 18

Treated by removal of the tumour/ treatment of malignant disease, water restriction, hypertonic (3%) saline infusion and furosemide, oral vasopressin antagonist demeclocycline, oral vasopressin V2 receptor antagonist tolvaptan, removal fo drug