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Frequently ask Questions:

Question Number 05


Question 05: I am a medical specialist in gynaecology and I also have HPU. I my pratice it strikes me that more HPU-patients have nausea and vomitting in pregnancy, than others. Did you find this too? Is there a relationship between TSH- and/or the prenancy hormone hCG and NVP?

Answer: Peak concentrations of hCG and the most rapid rate of rise correspond to the time of maximal NVP (nausea and vomiting in pregnancy) between 8-12 week gestation. Several authors have studied the hCG concentrations in women but the results are not consistent. Goodwin found that hCG was elevated in women with vomiting compared to gestational age-matched controls, but there was significant overlap. But there are women high in hCG which have no morning sickness at all.

The consistent finding that NVP is more common with multiple gestation in which hCG is significantly elevated compared to singletons supports this observations as well. It has also been noted that mothers carrying foetuses with Down's syndrome, a condition associated with elevated hCG, are more likely to have NVP. By way of contrast, women with trisomy 18, in which hCG is very low, report much less nausea in pregnancy.

The rise in hCG corresponds temporally to a consistent thyroid stimulation in the mother (Goodwin). Since hCG closely resembles its sister glycoprotein hormone, thyroid stimulating hormone (TSH), it has been stated that hCG is the thyroid stimulator of pregnancy. The observation is, that NVP correlates closely with the degree of biochemcial hyperthyroidism.

During early pregnancy, the high circulationg levels of hCG could be responsible for the transient thyroid stimulation leading to hyperemesis. The mechanism known as "specificity spillover" could explain the ability of hCG to stimulate the TSH-receptor. The specificity spillover is related to the structural homology between hCG and TSH molecules, and between there mutual receptors (Asteria, 1999).

In patients that excrete pyrroles with the urine, pregnancy problems are clear. The TSH is suppressed and is seldom above 2.0 mIU/l before pregnancy, although the FT4 and FT3 are within normal range. TSH is decreased much more clearly in the first decade of pregnancy when hCG rises. It seems as if hCG rises to higher levels as in other patients.


Asteria, C. (1999) TSH receptor mutations and familial gestational hyperthyroidism. European Journal of Endocrinology 141, 93-94.

Buckwalter, D.K., Buckwalter, J.G. (2001) Psychological factors and hyperemesis gravidarum. J. Womens Health Gend. Based Med. 10, 471-477.

Gherman, R.B., Mestman J.H., Satin A.J., Goodwin T.M. (2003) Intractable hyperemesis gravidarum, transient hyperthyroidism and intrauterine growth restriction associated with hyperreactio luteinalis. J. Reprod. Med. 48, 553-556.

Goodwin, T.M. (2003) Human chorionic gonadotropin and hyperemisis gravidarum.

Goodwin, T.M. (1998) Hyperemesis gravidarum. Clin. Obstet. Gynecol. 41, 597-605.

Goodwin, T.M., Hershman, J.M., Cole, L. (1994) Increased concentration of the free beta-subunit of human chorionic gonadotropin in hyperemesis gravidarum. Acta Obstet. Gynecol. Scand. 73, 770-772.

Goodwin, T.M., Montoro, M, Mestman, J.H., Pekary, A.E., Hershman, J.M. (1992) The role of chorionic gonadotropin in transient hyperthyroidism of hyperemesis gravidarum. J. Clin. Endocrinol. Metab. 75, 1333-1337.

Goodwin, T.M., Montoro, M., Mestman, J.H. (1992) Transient hyperthyroidism and hyperemesis gravidarum: clinical aspects. Am. J. Obstet. Gynecol. 167, 648-652.

Goodwin, T.M., Montoro, M., Mestman, J.H., Perkary, A.E., Hershman, J.M. (1991) The role of chorionic gonadotropin in transient hyperthyroidism of hyperemesis gravidarum. Trans. Assoc. Am. Physicians. 104, 233-237.

Safari, H.R., Alsulyman, O.M., Gherman, R.B., Goodwin, T.M. (1998) Experience with oral methylprednisolone in the treatment of refractory hyperemesis gravidarum. Am. J. Obstet. Gynecol. 178, 1054-1058.

Simpson, S.W., Goodwin T.M., Robins S.B., Rizzo A.A., Howes R.A., Safari, H.R., Fassett, M.J., Souter, I.C., Alsulyman, O.M., Goodwin, T.M. (1998) The efficacy of methylprednisolone in the treatment of hyperemesis gravidarum: a randomized, double-blind, controlled study. Am. J. Obstet. Gynecol. 179, 921-924.


Question 49: I have HPU with thyroid problems (Hashimoto disease. These problems started after the last pregnancy a few months's ago. A gained weight during pregnancy and was not able to loose some weight. My liver values after my pregnancy were increased. Also my cholesterol level was increased. Do I have an increased risk on hart and vascular diseases?

