Hypersecretion of Anterior Pituitary Hormones Flashcards
07.10.2019
Hyperpituitarism
Symptoms associated with excess production of adenohypophysial hormones
- Usually due to isolated pituitary tumours but can also be ectopic (i.e. from non-endocrine tissue) in origin
- can be associated with visual field and other (e.g. cranial nerve) defects as well as endocrine-related signs and symptoms
Bitemporal hemianopia
- loss of vision from the outer temporal vision fields
- can be caused by compression of the optic chasm by a suprasellar tumour
How do you asses bitemporal hemianopia?
Visual field test?
Excess ACTH leads to..
Cushing’s syndrome
Excess TSH leads to..
Thyrotoxicosis
Excess LH and FSH lead to..
precocious puberty in children
Excess Prolactin leads to…
Hyperprolactinaemia
Excess GH leads to..
Acromegaly, Gigantism
What are the 2 forms of hyperprolactinaemia?
- Physiological (in pregnancy and breastfeeding)
- Pathological (prolactinoma, often microadenomas < 10mm diameter)
High prolactin suppresses GnRH pulsatility!!!
How does hyperprolactinaemia due to pituitary adenoma show in women?
- galactorrhoea (milk production)
- secondary amenorrhoea (or oligomenorrhoea)
- loss of libido
- infertility
How does hyperprolactinaemia due to pituitary adenoma show in men?
- galactorrhoea uncommon (since appropriate steroid background usually inadequate)
- loss of libido
- erectile dysfunction
- infertility
-> presents with symptoms of testosterone deficiency
What receptors do lactotrophes express?
D2 receptors
Where does the dopamine that acts on lactotrophes come from?
HYPOTHALMIC DOPAMINERGIC NEURONES
How is the release of prolactin regulated?
Dopamine suppresses the release of prolactin.
How do you treat hyperprolactinaemia?
- 1st line treatment: D2 agonists (decrease PRL secretion, reduce tutor size)
What are examples of D2 agonists?
BROMOCRIPTINE
CABERGOLINE
-> oral administration
What are side effects of D2 agonists?
- Nausea and vomiting
- Postural hypotension
- Dyskinesias
- Depression
- Impulse control disorder e.g. Pathological gambling
- hyper sexuality
-> good to have a close relative to monitor them
What does excess GH result in in children and in adults?
Children: gigantism
Adults: acromegaly
-> usually due to a benign GH secreting pituitary adenoma
Tallest man recorded in world history
Robert Wadlow
died at age 22
Acromegaly
- insidious in onset
- signs and symptoms progress very gradually, can be undiagnosed for years.
- untreated, excess GH is associated with increased morbidity and mortality
-> soft tissue growth
What grows in acromegaly?
- periosteal bone
- cartilage
- fibrous tissue
- connective tissue
- internal organs (cardiomegaly, splenomegaly, hepatomegaly, etc.)
What additional screening do acromegaly patients have and why?
Bowel cancer screening as bowel cancer is common in patients with acromegaly.
What are the causes of death in acromegaly?
- Cardiovascular disease 60%
- Respiratory complications 25%
- Cancer 15%
Clinical features of acromegaly (8)
- excessive sweating (hyperhidrosis)
- headache
- enlargement of supraorbital ridges, nose, hands and feet, - thickening of lips and general coarseness of features
- enlarged tongue (macroglossia)
- mandible grows causing protrusion of lower jaw (prognathism)
- carpal tunnel syndrome (median nerve compression)
- barrel chest, kyphosis
-> old photos are useful with diagnosis
What are the metabolic effects of acromegaly?
- excess GH production ->
- increased endogenous glucose production, decreased muscle glucose uptake ->
- increased Insulin production = increased insulin resistance ->
- impaired glucose tolerance ->
- Diabetes Mellitus
What does GH do to muscle glucose uptake?
it suppresses it.
What are some complications of acromegaly?
- obstructive sleep apnoea
- Hypertension
- Cardiomyopathy
- increased risk of cancer (e.g. colonic polyps -> regular screening with colonoscopy)
Obstructive sleep apnoea in acromegaly
Bone and soft-tissue changes surrounding the upper airway lead to narrowing and subsequent collapse during sleep
Hypertension in acromegaly
- Direct effects of GH &/or IGF-1 on vascular tree
- GH mediated renal sodium reabsorption
Cardiomyopathy in acromegaly
- Hypertension
- DM
- direct toxic effects of excess GH on myocardium
What hormone is often co-secreted in acromegaly?
- Prolactin is often high in acromegaly – may reflect tumour secreting GH AND prolactin
- Hyperprolactinaemia will cause secondary hypogonadism (see clinical features of hyperprolactinaemia)
How do you diagnose acromegaly?
- Elevated serum IGF-1
- Failed suppression (‘paradoxical rise’) of GH following oral glucose load – oral glucose tolerance test
- measuring GH is unhelpful as it is pulsatile!!
Treatment of Acromegaly
- trans-sphenoidal surgery (first line)
- Medical (somatostatin analogues (e.g. octreotides), dopamine agonists (e.g. cabergoline))
- radiotherapy
Why are dopamine agonists sometimes used to treat acromegaly?
GH secreting pituitary tumours often express D2 receptors.
What are side effects of somatostatin analogues?
GI side effects common eg nausea, diarrhoea, gallstones can occur
How/when are somatostatin analogues given to treat acromegaly?
- Injection: short acting or monthly depot
- Pre-treatment before surgery may make resection easier
- Use post-operatively if not cured or whilst waiting for radiotherapy to take effect (slow)
What do somatostatin analogues do in acromegaly?
reduces GH secretion and tumour size
