Hypothyroidism in an Area of Endemic Goiter and Cretinism

in Central Java, Indonesia

B. M. GOSLINGS,1 R. DJOKOMOELJANTO,3 R. DOCTER,4 C. VAN HARDEVELD,2
G. HENNEMANN,4 D. SMEENK,1 AND A. QUERIDO1
Departments of Clinical Endocrinology and Metabolism,1 and Chemical Pathology,2 University
Hospital, Leiden, The Netherlands, Department of Internal Medicine,3 Diponegoro University,
Semarang, Indonesia, and Department of Internal Medicine (III) and Clinical Endocrinology,4
University Hospital "Dijkzigt", Rotterdam, The Netherlands
ABSTRACT. In an area of severe endemic goiter in
Central Java, Indonesia, clinical overt or mild
hypothyroidism appeared to be present in 7 out of
20 cretins and also in 12 out of 94 non-cretinous
subjects, all 5-20 years of age, living in the village
of Sengi. Hypothyroidism was not found in a control
group of 70 subjects of the same age living in
Londjong just outside the edemia. In hypothyroid
subjects the plasma PBI-concentration was 0.98
0.32 Mg/100 ml (mean SD) VS. 2.72 1.24 /Ag/100
ml in euthyroid subjects from Sengi and 4.86 0.80
/xg/100 ml in controls from Londjong. Values for
T3 were 56.3 31.7 ng/100 ml in hypothyroids,
140.5 38.5 ng/100 ml in euthyroids from Sengi
and 121.6 27.4 ng/100 ml in controls. The TSH
levels (geometric mean and range) in these 3 groups
were, respectively, 210.1 (108.0-342), 15.6 (3.0372) and 4.1 (0.8-7.0) nWm\. The differences be-

YPOTHYROIDISM, being an essential

phenomenon in sporadic cretinism, is
also often mentioned as one of the main
features of endemic cretinism. However, in
Switzerland as well as in most endemias
described in recent years, dwarfism and
hypothyroidism were infrequent or absent
(1-6). A notable exception is the hypothyroid form of endemic cretinism prevalent in
Zaire (7-9). The normal height and absence
of clinical hypothyroidism of most adult
cretins in the other endemic areas are considered to be the consequence of compensatory mechanisms resulting in adequate total
hormone output in the presence of severe
iodine deficiency. In view of decreased
plasma T4 concentrations in these subjects,
normal or slightly elevated T3 levels were
to be expected and are indeed described
in recent studies (10-15). In those cases
where cretinism is accompanied by clinical
Received May 11, 1976.

tween the mean concentration of PBI, T3 and TSH

in the hypothyroid and euthyroid groups were
highly significant (P < 0.001).
These data strengthen the clinical diagnosis of
hypothyroidism in cretins as well as in non-cretinous
subjects. All hypothyroid subjects had a PBI < 1.8
Mg/100 ml and T3 < 120 ng/100 ml and TSH > 100
/u,U/ml. In 8 hypothyroid subjects, restudied 18
months after iodized oil injection, hypothyroidism
was either corrected or markedly improved. It
therefore appears that iodine deficiency per se in
post natal life may lead to (juvenile) hypothyroidism,
which can be corrected by iodine therapy. Our
findings have implications for the definition and diagnosis of endemic cretinism. Not all hypothyroid
subjects in an area of endemic iodine deficiency
should be classified as cretins. (J Clin Endocrinol
Metab 44: 481, 1977)

hypothyroidism atrophy of the thyroid gland

has been assumed to be one of the mechanisms possibly involved in the development of thyroid failure (1,7,16,17). Another
possibility is that severe iodine deficiency
per se can lead to thyroid hormone deficiency in the presence of maximal compensatory activity of the thyroid gland (18).
The prevalence of hypothyroidism in
areas of severe iodine deficiency is difficult
to establish since clinically mild hypothyroidism is not easily detected (19) and the
interpretation of biochemical tests in this
regard is even more difficult in the presence
of iodine deficiency. Patel et al. (11) found
only one subject to be clinically hypothyroid out of 6 who had biochemical evidence
of hypothyroidism in 52 subjects studied in
Eastern New Guinea. They suggested, however, that hypothyroidism might be more
common in this situation than previously
suspected. Also the question whether hypothyroidism in a severely iodine deficient

