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RACP Written 2018 > Endocrine - Pituitary Disease > Flashcards

Endocrine - Pituitary Disease Flashcards

1
Q

Where does anterior pituitary get its blood supply?

A

From hypothalamic-pituitary portal plexus via SUPERIOR HYPOPHYSIAL ARTERY

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2
Q

What are the subunits of anterior pituitary hormones?

A

Alpha subunit: common to TSH, LH, FSH and hCG

Beta subunit: determines specificity

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3
Q

Growth hormone is secreted by which cells in response to what?

A

By somatotrophs in response to GHRH

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4
Q

When is GH secretion elevated?

A

Deep sleep
Exercise and physical stress
Trauma
Sepsis

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5
Q

When is GH secretion decreased?

A

Obesity

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6
Q

What stimulates GH secretion?

A

Ghrelin

Oestrogen

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7
Q

What inhibits GH secretion?

A

IGF-1
Chronic glucocorticoids
Somatostatin

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8
Q

What is the INDIRECT action of GH?

A

GH stimulates IGF-1 release from liver.

IGF-1 in skeletal muscle and cartilate then increases uptake of amino acids and protein synthesis.

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9
Q

What is the DIRECT action of GH?

A

In epithelium: stimulates mitosis

In adipose: stimulates breakdown of fatty acids and cells use fatty acids rather than glucose

In liver: stimulates glucogenolysis

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10
Q

How is IGF-1 circulated?

A

IGF-1 is bound to circulating IGFBP the main one is IGFBP3 is GH-dependent

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11
Q

Where is IGF-1 synthesised?

A

In the liver

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12
Q

What conditions have higher levels of IGF-1?

A

Higher levels in women and puberty

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13
Q

What conditions have lower levels of IGF-1?

A

Low in hypocaloric states with GH resistance (ie: cachexia, malnutrition and sepsis)

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14
Q

Function of IGF-1?

A

Induces hypoglycaemia, low doses improve with insulin sensitivity

Anabolic

Increased bone turnover

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15
Q

Laron’s Syndrome

A

= partial or incomplete GH insensitivity and growth failure

Diagnose with normal/high GH levels but decreased GHBP and IGF-1 levels

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16
Q

Clinical features of adult growth hormone deficiency?

A

Body composition changes:

  • reduced lean body mass
  • increased fat mass
  • selective deposition of intra-abdominal fat
  • increased waist:hip ratio

Hyperlipidaemia
LV dysfunction
Hypertension
Increased (x3) CVS mortality

Increased fibrinogen levels

Reduced bone mineral density
Increased fracture rates

Depression

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17
Q

Diagnosis of growth hormone deficiency?

A 
Insulin tolerance test
GHRH test
Arginine-L dopa test
Glucoagon-stimulation test
Serum-IGF
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18
Q

Causes of Acromegaly from Excess GH Secretion:

A

Pituitary:

  • carcinoma
  • McCune Albright
  • MEN1

Extra-Pituitary:

  • pancreatic islet cell tumour
  • lymphoma
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19
Q

Causes of Acromegaly from Excess GHRH secretion?

A

Central

Peripheral:

  • *** medullary thyroid cancer
  • bronchial carcinoid
  • pancreatic islet cell tumour
  • SCLC
  • Adrenal adenoma
  • pheochromocytoma
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20
Q

Clinical features of acromegaly

A

Frontal bossing / increased hand or feet / mandibular enlargement / widened incisors

Soft tissue swelling
Hyperhidrosis
Deep hollow voice
Oily skin
Acanthosis nigricans

Arthropathy
Kyphosis
Carpal tunnel syndrome
Proximal muscle weakness and fatigue

Visceromegaly
Cardiomegaly and diastolic failure
Hypertension
Obstructive sleep apnoea
Diabetes (>10%)

Increased risk colon cancer and thyroid cancers

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21
Q

Risk of which cancers is increased with acromegaly?

A

Colon cancer and thyroid cancer

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22
Q

Which clinical feature of acromegaly is irreversible?

A

Arthropathy

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23
Q

Diagnosis of Acromegaly?

A

Elevated IGF-1 (screen)

75mg oral glucose challenge: GH SHOULD suppress to 1-2 hours post intake
(** 20% get a paradoxical rise **)

Prolactin is elevated in 25%

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24
Q

When should someone with acromegaly get colonoscopies?

