Intrathyroid parathyroid gland and neonatal primary hyperparathyroidism

Neonatal hyperparathyroidism (NPHP) is exceedingly rare and often fatal. A neonate is presented with a serum calcium concentration of 33 mg/dL, an intrathyroid parathyroid gland, and a family history of hypocalciuric hypercalcemia (FHH). She underwent successful total parathyroidectomy. Six years later, the child is normocalcemic and developmentally normal, requiring calcium and calcitrol replacement. The results of this case support the concept that NPHP is associated with parathyroid hyperplasia and is part of a continuum that includes FHH.     

Histopathological study of the parathyroid gland in renal hyperparathyroidism

From July 1973 to July 1984, 50 patients underwent parathyroidectomy because of secondary hyperparathyroidism due to chronic renal failure. One hundred fifty-eight excised parathyroid glands in 41 of these patients were submitted to the histopathological examinations in the relations to their clinical features which revealed the following findings. Inspite of secondary hyperparathyroidism, eleven of 41 patients showed four unevenly enlarged parathyroid glands with one or two glands weighing less than 100mg. The glands were divided into three adenomas, 101 diffusely and 54 nodulary hyperplastic glands. The nodular type hyperplasia, which had a greater proportion of clear chief cells, vacuolated chief cells, transitional oxyphil cells and oxyphil cells, was more hyperplastic than the diffuse type. The patients with the nodular type showed more advanced clinical features in the secondary hyperparathyroidism.     

Parathyroid gland function in secondary hyperparathyroidism

The parathyroid glands play a critical role in the maintenance of calcium homeostasis. It has been suggested that the set-point for calcium-regulated parathyroid hormone (PTH) release is higher in uremic patients than normal subjects. However, these assessments of parathyroid gland function have been performed using methods that differed from the original four-parameter model. Dynamic testing of the parathyroid glands has been performed with standardized infusions of calcium gluconate and sodium citrate in dialysis patients with secondary hyperparathyroidism and in normal volunteers. In addition, similar studies have been carried out before and after 4 months of intermittent calcitriol therapy. The derived values for the set-point were 1.21+0.04 mmol/l and 1.24+0.06 mmol/l, respectively in control and dialyzed patients (NS). Furthermore, the values for set-point were 1.21+0.01 and 1.22+0.01 mmol/l (NS), before and after calcitriol therapy. In addition, when subjects were grouped according to the severity of secondary hyperparathyroidism, the set-point calcium-regulated PTH release did not differ between the groups. Calcitriol therapy alters the secretory capacity of the parathyroid glands during hypocalcemia. The degree of parathyroid enlargement and the type of cell proliferation may be more important determinants of the severity of secondary hyperparathyroidism.     

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.     

Relationship between parathyroid gland size and responsiveness to maxacalcitol therapy in patients with secondary hyperparathyroidism.

BACKGROUND: Although vitamin D has been reported to be useful in the treatment of patients with secondary hyperparathyroidism, it is not effective in some of them. The goal of this study was to see whether a relationship could be found between maxacalcitol responsiveness and parathyroid gland size. METHODS: Parathyroid gland size was measured by ultrasonography in 25 patients with secondary hyperparathyroidism [serum intact parathyroid hormone (PTH) >300 pg/ml, 58.1 +/- 2.8 years old, 15 males and 10 females], who were treated with maxacalcitol. Patients were divided into two groups according to the mean value of the maximum diameter of the glands: group S with a diameter <11.0 mm and group L with a diameter >or =11.0 mm. Between the two groups there were no significant differences in serum intact PTH, calcium or phosphate level or duration of haemodialysis. RESULTS: Mean (+/- SE) maximal diameter of detectable parathyroid glands was 11.0 +/- 0.7 mm before treatment. At 4-24 weeks after administration of maxacalcitol, intact PTH concentrations decreased significantly in group S (from 546 +/- 39 to 266 +/- 34 pg/ml at 24 weeks; P < 0.01), but did not significantly change in group L (from 481 +/- 39 to 403 +/- 49 pg/ml at 24 weeks). At 24 weeks after maxacalcitol administration, the number of detectable parathyroid glands was significantly decreased in group S (from 2.2 +/- 0.3 to 1.8 +/- 0.4; P < 0.05), but not in group L. Serum calcium increased significantly in group L (from 9.6 +/- 0.2 to 10.2 +/- 0.3 mg/dl; P < 0.05), but not in group S. There was a significant correlation between reduction in PTH and parathyroid gland size (r = -0.42, P < 0.05). CONCLUSIONS: These results indicate that the responsiveness to maxacalcitol therapy of secondary hyperparathyroidism is dependent on parathyroid gland size and that the simple measurement of maximum parathyroid gland diameter by ultrasonography may be useful for predicting responsiveness to maxacalcitol treatment.     