481

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482

GOSLINGS ETAL.

area occurs only in cretins or in noncretinous subjects as well, has not been
answered.
In order to study the occurrence of hypothyroidism among cretins and non-cretinous
subjects living in the endemic area of
Central Java, Indonesia, we made a thorough
clinical investigation to establish the diagnosis of overt or mild hypothyroidism. Since
in the area studied hypothyroidism did
occur in subjects lacking any signs of central nervous system damage classically related to endemic cretinism, we had to exclude hypothyroidism as a criterion for the
diagnosis of endemic cretinism. This
finding is of importance for the definition
of endemic cretinism (see Discussion).
In this paper we also present data on the
plasma concentration of circulating thyroid hormones and thyrotropin (TSH) in
cretins and non-cretinous subjects with
hypothyroidism and in euthyroid subjects in
the endemic area. These data are compared
with results obtained in normal subjects
living in a nearby control area without
endemic goiter.

JCE & M 1977

Vol 44 No 3

detected by physical examination (14,22). These

examinations were also made in all subjects of
the following groups.
Group 2
Group 2 included 94 subjects of the noncretinous population (NCP of Sengi, taken as a
random sample covering about 50% of the age
group of 5-20 years.
Group 3

Group 3 included 70 subjects randomly selected from a population of about 140 living
in the village of Londjong. This village, about 50
km distant from Sengi, was selected to provide a
control group of people living in the same socioeconomic circumstances (number of inhabitants,
area of rice fields, tax to be paid, schooling
data, distance from main road), but not affected
by endemic goiter or cretinism. The mean iodide
excretion of 41.4 /xg/g creatinine and the goiter
rate of less than 3% were consistent with compensated mild iodine deficiency. In all control
subjects plasma TSH was normal (see Results).
The diagnosis of hypothyroidism was established by scoring the following three criteria:
1) physical examination: overt hypothyroidism
or myxedema: 4 points, dryness of skin and hair
Subjects and Methods
or sluggishness: 2 points; 2) height: <85% of
mean
height (mean 3 SD) of Londjong controls:
Three groups of subjects, all 5-20 years of age,
3 points, <90% (mean - 2SD): 1 point; 3) Achilles
were studied.
tendon reflex time: >334 msec (mean + 3 SD of
Londjong controls): 3 points, >317 msec (mean
Group 1
+ 2 SD): 1 point. Hypothyroidism overt or mild
Group 1 included all 20 cretins of that age was diagnosed in those with a total score of 7 10 or 3-6 points, respectively.
group living in the village of Sengi, situated in
Group 1 and group 2 could thus be subrural Central Java, Indonesia, where severe
divided
into hypothyroid and euthyroid subjects.
endemic goiter is frequent. The endemia is
characterized by a mean iodide excretion of 15.6 Group la included 7 hypothyroid cretins (4
/xg/g creatinine, a goiter rate of 85%5 and a preva- overt, 3 mild). Group lb included 13 euthyroid
lence of cretinism of 8%. We identified a cretin cretins. Group 2a included 12 hypothyroid NCP
as a subject born in the endemic area showing (2 overt, 10 mild). Group 2b included 82 euthytwo of the following three symptoms: mental roid NCP.
None of the controls (group 3) showed signs
retardation (scored with Raven's progressive
suggestive
of hypothyroidism.
matrices test (A, AB and B), perceptive deafness
Eight
hypothyroid
subjects (4 from group la,
(>30 db hearing loss at 4000 Hz measured with
audiometry) and/or neuromotor abnormalities as 4 from group 2a) were restudied 19 months
after im injection with iodized oil (Lipiodol):
5
According to the modification by Stanbury et al. (20) 480 mg iodine/1 ml in subjects under 6 years
of the classification by Perez et al. (21), taking into of age and 960 mg iodine/2 ml in subjects over
6 years of age.
account all goiters, OB included.

