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Concurrent Plummer's disease and parathyroid adenoma. Diagnostic and therapeutic approaches to a difficult clinical problem.

When mild asymptomatic hypercalcemia occurs in a patient with hyperthyroidism, it may or may not be due to concurrent hyperparathyroidism and at times only the control of the hyperthyroidism will resolve the problem. Moreover, the presence of hyperfunctioning thyroid nodules will interfere with Tl-201/Tc-99m pertechnetate parathyroid scintigraphy. Initial treatment of hyperthyroidism with I-131 in this situation controls hyperthyroidism and permits successful localization of parathyroid adenomas, which may then be excised--a result that was achieved in three cases.

Adenoma↗

The changing face of parathyroid surgery.

This paper describes some of the earlier experiences of parathyroid disease in Birmingham. It goes on to describe the experience of the disease in patients with and without renal failure treated by one surgeon over the past decade. It should be read in conjunction with a previous publication in the Annals (3). A careful neck exploration by a surgeon experienced in parathyroidectomy gives a high (92.3%) cure of all comers with primary hyperparathyroidism. The majority of failures are cases with familial disease. The surgical treatment of secondary hyperparathroidism in renal failure is more controversial. The author's preference for total parathyroidectomy and autotransplantation is explained.

Aged↗

Double adenomas revisited: nonuniform distribution favors enlarged superior parathyroids (fourth pouch disease).

BACKGROUND: A double adenoma (DA) is a recognized clinical entity of primary hyperparathyroidism (HPT) and is presumed to have uniform location distribution. We reviewed our experience with 2-gland parathyroid disease to identify anatomic patterns and implications for surgical management. METHODS: Clinical characteristics were reviewed for 828 consecutive patients with HPT at 2 endocrine referral centers that practice bilateral neck exploration with intraoperative parathyroid hormone (IOPTH) measurement. RESULTS: Fifteen percent (127 of 828) of HPT patients demonstrated 2 enlarged glands; 13% (107 of 828), 3- or 4-gland hyperplasia; and 71% (592 of 828), single adenomas. DAs in superior parathyroids affected 57 of 127 (45%) patients, an observed frequency 3-fold higher than expected (P<.001, chi-square test). DAs were larger than normal glands (240+/-575 mg vs 28+/-23 mg, P<.001), and superior parathyroid adenomas were larger than adenomas at other sites (421+/-983 mg vs 202+/-353 mg, P=.002). Technetium 99 metastable (Tc99m)-sestamibi imaging and IOPTH identified DAs correctly in only 5 of 84 (6%) and 19 of 75 (25%) of patients tested, respectively. CONCLUSIONS: DAs have nonuniform anatomic distribution with predilection for abnormal growth in bilateral superior parathyroids-embryologic remnants of the fourth branchial pouch. Since additional abnormal glands were detected by observation with technetium 99 metastable (Tc99m)-sestamibi imaging and IOPTH rarely aiding detection, unilateral neck exploration may predispose to persistent or recurrent HPT.

Adenoma↗

Basal and pentagastrin-stimulated levels of calcitonin in thyroid and peripheral veins during normocalcemia and chronic hypercalcemia in humans.

The calcitonin secretion from the thyroid C-cells was studied with a peroperative method. The calcitonin concentrations in thyroid venous effluent and peripheral veins were determined in patients who underwent operations because of thyroid and parathyroid disease. In normocalcemia the thyroid vein level of calcitonin was significantly higher than that in peripheral vein. In chronic hypercalcemia no gradient over the thyroid was demonstrable. After injection of pentagastrin into a thyroid artery a very pronounced, but transient, increase in calcitonin concentration was registered. No difference in peak value between normo- and hypercalcemia was demonstrable. The peripheral vein level was unchanged. The peroperative method is very sensitive. A marked peak in thyroid vein corresponds to unchanged values in peripheral vein. The method invites further studies with other secretagogues and receptor-blocking substances.

Adolescent↗

Inverse correlation between serum magnesium and parathyroid hormone in peritoneal dialysis patients: a contributing factor to adynamic bone disease?

