ENDOCRINE: Pituitary/ HPA problems incl adrenals andCushings Flashcards Preview

Year 3 Medicine Block > ENDOCRINE: Pituitary/ HPA problems incl adrenals andCushings > Flashcards

Flashcards in ENDOCRINE: Pituitary/ HPA problems incl adrenals andCushings Deck (99)
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1
Q

What is Addisons disease?

A

Primary adrenal insufficiency. Destruction of the adrenal gland or genetic defects in steroid production

2
Q

What are the symptoms of Addison’s disease?

A

Very non-specific:
* Nausea
* Abdo pain
* Weight loss
* Fatigue
* Weakness
* Cramps
* Reduced libido
* salt craving
* Dizziness and hypotension due to mineralocorticoid deficiency (aldosterone)
* Hypoglycaemia due to glucocorticoid deficiency
* Pigmentation due to ACTH excess from reduced cortisol

3
Q

How do you treat an Addisonian Crisis?

A

1 litre IV fluids - saline over 30-60 mins
100mg IM or IVhydrocortisone
Continue hydrocortisone 6 hourly until pt stable.
After 24hrs = start oral replacement, reducec to maintence over 3-4 days

4
Q

What is the most common cause of Addison’s disease in the UK?

A

Autoimmune

5
Q

What is the relevance of TB to Addison’s disease?

A

TB can cause Addison’s- most common cause in developing countries

6
Q

What is the gold standard investigation for Addison’s disease?

What other inv may you do?

A

ACTH test aka Short Synacthen

Other inv:
* first line - U+Es and serum cortisol (see hyponatraemia, hyperkalaemia and low serum cortisol if unwell)
* renin and aldosterone levels (renin would be high, aldosterone would be low)
* glucose
* blood gas
* adrenal auto-antibodies
* CXR
* CT scan adrenal glands
* MRI brain

7
Q

In an unwell Addison’s pt, what would blood gas show?

A

Hyperkalaemic, hyponatraemic hypoglycaemic metabolic acidosis.

8
Q

Differential diagnosis for adrenal insufficency?

A
  • Chronic fatigue syndrome: Presents with persistent fatigue, cognitive difficulties, and other non-specific symptoms
  • Dehydration or septic shock: Hypotension and tachycardia can mimic adrenal insufficiency
  • Primary psychiatric illnesses: Depression or other psychiatric illnesses may present with fatigue, decreased appetite, and weight loss.
  • Graves disease
9
Q

How is adrenal insufficency / Addison’s managed?

A
  • replace what is missing - need hydrocortisone (to replace glucocorticoids) and fludrocortisone (to replace mineralocorticoids)
  • patient education on sick day rules - carry steriod card and wear medical alert bracelet
  • double regular steriod meds dose during any intercurrent illness
  • regular screening for complcations - adrenal crisis and osteoporosis.
10
Q

What are the complications of addison’s disease?

A
  • addisonian crisis
  • severe elcetrolyte imbalances
  • cardovascular collapse
  • hypoglycaemia
  • side effects of long term corticosteriod use - osteoporosis, secondary cushings
11
Q

What are the effects of a prolactinoma in a) women and b) men

A

a) Women- amenorrhea, galactorrhea and infertility

b) Men- erectile dysfunction, gynocomastia, reduced sex drive and less body hair

12
Q

What is the most common cause of primary adrenal failure?

A

Autoimmune, usually have positive adrenal antibodies present

13
Q

What are the hallmark biochemical features of primary adrenal failure?

A

Hyperkalaemia, hyponatraemia, raised urea and mild anaemia, hypoglycaemia

14
Q

Why does ACTH deficiency present like SIADH?

A

Cortisol deficiency leads to increased ADH secretion

15
Q

Where is the pituitary gland situated?

A

In pituitary fossa at the base of the brain

16
Q

What anatomy lies a) superior and b) laterally to the pituitary gland?

A

a) Superior - optic chiasm. b) Laterally - cavernous sinus

17
Q

What nerves/ blood vessels are in the cavernous sinus?

A

Occulomotor, Trochlear , trigeminal Va, Vb, abducens, internal carotid artery.

18
Q

How is growth hormone secreted?

