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Elderly Females, Two of Whom Had Each One Parathyroid Tumor, While the Third Had Two Distinct Tumors of Parathyroid Tissue

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Elderly Females, Two of Whom Had Each One Parathyroid Tumor, While the Third Had Two Distinct Tumors of Parathyroid Tissue FIBROCYSTIC DISEASE OF THE BONES ASSOCIATED WITH TUMOR OF A PARATHYROID GLAND * REPORT OF A CASE RAYmOND S. ROSEDALE, M.D. (From 1K Pathological Laboratory of the Buffalo City Hospal, and the University of Buffalo, Buffalo, N. Y.) Generalized fibrocystic disease of bone was first described as gen- eralized osteitis fibrosa cystica by von Recklinghausen' in a Fest- schrift to Virchow in I89I. The earliest references we have to tumor of the parathyroid glands are those of De Santi2 in I900 and Ben- jamins 3 published in 1902; bone disease was not mentioned. Erd- heim4 in 1903, Hulst I in 1904, and MacCailum6 in I905, also each reported a case without associated bone disease. Askanazy7 re- ported finding a parathyroid tumor in association with osteitis deformans in I904, and von Vereb6ly 8 reported a case of para- thyroid tumor with bone changes in 1907. Weichselbaum9 de- scribed a parathyroid tumor in I906 without associated bone changes. Erdheim 10 described three cases of osteomalacia with parathyroid enlargement in 1907. Thompson and Harris 11 described a similar case in I9o8. Seven cases of parathyroid tumor without mention of bone changes were collected and one of his own added by Da Costa 12 in I909. Bauer 13 in I9II reported a case of adenoma of the parathyroid in a 45 year old woman with a moderate degree of osteomalacia. In I9I3 Molineus14 described osteomalacia in three elderly females, two of whom had each one parathyroid tumor, while the third had two distinct tumors of parathyroid tissue. Har- bitz 15 in I9I5 noted the "relationship between enlargement of the parathyroid glands, rickets and other diseases affecting the bones." Tumors of the parathyroid gland have been reported as coincident findings in several diseases. Bergstrand 16 in I92I reported tumor of the glands in nephritis, tetany, epilepsy, eclampsia and osteomalacia. * This case was reported in abstract before the Buffalo Pathological Society on February I9, 1932. Received for publication April 5, 1932. 745 746 ROSDALE In So cases of nephritis he found one or more enlarged parathyroid glands. Other authors, induding MacCallum, have reported the coincidence of parathyroid enlargement with nephritis. Hoffheinz 7 in1925 collected 45 cases of parathyroid tumors; in I7 of these there was an assocated generalized osteitis fibrosa cystica, 8 cases with osteomalacia, and 27 with various other bone diseases. The concept of the relation between tumors of the parathyroid gland and generalized fibrocystic disease has been n ging within the last few years Erdheim in I9I1 put forth the hypothesis that the enlargement of the gland was a compensatory effort to assist in replacing lost calcium to the bones. This theory held sway for many years. In 1923 Dawson and Struthers 9 stated that the glandular hyper- plasia was an effort to prevent the ecessive excretion of lime salts and also control and prevent the development of an excess amount of guanidine, which was considered toxic. The first intimaton that hyperparathyroid function might be a cause of generalized fibro- cystic disease of bones through withdrawal of calcium was in I915, when Schagenhaufer 2 advised parathyroidectomy in two cases of generalized fibrocystic disee associated with a parathyroid tumor: Maresch favored the procedure but Bauer rejected the proposal. In 1925 MandlP1 transplanted parathyroid tissue into a patient with generalized fibrocystic disese and the patient's condition became worse. He then removed the transplanted parathyroid tissue and a parathyroid tumor, and there was improvement of the fibrocystic diseae. Gold 2 performed a parathyroidectomy in 1927, with Simi- lar improvement of the patient's bone disease. Barr and his coworkers 2h a parallel case in1929. Since this time there have been reported 23 cases of generalized fibrocystic disease of bones asociated with parathyroid tumor, in each of which the tumor was removed, with subsequent improvement of the bone condition. Collip in I925 24 described blood calcium elevation after parathor- mone was injected in dogs, and also an increase in blood phosphorus in parathyroidectomized rabbits. Greenwald and Gross in I925,25 and again in 1926,E* showed that daily parathormone injection of ioo units in animals elevated the serum calcum and caused excretion of urine calciumandphosphorus, the former to as much as six times normal. Hunter and Aub 7 also FIBROCYSTIC DISEASE OF BONES 747 found the same hypercalcemia with increased calcum excretion in man in 1926. Albright, Bauer, Ropes and Aub28 have demonstrated a negative calcium bance in animals and man receiving parathormone injec- tions. Finally, the disease picture, both gross and microscopic, of generalized fibrocystic disease of bones has been