A case of hyperparathyroidism

Studies

in

Clinical

Qral

Pathology

Associate Editor

LESTER R. C’AHN A CASE OF HYPERPABATHYROIDISM BERNARD LEVY,

D.D.S., NEW YORK? Tu’. ‘ir.

HIS is the case of a 34-year-old housewife who, on Dec. 4, 1948, present’rd herself complaining of a nonpainful swelling in the region of the right mandibular premolars. Examination showed e?pansion of the buccal cortical plate of the mandible in the canine-premolar region, The swelling was firm and was covered with a normal-appearing mucous membrane. There was no lymphadenopathy. Oral hygiene was good. The teeth in the affected area had been missing for some years and their 10~s was attributed to neglected caries. The pa& history given at this time was irrelevant. Roentgenographs showed a multiloculat8ed radiolucent lesion in the mandibular canine and premolar region. The b,orders of this radiolucent area WCI’C not well defined. Extensive thickening of the periodontal membranes of the right lateral and central incisors was noted (Figs. 1 and 2). Under regional block anesthesia, a generous mucoperiosteal flap was yetracted, exposing the expanded portion of the buccal plate. This part of the plate was removed and a solid mass of tissue, bluish in color and having a granular surface, was enucleated. The exposed bony walls were irregular and porous and this bone was removed until an apparently normal osseousst,ructrlrc was reached. The flap was returned and sutured into place. The tissue was sent for histological examination. The diagnosis of the pathologist was: ‘ ‘osteitis fihrosa of the giant
T

These results were all within normal limits. The operative wound healed uneventfully and the patient was asked t,o r’cturn from t,ime to time for observation. Four months later, March 4, 1949, the pat.ient returned complaining of a swelling in t,he region of the lower right t,hird molar. Examination now re-c_ Read at the Montllly (Xmference of the New York Institute Jan. 28, 1952. 549

of Clinical Oral Pathology,

550

BERNARD

LEVY

vealed a small, bluish-red mass with a granular surface growing out of a pocket distal to the third molar. Roentgenograms taken at this time showed that healing had occurred at the original site of operation but that now there was a small area at the apex of the vital, mandibular right third molar. The possibility of a giant cell tumor, a,ctivated by a parathyroid adenoma, was considered, and the patient was referred to a hospital for investigation along these lines. Because the blood values were again within normal limits a general

Fig. l.-Intraoral roentgenograms showing the widening of the periodontal the loss of the linea alba, and the irregular radiolucency of the bone. The third time appears uninvolved. (December, 1948.)

Fig.

‘Z.--An

extraoral

roentgenogram which (December,

shows 1948.)

the

intraosseous

lesion

membrane, molar at this

better.

surgeon reoperated upon the mandible. Not only was the former site recuretted but the freshly appeared lesion was radically attacked. Again healing was uneventful. On May 6, 1950, fourteen months later, the patient once more returned complaining of a swelling in the region of the upper left central and lateral

:,.-I 1

HYPPERPARATHYKOIDISM

irmisors. Examination revealed a large diffuse swelling extending from thy central incisor to the canine and from the free marginal gingivae high into the rnucohuccal fold. The lesion was extremely tender. While the teeth were nllrbile, they all responded within normal range t,o the electric pulp tester. Roengenograms showed a diffuse radiolucent area with ill-defined borders engulfing the roots of the central, lateral, ant1 mesial surfaces ol’ the canine tretli. ( Fig. 4.)

Fig.

3.-Photomicrograph

of the

tissue removecl. This (December, 1948.)

shows

typical

giant

cell

tumor

The patient was once more questioned, in order to bring out some pertinent past history, and now she disclosed the fact that she had had an operat,ion in 1947, in the same area where we had performed our first procedure. She said that healing had been protracted and that she remembered that several bone spicules had been exfoliated over a period of several weeks. No tissue examirrat,ion had been done at that time. We also noticed now that the patient had difficulty in walking and she volunteered the information that she had noticed this difficulty as far back as 1942 and that it had been getting progressively worse. A tentative diagnosis of giant cell tumor was once more made and the patient referred back to the surgeon who had last operated upon her. A biopsy of the maxillary lesion was done and a report of fibrous dysplasia was made. Since this was inconsistent with the picture, another biopsy was performed and this time a diagnosis of giant cell tumor was returned. By this time the patient was unable to walk and she was placed in the hospital. Once more the blood chemistry was studied and roentgenograms were made of the skeleton.

552

BERNARD

LEVY

This time the blood chemistry showed abnormal values and there were found multiple osteolytic lesions in other bones, notably the hip. The neck was explored and a parathyroid adenoma was found. The patient apparently made an uneventful recovery. She soon was able to walk without difficulty, the lesion in the upper left maxillary region regressed, and the blood levels for calcium, phosphorus, and alkaline phosphatase returned to normal.

Fig.

4.-The

maxillary lesion. bone has been

The periphery of the lesion seems vague and The teeth are vital. (May, 1950.) destroyed.