A

Pulsatile manner. Peak pulses during REM sleep

19
Q

Name the hormones positively and negatively controlling GH

A

Positive = GHRH. Negative = somatostatin

20
Q

Describe the adrenal axis

A

CRH stimulates ACTH release. ACTH release is circadian - peak pulses early in the morning and lowest at midnight. ACTH stimulates cortisol release. Cortisol has negative feedback on ACTH

21
Q

What are LH and FSH stimulated by and inhibited by?

A

Pulsatile GnRH stimulates. Testosterone and oestrogen inhibit

22
Q

What hormones does prolactin inhibit?

A

LH and FSH - directly inhibit.

23
Q

What are the 2 ways that pituitary tumours can present?

A

Compressive - compress surrounding structures - vision, cranial nerves, all hormones can be reduced. (non-functional pituitary tumour).

Excessive hormone production (functional pituitary tumours).

24
Q

How is prolactin predominantly controlled?

A

Mostly under negative control by dopamine and weak stimulatory control by TRH

25
Q

How can functional pituitary tumours present?

A

Acromegaly. Cushing’s disease. Prolactinoma. TSHoma.

26
Q

Pituitary tumours compressing optic chiasm cause which visual defect?

A

Bi-temporal hemianopia

27
Q

What should be assessed in pt with suspected pituitary tumour?

A

Assessment of visual fields
Biochemical assessment- divided into basal (prolactin, TSH, LH and FSH) and dynamic tests (synacthen test and insulin tolerance test)

28
Q

What time of day should LH, FSH and basal testosterone be checked in men?

A

0900 when deficiency is suspected.

29
Q

When should LH, FSH be tested in women?

A

Measured within 1st 5 days of the menstrual cycle

30
Q

IGF-1 is a marker of GH. What do a) low levels and b) high levels of IGF-1 show?

A

a) low levels - GH deficiency

b) high levels - excess GH.

31
Q

What is synacthen test?

A

Give synthetic ACTH to assess primary adrenal failure. Test how well adrenal glands work by measuring cortisol.

32
Q

What is the Insulin Tolerance Test?

A

Gold standard to test ACTH and GH reserve.

Cause insulin - induced hypoglycaemia. Should see ACTH and GH rise (from the reserve).

33
Q

Which patients should you NOT do insulin tolerance test for?

A

Pt with IHD - can triggery coronary ischemia

Pt with epilepsy - can trigger seizures

34
Q

What imaging would you order for pathology of pituitary gland?

A

MRI

CT if unable to have MRI

35
Q

Distinguish between micro and macro adenomas

A

Micro - less than a cm. More common in women

Macro - more than a cm. More common in men

36
Q

Name ddx for a finding of hyperprolactinaemia

A
Pregnancy - needs to be excluded first 
Medications - antiemetics, anti-psychotics 
Hypothyroidism (rare)
PCOS 
Large pituitary tumour 
Stress 
Renal failure, adrenal insufficiency.
37
Q

How do micro-prolactinomas present?

A

Menstrual disturbance
Hypogonadism in men
Galactorrhoea
Infertility

38
Q

How is PCOS distinguished from prolactinoma?

A

The presence of androgenic symptoms
Less elevated prolactin (<1,000 miU/L)
Absence of pituitary lesion on MRI

39
Q

How are prolactinomas treated?

A

Dopamine D2 agonists

40
Q

Name a D2 agonist

A

Cabergoline- given once or twice weekly, and better tolerated than bromocriptine
Bromocriptine- given daily

41
Q

Name common side effects of cabergoline

A

Nausea, postural hypotension

Rare - psych disturbance

42
Q

What is risk associated to reducing size of lesion/ tumour bulk of prolactinoma?

A

When size reduces rapidly, can get CSF leak which gives potential risk of meningitis

43
Q

What causes acromegaly?

A

Excessive growth hormone.
Most common cause if unregulated GH secretion by pituitary adenoma

Can also be secondary to malignancy elsewhere e.g lung or pancreatic cancer secreting ectopic GHRH or GH

44
Q

What can untreated acromegaly lead to?

A

Disfiguring features
CVD → premature death
Increased risk of bowel cancer

45
Q

How does acromegaly present?

