The human fetal thyroid I. Its weight in relation to body weight crown-rump length foot length and estimated gestation ageкод для вставкиСкачать
The Human Fetal Thyroid I. ITS WEIGHT IN RELATION TO BODY WEIGHT, CROWN-RUMP LENGTH, FOOT LENGTH AND ESTIMATED GESTATION AGE' THOMAS H . SHEPARD, HENNING J. ANDERSEN AND HELGE ANDERSEN Department of Pediatrics, University of Washington, Seattle, Washington, Fetal Laboratory, Department of Pediatrics, University o f Copenhagen, Denmark and Laboratory of Cyto- and Histochemistry, Department of Human Anatomy, University of Copenhagen, Copenhagen, Denmark The weights of 75 human fetal thyroids were analyzed in relation to ABSTRACT crown-rump length, foot length, weight, and estimated gestation age. The ratio of thyroid weight to body weight was lower in the smaller fetuses and gradually increased until the fetus was 7&90 m m in crown-rump length when the ratio attained a value close to that found in the newborn and adult. This period of development when the relative weight of the thyroid becomes constant coincides with the time of appearance of colloid and the onset of ability to concentrate iodine. A comparison of estimated age of fetuses in the Danish material and the fomalinfixed fetuses from the Carnegie Collection shows the Danish fetuses under 40 m m i n crown-rump length to be four to six days older than the average given by Streeter. Streeter may have made his average too low and probably the relative ages of the two groups are comparable. There are very few records of the weight of the normal human fetal thyroid during the first half of pregnancy. Jackson ('09) reported 11 thyroid weights in fetuses under 150 mm but only four of these were from fetuses of less than 100 mm in crownrump length. Seven fetal thyroid weights were given by Pulaska ('29) for human fetuses of 115 to 145 mm in crown-rump length and Lucien and George ('27) also reported two thyroid weights. In addition, a thorough analysis of the relation of the fetal age to the crown-rump length of the non-pathological fresh fetus has not been reported. The majority of the previous crown-rump measurements have been obtained from spontaneous abortions and in most cases the determinations were made after fixation. (Retzius, '04; Jackson, '09; Mall, '18; Streeter, '20; Scammon and Calkins, '29; Arey, '47; and Trolle, '48). The purpose of this report is to relate the weights of developing thyroids to crown-rump length, foot length, body weight, and estimated gestation age. A comparison is made also between the fresh crown-rump lengths of the Danish material and those from Streeter's fixed fetuses. MATERIAL AND METHODS The material consisted of 22 fetuses from the collection of the Carnegie Institution, Department of Embryology, and 57 fetuses from the laboratory located in the Department of Human Anatomy at the University of Copenhagen. If the fetal period is defined as beginning after Streeter's horizon XXIII (27-31 mm crown-rump length) five of our studied specimens would be embryos. In this paper they all have been placed in the fetal group for the sake of continuity. Eighteen of the fetuses from the Carnegie Collection were fixed in 4% formaldehyde, and four were fixed in other types of fixative. All the Danish material was obtained within one-half to two hours after elective operative removal of the fetus by Cesarean or lower cervical section. Seventeen thyroids were weighed after fixation in Lillie's acetic-alcohol-formalin solution' ('54), 35 after fixation in 4% 1 This work was performed in the Fetal Laboratory at the Department of Human Anatomy University of Copenhagen and in the Department df Embryology Carnegie Institution of Washington Baltimore Mary: land, and was supported by the fiational In'stitutes of Health (grant AM06799-01HED) and by the Association for Aid of Crippled Children, New York. 2 Lillie's fixative contains: 85 parts absolute ethyl alcohol, five garts glacial acetic acid, and ten parts 4% formalde yde. 123 124 T. H. SHEPARD, H . J. ANDERSEN AND H. ANDERSEN formaldehyde (10% formalin), and 19 were weighed in the fresh state. Four of the thyroids were fixed in other types of fixative. Some of those fixed in formalin were transferred to 70% ethyl alcohol after an undetermined number of months. The thyroid glands were removed under a dissecting microscope and the anterior approach was used in order to determine the presence of the pyramidal lobe; in most cases both lobes and the isthmus were removed intact. Some difficulty was encountered in the removal of unfixed glands in specimens of less than 50 mm crown-rump length. The glands were kept in a moist state with isotonic saline solution and weighed immediately on a microanalytical balance. To study the changes in weight due to fixation, six glands of 20 to 106 mg were reweighed at intervals of days or weeks after being blotted free of any surface fixative. The fetuses were weighed to the nearest 0.1 g. The whole fetus and the