The parathyroid glands: clinicopathologic correlation of parathyroid disease as found in 200 unselected autopsies.
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Adolescent↗
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[Hyperparathyroidism and intrathyroid parathyroid gland. 43 cases].
The rate of occurrence of intrathyroidal parathyroid glands in patients treated surgically for hyperparathyroidism (HPT) varies across studies. Among 1200 consecutive patients who underwent surgery for HPT at the Lille Hospital, France, between December 1965 and July 1992, 43 (3.6%) had 47 histologically-proven intrathyroidal parathyroid glands, including 44 lower and three upper parathyroid glands. Fifteen patients had a thyroid gland abnormality. Of the 14 patients who had a preoperative ultrasound study, eight exhibited an abnormal image. Thirty-four of the 47 intrathyroidal parathyroid glands were visible at the surface of the thyroid gland, five were felt on palpation, and eight were discovered upon examination of a lobectomy specimen. A normal or abnormal parathyroid gland can be completely concealed within the thyroid gland, even in the absence of concomitant thyroid gland disease. In most cases, the ectopia affects one or both lower parathyroid glands, although in some instances the two glands on the same side are intrathyroidal. There is no fail-proof means for detecting intrathyroidal parathyroid glands preoperatively. An apparently missing fourth parathyroid gland or a fifth gland should be looked for in the thyroid gland when the cause of HPT is not found during a first cervicotomy procedure. Pre- or intra-operative ultrasonography may be the most informative imaging method for detecting intrathyroidal parathyroid glands and should be performed routinely when a repeat procedure for persistent HPT is being considered.
Adolescent↗
The localization of abnormal mediastinal parathyroid glands.
The venous drainage of parathyroid glands ectopically located in the mediastinum is generally caraniad into the inferior thyroid veins. Parathyroid glands in the neck can cause elevated concentrations of parathyroid hormone in mediastinal veins because of thyroidalthymic anastomoses. Therefore venous sampling alone cannot distinguish cervical from mediastinal adenomas. Arteriography can localize mediastinal parathyroids and should be perfomred before any repeat exploration.
Adenoma↗
Effects of glucocorticoid on the ultrastructure of the mouse parathyroid gland.
Ultrastructural changes in the parathyroid glands of dexamethasone-treated mice were examined. Many chief cells of the treated mice contained a decreased number of prosecretory granules, secretory granules and storage granules, and an increased number of lipid droplets, compared with the control mice. In addition, myelin-like structures associated with cisternae of the granular endoplasmic reticulum were observed in the parathyroid glands of the treated mice. These findings suggest that cellular activity of the parathyroid gland may be suppressed by dexamethasone.
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Radionuclide imaging of the parathyroid glands: patterns, pearls, and pitfalls.
Optimal parathyroid scintigraphy requires an understanding of (a) the embryologic, anatomic, and physiologic features of the parathyroid glands and (b) the properties of the two common imaging agents, technetium-99m sestamibi and Tc-99m tetrofosmin. Normal parathyroid glands are too small to be visualized, but parathyroid disease often produces visibly enlarged glands. Enlarged parathyroid glands may be found near the thyroid gland or outside their expected locations. Characteristic abnormal scintigraphic patterns may be described as focal or multifocal, usual or ectopic in location, and associated with a normal or abnormal thyroid gland. Patients who are referred for parathyroid imaging should have an abnormal biochemical profile. The first step in evaluating images of a patient suspected to have parathyroid disease is correlating the normal or abnormal scintigraphic patterns with the clinical and surgical history. By integrating the interpretative and technical pearls and pitfalls of parathyroid scintigraphy, the radiologist can be more confident in establishing a correct diagnosis and can precisely guide the surgeon to a single parathyroid adenoma, multiple parathyroid adenomas, or multigland hyperplasia.
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Altered adenylate cyclase kinetics in hyperfunctioning human parathyroid glands.