A

From age 40yrs

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25
Q

Role of surgery in acromegaly?

A

First line for adenomas

Transphenoidal resection:

  • microadenoma remission 70%
  • macroadenoma remission <50%
    • swelling improves immediately
    • IGF-1 normalises within 3-4 days
    • GH normalises within an hour
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26
Q

Post transphenoidal resection for acromegaly how common is hypopituitarism?

A

15%

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27
Q

Action of somatostatin analogues?

A

ie Octreotide

Suppress GH secretion by binding to SSTR2 and SSTR5

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28
Q

How well does octreotide work in acromegaly?

A

Normalises IGF-1 in 60%

Half life is 2hours

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29
Q

Side effects of octreotide?

A
  • suppression of GI motility and secretion
    (–> diarrhoea, flatulance and fat malabsorption)
  • suppresses postprandial gallbladder contractions and delays gallbladder emptying
  • mild glucose intolerance
  • bradycardia
  • hypothyroxinaemia
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30
Q

Action of GH-Receptor Antagonists in acromegaly?

A

ie: Pegvisomat

Blocks PERIPHERAL GH binding to receptor
(and suppresses serum IGF-1_

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31
Q

How well does Pegvisomat work in acromegaly?

A

Normalises IGF-1 in 70%

Does not target adenoma (therefore serum GH will remain high)

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32
Q

Side effects of Pegvisomat?

A

LFT derangement

Lipodystrophy

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33
Q

Action of dopamine agonists in acromegaly?

A

ie: Bromocriptine and Cabergoline

Only MODESTLY suppresses GH secretinos SOMETIMES

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34
Q

Role for radiation in acromegaly?

A

GH levels reduce over time

50% of people require >8 years to suppress, therefore usually need interim medical treaments

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35
Q

What is octreotide?

A

Somatostatin analogue

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36
Q

What is pegvisomat?

A

GH-Receptor Antagonist

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37
Q

What is Bromocriptine?

A

Dopamine Agonist

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38
Q

What is Cabergoline?

A

Dopamine agonist

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39
Q

Prolactin is secreted by what cells?

A

Lactotrophs

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40
Q

When does prolactin secretion peak?

A

Between 4-6AM during REM sleep

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41
Q

What stimulates prolactin secretion?

A 
Prolactin Releasing Hormone (PRLH)
Thyrotropin-Releasing Hormone (TRH)
Vasoactive Intestinal Peptide (VIP)
Oestrogen
Oxytocin
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42
Q

What is the predominant central inhibition of prolactin secretion?

A

Dopamine D2 receptor

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43
Q

Elevated levels of prolactin are seen in…?

A 
Post exercise
Meals
Surgery
General anaesthesia
Chest wall injury
Acute MI
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44
Q

Decreased levels of prolactin are seen in…?

A

Thyroid hormone

Steroid use

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45
Q

How does prolactin act?

A

Signals via JAK –> STAT family

Induces and maintains lactation
Decreases oestrogen function

Decreases oestrogen

  • -> blocks folliculogenesis
  • -> inhibits granulosa cell aromatase
  • -> amenorrhoea

Decreases libido

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46
Q

Causes of Hyperprolactinaemia?

A

Pregnancy/Lactation

Physiologic (nipple or sexual organism, sleep or stress)

Prolactinoma

Pituitary:

  • stalk disruption or macroadenoma
  • lymphocytic hypophysitis
  • radiation and trauma

Primary hypothyroidism

Renal Failure

Pharamcologic:

  • Antipsychotics (risperidone)
  • metoclopramide (inhibits D2 receptor)
  • Methyldopa (inhibits dopamine synthesis)
  • CCBs (verapamil) block dopamine release
  • H2 antagonists
  • opioids
  • amitryptiline
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47
Q

Which drugs can cause high prolactin levels?

A
  • Antipsychotics (risperidone)
  • metoclopramide (inhibits D2 receptor)
  • Methyldopa (inhibits dopamine synthesis)
  • CCBs (verapamil) block dopamine release
  • H2 antagonists
  • opioids
  • amitryptiline
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48
Q

How does hyperprolactinaemia present?

A

Amenorrhoea
Galactorrhoea
Infertility
Visual loss from compression of optic chiasm (Bitemporal hemianopia)

Long term:

  • osteopenia
  • decreased libido
  • weight gain
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49
Q

Diagnosis of hyperprolactinaemia

A

Basal fasting prolactin level
Measure TFTs
MRI

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50
Q

Role of dopamine agonists in hyperprolactinaemia?

