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Robbins Path Endocrine > Pituitary Disease > Flashcards

Pituitary Disease Flashcards

Both hyperpituitarism and hypopituitarism, and mass effect

1
Q

Which part of the pituitary is the adenohypophysis?

A

The anterior pituitary

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2
Q

What is the alternative name for the posterior pituitary?

A

The neurohypophysis

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3
Q

T/F Most hormones released by the anterior pituitary are under positive-acting releasing factors from the hypothalamus

A

True. Except for prolactin, the release of which is inhibited by dopamine (aka PIF) from the hypothalamus

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4
Q

What are the major hormones released by the anterior pituitary?

A 
ACTH (adrenocorticotropic hormone)
TSH (thyroid-stimulating hormone)
FSH (follicle-stimulating hormone)
LH (luteinizing hormone)
GH (growth hormone)
PRL (prolactin)
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5
Q

What are the minor hormones released by the anterior pituitary?

A

Beta endorphins (pain relief)

MSH (melanocyte-stimulating hormone) produced as ACTH is cleaved from POMC

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6
Q

What can lead to hyperpituitarism?

A

Pituitary adenoma or carcinoma, secretion of hormones by non-pituitary tumours (esp lung cancers), and certain hypothalamic disorders

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7
Q

What can lead to hypopituitarism?

A

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.

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8
Q

How do we normally first recognise problems with the posterior pituitary?

A

Decreased ADH causing fluid loss

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9
Q

What is the most common cause of hyperpituitarism?

A

Adenoma arising in the anterior pituitary

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10
Q

How do you classify pituitary adenomas?

A

Based on how they appear histologically, and also on which hormone they produce

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11
Q

T/F Non-functional adenomas of the anterior pituitary do not lead to hyperpituitarism, and instead lead to mass effects

A

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

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12
Q

What are two less common causes of hyperpituitarism?

A

Pituitary carcinoma and some hypothalamic disorders

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13
Q

What are the three histological types of pituitary adenomas?

A

Chromophobe (70%)
Acidophil (15%)
Basophil (15%)

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14
Q

What are the characteristics of chromophobe pituitary adenomas?

A

Many are non-secretory
Some cause hypo-pituitarism
Half produce prolactin, a few produce ACTH or GH
Local pressure effect in 30%

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15
Q

What are the characteristics of acidophil pituitary adenomas?

A

Secrete GH or prolactin

Local pressure effect in 10%

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16
Q

What are the characteristics of basophil pituitary adenomas?

A

Secrete ACTH

Only rarely has a local pressure effect

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17
Q

What are the main signs of local pressure caused by a pituitary mass?

A

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

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18
Q

What is the most common hormone produced by pituitary adenomas?

A

Prolactin (35%)

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19
Q

What proportion of pituitary adenomas do not produce a hormone?

A

30%

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20
Q

What proportion of pituitary adenomas produce GH?

A

20%

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21
Q

What proportion of pituitary adenomas produce ACTH, and what condition does this lead to?

A

7%; Cushing’s disease

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22
Q

What age are pituitary adenomas usually found?

A

35-60 years

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23
Q

Are non-functional pituitary adenomas more likely to be found earlier or later?

A

Later; without hormone production they are mostly found when exhibiting mass effect on surrounding tissue

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24
Q

How often are pituitary adenomas found in the general population at autopsy?

A

In 14%

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25
Q

What conditions are associated with excess ACTH production?

A

Cushing’s disease

Nelson syndrome (lack of adrenal glands causing pituitary to increase in size)

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26
Q

What conditions are associated with excess GH production?

A

Gigantism (children)

Acromegaly (adults)

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27
Q

What conditions are associated with excess prolactin?

A

Galactorrhoea

Amenorrhoea

Sexual dysfunction

Infertility

28
Q

What conditions are associated with excess TSH production?

A

Hyperthyroidism

29
Q

What conditions are associated with excess FSH or LH production?

A

Hypogonadism

Mass effects (because they are usually non-functioning adenomas)

30
Q

How do most pituitary adenomas arise?

A

95% are spontaneous

5% caused by genetic mutations

31
Q

What are some genetic mutations that cause pituitary adenomas?

A

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)

32
Q

What are some complications of pituitary adenomas?

A

Mass effect

Pituitary apoplexy (acute haemorrhage into the adenoma leading to CVS collapse and death; presents similar to subarachnoid haemorrhage)

33
Q

What are prolactinomas prone to?

A

Calcification; can be small isolated psammoma bodies or extensive (pituitary stone)

34
Q

Describe the production of prolactin by prolactinomas

A

Efficient (even a micro prolactinoma produces enough excess prolactin to cause hyperprolactinaemia)

Proportional (serum prolactin reflects the size of the adenoma well)

35
Q

What proportion of amenorrhoea cases are caused by prolactinoma?

