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THE RESPONSE OF THE THYROID GLAND TO THYROID-STIMULATING HORMONE (TSH) IN INFANTS WITH MALNUTRITION

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THE

RESPONSE

OF

THE

THYROID

GLAND

TO

THYROID-STIMULATING

HORMONE

(TSH)

IN INFANTS

WITH

MALNUTRITION

Francisco Beas, M.D., Fernando M#{246}nckeberg, M.D., Isidoro Horwitz, M.D.,

with the technical assistance of Margarita Figueroa

Department of Pediatrics and Pediatric Research Laboratory, Hospital M. Arriardn,

School of Medicine, University of Chile, Santiago de Chile

(Received October 14, 1965; revision accepted for publication June 18, 1966.)

Read by title at the Thirty-fourth Annual Meeting, Soc. Ped. Res., Seattle, Washington, 1964. This work has been supported by research grant A-4226-05 from NIH, U. S. Public Health Service and Faculty of Medicine, University of Chile.

ADDRESS: (F.B.) Casilla 5370, Santiago, Chile.

PEDIATRICS, Vol. 38, No. 6, Part I, December 1966

1003

C

HRON1C MALNUTRITION produces

en-docnine alterations both in expenimen-tal animals and in man.1 Various endo-cnine changes have also been described in infants suffering from severe calorie-protein

malnutrition. Thus, in the malnourished

in-fant, thyroid function is involved and radio-iodine uptake is considerably diminished when compared with normal controls., Protein-bound iodine and butanol-extracted iodine are also decreased.I12 The reports

on basal metabolic rate of malnourished

in-fants are not in agreement mainly because of the different methods used for

measure-ment and lack of clinical uniformity: age,

type of malnutrition, etc.11 However, in a

study carried out with similar clinical mate-na! it has been possible to demonstrate that

oxygen consumption is significantly lower

ill the infant with severe calorie-protein malnutrition when compared with values

found in normal infants studied tinder

similar

The above described thyroid alterations could be due to a primary failure of this

gland and/or secondary to a lack of

hypo-physeal stimulation. In order to clarify this problem and to continue our previous re

port on the function of the thyroid in

malnutrition,15 the response of this gland to

the thyroid-stimulating hormone (TSH) in a

group of malnourished infants and in a

nor-mal control group of the same age was

studied. The radioiodine uptake, the buta-nol-extractable iodine (BEI), and the oxygen

consumption were determined before and

after TSH administration.

CLINICAL SUBJECTS AND METHOD

Sixteen infants suffering from calorie-protein malnutrition (marasmus#{176}) and nine normal control infants were studied. The main clinical characteristics of the manas-mic infants are shown in Table I. Their

weights were between 36 and 58% of the

av-erage normal values for their age and sex, as estimated by Chilean standands.#{176} All the marasmic patients were selected in the sense that none of them showed signs of weight gain during a period of observation (at least 20 days before and after the test) in spite of an adequate diet.

The etiology of malnutrition was

deficiency in the calorie and protein intake,

determined by social and economic factors.

All

patients were breast-fed for a very short period of time; they all had a very heavy background of hypoalimentation , were weaned to very diluted milk, with on

with-a From the clinical and etiological point of view, chronic malnutrition in the child can be classified in two main categories: (1) marasmus or calorie-protein malnutrition, where the cause

is a grossly dilninished intake of calories and also

of protein; (2) kwashiorkor or protein malnutrition, the cause of which is an insufficient protein intake

with a relatively acceptable calorie intake. In pure

cases clinical and biochemical characteristicscan

(2)

f Residual radioactivity of the material used was insignificant. 3 4 5 6 7 8 9 10 11 l2 13 14 15 16 19 5 5 1! 9 U 11 4 8 10 6 4 4 6 60 51 57 67 6 60 60 53 65 63 55 5’2 56 55 4.0 2.5 3.4 4.6 3.3 3.7 3.4 3.0 4.8 4.1 3.8 3.0 8.5 3.5 36 48 55 50 40 40 39 50 58 50 45 5 58 59 Normal infants

1 4 61 5.9 98

8 69 8.4 100

3 6 64 6.3 88

4 5 63 6.3 95

5 8 66 8.7 105

6 8 70 9.7 11

7 7 69 7.7 100

8 7 70 8.0 108

9 5 65 7.1 10

out the addition of carbohydrate. No evi-dence of edema was found and the changes of the skin and hair typical of kwashiorkor were not present. No organic cause (such as, parasitism, metabolic disease, etc.) was found in any of the infants studied.