A
  • suppress prolactin secretion and synthesis
  • suppress lactotrope cell proliferation

Once prolactin normal and tumour shrinks
–> Then after two years can withdraw medical treatment if >50% reduction in size and >5mm from vital structures

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51
Q

What is important monitoring when giving dopamine agonists in hyperprolactinaemia?

A

Need formal visual fields before treatment 6-monthly until mass shrinks annually afterwards

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52
Q

How many patients with hyperprolactinaemia will not respond to dopamine agonists?

A

20% of patients (especially males) are resistant to dopamine agonists

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53
Q

Which are the two dopamine agonists used in hyperprolactinaemia, and how are they different/similar?

A

CABERGOLINE (Preferred) (ergot-derived)

  • suppress prolactin for >14 days
  • success in 80% microadenoma, 70% macroadenoma
  • side effects less common than bromo

BROMOCRIPTINE (ergot alkaloid)

  • short acting
  • ** preferred in pregnancy ***
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54
Q

Side effects of the dopamine agonists used in hyperprolactinaemia?

A

Cabergoline and Bromocriptine:

  • constipation, dry mouth
  • nightmares and insomnia
  • vertigo
  • auditory hallucinations
  • cardiac valvulopathy (CABERGOLINE)
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55
Q

Role of surgery in treatment of hyperprolactinaemia?

A

Surgery if:

  • dopamine resistant / intolerant
  • compromised vision not improving

30% success for macroadenoma (50% long term recurrence)
70% success for microadenoma

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56
Q

Role of radiation in treatment of hyperprolactinaemia?

A

Only if aggressive and not responding to other treatments

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57
Q

Management of prolactinaemia in pregnancy

A

Microadenoma:

  • discontinue dopamine agonist
  • periodic visual loss
  • repeat MRI 6 weeks postpartum

Macroadenoma:
- consider surgery prior to pregnancy
- ensure BROMOCRIPTINE SENSITIVE before getting pregnant
- Give BROMOCRIPTINE as soon as vision is compromised
OR
continue if vision is already affected
- consider high dose steroids or surgery during pregnancy if vision is threatened or adenoma haemorrhage
- MRI postpartum at 6 weeks

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58
Q

Where is ACTH synthesised?

A

In corticotrophs in anterior pituitary

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59
Q

What protein is ACTH derived from?

A

POMC precursor protein

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60
Q

What suppresses ACTH synthesis?

A

Glucocorticoids

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61
Q

What induces ACTH synthesis?

A

CRH
AVP
IL-6
Leukaemia inhibitory factor

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62
Q

What stimulates the secretion of ACTH? And from where?

A

Stimulated release by CRH from the paraventricular nucleus

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63
Q

When does secretion of ACTH peak and trough?

A

Peak at 6AM

Trough at midnight

64
Q

What are the ACTH-inducing cytokines?

A

TNF
IL-1
IL-2
IL-6

65
Q

What is the receptor for ACTH? What type of receptor is it?

A

Melanocortin-2 Receptor (G-protein coupled receptor)

66
Q

Where is the ACTH receptor? What does it do?

A

Stimulation of ACTH receptor or ADRENOCORTICOID CELLS in the ZONA FASCICULATA to make glucocorticoids (cortisol and cortisterone)

67
Q

ACTH acts on which zones of the adrenals to stimulate synthesis of what?

A

Zona glomerulosa –> mineralocorticoids (aldosterone)

Zona fasciculata –> glucocorticoids (cortisol and corticosterone)

Zona reticularis –> adrenal androgens (DHEAS / andostenedione)

68
Q

What are the ACTH-Dependent Causes of Cushing’s Syndrome?

A

Cushing’s Disease (pituitary adenoma)
Ectopic ACTH production (ie bronchial carcinoid)
Ectopic CRH production

69
Q

What are the ACTH-Independent Causes of Cushing’s Syndrome?

A

Adrenal adenoma or carcinoma

Micronodular hyperplasia (primary pigmented nodule adrenal disease PPNAD)

Macronodular hyperplasia (ACTH-independent macronodular adrenal hyperplasia AIMAH)

70
Q

What is Primary Pigmented Nodular Adrenal Disease (PPNAD)

A
  • Sporadic PPKAR1A mutation or CARNEY COMPLEX (Autosomal Dominant)
    = hyperpigmented + excess endocrine
71
Q

Clinical features of Cushings Syndrome?

