W5 Growth hormone disorders (GSP) Flashcards

1
Q

Anterior lobe of pituitary gland is ‘more important’ as it controls production of..? (4)

Secretion of..?

A
  • Controls activity of other endocrine glands
  • Ovulation and pregnancy
  • Sperm production
  • Growth
  • Thyrotropin / Thyroid Stimulating Hormone (TSH)
  • Adrenocorticotropic hormones (ACTH)
  • Luteinising Hormone (LH)
  • Follicle Stimulating hormone (FSH)
  • Growth hormone (GH)
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2
Q

Growth Hormone (GH) / Somatotropin:
Function?

A
  • From somatotroph cells of anterior pituitary
  • Pulsatile release
    -Released throughout the day
    -Peaks in 1st hour of sleep
    -Diurnal variation → blood test for GH not reliable

Function (anabolic & metabolic):
* Postnatal longitudinal growth
* Affects bone growth
* Affects metabolism of glucose, protein, lipids, minerals

GH-IGF axis
* GH acts on liver → release somatomedin/ insulin-like growth factor (IGF)
* Primarily IGF-1

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3
Q

Growth hormone disorders:
2 types?

A
  • Deficiency – restricted growth (dwarfism)
  • Excess – gigantism, acromegaly
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4
Q

Restricted growth (dwarfism)
2 types?

A
  1. Proportionate short stature (PSS)
    * general lack of growth in the body, arms, legs
    * e.g. primordial dwarfism
  2. Disproportionate short stature (DSS)
    * arms and legs are particularly short due to
    poor bone growth
    * Most common type: achondroplasia
    * Genetic mutation : shorter long-bones →
    ‘disproportionate’ limb-to-torso lengths
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5
Q

Tests for adult GH deficiency
* Insulin tolerance test (ITT)

A
  • “gold standard” test.
  • IV insulin given → induce hypoglycaemia → stimulates pituitary →
    release GH and ACTH (GH stimulates liver to release glucose)
  • Requires controlled environment as hypoglycaemia may be life-threatening
    -blood samples taken regularly (e.g. 0, 15, 30, 60, 90 mins) to check glucose and GH levels
  • severe GH deficiency : peak GH is <9 mU/litre (3 ng/ml) in response to insulin-induced hypoglycaemia of <2.2 mmol/L
    (fasting blood glucose is 5-7 mmol/L)
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6
Q

Other Tests for adult GH deficiency? (3)
Which is done if ITT is contraindicated?

A

=Glucagon stimulation test
* SC/IM glucagon given, and serum GH measured.
* Unknown mechanism, possibly independent of
glucose/insulin effects.
* GHRH-arginine test
* IV GHRH then IV arginine, and serum GH measured.
* GHRH stimulates pituitary, arginine supresses somatostatin
* Growth hormone releasing peptide (GHRP-2) test
* Stimulate GH release, via different receptor to GHRH
Tests for adult GH deficiency (cont’d)

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7
Q

Somatropin in children

A
  • Look at both
    -born with SGA
    -catch-up growth at 4 years old
  • Dose is tailored to the individual
    -23-50 mcg/kg, or 0.7-1.4 mg/m2
    -6-7 times/week
    -Subcutaneous injection
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8
Q

Somatropin in adults

A
  • Dose is tailored to the individual
  • subcutaneous injection.
  • initial dose: 0.2–0.3 mg (0.6–0.9 IU) daily.
  • adjusted monthly based on serum IGF-1 and adverse effects, until
    reach maintenance dose.
  • median maintenance dose is 0.4 mg (1.2 IU) daily.
  • GH requirements may decrease with age
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9
Q

Complications of GH deficiency – how GH therapy helps? (3)

A

CVD / Cerebrovascular disease
* ↑ intima-media thickness of carotid arteries – improved
* ↓ left ventricular mass, ↓ left ventricular function, ↓ ejection fraction –improved
* ↑ LDL-C, ↑ triglycerides, ↓ HDL-C – ↓ LDL-C, ↑ HDL-C
* ↑ inflammatory markers (e.g. CRP, proinflammatory cytokines, adipokines) improved
* ↑ coronary calcium scores

Osteopenia / Osteoporosis
* ↓ bone mineral density → ↑ fractures – ↑ BMD, unchanged fracture rate

Body composition
* ↑ fat mass (mainly visceral fat) – ↓ fat
* ↓ muscle mass – ↑ muscle mass, possibly ↑ strength, exercise capacity

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10
Q

Common side effects of somatropin (for info)

