ACTA NEUROCHIRURGICA

Acta Neurochirargica 45, 287--299 (1979)

9 by Springer-Verlag 1979

Department of Paediatric Endocrinology, Children's Hospital and Clinic of Nenrosurgery, University of Essen, Federal Republic of Germany

Pre- and Postoperative Evaluation of HypothalamoPituitary Function in Children With Craniopharyngiomas*, ** By

W. Andler, K. Roosen, and H. E. Clar

Summary Pre- and postoperative evaluation of hypothalamic-pituitary function was performed in six children, aged 5.5 to 13.3 years with craniopharyngiomas. Before surgery growth hormone deficiency (GHD) was documented in four, hypothalamic hypothyroidism in three, and secondary ACTH-deficiency and hyperprolactinaemia in one patient. Diabetes insipidus was absent in all patients. After neurosurgical treatment GHD was present in all, hypothyroidism in five, ACTH-deficiency in three, hyperprolactinaemia in three, and diabetes insipidus in four children. The study shows that ai1 endocrine functions tested may be defective even before surgery, although diabetes insipidus seems to be a rare preoperative complaint. Surgical intervention, however, often leads to additional endocrine disorders. From the data presented here one may suggest that TRH stimulation tests, evaluation of serum prolactin, and lysin-vasopressin stimulation tests are the most useful investigations to distinguish between hypothalamic and primary pituitary disorders.

Key words: Craniopharyngioma; growth hormone deficiency; hypothyroidism, secondary adrenal insufficiency; hyperprolactinaemia; diabetes insipidus.

While the postoperative endocrine function in children with craniopharyngiomas has been studied in several investigations, the preoperative hormonal status has evoked less interest. We studied six consecutive patients prior to surgical treatment and several weeks thereafter in order to find out firstly which endocrinological disorders are due to the tumour itself, and which are due to the surgical inter* Acknowledgements: We wish to thank Miss U. Erwig and Miss U. Moos for excellent technical assistance. *::- Supported in part by Deutsche Forschungsgemeinschaft, Grant 91/2.

0001-6268/79/0045/0287/8 02.60

288

W. Andler et al.:

v e n t i o n , a n d s e c o n d l y w h i & e n d o c r i n o l o g i c a l m e t h o d s are u s e f u l for distinguishing between primary hypothalamic and primary pituitary disorders.

P a t i e n t s and M e t h o d s Patients: Six consecutive patients, admitted to our hospital between January 1976 and November 1977, were studied. The most important clinical data are summarized in Table 1. Diagnosis was indicated by neuroradiological investigations (pneumoencephalography, brain scanning, computer assisted tomography) and confirmed at operation. In no patient was the pituitary gland itself involved either by the tumour or by surgical intervention. Endocrinological examinations were performed just before as well as 20 to 30 days after surgery. No patient received any hormonal medication or anticonvulsant drugs at the time of study. Methods: Growth hormone (GH) was determined before and after both insulin induced hypoglycaemia (IIH) and propranolol-glucagon (PG), as described earlier 1. GH measurements were performed by means of a double antibody RIA (Serono). Standards were assayed against 1. IRP H G H 66/217 (WHO). Coefficients of variation of intraassay and interassay variability: 3.3 and 7.7~ Growth hormone deficiency (GHD) was considered to be proved by failure of sufficient GH responses (peak > 5 ng/ml) to both IIH and PG. Thyroid function was assessed clinically (coarse skin, constipation, reduced motor activity) and biochemically by determination of serum thyroxine (T4-RIA kit, Abbott), Ta-resin uptake (Triasorb, M-125 kit, Abbott), calculation of "free T(index" (FT~), and by determination of thyrotropin (TSH). The normal range for T 4 (newborns excluded) was 5.0-13.0 mcg/100 ml, for T3-resin uptake 21-33~ and for FT~ 1.5-4.7. TSH was analysed before and after stimulation with TRH (1(30 mcg/m2). Standards were assayed against the standard 68/38 (WHO). Coefficients of variation of intra- and interassay variability: 8.3 and 12.4~ The normal basal value of TSH in our laboratory was (newborns excluded) 2.8 -+ 1.1 (SD) mcU/ml. As a normal response (x +_ SD, n-42, age 1-16 years) to TRH we found an increase to 18.2 (5.7) mcU/ml after 20, to 13.7 (4.8) mcU/ml after 45, and to 10.4 (4.6)mcU/ml after 60 minutes. The TSH level at 20 minutes always exceeded the level at 45 minutes. Prolactin was determined by using a double antibody RIA (Serono) under the conditions of the TRH stimulation tests. Coefficients of variation of intraand interassay variability: 2.8 and 8.2~ The normal basal serum concentration (boys and prepubertal girls) is 0-20 ng/ml in our laboratory. Hypothalarnic-pituitary-adrenocorticaI function was evaluated from the determination of serum cordsol (RIA kit, Serono) during IIH, after PG, and after lysin-vasopressin (LVP), as described by Landon et al. 14. ACTH deficiency was assumed if basal cortisol level (at 9 a.m.) was diminished ( < 3.5mcg/100ml, x - - 2 SD) or failed to increase after both IIH and PG to a peak level of at least 9.1 mcg/100mI ( x - - 2 S D ) . Clinical diagnosis of secondary adrenaI insufficiency was assumed in the presence of clinical symptoms such as adynamia, weight loss, diarrhoea, salt-losing crises, and hypoglycaemia. Latent adrenal insufficiency was assumed in the presence of laboratory data mentioned above but absence of clinical symptoms. Diabetes insipidus neurohumoratis was diagnosed in the presence of polyuria and polydipsia, failure of increase in urine osmolality when thirst was present, and prompt correction of symptoms after intranasal application of DDAVP.

