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Endocrinology > Anterior pituitary pathology > Flashcards

Anterior pituitary pathology Flashcards

1
Q

What are some causes of anterior pituitary hyper function?

A

Pituitary adenomas
Cushing’s syndrome

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2
Q

What are pituitary adenomas?

A

Tumours arising from the cells of the anterior pituitary gland

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3
Q

What are the 2 main types of pituitary adenoma?

A

Sporadic
MEN1 associated (Wermer syndrome)

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4
Q

What are the 2 classes of pituitary adenomas based on size?

A

Micro-adenomas <1cm
Macro-adenomas >1cm

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5
Q

What is meant by a functioning adenoma?

A

A tumour that produces hormones to produce a clinical presentation

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6
Q

What is meant by a non-functioning adenoma?

A

A tumour that does not produce hormones, or produces that at a sub-clinical level

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7
Q

What are the most commonly produced hormones by functioning adenomas?

A
  • Prolactin (20-30%)
  • ACTH (10-15%)
  • FSH/LH (10-15%)
  • GH (5%)
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8
Q

By what classification system are pituitary adenomas classified by?

A

Modified Knosp classification

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9
Q

What are some common types of pituitary adenoma?

A

Prolactinomas
Somatotroph adenoma (GH secreting)
Corticotroph adenoma

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10
Q

What is the most common form of functional pituitary adenoma?

A

Prolactinoma

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11
Q

How will prolactinomas present in both males and females?

A
  • Weight gain
  • Delayed pubertal development
  • Hypogonadism
  • Infertility
  • Galactorrhea
  • Osteopenia or osteoporosis
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12
Q

How will prolactinomas present in males?

A
  • Loss of libido
  • Erectile dysfunction
  • Gynaecomastia
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13
Q

How will prolactinoma present in females?

A
  • Oligo-amenorrhoea
  • Vaginal dryness
  • Irritability
  • Depression
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14
Q

What are some symptom of macroprolactinoma?

A

Headache
Visual field defects
Hypopituitarism
All caused by mass effects

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15
Q

What investigations are required in prolactinomas?

A
  • Serum prolactin concentration
  • Baseline pituitary function
  • MRI of pituitary
  • Visual field testing
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16
Q

What is the first line management option in prolactinoma?

A

Dopamine agonist (E.g. Cabergoline)

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17
Q

What is the use of dopamine agonists in prolactinomas?

A

Effective in normalising prolactin and shrinking the tumour

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18
Q

What are some side effects of cabergoline?

A
  • Fibrosis (e.g. heart valves)
  • Decreased impulse control (e.g. gambling, shopping)
  • Psychiatric disturbance
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19
Q

What are some examples of dopamine agonists used in prolactinoma?

A

Cabergoline
Bromocriptine
Quinagolide

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20
Q

When is surgery indicated in prolactinoma?

A

Surgery is usually reserved for dopamine agonist resistant tumours, intolerance to dopamine agonists or patient preference of long term medical therapy

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21
Q

What hormone is secreted by somatotroph adenoma?

A

Growth hormone

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22
Q

How do somatotroph adenomas affect the body?

A

Growth hormone secretion causes an increase in insulin like growth factor (IGF), which stimulates growth of bone, cartilage and connective tissue

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23
Q

What with somatotroph adenoma cause in children (Pre-ossification)?

A

Gigantism

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24
Q

What will somatotroph adenoma cause in adults (Post-ossification)?

A

Acromegaly

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25
Q

What is acromegaly?

A

A condition resulting from excess growth hormone production, leading to excessive tissue growth

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26
Q

What are some symptoms of acromegaly?

A
  • Thickened soft tissue (Large jaw, hands, feet, facial features)
  • Obstructive sleep apnoea (Thickened nasopharynx)
  • Arthropathy (Vertebral fracture, osteoporosis, carpal tunnel syndrome)
  • Hypertension, LVH, cardiomyopathy
  • Headaches
  • Diabetes mellitus
  • Dyslipidaemia
  • Local pituitary effects (Visual effects, hypopituitarism)
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27
Q

What cancers does acromegaly increase the risk of?

