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MD1 endocrinologie > L'hypophyse > Flashcards

L'hypophyse Flashcards

1
Q

What’s the difference between the location of the hypothalamus and the pituitary gland?

A

Hypothalamus –> partie du cerveau

Hypophyse –> glande accrochée sous le cerveau

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2
Q

What are the main organs targetted by the pituitary gland? (6)

A
  1. Thyroid
  2. Adrenal glands
  3. Ovaries
  4. Testicles
  5. Liver
  6. Breasts
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3
Q

What are the three main levels of hormonal control?

A
  1. Hypothalamus
  2. Pituitary
  3. Target organ (effector)
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4
Q

What is the purpose of the hypothalamus?

A

Integration center for information within the brain

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5
Q

Where is the hypothalamus?

A

Around the third ventricle right above the pituitary gland

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6
Q

What does the hypothalamus “control”?

A

Anterior and posterior pituitary gland

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7
Q

Which hormones are secreted by the hypothalamus? (8)

A
  1. CRH
  2. GHRH
  3. Somatostatin
  4. TRH
  5. GnRH (or LHRH)
  6. Dopamine
  7. ADH (vasopressin)
  8. Oyxtocin
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8
Q

Which hormones are secreted by the anterior pituitary? (6)

A
  1. ACTH
  2. HGH (or GH)
  3. TSH
  4. LH
  5. FSH
  6. PRL
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9
Q

What is the main function of the hypothalamus?

A
  1. Stimulates the release of hormones from the anterior pituitary gland
  2. Secretes 2 hormones that inhibit the release of two hormones from the anterior pituitary gland
  3. Produces 2 hormones that are stocked in the posterior pituitary
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10
Q

Which hypothalamic hormones stimulate the release of which anterior pituitary hormones? (4:4)

A

CRH –> ACTH

GHRH –> HGH or GH

GnRH –> LH-FSH

TRH –> TSH

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11
Q

Which two hypothalamic hormones inhibit the release of which two anterior pituitary hormones?

A

Somatostatin -/-> GH

Dopamine -/-> prolactin

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12
Q

What are the two lobes of the pituitary gland and their functions?

A
  1. Anterior pituitary:
    • 2/3 of the pituitary
    • Embryo: provient des cellules ectodermiques
    • PRODUCES hormones
  2. Posterior pituitary:
    • 1/3 of the pituitary
    • Embryo: neurological cells
    • STOCKS hormones
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13
Q

What is the selle turcique?

A

saddle-shaped depression in the body of the sphenoid bone of the human skull in which the pituitary gland is located

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14
Q

Embryology of the pituitary:

A

ectoderme –> Poche de Rathke –> hypophyse antérieur

crête neurale –> hypophyse postérieur

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15
Q

How does the hypothalamus communicate with both parts of the pituitary?

A
  1. Anterior: via portal system (venous circulation)
  2. Posterior: not actually separate (embryologically/anatomically) from the hypothalamus, just a continuation of its axons/nerve endings
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16
Q

What are the six cell types within the anterior pituitary?

A
  1. Thyréotropes –> TSH and regulated by TRH
  2. Lactotropes –> PRL
  3. Gonadotropes –> LH/FSH and regulated by GnRH
  4. Somatotropes –> HGH and regulated by GHRH
  5. Corticotropes –> ACTH and regulated by CRH
  6. Chromophobes (colourless but job unknown for now)
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17
Q

MRI of the brain and the pituitary:

A
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18
Q

Which three important nerves are found in the optic chiasma?

A

3, 4, and 6: used for tracking and coordinating eye movement

If there’s a problem with the “sinus caverneux” and these three nerves are affected, it’ll cause diplopia

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19
Q

What is the name and function of the 3rd cranial nerve?

A

N. occulomoteur

Function: muscles de l’œil sauf grand oblique et droit externe

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20
Q

What is the name and function of the 4th cranial nerve?

A

N. pathétique/trochléaire

Function: muscles grand oblique de l’œil

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21
Q

What is the name and function of the 6th cranial nerve?

A

N. moteur oculaire externe/abducens

Function: muscle droit externe

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22
Q

What is the axe hypothalamo-hypophyso-thyoïdien?

A
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23
Q

What is the axe hypothalmo-hypophyso-gonadique in women?

