Z. Kinderheilk. 119, 211--215 (1975) 9 by Springer-Verlag 1975

Anorexia Nervosa with Transient Hypopituitarism G. F. P . H e r e m a n s , J . C. H . M. W i j f f e l s , a n d t I . H . v a n G e l d e r e n Paediatrie Department, University Hospital, Leiden Received November 4, 1974

Abstract. A case is presented with sudden onset of eachexia and anorexia with hypopituitarism, starting early and progressing gradually. After about 15 months the patient recovered; first he lost the anorexia, then the endocrine functions a n d growth became normal. Conflicting reports about hypopituitarism in anorexia nervosa and similar syndromes may be due to lack of longitudinal observations and the transient nature of the endocrine disorders. Key words: Anorexia nervosa - - Caehexia - - Transient hypopituitarism - - Longitudinal study

Transient endocrine disorder.

Longitudinal investigation of hormonal functions in severe weight rare; most of the studies are restricted to short periods of the disease. describe the course of a marked but transient ease of emaciation similar to nervosa which could be documented from the beginning until after a recovery.

loss a r e We here anorexia complete

CaseH i s t o r y A.V.S. was a d m i t t e d to a local hospital (care of Dr. S. E. Bos) at the age of 13.9 years because of weight loss; within a few months his weight was reduced from 50 to 42 kg. There were no preceding illnesses. U p until a few months earlier he had been a bright and active boy, keen on sports. His parents had neither noted a marked loss of appetite, nor change in behaviour or depression. The only complaint was some lassitude. On admission a low body temperature (35.9 ~C), bradycardia and constipation were noted. Secondary hypothyroidism was confirmed b y a reduced P.B.I. (2.8 ~g/100 ml), rising to 8.6 ~g/t00 ml after TSH administration. U p t a k e of j l a l was 13% after 24 and 16~o after 48 hrs. Test for growth hormone was normal (Table 1); fasting morning cortisol was 23 izg/100 ml. T r e a t m e n t with T h y r a n o n | (50 mg daily) was instituted and the boy was discharged. However, weight loss continued, anorexia now became more marked as well as a mild degree of a p a t h y b u t no depression. At the age of 14,3 years he was a d m i t t e d to our department. A p a r t from emaciation (Fig. 1) and bradyeardia (56/rain) no abnormal physical signs were noted. Pubic hair and genital size were stage I I I [1], testieular volume was 4 ml, in accordance with the bone age of 13 years [2, 3]. Voluntary food intake was estimated at a b o u t 1000 Cal. daily. There were no signs of neurological disease, EEG, X-rays of sella and skull, neurological and ophthalmological examination (including campimetry) and CSF remained normal. Hormonal studies were performed under t r e a t m e n t with T h y r a n o n | As can be seen in Table 1 at this time gonadotropie activity was low, as was already clear from the lack of further genital development since the earlier admission; possibly also growth hormone response to insuline was reduced, though still within the normal range. ACTH production seemed unimpaired (insulin test and metopyrone test).

G. F. 13. Heremans et al.

212

Table 1. Summary of endocrinological investigations Age (years: months) 13:9 14:4 14:7

15:0

16:4

31.7

15.5

8.2

28.2

9.8 22.9

10.0 15.2

14.4 10.8

12.4 23.2

ACTH Max. cortisol (~g/100 ml) after insulin 17 ketog.-steroids before after metopyrone

TSH

PBI (~g/100 ml) after TSH j1al uptake (24 hrs)

2.8 8.6

4.6 a

7.1 a

5.6 a

5.4

13%

Growth hormone (~U/ml)

Highest level after insulin

16.5

8

3.5

0.5

F S H (urine) 6 U

neg.

neg.

neg.

pos.

a On Thyranon | treatment.

Fig. 1. Patient at age 14.3 years Fig. 2. Patient at age 15.0 years

26

Anorexia Nervosa with Transient Hypopituitarism

213

kg 70

cm

178 174

weight/

/"

60

,,,"height

s"

170

166

9,

!

ll/.,

I 15

,,./,;

!50

/

40 I 16

I 17

Fig. 3. Data on height and weight

Table 2. Summary of growth data Age (years:months)

Height (era) ~Teight (kg) Bone age (years) Pubic hair stage (1--6) Testieular vol. Lean body mass (kg) F a t mass (kg)

14:0

14:4

14:7

14:11

15:6

15:11

16:4

17:r

163.0 41.7

163.2 37.6 13 3 4

163.5 34.8

163.5 44.5

168.7 63.0

171.3 66.9

176.4 65.7 15 5 14

178.0 68.0

3 4

3 4 30.4 4.4

4 12 52.4 14.5

The dose of T h y r a n o n was increased to 75 and 100 mg daily, b u t after discharge the boy did n o t improve. Height, weight and pubertal development remained unchanged. Investigations were repeated at the age of 14.7 and 15.0 years. A t this time b o t h growth hormone and ACTH production (release) were markedly deficient. Again no signs of neurological disease could be found. The boy h a d become somewhat depressed b u t was still cooperative, though unable to take an adaequate a m o u n t of food. Forced feeding for a few weeks h a d little effect and it was decided to start a trial of psychiatric t r e a t m e n t (Dr. R. N. Zeven) after discharge. This t r e a t m e n t was restrieted to talks once a week for only 2 months because the psychiatrist t h e n moved to another town. According to the psychiatrist the patient had had difficulties with his father who elaimed his help in the shop during free hours and showed little interest in his son because of long working hours. The boy had avoided conflicts, however. R a t h e r unexpectedly the boy then started to eat, for some time even exeessively. As can be seen from Figs. 2 and 3 this resulted in a rapid gain of weight. Resumption of the growth spurt was noted only a b o u t 5 months later. Sexual m a t u r a t i o n was resumed a t a b o u t the same time. The recovery can also be noted from the data of body composition (Table 2), which were estimated b y means of K a~ measurement in the Whole Body Counter. A t the age of 151/2 years t r e a t m e n t with T h y r a n o n was discontinued and a t the age of 16.4 years all endocrine tests were found to be normal. Immediately after the return of a normal appetite all complaints disappeared, pulse rate became normal, activity returned, the boy resumed his sporting hobbies with great enthusiasm and did well at school.

