Surgical treatment of secondary hyperparathyroidism in patients with chronic renal failure: reevaluation of indications for parathyroidectomy

On reviewing the preoperative clinical and laboratory findings and the surgical response seen in our series of 32 patients with renal hyperparathyroidism, the indication for parathyroidectomy was reevaluated. During the 5-year period from 1975 to 1979, parathyroid resection was performed in 9 patients who had various conditions for which surgery had been thought indicated. During the following period from January 1980 to March 1985, parathyroidectomy was carried out on 23 patients all of whom had roentgenologic evidence of generalized fibrous osteitis except for two whose indication for surgery was an elevation of the serum alkaline phosphatase level more than 45 KA units. The resected parathyroid glands had increased to 1 g or more in total weight in all the 25 patients who showed distinct postoperative improvement. Laboratory evidence indicating the presence of generalized fibrous osteitis, such as subperiosteal resorption on phalanx roentgenograms and high serum alkaline phosphatase level, along with marked elevation of the plasma immunoreactive parathyroid hormone level, proved to be a good indicator for medically uncontrollable secondary hyperparathyroidism. Fracture, heterotopic calcification, pruritus or persistent hypercalcemia was not a parameter of severe hyperparathyroidism warranting parathyroid resection, unless there was concomitant evidence of fibrous osteitis. The preoperative use of the recently developed noninvasive techniques for parathyroid localization also proved to be useful in detecting the parathyroid glands large enough to fulfill the requirements for parathyroidectomy.     

Endoscopic Ultrasound-Guided Fine-Needle Aspiration With Aspirate Assay to Diagnose Suspected Mediastinal Parathyroid Adenomas

ObjectiveTo describe our experience with mediastinal parathyroid adenomas diagnosed by endoscopic ultrasound-guided fine-needle aspiration (EUSFNA) and measurement of parathyroid hormone.MethodsWe describe the clinical and pathologic findings and diagnostic techniques used in 2 study patients.ResultsPatient 1 was a 54-year-old man with persistently elevated serum calcium and parathyroid hormone concentrations despite removal of a right inferior parathyroid adenoma. An echoendoscope was used to identify the lesion and to perform FNA. The parathyroid hormone concentration measured in the aspirated material was 1800 pg/mL. Pathologic examination of the resected specimen revealed a 29.7-g parathyroid adenoma. Patient 2 was an 86-year-old woman with recurrent hyperparathyroidism. A linear array echoendoscope was used to perform FNA of the lesion in her mediastinum. The parathyroid hormone concentration measured in the aspirated specimen was 6905 pg/mL.ConclusionsPreoperative localization of recurrent or persistent hyperparathyroidism is often difficult. EUSFNA allows evaluation of masses, such as those found in the mediastinum, that are poorly evaluated by other imaging modalities. This technique may be a useful adjunct in diagnosing mediastinal parathyroid adenomas. (Endocr Pract. 2010;16:437-440)     

'Suppressed' double adenoma--a rare pitfall in minimally invasive parathyroidectomy

Since the introduction of a quick intraoperative parathyroid hormone (QPTH) assay, complete removal of hyperfunctioning parathyroid tissue can be proven during surgery. We report on a scintigraphically and biochemically documented patient with persistent primary hyperparathyroidism (PHPT) caused by suppressed hyperfunctioning parathyroid tissue. A left lower enlarged parathyroid gland was resected by minimally invasive open parathyroidectomy. QPTH measurements confirmed complete resection of hyperfunctioning tissue and histology showed a tumorous enlarged left lower parathyroid gland. The patient was normocalcemic until 1 month after surgery, when serum calcium increased again. A MIBI scan 6 months after surgery showed no evidence of hyperfunctioning parathyroid tissue. After an increase of PTH, a third MIBI scan another 3 months later was performed. Increased tracer uptake behind the lower pole of the right thyroid lobe was seen and confirmed by ultrasonography. Another tumorous enlarged parathyroid gland was removed. These findings support the hypothesis that smaller yet abnormal parathyroid glands can be suppressed and may become hypersecretory if left in situ after surgical removal of the larger gland.     

