contribution to the study of the basal metabolism in goitre at puberty

From med. clinic 11, Serafimerlasarettet, Stockholm. (Physician-in-chief: Prof. H. C. JACOBBUS).

Contribution to the Study of the Basal Metnbo- lism in Goitre nt Puberty.

BY

SVEN M. ELDH.

After Magnus-I.evy had shown at the end of the 'nineties that the basal metabolism (i. e. production of CO, and consumption of 0, on fasting stomach and a t rest) was increased in morbus Basedovii, it was not until some 20 years later that his obaerva- tion became of any practical and clinical importance. The reason of this was that i t was only after Benedict, Krogh and others had succeeded in constructing clinically useful instruments for determining the basal metabolism that one began to take an interest in this and chiefly then in cases of thyroid affections. Before long a great deal was also written on these questions, especially in America, and as a result of these investigations the view was advanced that the most important and certain sign of hyperthyrosis was an increased basal metabolism, a view fairly generally accepted a t the present day.

With regard to the basal metabolism in goitre a t puberty, particularly girls, data are rather scarce and a certain amount of confusion seems to attach to this chapter, not least in regard to the clinical picture of this condition. In cases of goitre at this very age one often encounters rather great difficulties as regards the differential diagnosis. Thus i t happens not infrequently that the diagnosis of exophthalmic goitre is made even in cases where there is really a question of a diffuse (colloid) goitre with more or less prominent and often rapidly passing symptoms simulating hyperthyrosis.

,

STUDY OF THE BASAL METABOLISM IN QOITRE AT PUBERTY. 287

The clinical picture of goitre at this age.

Before dealing with the question of basal metabolism I would first like to submit, supported by the literature, a brief survey of goitre as i t occurs a t this age, its frequency and clinical signs and symptoms.

On this question it is stated by v. Pfaundler (in Feer’s text- book) that the parenchymatous form of goitre increases in frequency a t the time of puberty, in girls in particular. I n associa- tion with this we also get generalised cardio-vascular disturbances as the result of increased glandular function leading to ))Kropf- herz)) or morbus Basedowii. Children become taller. v. Pfaund- ler further says in the same paragraph that even in case of extensive goitres symptoms due to loss of function of the gland, enlarged through degeneration (hypothyrosis or acquired myxoedema and endemic cretinism) may be lacking.

C. Wegelin (in v. Bergmann-Staehelin’s handbook) makes a distinction, from patho-anatomical point of view, between a diffuse and nodular goitre. The diffuse goitre in its turn may either be a Basedow goitre with a diffuse hyperplasia of the thyroid gland or else a so-called diffuse colloidal goitre, histologi- cally impossible to differentiate from a normal gland. The diffuse colloidal goitre usually occurs in adolescence, often disappearing spontaneously a t the age of 20-30.

W. Palta (in v. Bergmann-Staehelin’s handbook) says as regards the differential diagnosis in Basedow’s disease that the occurrence of a goitre must be judged with care, particuIarIy in adolescence, as a goitre a t this age is likewise also diffuse and soft. It would seem clear, therefore, that Palta considers the Basedow goitre t o be soft. The importance of differential diagnosis here is further emphasized, as the goitre in adolescence generally subsides with iodine treatment without toxic symptoms occurring.

In a work published in 1909 I. Holmgren made a closer study of the effect of morbus Baeedowii and similar conditions on the increase in height and is the first t o have shown that the symptom complex goitre arid tachycardia in adolescent females proceed as a rule hand in hand with increase in height. This author is further of the opinion that some connection exists between hyperthyrosis (increased function of the thyroid) puberal phenomena and so-called functional albuminuria a t puberty.

288 SVEN M. ELDII.

Particularly in those cases where goitre and tachycardia have occurred in adolescence most of the cases have been tall individuals; while in those cases where the symptoms have appeared after adolescence, there have been normal proportions. The increase in height is average 5 em. I n the majority of these cases the tachycardia usually disappears after the patient has reached adult age. The following table from Holmgren’s work shows the height and weight of the body among the poorer classes in Stock- holm in 1906:

Table 1.

11 12 13 14 15 16 17 18 19 20

Ago Females TVoight Height in Kg. Height iu cm.

Weight.

years P

9

>

B

>

Y

>

,

. . . . . . . 140

. . . . . . . 144

. . . . . . . 152

. . . . . . . 155

. . . . . . . 157

. . . . . . . 159

. . . . . . . 160

. . . . . . . 160

. . . . . . . 159

. . . . . . . 159

29 32 36 39

49 51 54 56

-

-

139 143 148 153 158 167 169 170 170 170

30 32 34 37 42 46 52 57 61 63

21-25 > . . . . . . . 159 57 170 65

It will be seen from this table that the height in girls at the age of 13, 14 and 15 is 152, 155 and 157 cm. respectively and that as early as at 17 they have attained a height of 160 em., the average height for the female sex.

U. Hjgrne who, in investigating in 1921 the height, weight and state of nutrition, measured and weighed about 1,000 board- scliool girl8, found the body weight t o be definitely increased by about 7 per cent as compared with the weights submitted by C. fiunrlell in 1914. On the other hand there was no certain difference as regards the height. Holmgren’s, Sundell’s and Hjarne’s figures will be eyident from table 2.

Table 2. Board-school girls aged 12-14.

Body height in cni. 12 13 14

Body weight in kg. 12 13 14

years years years years years yrars IIolmgmn 1906 . . . . 144 152 155 32 36 39 Sundell 1914 . . . . . 145 151 156 34.3 38.6 42 Bjfirno 1921 . . . . . 145.9 150.6 155 37.: 41.4 46.2 ~-

Difference 1921-06 5.1 kg. 5.4 7.2

STUDY OF THE BASt\L METABOLISM IN GOITRE AT PUBERTY. 289

Patients with hyperthyrosis a t puberty are characterised by Holmgren as tall, early menstruating and mature girls of fair complexion, with goitre, tachycardia and tremor, pleasant t o look at, with shining eyes, abundant hair, lively and nervous and often with an intelligence above the average.

In a work by Hutinel in 1924, &es dystrophies de l’adolescence)) the author gives to my mind an exceedingly appropriate descrip- tion of the goitre a t puberty; I shall, therefore, take the liberty of giving a brief extract from his work.

