genitalia interna, vonden wij dikwijls algemene klachten, zoals boven reeds vermeld. Wij vonden dan een verlaagd B.M., een normaal P.B.I.
en een geringe bindingscapaciteit van het T.B.P. Bij een deel van deze vrouwen was er een verminderde "uptake" van J131 door de schild
klier. Een verlaagd B.M. vonden wij bij 18 van de 19 besproken pa
tienten. De meeste van deze 19 patienten waren meisjes rond de 20 jaar.
Bij deze groep van meisjes waren er 4, die opvielen door hun uiterlijk.
Zij waren zeer mager, aten slecht, hadden een laag B.M. {lager dan - 15 %). De algemene klachten waren bij hen sterk aanwezig, vooral de klacht over kouwelijkheid stond op de voorgrond. Bij 3 van de 4 meisjes bestond er een secundaire amenorrhoe en bij één een primaire amenorrhoe. De oestrogene werking was minimaal en de uterus was 1 14
zeer klein. Deze 4 meisjes werden behandeld met oestrogene stoffen en schildklierhormonen. Zolang er alleen schildklierpoeder gegeven werd, was er weinig reactie te zien op de algemene toestand en het B.M. In
dien er tevens trijodotyronine gegeven werd, zagen wij bij 3 van de 4 meisjes een algemeen gunstig effect optreden: de eetlust werd beter, het gewicht nam toe (verdubbelde in twee gevallen), het B.M. steeg, de klachten verdwenen en de cyclus werd beter gereguleerd en herstelde zich zelfs in enkele gevallen volkomen. Eén van deze meisjes trouwde, raakte in verwachting en beviel van een normaal kind.
De oestrogene stoffen veroorzaken een groei van de uterus en een stij
ging van het P.B.I. tot z.elfs waarden, zoais men die gedurende de zwan
gerschap ziet. Ook de bindingscapaciteit van het T.B.P. neemt toe, in
dien men oestrogene stoffen toedient. Dit wordt het fraaiste gezien bij de groep patienten met amenorrhoe. Men kan dit waarnemen doordat de radio-activiteit van de albuminefractie afneemt, waardoor blijkt, dat er meer thyroxine aan het T.B.P. wordt gebonden.
Het schildklierpoeder alleen toegediend doet het B.M. bij vele patienten uit de 2 groepen niet of onvoldoende stijgen. Het trijodotyronine daaren
tegen veroorzaakt, op enkele uitzonderingen na, een goede stijging vaak tot normale waarden van het B.M. Ook een reguleren van de cyclus wordt gunstig beïnvloed door het geven van trijodotyronine. De alge
mene klachten verdwijnen na het toedienen van schildklierhormon, spe
ciaal na het geven van trijodotyronine.
De resultaten van de door ons gegeven therapie zijn in het algemeen gunstig te noemen.
De overeenkomst tussen de 2 behandelde groepen patienten is dus het bestaan van algemene klachten, een verlaagd B.M. {lager dan O % ), een normaal P.B.I. (buiten de graviditeit) en een bindingscapaciteit van het T.B.P., die niet optimaal of verminderd was.
Bij de 2 groepen wordt van schildklierpoeder alleen in het algemeen een onvoldoende of geen reactie van het B.M. waargenomen, terwijl er wel een stijging van het P.B.I. gezien wordt.
Bij de 2 groepen patienten wordt er een stijging van het B.M. gezien, indien trijodotyronine gegeven werd, waarbij meestal het P.B.I. daalde.
Bij de bespreking van de literatuur wordt eerst een algemene beschrijving van de schildklierfunctie gegeven; zowel de opvattingen over het ont
staan van de schildklierhormonen, als het transport er van worden be
sproken.
In de volgende literatuurhoofdstukken wordt een overzicht gegeven over de betekenis van het P.B.I. in normale omstandigheden, gedurende de zwangerschap en onder verschillende pathologische omstandigheden.