A
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24
Q

What is the axe hypothalmo-hypophyso-gonadique in men?

A
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25
Q

What is the axe hypothalamo-hypophyo-surrénalien?

A
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26
Q

What is the circadian cycle?

A

Cortisol levels during the day:

  • High in the morning
  • Drops throughout the day
  • Low at midnight and at the start of the night
  • Raises again towards the end of the night

(this cycle changes depending on your sleep schedule)

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27
Q

What is the axe hypothalamo-hypophyso-somatotrope?

A
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28
Q

What hormone inhibits the axe somatotrope?

A

Somatostatin

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29
Q

What is the “axe de la prolactine”?

A
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30
Q

What are the three most important things to know about pituitary tumours?

A
  1. Benign
  2. Grow slowly
  3. Are intrasellar (stay inside the selle turcique)
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31
Q

What are the names of the most common benign and malignant pituitary tumours?

A

Benign –> adenoma

Malignant –> carcinoma (VERY RARE)

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32
Q

How big is a microadenoma?

A

< 10 mm

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33
Q

How big is a macroadenoma?

A

≥ 10 mm

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34
Q

What are the two main kinds of benign pituitary tumours?

A
  1. Tumeurs fonctionnelles (secrétantes): 80% secrètent une ou des hormones
  2. Tumeurs non-fonctionnelles (non-secrétantes): 20% ne secrètent pas des hormones
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35
Q

What do functional tumours secrete?

A

Prolactin (PRL) –> 50%

ACTH (Cushing) –> 10-15%

HGH (Acromegaly/gigantism) –> 10-15%

TSH (TSHome) –> Rare

LH-FSH –> Rare

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36
Q

What are the most common types of pituitary tumours?

A

The most frequent: prolactinoma

2nd: non functional

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37
Q

What are the two kinds of clinical manifestations of pituitary tumours?

A
  1. Local (neurological)
  2. Hormonal (endocrine)
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38
Q

What are the main local manifestations of pituitary tumours (neurological)?

A
  • Céphalées (rare except in acromegaly)
  • Anomalies visuelles:
    • Hémiansopsie bitemporale
      • Perte des champs visuels bitemporaux
        • ​Atteinte du chiasma optique
    • ​​Diplopie (3,4,6)
      • Double vision
        • Atteinte d’un ou des nerfs crâniens par envahissement (sinus caverneux)
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39
Q

What are the two kinds of hormonal manifestations caused by pituitary tumours?

A
  1. Surplus hormonal
  2. Déficit hormonal
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40
Q

What is the difference between a primary/secondary or tertiary illness?

A

Organe cible malade: maladie primaire

Hypophyse/hypothalamus malade: maladie centrale (2/3)

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41
Q

If there’s a surplus/deficit in cortisol what is it called?

A

Surplus: Cushing

Déficit: Insuffisance surrénale

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42
Q

If there’s a surplus/deficit in T4-T3 what is it called?

A

Surplus: hyperT4

Déficit: hypoT4

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43
Q

If there’s a surplus/deficit in LH-FSH, estrogen, testosterone what is it called?

A

Surplus: pas de syndrome

Déficit: hypogonadisme

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44
Q

What happens to LH and FSH during menopause?

A

If the hypothalamus or pituitary gland are normal, your LH-FSH levels SHOULD BE HIGH!

If they’re low, that’s an issue!

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45
Q

If there’s a surplus/deficit in HGH what is it called?

A

Surplus: gigantism (in kids), acromegaly (in adults when they’re done growing)

Déficit: déficit en hormone de croissance, déficit somatotrope

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46
Q

If there’s a surplus/deficit in PRL what is it called?

A

Surplus: hyperprolactinémie

Déficit: pas de terme

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47
Q

What does a surplus of PRL in women cause?

A

Chute d’estrogènes qui cause:

  • Aménorrhée-galactorrhée (écoulement de lait des mammelons)
  • Infertility
  • Osteoporosis
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48
Q

What does a surplus of PRL in men cause?

A

Chute de testostérone:

  • Loss of libido
  • Erectile dysfunction
  • Infertility
  • Osteoporosis
  • Loss of beard/pubic hair
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49
Q

What does a surplus in HGH cause in children/adults?

A

Children: gigantism

Adults: acromegaly

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50
Q

How can a hormonal deficit be caused by a tumour?