The volume of the thyroid gland steadily increases till adult age and in particular at puberty, a normal condition which has never escaped the attention of the medical man. The organ under- goes a development that may lead to pathological changes; usually, however, the enlargement of the thyroid soon disappears without leaving any symptoms. In these cases the neck of the young girl is a little thick. The gland is somewhat enlarged but its tissue soft and elastic. There are never any pains, inflamma- tory reaction, adventitious vascular sounds or any nervous phenomena. The hypertrophy is too slight to be called goitre.

Sometimes, however, girls are seen whose thyroid gland reaches such a great size as to give rise to a true parenchymatous goitre. This goitre may diminish in size but persistent symptoms ought to be reckoned with and efficacious treatment be initiated. In a11 these cases the functional troubles in connection with a certain amount of hyperthyrosis are more or less marked; they may be absent, however, and there exists no definite relationship between the thyroid enlargement and the properties usually ascribed to hyperfunction of the gland.

In other young girls the symptoms of hyperthyrosis are sufficiently obvious not t o leave one in doubt about the case; prominent eyes, voluminous thyroid with well-marked veins. Ner- vous and psychical features as well as cardio-vascular symptoms become more marked and emaciation is frequently obvious. It is easy to recognise a more or less pronounced morbus Basedowii.

There are other cases, on the other hand, small in number, in which contrary symptoms are met with. These girls are not very tall, but well covered with puffy features, cold and cyanotic extremities and with a dull and sleepy expression. They are slow in their movements and indolent in their work. It is not a question of true myxoedema but a t least an easily recognised sign of hypofunction of the thyroid gland.

290 W E N M. ELDII.

Toivo Kaartinen ())Zur Klinik der Prapubertatsstrumao, Hel- sinki 1926) who examined 3,613 school-children in Finland 10-15 years of age, found 18.6 per cent afflicted with goitre. He found that the goitre attained its maximum size and frequency in the 13th year of life. Kaartinen also emphasizes the difficulty of distinguishing a mild hyperthyrosis from a favourable hypothyrosis on the basis of general nervous symptoms. He does not seem to have investigated the basal metabolism.

Earlier reported irivestigatioris into the bnsal metabolism iii cases of goitre at puberty.

Great interest is attached to the question as t o how this condition affects the basal metabolism.

Investigations into the metabolic exchange have, it is true, been carried out in cases of goitre a t puberty, yet this has mostly been done in solitary cases and further, the methods used by different workers have varied so much that the results of the investigations are difficult to estimate; bome further contribution to this question would therefore seem to be of interest.

H’Doubler inveetigated in Quervain’s clinic 4 cases of diffuse goitre in gills a t the age of puberty and found the basal metabolism to be normal (Schmeiz. med. Wch. 38, 926, 1922). An abbreviated survey of H’Doubler’s case will be found in table 3.

Table 3. . Survey o f the most important symptoms in H’DouLler’s cases

I I I f ’ I

e Histological ex. C a s e

As is evident from the table there were no real symptoms of hypertbyrosis in these cases. In relation to this case 3 is of par-

STUDY OF THE BASAL METABOLISM IN QOITRE AT PUBERTY. 291

ticular interest as the histological examination proved the Base- dow goitre t o be of characteristic nature.

I n Miiller's work ())Clinical investigations into the basal metabolism in diseases of the thyroid gland)) Copenhagen 192'7)) mention is made of 11 cases a t the age of 12-17. Of these 6 are diagnosed as Basedow or nforme frusteo, the others as simple goitre. Re- garding the different symptoms in the first 6 cases they will be clear from the following table:

Table 4. Survev of the most important sumpioms in Mdler's cases.

137g 12 152 em.

16 Y 167 cm. B,, 16 u l56cm.

1* , r 2

10 months 6 D

Diagnosis .I

Diffuse goitre . Goitre, no other signs Large goitre, s l ight palpita-

tion, no other signs Goitre, s l ight palpit. other-

wise ni l Small goitre, palpit. Vago-

tonia. Goitre for 3 years, no real

discomfort

120 %

C,, 16 Y 160cm.

It is of course a striking fact that the metabolic exchange in the cases of Basedow or Basedow eforme fruste)) is almost normal. It is only in case B 79, a girl of 12, and possibly in case B 82, that there is a clearly increased metabolic exchange. In none of the cases are there any ocular symptoms, nor are there in B 81 and B 82 any tachycardia or increased perspiration. The

%0--251705. d c t n vied. Scandii im. I'd. Ll7-Y.

1 month

292 SVEN M. ELDH.

symptoms, therefore, are very much alike those not infrequently occurring in girls a t the age of puberty, of favourable nature and generally disappearing before long.

Regarding the 5 remaining cases, cases of simple goitre, Misller himself does not wish t o draw any more definite conclusions on the question of basal metabolism but points out that the patients were children and evidently caused some difficulty during the examination.

In his book, odie Krankheiten der endokrinen Driisen)), Zondek refers to a case of goitre of Holmgren’s type, a girl aged 14, 171 ern. in height with goitre, palpitation of the heart, vasomotor hyperbensibility and for the last two years irregular menstrna- tion. No ocular symptoms, glykosuria or any disturbance in the metabolism. The O? consumption per kg. body weight and minute was 4.1 cc., thus a normal figure.

Gardiner, Hill, Brett and Forrest-Smith have investigated 100 cases of goitre a t puberty, partly with reference to the condition of basal metabolism. They seem to have used Du Rois’s standard for the estimation. In the opinion of these authors the colloidal goitre would seem to be the most usual form of goitre at the age of puberty. The authors, however, do not submit any closer details of the clinical symptoms and signs. The most important results of their investigations will be apparent from the subjoined table.

Table 6.

Colloidal goitre Exophthalm. Basal Normal hyperfunrt. hypofnnct. goitre metab.

0 % . . . . . . . . . . 6 6 % 0 % 100 % above 10 %

1 0 0 % . . . . . . . . . . 3 4 % 63 % 0 x + l O - l O % o r 0 % 37 % 0 % below 10 x . . . . . . . . . .

Any further reference t o instances of investigations pertaining to this subject would seem unnecessary. Numerous investigations have been published particularly from America; all these publications, however, generally deal with reports of odd cases or express more generally held opinions, more or less contradic- ting each other. The basal metabolism is generally considered t o be normal.