A
  • Carpal tunnel syndrome
  • Fluid retention/ swelling
  • Headache
  • Joint pain/ myalgia
  • Lipoatrophy – advice: rotate subcutaneous injection sites
  • Paraesthesia/ pins & needles
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11
Q

Other treatment considerations

A
  • If on testosterone-replacement therapy: lower GH dose
  • If on oral oestrogen therapy: higher GH dose
  • Dual-energy X-ray absorptiometry (DXA) to check bone mineral density
    -Brittle bones due to disease itself, e.g. Turner syndrome
    -Working out ‘bone age’ for restricted growth in children
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12
Q

Leg lengthening surgery

A
  • Procedure
  • bone is broken and fixed to a frame/rod.
  • leg is stretched (distraction) via external
    mechanism ~1mm/day.
  • new bone forms in between the two broken
    ends.
  • Extended length
  • Femur < 8cm (3.1in)
  • Tibia < 5cm (2in)

Physical rehabilitation
* restore mobility to the joints
* increase strength of the muscles

Complications
* Pain due to surgery and deliberate fracture
* Poor bone formation, lengthening at an
inappropriate rate
* Nerve damage
* Infection on bone and/or surrounding soft
tissue
* Blood clots

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13
Q

Excess of Growth Hormone

A
  • Excess GH → excessive action of
    IGF-1
  • Gigantism
    -Occurs when epiphyseal growth plates
    still open in childhood (pre-puberty).
  • Acromegaly
    -Occurs when epiphyseal growth plates
    have fused/closed.

Epiphyseal plate ≈ cartilage at ends of long bones
Oestrogen & testosterone during puberty initiates plate closure: cartilage → bone

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14
Q

Acromegaly

A
  • Affects slightly more women than men
  • Usually due to pituitary adenoma (non-malignant
    tumour) → excess GH release
  • Mechanical pressure by growing tumour on nearby
    nerves
    -visual disturbance
    -headache
  • Late onset → high morbidity &
    mortality
    -associated CV, cerebrovascular,
    respiratory disorder
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15
Q

Gigantism

A
  • More ‘dramatic’ than acromegaly
  • Affects more men than women (~78%)
    -Men diagnosed later (~3.7 years delay in
    diagnosis)
    -X-linked acrogigantism (X-LAG; duplication of the GPR101 gene on X chromosome) → early onset of rapid growth
    -Female puberty is earlier: rapid growth in
    females ~11yo, in males ~13 yo.
  • Aryl hydrocarbon receptor interacting
    protein (AIP) gene mutations or deletions
    → predispose to pituitary adenoma
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16
Q

Tests for GH excess

A
  • MRI/CT of brain
    -check for tumours
    -monitor post-treatment
  • Glucose tolerance test / Glucose challenge test
    -Oral glucose 75-100g given → induce hyperglycaemia → inhibits GH release from pituitary
    -Blood samples taken regularly (e.g. 0, 30, 60, 90, 120 mins) to check GH levels
    -↑ GH (>10 ng/mL) + clinical picture = diagnosis of acromegaly
  • Random blood sampling for GH level = useless
    -Pulsatile/variation in GH secretion
    -Short half-life
  • IGF-1 and IGF binding protein 3 (IGFBP3)
    -Possible as a tool for diagnosis, or to monitor progress of treatment
    -Levels affected by age, puberty, starvation, obesity, diabetes mellitus, pregnancy.
17
Q

Management of GH excess:

A
  • Goal: Normalising GH and IGF-1 levels
  • Transsphenoidal surgery
    -First line treatment
    -Remove pituitary adenoma
  • Pharmacologic treatment
    1. Somatostatin analogues
  • Octreotide, lanreotide, pasireotide
  • Subcutaneous injection
  • May shrink tumours
    2. Dopamine receptor agonists
  • Bromocriptine, cabergoline
  • Usually not as standalone medical treatment
    3. GH-receptor antagonists
  • Pegvisomant
  • Recombinant hGH analogue → binds to GH receptors →
    GH action blocked → ↓ IGF-
  • Radiation
  • Not first choice; when surgery failed/contraindicated
  • Slow results: years to see normalisation of GH/IGF-1 levels
  • Hormone replacement therapy
  • If hypopituitarism post treatment → replace other pituitary hormones
  • Sex hormone replacement as sex hormones stimulate epiphyses closure
  • ↓ sex hormones → delayed closing of epiphyses → ↑ height growth
  • Long term monitoring
  • GH/IGF-1 levels
  • Comorbidities, e.g. heart disease, diabetes, sleep apnoea, possible malignancy
18
Q
A