A

Colonic polyps
Colon cancer
Thyroid cancer

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28
Q

How is acromegaly diagnosed?

A

IGF-1 levels
Oral glucose tolerance testing (Suppression test)

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29
Q

How is oral glucose tolerance testing performed?

A

Oral glucose tolerance testing is performed by giving 75g of oral glucose

GH levels are then checked at 0, 30, 60, 90 and 120 minutes

Normal response would be for growth hormone to be suppressed to <0.4ug/l after the glucose is given

In acromegaly, GH would not be suppressed and there may even be a paradoxical rise

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30
Q

What would a normal IGF-1 level show?

A

This would usually exclude acromegaly, unless there was significant liver disease

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31
Q

What is the first line management of acromegaly?

A

Pituitary surgery

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32
Q

What are some forms of 2nd line therapy in acromegaly?

A

Radiotherapy
Somatostatin analogues
Dopamine agonists
GH receptor antagonists (Last line)

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33
Q

What is the effects of somatostatin analogues in acromegaly?

A

Reduce GH levels
Cause tumour shrinkage

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34
Q

What are some examples of somatostatin analogues

A
  • Ocreotide
  • Lanreotide
  • Pasireotide
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35
Q

What is an example of a GH receptor antagonist?

A

Pegvisomant

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36
Q

What screening tests are required in acromegaly?

A

Colon cancer screening
Blood pressure monitoring
Echocardiogram

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37
Q

What hormone is secreted by corticotroph adenoma?

A

ACTH

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38
Q

What condition will usually occur as a result of corticotroph adenoma?

A

Cushing’s disease

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39
Q

What is Cushing’s syndrome?

A

This is a pathological increase in steroid and androgen levels

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40
Q

What are some causes of pseudo-Cushings (Hypercortisolaemia)?

A
  • Depression
  • Alcohol dependance
  • Diabetes
  • Obesity
  • Malnutrition
  • Pregnancy
  • Glucocorticoid resistance
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41
Q

What are the 4 main causes of Cushing’s syndrome?

A
  • Steroid usage
  • Pituitary adenoma (Cushing’s disease)
  • Cortisol secreting adrenal tumour
  • Ectopic ACTH production
42
Q

What are the most common locations for ectopic ACTH production

A

Thymus
Lung
Pancreas

43
Q

What is meant by ACTH independant Cushing’s syndrome?

A

Cortisol levels are increased despite ACTH being normal

44
Q

What are some ACTH dependant causes of Cushing’s syndrome?

A
  • Cushing’s disease (Conditions of the pituitary gland)
  • Ectopic corticotrophin syndrome
  • Unknown source of corticotropin
45
Q

What are some ACTH independant causes of Cushing’s syndrome?

A
  • Adrenal adenoma
  • Adrenal carcinoma
  • Macronodular hyperplasia
  • Primary pigmented nodular adrenal disease
  • McCune-Albright syndrome
  • Iatrogenic
46
Q

What are the 3 main types of hormone that can be overproduced in Cushing’s syndrome?

A

Cortisol
Mineralocorticoid
Androgen

47
Q

What are some complications of excess cortisol?

A

Protein loss
Altered carbohydrate and lipid metabolism
Altered psyche

48
Q

What are some symptoms of protein loss in excess cortisol in Cushing’s syndrome?

A
  • Myopathy
  • Osteoporosis
  • Thin skin
  • Abdominal striae
  • Easy bruising
49
Q

What are some symptoms of altered carbohydrate and lipid metabolism in excess cortisol in Cushing’s syndrome?

A
  • Diabetes mellitus
  • Central obesity
  • Round (Moon) face
  • Dorsocervical fat pad
  • Sleep apnoea
50
Q

What are some symptoms of altered psyche in excess cortisol in Cushing’s syndrome?

A
  • Psychosis
  • Depression
51
Q

What are some symptoms of excess mineralocorticoid in Cushing’s syndrome?