Methylene Blue for Rapid Identification of the Parathyroids

Rapid identification of parathyroid tissue has been rendered possible by preoperative intravenous infusion of methylene blue before exploration of the neck. The technique has been used on 17 patients with thyroid and parathyroid disorders. In all cases one or more of the parathyroids have been demonstrated with histological confirmation, but with greater experience almost all have been shown readily. This has resulted in an appreciable reduction in operating time, and the method should help to reduce the high incidence of clinical hypoparathyroidism after total thyroidectomy.     

Serum parathyroid hormone concentration measured by highly sensitive assay in post-thyroidectomy hypocalcemia of patients with Graves' disease

To investigate the role of parathyroid function in transient hypocalcemia after subtotal thyroidectomy for Graves' disease, the serum parathyroid hormone (PTH) concentration and nephrogenous (N) cAMP were measured in 16 patients before and after surgery. Serum PTH was measured with two commercially available kits (PTH-M, PTH-C), PTH-M is a recently developed highly sensitive assay using an antibody recognizing the mid-portion of human PTH and a synthetic 125I-tyr45-human PTH (43-68) as a radioligand. One of the 16 patients had severe clinical tetany and had a markedly lower PTH-M concentration and NcAMP after thyroidectomy. However, no significant change in serum PTH-M, PTH-C and NcAMP were observed in the other patients, although their serum calcium (Ca) concentrations decreased significantly. The Data were analyzed by dividing the patients according to the change in serum Ca or PTH. Serum PTH-M and PTH-C significantly decreased in 4 patients whose serum Ca clearly decreased after surgery. Serum Ca on the first postoperative day was significantly lower in patients whose serum PTH decreased after thyroidectomy than in patients whose serum PTH did not. Furthermore, the serum Ca concentration was significantly correlated with PTH-M, and with NcAMP on the third postoperative day. These data proved that hypofunction of the parathyroid gland is important in transient hypocalcemia after subtotal thyroidectomy for Graves' disease. The pathogenetic mechanism of transient hypocalcemia was discussed in comparison with the data from a patient who had overt parathyroid injury.     

A case report: Giant cystic parathyroid adenoma presenting with parathyroid crisis after Vitamin D replacement

ABSTRACT: BACKGROUND: Parathyroid adenoma with cystic degeneration is a rare cause of primary hyperparathyroidism. The clinical and biochemical presentation may mimic parathyroid carcinoma. Case Presentation: We report the case of a 55 year old lady, who had longstanding history of depression and acid peptic disease. Serum calcium eight months prior to presentation was slightly high, but she was never worked up. She was found to be Vitamin D deficient while being investigated for generalized body aches. A month after she was replaced with Vitamin D, she presented to us with parathyroid crisis. Her corrected serum calcium was 23.0 mg/dL. She had severe gastrointestinal symptoms and acute kidney injury. She had unexplained consistent hypokalemia until surgery. Neck ultrasound and CT scan revealed giant parathyroid cyst extending into the mediastinum. After initial medical management for parathyroid crisis, parathyroid cystic adenoma was surgically excised. Her serum calcium, intact parathyroid hormone, creatinine and potassium levels normalized after surgery. CONCLUSION: This case of parathyroid crisis, with very high serum calcium and parathyroid hormone levels, is a rare presentation of parathyroid adenoma with cystic degeneration. This case also highlights that Vitamin D replacement may unmask subclinical hyperparathyroidism. Consistent hypokalemia until surgery merits research into its association with hypercalcemia.     

Somatostatin analogues do not affect calcium metabolism in patients with acromegaly and primary hyperparathyroidism [corrected] due to MEN 1-like syndrome

Patients with clinical features of MEN 1 without mutations in the menin gene fulfill the criteria of MEN1-like syndrome. Primary hyperparathyroidism (PHP) is the most frequent clinical finding in both syndromes and is usually treated by surgery. However, PHP has been reported to respond to somatostatin analogues (SSA) in MEN 1 patients. 7 patients with PHP in the context of MEN 1-like syndrome (and absence of mutations in the menin gene) were enrolled in the study and treated with SSA for 6 months for the non-PHP disease before parathyroidectomy. Serum ionized calcium, phosphorus, and PTH concentrations, and 24-h urinary calcium and phosphorus excretion were measured before and after SSA therapy. Mean serum ionized calcium, phosphorus, and PTH concentrations did not significantly change after a 6-month course with SSA. SSA scintigraphy did not reveal uptake in the neck region corresponding to the parathyroid adenoma identified at surgery and confirmed at histology. However, immunohistochemistry revealed SS-type 2A receptor in parathyroid tissue samples of 6 out of 7 patients. SSA therapy does not affect calcium-phosphorus metabolism in patients with MEN 1-like syndrome, suggesting that the drug has no role in controlling PHP in these subset of patients.     