Current evidence suggests that parathyroid gland adenylate cyclase is involved in the control of parathyroid hormone (PTH) secretion. Thus, the altered control of PTH release in hyperparathyroidism may relate to altered adenylate cyclase activation. Therefore, we examined adenylate cyclase kinetics in membrane preparations from hyperfunctioning human parathyroid glands and normal human and bovine parathyroid tissues. There were no differences in the affinity for ATP between enzymes of normal and pathological tissue. However, the enzyme in 10 hyperfunctioning glands showed increased affinity for Mg++. The activation constant for Mg++ (KaMg) of adenylate cyclase in normal human glands was 10.6 +/- 2 mM, a value not different from that of normal bovine parathyroid tissue (9.5 +/- 1 mM). In contrast, the adenylate cyclase in membrane preparations from three of four hyperplastic and six of seven adenomatous human glands showed a markedly reduced KaMg, ranging from 0.85-1.64 mM and from 1.58-6.46 mM, respectively. In one adenoma and one hyperplastic gland, the Ka of the enzyme for Mg++ was close to normal. The addition of guanylylimidodiphosphate or GTP to the incubation mixture increased, in a dose-dependent manner, the apparent KaMg of the enzyme in the abnormal tissue toward normal, suggesting a defective nucleotide regulatory site in the adenylate cyclase of hyperparathyroid glands. In addition, the hyperparathyroid gland enzyme was less susceptible to inhibition by calcium, requiring 0.7-1 mM Ca++ for 50% inhibition, whereas comparable inhibition of the normal adenylate cyclase was seen at 0.22-0.28 mM Ca++. We conclude that the abnormal control of PTH secretion in hyperparathyroidism may be related, at least in part, to alterations in the characteristics of parathyroid gland adenylate cyclase.
Adenosine Triphosphate↗
Surgical significance of undescended parathyroid gland in renal hyperparathyroidism.
BACKGROUND: In renal hyperparathyroidism, in which basically all parathyroid glands are hyperplastic, overlooking one undescended parathyroid gland becomes important. METHODS: Between July 1973 and December 2004, 1750 patients in our department underwent parathyroidectomy for severely advanced renal hyperparathyroidism. We evaluated the frequency and location of undescended parathyroid glands and the clinical findings and the prognosis of patients with such glands. RESULTS: Undescended parathyroid glands in our series of renal hyperparathyroidism numbered 16 of 1750 cases (0.91%). In 9 patients, the glands were removed at the initial parathyroidectomy in our hospital. Two of these glands were detected by preoperative imaging; 6 glands were removed with an undescended thymus. The mean weight of the undescended parathyroid glands that were removed at initial operations was 470 mg (30 to 1392 mg). In 7 other patients, unrecognized undescended glands were responsible for persistent hyperparathyroidism in 6 patients and recurrent disease in 1 patient. In 4 of these 7 patients, the initial parathyroidectomy was performed at our hospital; in the other 3 patients, the initial parathyroidectomy had been done at another hospital, and the glands were removed on reoperation. The mean weight of these glands was 1295 mg (range, 444-2396 mg). In 12 of a total of 16 patients with undescended glands, there appeared to be an inferior parathyroid gland, and the other 4 glands appeared to be a superior gland. No glands were detected by sestamibi scans. CONCLUSION: In operations for renal hyperparathyroidism, an undescended parathyroid gland can be readily overlooked, which leads to persistent or recurrent hyperparathyroidism. Because an undescended parathyroid gland is not always an inferior gland, in surgery for persistent and/or recurrent renal hyperparathyroidism, it is very important to examine carefully the submandibular portion to detect such an undescended gland.
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Immunoheterogeneity of parathyroid hormone in venous effluent serum from hyperfunctioning parathyroid glands.
The immunoreactive parathyroid hormone (iPTH) in the plasma of hyperparathyroid man consists largely of carboxyl (COOH)-terminal fragments of the hormone. Although these fragments have been thought to arise principally or solely from peripheral metabolism of intact human PTH {hPTH(1-84)} secreted from the parathyroid gland, there is disagreement about the source of iPTH fragments in vivo. To reexamine this question, we fractionated peripheral and thyroid or parathyroid venous effluent sera from four patients with primary hyperparathyroidism using a high-resolution gel filtration system (Bio-Gel P-150 columns run by reverse flow). The column effluents were analyzed using two PTH radioimmunoassays, one directed toward the amino(NH(2))-terminal region of the molecule, the other toward the COOH-terminal region. In all four thyroid or parathyroid venous effluent sera studied, iPTH was 9-180 times higher than in peripheral serum from the same patient; after fractionation, hPTH(1-84) accounted for only a portion of the total iPTH (35-55% with the assay directed toward the COOH-terminal region of hPTH, >90% with the NH(2)-terminal directed assay.) The remaining iPTH eluted from Bio-Gel P-150 after hPTH(1-84) as NH(2)-or COOH-terminal hPTH fragments. These results suggest that parathyroid tumors secrete large quantities of hPTH fragments. Based on estimates of their molar concentrations in serum, tumor-secreted COOH-terminal hPTH fragments could account for most of these peptides in peripheral serum if their survival times were, as estimated by several other workers, 5-10 times that of hPTH(1-84). We conclude that, in contrast to published information, secretory products of hyperfunctioning parathyroid tissue are probably a major source of serum PTH immunoheterogeneity.