m

m m f f f

F.K.

B.H. V.W. S.S. M.K. P.T.

13.3 10.7 8.O 11.0 5.5

13.3

Age (years)

Bone age * (years)

9.5

13.0 10.0 5.0 8.5 4.0

Height (perc.)

3

25 10-25 3-10 3-10 50

* After Greulich and Pyle 8

Sex

Patient

50 75 25 50-75 3-10

50-75

Weight (perc.)

subtotal removal subtotal removal

total removal subtotal removal

subtotal removal

Surgical treatment

headaches, vomiting headaches, papilloedema headaches, vomiting, short stature partial loss of vision, headaches, vomiting, short stature partial loss of vision, headaches, vomiting

stature

subtotal loss of vision, headaches, vomiting, short

Clinical symptoms

Table 1. Clinical Data of Six Patients With Craniopharyngiomas at First Study

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290

W. Andler et al.

Results

Table 2 summarizes the hormonal situations in our six patients before and after neurosurgical treatment.

Growth and growth hormone deficiency: Table 3 shows the results of GH-measurements. GH failed to increase adequately in four out of six patients before treatment. After removal of the tumour GH responses were inadequate in all patients. At first study three patients showed retarded height and bone age (--2.5 to - - 3 . 8 years). All three patients were GH-deficient even before treatment. After surgery growth velocity was diminished in five, but has been made normal in three patients (V. W., S. S., P. T.) after thyroid replacement therapy. One patient (M. K.) with hypothyroidism on biochemical but not on clinical evaluation has received no substitution therapy yet. Only two patients (F. K., M. K.) showed stunted growth. One of them has been treated succesfully with hGH. Thyroid function: Table 4 gives the thyroxine levels, the results of Ta-resin uptake, free T4-indices, and T R H stimulation tests. Three patients (F. K., S.S., P.T.) showed T4-1evels at the lower normal limit but diminished FT4-values even before surgical treatment. TSH increases were prolonged (45 minute levels exceeded 20 minute levels) in these patients. After neurosurgery five patients were biochemically hypothyroid. All but one (M. K.) showed mild clinical signs of hypothyroidism. TSH increase was prolonged in all these patients, and even exaggerated in two of them (F. K., P. T.). Prolactin (Table 4): Hyperprolactinaemia was present before any treatment in one (B. H.), and in two additional patients after surgery (V. W., M. K.). Pituitary-adrenocortical axis: Table 5 shows the cortisol levels under basal conditions and when stimulated by IIH, PG, and LVP. Prior to treatment only one patient (F. K.) showed failure of adequate cortisol increase after both stimuli (IIH and PG) but responded adequately to LVP. After surgical treatment secondary adrenal insufficiency was assessed biochemically in two additional patients. All three patients responded sufficiently to LVP. Obvious clinical evidence of secondary adrenal insufficiency was present in two patients (F. K., P. T.) so far. Diabetes insipidus neurohumoralis (Table 2): Clinical and laboratory signs of diabetes insipidus were absent in all patients at first study. Diabetes insipidus was present in four patients after surgical treatment. However, in one of these patients (P. T.) polyuria and

before after before after before after before after before after before after

F. K

P.T.

present present present present absent present present present present present absent present

GHD

present mo~e pronounced absent absent absent present present present absent present present more pronounced

I-IT i

* Only manifest during temporary adrenocortical replacement therapy.