BACKGROUND: Secondary hyperparathyroidism (SHPTH) is present in many patients with end-stage renal disease (ESRD) and has been linked to uremic bone disease. Parathyroid hormone (PTH) levels are affected by calcium, vitamin D, and phosphorus. Recent data suggests that serum magnesium may also modulate PTH levels. OBJECTIVE: The aim of this retrospective study was to investigate the impact of different calcium (Ca) and magnesium (Mg) concentrations of dialysis solutions on serum Mg and serum PTH levels in peritoneal dialysis (PD) patients. PATIENTS AND METHODS: Two groups of PD patients-group A (n = 17) on "standard" Ca and Mg dialysis solution (SCa-MgD) (Ca: 1.62 mmol/l, Mg: 0.75 mmol/l and Lactate 35 mmol/l), and group B (n = 29) on "low" Ca and Mg dialysis solution (LCa-MgD) (Ca: 1.25 mmol/l, Mg: 0.25 mmol/l and Lactate 40 mmol/l), on PD for more than 6 months, were studied. Calcium carbonate (CaCO3) was used as the phosphate (P) binder in 87% (40/46) of the patients. Biochemical parameters were evaluated every 1-2 months over 6 months and the mean values were computed. RESULTS: No significant differences were found between the two groups in all parameters except for serum Mg and PTH. Serum Mg was higher in SCa-MgD group compared to those in the LCa-MgD group (1.05 +/- 0.19 vs 0.90 +/- 0.23 mmol/l, respectively) and serum PTH was higher in LCa-MgD group compared to those in SCa-MgD group (72.3 +/- 64.2 vs 31.1 +/- 39.0 pmol/l, respectively) even though serum Ca was not different. There was a statistically significant inverse correlation between serum Mg and PTH levels (r = -0.357, p < 0.05). CONCLUSION: Serum Mg is lower and serum PTH higher in patients dialyzed with lower Mg concentration dialysis solution compared to those with higher Mg concentration dialysis solution. Our study confirms previous reports that serum Mg may have a suppressive role on PTH synthesis and/or secretion, and thus may play a role in pathogenesis of adynamic bone disease that often develops in patients on chronic PD with high calcium and high magnesium concentrations.

Adult↗

Parathyroid imaging with Tc-99m sestamibi planar and SPECT scintigraphy.

Technetium-99m sestamibi planar and single-photon-emission computed tomographic scintigraphy is useful in the diagnosis of parathyroid gland disease. To understand the various patterns of parathyroid disease, it is important to understand parathyroid embryology and anatomy. The spectrum of parathyroid disease demonstrated with Tc-99m sestamibi scintigraphy includes eutopic disease, ectopic disease, solitary adenoma, double or multiple adenomas, cystic adenoma, lipoadenoma, multiple endocrine neoplasia, hyperfunctioning parathyroid transplant, entities with atypical washout, and nonparathyroid entities that take up Tc-99m sestamibi. The diagnosis of parathyroid tumors with Tc-99m sestamibi scintigraphy is based on the difference in clearance rates between the thyroid and diseased parathyroid glands, and any condition that interferes with radiotracer clearance will limit the effectiveness of the study. The technique is most clearly indicated for the preoperative evaluation of recurrent or persistent hyperparathyroidism, but it is increasingly being used before the initial surgical exploration as well. Subtraction Tc-99m sestamibi and iodine-123 scintigraphy may be helpful in difficult cases. Parathyroid hyperplasia, multisite parathyroid disease, and concomitant thyroid and parathyroid disease remain potential hurdles for this scintigraphic technique, and optimal handling of these problems still relies heavily on the skill and experience of the endocrine surgeon.

Adenoma↗

Multiple endocrine neoplasia type 2B: eighteen-year follow-up of a four-generation family.

Seven members with multiple endocrine neoplasia type 2B from a 15-member family have been followed for 18 years. All affected had the neuroma phenotype in a distribution compatible with autosomal dominant inheritance. The phenotype features have allowed 100% initial and continuing prediction of affected versus nonaffected status in as early as 1.5 years. Among the affected: immunoreactive plasma calcitonin (iCT) concentration was high in 100%; thyroid palpation was false-negative in 71%; and thyroid scintiscan was false-negative in 83%. All had total thyroidectomy, plus lymphadenectomy in three, for bilateral medullary thyroid carcinoma (MTC) or C-cell hyperplasia (in the youngest). None has died directly from MTC. The index case died at age 68 and his son at age 32 years from complications of the syndrome. All but the youngest have continuing high iCT concentrations. No patient has had parathyroid disease. During preoperative calcium infusion, immunoreactive serum parathyroid hormone concentration declined by 35% to 84% of basal. At operation, macroscopically and microscopically normal parathyroid glands were found in all. No patient has had chemical suggestion of pheochromocytomas: at postmortem the index case had no adrenal medullary disease; his son had bilateral nodular adrenal hyperplasia; his daughter has had adrenal medullary hyperplasia and a renin-secreting juxtaglomerular tumor. Initially nonaffected members remain so.