Answer: Hashimoto disease, in which antibodies are raised against your thyroid, most often thyroid peroxidase, starts very often between zero and three month's after delivery. This disease which is mark by a thyroid hypofunction, really starts with a period of thyroid hyperfunction. In a later phase, periods with hypofunction can alternate with periods of normal or hyperfunction.

In the beginning of the period with thyroid onderfunction the liver values GGT, ASAT and ALAT are increased. The increased liver values can be increased by inflammation of the gall ducts (for PBC look for antibodies against cell mitochondria; AMA) or liver. In the case the cholesterol is increased the relationship between LDL- and HDL-cholesterol is important. In the case that LDL-cholesterol is increased a treatment is necessary. When both LDL- and HDL-cholesterol are increased, treatment is less

important. In the case you don't have antibodies againts you own thyroid, you can use HPU-complex to losse wome weight. HPU-complex is a food supplement.


Question 02: I have HPU and get hormone substitution therapy because of the complaints during change of life. I recently read that hormone substitution increases the risk on brain haemorrhage with 56 percent. Now I want to take soy isoflavones. Can I use this without risk? (See: article)

‘Nach der Auswertung von 39.769 Fällen aus 28 verschiedenen Einzelstudien müsse allen Frauen mit erhöhtem Hirnschlag-Risiko von dieser Therapie abgeraten werden, heißt es in dem am Freitag veröffentlichten Beitrag der Fachzeitschrift "British Medical Journal".

Bei Frauen, die in den Wechseljahren auf Hormonersatz verzichteten, betrug das Hirnschlag-Risiko zwei Prozent. Bei den Frauen mit Hormonersatztherapie stieg das Risiko um ein Drittel an. Gravierender noch war die Steigerung der Gefahr, dass der Hirnschlag zum Tode führt. Dieses Risiko lag bei den Frauen mit Hormonersatztherapie um 56 Prozent höher.

Die Hinweise auf gravierende unerwünschte Effekte der Hormongaben in der Menopause verdichten sich. Ende vergangenen Jahres hatte eine Studie unter 55.000 Französinnen ergeben, dass das Brustkrebsrisiko durch die Hormongaben um 20 bis 40 Prozent zunahm - je nachdem, wie lange die Hormone genommen werden.’


Answer: During change of life in woman a lot of climacteric complaints occur like be sweltering of heat, flush, dizziness, sweating, insomnia, or even depression. These complaints start because the ovaries discontinue the production of ripe egg cells. Supplying hormones can stop these complaints, which can start after resection of the ovaries as well. The used hormones are on the list of well-known porphyrinogens.

A lot of woman therefore take soy isoflavones like genisteine or daidzeine, which also reduce the production of thyroid hormone, either by interfering with deiodase activity of by binding to proteins which normally bind thyroid hormones. Red clover is also used very often. We have discovered that red clover has the same effect on thyroid function in HPU-patients as soy isoflavones. We therefore prefer the stimulation of pituitary and/or adrenal. The adrenal liberates DHEA from which oestrogen or testosterone can be produced.


Question 01: What's the difference between the HPU-test® , the total pyrrol test and the kryptopyrrol test? What are the reasons to prefer an HPU-test above other tests?

Answer: Only the HPU-Ruin test® (with the registered trade mark sign ®) is the original HPU-test. Only in this test the ‘hydroxy-hemopyrrol pyridoxal-5-phosphate zinc chelate complex’ is measured. In the USA Dr. Taipan Audhya performs a test on hydroxy-hemopyrrol in the urine. This test only measures the hydroxy-hemopyrrol. From recent research it is clear that there is a good correlation between this test and the HPU-test®.  

Other tests that resemble the HPU-test are the total pyrrol test or the krypto-pyrroltest.

Although sometimes misleading designations like ‘OH-Hemopyrrol’ are used, all these test in fact are total pyrrol test in which pyrroles are determinated spectrophotometrically with the Ehrlich reagens. 

These tests normally are less expensive, because the determination of total pyrrols is much easier. The KEAC-Kryptopyrrol test is € 7,50 cheaper and the total pyrrol test even more. In the USA this difference is even much more, because the hydroxyhemopyrrol test is more expensive.

There are some reasons why one would prefer the HPU-urine test® above other tests. Pyrrols and other resembling compounds that can be formed from porphyrins quite easily can react with Ehrlich reagens too. Porphyrines are intermediates from the haem synthesis and can also be found in the urine of healthy persons. The use of certain drugs, food or stimulants does increase the amount of porphyrines and therefore the result of the total pyrrol test.

‘Hydroxyhemopyrrol pyridoxal-5-phosphate zinc chelate (HPL)’ is a quite specific compound which, as far as known nowadays, can only be formed from a disturbance in the haem synthesis or by oxidation of arachidonic acid via tissue adducts.

When you want to perform a KPU (kryptopyrrol test) because of financial or other reasons, this is no problem. Just ask for this test. Also in this case we will support you with our knowledge.


Question 51: I have a patient with HPU and she has spots without pigments all over her skin called virtiligo. Is their any connection with HPU?