214

G.F.P. }teremans et al. Discussion

The case history shows a rather sudden onset of weight loss without preceding illness and with gradually increasing hypopituitarism. Signs of psychiatric disturbance were mild; there was no severe aversion to food although for some time we noted that the boy furtively threw away food offered to him. Our first irapression pointed more to an organic dieneephalic illness than to a psychiatric disorder because the mentM signs were much milder than usually found in anorexia nervosa; therefore psychiatric treatment was delayed until late in the course of his disease. Whether this transient illness should be named anorexia nervosa is rather a semantic problem. The cachexia and anorexia without manifest organic disease are in accordance with the diagnosis of anorexia nervosa. The mild psychiatric disturbance but especially the rapid recovery, which seems to be spontaneous, is most unusual in anorexia nervosa. The first sign of recovery- was the disappearance of anorexia. Resumption of ample food intake before he started to gain height resulted in a period of obesity. I~eports about hormonal disturbances in anorexia nervosa are conflicting. I n a study of van Beugen et al. [4] of 38 eases no endocrine disorders could be found except for amenorrhea, frequently with low levels of gonadotrophins. The latter is a very common symptom in anorexia nervosa [5]. More recently secondary hypothyroidism, reduced ACTH activity and lack of response of growth hormone secretion to provocation tests have been reported in a number of cases [6, 7]. Remarkable is the occasional finding of high basal levels of growth hormone [6, 8], just as in protein caloric malnutrition [9, 10]. No correlation have been reported between growth hormone abnormMities and either the duration or the severity of the disease. There certainly are many eases of--even severe--anorexia nervosa who show normal responses upon tests of growth hormone, ACTH and TSH functions. Whether anorexia nervosa with and without (pan)hypopituitarism are different diseases or whether this endocrine disorder is only present for short periods in the course of the illness is not known, mainly because longitudinal studies are usually not performed. Another possible diagnosis: transient diencephalic disease could not be confirmed. Signs of trauma, encephalitis, tumour, vascular disease and neurological disease were lacking. Diencephalic syndromes usually concern younger children [11]. On the other hand the data of our patient suggest that loss of gonadotrophic and TSI-I functions oeeured at the beginning of the disease. Whatever the name that should be given to this illness, this study indicates need for more longitudinal observations, preferably including estimations of releasing factors, before the relationship between anorexia nervosa and hypopituitarism can be understood and discrimination between cause and effect is possible. References

1. Tanner, J. M. : Growth at adolescence, 2nd ed. Oxford: Blackwell Scientific Publishers 1962 2. Greulieh, W. W., Pyle, S. I. : Radiographic atlas of skeletal development of the hand and wrist. Stanford University Press. Stanford California-London: Oxford University Press 1966

Anorexia Nervosa with Transient Hypopituitarism

215

3. Dooren, L. J., Gelderen, H. H. van, Hamming, H. D. : Testisgrootte en pubesbeharing bij jongens van 10--15 jaar. Ned. T. Geneesk. 107, 1519--1522 (1963) 4. Beugen, L. van, Kropveld, E., Graeff, J. de, Smeenk, D., Querido, A. : Anorexia nervosa; ecn studie van 38 patienten. Ned. T. Geneesk. 105, 464--470 (1961) 5. Oberdisse, K., Solbach, G., Zimmermann, H.: Die endokrinologischenAspekte der Anorexia nervosa. In: Anorexia Nervosa (ed. J. E. Meyer and H. Feldmarm), pp. 21--31. Stuttgart: Thieme 1965 6. Wiegelmann, W., Solbach, H. G., Bethe, H., Zimmermann, H. : Growth hormone response to insulin-inducedhypoglycemia in anorexia ncrvosa. Acta endocr., Suppl. 159, 46 (1972) 7. Moshang, Th., Vaidya, V,, Park, J. S., Bongiovanni, A. M. : Abnormal anterior pituitary function testing in anorexia nervosa. Pedlar. Res. 7, 330/120 (1973) 8. Landon, J., Greenwood, F. C., Stamp, T. C. B., Nynn, V.: The plasma sugar, free fatty acid, cortisol and growth hormone response to insulin, and the comparison of this procedure with other tests of pituitary and adrenal function. II. I n patients with hypothalamic or pituitary dysfunction or anorexia nervosa. J. clin. Invest. 45, 437--449 (1966) 9. Samuel, A. M., Desphande, U. 1~.9Growth hormone levels in protein caloric malnutrition. J. clin. Endoer. 35, 863--869 (1972) 10. Godard, C., Zahnd, G. 1~.: Growth hormone and insuline in severe infantile malnutrition. II. Plasma insulin and growth hormone during intravenous glucose tolerance test. Helv. paediat. Acta 26, 276--285 (1971) 11. Pimstone, B. L., Sobel, J., Meyer, E., Eale, D.: Secretion of growth hormone in the diencephalic syndrome of childhood. J. Pediat. 76, 886--889 (1970) Dr. G. F. P. Heremans Paediatric Department of Pediatrics University Hospital Leiden, The Netherlands

15

Z. K i n d e r h e i l k . , B d . 119