S T ~ J D Y OF THE BASAL METABOLISM IN GOITRE AT PUBERTY. 293

The reasons of the partly conflicting statements with regard to the results of investigations.

What may be the cause, then, of the conflicting data submitted? One of the most important reasons would seem to be the fact that the different authors have not always been of the same opinion as to how the individual case should be classified in reference to the character of the gnitre and other clinical features. In doing this one has not always perhaps paid sufficient regard to the effect of different geographical and other circumstances, undoubtedly playing a great part in the production of different forms of goitre. Moreover, most authors have often been satis- fied with occasional examinations.

Another factor that adds still more to the difficulty of judging the different results of the investigations is the variable nature of the methods employed, both in regard to apparatus and basis of calculation. In order to elucidate this question it will be ne- cessary to enter a little more in detail into the factors upon which the basal metabolism is calculated.

The instruments usually employed would seem to be those of Benedict and Krogh. For estimating the normal caloric value there are several formulas in existence based on larger series of examinations of normal individuals, particularly carried out in America. Harris and Benedict who among others have carried out such examinations consider the basal metabolism to be de- pendei:t upon sex, age, body-weight and height. The tables elaborated on the basis of these investigations would seem to be considered by most authors as fairly reliable, a t least in regard t o adult persons. In dealing with children, however, most authors are, I suppose, agreed that the determination of the basal metabolism must be done along different lines. Some workers have, therefore, considered it more correct to use the size of the body surface as the basis of calculation. For the estimation of this different formulas have been advocated. Formerly Meeh’s formula was used, A = 12.3 \i 3 g2, where A = the surface in ema, g = the weight in grams. The constant 12.3 has subsequently been changed by new calculations but Meeh’s formula, being based on the weight alone, has been subjected to criticism.

In Du Bois’ formula, on the other hand, both weight (P) and height (L) enter as factors, the formula having the following

294 SVEN M. ELDH.

appearance: A =-1 P'),"' x L"."' 2: 71.84. This formula has been much in use and is not said to deviate from the mean value more than k 10 yo.

Benedict and his co-workers have tried to compute the basal metabolism for girls in the age period 12-17 on the basis of the body weight (Table 21 in Carpenter's collection of tables). From several quarters, however, even by Benedict himself, it has been maintained how exceedingly uncertain it is to base the estimation of the normal metabolism on the body weight alone.

Kestner and Knipping have by investigations of their own computed tables for the normal caloric value in persons below 21 years of age and thereby supplemented Harris-Benedict's tables. Kestncr-Knippinp consider their tables to be uncommonly reliable and the deviation within normal limits is not supposed to be greater than k 5 :!,. Following Kestner-Knipping's tables J have in what follows estimated the normal caloric value for girls a t rest in the age period 12-17 and of medium height and weight:

Table 6.

Age-Years Height cni. Wcight kg.

1 2 . . . . . . . . . . . . 144 3 2 13. . . . . . . . . . . . 153 36 1 4 . . . . . . . . . . . . 155 39 1 5 . . - . . . . . . . . . . 157 1 6 . . . . . . . . . . . . 159 49 1 7 . . . . . . . . . . . . 160 51

Calory consumption per 24 hours at rest.

1211 1259 1282

(1422) 1370 1386

Liebeschutz-Plaut-Schadow in their investigations of children a t puberty found a deviation from Kestner-Knipping's normal values from -4 yo to + 8 yo and considered figures below -8 :h and above + 12 yo as pathological. Of 4 cases with hyperthyroidism a*t this age the figures did not exceed $. 20 yo.

As will be clear from the aforesaid there are a good many formulas to chose from; in what way the values of basal metabolism estimated by various formulas, are related to one another, will be shown in what follows.

In the hope of being able to contribute to the knowledge of the basal metabolism in ca,ses of goitre a t puberty I have investigated 19 such cases at the physiological laboratory of ))Serafimerlssa- retteto and further examined the laboratory records of still another 21 cases in reference to this question. The persons examined ha,ve

STUDY OF THE BASAL METABOLISM I N GOITRE AT PUBERTY. 295

been partly out-patients, partly pat,ients treated in the medical and surgical clinics. The examinations have been carried out in accordance with Krogh’s method. In order t o obtain the most reliable results possible great stress has been laid on the importance of the patients lying down a t complete rest for a t least 30 minutes before the examination. By carefully instructing the patients as regards the respiratory technique we have endeavoured to ex- clude the effect of fright and nervousness prior t o the examination and the curves we have obtained are exceedingly even and pretty; only in a small number of cases have I been obliged to leave out the curves on account of their unevenness. I n those cases where there has been cause for uncertainty in the estimation of the curve repeated examinations have been made; on the other hand, more extensive serial examinations have only been made in a small number of cases; in the majoraty of cases, however, a t least two or three curves have been taken. As several different factors contribute to the production of too high a figure for the basal metabolism, the lowest obtained has generally been stated.

Furthermore, the material has in no way been selected but com- prises instead the aggregate number of patients in the age period 13-17 referred to the laboratory under the diagnosis of goitre for having their basal metabolism determined.

When i t came to judging the results of the examination, however, one was confronted with rather complicated questions. In the first place I am thinking, then, as already mentioned, of the uncertainty in regard to the standards. As a rule the figures have been calculated after several different formulas but some of these, e. g. that of Benedict-Baker-Hendry (table 21 in Car- penter’s collection of tables) give so decidedly abnormal figures as to be of no use. Aub-Du Bois’s formula, on the other hand, based on the law of the body surface, and that of Kestner-Knipping accord in a striking manner with one another due to the fact that partly common factors enter into both formulas. The former generally gives 7 units lower figures than the latter. These two formulas have, therefore, been used in the estimation. The values obtained, however, must be judged with great care in cases where the body height is abnormally great or small.

The figures in those cases, on the other hand, where the body height is very nearly normal, can therefore be considered t o be more reliable and will be especially examined further on.

Another matter t o which attention must be paid in dealing

296 SVEN M. ELIJII.

'2. D. W.

