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Heterogeneous gland size in sporadic multiple gland parathyroid hyperplasia.

BACKGROUND: The success rate for bilateral exploration in patients with primary hyperparathyroidism approaches 95%. Multiglandular parathyroid hyperplasia accounts for approximately 10% to 30% of primary hyperparathyroidism. The incidence of recurrent or persistent hyperparathyroidism is highest in familial forms of the disease, in which multiglandular disease is more common; this may be due to asymmetric enlargement of parathyroid glands. Because of improvements in tumor-imaging capability, some surgeons are now advocating unilateral exploration for primary hyperparathyroidism, but there is limited experience concerning how often these imaging methods fail. STUDY DESIGN: The outcomes of 7 patients who had sporadic primary hyperparathyroidism with multigland hyperplasia were reviewed. We gathered demographic data and laboratory values and reviewed radiologic tests, surgical findings, pathologic findings, and postoperative followup. RESULTS: All patients underwent preoperative localization with ultrasonography and technetium/sestamibi scans. The sensitivity of these two tests for the dominantly enlarged gland was 100% for both, but dropped to 0% and 5%, respectively, for all other enlarged glands. The sensitivity of CT and MRI for the dominant tumor was 67% (2 of 3) and 50% (1 of 2), respectively. Six of 7 patients underwent subtotal (3(1/2) gland) parathyroidectomy. The mean volume of all glands was 1.51+/-5.89 cm3 compared with a mean of 5.66+/-11.4 cm3 for all dominant glands and 0.123+/-0.1 cm3 for all nondominant hyperplastic glands. There was a large amount of variability between the volumes of dominant and other glands as demonstrated by large SDs from the mean. CONCLUSIONS: There is a marked heterogeneity in gland size in patients with sporadic multigland hyperplasia, which is similar to that found in multiple endocrine neoplasia type I. This heterogeneity may result in failure to recognize multigland disease if a unilateral neck exploration is performed. Intraoperative parathyroid hormone assay may prove to be an important adjunct in this population of patients who have unsuspected multigland disease.

Adult↗

Peptide-containing nerve fibres in normal human parathyroid glands and in human parathyroid adenomas.

There are only a few studies on the innervation of the human parathyroid glands and the content of neurotransmitters. We therefore studied the occurrence and distribution of peptide-containing and adrenergic nerve fibres and the coexistence pattern of neuromessengers by immunocytochemistry in normal (unaffected) and adenomatous parathyroid glands from patients undergoing surgery for parathyroid adenoma. The unaffected parathyroid glands had a moderate-to-rich supply of nerve fibres and terminals containing two general neuronal markers, protein gene product 9.5 (PGP 9.5) and synaptophysin, neuropeptide Y (NPY) and tyrosine hydroxylase (TH). They were seen close to blood vessels and, occasionally, among the endocrine cells. Only a few nerves contained calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), substance P (SP) and pituitary adenylate cyclase-activating peptide (PACAP). The general density of innervation, using PGP 9.5 and synaptophysin as markers, varied greatly among the different adenomas examined. This applied also to the density of fibres and terminals containing specific types of messengers. Some of the tumours had a rich supply of TH- and NPY-containing nerve fibres, while others contained only few scattered fibres. The CGRP-containing fibres varied from moderate in number to no detectable fibres. The PACAP-, SP- and VIP-containing fibres were always very few or not detectable. It is not inconceivable that the wide variation in general density of the innervation and frequency of peptide-containing nerves among individual parathyroid adenomas is of significance for their hormone secretory behaviour.

Adenoma↗

Intraoperative secretion of intact parathyroid hormone and amino-terminal parathyroid hormone fragments from normal parathyroid glands associated with solitary parathyroid adenoma.

The nonadenomatous parathyroid glands associated with parathyroid adenoma in patients with primary hyperparathyroidism (pHPT) are assumed to exhibit suppressed secretion of parathyroid hormone (PTH). Because the function of these glands is of clinical importance for calcium homeostasis after surgery for pHPT, we studied the decrease of serum levels associated with intact PTH (i-PTH) and amino-terminal PTH (N-PTH) after excision of a parathyroid adenoma. Blood samples were obtained from the cubital vein and the inferior thyroid vein in six patients with pHPT. The results show that the levels of both i-PTH and N-PTH decreased after removal of the parathyroid adenoma (p < 0.05 for both). Because the reduction was more pronounced for i-PTH than for N-PTH, the N/i ratio increased from 0.54 +/- 0.33 to 3.76 +/- 1.62 (p < 0.05). Furthermore, the levels of i-PTH and N-PTH were higher centrally than peripherally both before and after adenoma excision (p < 0.05). The results therefore suggest that the secretion of i-PTH and N-PTH in the remaining normal-size parathyroid glands is not completely suppressed. Furthermore, in these parathyroid glands the secretion of amino-terminal PTH fragments is relatively predominant when compared to the release of the intact PTH. The findings underscore the importance of the N-terminal PTH fragment for maintaining calcium homeostasis during the early postoperative period after surgery for pHPT and may explain the rarity of prolonged hypocalcemia after parathyroidectomy.