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HYPOTHYROIDISM AND ENDEMIC GOITER

Methods
Height. Height was expressed as per cent of the
mean height per age and sex class of the Longjong control group.
Achilles tendon reflex time. Achilles tendon
reflex time was measured by a Burdick FM-1
photomotograph. The time between the hammertop to one-half relaxation is called "reflex time."
Neck uptake. Neck uptake of 131I was measured
at 4 and 24 h with standard procedures according
to the International Atomic Energy Agency (23).
Protein bound iodine. Protein bound iodine
(PBI) was measured with an Auto-technicon
auto-analyzer technique based on the wet ashing
digestion method of Zak.

483

for iodination was kindly supplied by the

National Pituitary Agency (Bethesda, Md.). As a
standard the MRC standard A (supplied by the
National Institute of Medical Research, Mill
Hill, London) was used. Upper normal limit for
Dutch subjects is 8 /u,U/ml. Statistical analysis
was done by the method of Wilcoxon.
Results
Physiological parameters
The values for height and reflex time in the
different groups are shown in Figs. 1 and 2.
Mean values for each parameter show a
significant (P < 0.001) difference between
hypothyroid and euthyroid groups as can be
expected since these parameters were used
to define the hypothyroid groups. There is
however a considerable overlap of values.
The means of the euthyroid groups were not
significantly different from the Londjong
control group.

Triiodothyronine. Triiodothyronine (T3) was

determined by radioimmunoassay using the
method of Larsen (24) with slight modifications.
Antibody serum was prepared by immunizing
rabbits with T3-bovine serum-albumin conjugates (25). Binding of T3 to TBG was blocked
with salicylate. After 3 days incubation at 4 C Circulating thyroid hormone concentrabound and free hormone were separated with a tions
norit-dextran method. Normal range for Dutch
Plasma PBI concentrations in groups la
subjects is 70-170 ng/ml (mean 2 SD, n = 50).
(mean SD: 0.86 0.18 /xg%), l b (2.38
Thyrotropin. Thyrotropin (TSH) was analyzed 1.17),2a(1.12 0.42)and2b(2.79 1.26)
by a double antibody immunoassay according to are significantly different from the control
Odell et al. (26). Antiserum and human TSH group (4.86 0.80) (see Fig. 3). Differences

FlG. 1. Height of hypothyroid

and euthyroid cretins, non-cretinous subjects (NCP) and controls. Shaded area is mean 2
SD of control subjects from
Londjong.

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JCE & M 1977

Vol 44 No 3

GOSLINGS ET AL.

484
Reflex ti me
m sec

NCP Sengi

Cretins Sengi j

too

Londjong

FIG. 2. Achilles tendon reflex

time in hypothyroid and euthyroid cretins, non-cretinous subjects (NCP) and controls. Shaded
area is mean 2 SD of control subjects from Londjong.
Broken line is mean + 3 SD of
control.

350

i'i

:
.....................
;

300

'

'

'

':

'

'

'<.

250

' / / ' / /

..''./.'<

' ' " ;

. ,

'.''.'

'

' '

-"

. ; ;

"

'

. - ' ; . '
.

'

''

''

. :

'.'

' '

<*!'

'

'

" '

'/''"''

200
HYPOTHYROID

EUTHYROID

HYPOTHYROID

EUTHYROID

CONTROLS

P < 0.001. In the NCP there was some

overlap of values in the range between 75
and 120 ng%. Although the mean T 3 in the
euthyroid subjects, 140.6 38.5 ng%, was
clearly higher than in the control group,
121.6 27.4 ng%, this difference is not
statistically significant. However, 20 of the
86 euthyroid subjects in Sengi had a T3
value above 170 ng%, the upper normal limit
for Dutch controls, whereas only 3 of the 48

between hypothyroid and euthyroid groups

(la + 2a vs. l b + 2b) are highly significant
(P < 0.001), although there was a considerable overlap of values in the lower range
of euthyroid subjects.
The difference of mean plasma T3 concentrations (Fig. 4) between hypothyroid
(l a 42.2 22.8, 2 a 63.4 33.9 ng%) and
euthyroid groups (l b 134.4 28.0, 2 b 142.4
39.8 ng%) are also highly significant,
PBI
/