1. G . W. 15: Colloidal goitre 2. A. I). 17 Diffuse Basedow goitre 3. D. K. 16; Basedow goitre 4. M. J. 16$ Goitre+exophthalm. 5. E. Z. 141 Adeuomatoiis goitre 6. (i. C. 133 Diffuse goitre 7. J. G. 16 Colloidal goitre 8. G. S. 144 Hyperthyroidism 9. E. E. 16 Morbus Hasedowii

.O. K. 11. 15; Diffuse atoxie goitre 1. A. Z. 15: D > I

2. E. J. '15 basedow goitre a. V. F. 15 Morbus Baseduivii 4. V. A. 16 Simple goitre 5. I. J. 175 Colloidal goitre

Slight hvuerthvrosis

16 Morbus Basedowii? 165+ 6 56 u

167+ 9'52 k g

163+ 355 B

170+1453 n 159+ 6138 D

163 t 4'50 1

163+ 7 4 2 )>

171+1245 9

1 5 8 f 0 5 7 > 1597 1 4 9

156- 4 5 6 9

157- 357 ))

17 !4. A. F. I 1 3

172+15'5ti Y

166 i- 950 * 167t 856 r 167+ 7161 ))

1

Diffuse goit,re 165-1- 561 I

Goitre 158- 1 4 1 P

10. E. H. 171, l I a K . E . 1 3 1 l b E . E . 17 1% B. 5. 16;- 13. B. M. 15

15. I. L. 124 16. S. I%. 158

14. CT. A . 15a

'5. E. B. 114'1 n '158+ 3/46 ))

16. E. D. 14 Neurosis 17. S. C. lh l Diffuse zoitrc

3 I 9 156- 4147 B

r 8 n 1 6 1 1 9j46 u

Diffuse goitre 1166 -t- 6 50 3

P N I 1%- 169 D

Rapid growth in height I171 + 14 42 Y

Mild diffuse goitre 158+ Gl?3 B

3 r , 158-C 0134 9

n I P r 174+1653 ))

17. M. J.

19. A. S. 18. E. K.

3 years

23 D 1.) 9

3 3 1 year

2 years

3 r

1Si i D r D 156+ 4 52 > 15; B n n 1611 354 8

15: 3 > 2 ;161+ 240 P

2 .

0 1 year 0

I

2 B 2 monthe 2 years

Table

1 year 3 years 2 5

1 year % years 1 year 4 yeare 1 year 2 years 3 n 5 . 2 u 2 u 1 vear 3 ;ears

0 months 3 years 7 n 4 u 2 > 1 year 1 r 2 years 1 year 1 month

yeal'd 2 . 2 >>

1 year 4 years ? 5 > 1 year 4 years l+ 9

2 m o n t h

i ;z 4 r 1 year

+ - t + + + + 1-

+ t t i- i- + .t t i- + +

I

with these questions is the difficulty to decide whether or not a goitre really exists. In particular must one beware of diagnosing goitre in several of these young girls who just a t this age grow rapidly. A fully normal thyroid gland may a t this age stand in

298 SVEN 31. BLDH.

material cases are also examplified where merely a slight swelling of the front part of the neck has been labelled goitre, not only by the patient herself but also by her doctor, particularly in cases where some nervous vasomotoric symptoms have been present.

For estimating the results of the investigation I have divided the material into the following groups:

Group I: Cases of goitre with clinical symptoms of hyperthyrosis (morbus Basedowii) cases 2, 3, 4, 8, 9, 12, 13 and 15;

Group II: Cases of goitre without clinical symptoms of hyperthyrosis, cases 7, 10, 11, 14, 16, 17, 18, 19, 20, 23, 24, 25, 26, 27, 28, 29 and 30;

Group Ill: Cases of goitre of Holmgren’s type, cases 1, 5, 6 and 22 and from Group I 8, 9, 12, 13, 15.

Group IV: Cases of slight, diffuse enlargement of the thyroid, ))thick neck)), cases 21, 31a, 31b, 32, 33, 34, 35, 36, 37, 38 and 39.

The main symptoms will be clear from table 7. The diagnosis as taken from the medical and surgical reports is

probably based, besides on purely clinical signs and symptoms, partly on the rate o€ basal metabolism, partly on the patho- anatomical examination in cases operated upon. The bracketed figures indicate increase or reduction above or below the normal height. The following abbreviations are used: GI =; Glanzauge, M = Moebius’s symptom, Gr -- Graefe’s symptom. The basal metabolism is indicated with 100 % as the normal value and with a normal margin for variations of 10 %. The figures are given in the text in the order: AD/KK, AD = Aub-Du Bois’s, KK -- Kestner-Knipping’s standard.

When i t is a question of forming an opinion as to the condition of BMB a t the age we are concerned with here, it is not sufficient, as has already been emphasized, in consideration of the variable manner in which different individuals grow, only to pay attention to the individual value of BMB. By comparing, however, the resiilts obtained in those cases where the individuals present the greatest possible similarity as regards age, height, body weight and clinical symytonis it might perhaps be possible to obtain more trustworthy figures. On the basis of what has just been said I will now attempt to make a few com- ments.

The question as to whether and in how many cases a true hyperthyrosis has been present is not easy to answer, the more

STUDY OF THE BASAL METABOLISM IN GOITRE AT PUBERTY. 299

so as I have not had the opportunity of examining all the cases myself. Yet, there is no doubt that among the cases under review there have been those exhibiting the clinical picture oi hyperthyrosis. As evidence in support of this we have, for example, cases 2, 3, 4, 8, 9, 15 and 22, all in which the diagnosis was made by experienced investigators. In cases 12 and 13 hyperthyrosis would certainly seem to have been present.

In estima.ting the BMB figures in the cases mentioned the figures in cwes 31 b, 38, 28, 33, 34, 23 and 32 may be taken for comparison, the patients in the latter cases being of about the same age, height and weight as in the former and both signs and symptoms exceedingly slight, as is the case with the cases referred to Group IV. The same holds good also for some of the cases in Group 11.

Table H.

115/117\ 114 1181 105’113 1171128 l l l j l20 156,162

Symptoms simulating hyperthyrosis

31 b

38 . 28 . 33 . 34 .

1 Age Heigh case ~ years 1 cm.

1301146 ~

8 . 9 .

12 . 13 . 15 .

22 .

- .

