Pituitary Disease Flashcards
Both hyperpituitarism and hypopituitarism, and mass effect
Which part of the pituitary is the adenohypophysis?
The anterior pituitary
What is the alternative name for the posterior pituitary?
The neurohypophysis
T/F Most hormones released by the anterior pituitary are under positive-acting releasing factors from the hypothalamus
True. Except for prolactin, the release of which is inhibited by dopamine (aka PIF) from the hypothalamus
What are the major hormones released by the anterior pituitary?
ACTH (adrenocorticotropic hormone) TSH (thyroid-stimulating hormone) FSH (follicle-stimulating hormone) LH (luteinizing hormone) GH (growth hormone) PRL (prolactin)
What are the minor hormones released by the anterior pituitary?
Beta endorphins (pain relief)
MSH (melanocyte-stimulating hormone) produced as ACTH is cleaved from POMC
What can lead to hyperpituitarism?
Pituitary adenoma or carcinoma, secretion of hormones by non-pituitary tumours (esp lung cancers), and certain hypothalamic disorders
What can lead to hypopituitarism?
Deficiency of tropic hormones
Destructive processes including ischaemic injury, surgery, radiation, inflammatory reactions, and non-functional pituitary adenomas
Local mass effects can also lead to this, whereby the pituitary is crushed and loss of function is suffered.
How do we normally first recognise problems with the posterior pituitary?
Decreased ADH causing fluid loss
What is the most common cause of hyperpituitarism?
Adenoma arising in the anterior pituitary
How do you classify pituitary adenomas?
Based on how they appear histologically, and also on which hormone they produce
T/F Non-functional adenomas of the anterior pituitary do not lead to hyperpituitarism, and instead lead to mass effects
True. Non-functioning adenomas produce hormones, but do not lead to clinical symptoms of hormone excess. They do however sometimes exhibit more important mass effects
What are two less common causes of hyperpituitarism?
Pituitary carcinoma and some hypothalamic disorders
What are the three histological types of pituitary adenomas?
Chromophobe (70%)
Acidophil (15%)
Basophil (15%)
What are the characteristics of chromophobe pituitary adenomas?
Many are non-secretory
Some cause hypo-pituitarism
Half produce prolactin, a few produce ACTH or GH
Local pressure effect in 30%
What are the characteristics of acidophil pituitary adenomas?
Secrete GH or prolactin
Local pressure effect in 10%
What are the characteristics of basophil pituitary adenomas?
Secrete ACTH
Only rarely has a local pressure effect
What are the main signs of local pressure caused by a pituitary mass?
Headache
Visual field defects (bilateral temporal hemi-anopia)
Palsy of CN III, IV, VI (pressure or invasion of the cavernous sinus
Potential disturbance of hypothalamus leading to disturbance of temp, sleep and appetite control
Erosion through floor of sella turcica leading to CSF rhinorrhoea
What is the most common hormone produced by pituitary adenomas?
Prolactin (35%)
What proportion of pituitary adenomas do not produce a hormone?
30%
What proportion of pituitary adenomas produce GH?
20%
What proportion of pituitary adenomas produce ACTH, and what condition does this lead to?
7%; Cushing’s disease
What age are pituitary adenomas usually found?
35-60 years
Are non-functional pituitary adenomas more likely to be found earlier or later?
Later; without hormone production they are mostly found when exhibiting mass effect on surrounding tissue
How often are pituitary adenomas found in the general population at autopsy?
In 14%
What conditions are associated with excess ACTH production?
Cushing’s disease
Nelson syndrome (lack of adrenal glands causing pituitary to increase in size)
What conditions are associated with excess GH production?
Gigantism (children)
Acromegaly (adults)
What conditions are associated with excess prolactin?
Galactorrhoea
Amenorrhoea
Sexual dysfunction
Infertility
What conditions are associated with excess TSH production?
Hyperthyroidism
What conditions are associated with excess FSH or LH production?
Hypogonadism
Mass effects (because they are usually non-functioning adenomas)
How do most pituitary adenomas arise?
95% are spontaneous
5% caused by genetic mutations
What are some genetic mutations that cause pituitary adenomas?
GNAS mutation, causing G-protein signalling that tropic hormones are bound to receptor to not turn off, causing unstopped hyperplasia (GH)
MEN1 (GH, PRL, ACTH)
PRKAR1A (Carney complex)
AIP (GH esp younger patients)
What are some complications of pituitary adenomas?
Mass effect
Pituitary apoplexy (acute haemorrhage into the adenoma leading to CVS collapse and death; presents similar to subarachnoid haemorrhage)
What are prolactinomas prone to?
Calcification; can be small isolated psammoma bodies or extensive (pituitary stone)
Describe the production of prolactin by prolactinomas
Efficient (even a micro prolactinoma produces enough excess prolactin to cause hyperprolactinaemia)
Proportional (serum prolactin reflects the size of the adenoma well)
What proportion of amenorrhoea cases are caused by prolactinoma?
~25%
In which population is it easiest to diagnose prolactinoma?
Pre-menopausal women
This presents diagnostic challenges, because in men and older women they can become quite large as the hormone effect is subtle
What, other than prolactinomas, can cause hyperprolactinaemia?
