Lecture 18; Post Natal Growth 3 Flashcards
What is abnormal body proportion defined by;
%ile-height vs %-sitting height or arm span
What are the causes of disproportionate growth?
- Skeletal dysplasia (i.e. Abnormal growth plates, achondroplasia / hypochondroplasia
- Syndromes (Turner’s (45 XO, and variations)
- Precocious puberty (breast development <8 years in girls and testicular development <9 years in boys — premature fusion of epiphyses).
- Hypothyroidism
What can cause iodine insufficiency?
Overstimulation of the thyroid to produce T3,4
Autoimmune diseases
Describe T3,4 structure differences;
T4 = two tyrosine molecules each with 2 iodine molecules (x2 DIT)
T3 = two tyrosine molecules, one with 2 I and other with 1 I (1 DIT and 1x MIT)
What converts T4 to T3 in tissues?
Iodinase in target tissues
T3 is 5-8 fold more active that T4
What do the parafollicular cells in the thyroid make?
Calcitonin
Describe the synthesis of thyroglobulin;
Follicular cells;
- I/Na symporter down Conc. grad
- Diffuses into colloid and is oxidised and attached to rings of tyrosine on thyroglobulin (stabilising protein) (thyroid peroxidase does this)
- Two iodised tyrosine rings are added together forming T3,T4
- Endocytosis of Thyroglobulin containing T3,T4, into follicular cells. T3,T4 then can diffuse into the blood
- Thyroglobulin is recycled
How does TSH regulated T3,T4 production?
Promotes Iodine transport
Promotes endocytosis
What blocks iodine oxidation?
PTU (drug)
- Doesnt stop I uptake or endocytosis , therefore takes long time to start acting and finish (good control)
Describe T3,T4 loop;
Hyp
- TRH = +ive
- Dopamine or somatostatin = -ve
AP
- TSH (+ive)
Thyroid gland
- T3, T4 (-ive at AP and Hyp levels)
What is the problem?
FT4 6 pmol/L (N 11-20) TSH 65 (0.4-4.0iu/L)
Feedback dysinhibition!
Primary hypothyroidism (i.e. reduced activity of thyroid gland), e.g. autoimmune or I deficiency
What is the problem?
FT4 7.5 pmol/L TSH 3.5 iu/L
Central (secondary hypothyroidism) TSH “inappropriately normal”
Or… Sick euthyroid: major illness, starvation T4 converted to rT3\ Evolves over time
Where is the problem?
FT4 38 pmol/L (11-20) TSH < 0.04 (0.04-4.0)
Primary hyperthyroidism (i.e. excess activity of thyroid gland)
e.g. autoimmune disease of thyroid
Thyroid gland usually enlarged, depending on aetiology/timing
What enhances iodine uptake?
- TSH
- iodine deficiency (⇑ MIT:DIT ratios)
- TSH receptor antibodies (most stimulate!)
- autoregulation
What is iodine inhibited by?
- I- excess (Wolff-Chaikoff effect) e.g. surgery administration of excess iodine buffer needed as suddenly excess T4 production
- cardiac glycosides (digoxin)
- Oubain (inhibit Na+-K+ ATPase), and perchlorate (PClO4 -, competes with I- transport proteins).
In blood what is T4 bound to?
Approximately 99.98% of T4 is bound to 3 serum proteins: Thyroid binding globulin (TBG) ~75%; Thyroid binding prealbumin (TBPA or transthyretin) 15-20%; albumin ~5-10%
How much T4 is free?
Only ~0.02% of the total T4 in blood is unbound or free
How much T3 is free and whats its half life?
Only ~0.4% of total T3 in blood is free Half life?
T1/2 ~ 7 days
Are there variants of T3/
yes
T4 can form
T3 (step up)
or
rT3 (step down)
What do thyroid hormones do?
Regulate Long-term physiological homeostasis
Principal targets are: skeletal & cardiac muscle, liver, gut, and kidney
What specifically do thyroid hormones do?
T3 and T4 are lipophilic and bind Nuclear Hormone Receptors ⇒ affect gene transcription
⇑ O2 consumption and the Basal Metabolic Rate (BMR) by increasing Na/K ATPase (NOT brain)
Whats the role of T4 in skeletal growth?
T4 facilitates GH release
- Permissive for chondrocyte proliferation and differentiation
- Low T4 slows growth & epiphyseal ossification
- High T4 accelerates epiphyseal fusion ( advances bone age)
i.e high and low levels make you short
Whats the role of T3,T4 in catecholamine sensitivity?
T4/T3 increases sensitivity of target tissues to catecholamines
- Lipolysis
- Glycogenolysis
- Gluconeogenesis
What does T3 do to b adernergic receptors?
T3 ⇑ β-adrenergic receptors in the heart & skeletal muscles, adipose tissue, and lymphocytes