Adolescent↗

Distinguishing features of primary hyperparathyroidism in patients with breast cancer.

Thirty-five women with breast cancer and primary hyperparathyroidism (1 degree HPT) were admitted to Memorial Hospital during a 25-year period. The incidence of primary hyperparathyroidism in the breast cancer patients was similar to the incidence in the total patient population at Memorial Sloan-Kettering Cancer Center (0.15% and 0.14%, respectively). The patients with 1 degree HPT disease had clinical findings which distinguished them from those patients with cancer-related hypercalcemia. Eighty percent of the breast cancer patients with primary hyperparathyroidism had earlier stage disease (Stage 0, Stage 1, Stage 2); whereas 97% of the patients with breast cancer and hypercalcemia (not due to 1 degree HPT) had advanced disease. There appeared to be a trend towards improved survival in the breast cancer patients with primary hyperparathyroidism when compared to patients of similar stage of disease who did not have parathyroid disease.

Adult↗

Radionuclide imaging of parathyroid tumors: historical perspectives and newer techniques.

The increasing use of automated blood chemistry screens for serum calcium levels along with improved methods in measuring parathyroid hormone (PTH) levels have made the diagnosis of parathyroid disease a common clinical problem. Parathyroid adenomas account for the majority of primary hyperparathyroidism with diffuse hyperplasia and parathyroid carcinoma occurring less frequently. Early scintigraphic techniques to identify enlarged parathyroids used selenomethionine-75 which was considered to be incorporated into PTH. In general, the sensitivity of scanning the neck using this tracer was related to the size of the enlarged parathyroid, but in large series, the overall sensitivity was less than 50%. Recent work by Ferlin et al, using a Technetium-99m/Thallium-201 subtraction scintigraphic technique has yielded a sensitivity of 92% in identifying pathologically enlarged parathyroid glands. Winzelberg et al modified this technique to allow imaging the mediastinum plus simplifying the subtraction method. In a prospective study with high-resolution sonography, similar sensitivities and specificities were found with sonography and scintigraphy. Tl-201/Tc-99m pertechnetate subtraction scintigraphy appears to be an accurate technique in identifying pathologic parathyroid enlargement. Its ultimate role in the evaluation of patients with suspected hyperparathyroidism still needs to be determined.

Adenoma↗

Flow cytometric DNA analysis of benign hyperfunctioning parathyroid glands: significant difference in the S phase fraction and proliferative index between adenomas and hyperplasias.

AIMS: Flow cytometric DNA analysis was performed to measure the DNA content of benign parathyroid tumours in patients with primary hyperparathyroidism. METHODS: DNA analysis of paraffin-embedded parathyroid samples was performed on 51 parathyroid glands from 29 patients after parathyroidectomy. Histopathology showed parathyroid adenoma in 25 cases and hyperplasia in four patients. DNA ploidy status, DNA index (DI), percentage of cells in S phase and proliferative index (PI) were determined. RESULTS: Normal cells from normal glands were all diploid. DNA cytometry showed 12 aneuploid and 13 diploid adenomas. There were 12 diploid and four aneuploid hyperplastic glands. Incidence of aneuploid DNA histograms did not show a statistically significant difference between adenomas and hyperplasias (P=0.216). Mean S phase fraction was 3.45% in adenomas and 1.53% in hyperplasias (P= 0.015). Mean PI was 6.48% in adenomas and 2.78% in hyperplastic parathyroid glands. This difference was statistically significant (P=0.006). Diploid cases had a mean PI of 4.78% and aneuploid glands a mean PI of 7.7% (P=0.08). Aneuploid DNA content did not reveal statistically significant correlation with age, gender, pre-operative Ca, alkaline phosphatase, i-PTH levels, and tumour size. The mean S phase fraction and PI were 2.25% and 4.78% in diploid glands, and 4.5% and 7.7% in aneuploid cases. CONCLUSION: Aneuploid DNA content may be present in benign parathyroid diseases, but not in normal parathyroid glands. Aneuploid DNA histograms and higher PI occur more often in adenomas compared with hyperplasias, but the nuclear DNA analysis is unable to make a distinction between adenomas and hyperplasias.

Adenoma↗