Hyposecretion of anterior pituitary hormones Flashcards
Distinguish between primary, secondary and tertiary pituitary disease states relating to pituitary function.
Primary- disorder in endocrine gland itself (thyroid, gonads, adrenal cortex).
Secondary- disorder in anterior pituitary or signalling from it.
Tertiary- disorder in hypothalamus or signalling from it.
Define hypopituitarism.
Decreased production of all anterior pituitary hormones (panhypopituitarism) or of specific hormones.
What are the 3 main types of panhypopituitarism?
Simmond’s disease
Sheehan’s syndrome
Pituitary apoplexy
In what order does loss of secretion of hypopituitary hormones occur?
Gonadotrophins (LH and FSH) GH Thyrotrophin Corticotrophin Prolactin deficiency is uncommon/unrecognised
What may panhypopituitarism be caused by?
- Congenital defects (rare)
- Gene mutations (very rare)- e.g. PROP1 mutation, a transcription factor that allows the development of the pituitary gland to take place
Acquired causes:
- Tumours (hypothalamic- craniopharyngiomas; pituitary- adenomas, metastases, cysts)
- Radiation
- Infection (e.g. meningitis)
- Traumatic brain injury
- Infiltratrive disease
- Inflammation
- Pituitary apoplexy (haemorrhage/infarction)
- Peripartum infarction
Usually, panhypopituitarism will develop in an adult with progressive loss of pituitary secretion.
What are the general clinical features of panhypopituitarism?
Patients will be deficient in GH and at least one other anterior pituitary hormone.
Short stature.
Hypoplastic anterior pituitary.
Describe the onset of Simmond’s disease.
Insidious- develops very slowly.
Name some causes of Simmond’s disease.
- Infiltrative processes (e.g. lymphocytic)
- Pituitary adenomas
- Craniopharyngiomas
- Cranial injury
- Following surgery
Name some symptoms of Simmond’s disease.
- Secondary amenorrhoea or oligomenorrhoea
- Impotence
- Loss of libido
- Tiredness/fatigue
- Waxy skin
- Loss of body hair
- Hypotension
- Weight gain
What are symptoms of Simmond’s disease usually due to?
Decreased thyroidal, adrenal and gonadal function.
Describe the onset of Sheehan’s syndrome.
Very fast.
How does Sheehan’s syndrome develop?
Acutely following postpartum haemorrhage resulting in pituitary infarction.
Blood loss results in vasoconstrictor spasm of hypophysial arteries, leading to:
-ischaemia of the pituitary (which is enlarged during pregnancy)
-necrosis of the pituitary
ONLY WOMEN.
Name some symptoms of Sheehan’s syndrome.
Lethargy
Anorexia
Weight loss
Secondary hypothyroidism and hypoadrenalism
Failure of lactation (prolactin deficiency)
What is pituitary apoplexy?
Similar to Sheehan’s syndrome but not specific to women.
Due to an intra-pituitary infarction or haemorrhage.
Rapid presentation in patients with pre-existing pituitary tumours which suddenly infarct.
Can be precipitated by anticoagulants.
Name some symptoms of pituitary apoplexy.
Severe sudden onset headache
Bitemporal hemianopia (compressed optic chiasm)
Diplopia (cavernous sinus involvement, CNIV and CNVI)
Ptosis (cavernous sinus involvement, CNIII)
How is hypopituitarism diagnosed?
Measure basal plasma concentrations of pituitary or target endocrine gland hormones.
Can’t measure hypothalamic hormones.
Most hormones are released from the hypothalamus in pulses, so singular random measurements are useless.
Pituitary MRI- may reveal specific pituitary pathology, e.g. haemorrhage (apoplexy), adenoma; empty pituitary sella
What test is used to check whether a patient is producing a hormone at a normal level?
Stimulation/provocation test
Give 3 examples of stimulated pituitary function tests.
ACTH and GH = ‘stress’ hormones- released under stress.
Hypoglycaemia (<2.2mM) induced = ‘stress’.
Insulin-induced hypoglycaemia stimulates GH release and ACTH release (cortisol measured).
TRH stimulates TSH release.
GnRH stimulates FSH and LH release.
List three secondary endocrine gland failures.