A

Hypertension
Oedema

52
Q

What are some symptoms of excess androgen in Cushing’s syndrome?

A
  • Virilism
  • Hirsutism
  • Acne
  • Oligo/amenorrhoea
53
Q

What are the 3 main screening tests used in investigation of Cushing’s syndrome?

A
  1. Overnight 1mg dexamethasone suppression test
  2. Urinary free cortisol (24hr urine collection)
  3. Diurnal cortisol variation (Mignight/8am)
54
Q

What is a normal cortisol response to overnight dexamethasone suppression testing?

A

Cortisol <50nmol/L next morning

55
Q

How will diurnal cortisol variation testing cause suspicion of Cushing’s?

A

Loss of diurnal variation is suspicious

56
Q

What is the full diagnostic test performed in Cushing’s syndrome?

A

Low dexamethasone suppression test (48 hours)

57
Q

How is a low dexamethasone suppression test performed?

A

0.5mg dexamethasone is given every 6 hours for 48 hours (2mg per day)

If cortisol is <50nmol/l after the last dose, then Cushing’s is very unlikely

58
Q

What test is performed after a diagnosis of Cushing’s syndrome is made?

A

ACTH measuring:
- Low ACTH → ACTH independant cause (Adrenal)
- High or normal ACTH → ACTH dependant (Pituitary or ectopic)

59
Q

What is the 1st line management of Cushing’s disease?

A

Transsphenoidal hypophysectomy

60
Q

What treatment is used in recurrent Cushing’s disease?

A

External radiotherapy

61
Q

When will medical therapy be given in Cushing’s disease?

A

If the patient is unsuitable for surgery

62
Q

What management option is used in residual Cushing’s disease post-management?

A

Bilateral adrenalectomy

63
Q

What are the main forms of medical therapy in Cushing’s disease?

A
  • Adrenal steroidogenesis inhibitors (Block cortisol synthesis)
  • Somatostatin anologues
  • Dopamine agonists
  • Glucocorticoid receptor blockers
64
Q

What are some examples of adrenal steroidogenesis inhibitors?

A
  • Metyrapone
  • Ketoconazole (Hepatotoxic)
  • Osilodrostat
65
Q

What is an example of a somatostatin analogue?

A

Pasireotide LAR (10-20mg monthly)

66
Q

How is adrenal Cushing’s syndrome treated?

A

Adrenalectomy

67
Q

How is ectopic ACTH production managed in Cushing’s syndrome?

A

Surgical removal of the source or bilateral adrenalectomy

68
Q

What are some biochemical signs of a non-functioning pituitary adenoma?

A
  • ACHT deficiency
  • TSH deficiency
  • LH/FSH deficiency
  • GH deficiency
  • Raised prolactin
69
Q

How are non-functioning pituitary adenomas managed?

A

Trans-sphenoidal surgery is most often implicated in non-functioning adenoma, with hormone replacement indicated in hormonal deficiency

Post-operative radiotherapy may be required

70
Q

What are some physiological causes of raised prolactin?

A
  • Pregnancy
  • Breast or nipple stimulation
  • Stress
  • Sleep
  • Coitus
  • Exercise
71
Q

What are some pathological causes of raised prolactin?

A
  • Hypothalamic-pituitray stalk damage (Adenomas, craniopharyngiomas)
  • Pituitary disorders (Prolactinomas, acromegaly, lymphocytic hypophysitis)
  • Ectopic prolactin secretion
72
Q

What is a pharmacological cause of raised prolactin?

A

Dopamine receptor blockers

73
Q

What is meant by panhypopituitism?

A

A lack of release of all of the pituitary hormones

74
Q

What are some causes of pituitary hypofunction?

A
  • Surgery/radiation
  • Primary or metastatic tumours
  • Sudden haemorrhage
  • Ischaemic necrosis
  • Tumours extending into the sella turcica
  • Inflammatory
75
Q

What are some causes of ischaemic necrosis of the pituitary gland?