2 . ) 17 4 . 1 16% 3 . 1Gi

14+ 16 15 15 1 7%

16

166 157 163 163 171 172 166 167

165

Weigh kg.

56 57 55 42 45 56 50 61

56

-

No hyperthyrosis

Age Height Weigh1 years ~ cm. ~ kg.

17

15; 143 15

151

17

163

159 ~ 59

I 161 161 171 174

165

166

54 45 42 53

61

50

BMH g

-- 90195

90/98 98il05 951102

101j114

100/114

96/99

It is clear from the above comparison that in cases 12 and 13 the figures are obviously increased while in the others they are found to be within normal limits or only slightly increased.

Cases 2 and 4 are found to be almost identical as regards age, height, weight and chief symptoms. As the weight and height do not differ much from what is normal for the age in question, the figures for BMB may be considered fairly reliable. In case 2 morbus Basedowii was undoubtedly present, verified by patho- anatomical examination. In case 4 one was content with diag-

300 SVEN M. ELDH.

nosing goitre plus exophthalmos. It is quite certain, however, that also in this case sympt,oms were present usually at,tributable to hyperthyrosis. One had expected, therefore, t o find a con- siderably increased BMB, yet, such was not the case. The values 115/117 in case 2 and 114/118 in case 4 can, of course, be considered to be lying within normal limits. In case 4 repeated examinations were carried out and after 14 days' treatment in hospital the BMB fell to 90/94 per cent.

What t,he values of BMB are like in those cases where tremor was found to be present will be clear from table 9. Only those cases are included here in which the tremor has been described as being fine or rapid.

Table 9. Case Diagnosis Tremor BMB %

. . . . . . . . . . . 3 Basedow goitre + 105/113 (Path. anat. diagn. Colloidal

goitre) 8 . . . . . . . . . . . Hyperthyroidism ( + ) 117/128

12 . . . . . . . . . . . Basedow goitre + 1561162 13 . . . . . . . . . . . Morb. Basedowii + 130/146 15 . . . . . . . . . . . Colloidal goitre (+ ) 133-1121143

16 . . . . . . . . . . . Colloidal goitre + 113/118 21 . . . . . . . . . . . Diduse goitre f 94/101

. . . . . . . . . . . 92 ' 102 22 Morbas Basedowii? + Besides increased BMB, tachycardia and goitre tremor is of

course one of the cardinal symptoms in hyperthyrosis. In the two cases 12 and 13 where hyperthyrosis would undoubtedly seem to have been present we find tremor and an increased BMB. In cases 16, 21 and 22, on the other hand, which also showed typical tremor the figures are found to lie within normal limits. This was also the condition in case 3 where a colloidal goitre was found at the operation. It may be naturally assumed, then, that it is just such cases as the last mentioned that will be found in the literature with the diagnosis Basedow despite normal BMB and with the explanation that other factors than the thyroid gland may influence the BMB.

Although the clinical symptoms in these casea belonging to Group I are fairly similar and in favour of hyperthyrosis being present, we find that the BMB estimation in some of the cases have given values within normal limits or only slightly increased.

Regarding the BMB in the cases belonging to Group II we can probably also here get some idea about i t by comparing those

(Slight hyperthyrosis)


cases which best correspond with each other as regards age, height and weight.

Let us consider, for example, cases 10 and 27 with BMB values of 83/92 and 100/109 respectively. The first of these two cases was a colloidal goitre and the somewhat low BMB figure would seem to favour a certain degree of hypo-function of the thyroid.

The BMB figures in cases 11 and 20, 89 and 101 per cent respect- tively, lie within normal limits. In cases 18, 25 and 28, compa- rable with one another, the figures in the last two cases were fully normal, in case 18 the value 80187 per cent will probably have to be regarded as just below the normal. After about six weeks’ thyroid medication the figure went up to 108 per cent. Fully normal figures are also found in cases 19 and 23.

Regarding the other cases in Group I I we find from table 7 that they on the whole show figures for BMB lying withi?& i~ormal limits. Cases 29 and 30 were found to have the lowest figures, 83 and 86 per cent respectively, cases 14 and 16 the highest, 113 per cent.

To Group I I I have been referred those cases of goitre which in addition to symptoms resembling hyperthyrosis have showed an abnormal growth in height and had been regarded as of being of Holmgren’s type. In cases 12 and 13 we have undoubtedly to do with morbus Basedowii with figures for the BMB of 156 and 130 per cent respectively. These can be compared with the fully normal values obtained in cases 33 and 34, the latter accor- ding fairly well with the former as regards age, height and weight though lacking both signs and symptoms.

In all the remainiml cases beloibging to Group I I I the figures are quite normal with the exception of case 15 with a figure of 133 which, however, after some time’s hospital treatment fell t o 112.

In the cases referred to Group I V the symptoms are exceedingly slight, the signs being confined to a slight diffuse enlargement of the thyroid, ))thick neck)), scarcely justifying the name of goitre. Well in accord with this the BMB figures are also perfectly normal. It is only in case 39 that the BMB value, 74 per cent, is obviously lower than normal and might be in favour of a possible hypofunction of the thyroid. After some time’s thyroid medication the ))Goitre)) disappeared and the patient felt quite well.

Although, as already pointed out, great care must be exer- cised in judging the BMB value when dealing with patients of

302 SVEN M. ELDH.

this age, some conclusions can nevertheless be drawn from the results obtained of the above investigations.

In the first place one must count a t this age on a very much greater margin of variations concerning the limits of the normal BMR value than in the case of adults and this the more the individual height and weight deviate from the normal figures for the age in question.

Under this presumption one would seem justified in considering an obviously increased BMB value as supporting the diagnosis of hpperthyrosis but, as would also seem to be clear from the present material and from what other authors, too, have deemed right to state, a normal BMB value does not justify one to ex- clude the presence of hyperthyrosis in those cases where other clinical symptoms are in favour of it.

Because just as a single clinical symptom is not sufficiently characteristir for justifying the diagnosis of hyperthyrosis, i t is for the present impossible, in the case of patients of this age, t o consider the examination as emphatic in those cases where the result thereof is against a typical clinical picture of hyperthyrosis.

