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Histopathological diagnosis of parathyroid diseases.

Hyperparathyroidism is the predominant disease of the parathyroid gland. This disease is nowadays quite common and is often diagnosed at an earlier stage, mainly by means of serum calcium determinations on wide indications. This means that when detected, the glandular abnormalities may be less advanced, which could hamper differentiation of adenoma from chief cell hyperplasia, and of normal glands from slightly hyperplastic ones. Normal glands and pathological glands both show wide variations in size, cellular composition and arrangement, as described in this article. The usefulness of applying fat staining to distinguish between normal and abnormal glands is also reported. It is important to bear in mind that the parathyroid diagnosis is in fact an indirect diagnosis based on the assessment of an associated gland or glands.

Humans↗

Use of a rapid intraoperative parathyroid hormone assay in the surgical management of parathyroid disease.

OBJECTIVE: To evaluate the utility of a rapid intraoperative parathyroid hormone (PTH) immunoradiometric assay in the surgical management of parathyroid disease, particularly with reference to limiting extent of cervical exploration. DESIGN: Nonrandomized prospective study. SETTING: Academic tertiary care center. PATIENTS: Forty-three consecutive patients undergoing parathyroid exploration for adenoma or hyperplasia had rapid PTH assays performed from blood drawn at induction and 7 minutes after resection of all hyperfunctioning parathyroid tissue. OUTCOME MEASURES: Excision of all hyperfunctioning parathyroid tissue as assessed by bilateral neck exploration, postoperative normalization of serum calcium and PTH levels, and resolution of clinical symptoms. RESULTS: The intraoperative rapid PTH assay accurately reflected whether all hyperfunctioning parathyroid tissue was excised in every patient. In 41 patients, all hyperfunctioning parathyroid tissue was resected at the time of surgery and confirmed by a corresponding decrease in the intraoperative postexcision rapid PTH determination as well as by subsequent normalization of postoperative serum calcium and PTH levels and resolution of clinical symptoms. In 2 patients, the postexcision rapid PTH assay determination was not consistent with removal of all hyperfunctioning parathyroid disease and both patients demonstrated persistent hyperparathyroidism postoperatively. CONCLUSIONS: The intraoperative rapid PTH assay may be of significant benefit in permitting directed unilateral parathyroid explorations for adenoma when combined with preoperative localization with a technetium-99m sestamibi scan. Additionally, the rapid PTH assay has proved to be of benefit in confirming excision of all hyperfunctioning parathyroid tissue in patients with multiple gland hyperplasia, particularly those who may harbor ectopic parathyroid tissue.

Adenoma↗

Preoperative parathyroid localization: correlating false-negative technetium 99m sestamibi scans with parathyroid disease.

OBJECTIVE/HYPOTHESIS: The recent trend toward minimally invasive directed parathyroid surgery has increased the surgeon's reliance on preoperative parathyroid localization. Technetium Tc 99m sestamibi scanning is generally viewed as the gold standard for preoperative localization, with reported sensitivities of 75% to 100% and specificities of 75% to 90%. However, in each reported series there exists a group of patients in whom preoperative localization is either equivocal or negative. STUDY DESIGN: We focused on a subset of patients from our parathyroid database with false-negative sestamibi (MIBI) scans, in an attempt to elucidate features that could affect these studies. We identified 20 patients with negative preoperative scans and confirmed parathyroid disease. We compared them with 22 consecutive patients with positive scans, correlating the following variables: patient age, gender, concomitant thyroid disease (Hashimoto's thyroiditis, papillary thyroid carcinoma, thyroid adenoma), preoperative parathyroid hormone values, location and number of enlarged parathyroid glands, parathyroid weight, and the relative proportion of chief cells, clear cells, oxyphil cells, and adipose tissue. METHODS: Retrospective chart review of clinicopathological and radiological findings. RESULTS: We found that patients with false-negative scans were more likely to have an enlarged parathyroid containing a high proportion of clear cells (P =.01). A trend was seen (P =.1) correlating increased parathyroid fat content and false-negative scans. Conversely, positive preoperative scans were more likely to be associated with a higher percentage of oxyphil cells (P =.02). Univariate analysis for other variables, as well as logistic regression analysis, did not achieve statistical significance. CONCLUSIONS: To date, the present study is the largest clinicopathological review of patients with false-negative sestamibi scans. Technetium Tc 99m uptake correlates with parathyroid oxyphil cell content, and false-negative scans can occur with parathyroid glands containing predominantly clear cells.