/jg/i00ml

V;

Cretins Sengi

'

; N C P Sengij/;.,";?! \

Londjong

7'>'

6-

'}l''/,'

'<': '//,\'\'A'':,li','

5-

i-

*,,'''"<'.''''';

'''

'

'

'

'

.11.

'

FlG. 3. Serum PBI in hypothyroid and euthyroid cretins,

non-cretinous subjects (NCP)
and controls. Shaded area is normal range for Dutch subjects
(mean 2 SD).

' ' . ' ' / /

'

'

" '

t
3

1-

2-

t
1-

w
.W.
<:.
V

0
HYPOTHYROID

EUTHYROID

HYPOTHYROID

EUTHYROID

CONTROLS

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485

HYPOTHYROIDISM AND ENDEMIC GOITER

T3
ng/lOOml

NCP Sengi

Cretins Sengi

Londjong

250-

200

FIG. 4. Serum T3 in hypothyroid

and euthyroid cretins, noncretinous subjects (NCP) and
controls. Shaded area is normal
range for Dutch subjects.

150

'

''/',''/'

100-

50-

-f

t
0
HYPOTHYROID

controls from Londjong had comparable

high values.
Plasma TSH values (Fig. 5) were significantly increased in groups la (geometric
mean: 225.1 /uU/ml), lb (17.7 /LtU/ml), 2a
(211.6 /nU/ml) and 2b (15.2 /nU/ml) compared
to Londjong controls (4.1 /u,U/ml). As for PBI
and T3, differences between hypo- and
euthyroid groups are highly significant (P
< 0.001). All hypothyroid subjects showed

EUTHYROID

HYPOTHYROID

EUTHYROID

CONTROLS

TSH values above 100 /lU/ml. There was no

overlap of values in the two small groups of
hypothyroid and euthyroid cretins. In the
non-cretinous population of the iodine
deficient village, however, the highest
values of euthyroid individuals were in the
same range as those observed in hypothyroid NCP.
It should be noted that whereas all serum
TSH values of the Londjong control group

TSH

Cretins Sengi

NCP Sengi

Londjong

500

200-

100-

FIG. 5. Serum TSH in hypothyroid and euthyroid cretins, noncretinous subjects (NCP) and
controls. Shaded area is normal
range for Dutch subjects.

t:
t

50-

20-

10-

5-

'HYPOTHYROID

EUTHYROID

HYPOTHYROID

EUTHYROID

CONTROLS

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486

JCE & M 1977

Vol 44 No 3

GOSLINGS ETAL.
TABLE 1. Clinical and biochemical data of hypothyroid subjects

Subject

Sex/
age

Height
(% control)

Hypothyroid cretins
F/ll
1
M/12
2
F/13
3
M/9
4
F/12
5
6
F/10
7
M/5

75
72
69
96
95
82
72

T3 (ng/
100 ml)

Clin*
signs

252
385
298
325
275
435
363

+
++
++
+
+
++
+

0.7
0.8
0.8
1.0
0.8
0.7
1.2

++
++
+
+
+

+
+
+
+

++

0.7
1.6
1.1
0.9
0.7
1.2
0.8
1.7
1.2
0.6

70
109
92
50
53
90
54

4.9
0.8

122
27

Hypothyroid non-cretinous subjects (NCP)

8
F/9
85
400
9
F/13
90
420
87
10
M/14
285
11
M/12
87
415
12
M/18
89
335
99
F/20
13
355
14
F/9
83
315
M/10
15
80
330
M/7
16
87
270
F/9
17
83
390
M/15
18
103
395
M/17
19
89
430
Control s;ubjects Londjong
Mean
99.6
SD
4.9

