Hyperparathyroidism associated with intrathyroid parathyroid glands

Hyperparathyroidism Associated with Intrathyroid Parathyroid Glands d G. E. TOLSTEDT,

M.D.,

E. E. CAMMOCK, M.D.

From tbe Departments of Surgery, Veterans Administration Hos&tal and Universitv of Wasbineton School of* ” Medicine’, Seattle, Wasbin@&. -

J. W. BELL,

M.D.,

Seattle, Washington

SurgicaI expIoration of the neck on July I 7, 1959, revealed parathyroid gIands adjacent to each inferior thyroid artery. The Ieft gIand was larger and appeared adenomatous. VascuIar pedicles were seen passing from the inferior thyroid artery directIy to these gIands. A thorough search for superior parathyroid tissue was unrewarding. An obvious enlargement of the inferior poIe of the left Iobe of the thyroid was noted. (Fig. 2.) Because of this apparent soIitary thyroid adenoma a Ieft thyroid Iobectomy was performed including the structure identified as a Ieft parathyroid. PostoperativeIy the patient did weI1. Serum calcium feI1 to normal (Fig. I) and serum phosphorus began to rise. Microscopic examination of the surgica1 specimen showed the structure identified as Ieft parathyroid to be, instead, a thyroid adenoma. The enIargement of the inferior pole of the Ieft Iobe of the thyroid which appeared to be a thyroid adenoma at surgery was a Iarge parathyroid adenoma embedded in the thyroid gland. MicroscopicaIIy, it was composed of dense sheets of eosinophilic-staining ceIIs of the chief type. (Figs. 3A and B.)

the course of surgery for hyperparathyroidism the surgeon is frequentIy confronted with the probIem of identifying parathyroid tissue in a variety of anatomic locations. It is we11 known that adenomatous or hyperpIastic glands may be present in various areas of the neck as we11 as superior mediastinum. For the most part, these ectopic sites may find expIanation in the embryoIogic derivation of the parathyroid gIands from the third or fourth branchia1 cIefts. AIthough severa reports of parathyroid tissue within the substance of the thyroid gland are present in the Iiterature [~;,6], Cope [4] doubted the presence of parathyroid gIands in such a Iocation. The purpose of this communication is to report two cases which iIIustrate the intrinsic reIationship of parathyroid with thJrroid tissue. In the first case a parathyroid adenoma appeared to be such an integra1 part of the thyroid gIand that it was removed with the beIief that it was a thyroid adenoma. The second case, to our knowIedge, is the eIeventh case of primary chief ceI1 hyperpIasia to be reported. This case shows the diffIcuIties associated with subtota1 removal of hyperpIastic glands as we11 as the confusion resuIting from cervical extension of the thymus gIand.

D

AND

URING

Comment: This case is of interest in that the parathyroid adenoma presented on the caudaImost aspect of the Ieft hemithyroid gIand and when observed at surgery appeared to be a thyroid noduIe. On microsection it was obvious that this noduIe represented a parathyroid adenoma (Figs. 3A and B) which was adherent to the thyroid and partIy surrounded by thyroid tissue.

CASE REPORTS

CASE II. F. R., a thirty-eight year-old man, was admitted with symptoms suggestive of duodena1 uIcer and herniated intervertebra disc. The symptoms were of four months’ duration. Laboratory examination showed a serum caIcium of 15.5 mg. per cent and serum phosphorus of 3.1 mg. per cent. The twenty-four-hour urinary caIcium excretion was 462 mg. and the twentyfour-hour urinary phosphorus was 869 mg. Ab-

CASE I. C. P., a forty-one year-oId white man, presented with a one-year history of renaI Iithiasis, sciatic pain and peptic uIcer-Iike symptoms. The cIinica1 impression was probabIe primary hyperparathyroidism. Laboratory examination demonstrated a serum caIcium of 16.6 mg. per cent. (Fig. I.) Urinary calcium excretion was 683 mg. in Serum phosphorus was 2.2 twenty-four hours. mg. per cent. 757

American

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1960

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FIG. 1. Prompt decrease to norma of the serum calcium Ieve in the patient with a parathyroid adenoma. ProIonaed eIevation of the serum calcium foIIowing surgery in the patient with primary hyperplasia of the parathyroid gIands.