A

Chronic cortisol excess:

  • think skin
  • central obesity and moon facies
  • Hypertension
  • plethora
  • purple striae >1cm
  • easy bruising
  • diabetes
  • proximal muscle weakness
  • osteoporosis ** esp necrosis of femoral head

Hyperandrogenism: acne and hirsutism

Psych disturbance: mania and psychosis

Haem: leukocytosis, lymphopenia and eosinopenia

Hypokalaemic alkalsosis: if K<3.3 more likely ectopic ACTH

Hyperpigmentation

72
Q

Features MOST SUGGESTIVE of Cushings?

A

Plethora
Purple striae >1cm
Easy bruising
Proximal muscle weakness

73
Q

What are the features associated with an Ectopic ACTH cause of Cushings Syndrome?

A
  • higher ACTH
  • Rapid progression
  • severe myopathy
  • pigmentation
  • hypokalaemia
  • VERY HIGH cortisol and ACTH
74
Q

Occult ACTH production when causing Cushing’s Syndrome is usually the result of what types of tumours?

A

Bronchial carcinoid
Thymoma
SCLC

75
Q

Screening tests for suspected Cushing’s Syndrome?

A

1) 24 hour urine free cortisol

2) Late night cortisol
- late evening 11pm serum cortisol
if <50nmol/L –> excludes cushings
if >207nmol/L –> is y

  • late night/midnight salivary cortisol

3) Overnight 1mg dexamethasone suppression test
- give 1mg at 11-12pm then check morning cortisol between 8-9am. If normal then not Cushings.

76
Q

What are the special populations you need to consider when screening for Cushings Syndrome?

A

Pregnant: use UFC

Epilepsy: use measured NONSUPPRESSED cortisol

Renal failure: use 1mg overnight dexamethasone suppression test

Cyclical cushings syndrome: use UFC or midnight saliva

Adrenal incidentaloma: use 1mg DST or midnight saliva

77
Q

Which is better, the low dose 0.5mg 6hrly x 8 dexamethasone test or the 1mg dexamethasone suppression test?

A

Equally as effective

Do 0.5mg 6hrly x 8 times then measure 24 hour urinary cortisol in the 2nd 24 hour period.

78
Q

What further testing do you do once you have confirmed Cushings?

A

Test ACTH
if <10ng/mL –> ACTH independent
if 10-20ng/mL –> need CRH testing
if >20ng/mL –> ACTH depdendent

79
Q

What ACTH level suggests ACTH Independent Cushings?

If you confirm ACTH Independent Cushings Syndrome, what is the next test? What are your differentials?

A

if ACTH <10ng/mL –> ACTH independent

Need CT/MRI adrenals
ddx:
- unilateral mass of adrenal adenoma/carcinoma
- bilateral macronodular or micronodular hyperplasia

80
Q

What ACTH level suggests ACTH Dependent Cushings?

If you confirm ACTH Dependent Cushings Syndrome what is the next test? What are the differentials

A

if ACTH >20ng/mL –> ACTH depdendent

DDx:
70% Cushings Disease, 10% ectopic, 15% adrenal

Need

1st) MRI pituitary:
- if adenoma <6mm: do BPSS
- if adenoma >6mm AND concordant HDSST then is cushings disease, but if NOT concordant with HDSST then need BPSS

2nd) High dose dexamethasone suppression test (HDSST)
= 2mg dex 6hrly x 8
–> urinary free cortisol suppression >90% is HIGHLY SPECIFIC for Cushings (NOT sensitive)
*** if negative then need BPSS

3rd) Bilateral petrosal sinus sampling (BPSS)
if adenoma <6mm or MRI and HDSST are discordant it is the BEST test
Test before and after CRH
RATIO: inf petrosal ACTH : Peripheral ACTH
–> if >2 then Cushings Syndrome
–> if >=3 then PITUITARY ACTH TUMOUR
** lateralisation within pituitary is possible but less reliable to ddx pituitary versus ectopic

4th) if negative BPSS:
THEN do either:
- CT C/A/P
- PET or PET-CT
- Octreoscan
--> if positive then ectopic ACTH tumour
--> if negative then needs followup
81
Q