A

A tumour that squishes the pituitary gland causing damage and cellular destruction

  • Usually it’s a macroadenoma (> 10 mm otherwise it’s probably too small)
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51
Q

What can a hormonal deficit in TSH, LH-FSH, or ADH cause?

A

TSH –> hypoT4

LH-FSH –> hypogonadism, amenorrhea, delayed puberty

ADH –> insipid diabetes

52
Q

What investigation is typically done to diagnose pituitary tumours?

A

Histoire/examen physique:

  • recherche de sx et signes en lien avec: problèmes neurologiques, surplus/déficit hormonal
  • examen des champs visuels
53
Q

What kind of imagery is done to find pituitary tumours?

A

MRI of pituitary gland

  • MUST SPECIFY PITUITARY otherwise, slices are too big
54
Q

What is the difference between a static and dynamic blood test?

A

Static is a normal blood test but dynamic is done with hormonal suppression/stimulation

55
Q

How to investigate if you’re looking for a hormonal surplus?

A

Suppression test –> try to lower levels

56
Q

How to investigate if you’re looking for a hormonal deficit?

A

Stimulation test –> try to increase levels

57
Q

How to investigate if you think it’s a PRL surplus?

A

Static testing to look at PRL levels and this level orients the dx (more PRL usually means a bigger tumour)

NO DYNAMIC TEST AVAILABLE

58
Q

How to investigate if you think it’s an HGH surplus?

A

Static test:

  • No useful for dx but very useful for followup

Dynamic test:

  • Suppression test (hyperglycémie orale provoquée)
    • Normally a surcharge in sugar should cause a decrease in GH (<0.4 ug/L) but this won’t happen if you have gigantism or acromegaly
59
Q

How to test for a PRL deficit?

A

Static testing only, no stimulation test available

60
Q

How to test for an HGH deficit?

A

Static testing isn’t very useful

Stimulation test with arginine or hypoglycemia which should increase to normal levels when stimulated

61
Q

Static testing 1/2

A
62
Q

Static testing 2/2

A
63
Q

Dynamic testing available:

A
64
Q

What forms of treatment are available for pituitary tumours? (3)

A
  1. Surgery
  2. Medical treatment (Rx)
  3. Radiotherapy: if chx or rx doesn’t work
65
Q

Surgery for pituitary tumour treatment:

A

Should be used first for all tumours EXCEPT for ones that secrete PRL

Resection by the trans-sphenoid route (through nose to brain)

66
Q

Why isnt the first line tx for prolactinomas surgery?

A

They respond VERY well to medication to surgery usually isn’t necessary

67
Q

What are the indications for surgery for a pituitary tumour?

A
  1. If it is functional (secretes except PRL)
  2. If if causes “syndromes chiasmiques” –> perte de champs visuels
  3. Growing +++ in young patients
68
Q

What 3 kinds of Rx are available to treat pituitary tumours?

A
  1. Agonistes de la dopamine
  2. Analogues de la somatostatin
  3. hGH receptor blocker
69
Q

What do dopamine agonists do and how do they work?

A

Dopamine inhibits PRL release

Therefore they’re used to tx prolactinomas

70
Q

How do somatostatin analogues work and what do they do?

A

Somatostatin inhibits HGH release

Used to treat HGH releasing hormone (ex: acromegaly, gigantism)

71
Q

How do GH receptor blockers work and what do they do?

A

Used to treat hormones that produce GH if surgery doesn’t completely work

72
Q

What are the three most common dopamine agonists?

A
  1. Bromocriptine (Parlodel)
  2. Carbergoline (Dostinex)
  3. Quinagoline (Norprolac)
73
Q

What are the three most common somatostatin agonists?

A
  1. Octréotide (Sandostatin)
  2. Lanréotide (Somatuline)
  3. Pasiréotide (Signifor)
74
Q

What is the main hGH receptor blocker called?

A

Pegvisomant (Somavert)

75
Q

How should prolactinomas be treated?

A

First, treat with dopamine agonists

If they don’t work, look into surgical options but this is very rare

76
Q

How are HGH producing tumours treated?

A

First, surgery!

Then somatostatin analogues if levels stay elevated or it comes back and then HGH blocker if necessary

77
Q

How are ACTH and TSH producing tumours treated?

A

Always surgery first!