Clinical symptoms of hyperparathyroidism and sizes of the parathyroid gland tumors

Three groups of patients with different degrees of primary hyperparathyroidism were compared: 36 patients with asymptomatic tumors (incidentalomas) of the parathyroid glands, 20 patients with parathyreoadenomas of medium size and mild signs of hyperparathyroidism and 26 patients with large adenomas and severe manifestations of the disease. It was shown that asymptomatic tumors of the parathyroid glands (incidentalomas) might turn into clinically marked hyperparathyroidism as the size of the parathyroid tumors was growing.     

Recurrent hyperparathyroidism: A sixth mediastinal parathyroid gland.

We present the case of a 71-year-old woman with recurrent hyperparathyroidism. She underwent first a subtotal resection of the parathyroid glands associated with subtotal thyroidectomy in the setting of primary hyperparathyroidism and multi nodular thyroid. Pathologic findings were consistent with hyperplasia and demonstrated a fifth parathyroid gland in the thyroid. Two years later, the patient presented recurrent hyperparathyroidism associated with terminal renal insufficiency, fusion of Sesta Mibi scintigraphy and CT scan demonstrated a sixth mediastinal parathyroid gland in the aorto pulmonary window. Despite videomediastinoscopic attempts, resection was performed through manubriotomy approach. Pathologic findings demonstrated a parathyroid adenoma.     

Usefulness of preoperative Tc-mibi parathyroid scintigraphy in secondary hyperparathyroidism

Background and aims The usefulness of Tc-mibi parathyroid scintigraphy (Tc-PS) in planning parathyroidectomy for secondary hyperparathyroidism is not well known. The aim of this study was to review our experience with Tc-PS concerning: (1) the identification of hyperplastic glands, (2) detection of major ectopias and (3) prevention of recurrences. Patients and methods Thirty-three consecutive patients undergoing first-time subtotal parathyroidectomy for renal hyperparathyroidism had a dual-phase planar Tc-PS performed, and glands were classified as detected, weak, or not detected. The number and position of visualized glands were determined. Parathyroid weight, histology, and their relationship to Tc-PS were recorded after surgery. Results Of 132 potential glands, 48 (35%) were localized on the Tc-PS and 128 (96.9%) were identified intraoperatively. Tc-PS positive/weak glands were heavier than nonlocalized glands. Tc-PS contributed to successful surgery in four patients with a single difficult gland each (three retrieved from the neck and one—fifth gland—requiring mediastinotomy). There was one persistence (3%) because of a missed fourth undescended inferior parathyroid gland. Two recurrences 2 years after surgery were due to a fifth thoracic gland not shown in the preoperative Tc-PS. Conclusions Preoperative Tc-PS helped in the intraoperative identification of moderate or major ectopias in 4/33 patients but was not useful to prevent recurrences from highly ectopic glands not visualized before first-time surgery. Presented at the 2nd Biennial Congress of the ESES, May 2006, Krakow, Poland.     

Intraoperative parathyroid hormone measurement in patients with secondary hyperparathyroidism

HYPOTHESIS: Secondary hyperparathyroidism decreases renal clearance of parathyroid hormone (PTH). OBJECTIVE: To determine whether rapid PTH assays can be used to predict the success of a total parathyroidectomy to treat symptomatic secondary hyperparathyroidism. DESIGN: Case series from August 1 to December 31, 2000. SETTING: Tertiary referral center. PARTICIPANTS: Patients with symptomatic secondary hyperparathyroidism (n = 24) who underwent total parathyroidectomy and autotransplantation were included in the study. INTERVENTIONS: Blood samples for rapid PTH analyses were drawn from an indwelling catheter at the induction of anesthesia (baseline) and before (0 minutes), 10 minutes, and 30 minutes after the removal of the last parathyroid gland. Regular intact PTH (iPTH) assays were conducted later. MAIN OUTCOME MEASURE: If a patient's regular iPTH levels were below 65 pg/mL at 1 week or 3 months postoperatively, the operation was considered successful. RESULTS: All 24 patients had successful operations. Rapid PTH and regular iPTH correlated significantly at 0, 10, and 30 minutes. Rapid PTH levels decreased significantly at each time period and were 176 +/- 40.9 pg/mL (mean +/- SE) at 10 minutes. The percentage decrease in rapid PTH levels was 39.5% +/- 12.7% at 0 minutes, 75.1% +/- 6.2% at 10 minutes, and 91.0% +/- 0.1% at 30 minutes (mean +/- SE). A decrease of 60% or more from baseline PTH levels at 10 minutes and/or a decrease of 85% or more at 30 minutes predicted the successful removal of all parathyroid glands. CONCLUSIONS: A drop in PTH levels is delayed until 30 minutes after total parathyroidectomy; however, a rapid PTH assay 10 minutes after the removal of the last parathyroid gland is as accurate as an assay performed at 30 minutes postoperatively. Intraoperative PTH monitoring demonstrates relevant decreases in rapid PTH levels after parathyroidectomy that are similar to those previously documented in patients with primary hyperparathyroidism.     