thyroid were always in a similar state; namely both fixed in the same fixative or both fresh. In the Carnegie group of specimens, the crown-rump length was measured two weeks after fixation but in the fresh Danish material, over 35 mm in length, the vertebral column was straightened fmt by laying the fetus on a flat surface. Fresh specimens 35 mm or under were not straightened and were measured in their natural curved position. The foot length was measured according to Streeter (’20). The estimated gestation age for the Danish fetuses was obtained by subtracting 14 days from the menstrual age which was the period from the first day of the last menses to the day of operation. If the mother was unable to give the gynecologist a specific date for the time of onset of her last menstrual period, the age was not calculated. All available data on ovulation age from the Danish laboratory was plotted. The gestation ages for the fetuses from the Carnegie Collection were obtained by subtracting 14 days from the t o w7: THYRO/D $ 0 VS 60- c -R. L€ N e w x 0 0 F 50- ’9 x k x X 40- 0 30- X X x x 0 0 X x 20- x f f0.# xxrx X @x *‘: - 80 x . . . *. . ;o x * t o 125 HUMAN FETAL THYROID WEIGHT menstrual age but in some cases where the date of last menses was unknown the menstrual age was assigned by using Streeter's average sitting height. The sex of the Danish fetuses of less than 50 mm in length was determined by the presence or absence of the nuclear sex chromatin body of Ban. RESULTS The increase in thyroid weight with respect to crown-rump and foot length is illustrated in figures 1 and 2. There was a tendency for the glands fixed in Lillie's solution to be lighter while the weight of those fixed in formalin corresponded to the freshly weighed specimens. There were no differences noted in gland weights of male and female fetuses. As the fetus increased in length from 29 to 80 mm the thyroid weight in relation to body weight also increased (fig. 3). After 80 mm there was no apparent change in this ratio. The correlation coefficient between the thyroid to body weight ratio and the crown-rump length was 0.704 (p < + 0 wr THYROID VS FOOT L€NGTH a 0 0 I 5 .. I I 1 1 10 15 20 25 fOOT LlrNGTH mm. Fig. 2 Thyroid weight in mg plotted against the foot length in mm. The symbols are the same as in figure 1. One point could not be plotted because it was above the scale. 126 T. H. SHEPARD, H. J. ANDERSEN AND H. ANDERSEN .4 0 BODY W Z x100 0 0 0 0 \ 2 .03L a I i5 .@.Of- CROWN-RUMP LENGTH rnrn. Fig. 3 The ratio of the thyroid weight to body weight is plotted against crown-rump lengths in mm. The symbols are the same as in figure 1. CROWN-RUMP LENGTH mm. Fig. 4 Estimated gestation age is plotted against the crown-rump length in mm. Gestation was assumed to begin 14 days after the first day of the last menstrual period. The connected line is taken from Streeter's material and the dotted line from this study. x - Carnegie Collertion embryos used in this study. * - all available material from the Danish collection of fetuses. 127 HUMAN FETAL THYROID WEIGHT TH Y R 0 l B W € l G H T CHANGES A F T E R f I X A T I ON I 0 I 2 3 4 5 6 7 8 9 WEEKS Fig. 5 Thyroid weight changes after fixation in 10% neutral formalin (crosses, X ) and in Lillie's fixative (dots, .). 0.001) for the group below 80 mm whereas above 80 mm it was 0.002 which is not st atistically significant. The plots of gestation age and crownrump length of the Danish material were compared in figure 4 to Streeter's average which is a widely accepted standard in the United States. Below 40 mm all of the Danish ages are equal to or more than Streeter's average. Along this segment of the line (below 40 mm) 15 of the Danish specimens fall above, one on the line and none below. It is very unlikely that such a distribution could occur by chance. The thyroid weight changes during a seven week period following fixation are shown in figure 5 and it may be noted that there was a decrease with Lillie's fixative whereas with formaldehyde the reverse was usually seen. Thirty per cent of the glands had a pyramidal lobe; in eight it was in the midline, in six it was on the right side and in nine it was on the left side. The exact figures for the plotted measurements may be obtained from the senior author. + DISCUSSION The most striking finding is that the relative weights of the thyroid gland gradually increase until fetuses attain a crownrump length of 80 mm. This length represents an age of 80 days gestation and a developmental period which is functionally and histologically very significant. This period (75-85 days of gestation) is when the human thyroid first develops the ability to concentrate iodine (Chapman et al., '48; Hodges et al., '55; Andersen, '60). Although small amounts of colloid are present earlier there is also a very sharp increase in amount between 75 and 85 days (Norris, '16; Shepard et al., '64). After the 80 mm period the thyroid weight averages 0.0458% of body weight and this average is close to that of the newborn (0.049, Potter, '61) and adult (0.036). These findings do not agree with the few thyroid to body weight ratios reported by Lucien and George ('22) who observed an increase between the fourth and fifth months. However, they report only one thyroid weight for each month and do not clearly define their time periods. 