Adenoma↗

Oral calcium supplements to enhance early hospital discharge after bilateral surgical treatment of the thyroid gland or exploration of the parathyroid glands.

One hundred and seventy consecutive patients undergoing parathyroid gland exploration and bilateral thyroidectomy received, postoperatively, routine oral calcium supplementation, close monitoring of total serum calcium, and addition of vitamin D for specific criteria, all to accomplish a postoperative course free of symptomatic hypocalcemia and early discharge from the hospital. Twelve of these patients underwent simultaneous thyroid gland and parathyroid gland operation. Parathyroid gland manipulation during these operations was aggressive. Of the 58 patients undergoing parathyroid exploration, two required hospitalization for more than three days to treat hypocalcemia. No patients required intravenous calcium and 17 of the last 24 having total serum calcium greater than or equal to 9.0 milligrams per deciliter at 36 hours were discharged uneventfully on the morning of the second postoperative day. Of the 124 patients undergoing bilateral thyroidectomy, four required hospitalization in excess of three days for hypocalcemia, one required intravenous calcium and one still requires daily vitamin D after a year. Eighty-five of the last 96 patients having a total serum calcium greater than or equal to 8.5 milligrams per deciliter at 36 hours were discharged on the morning of the second postoperative day, without subsequent hypocalcemic events. These data suggest that a program of calcium supplementation combined with enthusiastic outpatient support can be the future basis for same day or one day admissions after parathyroid gland or extensive thyroid gland operations.

Administration, Oral↗

Pathologic intrathyroidal parathyroid glands.

BACKGROUND: Parathyroid glands originate from the third and fourth branchial pouches and migrate caudally to their final positions. Aberrations during migration result in anomalous locations. Intrathyroidal location is not common. METHODS: We reviewed cervical explorations performed from 1974 to 1993 in hyperparathyroidism patients. RESULTS: We found pathological intrathyroidal glands in six patients. Three patients had adenomas (left superior, left inferior and right inferior glands). The hyperplastic glands were left inferior in one patient and right inferior in the remaining two. Intraoperative diagnosis was made in three cases in which palpation of the thyroid gland showed a nodule that was suspected to be the parathyroid missing gland. In three patients it was a finding in thyroidectomy or hemithyroidectomy specimens, two of them with associated thyroid nodular disease. CONCLUSIONS: Ipsilateral thyroidotomy on the side of a palpable thyroid mass or blind hemithyroidectomy are justified if a presumably pathological intrathyroidal gland is suspected, when all other sites in the neck have been excluded.

Adenoma↗

[Cystic parathyroid gland adenomas: pathologic-anatomic variants of parathyroid gland adenomas or a separate disease entity?].

Between 01.01.1987 and 31.12.1990 a primary operation was performed on 126 patients in the Dept. of General Surgery, University of Marburg Hospital for primary hyperparathyroidism due to a parathyroid adenoma. Their clinically relevant data were prospectively documented. In 6 patients (4.8%) a total of 7 cystic parathyroid adenomas was found. While there was no difference in age- and sex-distribution, patients with cystic adenomas were found to have markedly higher serum parathormone and alkaline phosphatase levels than patients with solid adenomas. Calcium levels were similar in both groups. Cystic adenomas were much heavier than solid adenomas. A significant number of cystic adenomas was found to be displaced into the posterior mediastinum. The property of cystic parathyroid adenomas to be frequently located away from their usual anatomical position can make the intraoperative search for them difficult.

Adenoma↗

Protein kinase activities in the parathyroid gland: proparathyroid hormone, parathyroid hormone and secretory protein-I as substrates for phosphorylation.

We have identified two protein kinase activities in homogenates of bovine parathyroid tissue following fractionation on DEAE columns. One of these is a protein kinase C based upon its requirement for calcium and phosphatidylserine and the other one is probably M kinase. The protein kinase C phosphorylated both proparathyroid hormone and parathyroid hormone but not secretory protein-I (SP-I). Neither N [1-34] or C [35-84] terminal hormonal fragments were phosphorylated, suggesting that the structure of the intact PTH molecule is required for recognition by the enzyme. A second kinase activity behaving like M kinase was also obtained. This activity, which was not separable from a cAMP dependent kinase, was maximal with only 50 mM MgCl2 as cofactor. SP-I was readily phosphorylated by this activity but parathyroid hormone was not.