I by 0.5 cm., were removed. Microscopic examination of the parathyroid gIands showed irreguIar cords of chief ceIIs with smaI1 to round nucIei with a granuIar, sIightIy eosinophilic-staining cytopIasm. The ceI1 type was uniform. No ceIIs of the water-cIear type were seen. (Fig. 4.) What was thought to be right inferior parathyroid gland at surgery was shown microscopicaIIy to be thymus gland and, therefore, onIy two and one-half parathyroid gIands had been removed. FolIowing surgery the patient showed some reIief from the ulcer and intervertebra disc symptoms. However, Iaboratory data (Fig. I) showed the hyperparathyroid state to be onIy partiaIIy relieved. ExpIoration of the neck and anterior mediastinum was performed on June 27, 1958, using a cervica1 and sternal spIitting incision. The thymus gIand, a portion of which extended into the right part of the neck, and the right Iobe of the thyroid gIand were removed. The right inferior parathyroid gIand was identified in the surgical specimen. Thus, a tota of three and one-haIf grossIy enIarged parathyroid gIands were removed. Serum caIcium did not show a significant decline unti1 two months after the second surgica1 procedure. Today the patient is doing we11 and is asymptomatic with serum caIcium and phosphorus and urinary caIcium

dominaI roentgenogram suggested nephrocalcinosis. Rena1 biopsy showed renal calcinosis associated with secondary pyeIonephritis. The diagnosis of hyperparathyroidism was made and primary surgica1 expIoration of the neck was accomplished on May 21, 1958. At operation, four emarged parathyroid glands were thought to have been identilied. The left superior and inferior parathyroid and one-haIf of the right superior parathyroid, each measuring

FIG. 2. Gross surgica1 specimen of the patient with a parathyroid adenoma. The 1.5 cm. mass at the inferior pole of the thyroid is a parathyroid adenoma nearly embedded in the thyroid tissue.

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Hyperparathyroidism

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3A FIG. 3. Microsection of parathyroid may exist in a benign tumor.

adenoma.

and phosphorus within norma limits. phosphatase is no longer eIevated.

A, showing chief cells. B, showing

extreme

pleomorphism

which

finding, were treated at the Seattle Veterans Administration HospitaI during 1958 and 1939. Examination of the parathyroid glands in dogs and other experimenta animaIs shows wide variation in Iocation and size of the parathyroid gIands. The superior parathyroid gIands originating from the branchial clefts become attached to and may be embedded within the thyroid gIand, aIthough this rareIy happens in man [7]. Cope [G] stated that aIthough parathyroid tissue from the fourth branchia1 cIeft couId be embedded in the thyroid, he had never observed such a finding. He has found parathyroid tissue deep within the SUICUS of the thyroid. If the surgeon makes the diagnosis of primary hyperpIasia of the parathyroid glands after identifying a11 of these structures, then he must

The alkaline

Comment: In this case the failure to locate an obvious parathyroid adenoma at any of the usual sites led us to suspect the existence of diffuse hyperplasia of the four glands or the alternate possibility of a mediastinal location. Because of the apparent emargement of all four glands associated with a coffee brown coIor, it was elected to remove both superior and inferior glands on the Ieft as we11 as half of each gland on the right. Microscopic identification of the right inferior gIand as thymic tissue Ied to the belief that perhaps the right inferior gIand was adenomatous or hyperpIastic and was located in the superior mediastinum. The faiIure of the serum caIcium to fall to norma limits during the postoperative period confirmed our fears that the patient stiI1 harbored hyperfunctioning parathyroid tissue. Accordingly, when the superior mediastinotomy showed cervica1 extension of the thymus to the right inferior pole of the thyroid, it was cIear why thymic tissue had been obtained rather than the right inferior parathyroid gIand. In an effort to Iocate the fourth and remaining gIand the Iower poIe of the thyroid gIand was resected. Later examination demonstrated this tissue to contain the hyperplastic parathyroid in a subcapsular location partI,v surrounded by thyroid tissue. COMMENTS