Treatment of Cushings Disease 1st line

A

Trans-Sphenoidal Selective Resection
–> remission in 80% microadenoma, <50% macroadenoma
RARELY successful if negative MRI

82
Q

Pre-Operative Prep in Treatment of Cushing’s Disease

A

Either:

METYRAPONE:

  • inhibits 11beta-hydroxylase activity
  • normalises plasma cortisol in 75%

KETOCONAZOLE:
- inhibits several P450 enzymes to lower cortisol
S/E: gynecomastia, LFT, impotence, GI upset and oedema

MIFEPRISTONE:
- glucocorticoid receptor antagonist
- blocks PERIPHERAL cortisol action
- treats HYPERGLYCAEMIA in Cushings
BUT levels of cortisol and ACTH remain high
S/E: hypokalaemia, endometrial hyperplasia, hypoadrenalism, hypertension

83
Q

Role of METYRAPONE in pre-operative management in surgical treatment of Cushings Disease

A

METYRAPONE:

  • inhibits 11beta-hydroxylase activity
  • normalises plasma cortisol in 75%
84
Q

Role of KETOCONAZOLE in pre-operative management in surgical treatment of Cushings Disease

A

KETOCONAZOLE:
- inhibits several P450 enzymes to lower cortisol
S/E: gynecomastia, LFT, impotence, GI upset and oedema

85
Q

Role of MIFEPRISTONE in pre-operative management in surgical treatment of Cushings Disease

A

MIFEPRISTONE:
- glucocorticoid receptor antagonist
- blocks PERIPHERAL cortisol action
- treats HYPERGLYCAEMIA in Cushings
BUT levels of cortisol and ACTH remain high
S/E: hypokalaemia, endometrial hyperplasia, hypoadrenalism, hypertension

86
Q

If surgery is unsuccessful in treatment of Cushings Disease

A

1) total hypophysectomy
2) pituitary irradiation (cures in 15%)
3) PASIREOTIDE
4) bilateral adrenalectomy

87
Q

What is the role of Pasireotide in treating Cushings Disease for which surgery has been unsuccessful? What are the side effects?

A

Pasireotide = somatostatin analogue with high affinity for SST5 >SST2 receptors

  • used for treating ACTH-secreting tumours
  • in 25% lowers ACTH levels and normalises 24 hour UFC
S/E: 
- hyperglycaemia and diabetes (75%) 
(due to suppressed pancreatic secretion of insulin and incretins)
- GI discomfort
- gallstones (20%)
88
Q

What is the consequence of bilateral adrenalectomy in treating Cushings Disease for which surgery has been unsuccessful?

A

Requires permanent mineralocorticoid and glucocorticoid

If residual corticotrope adenoma can develop NELSON’S SYNDROME

89
Q

What is Nelson’s Syndrome and how can it be prevented?

A

Nelson’s Syndrome develops when there is residual corticotrope adenoma after bilateral adrenalectomy for Cushing’s DIsease.

  • rapid pituitary tumour enlargement
  • hyperpigmentation secondary to high ACTH

Can be prevented with prophylactic radiotherapy post adrenalectomy

90
Q

What medical followup is needed post hypophysectomy in treatment of Cushing’s Disease?

A

8AM cortisol: 24 hours post last hydrocortisol and 3-7 days postop

CURE = undetectable cortisol
and undetectable ACTH

91
Q

What is the size definition of a macroadneoma?

92
Q

Clinical features of sellar masses?

A
  • headaches
  • vision:
    Bitemporal hemianopia (ventral optic chiasm)
    Homonymous hemianopia (opstchiasmal compression)
    Monocular temporal loss (prechiasmal compression)
    Diplopia from ocular motor nerve palsy (cavernous sinus)
  • symptoms of hypersecretion
  • cranial nerve III, IV, VI palsies from impinged cavernous sinus
93
Q

Screening for functional pituitary adenoma?