Importance of a fifth parathyroid gland in the surgical treatment of hyperparathyroidism

Of 365 patients surgically treated for hyperparathyroidism at the University of Toronto hospitals, 3 had hypercalcemia due to an abnormal and ectopic fifth parathyroid gland. Autopsy studies have shown that a fifth gland may be present in 3% to 5% of patients with hyperparathyroidism. The possibility of an abnormal fifth gland as the cause of primary hyperparathyroidism should be considered when four glands of normal size and histology have been found in the neck, and such a gland should be sought in all patients with the diffuse hyperplasia of secondary hyperparathyroidism. The fifth gland is usually in the lower neck or upper mediastinum, frequently within the thymus. If present, it can usually be recognized and excised.     

Supernumerary parathyroid glands: Implications for the surgical treatment of secondary hyperparathyroidism

Of 20 patients who underwent parathyroidectomy for secondary hyperparathyroidism between 1978 and 1985, recurrent hypercalcemia occurred in 4. Three of the 4 patients had initially undergone total parathyroidectomy with autotransplantation (TP-A) and the fourth had been subjected to removal of 3 parathyroids with autotransplantation of a portion of 1 of these glands. None of the 5 patients treated by subtotal parathyroidectomy (STP) developed recurrence. One of the 3 cases of recurrent hyperparathyroidism after TP-A was due to graft overgrowth. Another was caused by supernumerary parathyroids subsequently removed at the time of reexploration of the neck. The third remains hypercalcemic after autograft excision and presumably still has a supernumerary gland in situ. The patient who developed recurrent hypercalcemia after removal of only 3 glands and autotransplantation remains hypercalcemic even after radical graft excision and reexploration of the neck and mediastinum. One patient treated early in the series by total parathyroidectomy without autotransplantation now has measurable levels of serum immunoreactive parathyroid hormone, presumably due to a small residual supernumerary gland. There is, thus, at least presumptive evidence of supernumerary parathyroid glands in 3 (15%) of the 20 patients in this series. The implications of this finding are discussed.

---

Resumen Entre 20 pacientes sometidos a paratiroidectomía por hiperparatiroidismo secundario entre 1978 y 1985, se presentó hipercalcemia recurrente en 4. Très de los 4 pacientes habían sido sometidos a paratiroidectomía total con autotrasplante (PT-A) y el cuarto había sido sometido a resección de 3 paratiroides con autotrasplante de una porción de 1 de las glándulas. Ninguno de los 5 pacientes tratados mediante paratiroidectomía subtotal (PTS) desarrolló recurrencia. Uno de los 3 casos de hiperparatiroidismo recurrente después de PT-A se debió a hipercrecimiento del trasplante. Otro fue causado por paratiroides supernumerarias, las cuales fueron ulteriormente resecadas en el curso de la reexploración del cuello. El tercero permanece hipercalcémico después de la resección del autotrasplante y presumiblemente tiene una glándula supernumeraria in situ. El paciente que desarrolló hipercalcemia recurrente después de la remoción de sólo 3 glándulas y autotrasplante permanece hipercalcémico aÚn después de la resección radical del trasplante y reexploración del cuello y del mediastino.Un paciente tratado al comienzo de la serie mediante paratiroidectomía total sin autotrasplante ahora exhibe niveles séricos mensurables de hormona paratiroidea inmunorreactiva, presumiblemente debidos a una pequena glándula supernumeraria residual. Existe, por lo tanto, por lo menos evidencia presuntiva de glándulas paratiroides supernumerarias en 3 (15%) de los 20 pacientes de esta serie. Se discuten las implicaciones de estos hallazgos.