Drugs (most common cause; dopamine antagonists, metoclopramide, antipsychotics, MDMA)
Pregnancy, nipple stimulation (as in suckling to stimulate production of next milk feed)
Damage to the dopamine system inhibiting prolactin (head trauma damaging pituitary stalk; dopamine neuron damage)
What is the normal level of serum prolactin?
<390mu/L
What are pathological levels of serum prolactin?
> 390mu/L
> 5000mu/L usually prolactinoma
Macroadenoma (>10mm) causes highest levels, eg 10000-100000mu/L
How do you treat hyperprolactinaemia?
Dopamine agonists (bromocriptine first, then cabergoline)(cabergoline less safe in pregnancy)
Surgery if indicated
Dopamine agonist/radiation follow up
T/F the effects of excessive GH in adults are marked
False. Effects are very subtle
How does GH hypersecretion cause acromegaly or gigantism?
Excess GH causes excess IGF-1 (insulin-like growth factor) production by the liver, which does most of the damage
List the causes of GH hypersecretion
Pituitary adenoma (99%)
Ectopic GH-releasing carcinoma
What determines whether a person with GH hypersecretion develops gigantism or acromegaly?
Whether or not the epiphyseal plates have fused
List the symptoms of acromegaly
Hypertrophy and hyperplasia of soft tissues (skin, hands, feet, viscera including thyroid, heart, liver, adrenals)
Bone density may increase (hyperostosis) esp in spine and hips
Enlargement of jaw (prognathism, malocclusion), brow ridges
Broadening of feet, hands, nose
To diagnose GH hypersecretion is a simple blood test enough?
No. Random [GH] unreliable as secretion is pulsatile and during peaks for a non-acromegalic [GH] can reach acromegaly levels.
Test [glucose] during oral glucose tolerance test
, [Ca2+], [IGF-1] (GH is suppressed with glucose load)
MRI, visual field test
What is the normal GH serum level?
<0.4ug/L or 1.2mIU/L
How do you treat GH hypersecretion?
Trans-sphenoidal resection often 1st line treatment
If unsuccessful, then somatostatin analogues (SSA; octreotide or lanreotide) or radiotherapy but SSA has side effects
GH antagonists used if resistant or intolerant to SSAs. Reduces IGF-1 but can increase GH and tumour size rarely
ACTH secreting adenomas lead to which disease?
Cushing’s disease (hypercortisolism)
What is paradoxical about ACTH secreting adenomas?
They lead to Cushing’s disease, which can be treated with bilateral adrenalectomy, which can make an ACTH secreting adenoma greatly increase in size leading to huge mass effects (Nelson syndrome)
What are the symptoms of an ACTH secreting adenoma?
The symptoms of Cushing’s disease, plus skin pigmentation
What is difficult to diagnose about LH and FSH secreting adenomas?
They are inefficient, variable and non-proportional
Also usually non-functioning
What is the usual presentation of LH and FSH secreting adenomas?
Mass effects in middle age
What is paradoxical about LH and FSH secreting adenomas?
Can be associated with secondary gonadal hypofunction
This is because of mass effect reducing the overall amount of LH and FSH released
Are pituitary carcinomas rare?
Yes, they account for <1% of pituitary tumours
What is mandatory for the diagnosis of pituitary carcinoma?
Evidence of craniospinal or systemic metastases (both occur in the late stage)
What is the major product of pituitary adenomas?
Prolactin and ACTH
How much parenchyma of the pituitary must be lost to have significant hypopituitarism?
75%
What does hypopituitarism with signs of diabetes insipidus mean?
Almost always problem with the hypothalamus
List the main destructive causes of hypopituitarism
Mass lesions
TBI (traumatic brain injury) and subaranchoid haemorrhage
Pituitary surgery or radiotherapy
Pituitary apoplexy (haemorrhage into pituitary, often into adenoma)
Sheehan syndrome
What is the pathogenesis of Sheehan syndrome
Pituitary usually increases in size during pregnancy
Blood supply does not increase however
Only need a small cardiovascular challenge to cause necrosis of the anterior pituitary (posterior has better supply, does not get affected)
What are some hypothalamic causes of hypopituitarism?
Hypothalamic tumours (craniopharyngiomas, metastases to the hypothalamus esp breast and lung)
Hypothalamic hormone production can be reduced with cranial or nasopharyngeal radiotherapy
What are symptoms of GH hyposecretion?
Dwarfism (in children)
Central obesity
Atherosclerosis
Decreased strength
Decreased CO, exercise ability
Decreased [glucose]
What are symptoms of FSH;LH hyposecretion?
Oligomenorrhoea or amenorrhoea
Decreased fertility and libido
Osteoporosis
Erectile dysfunction
Hypogonadism
Decreased muscle bulk
What are symptoms of TSH hyposecretion?
Hypothyroidism
What are symptoms of ACTH hyposecretion?
Tiredness and weakness
Depression
Abdominal pain/vomiting/constipation
All symptoms of Addison’s disease, except no pigmentation because POMC isn’t being cleaved
How do you treat hypopituitarism?
Hormone replacement