Animals↗

Immunocytochemical localization of parathyroid hormone in bovine parathyroid glands and human parathyroid adenomas.

Light and electron microscopic localization of parathyroid hormone (PTH) in human and bovine parathyroid tissue has been achieved using an indirect peroxidase labeled antibody method. Granular deposition of the reaction product was found throughout the chief cell cytoplasm. There was no nuclear staining. At the ultrastructural level, parathyroid hormone localized by this method appeared to be largely confined to the secretory granules in the cytoplasm of cells. Mitochondria and nuclei were free of reaction product. Aggregated sacs of granular endoplasmic reticulum were minimally reactive, and Golgi apparatuses did not show reaction product.

Adenoma↗

Genetic ablation of parathyroid glands reveals another source of parathyroid hormone.

The parathyroid glands are the only known source of circulating parathyroid hormone (PTH), which initiates an endocrine cascade that regulates serum calcium concentration. Glial cells missing2 (Gcm2), a mouse homologue of Drosophila Gcm, is the only transcription factor whose expression is restricted to the parathyroid glands. Here we show that Gcm2-deficient mice lack parathyroid glands and exhibit a biological hypoparathyroidism, identifying Gcm2 as a master regulatory gene of parathyroid gland development. Unlike PTH receptor-deficient mice, however, Gcm2-deficient mice are viable and fertile, and have only a mildly abnormal bone phenotype. Despite their lack of parathyroid glands, Gcm2-deficient mice have PTH serum levels identical to those of wild-type mice, as do parathyroidectomized wild-type animals. Expression and ablation studies identified the thymus, where Gcm1, another Gcm homologue, is expressed, as the additional, downregulatable source of PTH. Thus, Gcm2 deletion uncovers an auxiliary mechanism for the regulation of calcium homeostasis in the absence of parathyroid glands. We propose that this backup mechanism may be a general feature of endocrine regulation.

Animals↗

Effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) on the ultrastructure of parathyroid glands and plasma immunoreactive parathyroid hormone in pregnant cows fed a low calcium diet.

The long term (70 days) effects of administering ethane-1-hydroxy-1,1-diphosphonate (EHDP) (4 mg. per kg. per day) on parathyroid function was investigated in pregnant cows fed a low calcium diet. Serum calcium and phosphorus were significantly lower at parturition and postpartum in EHDP-treated cows compared to pregnant control cows fed the low calcium diet. Plasma immunoreactive parathyroid hormone levels were similar prepartum, at parturition, and postpartum in cows administered EHDP and control cows. Immediately available calcium reserves were greater preparation in control cows than in cows receiving EHDP as indicated by a more rapid rate of return of serum calcium toward normal levels following ethylenediaminetetraacetic acid (EDTA)-induced hypocalcemia approximately 10 days prepartum. EHDP-treated cows responded to the hypocalcemic challenge with similar changes in plasma immunoreactive parathyroid hormone levels as in control cows; however, urinary hydroxyproline excretion increased at certain intervals only in control cows. Ultrastructurally, chief cells in parathyroid glands of both groups of cows were in an active stage of the secretory cycle with well developed organelles concerned with hormonela synthesis. Chief cells in cows administered EHDP were degranulated and contained fewer secretory granules in response to the hypocalcemia than those in control cows. Chief cells in EHDP-treated cows often had prominent perinuclear accumulations of microfilaments, scattered vacuolated mitochondria, and lysosomal bodies in the cytoplasm. Thyroid C-cells were densely granulated and thyroid calcitonin content was similar in both groups of cows. The principal defect in calcium homeostasis of EHDP-treated cows appeared to be an impairment both in bone calcium mobilization and bone matrix catabolism in response to the secretion of parathyroid hormone. In vitro uptake of 45Ca by duodenal mucosa and urinary excretion of cyclic adenosine monophosphate were similar in both groups of cows. The ability of the parathyroid glands to synthesize and secrete parathyroid hormone in response to hypocalcemia induced either by EDTA or associated with parturition was not impaired by the administration of EHDP.

Animals↗

Weight of normal parathyroid glands in patients with parathyroid adenomas.

