Postoperative parathyroid high-frequency sonography: evaluation of persistent or recurrent hyperparathyroidism.

Sixty consecutive postoperative patients with recurrent or persistent hyperparathyroidism were scanned before reoperation using high-frequency (10 MHz) real-time sonography. The sonograms were interpreted prospectively, and the results correlated with subsequent surgical findings to determine the diagnostic accuracy of this technique in the localization of enlarged parathyroid glands. A total of 59 abnormal glands were found in 51 patients at operation: 45 in the neck and 14 in the mediastinum. Sonography identified 37 of the 45 cervical glands for a sensitivity of 82% in the neck. The mediastinum cannot be evaluated by sonography due to the bony thoracic cage, although if the mediastinal glands are included, the overall sensitivity was 63%. In the 14 patients with negative neck explorations but positive mediastinal explorations, sonography was negative in 12 patients, but false-positives were suspected in two patients, yielding a specificity of 86% in the neck. High-frequency sonography is a sensitive, rapid, and noninvasive technique for localizing enlarged cervical parathyroid glands in patients with recurrent or persistent hyperparathyroidism.

High-resolution parathyroid ultrasonography in familial benign hypercalcemia (familial hypocalciuric hypercalcemia).

Familial benign hypercalcemia, or familial hypocalciuric hypercalcemia (FHH), is frequently confused with primary hyperparathyroidism, but the consistent failure of subtotal parathyroidectomy to normalize serum calcium levels in FHH makes accurate distinction from familial hyperparathyroidism imperative. Because ultrasonography frequently demonstrates enlargement of the parathyroid glands in hyperparathyroidism, we examined 14 hypercalcemic adults (who had not undergone operation) from seven kindreds with FHH by using a high-resolution real-time scanner. We compared our results with those from 156 patients (who had undergone scanning preoperatively) with surgically confirmed hyperparathyroidism. Enlargement of the parathyroid glands was detected ultrasonographically in 137 of 156 (88%) of the total group of patients with hyperparathyroidism and in 17 of 24 patients (71%) with hyperparathyroidism who had hypercalcemia (serum calcium, 10.6 to 11.0 mg/dl) comparable to that of the FHH group (mean value, 10.7 mg/dl). In contrast, the single possible parathyroid lesion seen in the FHH group was substantially smaller (4 mm) than the smallest (7 mm, 75 mg) abnormal gland reliably detected by ultrasonography in the group with hyperparathyroidism and was conceivably normal in size. Patients with FHH have a dramatic absence of ultrasonographic parathyroid enlargement. High-resolution parathyroid ultrasonography may be of ancillary diagnostic benefit in patients with familial hypercalcemia.

The reasons for persistent hypercalcaemia after cervical exploration for presumed primary hyperparathyroidism.

Of 500 consecutive patients who underwent cervical exploration for presumed primary hyperparathyroidism, 461 (92.2 per cent) were cured, as judged by an immediate return of serum calcium levels to normal. Thirty-nine patients (7.8 per cent) had persistent hypercalcaemia after the initial operation. The clinical profiles, operative and pathologic findings, surgical procedures performed and subsequent management of these 39 patients were reviewed. At reevaluation, 4 patients were noted to have been cured of their hyperparathyroidism. Twenty-one patients had persistent hyperparathyroidism: in 6, all 4 parathyroid glands had not been identified at the initial operation and in 15, hypercalcaemia persisted after the identification of 4 glands. One patient had recurrent hyperparathyroidism after the removal of a 720 mg adenoma and the identification of 3 normal parathyroid glands. Nine patients had nonparathyroid causes for the hypercalcaemia: 2 had occult malignant neoplasms, 6 had benign familial hypocalciuric hypercalcaemia and 1 had immobilization hypercalcaemia. In 4 patients the reason for the persistent hypercalcaemia remained unclear. We suggest a schema that may be used as a guideline in the investigation and management of patients with persistent hypercalcaemia after primary neck exploration for presumed hyperparathyroidism.

Primary hyperparathyroidism associated with hypernephroma: a diagnostic challenge.

During the past 16 years, in which 1,600 patients were surgically treated for primary hyperparathyroidism, 10 of these patients also were operated on for hypernephroma; in another patient a hypernephroma was detected 7 2/3 years after treatment for hyperparathyroidism. Four additional patients have elevated serum calcium and immunoreactive parathyroid hormone values after nephrectomy for hypernephroma, and a provisional diagnosis of primary hyperparathyroidism has been made in these patients. Thus, the occurrence in the same patient of two disorders that may have similar biochemical abnormalities produced by similar pathophysiologic mechanisms provides a unique diagnostic challenge to the physician. The correct diagnosis of these occasionally associated disorders is facilitated by a high degree of alertness and the performance of adequate renal radiographic procedures. These should include excretory urography in patients with persistent hypercalcemia unless the procedure is contraindicated.

