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Fibroblast growth factors and their receptors in parathyroid disease.

Fibroblast growth factors (FGFs) comprise a family of polypeptide growth factors implicated in the control of proliferation of glandular tissues. The aim of this study was to determine whether FGFs are produced in normal and abnormal parathyroid glands and if these tissues have the potential to respond to this growth factor family. We have examined the expression of FGF receptor (FGF-R) types 1 and 2 and of FGFs 1, 2, 3, and 7 in a series of human parathyroid tissues using the reverse transcription polymerase chain reaction (RT-PCR). Samples of 10 parathyroid adenomas and 10 hyperplastic glands from patients with renal hyperparathyroidism (HPT) were compared with samples from normal parathyroid glands from patients with primary HPT in the study. FGF-R1 was expressed in all samples and FGF-R2 in most. FGF1 and FGF2 were expressed in all samples at variable levels, with no correlation between disease type and amplified RT-PCR product levels. FGF7 was expressed in normal parathyroid tissue and in all adenomas but was absent in all but one of the hyperplastic parathyroid glands from renal failure patients. FGF3 was expressed at low levels in normal tissue and variably expressed in diseased tissue, in some instances at high levels. These findings suggest that parathyroid tissue is potentially responsive to FGFs. The absence of FGF7 expression in all but one of the renal parathyroid samples compared with normal and adenomatous tissue requires further investigation. The presence of elevated levels of FGF3 expression in abnormal parathyroid tissue may be significant, as the FGF3 gene (int-2 proto-oncogene) is located on chromosome 11q13.3, a region already identified as being susceptible to rearrangement/mutation in parathyroid disease.

Adenoma↗

[Genes causing parathyroid diseases].

Discovery of Gcm2 as an essential transcription factor for parathyroid gland development disclosed another, unexpected source of circulating parathyroid hormone (PTH), the thymus. A recent phylogenetic analysis of Gcm2 has led to a new theory that parathyroid glands in tetrapods were transformed from the gills of fish during evolution. I review genes involved in the pathogenesis of hyper- and hypo-function of parathyroid glands as well as in the development of parathyroid tumors.

Animals↗

Operative experience of U.S. general surgery residents in thyroid and parathyroid disease.

BACKGROUND: We wanted to determine whether the experience of general surgery residents is adequate and effective. METHODS: The Resident Statistic Summaries (Report C) of the Residency Review Committee (Surgery) for 8 academic years from 1986 through 1994 were analyzed. The main outcome measurements were total number of residents and programs, average number of operations performed, maximum number of operations performed, standard deviation, and the most common number of operations performed. RESULTS: For thyroidectomy the average per resident ranged from 10.3 to 12.6. The maximum ranged from 52 to 102. The standard deviations ranged from 6.96 to 8. The most common number of thyroidectomies performed ranged from 7 to 10 per graduating resident. For parathyroidectomy the average ranged from 4.1 to 5.1, the standard deviations were 3.44 to 4, the maximum ranged from 25 to 60, and the most common number performed was 2. CONCLUSIONS: U.S. graduates have highly variable experience in thyroid and parathyroid surgery. Most residents have inadequate experience in parathyroid surgery and marginal experience in thyroid surgery.

Humans↗

Coexisting thyroid and parathyroid disease--are they related?

A high prevalence of non-C cell, thyroid gland disease associated with primary hyperparathyroidism (HPT) has been reported in 11 uncontrolled studies. Yet experimental evidence linking these thyroid and parathyroid gland lesions is lacking. To test the hypothesis that the coexistence of these lesions is significant, we analyzed 124 consecutive cases of parathyroidectomy (110 women, mean age 53.5 +/- 12.7 years). Patients in the group with HPT who had visible or palpable thyroid disease at the time of operation were age-, sex-, and race-matched with autopsy controls. There was no statistical difference in the prevalence of total macroscopic thyroid lesions between the autopsy control group (46.4%) and the group of patients with HPT (54%, P = 0.8). Microscopic lesions in the absence of macroscopic abnormalities were found in an additional 26% of the autopsy control patients. Since in the surgical group, only those with macroscopic abnormalities underwent thyroid biopsy, no accurate calculation can be made of the microscopic lesions in those 55 patients with HPT who did not have macroscopic abnormalities. There was no difference in the prevalence of autoimmune or thyroid nodular disease between the two groups except for the presence of seven macroscopic nonmedullary thyroid carcinomas in the HPT group and none in the autopsy control group (P less than 0.001). One microscopic carcinoma was found in the autopsy group, however. An increased prevalence of parathyroid adenomas in nonmedullary thyroid disease has been suggested by other studies. We were unable to confirm this association. In fact, the incidence of parathyroid adenomas found unsuspectedly in 229 consecutive thyroidectomies was 0.43%. Thus with the exception of macroscopic, nonmedullary carcinomas, there was no evidence that thyroid disease accompanies HPT. Furthermore, parathyroid adenomas were not more frequent in surgical thyroid disease. Lesions of the thyroid and parathyroid glands are prevalent in middle-age women. This probably is the major factor that accounts for their coexistence.

Biopsy↗

Blood magnesium status of patients with parathyroid disease.