A

Acromegaly:

  • serum IGF-1
  • Oral GTT (normal patient will suppress GH)

Prolactinoma: serum prolactin

Cushings:

  • 24hr UFC
  • 1mg dex suppression test
  • ACTH assay
94
Q

Treatment of hypothalamic/pituitary sellar masses

A

SURGERY

  • trans-sphenoidal preferred
  • surgery decompression / resection

S/E: operative mortality 1%

  • 20% transient diabetes insipidus / hypopituitarism
  • 10% permanent diabetes insipidus / cranial nerve damage / nasal perforation / visual disturbance
  • 4% CSF leaK

RADIATION:

  • slow onset of action (reserved for post surgical treatment)
  • used as adjuvant to surgery
95
Q

Hypothalamic Lesions: features of an anterior/pre-optic region mass

A

Paradoxical vasoconstriction
Tachycardia
Hyperthermia

96
Q

Hypothalamic Lesions: features of a posterior region mass

A

Thermo-dysregulation
- “periodic hypothermia syndrome”
= episodes of temps <30, sweating, vasodilation, vomiting and bradycardia

97
Q

Hypothalamic Lesions: features of a ventromedial nucleus lesion

A

Hyperphagia

Obesity

98
Q

Hypothalamic Lesions: features of a preoptic nucleus lesion

A

Polydipsia

Hypodipsia

99
Q

Hypothalamic Lesions: features of a central region lesion

A

stimulation of sympathetic system with increased catecholamines and increased cortisol

100
Q

How do craniopharyngiomas present?

A 
Usually present <20yrs old
Headaches
Visual field defects
Hypopituitarism (90%)
Diabetes insipidus (10%)
Calcified appearance on MRI
101
Q

What are Ranthke’s Cysts?

A

Found in 20% of people from developmental failure of Rathke’s pouch obliteration

80% present in adulthood with compression symptoms, hyperprolactinaemia and diabetes insipidus

102
Q

What is Hand-Schuller-Christian Disease?

A

Diabetes insipidus
Exophthalmos
Punched out lytic bone lesions

Assoc granulomatous lesions on MRI

103
Q

Hypothalamic hamartomas overexpress which hypothalamic neuropeptides?

A

GnRH
GHRH
CRH

104
Q

Hypothalamic hamartomas are associated with which genetic syndrome?

A

Pallister Hall Syndrome
(from mutation in GLIS)

Assoc. with:

  • imperforate anus
  • cardiac / renal / lung disorders
  • pituitary failure
105
Q

Where in the pituitary do systemic metastases go?

A

Posterior pituitary

106
Q

Where do the majority of pituitary metastases originate from?

A

50% of pituitary metastases are from breast cancer

107
Q

What are the types of pituitary adenoma?

A

40% are non-functional

  • most stain for FSH
  • can cause mass effect
  • can cause VERY HIGH prolactin due to stalk pressure
  • 30% recur post surgery

30% prolactinoma (lactotroph)
15% GH (somatotroph)
10% ACTH (corticotroph)
<5% are TSH (thyrotrope) or FSH (gonadotrope)

108
Q

How many pituitary adenomas recur post surgery?

109
Q

What gene and what features are part of MEN1?

A

= tumour suppressor gene on Ch11q13

Autosomal dominant
Parathyroid
Pancreatic
Pituitary

110
Q

What gene and what features are part of MEN4

A

= gene CDKNIB on Ch12p13

Parathyroid
Pituitary

111
Q

What is Carney Complex?

A

= mutation of R1alpha regulatory subunit of Protein Kinase A (PPKAR1A)

Features:

  • atrial myxoma
  • spotty skin pigmentation
  • endocrine tumour: testicular, adrenal and pituitary
  • acromegaly (20%)
112
Q

What is McCune-Albright Syndrome?

A

= inactivation of GTPase activity of GSalpha

Features:

  • polyostotic fibrous dysplasia
  • pigmented skin patches
  • acromegaly
  • adrenal adenoma
113
Q

What is Familial Acromegaly?

A

= germline mutation in AIP

Generally young onset
Acromegaly and gigantism

114
Q

FSH secretion is stimulated by what?

A

Gonadotropin Releasing Hormone (GnRH) at low frequency pulses

115
Q

FSH secretion is inhibited by?

A

Inhibin

  • inhibits FSH but NOT GnRH
  • produced by females by ovarian granulosa cells in response to FSH
  • produced in males by Sertoli cells in response to androgens
116
Q

Mechanism of action of FSH

A

Stimulates germ cell maturation

FEMALES: initiates follicular selection and growth

MALES: initiates meiosis of primary spermatocytes and enhances ANDROGEN BINDING PROTEIN production from Sertoli cells

117
Q

LH secretion is stimulated by?