In such cases or goitre showing a number of definite clinical symptoms of hyperthyrosis but with a BME figure lying nithin normal limits, one can, as assumed by Zondek among others, count on the possibility that we are not dealing with a pure hyperfunction of the thyroid but rather a dysfunction as a result of the effect of other endocrinic organs.

On these hypothetic lines it would perhaps be possible t o explain the peculiar mixture of symptoms reminding of hyperthyrosis and such usually considered due to a hypofunction of the thyroid, a symptomatological picture not infrequently met with in case of goitre in girls a t the age of puberty.

Cases.

1. G. W. Colloidal goitre. Mother and one sister goitre. When 8 years old had a swelling of the neck, rapidly growing during the last year. Been nervous and restless, often palpitation of the heart, tre- inor in hands. Has not lost weight. No diarrhoea. Present condition: seenis quiet. Skin not moist. No ocular symptoms. Swelling in the neck, quite the size of a child’s fist, of a consistency as hard as cartilage. Operalion: resection of colloidal goitre, verified by Fathoanatomical examination.


2. A. E. Diffuse goitre. [Basedow.] One brother goitre. Menstrua- tion began three years ago, the thyroid gland began to grow a t the same time, difficulty in breathing, nervous and restless, eyes commenced to show prominency, palpitation of the heart, was given roentgen treatment, but symptoms became worse Present condition: pulse 120. Graefe pos. Marked exophthalmos. Thyroid smooth uniformly enlarged: operation. Path. anat. diagn.: typical Basedow goitre.

3. D. I(. Basedow goitre. Always weakly. At age of thirteen albuminuria. For several years goitre which increased in 1921; in connection with that, nervousness and palpitation of the heart. No diarrhoea. Been given iodine pills and roentgen treatment. Goitre diminished, but other symptoms rather increased. Subsequently tremor. Has not lost weight. Present cond.: well developed girl, nervous, pulse 120, heart systolic murmur, blood pr. 160,BO. Symmetrical tumour in the neck: solid and the size of a goose-egg. Tremor. No ocular symptoms. Operation: partial resection. Out surface dry, grey-brown, not quite so poor as a Basedow goitre in colloids. Path. anat. diagn.: colloidal goitre.

4. M. I. Goitre and exophthalmos. Two aunts goitre. At age of twelve had a thick neck, but no discomlort. Goitre increased in size during 1924. At the same time became short of breath, palpitation of the heart set in, restlessness, sweating, got thinner, eyes became prominent. Menstruation commenced a t fourteen, a t first regular, but ceased concurrcntly with the aggravated symptoms, returned subsequently. Never been troubled by tremor or diarrhoea. Present cond.: moist skin, slight tremor. Exophthalmos. Graefe negative. Moebius + on the left, Stellwag pos. Thyroid diffusedly enlarged, smooth. During treatment with insulin weight increased from 57 to 61 kg.

5 . E. Z. Adenomatous goitre. 3-4 years ago the lower part of the neck became thicker. Restless and nervous, lost weight, no palpitation of the heart. Menstruation for the last eighteen months. Pre- sent cond: pulse 80, thyroid enlarged and hard. No ocular symptoms.

6. G. C. Diffuse parenchymatous goitre. For the last year troubled with goitre, that has lately grown rapidly; has easily became short of breath, very nervous, and been troubled with palpitation of the heart. No perspiration. Has not lost any hair, no diarrhoea, no tremor. Present cond.: thyroid moderately diffusedly enlarged, soft, no vascular sounds. No ocular symptoms.

7. J. G. Diffused colloidal goitre. The youngest of five sistem and brothers, who have all suffered from goitre in a greater or lesser degree. In the eldest of these three, the goitre has subsequently disappeared spontaneously. Patient has noticed her goitre, for the last 3-4 years, it has grown gradually and has not altered in shape. No subjective symptoms. Has not got thinner. Menstruation normal. Present cond.: thyroid diffusedly arid symmetrically enlarged, gIanular, soft and elastic.

8. 0. S. Hyperthyroidism. For a couple of years swelling of the neck gradually increasing in size. Slight nervousness and restlessness. Cardiac palpitation and sweating. No diarrhoea. Present cond.: some- 'what widened and stiff look [Glanzauge]. No real Basedow appcarance. Slight tremor in the fingers. Thyroid cliffusedly enlarged and soft.

504 SVEN 111. ELDH.

9. E. E. Basedow goitre. Two years ago patient noticed a swelling of tlir site of the thyroid, at the same time as developing exophthalmos. Palpitation of the heart. Despite operation, exophthalmos and palpitation remained. Present cond: right lobe of the thyroid extirpated, left lobe and isthmus enlarged, of firm consistency. No obvious tremor. Skin riot moist. Obvious exophthalnios. Pulse 96.

10. K. I,. Atoxic diffused goitre. Goitre since birth, grown for the last three yeais. Has begun to be nervous and perspires a great deal. Menstruation for three years. Present cond.: well developed for her age. Thyroid diffueedly enlarged and firm. No vascular sound. No ocular symptoms, no tremor, pulse about SO. Operated upon under the diagnosis diffused atoxic colloidal goitre. Path. anat. diagn.: colloidal goitre without Basedow symptoms.

11. A. Z. Atoxic diffused goitre. Two sisters goitre without symptoms. Beer, living in Giivle. Goitre for the last five to six years. No symptoms. Menstruation for the last eighteen months. The goitre has not grown in connection with the puberty. Present cond.: thyroid diffusedly enlarged and soft. No ocular symptoms. No tremor. Opera- tion. Path. anat. diagn.: large follicles with thin contents. Here and there the picture reminds in no small degree of Basedow.

12. E. J. Rasedow goitre. For the last two years been restless and nervous. Cardiac palpitation and loss of hair. Been loosing S lip in weight in a few months. Perspirations. Present condition: not thin, skin moist. Fine tremor. Pulse 120. Thyroid diffusedly enlarged, even and soft. Vascular sound. Slight exophthalmos, ehiny look. Moebius -+. [The left eye deviates outwards a t a distance of 5 cm. from glabella.]

Operation. Path. anat. diagn.: typical Basedow. 13. V. F. Basedow. Menstruation a t 13. Always been nervous and

of hasty temper. Goitre for a couple of years. Lately cardiac palpitation, sweating and diarrhoea. Eyes more prominent than before. Pre- sent condition: tremor, exophthalmos. Tachycardia. Glycosuria,. Thy- roid moderately enlarged. [Patient is now still and quiet.] Exophthal mos and palpitation gone after three months.

