Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

ERS > ERS13 The Treatment Of Pituitary Disorder > Flashcards

ERS13 The Treatment Of Pituitary Disorder Flashcards

1
Q

Hypothalamic control on Pituitary

A
  1. Releasing / Inhibiting factors

2. Tuberoinfundibular dopaminergic pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Hypothalamic hormone use

A
  1. Diagnostic tests

2. Stimulate pituitary secretion (if hypopituitarism is due to Hypothalamic defect)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Long + Short negative feedback pathway

A

Long: Hormones from peripheral gland —> Hypothalamus / Anterior pituitary
Short: Anterior pituitary —> Hypothalamus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Hypopituitarism

A

Causes:

  1. Ischemia
  2. Radiation
  3. Inflammation
  4. Non-functioning neoplasm of pituitary gland (unable to produce hormone but compressive —> ↓ blood flow to pituitary)

One / more hormones affected

More common:

  • ↓ GH
  • ↓ Gonadotropin
  • ↓ ACTH

Very rare:

  • ↓ Thyrotropin
  • ↓ Prolactin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Effects of growth hormone

A

GH (act on hepatocytes):
- ↑ Somatomedin (IGF-1) production by liver

Somatomedins (from liver):

  • ↑ SO4 uptake into cartilage (chondroitin sulphate)
  • ↑ Bone growth by ↑ Thymidine incorporation into DNA + ↑ Uridine incorporation into RNA

GH + Somatomedins (both act on peripheral tissue):

  • ***↑ Protein synthesis + uptake of a.a. into cells
  • Initially: Insulin-like effect —> ↑ glucose uptake + ↓ lipolysis
  • ***After a few hours: Insulin antagonistic effect —> ↓ glucose uptake + ↑ lipolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Growth hormone deficiency (Hypopituitarism)

A

Pituitary dwarfism

Treatment: ***Somatropin (replacement therapy: synthetic growth hormone)

SE:
1. **Hypothyroidism (GH ↑ conversion of T4 to T3)
2. **Impaired glucose tolerance (∵ antagonise Insulin effect)
3. ***Edema
—> Peripheral edema (activation of Na channel in collecting duct —> Na retention)
—> Papilloedema —> Visual changes
—> Intracranial hypertension —> Headache

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Effects of Gonadotropins

A

Female:
FSH:
- **Development of Graffian follicles into Ovum
- Stimulate Graffian follicles to secrete **Estrogen
—> **Proliferative phase of endometrium
—> **Secondary sexual characteristics

LH:
- **Ovulation
- Remaining follicle: Corpus luteum —> secrete **Progesterone
—> ***Secretory phase of endometrium (wall develop blood vessels, glands) for implantation

Male:
FSH:
- ↑ Spermatogenesis

LH:
- Stimulate testes to secrete **Testosterone
—> **Secondary sexual characteristics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Gonadotropin deficiency (Hypopituitarism)

A

Women:

  • Amenorrhea
  • Regression of secondary sexual characteristics
  • Infertility

Men:

  • Impotence
  • Testicular atrophy
  • Regression of secondary sexual characteristics
  • ↓ Spermatogenesis —> Infertility
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Treatment of Gonadotropin deficiency

A

Replacement therapy

FSH:

  1. ***Follitropin α/β (recombinant FSH)
  2. Human menopausal gonadotropin (HMG) (contain both LH and FSH, from urine of postmenopausal women)

LH:

  1. ***Lutropin α (recombinant LH)
  2. Human chorionic gonadotropin (HCG) (structurally different from LH but same action, secreted by placenta, obtained from urine of pregnant women)
  3. Choriogonadotropin α (recombinant HCG)

FSH (Follitropin α/β, HMG) must be used with LH (Lutropin α, HCG, Choriogonadotropin α)
—> permit ovulation + implantation in women
—> permit testosterone production in men

SE:
FSH:
1. **Ovarian hyperstimulation syndrome
- Ovarian enlargement —> burst in blood vessels —> 2. **Hemoperitoneum
- Ascites (water leak out in blood vessels)
- Hydrothorax —> difficult to breathe
- Hypovolemia —> electrolyte imbalance + platelet closer together —> 3. **Arterial thromboembolism
4. **Gynaecomastia (FSH, LH stimulate Aromatase (skin, fat, muscle) —> convert Testosterone to Estrogen —> breast enlargement)
5. Multiple birth (~20%, ∵ >1 mature ovum released)
6. Fever

LH:

  1. Headache
  2. Depression
  3. Edema
  4. Gynaecomastia
  5. ***Precocious puberty (∵ ↑ Testosterone)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

***Effects of ACTH

A
  • Stimulates adrenal cortex
  • ↑ Corticosteroids (Cortisol + Aldosterone (minor)) synthesis and release

(Majority of Aldosterone secreted by RAAS system)

