Hypersecretion of anterior pituitary hormones Flashcards
What is a common feature of hypersecretion of anterior pituitary hormones
Usually just one type of hormone- not the whole gland
Summarise 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 quite often be associated with visual field and other (e.g. cranial nerve) defects
as well as endocrine-related signs and symptoms
What is meant by an ectopic cause
Neuroendocrine tumours- densely packed tumour full of peptide hormones- similar to peptide hormones
Carcinoid tumours of the gut can release too much ACTH- Cushing’s- but the pituitary gland is itself fine.
Why are both eyes affected by bitemporal hemianopia
o Both eyes may be affected by bitemporal hemianopia as the decussation of nerves is at the optic chiasm (where the pituitary is)
Describe the optic chiasm
At the optic chiasm, fibres from the nasal retinae cross. Light from the outer (temporal) aspects of the visual fields strikes the nasal aspect of the retina. Hence compression (by growth of a suprasellar tumour) of these crossing fibres at the optic chiasm means that there is loss of vision from the outer temporal visual fields.
Describe perimetry
Look straight ahead- look at screen with flashes and press button when you see the flashes- normal person can see all the flashes- no black.
However, a person with bitemporal hemianopia may not be able to see all of the flashes- some black spots
Describe what the consequences of excesses in each hormone
ACTH (corticotrophin) à Cushing’s disease.
TSH (thyrotrophin) à Thyrotoxicosis.
LH, FSH (gonadotrophins) à Precocious puberty in children.
Prolactin à Hyperprolactinaemia.
GH à Gigantism, Acromegaly.
What is the usual cause of hypersecretion of anterior pituitary hormones?
Pituitary adenoma
Differentiate between the pathological and physiological causes of hyperprolactinaemia
Physiological pregnancy breastfeeding Pathological prolactinoma (often microadenomas < 10mm diameter)
What happens to GnRH pulsatility during puberty
Becomes much more frequent and much more rapid
List the symptoms of hyperprolactinaemia due to a prolactinoma seen in females
galactorrhoea (milk production)
secondary amenorrhoea (or oligomenorrhoea)- often the presenting complaint and why picked up earlier in women- due to lack of FSH and LH
loss of libido
infertility
List the symptoms of hyperprolactinaemia due to a prolactinoma seen in males
galactorrhoea uncommon (since appropriate steroid background usually inadequate) loss of libido erectile dysfunction infertility
Can men with prolactinomas present with galactorrhoea
Galactorrhoea occurs in oestrogen-primed breasts
Generally, men don’t have enough oestrogen to be able to lactate
However, some men with breast hypertrophy (gynaecomastia) complain of milk production
Differentiate between loss of libido and impotence
Loss of libido-due to low testosterone
Lack of testosterone causes a lack of sexual drive, which is unlike the impotence which is seen in diabetes for example.
In the latter case, diabetic patients have a normal sex drive (libido), but seek medical attention for their erectile dysfunction (impotence) usually due to associated cardiovascular problems.
How do prolactinomas often present in male patients
In the male with a prolactinoma, the patient does not perceive any problem at all, and occasionally a spouse might complain about ‘lack of interest’ and encourage referral, or eventually the patient presents with a large prolactinoma and features of hypopituitarism .
What is a consequence of a difference in timings of the presentation of prolactinomas in males and females
Female patients- often see microprolactinomas
Male patients - often see macroprolactinomas
Probably true only because we fail to diagnose the males when their tumours are small.
Summarise the pathophysiology of treatment for prolactinomas
Dopamine from dopaminergic neurones binds to D2 receptors on the lactotrophs and switches OFF prolactin secretion.
Will reduce the size of the tumour too- only tumour tat can be managed medically (without surgery)
What are D3 receptors involved in
The reward system in the brain.
Summarise the treatment of hyperprolactinaemia
Medical treatment is 1st line Dopamine receptor (D2) agonists Decrease prolactin secretion Reduce tumour size Examples: BROMOCRIPTINE CABERGOLINE Oral administration
What should we do when the tumour does not shrink whilst being treated with dopamine agonists
If the tumour does not shrink, it is important to reconsider the diagnosis, as it is possible that the patient always had disconnection hyperprolactinaemia , and this differential diagnosis is difficult to confim
State the side effects of dopamine receptor agonists
Nausea and vomiting
Postural hypotension
Dyskinesias (loss of voluntary movement)
Depression (exhaustion of dopamine stores)
Pathological gambling (see BNF!)- dopamine receptors are part of the reward system (D3)- some of these are activated- need someone who knows the patient well to monitor them- individual will have no insight on this.