M.K.

S.S.

V.W.

B.H.

Neurosurgery before/after

Patient

present more pronounced absent absent absent absent absent present absent absent absent present

Sec. AI

N.D. absent present present absent present absent absent absent present absent absent

HPrl

absent present absent absent absent present absent present absent absent absent present *

D.I.

Table 2. Hormonal Status Prior to and A~ter Neurosurgi~al Treatment in Six Children With Craniopharyngiomas (GHD = growth hormone deficiency, l-iT = hypothyroidism, sec. AI = secondary adrenal cortical insufficiency, D.I. = diabetes insipidus, H P r l = hyperprolactinaemia)

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o

o

E ~.

~.

o

?

P.T.

M.K.

S.S.

V, W.

B.H.

0.4 0.9 1.8 4.4 > 20.0 2.3 N.D. 0.9 1.2 1.0 3.8 3.0

before after before after before after before after before after before after

F.K.

0.4 1.1 1.8 2.4 1.5 1.3 1.2 0.7 0.8 0.9 2.8 2.6

I'qeurosurgery Basal Peak before/after (IIH)

Patient

0.9 1.2 N.D. 3.6 > 20.0 3.2 2.2 1.4 2.5 2.5 11.5 3.0

Peak (PG)

50

3 10

3-10

10-25

25

3

~ 3

3-10

~ 3

~ 3

25

< 3

Height (perc.) Postoperative at first study growth rate (perc.)

25

N.T.

50

50 75

N.T.

< 3

Postoperative growth rate (perc.) with thyroid replacement therapy

N.T.

N.T.

N.T.

N.T.

N.T.

10-25

Growth rate (perc.) after hGH-treatment (6 E/week)

Table 3. GH Responses to IIH and PG Before and After Surgical Treatment in Six Patients With Craniopharyngiomas and Clinical Data on Postoperative Growth (N.D. = not detected, N.T. -- not treated) G H (ng/mI)

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t-o

~




P.T.

M.K.

S.S.

V.W.

B.H.

F. K.

Patient

before after before after before after before after before after before after

Neurosurgery before/after

6.0 4.1 6.6 10.0 10.9 3.7 5.2 4.7 9.5 7.1 5.0 2.5

T4 mcg/lO0 ml

20.9 17.8 25.3 25.7 24.6 20.5 17.2 18.5 22.1 16.1 21.0 N.D.

Ta-resin uptake ~ 1.2 0.7 1.7 2.6 2.7 0.8 0.9 0.9 2.1 1.1 1.1 N.D.

FT4

1.3 1.3 1.0 0.9 0.8 1.5 3.3 3.2 3.9 2.0 3.0 4.3

12.1 36.0 12.2 11.0 3.8 4.2 12.4 8.5 11.3 9.5 14,5 37,0

27.2 > 40.0 10.5 9.3 3.5 8.8 14.8 16.3 9.5 12.2 18.9 > 40.0

TSH (mcU/ml) before and after TRI-I (100 mcg/m =) Basal 20 min. 45 rain.

33.0 > 40.0 6.1 5.9 2.5 12.0 14.5 15.6 6.3 9.0 27.9 > 40.0

60 min.

N.D. 12.6 75,4 82.9 13.2 21.5 4,0 4.0 17.4 49.9 12.5 7.7

N.D. 33.4 > 100.0 > 100.0 33.8 36.3 10.4 11.2 60.9 78.3 36,9 14.4

Prolactin (ng/ml) before and after T R H Basal Peak

Table 4. Thyroxine (T4), Ta-Resin Uptake, "Free-T4 Indices" (FT4) and Results of TRH-Stimulation Tests Before and After Surgical Treatment in Six Patients With Craniopharyngiomas (N.D. = not detected)

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Pre- and postoperative evaluation of hypothalamo- pituitary function in children with craniopharyngiomas.

ACTA NEUROCHIRURGICA Acta Neurochirargica 45, 287--299 (1979) 9 by Springer-Verlag 1979 Department of Paediatric Endocrinology, Children's Hospital...
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