78
Q

How are LH-FSH secreting tumours treated?

A

Surgery only if they are causing problems (+++ sx) cause usually an increase has no/little clinical manifestations

79
Q

How are non-functional tumours treated (no secretion)?

A

Only treated if it’s growing +++ or has a neurological impact,

otherwise tx w/ Rx not chx and chx if +++ impact of Rx not working

80
Q

What is PRL and what does it do?

A

Polypeptide hormone that comes from lactotropic cells

Role:

  • Mature breasts during pregnancy
  • Production of breast milk and oxytocin is necessary for It to be secreted
  • It is physiologically increased during pregnancy and when breast feeding
81
Q

How are PRL levels controlled?

A

Under hypothalamic control

Inhibited by dopamine

  • passes from the hypothalamus to pituitary through the venous portal system (through the tige)

BUT

Levels can be increased by hypoT4 as an increase in TRH can stimulate PRL

82
Q

What is the “effet de tige”?

A

An increase in PRL caused by a tumour (usually macroadenoma) compressing the tige as there is no longer any dopamine inhibiting PRL release

  • LARGE tumour with relatively low (still increased) PRL levels
83
Q

Effet de tige vs prolactinoma:

A

Effet de tige:

  • PRL < 100ug/L: usually quite a big tumour found on MRI

Prolactinoma:

  • PRL >> 100ug/L but can be lower if tumour is small
  • PRL levels and size of tumour are correlated
84
Q

What happens to PRL levels in primary hypothyroidism?

A

The pituitary is normal… there’s an inherent problem with the thyroid

  • Increased TRH levels to try to stimulate thyroid will cause a small increase in PRL
    • when the hypothyroidism is treated… PRL levels will return to normal!
85
Q

What are the most common clinical manifestations of hyperprolactinemia?

A

Too much PRL –> hypogonadism so most sx are associated with that:

  • Aménorrhée
  • Gallactorhée (rare in men, more common in women who have been pregnant/have breastfed before)
  • Gynécomastie
  • Ostéoporose
  • Infertilité
  • Perte de libido
  • Problème érectile
86
Q

What are 5 physiological causes of hyperprolactinemia?

A
  1. Grossese
  2. Allaitement
  3. Sommeil
  4. Nourriture
  5. Stress
87
Q

What are 7 “pathological causes” of hyperprolactinemia?

A
  1. Prolactinoma
  2. Compression du tige hypophysaire
  3. Médication
  4. HypoT4 primaire
  5. Lésion thoracique/stimulation locale (brain associates this with suckling)
  6. Insuffisance rénale chronique (PRL can’t be eliminated)
  7. Idiopathique
88
Q

What kinds of Rx can cause hyperprolactinemia?

A
  1. Antipsychotics
  2. Antidepressants
  3. Morphine

BUT levels usually still < 100 ug/L

89
Q

What is HGH/GH and what does it do and how does it work?

A

Polypeptide hormone secreted by somatotropic cells in the pituitary

Typically low amount in circulation:

  • Pulsatile secretion
  • Peak with: meals, exercise, sleep
  • Max levels during puberty and from there keep decreasing
90
Q

What are the main roles of GH?

A
  • Growth (dim = nainisme, inc = gigantism/acromegaly)
  • Protein metabolism
  • Lipid metabolism
  • Glucose metabolism (important cause acromegaly can cause Db due to a decrease of glucose uptake and increase of gluconeogenesis –> tx acromegaly = Db goes away)
91
Q

How does GH work?

A

Indirect action via somatomedins in the liver

  • small proteins produced by liver when stimulated by GH
  • the most common is somatomedin C (IGF-1)
92
Q

How is GH controlled?

A

Stimulated by GHRH (hypothalamus –> pituitary)

Inhibited by somatostatin

also stimulated by:

  • hypoglycemia/jeûne
  • stress
  • sleep
  • meals rich in arginine

also inhibited by:

  • hyperglycemia
  • lack of emotional support/love
  • obesity
93
Q

How to investigate hyperGH?

A

Static: IGF-1 measure

Dynamic: hyperglycémie orale provoquée

94
Q

How to investigate hypoGH?

A

Static: measure IGF-1 levels (not that useful)

Dynamic: stimulation testing

  • Test à l’arginine: better test
  • Stress à l’insuline (induce hypoglycemia)
95
Q

Which three pathologies are associated with altered GH levels?