High-resolution parathyroid sonography.

A total of 165 consecutive patients with suspected primary hyperparthyroidism was scanned preoperatively using high-resolution real-time sonography. The sensitivity of the procedure was 69% and the specificity 94% in the localization of individually enlarged parathyroid glands. In the subgroup of 21 patients undergoing reoperation in the neck, the sensitivity and specificity were 80% and 92%, respectively. In patients with a single parathyroid adenoma, there was a close but not linear correlation between sonographic diagnostic accuracy and the size of the adenoma, which in turn was directly related to the serum calcium and immunoreactive parathyroid hormone levels. High-resolution sonography has become the procedure of choice in our institution for the preoperative localization of enlarged parathyroid glands in the neck.

Small-part ultrasonography in primary hyperparathyroidism: initial experience.

Small-part, real-time ultrasonography using a high-resolution real-time ultrasound scanner was evaluated in 100 consecutive patients undergoing cervical exploration for primary hyperparathyroidism. The radiologic accuracy was 76%. This accuracy was related directly to the weight of the resected gland(s). The surgical success rate with ultrasonography was 96%, whereas the rate without ultrasonography was 97%. Operating time was not appreciably decreased. The exact role of this new modality in the management of primary hyperparathyroidism is as yet unclear.

Development and validation of a new radioimmunoassay for parathyrin (PTH).

A radioimmunoassay for human parathyrin has been developed and characterized with whole-molecule (residues 1-84) human parathyrin and with the 1-34, 44-68, and 53-84 amino acid residue fragments of it. The antiserum used reacted with the whole molecule and with the 44-68 and 53-84 fragments, but not with the 1-34 fragment. Parathyrin concentrations in the serum of 118 normal subjects and of 112 patients with surgically proved primary hyperparathyroidism were determined with this assay. The mean results were 39 (SD 13) microL-Eq/mL for the normals and 111 (SD 77) microL-Eq/mL for the patients with primary hyperparathyroidism (p less than 0.0005). The upper 95% confidence limit of the normal range was 60 microL-Eq/mL. For 54 patients with primary hyperparathyroidism, the preoperative values for serum parathyrin, calcium, and phosphate--but not creatinine--were statistically different from the postoperative values (paired t-test, p less than 0.0005). Normal subjects showed significant (p less than 0.0005) differences in serum calcium concentrations but not in parathyrin concentrations, compared with concentrations found in cancer patients and patients who had thiazide-induced hypercalcemia. Phosphate concentration in serum, although not a specific indicator of disease, is a valuable clue to the diagnosis of primary hyperparathyroidism.

Asymptomatic primary hyperparathyroidism. 10-year prospective study.

Because factual basic knowledge is lacking regarding the natural history of primary hyperparathyroidism, it has been impossible to make a reasonable prognostication of the risks inherent to judicious observation as a justifiable alternative to neck exploration in patients with mild asymptomatic and uncomplicated hyperparathyroidism. Therefore, in January 1968 a prospective study was initiated at the Mayo Clinic in an effort to provide more information regarding the natural history of this disease. The cumulative 10-year findings of this study are presented. On the basis of the findings, it was not possible to define criteria that will predict which patients with primary asymptomatic hyperparathyroidism will ultimately require surgery.

Urinary cyclic 3',5'-adenosine monophosphate responses to exogenous and endogenous parathyroid hormone in familial benign hypercalcemia and primary hyperparathyroidism.

FBH is characterized by symptomless hypercalcemia, low urinary calcium excretion, normal iPTH values, generally normal parathyroid histology, and failure of subtotal parathyroidectomy is normalize serum calcium. We studies six patients with FBH from three kindreds, six patients with sporadic 1 omicron HPT, and six healthy volunteers. To characterize the renal response to PTH, 14 of the subjects had infusions of bovine PTE (300 U intravenously over 15 min) and, separately, stimulation of endogenous PTH release by infusion of disodium EDTA (50 mg/kg over 2 hr). PTE induced striking increases of UcAMP (nM/100 ml of GF) that were indistinguishable between controls and subjects having FBH. However, the rise of UcAMP in 1 omicron HPT was significantly reduced (p < 0.001) compared to controls or the FBH group. EDTA-induced hypocalcemia raised serum iPTH and UcAMP in all three groups; the increases of iPTH (two assays of differing specificity) were greatest in 1 omicron HPT and least in FBH. In contrast, increases of UcAMP were greatest in FBH and 1 omicron HPT and indistinguishable from one another. The increase of UcAMP considered as a function of the increase in PTH showed significantly greater UcAMP responses in FBH than in the other groups. These results are consistent with primary or secondary alterations of renal responsiveness to PTH in both FBH and 1 omicron HPT, which may in part explain the different renal tubular calcium handling in the two conditions.