False Negative Reactions↗

Neurologic complications of thyroid and parathyroid disease.

Common thyroid and parathyroid disorders present with reversible neurologic signs and symptoms affecting the central and peripheral nervous system, musculature, and mental function. Patients with thyrotoxicosis may have myopathy, spasticity, seizures, and multiple psychiatric symptoms. A deficiency of thyroid hormone also causes muscle weakness and may be accompanied by reversible muscle hypertrophy or movement disorders. The chronic hypercalcemia that develops secondary to hyperparathyroidism produces many psychiatric and cognitive symptoms, as well as a reversible myopathy. Calcium deficiency leads to neuromuscular irritability, paresthesias, and tetany. Psychiatric disorders are also common in this disorder.

Diagnosis, Differential↗

Unexpected parathyroid disease discovered at thyroidectomy in irradiated patients.

Eight of 23 patients undergoing total thyroidectomy for radiation-associated nodular thyroid disease were found to have unsuspected parathyroid hyperplasia or adenoma at operation. The total serum calcium level was normal preoperatively in each patient. Serum ionized calcium and parathyroid hormone levels were measured in five patients preoperatively and were normal in each case. These pathologic findings in normocalcemic patients may represent a preclinical form of hyperparathyroidism, which would be further evidence linking radiation to the pathogenesis of hyperparathyroidism. The parathyroid glands should be evaluated both pre-operatively and at operation in all patients who have a history of radiation and require thyroidectomy.

Adenoma↗

Chief cell intracytoplasmic fat used to evaluate parathyroid disease by frozen section.

The chief cells of parathyroid adenomas were found to contain less intracytoplasmic fat than normal parathyroid glands and/or the adjacent rims of nonadenomatous parathyroid tissue. The amount of sudanophilic material in the chief cells was relatively uniform for each individual adenoma, but varied between patients. In half of the patients with parathyroid adenomas, Sudan-positive granules were generally absent from the adenomatous cells, whereas in the other half the granules were easily identifiable. The chief cells of secondary hyperplasia showed a less uniform pattern in each gland. In some areas, the stain for intracellular fat was negative, while adjacent cells contained prominent Sudan-positive granules. These findings suggest that staining frozen sections for intracellular fat is a useful but limited aid in the differentiation of parathyroid adenomas from normal parathyroid gland tissue.

Adenoma↗

Fat staining in parathyroid disease--diagnostic value and impact on surgical strategy: clinicopathologic analysis of 191 cases.

The study comprised 191 cases of surgically treated hyperparathyroidism, with all principal types of parathyroid disease represented. At least two complete glands stained with a modified isopropanol oil red O method for fat, in addition to sections stained with hematoxylin-eosin, were available in each case. On the basis of the morphologic evaluation and the clinical follow-up data, it is concluded that access to two complete glands and the use of fat staining allow highly reliable intraoperative distinction between adenoma and hyperplasia. Of 105 patients followed up for at least one year (mean, 20 months) in whom adenomas were diagnosed, a single possible error was identified. In each of 68 cases classified as hyperplasia on the basis of two abnormal glands, every additional complete gland available (total, 182 glands) was at least partially abnormal, with distinct signs of hyperactivity, irrespective of size. The rate of equivocal findings for cases in which two glands were available (probably adenoma but hyperplasia not excluded) was 8 per cent in 165 cases of primary hyperparathyroidism. These results justify limitation of surgery to one side of the neck in patients in whom adenoma is diagnosed on the basis of a complete, functionally normal (inactive) gland in addition to the presumed adenoma. Thus, the methods described provide a basis for optimal utilization of imaging techniques that allow preoperative localization of parathyroid adenomas.

Adenoma↗

Mitotic activity in benign parathyroid disease.

Tissue sections from 17 cases of parathyroid adenoma and ten cases of parathyroid hyperplasia were examined for mitotic activity. Mitoses were identified in 12 of the 17 cases of parathyroid adenoma and in eight of the ten cases of parathyroid hyperplasia. Clinical follow-up of all patients, even the four patients in whom numerous mitoses were present, showed no evidence of recurrent or aggressive disease. Mitotic activity alone is an unreliable indicator of aggressive potential in parathyroid disease.

Adenoma↗