---

Résumé Des 20 patients qui subirent une parathyroÏdectomie pour hyperparathyroÏdisme secondaire entre 1978 et 1985, quatre présentèrent une récidive de l'hypercalcémie. Trois parmi ces 4 avaient subi d'emblée une parathyroÏdectomie totale avec autotransplantation et la quatrième avait été soumis à l'ablation de 3 parathyroÏdes avec auto-transplantation d'une partie d'une de ces glandes. Aucun des 5 malades traités par parathyroÏdectomie subtotale ne fut victime de récidive. Un des 3 cas d'hyperparathyroÏdisme récidivant, après parathyroÏdectomie totale avec auto-transplantation, eu pour cause une hypertrophie de la greffe. Un autre fut provoqué par des parathyroÏdes en surnombre dont l'ablation fut pratiquée lors de la nouvelle exploration chirurgicale. Le troisième resta hyperclacémique après l'excision de la greffe, ce fait étant du probablement à l'existence d'une parathyroÏde surnuméraire laissée en place. Le patient qui développa une hypercalcémie, après exérèse de 3 parathyroÏdes suivie d'auto-transplantation, est resté hypercalcémique après ablation du greffon et réexploration du cou et du médiastin.Un malade traité précocément dans la série par parathyroÏdectomie totale sans auto-transplantation présente actuellement des quantités mesurables d'hormone parathyroÏdienne active sérique, fait dû vraisemblablement à la présence d'une petite glande surnuméraire résiduelle. Ces faits par conséquent plaident en faveur de la présence de glandes parathyroÏdes surnuméraires chez 3 (15%) des 20 patients de la série. Les implications de ces faits sont discutés dans l'article.

     

Contemporary surgical treatment of primary hyperparathyroidism without intraoperative parathyroid hormone measurement

Introduction

Primary hyperparathyroidism (pHPT) is usually the result of a single adenoma that can often be accurately located preoperatively and excised by a focused operation. Intraoperative parathyroid hormone (IOPTH) measurement is used occasionally to detect additional abnormal glands. However, it remains controversial as to whether IOPTH monitoring is necessary. This study presents the results of a large series of focused parathyroidectomy without IOPTH measurement.

Methods

Data from 2003 to 2014 were collected on 180 consecutive patients who underwent surgical treatment for pHPT by a single surgeon. Preoperative ultrasonography and sestamibi imaging was performed routinely, with computed tomography (CT) and/or selective venous sampling in selected cases. The preferred procedure for single gland disease was a focused lateral approach guided by on-table surgeon performed ultrasonography. Frozen section was used selectively and surgical cure was defined as normocalcaemia at the six-month follow-up appointment.

Results

Focused surgery was undertaken in 146 patients (81%) and 97% of these cases had concordant results with two imaging modalities. In all cases, an abnormal gland was discovered at the predetermined site. Of the 146 patients, 132 underwent a focused lateral approach (11 of which were converted to a collar incision), 10 required a collar incision and 4 underwent a mini-sternotomy. At 6 months following surgery, 142 patients were normocalcaemic (97% primary cure rate). Three of the four treatment failures had subsequent surgery and are now biochemically cured. There were no complications or cases of persistent hypocalcaemia.

Conclusions

This study provides further evidence that in the presence of concordant preoperative imaging, IOPTH measurement can be safely omitted when performing focused parathyroidectomy for most cases of pHPT.     

Function in athymic nude mice of parathyroid heterografts from patients with primary hyperparathyroidism and secondary hyperparathyroidism

Heterotransplantation of adenomatous parathyroid glandular tissue from humans with primary hyperparathyroidism into athymic nude mice creates a unique animal model of this disease. The mice manifest high concentrations of both midregion/C-terminal human parathyroid hormone and biologically active intact human parathyroid hormone relative to either mice with no implants or mice that received normal human parathyroid tissue. Secretion of these substances is maintained in most mice for at least 9 to 13 months after implantation. In addition, animals that have experienced implantation exhibit other characteristics associated with human primary hyperparathyroidism including relative hypercalcemia and increased renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity. We also measured these parameters in a group of nude mice that received transplantation of a similar mass of hyperplastic parathyroid tissue that was obtained from patients with uremic secondary hyperparathyroidism. Although we hypothesized that the level of human parathyroid hormone secretion from these implants would fall over time in response to the normal host environment, hormone levels remained as high as those in recipients of adenomatous heterografts, even after 9 to 13 months. Moreover, similar biologic effect of the excess parathyroid hormone (i.e., relative hypercalcemia, hyperphosphatasemia, and increased 1,25-dihydroxyvitamin D biosynthesis) were detected. These animal models should prove extremely useful in supplementing our understanding of hyperparathyroid disorder in man.