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Parathyroid gland involvement by papillary carcinoma of the thyroid gland.
OBJECTIVE: To describe the phenomenon of parathyroid gland involvement by thyroid carcinoma and to explore its clinicopathologic significance. DESIGN: We reviewed the clinicopathologic features and described the histopathologic characteristics of 20 cases of parathyroid involvement found in a series of 911 papillary thyroid carcinomas. RESULTS: Parathyroid involvement occurred in 3 patterns: (1) direct invasion from the main tumor with an infiltrative growth, (2) invasion of the parathyroid gland with an expansive growth and formation of a pseudocapsule between the carcinoma and the parathyroid gland, and (3) metastatic deposition within the parathyroid gland itself. Among the 20 cases, 6 (30%) had primary tumors measuring 1 cm or less, and 14 (70%) had primary tumors measuring more than 1 cm. The cases with smaller primary tumors had a comparatively lower rate of nodal metastasis (50% vs 100%, P =.02). Furthermore, none of the cases with smaller primary tumors had invasion of extrathyroid structures other than parathyroid gland, but such invasion was common among the cases with larger primary tumors (0% vs 71%, P =.01). CONCLUSION: To the best of our knowledge, this is the first report showing that parathyroid involvement occurs in papillary thyroid carcinomas even in the early stage of the disease.
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Lipoadenoma of the parathyroid gland.
An unusual parathyroid adenoma containing abundant adipose tissue is described in four patients. In one patient, hyperparathyroidism was documented; in another, studies were incomplete but the adenoma was probably functioning. Prior reports of similar lesions have been called "parathyroid hamartoma or parathyroid adenoma with myxoid stroma," and some of these also have been shown to be functional. They may create diagnostic difficulties because of the presence of adipose tissue, a feature associated with normal parathyroid glands.
Adenoma↗
DISCUSSION on the physiology and clinical disorders of the parathyroid glands.
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Humans↗
[Intraoperative extemporaneous examination of the parathyroid gland: what is the role of the pathologist in parathyroid pathology?].
Hyperparathyroidism (HPT), once considered a rare disease, is nowadays observed and diagnosed more frequently. Consequently, surgical treatment of HPT is often performed with good therapeutic results. The success of parathyroid surgery depends mainly on the accuracy of histopathologic diagnosis through intraoperative examination of frozen tissue specimens. Yet, parathyroid gland pathology is very complex and some of its topics even controversial. Terminology and clinico-pathological concepts in this field are constantly changing and even basic characteristics such as weight, stromal fat content and "normal " histologic patterns of these glands are still actively discussed. The pathologist must often determine, merely by studying a small bioptic specimen, not only the parathyroidal (or non-parathyroidal) origin of the examined tissue, but also the histological "normal" or "abnormality" of the tissue. In carrying out his work the experienced pathologist takes on an important task and responsibility in distinguishing between normal, early hyperplastic (asymmetric), hyperplastic or adenomatous parathyroid glands. New diagnostic technical approaches (such as Electron Microscopy, intracellular fat morphometric evaluation, parenchymal cell mass study by density gradient, etc.) enhance the possibility of reaching a reliable pathologic diagnosis, but they do not solve all the present problems and sometimes can even lead the pathologist astray. Presently the diagnosis and treatment of primary HPT should be considered an open and current problem inasmuch as definite criteria to be followed in distinguishing between normal or single enlarged glands microscopically are still lacking. Neither the degree of accuracy of intraoperative frozen section examination during parathyroid surgery nor the possibility of misleading observations in such a study has been fully evaluated. A close cooperation between the pathologist and head and neck surgeon is of utmost importance to assure the best therapeutical results obtainable from parathyroid surgery in HPT.