A

Stimulated by gonadotropin releasing hormone (GnRH) at HIGH frequency pulses

118
Q

LH mechanism of action?

A

FEMALES: “LH surge” triggers ovulation and converts residual follicule into corpus luteum to release progesterone and prepare endometrium for implantation

MALES: acts on testicular Leydig cells to produce testosterone

119
Q

TSH is produced where and in response to what?

A

Produced in anterior pituitary by thyrotropes in response to TRH

120
Q

TSH secretion is inhibited by what?

A 
Growth Hormone Inhibiting Hormone (GHIH)
(aka Somatostatin)
and
Thyroid Hormone
and
Dopamine
121
Q

Action of TSH?

A

Stimulates synthesis and secretion of thyroid hormones by binding to TSH receptor on thyroid follicular cells

122
Q

How do TSH-omas present?

A

Present with goitre and hyperthyroidism

Suggested by pituitary mass and beta-subunit elevated levels

Need to EXCLUDE resistance to thyroid hormone (= dominant negative thyroid receptor mutation)

123
Q

Developmental causes of Hypopituitarism

A
  • Pituitary dysplasia
  • Tissue specific factor mutations
  • Kallman syndrome
  • Bardet-Beidl Syndrome
  • Leptin and Leptin Receptor mutations
  • Prader Willi Syndrome
124
Q

What are the tissue specific factor mutations that cause developmental hypopituitarism?

A

PIT-1 and PROP1 needed for lineages:

TPIT: deficiency of ACTH
PROP1: deficiency of GH, PRL, TSH, Gonadotropin

125
Q

What are the features of Kallman Syndrome?

A

= defective hypothalamic GnRH (both Autosomal Recessive and Dominant)

Features:

  • Anosmia
  • Colour Blindness
  • Optic atrophy
  • Sensorineural deafness
  • Cleft palate
  • Renal abnormalities
  • Cryptorchism
  • Neuro: mirror movements
126
Q

What are the features of Bardet-Biedl Syndrome?

A
  • mental retardation
  • obesity
  • renal abnormalities
  • syndactyly
  • central diabetes insipidus
  • childhood retinal degeneration
127
Q

What are the features of Leptin and Leptin Receptor Mutations?

A

Hyperphagia
Obesity
Central hypogonadism

128
Q

What are the features of Prader Willi Syndrome?

A

= deletion of paternal SNRPN and NECDIN on Ch15

Features

  • hypogonadotropic hypogonadism
  • hyperphagia / obesity
  • chronic muscle hypotonia
  • mental retardation
  • diabetes mellitus
129
Q

Acquired Causes of Hypopituitarism?

A

Infiltrative Disorders

  • Sarcoidosis
  • Histiocytosis X
  • Amyloidosis
  • Haemochromatosis

Inflammatory Disorders

  • TB
  • opportunistic fungal infections
  • tertiary syphilis

Cranial irradiation
- usually after 5 - 15 years
GH deficiency most commonly

Lymphocytic Hypophysitis

Pituitary Apoplexy

Empty Sella

130
Q

What are the features of Lymphocytic Hypophysitis?

A
  • especially postpartum women
  • presents with hyperprolactinaemia
  • ESR elevated
  • Rx: several months of glucocorticoids
131
Q

What are the features and associated conditions of Pituitary Apoplexy?

A
  • pituitary adenoma haemorrhage
  • Sheehan’s syndrome postpartum

Assoc. conditions:

  • Sickle Cell
  • Diabetes
  • Hypertension

Features:

  • Sudden onset headache
  • vomiting and neck stiffness
  • visual fields: bitemporal superior quadrant defect
  • extraocular nerve palsies
  • features of pituitary insufficiency
132
Q

What are the features of ACTH deficiency? How is it diagnosed?

A

Fatigue, n+v and hypoglycaemia

NOT hyperpigmentation or mineralocorticoid deficiency

Diagnosis:
- insulin tolerance test (cortisol SHOULD increase if glucose decreases)
- CRH test
- basal cortisol
SYNACTHEN TEST: increases cortisol
133
Q

How to diagnose TSH deficiency

A

Basal test TFTs

TRH stimulation test –> should increase TSH

134
Q

How does deficiency of FSH and LH present? How do you diagnose?