14. V. 4. Simple goitre. Six months ago enlarged thyroid. Present coiidition: no obvious nervousness. Pulse 96. No tremor. No ocular symptoms. Thyroid diffusedly enlarged, fairly firm. Hm since become nervous. No exophthalmos.

15. I. J. Colloidal goitre. Slight hyperthyroidism. Three years ago goitre was incidentally found. Was given iodine pills for a year. The goitre has since increased. Been nervous during the last month. Pal- pitation of the heart, sweating. [Domestic troubles.] Present condition: depressed. No ocular symptoms. Slight trembling but no typical tremor. Tachycardia. Thyroid moderately and diffmedly enlarged, mainly isthmus, even, tough and soft consistence. No obvious reaction to 0.5 mgrm. adrenalin.

16. T. T. Colloidal goitre. Noticed a goitre ten months ago. Short of breath on climbing stairs. Been perspiring a great deal. Present condition: tremor. Thyroid, especially isthmus and the left lobe, enlarged.. Pulse 72.

STUDY OF THE BASAL METABOLISM IN GOITRE AT PUBERTY. xo5

17. M. J. Diffuse colloidal goitre. Has had goitre for several years. Reen aggravated especially during menstruation. Difficulty in swollo- wing. No nervousness, sweating or emaciation. Dull and tired lately. Present condition: enlargement of both lobes, mostly the right and isthmus. No ocular symptoms. No tremor. No tachycardia. Operation. Patho-anat. diagnosis: colloidal goitre.

18. I. 5. Goitre [hyperthyroidisin]. Treated for pulmonary disease a t Styrso 1920. Goitre was then found, subsequently increased somewhat in size. Been feeling anxioiis and restless. Perspires easily. Menstruation regular since the age of 11. Present condition: thyroid obviously enlarged and Hoft. No tremor. Wo ocular symptoms. Been given thyroid tablets.

19. M. S. Diffuse goitre. Goitre for many years and been having a husky voice as long as she remembers. For the last few months been tired, restless and nervous. Has not got thinner. Present condition: healthy appearance. Pulse 100. No ocular symptoms. No tremor. Thyroid diffusedly enlarged and the Fize of a tangerin.

20. A. V. Adenomatous goitre. Goitre two years ago which subsequently grew bigger. No discomfort. Present condition: no signs except for the thyroid, both lobes equadly enlarged.

21. A. 0. Diffuse goitre One sister, aged 12, goitre. Had a thick neck one pear ago. Has lately been nervous and had a iapid action of the heart. No diarrhoea. Sweating much. Present condition: thyroid somewhat diffusedly enlarged, fairly soft and even. Fine tremor. no ocular symptoms.

22. D. W. 1. Morbus Basedowii. For the last year goitre, nervousness, cardiac palpitation and sweetings. Eyes more shiny, has not lost weight. Dyspnoea on exertion. Present condition: seeins quiet, skin somewhat moist. Tremor. Pulse about. 100, ))GlanzaugeH. Thyroid: slightly enlarged and of a soft consistence.

23. K. E. Diffuse goitre. Parents, gisters and brothers tall. Two years ago neck began to get thick. Sweating but no loss of hair. No cardiac palpitation. Is quick of temper. Menstruation began a t the age of 15 [tw-o years ago]. Present condition: thyroid uniformly enlarged a,nd firm. Does not seem to be nervous. Piilse 70-80. No ocular symptoms, no tremor.

24. A . F. Goitre. One sister, aged 14, goitre. About one year ago her neck began to swell without any discomfort. Otherwise no abnormal signs.

25. E. B. Goitre. Neck began to swell about one month ago. No cardiac palpitation or nervousness. Not lost weight. Has not been sweating. No tremor. Has not begun her menstruation. Present codition: pulse 84. Moderate, uniform and diffuse enlargement of the thyroid. Soft. elastic and smooth. No vascular sounds. No ocular symptoms. No tremor. Was given thyroid tablets on discharge.

26. E. D. Neurosis. In the spring 1927 nervous aad tired. Cardiac palpitation. Depressed. Menstruation regular and painful. ))Glaaz- augeo. Thyroid moderatley and diffusely enlarged. Slight tachy- caIdia.

306 SVEN M. ELDH.

27. 8. C. Mild diffuse goitre. No goitre in the family. Not begun to menstruate. Goitre for a couple of years, lately increasing in size; no discomfort but has been a, little short of breath. Has herself noticed a certain amount of torpidity, has had difficulty in comprehending. In the last year been gaining 15 kg. in weight. Present condition: big for her age, seems somewhat slow psychically. Diffuse moderate enlargement of the thyroid, fairly firm, weak vascular sounds. No ocular symptomR, no tremor. Pulse 80. Marked cyanosis of hands

. . and forearms.

29. M. C. Diffuse goitre. No goitre in the family. In 1925 lymphoma of the neck. Has a.lways been somewhat filled out in the neck. This has never caused any discomfort. Slugyish bowels. Periods at 12. Present condition : thyroid diffiisedly enlarged, fairly soft and elastic. Eyes lying deeply. No ocular symptoms. No tremor. Pulse 108.

29. E. I?. Diffuse goitre. Mother goitre. Herself always been well. Goitre since childhood. Been getting bigger during the last year. Has not become nervous. No cardiac palpitation. She thinks she has increased in weight by 5 kg. in one year. No sweating. Slight trembling in fingers. No ocular symptoms. Has noticed no psychical change. Menstrual periods since the age of 14, Formal. Present condition: stout and plump. Thyroid moderately and diffusedly enlarged, fairly soft. No vascular sounds. No tremor. Pulse 74. Eyes normal.

30. E. H. Slight diffuse goitre. Mother goitre. In good health before. Menstruation began a t 13. Goitre present for the last three years, growing large particularly during the last year. Always tired. Itching over the body during tho last month. Very nervous and restless. Often palpitation of the heart, especially on exercise. No ocular changes. No tremor. Hand-sueat. Present condition: moderately diffuse enlargement of the thyroid, fairly soft. Otherwise nil. Eyes rather tending to be more deep-lying than otherwise.

