Nephrocalcinosis in Cretinism

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1965, Brit. J. Radiol.

, 38, 581-584

Nephrocalcinosis in cretinism
By Eric M. Bateson, M.D., D.M.R.D., F.F.R.,* and Subhash Chander, M.R.C.P.,
D.M.R.D., D.M.R.T., F.F.R.
The United Sheffield Hospitals
(Received August, 1964)

The characteristic radiological changes in cretinism Some improvement resulted and teeth appeared whereas
are the delay in the appearance of and growth of previously there had been none. Thyroid medication ceased
at the age of three years and as far as it was known she
ossification centres, with deformity and fragmenta- received no further treatment.
tion of epiphyses, hypoplasia of one or more verte- On examination, following admission to hospital, the
patient was found to have the stature of a child of four
bral bodies near the dorso-lumbar junction, and years, typical hypothyroid facies, a gruff voice, supra-
lines of increased density in the metaphyses and in clavicular pads of fat and a dry, scaly skin. Her blood pres-
the upper and lower surfaces of the vertebral bodies sure was 140/90 and pulse rate was 80. A low voltage tracing
was obtained on electrocardiography. The tendon reflexes
(Astley, 1958). Middlemass (1959) mentions com- were delayed. She was anaemic (the haemoglobin varied
plete absence of the para-nasal air sinuses and en- between 65 and 78 per cent), her serum cholesterol was
largement of the pituitary fossa in some cases. 290 mg per cent. A radioactive iodine tracer test gave a result
with hypothyroidism.
There are, however, two radiological features in Biochemical changes are shown in Table I.
cretinism which are not well known.
Firstly, there may be generalised osteosclerosis, Radiological appearances
The skull vault was normal. Several unerupted molar
similar to, but not identical with the sclerosis seen teeth were present. The skull base appeared to have in-
in osteopetrosis (Jeune and Muller, 1959), and creased density, but it was difficult to be sure if this was due
cretins showing this radiological feature have been to sclerosis or to the fact that the sphenoid sinuses had not
developed (Fig. 1). The other accessory nasal sinuses had
described by Jeune, Beraud and Bouvet (1955), also not developed.
Johnson and White (1952), Mikulowski (1960), and There was increased density of the bodies of the dorsal
Schmidt (1962). Generalised osteosclerosis is rare, (Fig. 2) and lumbar spine (Fig. 3) with a tongue-shaped
deformity of the body of the 1st lumbar vertebra.
but a forme fruste affecting only the cranio-facial The upper femoral epiphyses were irregular, with frag-
bones is more common (Jeune and Muller, 1959). mentation, stippling and increase in density (Fig. 4). Many
Following the administration of thyroxine, this bony of the epiphyses showed incomplete fusion with the adjoin-
ing metaphyses.
sclerosis usually disappears (Jeune and Muller, 1959; The heart was enlarged. Gross calcification of the whole
Mikulowski, 1960; Royer, Lestradet and Habib, of the thoracic aorta (Fig. 2) and also part of the common
1958; Pathe, Ernould and Morel, 1961). carotid arteries was present.
Bilateral nephrocalcinosis was demonstrated on a radio-
Secondly, there may be nephrocalcinosis or graph of the abdomen (Fig. 3). The right renal shadow was
nephrolithiasis, or both. Cases showing these radio- small and there was a small opacity in the right side of the
pelvic cavity which could have been a stone in the ureter
logical features have been reported by Naylor (1955) (Fig. 4).
Jeune and Muller (1959) Royer et al. (1958),
Schmidt (1962), Tumay, Bilger and Hatem (1962) DISCUSSION
and Charlas and Slomic (1962). Many of these cases As there was no evidence of biochemical abnor-
also had osteosclerosis. Richardson (1962) mentions mality in the present case, the nephrocalcinosis was
an adult with myxoedema and nephrocalcinosis. not due to hyperparathyroidism. There was no
A further case of cretinism, showing typical radio- evidence of hypervitaminosis D or sarcoidosis. The
logical features, with marked nephrocalcinosis and possibility of a self-limiting condition in childhood,
sclerosis of the spine, is described below and the such as renal tubular acidosis or idiopathic hyper-
relationship of the radiological changes to the hypo- calcaemia which had cleared up but had resulted in
thyroid state is discussed. nephrocalcinosis, cannot be excluded.
It is also possible that the nephrocalcinosis was
Case report due to some factor as yet unknown (Bateson, 1962) and
The patient, a female, aged 41 years, was first admitted to
hospital in 1962, following the death of her mother. She was a significant proportion of cases in published papers
diagnosed as having "lack of thyroid" at the age of two and on nephrocalcinosis (Mortensen and Emmett, 1954;
a half years and received thyroid tablets for six months.
Pyrah and Hodgkinson, 1960; Kreel, 1962) had no
known cause for their nephrocalcinosis and were
* Present address: X-ray Department, Royal Perth Hospital,
Perth, Western Australia. classified as idiopathic.
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VOL. 38, No. 452
Eric M. Bateson and Subhash Chander
TABLE I
BIOCHEMICAL CHANGES