The blood magnesium status--plasma and red blood cell (RBC) concentration and mononuclear blood cell (MBC) content of magnesium and parathyroid hormone (PTH) were determined in 6 patients with chronic hypoparathyroidism and 9 patients with primary hyperparathyroidism before and after surgical cure of the disease. The magnesium content of MBCs and concentration of RBCs increased significantly (p less than 0.01) after the surgical correction of primary hyperparathyroidism. Patients with chronic hypoparathyroidism had significant increase (p less than 0.05) of magnesium in RBCs and MBCs compared with the control group. No significant difference was observed for the plasma magnesium concentration for hypoparathyroid patients compared with the control group and hyperparathyroid patients before and after surgical care. These results suggest that endogenous PTH affects the concentration of magnesium in RBCs and magnesium content in MBCs but does not alter significantly the concentration of magnesium in plasma.

Erythrocytes↗

Surgical treatment of parathyroid disease: a review.

Since the first parathyroidectomy was performed by Mandl in 1925, there have been many advances in our understanding of the parathyroid gland and its related disorders of calcium homeostasis. Our ability to establish the diagnosis of parathyroid neoplasia and locate the source of autonomous parathormone production has also dramatically improved. Nevertheless, it was the advent of the routine calcium and phosphate screening done on the sequential multiple analyzer (SMA-12) that has caused a tremendous increase in the number of patients who are diagnosed to have hyperparathyroidism and who therefore present for surgical treatment. Essential for successful and uncomplicated treatment of this disorder is a thorough understanding of the anatomy, physiology, and pathology of the parathyroid glands. This review will consider the parathyroid glands in their normal state, as well as the diagnosis and management of the various disorders associated with them.

Calcitonin↗

Surveillance for early detection of aggressive parathyroid disease: carcinoma and atypical adenoma in familial isolated hyperparathyroidism associated with a germline HRPT2 mutation.

UNLABELLED: Familial hyperparathyroid syndromes involving mutations of HRPT2 (also CDC73), a tumor suppressor, are important to identify because the relatively high incidence of parathyroid malignancy associated with such mutations warrants a specific surveillance strategy. However, there is a dearth of reports describing experience with surveillance and early detection informed by genetic insight into this disorder. INTRODUCTION: Familial isolated hyperparathyroidism (FIHP) is a rare cause of parathyroid (PT) tumors without other neoplasms or endocrinopathies. Germline mutations in CASR, MEN1, and rarely, HRPT2 have been identified in kindreds with FIHP. HRPT2 mutations may be enriched in FIHP families with PT carcinoma, underscoring the importance of identifying causative mutations. MATERIALS AND METHODS: A 13-year-old boy, whose father had died of PT carcinoma, developed primary hyperparathyroidism. A left superior PT mass was identified by ultrasonography and removed surgically. Aggressive histological features of the boy's tumor included fibrous trabeculae, mitoses, and microscopic capsular infiltration. Two years later, under close biochemical surveillance, primary hyperparathyroidism recurred 5 months after documentation of normocalcemia and normal parathyroid status. Ultrasound and MRI identified a newly enlarged right superior PT gland but indicated no recurrent disease in the left neck. Histologic features typical of a benign adenoma were evident after surgical extirpation of the gland. RESULTS: Leukocyte DNA analysis revealed a frameshift mutation in exon 2 of HRPT2. The initial tumor manifested the expected germline HRPT2 mutation, plus a distinct somatic frameshift mutation, consistent with the Knudson "two hit" concept of biallelic inactivation of a classic tumor suppressor gene. Genetic screening of the patient's 7 asymptomatic and previously normocalcemic siblings revealed three with the same germline HRPT2 mutation. One of the siblings newly identified as mutation-positive was noted to be hypercalcemic at the time of the genetic screening. He was found to have a PT adenoma with aggressive features. Two of the five children of another mutation-positive sibling also carry the same HRPT2 mutation. CONCLUSIONS: Despite the reported rarity of HRPT2 mutations in FIHP, a personal or family history of PT carcinoma in FIHP mandates serious consideration of germline HRPT2 mutation status. This information can be used in diagnostic and management considerations, leading to early detection and removal of potentially malignant parathyroid tumors.

Adenoma↗

The operative management of coexisting thyroid and parathyroid disease.

Three hundred eight patients who underwent operation for hyperparathyroidism were studied. Fifty-two (17%) were identified who had a concomitant thyroid nodule. All 52 underwent parathyroidectomy and thyroid resection in a single operation. Eleven of these patients (21% of those with a thyroid nodule) had differentiated thyroid cancer. One patient with parathyroid hyperplasia developed permanent hypocalcemia. None had permanent vocal cord paralysis and none required tracheostomy. Thorough visual inspection and palpation of the entire thyroid gland should be performed during operations for hyperparathyroidism. Incidentally discovered thyroid nodules should prompt formal lobectomy with frozen section diagnosis; unanticipated thyroid malignancies should then be treated as independent entities. Treating simultaneous hyperparathyroidism and nodular thyroid disease with a single operation can be done safely; it avoids the expense and risk associated with neck reexploration and can detect unsuspected cancers.

Adenoma↗