A

Increased size of hands and feet
Frontal bossing of forehead
Protrusion of chin
Widely spaced teeth
Enlargement of tongue and soft palate due to soft tissue swelling - sleep apnoea, snoring
Puffiness of hands - carpal tunnel syndrome

46
Q

Name specific features of active GH hypersecretion

A

Sweating, headaches, HTN, DM

47
Q

What investigation would you do for suspected acromegaly? And what would you see?

A

Oral glucose tolerance test. Failure to supress GH after OGTT ad elevated IGF-1.

48
Q

List management options available for acromegaly

A

Surgery - remove adenoma
Medical - somatostain analogue or dopamine agonist.
External beam or stereotactic radiotherapy- stereotactic radiotherapy only suitable for lesions well away from the optic chiasm

49
Q

How does the chance of remission differ between patients with pituitary micro-adenomas vs macro-adenoma

A

Micro-adenoma, high chance of remission

Macro-adenoma- only achieved in 60% of patients

50
Q

How is acromegaly monitored?

A

Repeat OGTT after surgery
Long term follow up needed - to control GH and IGF-1 levels.
Periodic screening colonoscopy as there is risk of neoplasia.
Assess for sleep apnoea, DM, CVD risk, symptoms of recurrance

51
Q

What are Non-functioning pituitary adenomas (NFPA)?

A

Biochemically inactive tumours

52
Q

How do non-functioning pituitary adenoma present?

A

Visual field loss, headache, hypopituitarism

53
Q

How does hypopituitarism present?

A

Non specific - lethargy, weight gain, sexual dysfunction
Can present with hypo-adrenal crisis - hyponatraemia, hypotension - MEDICAL EMERGENCY
Short stature in children

54
Q

How is hypopituitarism investigated?

A

Exclusion of adrenal insufficiency
Investigate levels of all hormones.
MRI could show empty fossa or pituitary tumour

55
Q

How is hypopituitarism treated?

A

Depends on the deficiency - ACTH-hydrocortisone replacement
TSH-thyroxine replacement
gonadotropin- Men- testosterone via gel or injection
Women- oestrogen and progesterone via COCP or HRT
GH- daily subcut injection

56
Q

Differentiate between Cushings syndrome and Cushing’s disease

A

Cushing’s syndrome- collection of symptoms

Cushing’s disease- excessive ACTH secretion from a PITUIATARY adenoma, can cause cushings syndrome

57
Q

How does Cushing’s syndrome present?

A

Central obesity
Dorso-cervical fat pad
Increased roundness of the face
Pt has red face, thin skin, proximal myopathy
May be HTN, premature osteoporosis, DM, depression, cardiac hypertrophy (due to too much stress hormone)

58
Q

Why is it dangerous to leave Cushing’s syndrome untreated?

A

Significant morbidity. 5-yr mortality approaching 50%

59
Q

What are the causes of Cushing’s syndrome?

A

Exogenous steroids
Cushing’s disease
Adrenal adenoma
Paraneoplastic Cushing’s (ectopic ACTH secretion e.g. small cell lung cancer)

60
Q

What investigations would you do for suspected Cushing’s syndrome?

A

24hr urine free cortisol, low dose dexamethasone suppression test, overnight dexamethasone suppression test.

Screening tests - alcoholism and severe depression can make pts look like they have cushings syndrome but tests come back as normal

61
Q

Explain the dexamethasone supression tests.

A

Low dose 1mg- give dexamethasone at 10pm, check free cortisol at 9am. NORMALLY, should be suppressed, in Cushing’s SYNDROME, it will not be suppressed, therefore you now do the HIGH dose to find out the underlying cause

High dose dexamethasone supression test 8mg. Process is same as above:

Cortisol is surpressed- cushing’s disease- pit adenoma

Cortisol is NOT supressed but ACTH is surpressed- adrenal adenoma (secreting cortisol independently)

Neither cortisol or ACTH surpressed- ectopic ACTH

62
Q

Name differential for Cushings syndrome

A

Pituitary, adrenal or ectopic ACTH

63
Q

What may be in pt’s Hx to point towards them having ectopic ACTH secretion, causing Cushings syndrome?

A

Hypokalaemia
SMoking Hx
Weight loss
By lung cancer or other malignancy.

64
Q

What presenting complaint directly points towards adrenal tumour?

A

Significant, accelerated hirsutism

65
Q

How is adrenal tumour managed?

