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ASSESSMENT AND DIAGNOSTICS/FUNCTIONAL TESTING 2 (THYROID (THYROID…
ASSESSMENT AND DIAGNOSTICS/FUNCTIONAL TESTING 2
THYROID
Thyroid Stimulating Hormone (TSH)
Levels are increased in hypothyroidism and decreased in
hyperthyroidism, also used to monitor thyroid replacement therapy
(Levothyroxine) in hypothyroid (or Hashimoto’s) patients.
Thyroxine (T4) and Triiodothyronine (T3)
.
Elevated in hyperthyroidism and decreased in hypothyroidism.
• If T4/T3 levels are low and TSH is not elevated, the pituitary gland is
more likely to be the cause of hypothyroidism
Reverse T3
Inactive isomer of T3
• Same chemical formula, but one Iodine binds to a different carbon.
• Created by 5’ Deiodinase Type III (Active T3 uses type I and II).
• Upregulated by:
Se deficiency
Excess cortisol and adrenalin (Stress)
Low cortisol (Adrenal fatigue)
Inflammatory cytokines
Free Radicals (ROS)
Fasting and Ketosis
• Can cause the symptoms of Hypothyroidism and slow metabolism
THYROID ANTIBODIES
Anti-Thyroid Peroxidase (TPO) Antibodies
• Most common antibody test performed via GP
• 90% of Hashimoto’s patients will test positive.
• 75% of Grave’s Disease patients test positive
Anti-ThyroGlobulin (TG) Antibodies
• Not routinely tested via GP where Thyroiditis is suspected.
• Present in 60% of cases of Hashimotos and 30% of cases of Graves
Anti-Thyrotropin Receptor (TRAbs) Antibodies
• Least common test – rarely performed privately or via GP.
• Usually only if Graves suspected – more than 70% incidence
Subclinical hypothyroidism
A reading of TSH and T4 may fall in the normal range but the person
still exhibits symptoms of hypothyroidism
High TSH with normal T4 suggests probably subclinical
hypothyroidism and should trigger comprehensive testing esp.
antibody testing.
Full thyroid analysis panels can determine a number of things:
– Poor conversion of T4 to T3 (due to Se deficiency)
– Presence of antibodies towards the thyroid gland
– Increased ROS (free radical) inhibition
Urine Test:
• The elevation of hormone levels in urine assesses tissue exposure to
thyroid hormones over a 24-hour period.
• The urine thyroid test therefore serves as a valuable tool for detecting
thyroid dysfunction that may otherwise go undetected through
standard blood tests.
IMMUNOGLOBULINS
IgG
700-1600 mg/dL
HIGH
Can indicate acute immune activation against
antigen or remaining immunity after antigen
contact
LOW
Chemotherapy (up to 2 months after), radiation,
chronic distress, cortisone medication,
Diabetes, kidney problems. smoking, allergies
IgM
40-230 mg/dL
HIGH
With first contact with antigen, also in relapses,
reliable indicator for any new infection, no matter
where in the body; present with liver disease
LOW
Chemotherapy, immune suppressive
medication, cachexia (eg. Cancer, HIV/AIDS),
muscle wasting disorders.
IgA
70-400 mg/dL
LOW
Chemotherapy (up to 2 months after), radiation,
chronic distress, allergies, surgery, genetics,
SLE (Lupus – high or low), Cirrhosis.
HIGH
Multiple Myeloma; Chronic Infections; Chronic
Liver Disease; SLE (Lupus), RA (Rheumatoid
Arthritis), Sarcoidosis, Thymic Aplasia, Leukaemia
IgE
150-300mg/dL
HIGH
Originally acute parasitic
Today main diagnostic parameter for acute
allergic reactions
RAST (Radioallergosorbent test)/ IgE
RAST testing uses blood screens for specific IgE antibodies to
diagnose allergies to specific allergens.
RAST testing is VERY expensive and therefore tests usually involve
only one to four allergens screened at a time.
As specific antibodies to specific antigens are being measured, you
must have some idea of which allergens are most strongly
suspected.
This is second line testing for allergies –
the first line testing is the
Skin Prick Allergy Test.
ALLERGY TESTING
SKIN PRICK ALLERGY TESTING
1
st line of allergy testing available via primary healthcare.
Cheaper than RAST testing and allows for a wider range of allergens to be
tested simultaneously.
Skin is pricked with a needle or pin containing microdose of an antigen
(allergen)
Localised IgE mediated histamine release by mast cells causes “wheal and
flare” reaction – red, swollen, itchy skin (urticaria)
LIMITATIONS
Decreased sensitivity of the skin in infants and elderly
Different body tissues show different types of mast cell responses therefore it
is less reliable for non-urticarial reaction eg. Reactions in intestines.
Does not assess for delayed onset food allergies
INDICATIONS
Severe skin disease (eg. Eczema)
Non-reactive skin
Hyper-reactive skin (urticaria)
NB: Skin test might be hazardous
– e.g. penicillin, bee or wasp venom sensitivity
Other less invasive alternatives are sometimes used, such as Patch
testing, which uses patches containing antigens rather than needles.
This is preferred with infants and young children, though skin prick
testing is still widely used in infants.
COMMON IGE ALLERGIES
• Aspergillus • Grass mix • Bee venom horse hair • Blue mussel • Latex • Cat dander • Egg • Wasp venom • Fish • Wheat
• Mould mix • Cheese • Peanut • Cow’s milk • Penicillin • Dog fur • Shrimp • Dust mite • Soya bean • Gluten • Yeast
NOTE ON IGE
•
A positive result on any form of IgE testing does not always mean the
patient will suffer an allergic illness when exposed to that allergen.
• A negative result does not entirely exclude sensitivity.
– False negatives are more common in children under the age of 5.
• The food tests are the least reliable.
• A negative result does not exclude sensitivit
y
VITAMIN D
25-OH-Vitamin D
• Most nutritionally relevant form of Vitamin D testing.
• Another test (1-25-OH-Vitamin D) is less useful so always specify.
• Available by serum (via GP) or pin prick (Better You or
Vitamindtest.org.uk)
• Low levels associated with increased inflammation, autoimmunity,
cancer mortality, infections.
• U-Curve trend has been noted: Long term high levels are as harmful
as long term low levels.
RANGE
Many labs now use the reference range 75-125nmol/L (some variance).
• Research on autoimmune diseases eg. SLE has found that increasing
vitamin D to 85-125nmol/L improved T-reg cells. It isn’t clear what impact
this has long term however. Eg
AUTOIMMUNITY
• Studies tend to show lower levels of vitamin D in those with autoimmune
conditions such as RA and SLE. Eg.
http://www.scielo.br/scielo.php?pid=S0482-
50042010000100007&script=sci_arttext&tlng=en
• Unclear if this is a cause or effect
• Increased risk of VDR polymorphisms in some autoimmune conditions.
• Some research shows increased incidence of Th2 dominance (allergies) with
long term high doses. Example:
http://www.ncbi.nlm.nih.gov/pubmed/15699498/
• Other hypotheses suggest potential risk of infection with long term high
vitamin D in autoimmunity: cross-reactivity and premature T-cell maturation in
the thymus could worsen or cause additional autoimmune diseases, due to
Th1 suppression. Re
An increasing amount of research suggests vitamin D has a golden zone of 70-
80nmol/L or even 75-80nmol/L.
• Above or below this risks increase for a range of diseases including cancer,
CVD, mortality
ADDITIONAL VITAMIN AND MINERAL ASSAYS
– A - 0.7-2.8 µmol/L
– C - Serum: 30-80 µmol/L; Leukocytes: 1.1-3.0 µmol/109
leukocytes.
• They do not necessarily always indicate a vitamin deficiency
• Strategy is based on assumption that circulating concentrations reflect organ and
tissue content
• Micronutrients are directed to circulation, storage and tissue pools
• Physiological stress, recent dietary intake and acute phase response alter
plasma levels of micronutrients. CRP might be a useful co-indicator
Functional Vs Diagnostic Testing
FUNCTIONAL
Not always associated with specific pathologies.
Not always directly to formal diagnosis confirmation
Focus on functional imbalances
Aim to identify potential subclinical variations away from
optimal function
Many biomarkers have specific links to nutritional
applications/pathways
Often have controversial or weak evidence base
• Instead of focusing on disease pathology functional testing highlights
the functioning capability of the body, so that the practitioner can
steer their client back towards optimum homeostatic functioning.
• Functional biochemical tests may involve the measurement of a
metabolic product or intermediary by-product in the blood/urine which
can indicate a lack of a nutrient dependant enzyme.
• It helps to ascertains the person’s specific needs and helps you the
practitioner to tailor your dietary and nutraceutical choices
specifically.
DIAGNOSTIC
Often associated with specific pathologie
May be confirm/negate formal diagnosis
Focus on disease states and diagnostic criteria
Not always sensitive to subclinical compromise in
function
Not always directly focused on nutritional applications
Often have a strong evidence base
TYPE OF SENSITIVITY REACTIONS
IgE mediated allergies
• “True” allergies.
• More consistent immunological reaction, with memory. Tests likely repeatable.
• Reactions may worsen or get more life-threatening with repeated antigenic
exposure.
• These may be lifelong issues
IgG mediated INTOLERANCES
• Though antibodies may be involved they are not considered a true
immunologically mediated allergy – they are an intolerance.
• Immunological memory is not strongly evidenced and hence not life-threatening
and not always life-long.
• Test results may not be repeatable within a few months of avoidance
Non-antibody Mediated Sensitivity
Biogenic Amine Intolerance
Histamine and Tyramine are the most common
• Dose Dependent
• No overt antibody mediation
• Multi-factorial (eg. Bacterial synthesis, hypomethylation, SNPs, DAO
insufficiency, stress, dietary load – amine containing/releasing foods)
• Can test for indirect markers but no specific food tests available.
• Not life long as no memory involvement – but can be complex to
overcome due to multiple influences.
• Symptoms can mimic IgE mediated reactions inc. anaphylaxis in rare
cases.
Polyphenol Intolerance
Salicylates and other naturally occurring phenols, occur in plant foods and are
also found in many medications and cosmetics.
Some people can develop symptoms similar to other intolerances due to poor
metabolism
No immunological influence at all.
• Often linked to multiple factors (eg. which metabolites of the phenols are
created by bacteria in the gut; hypomethylation; dose; SNP’s).
• There are no tests available, though occasionally organic acid tests may show
some metabolites in urine which can sometimes be caused by bacterial
metabolism of phenols – but this hasn’t actually been linked to intolerance in
research at all.
Food intolerance - IgG
IgG testing is the most common form of food sensitivity testing offered by nutritional
therapists.
If a client comes to you in clinics reporting they have food allergies or intolerances, ask
them how they were informed of this (eg. Trial and error, elimination diet, IgE mediated
testing, Bio-energetic Stress Testing, or IgG testing).
• IgG intolerance is thought to be the presence of an adverse reaction to a specific food or
food ingredient
• Not necessarily associated with clearly defined immune reactions in the same way as
food allergy, and may involve a number of different reactions
• Research is available on IgG testing for dietary exclusion – though the quality,
methodology, results and repeatability/relevance are highly controversial.
• Many practitioners believe there is at least good anecdotal evidence for its use- it is
often a good place to start creating a grand elimination diet (gold standard) – though
there could be multiple influences here to consider.
IgE: A closer look
• IgE mediated allergies indicate an atypical picture: Antibodies have
been formed to an antigen which in most people is not considered
harmful.
• IgE antibodies form complexes with mast cells when they bind to
receptors, triggering mast cell degranulation and histamine release.
• People will manifest predictable clinical symptoms and will usually
test IgE positive even if they have not recently been exposed to the
antigen.
• Whilst the tests are far from perfectly consistent, they do offer a good
level of predictability and are based on larger bodies of evidence.
IgG: A closer look
•
IgG food intolerance tests can look at IgG or a more specific IgG4
antibody presence.
• IgG4 antibodies are unique amongst the IgG antibodies in that they
do not activate the complement inflammatory cascade but are
present in only small amounts as a proportion of IgG (about 5%) in
the blood.
• IgG4 antibody responses increase when there has been regular and
recent exposure to food antigens.
• They are not associated with the same mast cell degranulation
responses and hence do not show the same types of responses as
true allergies.
Ig G AN OVERVIEW
Proponents of IgG testing state that regular exposure to an unvaried diet, along with
other factors such as leaky gut, can increase sensitivity to foods.
• It is has been found that with food allergens specifically (IgE), intestinal permeability is
an important mediating factor and that repeated exposure exacerbates the symptoms.
Removal of the allergen improves intestinal permeability and allows tight junctions to
repair. See:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170794/
for more info.
• Many practitioners believe that the same is true with IgG reactions and that by
supporting gut repair and reducing exposure to IgG-positive foods, it reduces the
overall antigenic load and reduces IgG levels, improving symptoms.
• By keeping the diet well rotated, it is possible to avoid further intolerances developing.
• Many people find that within a few months of avoidance, their food intolerances can be
retested and show changes.
95 C
IgG4
• IgG4 antibodies have been found to be elevated with gastrointestinal and
immune issues.
• Eg. A study in 2016 looking 200 children, comparing 50 healthy vs. 50 with
wheat allergy (IgE), 50 with Coeliacs and 50 with H. Pylori found looked at IgG
and IgG4 response to wheat and rice, when eliminated and consumed:
No correlations with IgG/IgG4 in healthy children – any levels which were present with
consumption were reduced with elimination of food.
IgG and IgG4 were elevated for wheat and rice in all the GI disorder groups, even after
elimination.
IgG4 present with wheat allergy group for both rice and wheat even though
asymptomatic with rice.
• Conclusion: IgG presence in GI groups seemed correlated to dysfunction of the gut and
immune system, rather than to wheat per se.