Answer: Almost all patients with virtiligo have raised antibodies against their own thyroid especially thyroid peroxidase (anti-TPO). 90 Percent of the patients has Hashimoto disease. As a lot of HPU patients have Hashimoto too, there is a connection between HPU and virtiligo. The risk of developing an auto-immune disease is much higher if one has already a certain auto-immune disease. The use of sodium selenite or seleniumcystein 200 mcg reduces the amount of antibodies gradually.


Question50: There is a letter of Dr. Kuklinski to Anna (a patient) in which he writes: "HPU can be both inherited and acquired. The cause should be located. HPU is just a symptom. Normally you will find a lot of multi-organ complaints. HPU is just one of the many symptoms" Probably this statement can be formulated much clearly, if Dr. Kamsteeg has the same opinion.

Answer: HPU belongs to the porphyrinuria disease (toxic induced porphyria). Pyrroles and porphyrines are excreted in the urine after a burden. One of these pyrroles is HPL (hydroxy-haemopyrrollactam). This compound is normally excreted, complexes with zinc and pyridoxal-5-phosphate. There is an inherited variant, which starts after a disturbance of the haem synthesis. In this case the methylhydroxybilan is forming a ring spontaneously (not enzymatic) and finally forms coproporphyrinogen I.

HPU is also strongly associated with depletion of arachidonic acid, which is attacked by free radicals to form levuglandins and isolevuglandins, which in turn produce pyrrolic tissue adducts. These pyrrolic adducts consistently auto-oxidise to form a hydroxy-lactam, and the pyrrolic moiety of these adducts corresponds precisely to the structure of HPL. Urinary pyrroles are known to result from the formation of pyrrolic tissue adducts. Hydroxyhemopyrrol inhibits haem syntheses. The formed hydroxylactam can also be complexed to pyridoxal-5-phosphate and zinc (or in case of zinc deficiency with manganese or iron) and be excreted with the urine. In the haem synthesis the not-enymatic conversion of hydroxymethylbilan in coproporphyrinogen I in spite of the enzymatic production of coproporphirinogen III. This increases HPL-formation.

The formation of tissue adducts results to a variety of autoimmune diseases, often at a young age. Autoantibodies against the thyroid (thyroid peroxidase) are found most often. In case of HPU the TSH is always below 2 IU/ml; at a value below 1, the fertility is strongly reduced. At a vale of 3 and more a test on thyroid antibodies (anti-TPO) should be performed. In almost al the cases normally levels of Ft3 and Ft4 are found, although the patients history is typical for hypothyroid function. The production of T3 and T4 in a 24-hours urine often is not normal.


Question of the week 48

Question 48. Which supplementary medical research can be performed when the HPU-test is positive? Are there any clinical chemical researches that can be supporting the positive test result?

Answer: HPU does not develop to a certain disease, but to a variety of symptoms from moderate to very severe. Complaints such as problems with your joints (hyper mobility, pelvic instability, pain in the knee's), menstrual complaints, infertility, depression, anxiety disorders, schizophrenia, hart- and vascular diseases, anaemia, diabetes type 2, thyroid problems and overweight (especially after pregnancy) are often found. A lot of patients have complaints about stomach and gut, muscle weakness, hair loss, cannot remember complaints, blood sugar problems, reduced detoxification and so one.

These symptoms are regularly caused by a disturbed hormonal regulation. The histamine level is reduced ver often. This causes chronic fatigue, allergy, migraine, blood saturation and depression.

HPU is seen as missing link in psychiatric complaints. Especially in ADHD and autism high percentages HPU are found. Disturbed hormonal regulation is often found.

A lot of people with increased HPU-values often have problems with stabilising their blood sugar levels. Especial children and young adults often have reactive hypoglycaemia because of malaborption of fructose (fruit sugar) and reduced conversion into glucose. In women from 30 years and older, glucose intolerance or prediabetes can be present.

Part of the cause can be found in the decrease of the TSH-hormone and the hypophyse function. Another reason is that antibodies are raised against thyroid peroxidase (anti-TPO). Already at low age the activity of the hypophyse activity is decreased, and serum gastrin is decreased. Stomach complaints, as a filled feeling during or just after dinner is one of the first complaints. The decreased activity of the hypophyse also decreases the adrenal function. This causes low blood pressure, frequently have a pee (urinate) and fatigue are the most common complaints.

Last but not least a lot of HPU patients react on gluten from wheat, rye, oat and barley.

When the result of the HPU-test is positive (above 0.6 HPL µmol/l) a treatment should be started of at least four months with Depyrrol basic or pyridoxal-5-phosphate 50 mg, zinc 30 mg en manganese 5 mg.

The following supplementary test can be considered:

TSH, fructosamin (not HbA1c), IgA-total gluten (not IgA-alfa-Gliadin) en whole blood histamine. Only when these results are known more specific advice can be given.

For more information about HPU-screening (with or without allergy research) see hputest.nl website.


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