The procedure for the TSH test as de-scnibed by Jefferies,

et

al.17 was followed, except that 1-131 uptake was measured after 6 instead of after 3 hours, in order to be sure of a more complete absorption from the gastrointestinal tract and to demon-strate a more definitive difference in the rate of 1-131 uptake as recommended by Skillern and Evans.’8 On the first part of the test, a sample of serum was taken for

1 U.S.P. unit per kilogram body weight (see clinical data) of TSH in freshly prepared saline solution was given 3 to 5 days after the administration of the first dose of ra-dioactive iodine, so that the amount of re-sidual radioactive iodine was minimum. Next day, a new sample of serum was taken for BEI and the oxygen consumption of the patient was measured; after this, the residu-a! activity in the thyroid gland was mea-sured and a second tracer dose containing

0.5

to 1 tc of 1-131 was administered under the same conditions as those for the first tracer. The 1-131 uptake over the thyroid was measured 6 hours later, and the residu-al radioactivity of the first dose was sub-tracted from the measurement of the see-ond tracer. The 1-131 uptake was per-formed following the recommendations of the Group of Consultants of the Interna-tional Organization of Atomic Power,19 with some modifications because the pa-tients were infants : the distance from the thyroid to the crystal was 20 cm, which al-lowed measurement of the total body ra-dioactivity; subsequently, the thyroid area was protected by means of a lead collar thick enough to block the gamma rays from the thyroid area, thus obtaining the ra-dioactivity of the rest of the body. Knowing the radioactivity of the iodine administered at the moment of measurement (maintain-ing a standard solution) and the amount of radiation coming from the thyroid area, the percentage of iodine uptake was estimated.

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pa-TABLE II

1-131 UPTAKE, BEI, AND OXYGEN CONSUMPTION IN MALNOURISHED AND NORMAL INFANTS

(Before and After TSII Administration)

Infant.s

1-1.11 Uptake

fey

\/C

Before TSI! After TSII

BE!

(.ig/100 in!)

Normal 39±3.S.D. 60±3.6S.1).

P<0.001

Before TSII After TSI1

‘SIarILsIlIie

02 Consumption (liters/hours/lOl) cm height)

Before TSJI

5.4±1.3S.D. 7.9±1.7 SI).

p<0.0l

After TSH

8±5.() S.D. 50±10.5 S.D. 3.4±0.9 S.D. 5.9±0.5 SI).

I’<O.OOl p<0.001

4.2±0.3 S.D. 4.2±0.4 S.D.

P*< 0.001 0.01 0.001 0.001

*1) represents the significance l)etween normal aIld marasmic infants in each period of study.

ARTICLES 1005

tients or in the controls to eliminate the error by scattering, but special care was

taken so the geometry in both groups was the same. Butanol-extractable iodine was performed using the technique of Danow-ski, ci al.20 with some modifications.21

Oxy-gen consumption was determined in a

closed circuit as described elsewhere.15 The effect of TSH was evaluated by comparing

the 6-hour 1-131, the BEI, and the oxygen

consumption before and after the

adminis-tration of the hormone.

RESU LTS

Table II shows the values obtained in the 1-131 uptake, BEI, and the oxygen con-sumption in marasmic and normal infants before and after the TSH administration.

The 1-131 uptake in manasmic infants was significantly lower when compared with the average values of the normal in-fants under similar basal conditions : 39% in normal and 28.8% in marasmic infants (Table II). After the administration of TSH both percentages increased significantly to 50% in marasmic and 60% in normal infants (Table II and Fig. 1).

Under basal conditions the BEI was also

significantly lower in the manasmic than in the normal infants (Table II). Both groups

BE! was performed at Bio-Science Labora-tories, Los Angeles, California.