Risk of renal stone events in primary hyperparathyroidism before and after parathyroid surgery: controlled retrospective follow up study

AimTo study the risk of renal stone episodes and risk factors for renal stones in primary hyperparathyroidism before and after surgery.DesignRegister based, controlled retrospective follow up study.SettingTertiary hospitals in Denmark.Participants674 consecutive patients with surgically verified primary hyperparathyroidism. Each patient was compared with three age- and sex-matched controls randomly drawn from the background population. Hospital admissions for renal stone disease were compared between patients and controls. Risk factors for renal stones among patients were assessed.ResultsRelative risk of a stone episode was 40 (95% confidence interval 31 to 53) before surgery and 16 (12 to 23) after surgery. Risk was increased 10 years before surgery, and became normal more than 10 years after surgery. Stone-free survival 20 years after surgery was 90.4% in patients and 98.7% in controls (risk difference 8.3%, 4.8% to 11.7%). Patients with preoperative stones had 27 times the risk of postoperative stone incidents than controls. Before surgery, males had more stone episodes than females and younger patients had more stone episodes than older patients. Neither parathyroid pathology, weight of removed tissue, plasma calcium levels, nor skeletal pathology (fractures) influenced the risk of renal stones. After surgery, younger age, preoperative stones and ureteral strictures were significant risk factors for stones.ConclusionsThe risk of renal stones is increased in primary hyperparathyroidism and decreases after surgery. The risk profile is normal 10 years after surgery. Preoperative stone events increase the risk of postoperative stones. Stone formers and non-stone formers had the same risk of skeletal complications.

What is already known on this topic

Patients with primary hyperparathyroidism have an increased risk of renal stone eventsThe extent to which parathyroid surgery reduces the risk of further stones is unclear

What this study adds

The risk of a new stone event was 8.3% higher in patients than in controls after surgeryIn patients with stone disease before operation the risk rate for a postoperative stone event was 27times that in controlsThe risk of a renal stone event was higher than the risk among controls until more than 10 years after surgery     

Chirurgie de l’hyperparathyroïdie primaire en 2008

In recent years, different minimally invasive techniques of parathyroidectomy have been described. The concept of these limited explorations is based on the fact that 85% of patients will have a single-gland disease. Minimally invasive techniques are targeted on one specific parathyroid gland and in most cases the exploration of other glands is not performed. These interventions are today possible for three main reasons: the available imaging techniques permit to localize the diseased gland, the use of rapid intraoperative PTH assay can confirm the successful extirpation, new instrumentation and miniaturized cameras have been adapted for this kind of surgery. Not all patients presenting with primary hyperparathyroidism are candidate for this surgery. Contraindications are mainly due to a large goiter, previous surgery in the parathyroid vicinity, suspicious multiglandular disease and equivocal preoperative localization studies. Currently 60% of patients with primary hyperparathyroidism can benefit of these techniques. Studies comparing conventional parathyroid surgery to minimally-invasive techniques have shown a diminution of postoperative pain and better cosmetic results with minimally-invasive techniques. If early results are similar to those obtained with conventional parathyroidectomies, it is still too soon to evaluate what will be the recurrence rate of these new techniques. One can expect that minimally invasive and conventional parathyroid surgery will probably turn out to be complementary in the near future.     