PBI
(fig/
100 ml)

Reflex
(m. sec)

262
27

1.7
1.1

TSH
(MU/ml)

48

295.5

22
78
53
37
15

278.8
265.3
128.3
246.0
188.7

15

132.3
195.4
108.0
235.7
261.3
186.9
231.9

21

22
69
116

269.7
342.5
232.2
237.8
4.1

(0.8-7.3)t

Goiter**
grade

131

I uptake (%)

0a
0a
0a
1
0"
1
0a

61
47

66
69
75
41
40

0"
0b
0bN
2

57

78

2
2N
IN
1
0a
0bN
2N

62
91
43

39
53.2
13.8

* ++ = Clinical myxedema; + = dry skin or hair, sluggishness.

** According to the modification by Stanbury et al. (1974) of the classification by Perez et al. (1960).
t Geographic mean and range.

were within normal limits for Dutch subjects, 61% of the euthyroid NCP from Sengi
had an increased serum TSH level.
Clinical and biochemical data in hypothyroid subjects
Clinical and biochemical data of hypothyroid cretins and hypothyroid non-cretinous subjects from Sengi are shown in
Table 1. From the 7 hypothyroid cretins 4
had overt hypothyroidism, but this was only
evident in 2 of the 12 hypothyroid noncretinous subjects. In all others hypothyroidism was mild or could only be suspected
on the basis of minor clinical symptoms.
In 2 non-cretinous subjects the only presenting symptom was a marked elongation of
the Achilles tendon reflex time.
It is evident from the data presented in
Figs. 3, 4, and 5, that none of the biochemi-

cal parameters gives a clear-cut separation

between hypothyroid and euthyroid values.
The values of the plasma hormone concentrations as shown in Table 1 are, however,
in accordance with the diagnosis of overt
or mild hypothyroidism in all subjects
selected on clinical grounds as probably
being hypothyroid. There appeared to be a
negative correlation between PBI and TSH,
which was lacking for T3 and TSH as described by several others (12,15). By analyzing the data in this way it became clear
that the combination of very low PBI values,
<1.8 ng%, with increased TSH, MOO /xU/
ml, was present in all hypothyroid subjects
and only in 3 subjects, who showed none of
the clinical signs used as criteria for the
diagnosis of hypothyroidism. T3 values in
these subjects were 103118185 ng%.
Thus adding a T3 value, <120 ng% gave
only a small additional advantage in de-

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487

HYPOTHYROIDISM AND ENDEMIC GOITER

TABLE 2. Hormone concentrations before and 18 months after iodized oil
T;3 (ng/100 ml)

PBI Oug/100 ml)

Subject*

pre

post

0.7
0.8

4.6
4.0
3.5
3.2

TSH (AtU/ml)

pre

post

pre

post

48

22
78
53

144
138
112
106

295.5
278.8
265.3
128.3

9.6
330.0
3.0
8.7

15
69
109
50

71
130
140
136

132.3
235.7
231.9
269.7

6.9
8.9
5.3
6.7

52.2 24,.5

122.1 24.7f

219.9

10.8$

Hypothyroid cretins
1
3
4

1.0
0.8

Hypothyroid non-cretinous subjects (NCP)

8
1.6
0.7
11
4.2
0.9
14
6.0
0.7
15
0.8
5.6
Mean SD

0.8 0,.1

4.1 1.4f

Differences between pre- and post treatment values (paired t test).