Investigations Result Relation to normal


Serum calcium 9-4 mg% (4-7 mEq/1.) Normal
Serum phosphorus 3-6 mg% (2-06 mEq/1.) Normal
Serum chloride 353 mg% (99-5 mEq/1.) Normal
Serum sodium chloride 578 mg% (98-9 mEq/1.) Normal
Serum CO2 50 ml% (22-3 mEq/1.) Slightly diminished
Serum bicarbonate 22-5 mEq/1. Slightly diminished
Serum alkaline phosphatase 18 King-Armstrong units Slightly raised
Blood urea 42 mg% Slightly raised

FIG. 1. Lateral radiograph of skull showing absence of pneumatisation of the sphenoid and possible sclerosis of this bone.
FIG. 2. Antero-posterior radiograph of the dorsal spine showing sclerosis of the vertebral bodies and extensive calcifi-
cation of the entire thoracic aorta.
FIG. 3. Antero-posterior radiograph of the lumbar spine showing sclerosis of the vertebral bodies, a small right kidney
and bilateral nephrocalcinosis.
FIG. 4. Antero-posterior radiograph of the hips (print reversed) showing fragmentation, stippling and increased density
of the femoral epiphyses, with opacities in the pelvis, of which one small opacity on the right side could be a ureteric
calculus.
582
AUGUST 1965
Nephrocalcinosis in Cretinism
TABLE II

Serum calcium Sclerotic bone Relationship of nephrocalcinosis


Author Age Sex (mg/100 ml.) changes to cretinism

Johnson and White (1952 21 months F 11-6 12-2 Generalised No treatment Autopsy
Xaylor (1955) 4J years F 6-1 15-1 No sclerosis No treatment X-ray
?
6J months 13-0 16-0 Skull base Before treatment X-ray
Rover et al. (1958) '.'. 4 years j Normal ? Autopsy
4 years p Normal '•
3
Autopsy
20 months '•>

Normal Autopsy
Jeuneand Muller (1959)* 2 years F 9-9 11-4 Generalised Followed treatment X-ray
3
Schmidt (1962) 2 years 11-7 Generalised Before treatment X-ray
Tumav et al. (1962) 6 years F 9-8 Skull base Before treatment X-ray
Charlas and Slomic (1962) 25 years M 11-2 None No treatment Stones
Bateson (1962) 41 years F 9.4 ? skull base ? before or after X-ray
and spine treatment

* Also reported by Jeune and Beraud (1955).

In view of the fact that there have been at least 1950; Wilkins, 1957). Braid (1951) reported a cretin
nine cases of cretins with nephrocalcinosis demon- with metastatic calcification which disappeared fol-
strated either radiologically or histologically, re- lowing thyroid treatment. Lowe, Bird and Thomas-
ported in the literature, it seems quite reasonable to (1962) found intolerance to ingested calcium in myxo-
assume that the hypothyroid state was responsible for edema. Goormatigh and Handovsky (1938) found
the nephrocalcinosis. A summary of these nine cases that thyroidectomised dogs were hypersensitive to
and of a tenth case with nephrolithiasis is given in vitamin D, probably due to slow breakdown of
Table II. sterols associated with myxoedema. Lamy, Nezeloff,
From Table II it can be seen that all but one of Faure, Jammet and Aussinaire (1958) noted simi-
the cases of cretinism with nephrocalcinosis also had larity between the sclerosis seen in cretinism and
bony sclerosis. Three of the cases had hypercalcae- that seen in idiopathic hypercalcaemia. The fact that
mia and the absence of this in the other cases does hypercalcaemia, bony sclerosis, and nephrocalci-
not exclude the possibility that it may have been nosis are only seen in a few instances of cretinism is
present at some time during the hypothyroid state. explained by Tumay et al. (1962) who said that in
Aub, Bauer, Heath and Ropes (1929) found that cretinism the over-absorption of calcium from the
calcium and phosphorus were deposited in greater intestine and the increased deposition in the bones
quantity in the bones and were eliminated less fre- are in equilibrium, but in some instances the
quently in the urine and faeces in cases of hypo- absorption of calcium predominates giving rise to
thyroidism than in the normal. Robertson (1941) hypercalcaemia.
confirmed this by finding a diminished calcium out- Therefore, by correlation of the above observa-
put (chiefly in the urine) in myxoedema and noted tions, the following explanation of the presence of
that thyroid treatment increased the calcium output nephrocalcinosis in cretinism can be made.
(chiefly in the urine). He (Robertson, 1942) sug- In the hypothyroid state there is increased re-
gested that thyroxine directly affects the renal tention of calcium and phosphorus, with the de-
threshold for calcium, the deficiency of thyroxine position of greater than normal quantities of calcium
raising the threshold. This retention of calcium in the bones causing sclerosis. There is also, at least
would account for the bony sclerosis, but not for in some cases, a hypersensitivity to vitamin D, and
nephrocalcinosis in cretinism. Following the ad- this, together with the increased retention of
ministration of thyroxine, the excess of calcium is calcium, leads to hypercalcaemia and also to nephro-
mobilised from the bones and results in the positive calcinosis.
calcium balance of hypothyroidism becoming the In the present case, a combination of bony
normal negative calcium balance. One would expect sclerosis and nephrocalcinosis was present. The
hypercalcaemia to result and this was observed in nephrocalcinosis may have been due to hyper-
the cases reported by Jeune and Muller (1959), calcaemia which, although no longer present, had
Naylor (1955) and Royer et al. (1958), and in the been present at some time in the past. The marked
case of Jeune and Muller, nephrocalcinosis also aortic calcification could have been metastatic and,
developed. therefore, would support the possibility of a previous
Evidence of hypersensitivity to vitamin D in hypercalcaemic state, but severe atheroma is com-
hypothyroidism also exists (Fanconi and Chastonay, mon in myxoedema (Douglass and Jacobson, 1957;
583
VOL. 38, No. 452