Fig. 5.-These roentgenograms were taken jaw (acthally, as we later learned, this was the There the removal of the parathyroid adenoma. this is Particularly marked between the teeth.

the

interseptal

three years after the flrst operation On the second operation) and fOu!‘teen months after is evidence of fllling in with new bone and (December, 1951.)

On Dec. 11, 1951, three years following our first operation, and one and one-half years following the removal of the parathyroid adenoma, the patient came back. Once more she complained of a swelling in the left maxilla in the same region as reported in May, 1950. Roentgenograms again disclosed a radiolucent area that was not as diffuse as the former one and seemed to have a more defined periphery. The roentgenogram showed a considerable amount of healing. Where, in the first lesion, the alveolar bone between the teeth had apparently been replaced by pathologic tissue, there was now regeneration. (Fig. 5.) The swelling was fluctuant and there were all the signs and symptoms of a suhperiosteal abscess. The central and lateral incisors were found to be non-

v-i. .f.,,i

HYPERPARATllYROIUtSM

surface 1951.)

Fig. 6.-Photomicrograph of tlw wall is composed

of tissue removed. There of inflammatory rolls anil

is no epithelial lining. fat-laden niacrophnges.

Fig. 7.-Another portion of the same specimen. Toward giant cell tumor is still present. At the left is connective tissue :lnd some islnnds of calcification. (December. 1951.1

the right in which

and bottom, is an osteoid

The inns ( rkccmbc r.

inflamed trabevula

554

BERNARD

LEVY

vital. It was felt that the condition represented an acute infection arising from the nonvital teeth. An incision was made which allowed for the drainage of a considerable amount of pus. The patient was also placed on penicillin therapy. Six days later the teeth were extracted .and the tissue was surgically removed. This tissue was submitted for pathological examination. Pathological Examination-The important parts of the report are recorded here. The tissue apparently was a cyst wall without any epithelial lining. The inner surface of the wall was a granulation tissue made up of polymorphonuelear leukocytes, lymphocytes, plasma cells, and numerous fat-containing macrophages. Occasional areas of cholesterol slits were present. At the periphery of the wall there were numerous multinucleated giant cells in a st,roma made up of spindle-shaped cells. In other zones the periphery showed a bony plate disclosing resorption and marked repair. There was osteoid covering in a broad seam, remnants of bone t,rabeculae. Some trabeculae were entirely composed of osteoid. In some areas round and irregular calcific masses and scattered lymphocytes within connective tissue were seen. In places the connective tissue blended into the osteoid. Diagnosis: “Granuloma with cavity formation. Small areas suggesting osteitis fibrosa of the giant cell tumor variety” (Figs. 6 and 7). Postoperative healing was uneventful. Comment (Lester R. Calm) This case is of extreme interest particularly from the standpoint of diagnosis. Both Dr. Levy and the pathologist, Dr. Freund, suspected the possiThey were misled by the normal blood chemistry bility of hyperparathyroidism. findings. For that matter, so was the general surgeon who operated upon the second lesion, or rather, as it turned out, upon the third one. As Dr. Snapper1 has so well pointed out, the blood chemistry may well b,e within normal limits’ in patients with hyperparathyroidism. The kidney tubules normally reabsorb sufficient calcium to maintain a blood level of from 9.5 to 10.5 mg. per cent. Under the influence of excessive parathormone or vitamin D the tubules no longer efficiently reabsorb calcium so that increased amounts of this mineral are lost in the urine (hypercalciuria) . Compensation for this loss of calcium must come either from the skeleton or from food. We, in this country, are large consumers of milk and cheese, foodstuffs rich in calcium, so that the von Recklinghausen type of hyperparathyroidism is not as common as it is in Europe. Albright and Reifenstein* also mentioned that primary hyperparathyroidism can be present without classical prima facie evidence of the disease either roentgenologically, histologically, or chemically. It. is their opinion that “hyperparathyroidism brings about a change in the blood chemistry of the body which results in there being an increased excretion of calcium in the urine. Other things being equal, this increases the chances of the patient being in negative calcium balance. If the patient is in negative calcium balance, bone disease develops ; if the patient happens to ingest suf-

-_ . I:).)