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Immunocytochemical localization of parathyroid hormone in rabbit parathyroid glands.
Immunocytochemical localization of parathyroid hormone was examined in the rabbit parathyroid gland by means of protein A-gold technique. Protein A-gold particles were observed on the secretory granules and the large secretory granules thought to be storage granules. No protein A-gold particles were observed on cisternae of the endoplasmic reticulum and the Golgi apparatus.
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[Imaging of the parathyroid gland].
Diseases of the parathyroid gland are rare and are especially in case of hyperparathyroidism associated with hyperacalcaemia. Enlarged glands are, therefore, generally not detected with imaging modalities. The aim of imaging studies is to locialize abnormal glands. Ultrasound is the modality of choice for the primary investigation followed by nuclear medicine studies. Computed tomography or angiography with vein sampling should only be performed if the results of other investigations are equivocal. Magnetic resonance imaging is performed rarely in Austria with its high prevalence of endemic goiter.
Adenoma↗
[Ultrasonic study of the parathyroid glands in patients with coralliform nephrolithiasis].
Functional activity of the parathyroid glands (PTG) is important for the choice of proper therapeutic policy in patients with dendritic nephrolithiasis. The location of the hyperfunctioning gland (usually adenomatously or hyperplastically changed) is a complicated problem as the dimensions of the gland are extremely small. Ultrasonic investigation of the parathyroid gland area for detection of the enlarged gland is used at the Research Institute of Urology, the RSFSR Ministry of Health. Linear (7.5 mHz) and sector (5 mHz) transducers have been used through the water medium and by the immediate contact with the surface of the patient's neck. A total of 24 subjects were enrolled in the study (13 females and 11 males aged 23-64 years). Enlarged parathyroid glands situated in the lower thyroid lobe (low parathyroid glands) or in the upper medial third of the thyroid lobe (upper parathyroid glands) were recorded in 9 patients and confirmed in the course of surgeries. In one case, the enlarged parathyroid gland was found in the thyroid tissue. Its length varied from 0.6 to 1.5 cm and its thickness, from 0.4 to 0.9 cm. All the glands were echographically evidenced as oval formations with a low-rate echogeneity and clear-cut smooth contours. In 3 cases the site of the gland was confirmed by a selective testing of the neck venous blood for parathyroid hormone. Histological examination of the removed glands revealed that hyperplastic changes were more common than the adenomatous ones.
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Variations of topography of the parathyroid glands. Clinical aspects.
In 120 cadavers four parathyroid glands were found in 56.7% of cases. In most investigated specimens (above 90%) the superior parathyroid glands are localized posteriorly to the recurrent laryngeal nerve, whereas inferior parathyroid glands lie anteriorly to the nerve. The parathyroid glands are localized within a radius of 2 cm from the crossing of the recurrent laryngeal nerve and the inferior thyroid artery.
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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.
Adult↗
Fluorescence-guided minimally invasive parathyroidectomy: a novel detection technique for parathyroid glands.
BACKGROUND: Detection of normal and pathologic parathyroid glands often is difficult because of their variability in number and location. The feasibility and efficacy of a fluorescence technique for identifying parathyroids have already been proved in an experimental setting. This is the first report of human fluorescence-guided parathyroidectomy. METHODS: A 72-year-old man with primary hyperparathyroidism underwent minimally invasive videoscopically assisted parathyroidectomy after photosensitization with aminolevulinic acid. Under special fluorescence illumination by the D-light, a unilateral directed neck exploration was performed. RESULTS: The enlarged adenoma and an atrophic parathyroid gland could be identified rapidly and removed because of their intense red fluorescence. Surrounding structures such as thyroid, muscles, and soft tissue remained nonfluorescent and could easily be distinguished from the parathyroid glands. CONCLUSIONS: The aminolevulinic acid-induced fluorescence technique represents a convincing visual detection method for intraoperative identification of parathyroid glands. The technique serves as an additional tool requiring only moderate technical and clinical expenditure for help in guiding dissection down to a preoperatively localized adenoma. When used together with preoperative ultrasonography and sestamibi scan, the fluorescence technique may justify a unilateral, minimally invasive approach for selected patients.
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