Eric M. Bateson and Subhash Chander


Creed, Baird and Fisher, 1955; Spain, Greenblatt, CREED, D. L., BAIRD, W. F., and FISHER, E. R., 1955, Amer.
Snapper and Cohn, 1956) and is related to the hyper- J. Med. Set., 230, 385.
DOUGLASS, R. C , and JACOBSON, S. D., 1957, y. Clin.
cholesteraemia which is usually present. This, Endocrin., 17, 1354.
rather than hypercalcaemia, may have caused the FANCONI, G., and CHASTONAY, E. DE, 1950, Helv. paediat.
Acta, 5, 5.
aortic calcification. However, with a history of thy- GOORMATIGH, N., and HANDOVSKY, H., 1938, Bull. Acad.
roid treatment many years ago, it is also possible Roy. Med. Belg., 3, 132.
that the nephrocalcinosis may have resulted from JEUNE, M., and BERAUD, C , 1955, Arch, franc. Pe'diat., 12,
368.
the hypercalcaemia and increased urinary output of JEUNE, M., and BERAUD, C , and BOUVET, 1955, J. Radiol.
calcium which can occur during thyroid treatment of Electrol., 36, 237.
cretinism. The prolonged hypothyroid state may JEUNE, M., MULLER, J. M., 1959, Pe'diatre, 14, 43.
JOHNSON, W., and WHITE, F., 1952, Case Rep. Child. Hosp.
have intensified the nephrocalcinosis. Chicago, 10, 2030.
KREEL, L., 1962, Clin. Radiol., 13, 218.
ACKNOWLEDGMENTS LAMY, M., NEZELOFF, C , FAURE, C , JAMMET, M. L., and
We wish to thank Dr. D. Munro for his permission to AUSSINAIRE, M., 1958, Arch, franc. Pediat., 15, 1001.
publish this case and Dr. J. Wilkie for allowing us to LOWE, C. E., BIRD, E. D., and THOMAS, U. C , 1962,^. Clin.
reproduce the radiographs. Endocrin., 22, 261.
We are grateful to the Photographic Department of the MIDDLEMASS, I. B. D., 1959, Brit.y. Radiol, 32, 685.
United Sheffield Hospitals for the reproduction of the MIKULOWSKI, V., 1960, Mschr. Kinderheilk, 108, 473.
radiographs. MORTENSEN, J. D., and EMMETT, J. L., 1954, y. Urol, 21,
We would also like to thank Mrs. E. M. Bateson for her 398.
help in the preparation of this paper and Mrs. I. Deans for NAYLOR, J., 1955, Arch. Dis. Childh., 30, 165.
typing the manuscript. PATHE, G., ERNOULD, H. J., and MOREL, A., 1961, Sem. Hop.
Paris, 37, 1172.
SUMMARY PYRAH, L. N., and HODGKINSON, A., 1960, Brit. y. Urol,
The possibility of nephrocalcinosis developing in cretins, 32, 361.
or following the treatment of cretins with thyroid hormone, RICHARDSON, R. E., 1962, Clin. Radiol, 13, 224.
is discussed, with a review of cases of cretinism with ROBERTSON, J. D., 1941, Lancet, 1, 216; 1942, Lancet, 1,
nephrocalcinosis which have been reported in the literature. 672.
A further case of cretinism with nephrocalcinosis is ROYER, P., LESTRADET, H., and HABIB, R., 1958, Arch.
reported. Pediat., 15, 896.
SCHMIDT, J., 1962, Z. Kinderheilk, 86, 602.
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ASTLEY, R., 1958, Brit.J. Radiol., 31, 346. T., 1956, Amer. y. Med. Sci., 231, 165.
AUB, J. C , BAUER, W., HEATH, C , and ROPES, M., 1929, TUMAY, S. B., BILGER, M., and HATEM, N., 1962, Arch.
J. Clin. Invest., 7, 97. Dis. Childh., 37, 543.
BATESON, E. M., 1962, Clin. Radiol, 13, 231. WILKINP, L., 1957, The diagnosis and treatment of Endocrine
BRAID, F., 1951, Brit. med.J., 1, 1169. disorders in children and adolescents, 2nd edn., 81; 416
CHARLAS, A., and SLOMIC, A., 1962, Maroc. Med., 41,1178. (C. C. Thomas, Springfield, 111.)

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