A

Deficit: growth retardation

Surplus: gigantism and acromegaly

96
Q

What usually causes acromegaly?

A

Usually cause by a pituitary tumour (usually a macroadenoma) but dx is usually quite late in disease progression

97
Q

What are the most common clinical manifestations of acromegaly?

A

Local manifestations (due to compression):

  • Headaches
  • Visual problems (diplopia, hémianospie bitemporale)

Hormonal deficit (autres axes) due to compression:

  • hypofonction hypophysaire (déficit en LH-FSH, TSH, et ACTH)

Surplus in GH:

  • Hypertrophy of extremities (hands, feet, jaw (usually only bottom), nose, ears, larynx (deepen voice)
  • Arthrosis
  • Soft tissues (hypertrophy of skin and sub-cue tissues, hyperhidrosis, intestinal polyps)
  • Visceromegaly (ex: megacolon (non-toxic), cardiomyopathy/valvulopathy/arrhythmias)
  • Metabolic effects (diabetes/glucose intolerance)
98
Q

How to investigate for acromegaly? (4 main things)

A

Static testing:

  • IGF-1 levels
  • HGH levels –> cannot be used to establish dx

Dynamic testing: suppression

  • hyperglycémie orale provoquée (normally should cause HGH < 0.4ug/L)

Imagery: pituitary MRI

Finally, evaluation of the other axes to look for hormonal deficits caused by the tumour (compression)

99
Q

How to treat an adenoma that secretes HGH?

A
  1. Trans-sphenoid resection
  2. Medical tx if surplus still present after chx
  • Somatostatin analogues
  • Dopamine agonists
  • HGH receptor blockers
  1. Radiotherapy but really only used in RARE cases
100
Q

How to treat returning/persistent acromegaly?

A

Tx with somatostatin agonist

  • somatostatin lowers levels but has a quite short half-life
  • therefore agonists with a longer half-life are used to help lower levels for longer periods of time
101
Q

What is an “insuffisance hypophysaire” causing a deficit of all hormones called?

A

Panhypopituitarism

102
Q

What can cause pituitary insufficiency?

A

Tumours: adenomas, craniopharyngiomas

Congenital reasons: natural deficit in 1+ hormones

Vascular: infarctus de l’hypophyse, Syndrome de Sheehan

Rx: immunotherapies used for cancer tx

  • (ex: Ipilimumab and Nivolumab)

Granulomatous causes: tuberculosis, sarcoidosis, histiocytosis

Mechanical damage: chx, radiotx, trauma

103
Q

What is Sheehan Syndrome?

A

a condition that affects women who lose a life-threatening amount of blood in childbirth or who have severe low blood pressure during or after childbirth, which can deprive the body of oxygen.

  • This lack of oxygen that causes damage to the pituitary gland is known as Sheehan’s syndrome
    • This Is permanent, cannot recover from this and will cause need for long-term hormonal replacement therapy
104
Q

What changes the clinical presentation of pituitary insufficiency?

A

Déficit hypophysaire

Installation rapide vs lente (années)

Durant l’enfance vs adulte

105
Q

What are the clinical manifestations of a pituitary insufficiency that causes a deficit in LH-TSH?

A

Hypogonadism:

  • Delayed puberty
  • Aménorrhée
  • Infertilité
  • Perte de libido
  • Dysfonction érectile
  • Perte de poils-barbe
  • Dim. masse musculaire
  • Ostéoporose
106
Q

What are the clinical manifestations of a pituitary insufficiency that causes a deficit in GH?

A
  • Delayed growth
  • Loss of muscle mass
  • Increased fat %
  • Osteoporosis
107
Q

What are the clinical manifestations of a pituitary insufficiency that causes a deficit in PRL?

A

Absence of breastmilk production after birth

108
Q

What are the clinical manifestations of a pituitary insufficiency that causes a deficit in TSH?

A

HypoT4:

  • Fatigue
  • Chills
  • Constipation
  • Dry skin
  • Depression
109
Q

What are the clinical manifestations of a pituitary insufficiency that causes a deficit in ACTH?