produced repeatedly by Jaffe, Bodansky and Blair,2' and also by Byrom working with Hunter and Turnbull.Y More recently Johnson and Wilder t re- ported that repeated injections of parathyroid extract produced in puppies and young rats uniform bone lesions characteristic of gen- eralized fibrocystic disease of the bones, and conduded that the dis- ease observed in man was due to an oversupply of parathyroid hormone with consequent loss of bone calcium. Thus the interrelationship of generalized fibrocystic disease of bone and hyperparathyroidism has gradually been established. We have found 3I reported cases of generalized fibrocystic disease of bones associated with enlargement of a parathyroid gland. Some of these were reported as hyperplasia, others as adenomas, and one as a malignant adenoma. All of these present definite clinical and laboratory data to establish further the causal relationship of these two conditions. One additional case is presented herewith. CASE REPORT Clinical History: D. S., age So years, white, female, married housewife, entered the Buffalo City Hospital April 9, 1931, complaining of muscle aches, fatigability, pain about the knee joints and lower part of the right tibia, and loss of use of the lower limbs because of weakness. As a young girl she had had a goitrous sweUling of the neck for which she was treated with iodine. Following this the swelling disappeared. At the age of 27 years she had a periapical tooth infection that left her with a condition that was termed chronic osteomyelitis; this resisted all ordinary attention, a sinus persisting until a radical surgical procedure caused it to heal after two years. Constipation had been obstinate for thirteen years. Seven years ago she had what was interpreted as sciatica, the pain being in both gluteal regions. For the past three years a sense of soreness was present in both heels; this was aggra- vated by weight-bearing. She had lost 7I lbs. in weight in this three year period, the former maxmum weight being i6o lbs. About three years prior to hospital admission she had had an attack of sharp, right upper quadrant pain with sudden onset and cessation, which was interpreted at the time as renal colic. For the last two years needle-like pain was experienced around the knees; for the past five months a pain was sensed over the lower third of the right tlbia. This, aggravated by motion, has been present constantly. She had been conscious of a firm swelling in the right thyroid region, and more recently a sense of tightness. There had been no dysphagia. Nervousness, force- 748 ROgv-nALE ful pulsation of the neck vessls, and a fine tremor had been present for three years. Aprecordial pain had been interpreted at one time aspericarditis. Night and day fiequency of urination was constant. The patient was an elderly, emaciated female with drawn and haggard fea- tun The bonyprominences andhollows were mared The skull was seemingly larg than normal in contrast with the face bones. There was a slight exoph- thalmos and a suggestion of nystagmus; the sclerae had an icteric tinge. The neck vessels pulsated forcibly; a tender firm nodule was palpble in the lower lateal portion of the right thyroid lobe. Most of the teeth wre missing; the few remaining onms we carious The heart was slightly enlarged to percusson, the left border measuri 8.5 cm- to left of the midine in the fifth intercostal space, and the right 3.5 to the right of the midline in the fourth interspace; there were two cardiac murmurs, a mitral systolic blow and a rough aortic systolic. Extra systoles were frequent The systolic blood pressure Was 122, and the diastolic 68. No arteriosclerosis was detected. The mus of the extrei- ties were atrophic, their tone poor. A slightly tender area was found over the lower third of the right tibia. The lc eal regions were tender. Pulse and respirations were normaL The temperature occsonally rose to 99.8 and io00 F. AU other points of the anainnesis were negative. Laboratory Studies: Red blood cel 2450,000; eMOglobin 58 per cent (Sahli); color index 1.2; white blood cells Io,Ioo; differtial normaL A series of blood calcium deteminations yielded I6.5, 13.82, I4.52 mg. pe Ioo cc. The blood phosphorus was 2.3 mg. per I00 cc. of blod. Urie: specific gravity anged con- stantly between Ioo6 and I013; albumin was I Plus to 4 Plus; rare granular cast. Bence-Jones protein action was positive on one occasion and negative on another. Basal metabolic rate was within normal limits. IThe X-ray revealed cystic areas in the ribs, clavide, lae, humii, tibiae and mandible, vacuolization of the skull and a generalized loss of density of all the bones. Biopsy m atl from the right tibia was obtained April i8, and was diag- nosed as fibrocystic disease of bone. On May I5, 193I, a tumor mass was roved from behind the right thyroid lobe. Local anesthesia was used. Following this the patient became stuporous with nervousness, apprension, cdonic twitchings of hand and face muscles, and could be aroused only by parathyroid and aldum therapy.
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