A

Sheehan’s syndrome (Post-partum necrosis)
Apoplexy

76
Q

What are some tumours that can lead to hypopituitism?

A
  • Benign - Craniopharyngioma
  • Malignant - Glioma or metastases
77
Q

How will adults present with TSH deficiency?

A

Tiredness
Cold intolerance
Constipation
Hair loss
Dry skin
Hoarseness
Cognitive slowing

78
Q

How will children present with TSH deficiency?

A

Growth and developmental impairment

79
Q

How would chronic ACTH deficiency present?

A

Fatigue
Pallor
Anorexia
Weakness

80
Q

How would acute ACTH deficiency present?

A

Weakness
Dizziness
Nausea
Vomiting
Shock

81
Q

How would children present with ACTH deficiency?

A

Delayed puberty
Failure to thrive

82
Q

What would investigations show in ACTH deficiency?

A

Hypoglycaemia
Hypotension
Anaemia
Hyponatraemia

83
Q

What is a craniopharyngioma?

A

These are tumours derived from the remnants of Rathke’s pouch, an embryological structure

84
Q

What ages are most at risk of craniopharyngioma?

A
  • 5-15 years
  • 6-7th decade (70-80)
85
Q

Describe the pathology of craniopharyngiomas

A

They are slow growing, often cystic and may calcify

86
Q

How will craniopharyngiomas usually present?

A

They usually cause headaches and visual disturbances

In children, they can causes poor growth

87
Q

Describe the prognosis of craniopharyngioma

A

They usually have a very good prognosis, especially if they are smaller than 5cm

Following radiation, however, there is a very small risk of SCC development

88
Q

What is pituitary tumour apoplexy?

A

Pituitary tumour apoplexy is a rare clinical syndrome resulting from the rapid expansion, usually of a pituitary tumour due to either haemorrhage or infarction

89
Q

What are some predisposing factors to pituitary apoplexy?

A
  • Major surgery
  • Medications (GnRH analogues)
  • Anticoagulation
  • Hypertension
  • Diabetes
  • High altitude
90
Q

How will pituitary apoplexy present?

A
  • Severe headache
  • Nausea and vomiting
  • Vision (Visual acuity and visual field defects)
  • Ocular palsy (Cranial nerve compression)
  • Hypopituitarism
  • Reduced GCS
91
Q

What investigations are required in pituitary apoplexy?

A

Pituitary function tests, MRI and formal visual field assessment are the main tests required in diagnosis and grading of apoplexy

92
Q

How is pituitary apoplexy managed?

A

The first stage of management is treatment of acute hormone deficits, such as emergency steroid dosing

Steroids should be given before thyroid hormones, as thyroid hormones increase metabolism and can precipitate an adrenal crisis

Conservative or surgical management can then be used dependant on clinical features

93
Q

What is hypophysitis?

A

Hypophysitis is defined as inflammation of the pituitary gland that is primary or secondary to a local or systemic process

94
Q

What are some causes of hyophysitis?

A
  • Autoimmune
  • Systemic inflammation (e.g. granulomatous disease, sarcoidosis)
  • Medication
  • Infection
  • Paraneoplastic
95
Q

What are the 7 main types of hypophysitis?

A
  • Lymphocytic
  • Granulomatous
  • Xanthomatous
  • Necrotising
  • IgG4-related
  • Immunotherapy induced
  • Other autoimmune
96
Q

What are the general symptoms of all types of hypophysitis?

A
  • Headache
  • Hypopituitarism
  • Arginine vasopressin deficiency (DI)
  • Mass effect
97
Q

How is hypophysitis investigated?

A

Diagnosis is made using MRI, pituitary function testing and disease specific investigations such as pituitary biopsy

98
Q

What will MRI show in hypophysitis?

A

MRI will show pituitary stalk thickening and homogenous pituitary enlargement

99
Q

How is hypophysitis managed?

A

Treatment of the underlying cause is most important, mostly with steroids to reduce inflammation

Hormone deficit replacement can then be used, such as steroids or desmopressin

100
Q
A

Endocrinology (42 decks)

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