128 T. H. SHEPARD, H. J. ANDERSEN AND H. ANDERSEN LITERATURE CITED The incidence of pyramidal lobes does J. 1960 Studies of hypothyroidAndersen, H. not seem to differ with age. The incidence ism in children. Acta Paed. Scand., Suppleof 40% in adults (Huber, ’30) is fairly ment, 125: 106-111. close to the 30% observed in this study. Arey, L. B. 1947 A new rule for correlating the age of human fetuses with size indices. Am. J. Pulaska (’29) found eight pyramidal lobes of Obst. and Gyn., 54: 872-873. out of a total of 64 fetal glands. Chapman, E. M., G. W. Corner, D. Robinson and The discrepancy between the gestational R. D. Evans 1948 Collection of radioiodine by the human fetal thyroid. J. Clin. Endocrinol., age of the Danish fetuses and Streeter’s 8: 717-720. “average” can be explained by the fact that Hodges, R. E., T. C. Evans, J. T. Bradbury and Streeter’s “average” up to 40 mm length W. C. Keettel 1955 The accumulation of radioactive iodine by human fetal thyroids. J. was calculated from timed monkey matClin. Endocrinol. and Metab., 15: 661-667. ings rather than human (Streeter, ’20; Huber, G. C., editor 1930 Piersol’s Human Streeter et al., ’51). If Streeter’s 11 plotted Anatomy. Ninth edition, Pages 1790,J. B. Lipspecimens under 40 mm are scrutinized it pincott, Philadelphia. can be seen that eight were above the Jackson, C. M. 1909 On the prenatal growth of the human body and the relative growth of the average line actually giving a distribution various organs and parts. Am. J. Anat., 9: quite similar to those of the Danish fetuses. 119-166. Scammon and Calkins (’29) and Schultz Lillie, R. D. 1954 Histopathologic Technic and Practical Histochemistry, page 35. McGraw (’19) have thoroughly discussed factors Hill Book Company, New York. which may alter the measurements of Lucien, M., and A. George 1927 A propos de l’evolution ponderale de quelques organes endofetuses. criniens chez le foetus humain. Compt. rendus Thyroid weights calculated from Jackde l’Ass. des Anatomistes, 22: 176-183, Lndres. son’s data (’09) are heavier and fit poorly, Mall, F. P. 1918 On the age of human embryos. if at all the data reported in figure 1. Am. J. Anat., 23: 397-422. Pulaska’s thyroid weights (‘29) determined Norris, E. H. 1916 The morphogenesis of the follicles in the human thyroid gland. Am. J. on fetuses from Hamburg fit the data on Anat., 20: 411-448. figure 1 but the three fetuses from Bern Potter, E. L. 1961 Pathology of the Fetus and the Infant, 2nd edition, page 14, Year Book had lighter thyroid glands. Medical Publishers Inc., Chicago, Ill. The weights of fetal thyroids from the Pulaska, Alfred 1929 Vergleichende histologische Danish and Carnegie group were found to Untersuchungen a n fotalen Schilddriisen aus Hamburg und Bern. Frankfurter Zeitschrift be comparable when the fixation was in fur Pathologie, 38: 29-63. formalin. In fact, the formalin fixed ma- Retzius, G. 1904 Zur Kenntnis der Entwicklung terial was quite similar in weight to the der Korperformen des Menschen wahrend der fotalen Lebensstufen. Biol. Untersuchungen, fresh glands from embryos of the same 11: (N.F.) 33-76. length. Unfortunately the data in figure 5 R. E.,and L. A. Calkins 1929 Growth does not answer the question of what Scammon, in the Fetal Period. Part I, pages 1-55, part 111, happens to the weight of the gland after pages 75-91. University of Minnesota Press, Minneapolis. the ninth week of fixation. Schultz, A. H. 1919 Changes in fetuses due to formalin fixation. Am. J. of Phys. Anthropol., ACKNOWLEDGMENTS Gratitude is expressed to the Chief Physicians: A. Christensen, M.D., Dept. of Gynecology, Bispebjerg Hospital, A. Fuchs, M.D., Dept. of Gynecology, Municipal Hospital of Copenhagen, V. Madsen, M.E., Dept. of Gynecology, Gentofte Amts Sygehus, and S. Stamer, M.D., Dept. of Gynecology, Sonderbro Hospital for the valuable cooperation in supplying the Danish fetal material. The senior author appreciates help given by Drs. James Ebert, Mary Rawles and Elizabeth Ramsev. 2: 35-41. Shepard, T. H., Helge Andersen and Henning Andersen 1964 The human fetal thyroid. 11. Histochemical studies during the first half of fetal life. To be published. Streeter, G. L. 1920 Weight, sitting height, head size, foot length and menstrual age of human embryos. Carnegie Inst. Wash., Pub. 274, Contributions to Embryology no. 55, vol. 11, 143-170. Streeter, G. L., C. H. Heuser and G. W. Corner 1951 Developmental horizons in human embryos. Contributions to Embryology no. 230, Reprint vol., 11s 166-186. Trolle, Dyre 1948 Age of foetuses determined from their measures. Acta Obst. et Gyn. Scand., 27: 327-337.