A

“Déficience surrénalienne”:

  • Fatigue
  • Weight loss
  • Anorexia
  • N/V
  • Abdominal pain
  • Arthralgia/myalgia
  • Orthostatisme: ensemble de troubles observés chez certains sujets dans la station debout
110
Q

How do you investigate suspected pituitary insuffiency?

A

MRI of pituitary

Biochemical testing:

  • Static
  • Dynamic: stimulation testing depending on hormones
    • HGH: arginine/insulin
    • Cortisol: insulin stress test (not ideal for pituitary… used more for primary adrenal insufficiency)
111
Q

How to treat pituitary insufficiency?

A

Hormonal replacement therapy depending on hormones missing:

  • ACTH: hydrocortisone (Cortef)
  • TSH: Levothyroxine sodium (Synthroid)
  • LH-FSH:
    • Women: estrogen + progesterone if premenopausal
    • Men: testosterone
  • HGH: take HGH
  • PRL: no replacement therapy available
112
Q

What is oxytocin?

A

Hormone produced by the hypothalamus stored in the neurohypophysis/posterior pituitary

Stimulates: (+ feedback)

  • Contraction of uterus while giving birth
  • Expulsion of breast milk when feeding

No pathologies associated with it

113
Q

What is vasopressin?

A

Another name for ADH

Hormone used to maintain volume of circulating extracellular fluid/seric osmolality

Stocked in the posterior pituitary, but synthesized in the hypothalamus

114
Q

What are the three main roles of ADH?

A
  1. Reabsoption of water in collector tubules
  2. Maintain VCE
  3. Maintain seric osmolality
115
Q

Which pathologies are associated with a deficit and surplus of ADH?

A

Deficit: DI (insipid diabetes)

Surplus: SIADH (syndrome inapproprié de sécrétion d’ADH)

116
Q

What are the 6 most common causes of SIADH?

A
  1. Rx
  2. HypoT4
  3. Insuffisance surrénalienne
  4. Pathologie cérébrale (tumeur, ACV, infection, hémorragie…)
  5. Pathologie pulmonaire (tumeur, pneumonie …)
  6. Chx majeure
117
Q

How is SIADH dx?

A

Hyponatremia (surplus of water not loss of Na)

Osm sérique diminuée

Osm urinaire > 100 mOsm/kg

  • Osm urinaire > sérique

Make sure to exclude:

  • HypoT4 –> tx with L-thyroxine
  • Insuff. surrénalienne –> tx with hydrocortisone
118
Q

How to treat SIADH?

A

You have to treat the cause, not the symptom!

You can also use water restriction to tx (800-1500ml of liquid/24hrs)

119
Q

What is diabetes insipidus?

A

Deficit in ADH causing +++ water loss because the kidneys cannot concentrate the urine

120
Q

What are the two “forms” of diabetes insipidus?

A
  1. Central: deficit in ADH
  2. Nephrogenic: kidneys resistant to ADH
121
Q

What are the main causes of central diabetes insipidus?

A
  1. Pituitary:
    • post-chx
    • metastasis
    • cranial trauma
  2. Hypothalamus:
    • tumour
  3. Tige hypophysaire:
    • trauma
    • tumour
    • chx
  4. Idiopathic:
122
Q

What are the main causes of nephrogenic diabetes insipidus? (4)

A
  • Congenital/familial
  • Rx (lithium +++)
  • Hypercalcemia
  • Pregnancy
123
Q

What are the most common clinical manifestations of diabetes insipidus?

A

Polyuria/nycturia

Polydipsia

Dehydration

124
Q

What tests are used to investigate diabetes insipidus?

A

Static:

  • hypernatremia
  • seric osm increased (due to dim. water reabsorption)
  • urinary osm decreased (+++ water)

Dynamic:

  • dehydration test if partial diabetes insipidus
125
Q

How to treat diabetes insipidus?

A

Drink when you’re thirsty (always keep water next to patient)

DDAVP = desmopressin

  • man-made form of ADH and is used to replace a low level of ADH
  • give at nighttime before bed… but can also be given during the day
126
Q

What to do if you have a pituitary insufficiency with low thyroid levels AND low cortisol levels?

A

ALWAYS TREAT CORTISOL FIRST! C before T

Treating the thyroid first can cause an increase in cortisol metabolism and lower levels even more which is VERY VERY dangerous

  • can cause choc surrénalien

MD1 endocrinologie (6 decks)

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