31a. K. E. Mild diffuse goitre. Maternal grandmother goitre. Pre- viously in good health. Has been somewhat filled-out in the neck since quite small. Peels quite well. geeking advice for her neck from esthetic reasons. No discomfort. The left ocular fissure always been somewhat narrower than the right. Not yet begun menstruation. Present condition: thyroid slightly diffusedly enlarged. Left ocular fissure somewhat narrower than the right. Ptosis? Otherwise nil.

31b. E. E. Mild diffuse goitre. No goitre in the family. Menstrua- tion fiince the age of 15 Rince the age of 12 been thick on the front of the neck. No discomfort. Easily nervous when excited. Has particularly grown much since the age of 12. Present condition: stout, appears somewhat slow. Thyroid diffusedly and very moderately enlarged. No ocular symptoms. Pulse 65.

32. B. J. Diffuse goitre. Mother operated on for goitre. An elder sister goitre. In February 1924 nervous and slept badly. Easily excited. Since then palpitation any more and more restless. Patient had not herself noticed any swelling of the neck. Has not got thinner. Slight trembling in hands. Present condition: pulse 98. Thyroid slightly diffusedly enlarged. No ocular symptoms, no tremor.

STUDY OF THE BASAL METABOLISM IN UOITRE AT PUBERTY. 307

33. B. M. Has rapidly grown taller. The last year been weakly and thin. Has grown a great deal. No ocular symptoms. No palpitation. Not nervous. No diarrhoea. Present condition: Pulse 90. Otherwise no abnormal signs. Thyroid gland enlarged?

34. G. A. Always in good health before. Menstrual periods commenced just before the 14th year. Always regular. Since then grown taller. No ocular disturbances. No palpitation. Has not got thinner. No sweatings. Thyroid gland not enlarged. Tachycardia. Pulse 90- 100.

35. I. L. Diffuse goitre. An aunt has goitre. Besides her there is no goitre in the family. Menstruation began in Nov. 1927; a t about the same time the thyroid began to swell. It caused no discomfort. Present condition: looks well and strong. Bright and lively. Mild diffuse enlargement of the thyroid.

36. S. B. Diffuse goitre. A younger brother asthma. A cousin of the mother goitre. Otherwise nothing of interest in the family. Pneu- monia a t the age of 4-5. Has lost some weight lately. No sweating, no palpitation. Her hair has got somewhat thinner. Slight trembling in the hands. Goitre since the summer 1927, menstruation since 1925. Feels a little tired, otherwise well. No ocular symptoms. Present condition: pulse 110. No tremor. No ocular symptoms. Slight diffuse enlargement of thyroid with soft murmurs.

37. M. J. Diffuse goitre. No goitre in the family. Parents ingood health. Patient has herself been well and strong. For a couple of years there has been a slight swelling of the front part of the neck. No discomfort. Not yet menstruating. Present condition: slight diffuse enlargement of the thyroid which is soft. No ocular symptoms. Pulse 90. No tremor.

38. F,. K. Mild diffuse goitre. No goitre known in the family. Men- struation for the last 31/, years. Goitre for the lmt 4-5 years. Is sometimes increasing in size. Has felt a little restless during the last two years. No sweating. The only discomfort is a certain amount of pressure in the neck. Present condition: well developed girl. Some diffuse enlargement of the thyroid, soft and elastic. Otherwise nil.

39. A. S. Diffuse parenchymatous goitre. One year ago a slight swelling of the neck. Lately grown bigger. Present condition: no nervousness, no tremor, no ocular symptnms. Thyroid enlarged, particularly on the right side, soft and smooth. Was given thyroid tablets on discharge.

Literature.

I. Holmgren, Ueber den Einfluss der Basedowschen Kranltheit und verwandten Zustande auf das Langenwachstum nebst einigen Gesetzen der Ossifikation. Hygiea 1906, Leipzig 1909. Eggert Moller, Clinical investigations into t h e basal metabolism in diseases of the thyroid gland. Copenhagen 1927. Kestner-Knipping, Die Ernahrung des Men- schen, Berlin 1926. H’Doubler, I?., Schweiz. med. Wcli. 52, 926, 1922. Plummer, Am. J. Med. Sc. 146, 790, 1913. -, J. Am. med. Ass., 77 ,

21-281 705. Acta med. Scnnilinuv. 1’01. L X I X .

:io8 EVEN M . ELDlI.

243, 1921. Boothby, J. Am. med. Ass., 76, 84, 1921. -, J. Am. med. Ass., 74, 255, 1921. Talbot, J. Am. med. Ass., 77, 1921. DuBois, J. Am. med. Ass., 77, 352, 1921. Zondek, Die Krankheiten der endokrinen Driisen, Berlin 1926. Carpenter, Tables, factors and formulas for computing respiratory exchange, Washington 1921. Troell, Hygiea 1925, 1927. -, Svenska Lakarsallskapets Handlingar 1922. Bene- dict, Hendry and Raker, Proceedings National Academy of sciences 1, 1921. Malade, Struma puerperalis. Berlin. k h . Wch. 1903. Jolin, Hygiea 1906. Kjerrulf, Hygiea 1920. Catell, Erdocrinology, vol. XI, n:o 1, 1921. Lindau, Lunds lakarsallskaps forhandlingar. 2, 23, 1926. Castex and Schteingart, J. Am. med. Ass., 88, 11 18. Bchadow, Monat- schr. f . Kinderheilkunde 34: 145, 1926. Archiv f . Kinderheilkunde 78, 302, 1926. Kestner, Liebschutz, Plaut, Schadow: Klin. Wch. 1926. V. Hutinel, Les dystrophies de l'adolescence, Paris 1924. U. Hjlrne, Acta paediatr. vol. 1, 1921. Mc Carrison, The etiology of endemic goitre. London 1913. - , The thyroid gland. London 1918. Quarterly Jour- nal Med. Oxford 1924, 133. Asher-Spiro, Ergebnisse der Physiologie, Band XXI, 1923. Kaartinen, Zur IUinik der PriipuberLiitsstruma. Helsinki 1926. Wahlberg, J., Finska Lakarsiillskapets Han dlingar, Band LXX, 1928.

contribution to the study of the basal metabolism in goitre at puberty

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