Aan de electroforese van serumeiwitten, waaraan in vitro radio-actief thyroxine is toegevoegd, om de binding hiervan aan het T.B.P. en het albumine na te gaan, wordt een hoofdstuk gewijd.
Het laatste literatuurhoofdstuk handelt over de vorming, de werking en de therapeutische mogelijkheden van het trijodotyronine.
Tenslotte wordt een korte bespreking aan het trijodotyronineacetaat ge
wijd.
INTRODUCTION.
Often slight deviations of the thyroid function have been observed in the endocrinological examination which as a rule is carried out on women with an amenorrhea or an oligomenorrhea at the women's clinic of the Groningen University. These deviations were observed in patients with a primary amenorrhea or a secondary amenorrhea which had existed for some time, in whom a reduced estrogenic activity could be demonstrated by means of the cytological-hormonological examination of the vagina! epithelium in the "vagina! smear"; nearly always the uterus was found infantile. In many cases it was noticed that the metabolism was low-normal (between O and - 15 per cent) or reduced (less than - 15 per cent) while it was not possible to establish the diagnosis "hy
pothyroidism". A great number of these girls when questioned com
plained of chilliness and a dry skin, a smaller number were troubled with brittle nails, hair falling out and slow defecation; only a few had almost no complaints.
In addition, the research as to the cause of the death of the foetus or of the premature birth of a child, whether viable of not, or dead in many cases revealed no obvious reason, except that the metabolism was often rather low or clearly too low.
Finally, a metabolism too low for a gravida was sometimes found with a group of patients who were pregnant. They were women with whom pregnancy had one or more times ended in the premature birth of a dead or a living child.
With the pregnant women, we were of the opinion that a basic meta
bolism below O per cent should not be considered as normal for the pregnancy.
Along with the metabolism the cholesterol content of the blood and the Protein-Bound-lodine were fixed in those cases mentioned above. With non-pregnant patients a test was conducted with }131 of which the se
cretion in the urine and the amount of radio-active iodine in the blood were fixed; and later, instead of performing the examination in the urine, a direct counting of the thyroid as to radio-activity was carried out.
We required the patients to be in basic condition for the determining of the metabolism. To ensure this the patient carne to the clinic the night before and the next morning the metabolism was fixed. More recently the patient was admitted a separate room; hete she stayed during the night and the next morning the patient was metabolised in bed in the same room. After that a vein-puncture was executed for the fixing of Protein-Bound-lodine and cholesterol. The first two times the metabolising took place in the manner described above; for further
metabolistic determinations a policlinical determination sufficed. The women who were to come for a policlinical determination were directed to the clinic early in the morning without having had breakfast. They were to rise at home, perform no domestic duties at all, and come to the clinic bij means of conveyance.
In the clinic the women had tot lie on a stretcher for at least an hour, preferably alone in a room, before the metabolism was determined.
Breatingh through a tube was kept up for at least five minutes.
Is was not always possible to perform a vein-puncture for the deter
mination of Protein-Bound-lodine with every examination, because the laboratory could only complete a limited number of determinations per week. At the same time an electro-phoretic examination of this blood was executed, during which radio-active thyroxine was "incubated" to the serum in various concentrations before the serum was placed on to a marked spot on paper that had been immersed in a veronal buffer at a P.H. of 8,6 (an ample discussion of this will be found in the chapters I, III and V.).
At the routine visits the usual pregnancy examination was performed on the pregnant women (blood pressure, weight, examination of the urine on albumen and reduction, and external pregnancy examination).
After this therapeutics were discussed. With the girls with an ame
norrhea the course of the cycle of the last months was checked and a vaginal smear was made, after which therapeutics for the next period were discussed.
In general there was no question of a hypothyroidism with the groups of patients mentioned; the symptoms were too slight to indicate this.
With all of them the basic metabolism was too low or low-normal.
Often there were general complaints, with the complaint of chilliness especially prominent. Furthermore, several women complained of a dry skin, brittle nails, slow defecation, nervousness and apathy. All these complaints disappeared if thyroid hormone was used. At the same time many women declared that they feit much better and were capable of doing more work.