HYPERPARBTHYROIDISiM

ficierl t calcium to compensate for the loss in t,he urine and feces, the calcillnl balance is not negative and bone disease does not develop. For all practic>al purposes, it usually comes down to whether or not the patient drinks milk. Ii’ he does the calcium intake will be sufficient to keep a positive calcium llalatt~c~ even if he has marked hyperparathyroidism.” It is therefore very apparent that the excretion of urinary caleilun m11s1 he carefully det,ermined. In health about ‘75 per cent of the ingested c,alei~!~~ is excret.ed in the feces and about 25 per cent by way of the urine. In hyrJ”‘l’parathproidism the reverse takes place. When there are signs and synrpto~r~ of hyperparathyroidism and t,he blood chemistry is apparently normal. cartfully controlled studies of calcium excretion in the urine must be d~;t:. Snapper’ has reported the case of multiple, recurrent tumors of the ,jaws th:lt were variously described as giant cell tumors and osteofibromas with no other roentgenographic changes in the skeleton. Numerous blood chemistqv stuclies Only after calrium cscrcticm were so equivocal as to be considered normal. studies of the urine were made was it seen that the patient, was in negat,i\e ~1~ cium balance. An exploratory operation of the neck disclosed a parathyroitl adenoma. Urinary calcium excretion studies are best done with the patient, in I h(! hospital. A diet that has not more than 100 to 125 mg. of calcium per day is taken. The Bauer-Aub diet is the one generally used. The patient is kept on this diet for three days and then a twenty-four hour specimen of urine is Wamined for calcium. This is repeated for three days. Normally a patient on this diet would not excrete more than from 100 to 150 mg. of calcium per diet)]. Any amount above this would be significant of a negative calcium balance. In primary hyperparathyroidism three times the normal is usually escret.ed. There is a rough test that gives fairly accurate results and that (aarj hc dnnr in the office. This is the Sulkowitch test. A solution

known

as the Sulkowitch

Oxalic acid Ammonium oxalate Glacial acetic acid T)ist.illed water

solution

is used.

This cwnsists oi‘:

2.5 Gm. 2.5 Cm. 5.0 C.C. qs. a(1 350.0 (‘.(‘.

The patient is asked not to drink any milk or eat any cheese for three days. in ot,her words, to cut down on the calcium intake. The morning specimen oj‘ the fourth day is examined. The urine should be neutral or slight.ly acid. This can be determined either with litmus or, better, nitrazine paper. If the urinf~ is alkaline a drop or so of glacial acetic acid is added until it ‘is slightly acid. Five cubic centimeters of urine are placed in a test tube and about t,wo cubic centimeters of the Sulkowitch solution are added. The speed with which the precipitate forms and its degree of intensity are noted. The results arc’ registered as from zero to four plus. A zero test would signify a hypoca.lciuria and a hypocalcemia, while a three t,o four plus finding would indjcat,e a hyper-

556

BERNARD LEVY

calciuria and strongly suggest a hypercalcemia. As was said this is a rough test, but if there is a consistently high positive Sulkowitch over a period of time, more detailed studies of the urinary calcium excretion must be done. In the patient under discussion, if calcium studies had been done immediately, regardless of the blood chemistry, an earlier diagnosis of hyperparathyroidism could have been made. Even using the Sulkowitch test might have given a true clue to the mischief. And now we come to the last episode. This was undoubtedly an infected lesion and whether it was a true cyst or cavitation of a persistent giant cell lesion is open to question. Histologically there was no epithelial lining anywhere to be found. The only possibility that it might have been a cyst was the finding of the cholesterol slits. It is possible that infection from the devitalized teeth may have resulted in abscess formation of the residual giant cell tumor with the formation of central necrosis and cavity formation. That there was still evidence that there was giant cell tumor at the periphery would lead me to think that this was the case. The fact that giant cell tumor still persists makes one wonder whether there might not be another parathyroid adenoma present. Caseshave been recorded3 where a second tumor had been found on reoperation, after all symptoms and signs had failed to regress completely after the removal of the first growth. It would be a good idea to have this patient re-examined, especially with emphasis on the urinary calcium excretion, to rule out the possibility of another hyperfunctioning parathyroid adenoma. It is interesting to note that quite a few casesof hyperparathyroidism have now been reported4 where only the jaws have been noticeably affected, the rest of the skeleton being free from changes at least, roentgenologically. Lesions of many diseases frequently develop at points of irritation and trauma. The jaws are continually subjected to trauma, particularly if teeth are present, which makes the jaws vulnerable and renders them a fertile diagnostic field. At the point of being repetitious and monotonous, it must be reiterated that no case of giant cell tumor, loss of the linea alba, widening of the periodontal shadow, and increase of the intertrabecular spaces should be allowed to go unchallenged, until every means has b.een exhausted to rule out hyperparathyroidism. For over four years this patient had been suffering from hyperparathyroidism without any signs of kidney damage. In this she has been very fortunate. Damage to the kidneys, because of metastatic calcification, is more serious as to mortality than are the changes that take place in the bones. Kidney damage is irreversible and it is for this reason that hyperparathyroidism must be detected early. JVe are frequently in a position to do this. References 1. Snapper,I.: Medical Clinics on Bone Diseases,New York, 1949, Interscience Publishers, Inc. 2. Albright, F., and Reifenstein, E. C.: The Parathyroid Glands and Metabolic Bone Disease, Baltimore, 1948, Williams 8; Wilkins Company. 3. Cahn, L.: The Jaws in Generalized Skeletal DSsease, Ann. Roy. Coil. Surg. England 8: 115. 1951. 4. Cahn, L.: hone Pathology as It Relates to Some Phases of OSal Surgery, ORAL SUFCG.,

ORAL MED., AND OXAL PATH.~: 917,194&J.