A

~25%

36
Q

In which population is it easiest to diagnose prolactinoma?

A

Pre-menopausal women

This presents diagnostic challenges, because in men and older women they can become quite large as the hormone effect is subtle

37
Q

What, other than prolactinomas, can cause hyperprolactinaemia?

A

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)

38
Q

What is the normal level of serum prolactin?

A

<390mu/L

39
Q

What are pathological levels of serum prolactin?

A

> 390mu/L

> 5000mu/L usually prolactinoma

Macroadenoma (>10mm) causes highest levels, eg 10000-100000mu/L

40
Q

How do you treat hyperprolactinaemia?

A

Dopamine agonists (bromocriptine first, then cabergoline)(cabergoline less safe in pregnancy)

Surgery if indicated

Dopamine agonist/radiation follow up

41
Q

T/F the effects of excessive GH in adults are marked

A

False. Effects are very subtle

42
Q

How does GH hypersecretion cause acromegaly or gigantism?

A

Excess GH causes excess IGF-1 (insulin-like growth factor) production by the liver, which does most of the damage

43
Q

List the causes of GH hypersecretion

A

Pituitary adenoma (99%)

Ectopic GH-releasing carcinoma

44
Q

What determines whether a person with GH hypersecretion develops gigantism or acromegaly?

A

Whether or not the epiphyseal plates have fused

45
Q

List the symptoms of acromegaly

A

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

46
Q

To diagnose GH hypersecretion is a simple blood test enough?

A

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

47
Q

What is the normal GH serum level?

A

<0.4ug/L or 1.2mIU/L

48
Q

How do you treat GH hypersecretion?

A

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

49
Q

ACTH secreting adenomas lead to which disease?

A

Cushing’s disease (hypercortisolism)

50
Q

What is paradoxical about ACTH secreting adenomas?

A

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)

51
Q

What are the symptoms of an ACTH secreting adenoma?

A

The symptoms of Cushing’s disease, plus skin pigmentation

52
Q

What is difficult to diagnose about LH and FSH secreting adenomas?

A

They are inefficient, variable and non-proportional

Also usually non-functioning

53
Q

What is the usual presentation of LH and FSH secreting adenomas?

A

Mass effects in middle age

54
Q

What is paradoxical about LH and FSH secreting adenomas?

A

Can be associated with secondary gonadal hypofunction

This is because of mass effect reducing the overall amount of LH and FSH released

55
Q

Are pituitary carcinomas rare?

A

Yes, they account for <1% of pituitary tumours

56
Q

What is mandatory for the diagnosis of pituitary carcinoma?

A

Evidence of craniospinal or systemic metastases (both occur in the late stage)

57
Q

What is the major product of pituitary adenomas?

A

Prolactin and ACTH

58
Q

How much parenchyma of the pituitary must be lost to have significant hypopituitarism?

A

75%

59
Q

What does hypopituitarism with signs of diabetes insipidus mean?

A

Almost always problem with the hypothalamus

60
Q

List the main destructive causes of hypopituitarism

A

Mass lesions

TBI (traumatic brain injury) and subaranchoid haemorrhage

Pituitary surgery or radiotherapy

Pituitary apoplexy (haemorrhage into pituitary, often into adenoma)

Sheehan syndrome

61
Q

What is the pathogenesis of Sheehan syndrome

A

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)

62
Q

What are some hypothalamic causes of hypopituitarism?

A

Hypothalamic tumours (craniopharyngiomas, metastases to the hypothalamus esp breast and lung)

Hypothalamic hormone production can be reduced with cranial or nasopharyngeal radiotherapy

63
Q

What are symptoms of GH hyposecretion?

A

Dwarfism (in children)

Central obesity

Atherosclerosis

Decreased strength

Decreased CO, exercise ability

Decreased [glucose]

64
Q

What are symptoms of FSH;LH hyposecretion?

A

Oligomenorrhoea or amenorrhoea

Decreased fertility and libido

Osteoporosis

Erectile dysfunction

Hypogonadism

Decreased muscle bulk

65
Q

What are symptoms of TSH hyposecretion?

A

Hypothyroidism

66
Q

What are symptoms of ACTH hyposecretion?

A

Tiredness and weakness

Depression

Abdominal pain/vomiting/constipation

All symptoms of Addison’s disease, except no pigmentation because POMC isn’t being cleaved

67
Q

How do you treat hypopituitarism?

A

Hormone replacement

Robbins Path Endocrine (1 decks)

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