* Subject numbers correspond to table 1.
t P < 0.001.
\ P < 0.005.
Geometric mean.

fining the best biochemical criteria for the

diagnosis of hypothyroidism in the studied
circumstances. The two subjects with low
T3 values might be called biochemical or
subclinical hypothyroid, but we hesitate
to do so, since the clinical implication of
these biochemical findings is by no means
clear (19).
The effect of iodized oil injections.
Table 2 shows the effect of iodized oil
injections on the biochemical parameters
of thyroid function in 8 hypothyroid subjects (4 from group la, 4 from group 2a,
see Table 1). For all these parameters there
was a highly significant change towards
euthyroid values. PBI rose to normal or near
normal levels in all except one. We have
no explanation for the unexpected finding
of a persistent high TSH level in 1 subject
(no. 3). Clinical examination by one of us
(R.D.) also showed marked improvement
of clinical symptoms in all hypothyroid
subjects.
Discussion
The results of our study clearly show that
hypothyroidism was not only present in cre-

tins living in the area (where endemic

cretinism was of the neurologic type), but
also in a considerable number of noncretinous subjects living in the same village.
Because strict criteria were used for the
diagnosis of cretinism and sensitive techniques were used to detect mental retardation, perceptive deafness and neuromotor
disorders, even mild forms of cretinism,
not easily detectable by simple clinical survey, were included in the group of cretins.
Of the non-cretinous hypothyroid subjects
none showed neuromotor disorders. One
boy (subject 19, Table 1) had a small hearing
loss, maximal at 2000 Hz and normal intelligence (22). One girl showed some degree of
mental retardation without any other sign
of cretinism. Since she (subject 13, Table 1)
had a normal height her hypothyroidism
apparently only developed after puberty
and cannot easily be related to her mental
retardation. In all other hypothyroid NCP
intellectual performance was within the
"normal" range. It can therefore be concluded that hypothyroidism in these noncretinous subjects started after the age of 3
years (27) and thus may be called endemic
juvenile hypothyroidism. Although the
frequency of hypothyroidism was higher in

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488

GOSLINGS ETAL.

cretins (35%) than in the non-cretinous

population, its prevalence (13%) was much
higher than expected by us and reported
thus far (11).
We have no reason to suspect that the
cause of hypothyroidism in the non-cretinous subjects is different from that of
hypothyroid cretins. From several factors
possibly involved in the pathogenesis of
hypothyroidism genetic defects in hormone
synthesis are very unlikely to play a significant role (17,28,29). As mentioned
earlier, thyroid atrophy and fibrosis have
been implicated as a possible mechanism,
de Quervain and Wegelin (1) noted that in
most dwarfed cretins goiter is either absent
or small and that there is in general a negative correlation between growth retardation
and goiter weight in endemic cretins. Similarly goiter was absent in almost all hypothyroid cretins studied by Bastenie et al.
(7), in the Uele Region in Zaire. In accordance with the hypothesis of primary thyroid failure by reduction of the amount of
functioning thyroid tissue, these subjects
showed a markedly low radioiodine uptake,
poor response to TSH administration and a
very small thyroid exchangeable iodide pool
with very fast turnover rate (7,17). The very
high TSH levels reported in this study and
several others (11,12,15,30) also indicate that
the thyroid remnant in this situation seems
to work at the maximum of a limited capacity
under maximum endogenous TSH secretion. The cause of the damage to the thyroid
gland, however, remains unclear. An autoimmune response seems to be unlikely since
anti-thyroid antibodies were absent in the
sera of our hypothyroid subjects (by courtesy
of D. Doniach), as reported by others in
hypothyroid cretins (3,7,31). Overstimulation by TSH has been suggested as a possible cause by Dumont et al. (17), but this
has not been proved.
Some of our data also seem consistent with
thyroid atrophy as a causal factor in the
pathogenesis of hypothyroidism. As shown
in Table 1, in 4 of 7 hypothyroid cretins
no goiter could be palpated. All 12 euthyroid
cretins had goiters varying from grade OB