**Cortisol (Glucocorticoid)
- ↓ **Glucose uptake and utilisation
- ↑ Gluconeogenesis in liver
—> ↑ blood glucose level —> Insulin secretion
- ↑ Liver glycogen stores (insulin effect ∵ triggered by ↑ blood glucose)
- ↑ **Protein catabolism
- ↑ **Lipolysis
- Maintenance of CVS function by ***potentiation of E + NE effects

Aldosterone (Mineralocorticoid)
- ↑ Na reabsorption + ↑ K / H secretion in Distal tubule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

ACTH deficiency (Hypopituitarism)

A

Hypoadrenalism (low Cortisol):

  • Hypoglycaemia
  • Hypotension (∵ ↓ effects of E/NE —> ↓ CO)
  • Tiredness, Dizziness (∵ ↓ effects of E/NE —> ↓ CO)
  • Intolerance to stress / infection (∵ ↓ effects of E/NE —> ↓ CO —> ↓ energy to overcome stress)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Treatment of ACTH deficiency

A

ACTH deficiency (Hypopituitarism):
- patient can still produce Aldosterone (via RAAS system)
- only Cortisol is affected
—> Use Corticosteroid with ONLY Glucocorticoid effect is good enough

Addison’s disease (Adrenal insufficiency):
- BOTH Aldosterone + Cortisol affected
—> Use Corticosteroid with BOTH Glucocorticoid + Mineralocorticoid effect
—> e.g. Hydrocortisone + Fludrocortisone (high mineralocorticoid activity)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Choice of Corticosteroid

A

ALL Corticosteroid have 3 effects:

  1. Glucocorticoid effect
  2. Mineralocorticoid effect (no need to consider for ACTH replacement therapy)
  3. Anti-inflammatory / Immunosuppressive effect

ACTH replacement:

  1. Hydrocortisone (synthetic Cortisol)
    - adequate Glucocorticoid effect with minimal Anti-inflammatory / Immunosuppressive effects
  2. Cortisone
    - weak Glucocorticoid effect initially —> converted to Hydrocortisone in body

Prednisolone, Methylprednisolone, Triamcinolone, Dexamethasone, Betamethasone, Fludrocortisone (also high Mineralocorticoid activity):
- high Glucocorticoid effect BUT also high Anti-inflammatory / Immunosuppressive effects
—> unwanted side effects (↑ infection risk)

MOA:
Steroid cross cell membrane
—> bind to Intracellular receptor
—> Steroid-receptor complexes in nucleus then bind to Chromatin
—> Steroid-receptor-chromatin complex stimulate mRNA + protein production
—> produce characteristics action of hormone (effects see Effects of ACTH)

SE: ***Iatrogenic Cushing’s syndrome
1. Muscle wasting
2. Redistribution of fat
—> Moon face
—> Buffalo hump
—> ↑ Abdominal fat
—> Thin arm and legs
—> Thinning of skin
3. Hyperglycaemia
4. Hypertension (potentiate E, NE effects)
5. Growth suppression in children (inhibit effects of GH)
6. Osteoporosis (↓ Ca absorption + ↑ Ca excretion + inhibition of vitamin D activity in osteoblasts)
7. Susceptibility to infection (high dose)
8. Peptic ulcer (∵ infection)
9. Psychological disturbances
10. Cataracts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Hyperpituitarism

A

Causes:

  1. Pituitary adenoma (actively producing hormone)
  2. Drugs (e.g. Haloperidol —> D2 blocker —> ↓ inhibitory effect on pituitary)

One / more hormones affected

More common:

  • ↑ GH
  • ↑ Prolactin
  • ↑ ACTH

Very rare:

  • ↑ Thyrotropin
  • ↑ Gonadotropin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Effects of Prolactin

A
  • Lactation
  • Inhibitory effects on Hypothalamus (↓ GnRH secretion)
    —> ↓ Gonadotropin
    —> lack of ovulation
    —> protect premature pregnancy in lactating women
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Treatment of Prolactin deficiency

A

No available preparation

17
Q

Hypersecretion of Prolactin (Hyperpituitarism)

A

Hyperprolactinaemia

  • Galactorrhoea
  • Hypogonadism (∵ ↓ GnRH)
  • Amenorrhea (∵ ↓ GnRH)

Treatment:
Dopamine agonists (cannot give Dopamine ∵ cannot pass through BBB) (also used in Acromegaly, Parkinson’s)
- **Bromocriptine
- **Cabergoline (long t1/2 + higher selectivity for dopamine receptor)

MOA:
1. Stimulate D2 receptors on Anterior pituitary
—> Inhibit Anterior pituitary
—> ↓ Prolactin
2. Cause significant reduction in size of Prolactin-secreting adenomas

SE:

  • ***Postural hypotension (∵ Dopamine cause vasodilation)
  • ***N+V (∵ stimulate Dopamine receptor in CTZ —> induce vomiting)
  • ***Constipation (∵ stimulate Dopamine receptor in GI tract —> ↓ peristalsis)
  • Dizziness
18
Q

Hypersecretion of Growth Hormone (Hyperpituitarism)

A
  1. Acromegaly (adult after puberty)
    - enlargement of facial structure, hands, feet
    - osteoarthritic vertebral changes (swollen joints)
  2. Gigantism (childhood / puberty before closure of epiphyses)
    - very tall
    - exaggerated skeletal growth
    - enlargement of facial structure, hands, feet
19
Q

Treatment of Acromegaly / Gigantism

A
  1. Octreotide
    - longer acting analogue of Somatostatin with less hyperglycaemic effect (cannot used Somatostatin ∵ quickly metabolised)
    - also ↓ tumour size in Pituitary adenoma
  2. Lanreotide
    - even longer acting analogue of Somatostatin
    - also ↓ tumour size in Pituitary adenoma

MOA:

  • ***Somatostatin analogue: Inhibit GH release from Anterior pituitary
  • Reduce tumour size in minority of patients

SE:

  • GI disturbance: N+V, abdominal cramps, flatulence, steatorrhea (∵ Octreotide/Lanreotide inhibit secretion of GI peptide e.g. gastrin, secretin, motilin etc. —> important for digestion + GI movement)
  • Gallstones (∵ inhibition of gall bladder motility —> precipitation of bile salt)
  • **Impaired glucose tolerance (∵ **Somatostatin inhibit insulin secretion from pancreas)
  1. Pegvisomant
    - GH receptor antagonists

MOA:
Block GH receptor
—> Interfere with GH signal transduction + Somatomedins production from liver

SE:

  • ↑ liver enzymes (AST, ALT) —> Hepatotoxicity? Hepatitis? (unknown long term effect)
  • nausea + diarrhoea
  1. Dopamine agonists
    - Bromocriptine, Cabergoline
    - normal situation: D2 agonists stimulate GH secretion
    - Acromegaly: D2 agonist cause ***paradoxical ↓ GH secretion (unknown mechanism)
    - more effective in patients with pituitary tumours that secrete both Prolactin + GH
20
Q

Hypersecretion of ACTH (Hyperpituitarism)

A

Cushing’s disease (Too much Cortisol + Aldosterone)

Treatment:

  1. Metyrapone
    - inhibit 11-β-hydroxylase (required for synthesis of Corticosteroid)
  2. Trilostane
    - Inhibit 3-β-dehydrogenase (required for synthesis of Corticosteroid)

SE:

  1. Hypotension (∵ ↓ Cortisol —> ↓ effects of E/NE —> ↓ CO)
  2. N+V
  3. Headache, dizziness
  4. Rash
21
Q

Effects of ADH

A

↑ Plasma osmolarity (e.g. dehydration) / ↓ Circulating blood volume (e.g. haemorrhage) / ↓ BP (e.g. heart failure)
—> Stimulate Posterior pituitary
—> secrete ADH
—> act on Distal tubule + Collecting duct
—> V2R (+ V1R —> vascular smooth muscle —> **Vasoconstriction)
—> ↑ cAMP
—> **AQP2 trafficking + insertion on **apical membrane (AQP3, 4 constitutively expressed)
—> **↑ water reabsorption

22
Q

Impaired secretion of ADH

A 
Diabetes insipidus (tasteless urine)
- continuous production of large amount of hypotonic urine

Treatment:
Replacement therapy:
1. Vasopressin (synthetic, identical to ADH)
2. **Desmopressin
- analog of vasopressin
- longer acting
- less vasopressor effect (∵ more **V2 selective)

SE:
1. **Fluid retention
2. **Dilutional hyponatraemia
3. Headache
4. Nausea
5. Allergy
6. ***Spasm of coronary artery —> Angina (Vasopressin: stimulate V1R —> vasoconstriction)
7. Abdominal + Uterine cramps (Vasopressin: stimulate V1R)
—> Desmopressin less selective for V1R —> less side effects

23
Q

Summary

A

Treatment of hypopituitarism

  1. Pituitary dwarfism: Somatropin
  2. Gonadotropin deficiency: Gonadotropin
    - FSH: Follitropin α/β, HMG
    - LH: Lutropin α, HCG, Choriogonadotropin α
  3. ACTH deficiency: Corticosteroid (Hydrocortisone, Cortisone)

Treatment of hyperpituitarism

  1. Hyperprolactinaemia: Dopamine agonists (Bromocriptine, Cabergoline)
  2. Acromegaly, Gigantism: Octreotide, Lanreotide, Pegvisomant, Dopamine agonists
  3. Cushing’s disease: Trilostane, Metyrapone

Treatment of posterior pituitary disorder
1. Diabetes insipidus: ADH (Vasopressin, Desmopressin)

ERS (41 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions