Mould Illness Medical Testing

Short answer

In 2003 Dr. Shoemaker said at least 3 of  6 of biomarkers (known at that time) if symptom and environmental criteria were met. Speaking on the Low Tox Life podcast (#55, 50m02s) Dr. Sandeep Gupta said “Once you have around 3 abnormal markers, that should be sufficient.”

Other doctors will diagnose on other testing such as a positive urinary mycotoxin test. Whether this means the patients has CIRS, mycotoxicosis or mycotoxins coming from a normal diet is matter of some debate.

Long answer

From Dr. Shoemaker’s original Sick Building Syndrome (SBS) criteria from 2003 (note, this was before the discovery of C4a and TGF-b1 being elevated, and VIP being lowered, in CIRS):

1. We propose that a definition of a case of SBS include each of the following elements
– potential for exposure to buildings with a documented toxigenic fungi, evident fungal growth or a history of water intrusion with musty smells;
– presence of multiple symptoms in at least 4 of 8 system categories
– absence of confounders
2. At least 3 of the following 6
– VCS deficits
– MSH deficiency
– MMP9 elevation
– HLA genotype
– ADH/osmolarity dysregulation
– ACTH/cortisol dysregulation
3. Final criteria for case management
– Response to CSM, with abatement of symptoms and resolution of VCS deficit to control levels
– Reduction of leptin, if elevated, with treatment
– Reduction of MMP9, if elevated, with treatment
4. Clinical note needs to be made of
– Presence of MARCoNS in deep nasal spaces
– Elevated levels of myelin basic protein antibodies”

From a 2020 paper:

…The difference is that CIRS literature has data on many recognized biomarkers and a published treatment protocol [7], but PICS does not. These biomarkers include symptom clusters for CIRS acquired following environmental exposures to biotoxins and inflammagens in water-damaged buildings (WDB), finding at least 8 of 13 clusters present.
Proteomic biomarkers compared to controls [4] include
(i) increased relative risk for specific HLA haplotypes;
(ii) presence of a distinctive deficit seen in visual contrast sensitivity (VCS);
(iii) reduction of mean levels of melanocyte-stimulating hormone (MSH);
(iv) dysregulation of ACTH to cortisol and
(v) ADH to osmolality;
(vi) elevated C4a,
(vii) TGF beta-1, and
(viii) MMP9;
(ix) suppression of vascular endothelial growth factor (VEGF);
(x) increased incidence of antigliadin and
(xi) anticardiolipin antibodies [7].
Functional CIRS WDB biomarkers include
(a) a distinctive “fingerprint” of volumetric abnormalities [22-24] seen on NeuroQuant™;
(b) reduction of VO2 max and
(c) anaerobic threshold shown by pulmonary stress testing;
(d) elevated pulmonary artery pressures at rest, or (e) after exercise on echocardiogram;
(f) transcriptomics.

The HLA DR/DQ gene test show haplotypes (gene combinations) of susceptibility to CIRS-WDB/mould illness, Post Lyme Syndrome (PLS) and multi-susceptible (susceptibility to mould, PLS and dinoflagellates/ciguatera/toxic algae).

Having a HLA positive does not mean you have CIRS or are destined to develop CIRS but you may be more susceptible to develop it after sufficient exposure to damp and water-damaged buildings or other biotoxin exposures.

Correct laboratory group — Sonic Pathology

Sonic Pathology Australia are a network of pathology laboratories in every Australian state. See their website or the picture on the right (or above) for locations in your state.

Test information: HLA Panel Screen (DR and DQ)

Test name: Ask the GP to request “HLA DR-DQ typing” — Do NOT write coeliac

Medicare rebate

It can be fully or partly Medicare rebateable depending on your practitioner and laboratory. Medicare item number 71151. No rebate is available via NutriPATH.

Price varies from lab to lab but ranges from $119 to $180.

NutriPATH

NutriPATH do report the HLA DR/DQ test in the correct format also.

Test name: HLA DQ/DR Genetic Studies
Test number: 3401
Test cost: $180

Interpretation

Interpretation can be done by a Mould Illness/CIRS-aware health professional or via the HLA calculator. If you are still unsure please post your results in the TMSA Facebook group.

FASTING TEST

What it Is: VIP is produced in many tissues including the gut, pancreas, and suprachiasmatic nuclei of the hypothalamus in the brain. VIP stimulates contractility in the heart, causes vasodilation, increases glycogenolysis, lowers arterial blood pressure and relaxes the smooth muscle of trachea, stomach and gallbladder.

Significance in CIRS: VIP is  often, but not always, low in CIRS. Low levels can lead to inflammation, immune dysregulation, post-exertional malaise/exercise intolerance and, according to Dr. Shoemaker, multiple chemical sensitivity (MCS). Replacement via VIP nasal spray is the last step in CIRS therapy.

Collection: Most Australian pathology labs can collect and send to Royal Prince Alfred/Sydney Southwest Pathology. A special collection tube is required and will usually have to be ordered in before the blood draw. Consult with your local path lab to arrange. VIP collection and information page.

Medicare: Medicare item number 66695.
Normal Range:  6.81-18.65 pmol/L (23-63 pg/mL, conversion ref).

About: Serum (or plasma) osmolality measures the body’s electrolyte–water balance.

Significance in CIRS: Dr. Shoemaker has found 60% of biotoxin illness patients have dysregulated ADH/osmolality — seen as low ADH with high serum osmolality. Such patients have excessive thirst and may need to urinate every 30 minutes, or more, due to low ADH causing an inability to retain the water that has been drunk. As the salt level in blood rises, due to the lack of free water, some salt is released on the skin creating a battery like effect leading to frequent static shocks. Additionally migraine-like headaches due to dehydration may occur.

Notes: This should be drawn at the same time as Copeptin (see below).

Medicare: Medicare item number 66563.
Normal Range: 280-295-297 mmol/kg.

What it Is: Testosterone is often low while Oestradiol is often elevated in CIRS due to upregulation of the aromatase enzyme. Testosterone replacement is not generally recommended in CIRS as it will just convert to Oestradiol.

What it Is: Adrenocorticotropic Hormone (ACTH) is a hormone made by the pituitary gland and controls the production of another hormone called cortisol. Cortisol is made by the adrenal glands, two small glands located above the kidneys and helps to respond to stress among other functions.

Significance in CIRS: ACTH and cortisol are often high early in the disease while later they may drop to low-normal or below normal levels. Ideally measure these in blood, as opposed to saliva or urine, in the morning.

What it Is: Dehydroepiandrosterone (DHEA) is a hormone that your body naturally produces in the adrenal gland. DHEA helps produce other hormones, including testosterone and estrogen. Natural DHEA levels peak in early adulthood and then slowly fall as you age.

Significance in CIRS: DHEA is often low in CIRS. Ideally test blood levels of DHEA-sulphate (DHEA-S).

Significance in CIRS: Sometimes elevated in CIRS due to low MSH and not coeliac disease.

Normal Range: 0-19

What it Is: Cardiolipin antibodies are autoantibodies produced by the immune system that mistakenly target the body’s own cardiolipins, substances found in the outermost layer of cells (cell membranes) and platelets. These autoantibodies can affect the body’s ability to regulate blood clotting.

Significance in CIRS: These are sometimes elevated in CIRS due to its dysregulation of the immune system.

Normal Range: IgA – 0-12; IgG 0-10; IgM 0-9

iMedical allow patients to build their own blood tests with no doctor’s referral needed.

• $19 – base fee
• $39 – VIP
• $29 – ACTH
• $29 – Cortisol
• $29 – Osmolality (Serum)
• $29 – DHEA-S
• $49 – Testosterone Free/Total + SHBG
• $29 – Antigliadin antibodies
• $86 – Antiphospholipid antibodies

Note: The HLA DR/DQ test is not available via iMedical. Prices current as of January 2025.

FASTING TEST

What it Is: Leptin is an adipokine, a cytokine released by adipose (fat) tissue. High levels can lead to persistent weight gain that is unresponsive to diet and lifestyle interventions.

Significance in CIRS: It is frequently, but not always, elevated in cases of CIRS. It is hypothesised by Dr. Shoemaker that inflammatory cytokines damage the leptin receptor in the hypothalamus thus not allowing leptin to dock and instead recirculate.

Collection: Most Australian pathology labs can collect and send to Royal Prince Alfred/Sydney Southwest Pathology, but total cost (collection plus test) varies from lab to lab. Prices for collection vary so check with your local pathology centres for the best price. In Queensland QML are the cheapest ($60). Leptin collection and information page from SSWP.

Dr. Shoemaker’s normal range: Depends on age, sex and BMI. Dr. Shoemaker gives the following normal range: Male: 0.5-13.8 ng/mL; Female: 1.1-27.5 ng/mL.

INTERPRET WITH SERUM OSMOLALITY (SAME DRAW)

What it Is: Antidiuretic Hormone (ADH) or vasopressin is a neuroimmune peptide hormone made by the hypothalamus in the brain and stored in the posterior pituitary gland. It tells your kidneys how much water to conserve. ADH constantly regulates and balances the amount of water in your blood.

Significance in CIRS: Dr. Shoemaker has found 60% of biotoxin illness patients have dysregulated ADH/osmolality — low ADH with high serum osmolality. Such patients have excessive thirst and may need to urinate every 30 minutes, or more, due to low ADH causing an inability to retain the water that has been drunk. As the salt level in blood rises, due to the lack of free water, some salt is released on the skin creating a battery like effect leading to frequent static shocks. Additionally migraine-like headaches due to dehydration may occur.

Notes: Most labs including the one below now offer the precursor C-Terminal Pro Arginine Vasopressin (copeptin) as a marker which has 1:1 compatibility with ADH.

Collection: Most Australian pathology labs can collect and send to Royal Prince Alfred Hospital via Sydney Southwest Pathology. Prices for collection vary so check with your local pathology centres for the best price. Copeptin collection and information page.

Dr. Shoemaker normal range: 1.0-13.3 pg/ml.
RPA normal range: < 15.2 pmol/L (fasting) < 16.3 pmol/L (non-fasting), < 14.5 pmol/L (non-fasting paediatric)
Quest (US) normal range: < 14 pmol/L

What it Is: Vascular Endothelial Growth Factor (VEGF) is a protein produced by many cells that stimulates the formation of blood vessels.

Significance in CIRS: VEGF can be low, normal, or high in CIRS patients. Low levels may be due to increased TGF-b1 levels, and contribute to capillary hypoperfusion, causing symptoms such as fatigue, muscle cramps, and shortness of breath due to mitochondrial dysfunction.

Significance in other diseases: High levels are seen in bronchial asthma, diabetes mellitus, some cancers and Bartonella infection.

Collection: Most Australian pathology labs can collect and send to Peter MacCallum Cancer Centre, Royal Melbourne Hospital. Prices for collection vary so check with your local pathology centres for the best price. In Queensland the cost is $200, via QML.

Dr. Shoemaker/Quest (US) normal range: 31-86 pg/mL

iMedical allow patients to build their own blood tests with no doctor’s referral needed.

• $19 – base fee
• $98 – Copeptin
• $76 – Leptin
• $189 – VEGF

Many of Dr Shoemaker’s core CIRS tests — the inflammatory markers Transforming Growth Factor Beta-1 (TGF-b1), Complement C4a (C4a), and Matrix Metalloproteinase 9 (MMP-9), plus the protective neuropeptide hormone alpha-Melanocyte Stimulating Hormone (MSH) — are not currently available via any NATA accredited Australian laboratories.

More details on these tests, including normal ranges, can be found on Surviving Mold’s Lab Tests for Mold Illness.

The GENIE transcriptomic test looks at the RNA expression of 215 genes, developed by Dr Shoemaker and Dr Jimmy Ryan, PhD to diagnose, track, and enable subtyping of, CIRS. It is only available in Australia via Mycotox at present.