A

Adrenalectomy

66
Q

How is cushings disease managed?

A

Trans-sphenoidal removal of pit adenoma

67
Q

What are some side effects of long term steroid use - many think of a few from different systems

A
endocrine:
impaired glucose regulation
increased appetite/weight gain
hirsutism
hyperlipidaemia

Cushing’s syndrome:
moon face
buffalo hump
striae

musculoskeletal:
osteoporosis
proximal myopathy
avascular necrosis of the femoral head

immunosuppression:
increased susceptibility to severe infection
reactivation of tuberculosis

psychiatric:
insomnia
mania
depression
psychosis

gastrointestinal:
peptic ulceration
acute pancreatitis

ophthalmic:
glaucoma
cataracts

suppression of growth in children

intracranial hypertension

neutrophilia

68
Q

What is Sheenhan’s syndrome? What causes it?

A

What?
Ischaemia of pituitary gland causes necrosis of secretory cells - get panhypopituitarism.
Leads to : amenorrhea, failure to lactate and death

Cause?
Hypotension/ hypovolaemia due to obstetric haemorrhage. Pituitary gland becomes large and vascular during pregnancy so is vulnerable to hypotension and hypoxia.

69
Q

What is a pituitary apoplexy? What causes it? What is commonly lost? Tests?

A

What?
Endocrine Emergency —-> Haemorrhage / infarction of a pituitary tumour

Cause?
Commonly hypertension or surgery

Commonly lost?
Anterior pituitary hormones- especially ACTH.
Causes 2ndary Adrenal Insufficiency

Tests: Electrolytes / Pit hormones / Glucose / MRI or CT if none

70
Q

How would a patient with pituitary apoplexy present?

A

Sudden onset severe headache (thunderclap) retro-orbital

Nausea, vomiting, reduced consciousness

Opthalmoplegia (paralysis / weakness of 1 or more extraocular muscles)

Visual disturbance - bitemporal hemianopia most common

+ deficiency in Ant Pit hormones - especially ACTH

71
Q

Most common functioning tumour of the anterior pituitary gland?

A

Prolactinoma

72
Q

How large is a macroadenoma of the pituitary? what sign might a patient have ?

A

> 10mm

Bitemporal hemianopia due to compression of optic chiasm

73
Q

What is 1st line treatment for Prolactinomas in men and women? 2nd line?

A

1st line:
Dopamine agonist - Cabgergoline reduce tumour size and prolactin level

2nd line: Trans sphenoidal surgery if medical treatment not tolerated or unsuccessful

74
Q

How does Prolactinoma present in men vs women

A
Men:
Loss of libido 
Lethargy
Galactorrhea
impotence 
hypogonadism (small testes)

Women:

  1. Menstrual disturbance: Amenorrhea/Oligomenorrhea/Menorrhagia
  2. Infertility
  3. Galactorrhea
75
Q

How might a non-functioning adenoma present?

A

Compression might cause:

Visual disturbance - bitemporal hemianopia

Headache / vomiting / papilloedema (ICP +)

Oligomenorrohea and amenorrhea in women

Reduced libido and fertility in men

Cranial nerve palsy

76
Q

How might a non functioning pituitary adenoma cause hyperprolactineamia?

A

Non functioning can cause as it removes the dopaminergic inhibition of prolactin release

77
Q

What investigations for Hyperpituitarism ? (4)

A
  1. Visual
    Optic chiasm - bitemporal hemianopia
    Cavernous sinus - diplopia
2. Blood hormones (morning )
TSH / thyroxine
Prolactin
ILGF-1
FSH / LH / oestrogen / testosterone
ACTH / Cortisol 
  1. Imaging
    MRI / CT
    radio-labelled dopamine antag. can visualise prolactinoma
  2. SUPPRESSION tests (reduced -ve feedback)

Oral glucose tolerance test - should normally suppress GH

ACTH in response to dexamethesone should suppress CRH and ACTH

78
Q

What drugs can cause hyperprolactinaemia?

A

D2 antagonists

Antipsychotics 1st + 2nd:
Haloperidol 1st
Clazapine 2nd

Cyclic Antidepressants:
Amytryptilline

SSRIs:
Citalopram

Anti emetics:
Domperidone
Metoclopramide

79
Q

How does a prolactinoma lead to infertility?