.8±0.4 S.D. 3.5±0.4 S.D. p<0.0l

0.001 0.001

showed a significant increase in the BEI values after the TSH: 5.9 p.g in the maras-mic and 7.9 in the normal infants (Table II and Fig. 1).

Oxygen consumption of the normal in-fants was similar to that reported in the lit-erature using the same method.15 Oxygen consumption of manasmic infants expressed in liters per hours per 100 cm of height was significantly lower (Table II), as we have

described 15 The administration

of TSH to the normal infants did not pro-duce any modification in the oxygen con-sumption (Fig. 1 and 2). The response of the manasmic group was variable; some of them reached normal values (four patients) and others did not respond at all (Fig. 2).

COMMENT

Basal Thyroid Function in Marasmic Infants

The significantly lower radioiodine

up-take values, BEI, and oxygen consumption in the marasmic infants show that the basal thyroid function is diminished. This modification produced by chronic malnutni-tion has already been demonstrated in ex-perimental animals,13 in adult human beings, and in children.9,bo22 However, with the information available, it is hard to

determine with accuracy if the decrease of

(4)

E

0 0 I.

a, p.

a’

t

‘Ii aO

a-“5

‘Ii

r 3

0

a’,

0 U

0

0

%0

I 31

UPTAK

IEFOR( TSH AFT(R TSH BEFORE TSH AFTR ISH

FIc. 1. 1-131 uptake, BEI and oxygen

consump-tion in marasmic infant before and after TSH administration. The mean values are represented

by the height of the bar.

BE

.L per 100 n1

OXYGEN

LiTERS

per 100cm HEIGHT

per HOUR

PTJENT C

FiG. 2. 1-131 uptake, BE! and oxygen consump-tion in marasmic infant before and after TSH

stimulation. The dotted line represents 2 standard

deviations from the normal.

Thyroid Function in Marasmic Infants

after TSH Stimulation

After the administration of TSH, the marasmic patients corrected the low values of radioiodine uptake from an average of 28% to 50%, which is very similar to the re-sponse of the control group (Fig. 1), so it became probable that the fundamental cause of the failure in the iodine uptake is the absence of TSH.

The marasmic patients as well as the con-trols responded increasing the BEI after the TSH administration. Nevertheless, the

volved to a greater extent in manasmic mal-nutrition.

(5)

condi-ARTICLES 1007

tions, the response of oxygen consumption

to TSH takes several days 2223

The oxygen consumption response to TSH administration in the marasmic group was significant but did not reach normal values. The individual analysis of each

pa-tient showed that, in four cases, the oxygen consumption increase reached normal val-ues, in five cases it increased without at-taming the normal level, and in six patients there was no response at all. Probably, it is

necessary to administer more than a single

dose of TSH in order to obtain a

satisfacto-ry response. On the other hand, the lack of

response to TSH stimulation may be a con-sequence of changes in the peripheral tis-sues secondary to malnutrition. It should be remembered that marasmic malnutrition, tinlike kwashiorkor, is not accompanied by hypoproteinemia. The results cannot, there-fore, be an artefact related to any decrease of protein binding of thyroid hormone.24’25

These results allow us to conclude that in chronic marasmic infants there is a real deficiency of the function of the hypophy-sisthyroid axis and probably of the periph-enal tissue. Our previous report shows that a similar phenomenon explains the adrenal hypofunction characteristic also of this type

of patients.7 There are also certain facts

which suggest a deficit in hypophyseal

so-matotnophin production.26 All these facts lead us to suggest that drastic and chronic restriction of calories and protein in infants

bring into operation an adaptive pituitary hypofunction.

SUMMARY

The thyroid response to TSH was studied in a group of 16 infants with severe manas-mus and 9 normal controls of the same age.

The radioiodine uptake, the BEI, and the oxygen consumption were determined in both groups before and after the adminis-tration of a single dose of TSH.

The results suggest that the low function of thyroid gland found in marasmic infants is due mainly to a decrease of TSH stimula-tion, but there is also a deficit of thyroid function per se.

These results are discussed in relation to previous data.

REFERENCES

1. Mulinos, M. C., and Pomerantz, L.: Pituitary replacement therapy in pseudohypophysec-tomy: effects of pituitary inplants upon organ weight of starved rats. Endocrinology, 29:558, 1941.