Hypogonadism (lack of gonadotrophins)
Hypothyroidism (lack of thyrotrophin)
Hypoadrenocorticalism (lack of corticotrophin)
What does a lack of somatotrophin (GH) result in in children and adults?
Children- pituitary dwarfism
Adults- effects unclear
List causes of short stature in children.
Genetic (e.g. Down’s, Turner’s, Prader-Willi syndrome)
Malnutrition
Emotional deprivation
Systemic disease (e.g. cystic fibrosis, rheumatoid arthritis)
Malabsorption (e.g. coeliac disease)
Endocrine disorders (e.g. Cushing’s syndrome, hypothyroidism, GH deficiency, poorly controlled T1DM)
Skeletal dysplasias (e.g. achondroplasia, osteogenesis imperfecta)
List congenital causes of GH deficiency in children.
Deficiency of hypothalamic GHRH
Mutations of the GH gene
Developmental abnormalities (e.g. aplasia or hypoplasia of the pituitary gland)
List acquired causes of GH deficiency in children.
Tumours of the hypothalamus or pituitary Other intracranial tumours nearby (e.g. optic nerve glioma) Irradiation Head injury Infection or inflammation Severe psychosocial deprivation
What are three types of dwarfism?
Achondroplasia
Pituitary dwarfism
Laron dwarfism
What is achondroplasia?
Mutation in fibroblast growth factor receptor 3 (FGF3)
Abnormality in growth plate chondrocytes- impaired linear growth
Average-sized trunk
Short arms and legs
What is pituitary dwarfism?
Childhood GH deficiency
Normal proportions
What is Laron dwarfism?
Mutation in GH receptor
IGF-1 treatment in childhood can increase height
How is short stature diagnosed?
Mid-parental height: a predicted adult height based on father’s and mother’s height.
List causes of acquired GH deficiency in adults.
Trauma
Pituitary tumour
Pituitary surgery
Cranial radiotherapy
How is GH deficiency diagnosed?
Stimulation test (random GH is useless because it is pulsatile)- lack of response to e.g. insulin-induced hypoglycaemia.
Low plasma IGF-1
Low plasma IGF-BP3
List GH provocation tests.
GHRH + Arginine (i.v.)- in combination more effective than each alone
Insulin (i.v.)- via hypoglycaemia
Glucagon (i.m.)
Exercise (e.g. 10 minute step climbing- when appropriate)
Measure plasma GH at specific time points (before and after).
Describe the preparation and administration of GH therapy.
Preparation: human recombinant GH (somatotropin).
Administration: daily subcutaneous injection; monitor clinical response and adjust dose to IGF-1.
What are the signs and symptoms of GH deficiency in adults?
Reduced lean mass
Increased adiposity
Increased waist:hip ratio
Reduced muscles strength and bulk leading to reduced exercise performance
Decreased plasma HDL-cholesterol and raised LDL-cholesterol
Impaired psychological wellbeing and reduced quality of life
What are the potential benefits of GH therapy in adults?
Improved body composition- decreased waist circumference, less visceral fat
Improved muscle strength and exercise capacity
More favourable lipid profile- higher HDL-cholesterol, lower LDL-cholesterol
Increased bone mineral density
Improved psychological wellbeing and quality of life
What are the potential risks of GH therapy in adults?
Increased susceptibility to cancer
Increased risk of cardiovascular accidents
Increased soft tissue growth, e.g. cardiomegaly
What is used as a replacement in ACTH deficiency and what parameter is checked?
Hydrocortisone
Serum cortisol
What is used as a replacement in TSH deficiency and what parameter is checked?
Thyroxine
Serum free T4
What is used as a replacement in women in LH/FSH deficiency and what parameter is checked?
Ethinyloestradiol; medroxyprogesterone; HRT (E2 plus progestogen)
Oestrogen deficiency; libido; symptom improvement; withdrawal bleeds
What is used as a replacement in men in LH/FSH deficiency and what parameter is checked?
Testosterone (undecanoate)
Libido; serum testosterone; symptom improvement
What is used as a replacement in GH deficiency and what parameter is checked?
GH
IGF1, growth chart (children)
What are the expected results of GH therapy in children?
Acceleration of linear growth (GH stimulates protein synthesis)
Decreased body fat
Younger and obese children respond better
What is the problem with GH therapy in children?
Resistance may develop (antibody formation), so need to consider this when deciding when to start treatment