What should be done in patients who cannot tolerate dopamine receptor agonists
i.e those with schizophrenia are made much worse by dopamine agonists, surgery and/or radiotherapy are options to be considered
Essentially, how do we diagnose prolactinomas
The combination of a raised circulating prolactin level with a visible prolactin tumour on the MRI scan suggests that there is a prolactinoma but it is essential that the diagnoses of disconnection hyperprolactinaemia or other causes of hyperprolactinaemia are excluded. The size of the tumour and the relative height might be useful. For example, a prolactin level over 6000 mU.L-1 can only be due to a prolactinoma. Levels between 1000 and 6000 mU L-1 are more difficult to interpret, and can be due to a small macroprolactinoma, or to a large tumour causing disconnection from the hypothalamus- patients should be reviewed by MDT
Compare the effects of excess growth hormone in humans and in adults
§ Childhood = gigantism. Adulthood = acromegaly.
§ Usually due to BENIGN GH secreting pituitary adenoma (of the somatotrophs)
Why don’t we see gigantism in adults
The epiphyses of long bones have fused, therefore linear growth is unlikely but other tissues undergo hypertrophy where possible, and a very stereotypic appearance occurs. Prognathic Jaw Frontal Bossing Spade Hands Wide spaced teeth
Summarise the metabolic defects of acromegaly
The metabolic effects of excess GH cause increased risk of diabetes, hypertension and vascular disease resulting in a raised morbidity.
Can lead to impaired glucose tolerance (diabetes mellitus)- increasing the risk of infection.
Summarise acromegaly
Insidious in onset
Signs and symptoms progress gradually (can remain undiagnosed for many years)
Untreated, excess GH is associated with increased morbidity and mortality
Death =
Cardiovascular disease 60%
Respiratory complications 25%
Cancer 15%
What are the most serious complications of excess growth hormone?
Cardiovascular problems (majority) and respiratory problems This is mainly due to organ growth
What are the metabolic effects of acromegaly?
Increased insulin response to oral glucose leading to insulin resistance
This causes impaired glucose tolerance (in 50%) and diabetes mellitus (in 10%)
What grows in acromegaly
periosteal bone cartilage fibrous tissue connective tissue internal organs (cardiomegaly, splenomegaly, hepatomegaly, etc.)
Summarise the clinical features of acromegaly
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
Which symptoms does treatment for acromegaly relieve
Excessive sweating (hyperhydrosis) Headache
What can be used to aid the diagnosis of acromegaly
Photo- showing the changes in features of the patient
Describe the risk of cancer in patients taking GH replacement
Non-existent (unlike patients suffering from acromegaly)- as GH is not being released all the time
Summarise the management of cancer risk in patients with acromegaly
Whilst cancer is not a common presentation of acromegaly, once they are diagnosed, we need to organise regular cancer screenings (colonoscopies)- to monitor their risk
Why do patients with acromegaly have gaps between their teeth
Lantern Jaw
Rapid growth of jaw creates gaps between the teeth
Why is it futile to measure GH in patients with acromegaly
Because the secretion of GH is pulsatile in normal individuals, a random blood GH concentration measurement is unlikely to be useful unless it is zero, in which case it excludes acromegaly.
A high level could be due either to acromegaly, or to the chance of hitting the pulse of a normal GH secretion.
Outline how acromegaly can lead to diabetes Mellitus
Increased endogenous muscle production, decreased muscle glucose uptake.
Increase insulin production- eventually leading to insulin resistance
Impaired glucose tolerance
Diabetes mellitus
List the common complications of acromegaly
Obstructive sleep apnoea
Hypertension
Cardiomyopathy
Increased risk of cancer
Describe obstructive sleep apnoea
Bone and soft tissue changes (growth) surrounding the upper airway- leading to narrowing and subsequent collapse during sleep
Describe hypertension
Direct effects of GH/IGF-1 on vascular tree
GH mediated renal sodium absorption
Describe cardiac myopathy
Damage to heart muscle- big, baggy heart that cannot pump properly- excess GH is toxic to the heart
Hypertension, DM, direct toxic effects of GH on myocardium
Describe the increased risk of cancer
GH makes everything grow and it’s being released all the time
Colonic polyps, regular screening with colonoscopy
Describe the co-secretion of prolactin with GH in patients with acromegaly
Prolactin is often high in patients with acromegaly- reflecting the fact that the tumour is secreting both GH and prolactin
Hyperprolactinaemia will cause secondary hypogonadism (see clinical features of hyperprolactinaemia)- need pulsatility to drive LH and FSH- high prolactin has an inhibitory effect- stopping pulsatility- no signal to make LH or FSh
Describe the diagnosis of acromegaly
If diagnosis is suspected, suppression of GH secretion using a glucose tolerance test should be performed. GH levels fall to zero during glucose tolerance testing in normal individuals, but this does not happen in patients with acromegaly.