A

Presents as amenorrhoea, infertility and reduced libido

Diagnose:

  • basal tests: LH, FSH, testosterone and oestrogen (low levels indicate insufficiency)
  • GnRH test: should normally increase FSH and LH
135
Q

Where is Vasopressin (AVP / ADH) produced

A

Encoded on Ch20 then packaged and transported down neurohypophysis axon to posterior pituitary and is then processed to ADH, neurophysin and copeptin

136
Q

What stimulates vasopressin secretion?

A

Increased osmolality

Angiotensin II

137
Q

What inhibits vasopressin secretion?

A

ANP
Alcohol
Cortisol

138
Q

What is the mechanism of vasopressin?

A

Acts on receptors:

Vasopressin 1A Receptor:

  • in liver, kidney, brain and peripheral vascular
  • vasoconstriction
  • platelet aggregation
  • gluconeogenesis

Vasopressin 2 Receptor:

  • on basolateral membrane in cortical collecting duct
  • stimulates insertion of AQP2 channel
139
Q

Where is Vasopressin 1A Receptor found and what does it do?

A

Found in liver, kidney, brain and peripheral vascular

  • vasoconstriction
  • platelet aggregation
  • gluconeogenesis
140
Q

Where is Vasopressin 2 Receptor found and what does it do?

A

Found on basolateral membrane in cortical collecting duct

Stimulates insertion of AQP2 channel

141
Q

Where is oxytocin synthesised?

A

In paraventricular nucleus of the hypothalamus

142
Q

What stimulates secretion of oxytocin?

A
  • uterus or cervical distention
  • nipple stimulation
  • oestrogen
143
Q

What is the action of oxytocin?

A

Milk ejection

Uterine contractions

144
Q

What is the most common genetic inheritance of pituitary diabetes insipidus?

A

Most common form is autosomal dominant (some are autosomal recessive)

145
Q

What is Wolfram’s Syndrome?

A

also known as DIDMOAD
= Autosomal recessive mutation in WFS1

Diabetes Insipidus
Diabetes Mellitus
Optic Atrophy
Deafness

146
Q

What is the effect of primary polydipsia on ADH?

A

Primary polydipsia excessive fluid intake inhibits ADH secretion

147
Q

What is the most common genetic form of nephrogenic diabetes insipidus?

A

Most common is semirecessive X-linked

148
Q

What medications can cause nephrogenic diabetes insipidus?

A

Lithium
Aminoglycosides
Cisplatin

149
Q

What are the causes of nephrogenic diabetes insipidus?

A

Genetic
Medications (lithium / aminoglycosides / cisplatin)
Obstructive
Granulomas (ie sarcoidosis)
Infiltrative (ie amyloidosis)
Metabolic (ie hypercalcaemia / hypokalaemia)

150
Q

How is diabetes insipidus diagnosed?

A

Water deprivation:
- FAILS to concentrate urine Osm >600 despite a raised serum Osm >300

Then CONFIRM CENTRAL iwth desmopressin ddAVP –> central if urine Osm >600

151
Q

Treatment of central diabetes insipidus?

A

If temporary/mild: ensure access to fluid

If severe/permanent: desmopressin nasal spray or tablets

152
Q

What percentage of patients with acromegaly have a MEN syndrome? Which one is it?

A

6% have MEN-1

153
Q

What are the primary and secondary causes of hypoadrenalism?

A

PRIMARY:

  • TB
  • metastases (ie bronchial carcinoma)
  • meningococcal septicaemia (Waterhouse-Friderchsen syndrome
  • HIV
  • antiphospholipid syndrome

SECONDARY

  • pituitary disorders
  • exogenous glucocorticoids
154
Q

Causes of gynaecomastia?

A

physiological: normal in

puberty
syndromes with androgen deficiency:
- Kallman’s
- Klinefelter’s

testicular failure:
- mumps

liver disease

testicular cancer
- seminoma secreting hCG

ectopic tumour secretion

hyperthyroidism

haemodialysis

drugs

155
Q

Common drug causes of gynaecomastia?

A

spironolactone (most common drug cause)

cimetidine

digoxin

cannabis

finasteride

gonadorelin analogues

  • Goserelin
  • buserelin

oestrogens

anabolic steroids

156
Q

Very rare drug causes of gynaecomastia?

A

tricyclics

isoniazid

calcium channel blockers

heroin

busulfan

methyldopa

RACP Written 2018 (167 decks)

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