The undescended "parathymus". An occasional cause of failed neck exploration for hyperparathyroidism.

Arrested descent of the inferior parathyroid gland ("parathymus") during embryologic development may leave the gland stranded high in the neck. Adenomas of such undescended glands are a rare cause of primary hyperparathyroidism, but they may not be uncommon among patients who have already had a failed cervical exploration. Unless the surgeon is aware of this entity, he will probably overlook it. If one is to find these tumors, it is necessary to extend the dissection upward above the superior pole of the thyroid gland, sometimes as far as the angle of the jaw. Adenomas of undescended "parathymus" glands were encountered in seven patients during a recent 20 month (May 1975 through December 1976) surgical experience encompassing 414 primary operations and 27 reoperations for hyperparathyroidism. These tumors were found at initial exploration in one patient and at reoperation in six patients. The individual case histories are presented to illustrate the difficulties posed by this anatomic variant.

Cancer of the parathyroid glands.

Hyperfunctioning parathyroid carcinoma is a relatively rare endocrine tumor, accounting for approximately 1% of all cases of primary hyperparathyroidism. The diagnosis is suspected when the tumor is large, parathyroid hormone (iPTH) levels are high, and a palpable tumor is present in the neck. Patients who have recurrence of hyperparathyroidism several months after surgical treatment should be suspected of having a recurrent or persistent parathyroid carcinoma. At operation, a large invasive tumor is usually found. The fibrous, inflammatory-like reaction is the most characteristic indication of malignancy. Even in tumors with minimal invasiveness, the possibility of a carcinoma should be considered if the tumor has mitotic activity and a monotonous instead of a pleomorphic cellular population. If the surgeon can recognize the possibility of parathyroid malignancy and adequately treat the patient during the initial operation, more gratifying results should be obtained.

Primary hyperparathyroidism with multiple parathyroid gland enlargement: review of 53 cases.

Of 53 patients who had hyperparathyroidism assocated with multiple parathyroid gland enlargement, 39 (74%) had primary hyperparathyroidism without clinical or laboratory evidence of associated endocrine gland dysfunction, 2 had documented familial primary hyperparathyroidism, and 12 had hyperparathyroidism as part of the multiple endocrine neoplasia syndrome. When last studied, 31 of the 39 patients with nonfamilial hyperparathyroidism had normal serum calcium levels, 3 had permanent hypoparathyroidism, 2 had recurrent hyperparathyroidism, and 3 were lost to follow-up. The two patients with familial hyperparathyroidism were treated by removal only of enlarged parathyroid glands, and in each, hyperparathyroidism recurred. Five patients with multiple endocrine neoplasia, type 1, were treated by removal only of enlarged parathyroid glands, and hyperparathyroidism recurred in four. Four patients with multiple endocrine neoplasia, type 1, were treated by removal of three or more parathyroid glands, and there were no instances of recurrent hyperparathyroidism. In one patient, permanent hypoparathyroidism developed. Three patients with multiple endocrine neoplasia syndrome, type 2, had total parathyroidectomies as a part of thyroidectomy for medullary thyroid carcinoma. In each patient, permanent hypoparathyroidism developed. When primary hyperparathyroidism occurs in the absence of a definite history of polyendocrine or familial disease, only the glands that are definitely enlarged should be removed, and normal-appearing glands should be tagged rather than risk the possibility of permanent hypoparathyroidism that may attend routine subtotal parathyroid gland excision.

Unusual problems in parathyroid surgery.

Although parathyroid surgery is difficult because of the smallness of the glands and the variability in their location and number, a surgeon who is well versed in the embryology, gross anatomy, pathology of the glands, and the fine points of gross identification of normal and abnormal tissue should be able to identify these glands in most instances. In a review of 122 cases during a two year period, pathologic change was found in 96 per cent, even though 11 per cent were secondary cervical explorations and the mediastinum was entered by a sternal split approach in only two cases. Although the abnormal glands were found in varying locations and ten were outside the usual areas of search, all were consistent with failure to descend or excessive descent and with a relationship to anatomic structures having similar embryologic origin. Sophisticated localizing procedures such as arteriography and selective venous sampling for parathormone are rarely necessary.

Hyperparathyroidism due to single gland enlargement: prospective postoperative study.

Subtotal parathyroidectomy in all patients with primary hyperparathyroidism has been proposed by several authors. Their data suggest that hyperparathyroidism may recur in up to 30% of patients treated by a conservative operation. This recurrence is attributed to chief-cell hyperplasia as the pathology in one third to one half of all patients. A conservative operation was performed on 198 hyperparathyroid patients with a single enlarged parathyroid gland between 1968 and 1970. Mild elevation of the serum calcium level was noted in two patients three months after operation. Normal serum calcium values were noted each time they were measured in the remaining patients. The present study does not support subtotal parathyroidectomy in all patients with hyperparathyroidism.