2. Mulinos, M. C., and Pomerantz, L. :

Pseudo-hypophysectomy: a condition resembling

hypophysectomy produced by malnutrition. J. Nutr., 19:492, 1940.

3. Platt, B. S., and Stewart, R. J. C.: The thyroid glands of protein-malnourished pigs. Proc.

Nutr. Soc., 21:5, 1962.

4. Perloff, W.: The starvation state and func-tional hypopituitarism. J.A.M.A., 175:137, 1959.

5. Zulivan, S., C#{243}mez,F., and Laguna, J.: Alter-aciones endocrinas en Ia desnutrici#{243}n. Fac-tores diet#{233}ticosy mecanismos de producci#{243}n. Rev. Invest. Clin., 6:395, 1954.

6. Paullada, J. J.: Alteraciones endocrinas en Ia

desnutrici#{243}n. Rev. Invest. Clin., 7:29, 1955.

7. Monckeberg, F., Beas, F., and Perretta, M.: Funci#{243}n suprarrenal en distr#{243}ficos. Rev. Chile Pediat., 27:187, 1956.

8. Zubir#{225}nS., and C#{243}mez,F. : Endocrine

distur-bance in chronic human malnutrition. Vita-mins Hormones (N.Y.), 11:97, 1953. 9. MOnckeberg, F., Barzelatto, J., Beas, F., and

Waissbluth, H. : Captaci#{243}n de yodo

radio-activo por el tiroide en el lactante distr#{243}fico. Rev. Chile Pediat., 28: 173, 1957.

10. Valledor, Y., Lavernia, F., Borbolla, L., Sata-nowsky, C., Costales, F., Prieto, E., and Bardelas, A. : Thyroid function disturbances in malnourished infants and small children. Rev. Cuba. Pediat., 31:533, 1959. 11. G#{243}mez,F., Ramos Galv#{225}n, R., and Cravioto,

C. : Determinaci#{243}n de iodo unido a Ia

proteina en ni#{241}osdesnutridos y durante su recuperaci#{243}n. Rev. Mex. Pediat., 24:94,

1955.

12. Lifshitz, F., Chavarria, L., Cravioto, J., Frenk, S., and Morales, M. : Iodo hormonal en Ia desnutrici#{243}n avanzada del ni#{241}o.Bel. Hosp.

Inf. M#{233}x., 19:319, 1962.

13. Talbot, F., Dalrymple, A., and Hendry, M.: Skin temperature and basal metabolism

dur-ing fasting. Amer. J. Dis. Child., 30:491, 1925.

14. Varga, F. : The respective effects of starvation and changed body composition on energy

metabolism in malnourished infants.

Pm-ATRICS, 23:1085, 1959.

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con-thyroid-stimulating hormone (TSH) test. Arch. Intern. Med., 99:234, 1957.

19. Normalizaci#{243}n y calibrado de las medidas de captaci#{243}ntiroidea de radioyodo.

Recomen-daciones del grupo de consultores del

Organismo Internacional de EnergIa Atom-ica. Viena: Noviembre 28, 1960.

20. Danowsky, Y. S., Mateer, F., Wegand, F. A., Peters, J. H., and Creenman, J. H.: Serum

tion. Washington, D.C.: National Academy of Sciences-National Research Council. p.

168, 1966.

25. Dean, R. F. A.: Kwashiorkor. In Advances in Pediatrics. London: J. and A. Churchill, p. 234, 1965.

26. Monckeberg, F., Donoso, G., and Oxman, S.: Human growth hormone in malnutrition.

PEDIATRICS, 31:58, 1963.

CORRECTION

There is an error in spelling in the “XI International Congress of Pediatrics Tokyo, November

1965,” (PEDIATRICS, 38:502, 1966). The first author on page 510 should be Dr. Derrick B.

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1966;38;1003

Pediatrics

Francisco Beas, Fernando Mönckeberg and Isidoro Horwitz

HORMONE (TSH) IN INFANTS WITH MALNUTRITION

THE RESPONSE OF THE THYROID GLAND TO THYROID-STIMULATING

Services

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(8)

American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

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