Occasionally the serum-cholesterol had increased. In genera! the Pro
tein-Bound-lodine was not reduced (except with the pregnant patients examined). The radio-activity in the albumen apex was rather high or too high in the electro-phoresis where radio-active thyroxine was added to the serum "in vitro" (see the chapters mentioned). The radio-activity in the albumen apex became low or normal after thyroid hormones and/or estrogens had been administered1 to the patients.
In the relevant literature, the above data were also mentioned. Gooiden and Burrell, Kurland, Hamolsky and Freedberg and Tittle state in their articles that there are more people with a slightly reduced thyroid ac
tivity than there are really hypothyroidal patients. They found with this group of patients possessing a slightly reduced thyroid activity a reduced basic metabolism, a normal Protein-Bound-lodine, a normal cholesterol content of the serum and a normal "uptake" by the thyroid gland of J131.
All these people had varying complaints: apathy, early fatigue, ner
vousness, irritability, psychic lability, sensitiveness to cold, headache, undefinable pains of the bones, reduced potency in man and menstru
ation disturbanses in woman.
The adrninistering of thyroid powder often had no influence on the basic metabolism or on the complaints. Thyroxine, in some cases, im
proved the complaints, hut had no influence on the basic metabolism.
Trijodotyronine caused the cornplaints to disappear and a rise of the basic metabolism in all patients.
According to Kurland, Hamolsky and Freedberg a combination of tri
jodotyronine and thyroxine should give still better results than tri
jodotyronine alone; especially the basic metabolism could then rise to normal values. The authors wonder whether the cause really lies in the thyroid gland, or if the action of the hormone in the periphery is disturbed since it cannot exercise its normal activity on the cells of the body because of an unknown impeding factor. The authors call this condition "hypometabolism".
We have treated with thyroid powder and/or trijodotyronine a number of women with whom, after ithe examination described above, we thought we had to diagnose a reduced thyroid function. We have checked in these patients the reaction of the basic metabolism, the Protein-Bound-lodine and the changes of the binding capacity of the Thyroxine Binding Protein in relation to the clinical course.
The research described was perfomed on 19 girls with an amenorrhea or an oligomenorrhea, and on 19 women with a bad obstetrica! anam
nesis before and during pregnancy. Furthermore one pregnant woman with a very low Protein-Bound-Iodine and a threatening abortion.
At the first examination the following was found:
Basic metabolism
between O tot - 15 per cent below - 15 per cent Increased cholesterol Reduced P.B.I.
with the group with amenorrhea:
8 2 11 7
bad obstetrie anamnesis:
between O till
+
10 % 314 6 1 3
This table does not give a complete impression because a Protein
Bound-Iodine determination was not made for alle patiens at the first examination, and moreover several pregnant women had been treated with thyroid hormone and/or estrogens before their pregnancy.
As to the clinical course, out of the 20 pregnant women who were treated 16 have been delivered of a living child while 4 are still pregnant.
Of the 19 girls with an amenorrhea or an oligomenorrhea treated, 19 have shown an improvement in the genera! condition, the basic meta
bolism, a better regulation of the cycle and a decrease of the genera!
118
complaints. One of these girls has been married, became pregnant and gave birth of a living child.
With the groups of patients mentioned there has also been an investi
gation as to the influence of the thyroid hormone and/or estrogens on the bindings ca pacities of the Thyroine-Binding-Iodine. Here one sees a very good influence especially of the estrogenic matter on this binding capacity. However, it is hard to express this in figures. An evidently favourable influence of the administering of estrogens on the Protein-Bound-Iodine can also be observed. This is noticed especially in women who show a reduced estrogenic activity in the cytological
hormonal image of the vaginal smear.
All this is discussed more amply in the chapters VI, VII and VIII.
Especially the trijodotyronine was used for the groups of patients men
tioned above, because the literature showed:
1. that trijodotyronine exercises a favourabie influence on sterility