JCE & M 1977

Vol 44 No 3

to 2. Also the mean thyroid radioiodide

uptake was lower in hypothyroid than euthyroid cretins, although the difference between these two small groups was not significant. In the hypothyroid non-cretinous
subjects, the mean maximum radioiodide
uptake of 56.4 19.6% was significantly
(P < 0.005) lower than the uptake of 77.9
10.6% in euthyroid non-cretinous individuals. There was, however, no clear correlation between goiter grade and thyroid uptake and the absence of goiter was not a
striking feature in the group of hypothyroid
non-cretinous subjects. This might be explained by the fact that extensive degenerative changes can also be found in large
goiters. On the other hand it is evident
that a definitely increased 131I uptake was
found in about 50% of all hypothyroid subjects, which suggests to us that thyroid
failure might occur in spite of active compensatory mechanisms. In these cases failure of the thyroid gland to provide adequate
hormone output may very well be a direct
result of extreme iodine deficiency. That
iodine deficiency per se can be an important
causal factor in the pathogenesis of hypothyroidism is strongly supported by our
finding that "iodine prophylaxis" by iodized
oil injection corrected or markedly improved
thyroid function in all the 8 subjects restudied 18 months later (see Table 2). This
was not only the case in those with large
goiters and high radioiodine uptake, but
also in those where goiter was absent or
uptake very low.
Evidently also in so-called atrophic glands
enough functioning thyroid tissue may be
present for normal hormone production if
adequate iodine intake is provided. This
is more likely than may be expected at first
thought when one realizes that in the adult
after subtotal thyroidectomy less than 10 g of
thyroid tissue is sufficient for adequate hormone production. In this respect it is
interesting to note that Koening (32), when
he restudied a number of old Swiss cretins,
found most of them to be clinically and biochemically euthyroid even when the clinical
picture strongly suggested that in previous

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HYPOTHYROIDISM AND ENDEMIC GOITER

years hypothyroidism must have existed.
Although the efficiency of iodine prophylaxis for the prevention of cretinism (3336) and for the correction of different parameters of thyroid function has been well
documented (13, 36, 37) its effect on hypothyroidism in endemic goiter areas has to
our knowledge not explicitly been studied
before. This is comprehensible since on the
one hand thyroid hormone substitution
seemed to be the most efficient form of
treatment in those cases where one hopes
to get some improvement in the clinical
condition of the cretins studied, while on the
other hand mild forms of hypothyroidism
in endemic goiter areas have escaped detection thus far.
Our findings also bear on the definition
of endemic cretinism. Since the described
form of hypothyroidism could be corrected
by iodine prophylaxis it should have to be
included in the epidemiological definition
of endemic cretinism formulated by Choufoer et al. (3). On the other hand to use
the term endemic cretinism in the absence
of any sign of damage to the central nervous
system would be confusing. Also the purely
descriptive definition, as put forward at the
Goroka conference (18), which recognizes
damage to the central nervous system and
hypothyroidism as two components present
in endemic cretins in different degrees,
cannot without further amendment be
used to classify an individual as being
cretin or not. The finding of a considerable
number of hypothyroid individuals lacking any of the signs classically related to
endemic cretinism, at least strongly reduces
the value of hypothyroidism as a criterion
for the diagnosis of endemic cretinism. In
our opinion with the present knowledge an
endemic cretin can best be defined as a subject, born in an area of endemic goiter,
with irreversible damage to the central
nervous system, resulting in mental retardation and/or perceptive deafness and/or
neuromotor disorders, which may be accompanied by stunted growth and clinical
hypothyroidism. Although intra-uterine
hypothyroidism caused by very severe io-

489

dine deficiency of the fetus seems to be the

most likely pathogenesis for the damage
to the central nervous system, mental retardation may also result from hypothyroidism in the first three years of life (27).
Perceptive deafness and neuromotor abnormalities, however, almost certainly
have their origin in early fetal life (22,38).
The striking difference between the socalled nervous form of endemic cretinism
and the myxedematous form as described in
Zaire therefore seems to be the fact that in
the former the fetus is probably damaged
during the total period of intra-uterine life
(i.e., at least from the 10th week onward),
while in the latter only the late fetal and
early postnatal period seems critical in the
pathogenesis. It remains possible that unknown factor(s) other than iodine deficiency
of the mother, are responsible for this
difference.
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GOSLINGS ET AL.

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