A

Prolactin interferes with GnRH release. This inhibits the release of LH and FSH causing hypogonadism

80
Q

What outside of the pituitary gland in surrounding tissues could cause hypopituitarism?

A

Tumours of surrounding tissues that could compress.

Gliomas (in optic chiasm)
Meningiomas
Craniopharyngiomas
Mets - breast, bronchus, kidney

81
Q

What is the medical treatment of hyperprituitarism? (4) Risk of treatment?

A

All risk of inducing hypopituitarism

Cabergoline - dopamine antagonist to reduce prolactin

Somatostatin analogue - Octreotide to reduce GH

Surgical removal

Irradiation to prevent recurrence

82
Q

What is a microadenoma?

A

adenoma <10mm

more common

83
Q

What investigations needed to diagnose hypopituitarism?

A

Visual field assessment
Basal blood tests
MRI or CT

STIMULATION TESTS
GH - does GH rise in response to insulin tolerance test?

Cortisol - does it rise after ACTH (Synacthen)

LH / fSH in response to GnRH or clomifene (anti oestrogen)

84
Q

What is the treatment for Pituitary Apoplexy?

A

High dose IV hydrocortisone

Transsphenoidal surgical decompression w/in 1 week
( Surgery for pts with neuro-opthalmic signs / deteriorating consciousness)

85
Q

Group the major disorders of the anterior pituitary into 2 main categories

A
  1. Hormone excess due to functioning adenomas
    e. g. GH- acromegaly, ACTH- Cushing’s disease
  2. Hormone deficiency due to non functioning adenoma (SOL). Present later as a macroadenoma - compress secretory cells or portal vessels
86
Q

List 4 ways that pituitary tumours can present

A
  1. Visual disturbance / headache
  2. Inappropriate hormone excess ACTH- Cushing’s disease, Prolactinaemia, GH- acromegaly
  3. hormone hypo / hyper secretion due to compression
  4. Amenorrhea or loss of libido
87
Q

What are some infective / inflammatory cause of pituitary failure?

A

Infective:
TB / syphyllis

Inflammatory:
sarcoidosis
haemochromatosis

88
Q

What investigations needed to diagnose hypopituitarism?

A

STIMULATION TESTS

89
Q

What are the differentials of Diabetes Insipidus clinical presentation?

A

Psychogenic polydipsia, DM, Diuretic use, Hypercalcaemia ( as serum calcium is elevated)

90
Q

Acid base balance in addisons/adrenal insufficiency?

A

Hyperkalaemic metabolic acidosis

91
Q

Treatment for ectopic Cushing’s syndrome?

A

Treat underlying malignancy

92
Q

Why are ACTH levels low in an adrenal cause of Cushing’s syndrome?

A

Increased cortisol causes negative feedback.

93
Q

What are levels of ACTH in Cushing’s syndrome caused by pituitary adenoma or paraneoplastic?

A

Normal or high

Pit adenoma= excessive ACTH secretion
Paraneoplastic= tumour secreting ACTH that is NOT pit adenoma

94
Q

What are cortisol levels following high dose dexamethasone suppression test in a pituitary adenoma?

A

Reduced cortisol

95
Q

What are cortisol levels following high dose dexamethasone suppression test in ectopic Cushing’s syndrome?

A

No suppression - cortisol remains high.

96
Q

Following High dose DST for pituitary adenoma secreting ACTH, what is next step in management ?

A

MRI of the pituitary gland.

97
Q

If MRI of pituitary gland in Cushing’s syndrome does not show pituitary adenoma, what is next step?

A

Inferior Petrosal Sinus Sampling = shows clear gradient between central and peripheral ACTH levels after an injection with CRH. (Sampling the veins that drain the pituitary gland)

98
Q

In suspected ectopic ACTH in Cushing’s syndrome, what is next step following High Dose DST?

A

Whole body CT scan or PET imaging - to find carcinoma.

Note: common place = thorax.

99
Q

Medical treatment options for Cushing’s syndrome?

A

Metyrapone - block steroid synthesis pathway
Ketocanazole - adrenolytic agent
Radiotherapy - help reduce size of tumours before surgery. Or mainstay of treatment if tumours are unresectable.

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