FIG. 4. Microsection

Two patients with hyperparath.vroidism, each presenting a comparativeIy rare surgical

patient thyroid

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with primary glands.

of surgica1 specimen from the chief cell hyperplasia of the para-

ToIstedt, Cammock and Be11 determine the amount and probable vascuIarity of remaining tissue if hypoparathyroidism is to be prevented. Both Cope [4] and BIack [I] recommended subtota1 resection of parathyroid tissue; the Iatter author suggests leaving a vascuIarized segment of tissue two or three times the size of norma parathyroid tissue. Primary hyperpIasia of the parathyroid gIands is found in approximateIy IO per cent of patients with primary hyperparathyroidism [I]. The usua1 cases are characterized by hyperpIasia of the water-cIear or “wasserhehe” ceIIs rather than the chief cehs. Cope [3] has recentIy described a new entity of chief cell hyperpIasia occurring in ten patients. Case II appears to represent the eIeventh case of this type. In addition, Case II shows the faiIure of cure of this disease when onIy two and one-haIf hyperplastic glands were removed and, in turn, the successful treatment of primary hyperplasia of the parathyroids when three and one-haIf gIands were removed. In this case a11 parathyroid tissue removed appeared simiIar microscopicahy (Fig. 4) and was consistent with a diagnosis of chief ceI1 hyperpIasia of the parathyroids. In these two cases the success of surgery can be attributed to hemithyroidectomy, as the abnorma1 parathyroid tissue was found in the surgica1 specimen after it had been removed. It wouId be our opinion that any abnormaIity detectabIe in the thyroid grand at the time of expIoration of the neck for hyperparathyroidism shouId be treated with hemithyroidectomy. Case II demonstrates a very sIow faII in the serum caIcium IeveIs foIlowing surgery. (Fig. IB.) This was disturbing to the physicians foIIowing the case and is presented onIy as an unusual variation of the cIinica1 response of this disease to surgery for which we have no expIanation at present. The presence of thymic tissue in the neck in Case II is presented as an additiona finding which may cause confusion while trying to identify the parathyroids at surgery. Consider-

ing its embryonic origin, it is not surprising to find part of the thymus in the neck associated with the inferior parathyroid gland, which aIso arises from the third branchia1 cIeft. Realization that thymic tissue may be in the neck and carefu1 study of such tissue by frozen section may serve to differentiate this from parathyroid tissue. SUMMARY

A single case of primary chief cell hyperpIasia of the parathyroid gIands is presented and the technica probIem of differentiating parathyroid gIand from thymus gland is described. A singIe case of a parathyroid adenoma found within the thyroid gIand is presented and the reIationship of the parathyroid gIands to the thyroid gIand is discussed. Acknowledgment: We wish to thank Dr. Benjamin CastIeman, Professor of PathoIogy, Harvard University, Cambridge, Massachusetts, for kindIy reviewing the shdes in Case II. REFERENCES I. BLACK, B.

M. Tumors of the parathyroid glands and primary hyperparathyroidism. Am. J. Surg.,

95: 395, ‘958. 2. CASTLEMAN.B. Fascicle on tumor of the parathyroid glands. In: AtIas of Tumor PathdIogy. Washington, D. C., 1952. LJ. S. Armed Forces Institute of PathoIogy. 3. COPE, O., KEYNES, W. M., ROTH, S. I. and CASTLEMAN, B. Primary chief ceII hyperplasia of the parathyroid glands. Ann. Surg., 148: 375, 1958. 4. COPE, 0. Surgery of hyperparathyroidism: the occurrence of parathyroids in the anterior mediastinum and the division of the operation into two stages. Ann. Surg., I 14: 706, 1941. 5. HUNTER, D. and TURNBULL, H. M. Hyperparathyroidism: generahzed osteitis fibrosa: with observations upon the bones, the parathyroid tumors, and norma parathyroid gIands. &it. J. Surg., 19: 203, 1931. 6. LAHEY, F. H. and HAGGART, G. E. Hyperparathyroidectomy. Surg., Gynec. ti Obst., 60: 1033, 7. SC~~?I&ER, J. P. Morris’ Human Anatomy, 10th ed., p. 1499. P hiladeIphia, 1942. BIakiston Co.

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