A somatotroph adenoma paradoxically will have the opposite effect, and may result in an increase in GH levels which will confirm the diagnosis. The final diagnostic test is to measure the level of IGF-1, which is used as a marker of long term GH exposure
Why is it essential to measure IGF-1
Starvation can give a false positive response. In addition, levels of GH and IGF-1 need to be measured to monitor response to treatment.
Summarise the diagnosis of acromegaly
GH pulsatile – so random measurement unhelpful Elevated serum IGF-1 Failed suppression (‘paradoxical rise’) of GH following oral glucose load – oral glucose tolerance test
Summarise the treatment of acromegaly
Surgery (trans-sphenoidal) – 1ST LINE Medical Somatostatin analogues e.g. OCTREOTIDE Dopamine agonists (GH secreting pituitary tumours frequently express D2 receptors) e.g. CABERGOLINE Radiotherapy
What is the first line treatment for acromegaly and describe the procedure
Tran sphenoidal surgery - by which the tumour is removed by suction through a hole made in the body of the sphenoid bone approached up through the nasal sinus). Following the surgery- all the patient’s pituitary axes need to be reassessed.
State the treatment options for acromegaly
Transsphenoidal Hypophysectomy Radiotherapy Chemotherapy: · Octreotide (somatostatin analogue) · Bromocriptine and Cabergoline (dopamine receptor agonists
Summarise the use of somatostatin analogues
‘Endocrine cyanide’
Injection: sc (short acting) or monthly depot
GI side effects common eg nausea, diarrhoea, gallstones can occur (can’t absorb fats properly)
Reduces GH secretion and tumour size
Pre-treatment before surgery may make resection easier
Use post-operatively if not cured or whilst waiting for radiotherapy to take effect (slow- radiotherapy effects take a while to kick in)
Why should surgery be the first line treatment in patients with acromegaly
Unlike prolactinomas, shrinkage of somatotrophinomas doesn’t occur- making surgery a viable early option for patients.
Give 2 examples of somatostatin analogues
lanreotide
octreotide
Which symptoms do patients tend to notice first
Changes in ring size or shoe size
What is IGF-2 more important for
The growing foetus
Describe the follow up that should be done post-operation
if the GH levels are low enough, no further therapy will be warranted. Some patients progress to requiring radiotherapy and drugs. All patients with acromegaly require annual pituitary review, to ensure that they are in optimum pituitary hormone replacement therapy if needed.
- What are the clinical uses of octreotide?
It can be used short-term before surgery to shrink the size of the pituitary adenoma
It can be used long-term if it can’t be controlled by other means
It is used as a treatment for other neuroendocrine tumours e.g. carcinoid tumours
Describe the administration, distribution and metabolism of octreotide.
Octreotide is administered SC or IM 3/day
It is retained in extracellular fluid
Half-life = 2-4 hour
State some of the side effects of octreotide.
GI tract disturbance (because somatostatin is produced by the small intestine as well)
Initial reduction in insulin secretion causing hyperglycaemia (octreotide inhibits the production of insulin by the beta cells)
Rarely gallstones
What is used to treat hyperprolactinaemia?
Dopamine agonists – bromocriptine and cabergoline
Describe the pharmacokinetics and side-effects of bromocriptine.
Administered orally 1/day Heavily plasma protein bound Half-life = 7 hours (hepatic metabolism) Side effects: · Nausea/vomiting/abdominal cramps · Dyskinesias · Psychomotor excitation · Postural hypotension · Vasospasm in fingers and toes
State some other uses of bromocriptine.
Suppression of lactation
Cyclical benign breast tumours (and cyclic breast pain)
Also used in acromegaly but doesn’t have the same beneficial effect on tumour size
Parkinson’s disease
Describe the pharmacokinetics and side-effects of cabergoline
Taken orally 1-2/week
Half-life = > 45 hours
Side effect: same as bromocriptine but less pronounced