Although the size and weight of a parathyroid gland are frequently the only intraoperative determinants of abnormality, these parameters have not been examined in living patients with primary hyperparathyroidism (PHP). The records of 240 patients who underwent parathyroidectomy according to standard surgical practice by a single surgeon were reviewed to identify those who were euparathyroid after in toto removal of a histologically confirmed normal gland and a histologically confirmed adenoma. The 25 (86%) females and 4 (14%) males who met the study criteria had a mean age of 60 yr (range, 33-82 yr). The mean PTH level was 130.1 pg/ml (range, 58-278) before parathyroidectomy and 32.4 pg/ml (range, 1-68) after parathyroidectomy. The mean calcium level was 11.1 mg/dl (range, 10-14) before and 8.7 mg/dl (range, 8-10) after parathyroidectomy. Thirty-four intact normal glands were removed and available for analysis. Their mean weight was 62.4 +/- 31.6 mg (range, 18-161 mg), and 15 (44%) weighed 60 mg or more. The mean weight of the adenomas was 553.7 +/- 520.5 mg (range, 66-2536). Adenomas were clearly distinguished from normal glands by cellularity, stromal fat, and intracellular fat in chief cells. The weight of normal parathyroid glands removed at surgery in patients with PHP may be greater than that reported in autopsy studies. Therefore, certain histological features are a better measure than weight in determining whether a gland is normal, and intraoperative identification of slightly enlarged glands should not lead to immediate subtotal parathyroidectomy.

Adenoma↗

[99m-Tc-MIBI SPECT parathyroid gland scintigraphy for the preoperative localization of small parathyroid gland adenomas].

AIM: It was the of this study to assess the value of the 99mTc-MIBI scintigraphy in SPECT technique in the preoperative lateral location of small parathyroid adenoma (PTA). METHODS: 25 consecutive patients (8 male, 17 female, mean age 63 +/- 13 years) with the established diagnosis of primary hyperparathyroidism and non-diagnostic ultrasonography were scanned preoperatively. After a thyroid examination to exclude radionuclide accumulating thyroid adenoma, planar and tomographic images were acquired 20 min. and 120 min. after i.v. injection of 740 MBq 99mTc-MIBI using a 3 head gamma camera (Picker Prism 3000). The first 10 patients underwent an additional 201Tl/99mTc subtraction scintigraphy in a 2 days protocol. RESULTS: All patients had small, solitary PTA (< 1 g). 201Tl/99mTc subtraction scintigraphy (n = 10) showed only a sensitivity of 50%. Using planar MIBI-scintigraphy lateral location of PTA was possible in 18 cases (sensitivity: 72%). There was an increase in sensitivity up to 96% using the SPECT technique and the 3D display (volume-rendered reprojection). CONCLUSION: In contrast to 201Tl/99mTc subtraction scintigraphy, which showed only a low sensitivity, a reliable lateral location of small PTA was obtained using the tomographic 99mTc-MIBI scintigraphy. This method offers e.g. the possibility for the surgeon to perform an unilateral parathyroidectomy.

Adenoma↗

Biosynthesis of proparathyroid hormone and parathyroid hormone by human parathyroid glands.

Human parathyroid glands obtained at autopsy were incubated with [(3)H]leucine and [(3)H]lysine. After incubation, nonradioactive parathyroid tissue of either human or bovine origin was added. Radioactive parathyroid hormone and proparathyroid hormone were isolated from the gland and medium by organic solvent and salt fractionation, trichloroacetic acid precipitation, Sephadex G-100 gel filtration, and carboxymethyl cellulose column chromatography. The human hormonal peptides were identified in the ion-exchange column eluates by their relatively high levels of radioactivity, their elution positions, and their immunoreactivity to anti-PTH antiserum. The time-course of radioactive amino acid incorporation into these peptides and a brief incubation of the gland with radioactive amino acids, followed by various lengths of incubation with nonradioactive amino acids, indicated that a precursor-product relationship exists for the two peptides. An alternate method for isolation of the hormone and prohormone, which involves separation of peptides by urea-polyacrylamide gel electrophoresis, confirmed the identities of the human parathyroid hormone and proparathyroid hormone.

Amino Acid Sequence↗

[Ultrasonographic diagnosis of parathyroid glands].

Enlarged parathyroid glands are, if their localization is typical behind the thyroid gland, during basic USG examination with 5 MHz to 10 MHz using a linear probe, hypoechogenic or anechogenic, larger than 0.5 cm, oval in shape, elongated in a cranoiocaudal direction, separated from the thyroid gland. During swallowing they move upwards. Such a picture may be simulated also by enlarged lymph nodes, sympathetic ganglia a cranked vessel or oesophagus. By using coloured Doppler sonography in the algorithm of examinations the percentage of falsely positive findings may decline. Between 90 degrees and 270 degrees the vascular arch is sought which is formed by the branch of the a. thyroidea inferior. This vascular arch is found only when the parathyroid is involved, even when it is located in the parenchyma of the thyroid gland.

Humans↗