Scintigraphie des parathyroïdes double isotope Tc-MIBI/I dans l’hyperparathyroïdisme primaire : comparaison entre un protocole d’acquisition planaire et une TEMP de soustraction couplée à la TDM

In patient with primary hyperparathyroidism, preoperative imaging first objective is to determine accurately and reliably position and anatomic localization of enlarged parathyroid gland in order to guide surgeon for gland removal and to permit minimally invasive surgery. Although subtraction planar scintigraphy is an efficient imaging to diagnose hyperfunctioning parathyroid, the lack of anatomical reference for this single imaging technique could be obviated by hybrid imaging. We compared, in 23 patients with primary hyperparathyroidism, a planar scan of neck and mediastinum associated with a cervical anterior pinhole scan to a subtraction (¹²³I/^99mTc-MIBI) SPECT scan of neck and mediastinum fused with CT. Surgical and histopathologic findings were used as the standard of truth. Subtraction SPECT/CT appeared to be more sensitive and specific than planar protocol to diagnose and to accurately localize pathologic parathyroid. Sensitivity was 76 and 56 %, specificity was 100 and 80 % for hybrid SPECT/CT and planar protocol respectively. SPECT protocol was typically more efficient to diagnose pathologic parathyroid derived from upper gland and for patient with concomitant nodular goiter.     

Mediastinal parathyroidectomy with the da Vinci robot

Mediastinal parathyroid glands are often located in a position which is inaccessible through a cervical approach. Because of the significant morbidity of open surgery, the need for minimal invasive approaches is high. More recently, robotic systems have been introduced to refine the dissection and optimize the view in the mediastinal region. We present two cases. The first case is a 34-year-old woman who was diagnosed with primary hyperparathyroidism. Because a bilateral neck dissection disclosed no parathyroid adenoma, we performed a parathyroid sestamibi scan and computed tomographic scan of neck and mediastinum to look for aberrant parathyroid glands. Both showed a parathyroid adenoma in the mediastinum on the left side. The second case is a 66-year-old man. A sestamibi scan showed a parathyroid adenoma of 3 cm in the superior mediastinum which was confirmed by and computed tomographic scan. In both cases, we performed a parathyroidectomy with the da Vinci robotic system through a left-sided approach. Three thoracoports were inserted around the mammary gland for the robot and a fourth auxiliary port was positioned in between. Single-lung ventilation was installed, and the mediastinum was entered by opening the parietal pleura along the left phrenic nerve. The upper margin for dissection was the left brachiocephalic vein that was followed until the right pleura. All the tissue in front of the pericardium was dissected en bloc. The sinking test of the nodule and a preoperative frozen section analysis confirmed the diagnosis of parathyroid adenoma, which was also proven by rapid parathyroid hormone analysis. The resection of a parathyroid adenoma from the aortopulmonary window represents an ideal case for robotic surgery.     

Coexistence of tumor-induced osteomalacia and primary hyperparathyroidism

ObjectiveTo present an unusual case of coexisting tumor-induced osteomalacia (TIO) and primary hyperparathyroidism (PHPT).MethodsWe report the clinical features, imaging studies, and the results of laboratory investigations before and after surgical resection of both a soft-tissue tumor and a parathyroid adenoma.ResultsA 44-year-old woman was referred to the endocrinology department with a diagnosis of PHPT accompanied by unusually severe hypophosphatemia, despite having received treatment with cinacalcet. Debilitating muscle weakness and bone pain, severe phosphaturia and hypophosphatemia, inappropriately normal calcitriol, and elevated fibroblast growth factor-23 and intact parathyroid hormone levels raised the suspicion of coexisting TIO and PHPT. Imaging studies were negative, but histologic characteristics of a palpable subcutaneous mass from the patient’s thigh revealed a phosphaturic mesenchymal tumor. Complete remission after surgical removal of both the soft-tissue tumor and the parathyroid adenoma confirmed the diagnosis.ConclusionThe coexistence of TIO and PHPT has not been described before and can cause life-threatening hypophosphatemia. Diagnosis and localization of the tumor is of paramount importance since surgery is the treatment of choice for both TIO and PHPT. (Endocr Pract. 2011;17:e144-e148)     

终末期肾病患者行甲状旁腺切除对颈动脉钙化的影响

目的:探讨对终末期肾病患者行甲状旁腺切除对颈动脉钙化的影响.方法:选择我院2009年10月至2010年12月收治的20例继发性甲状旁腺功能亢进的终末期肾病患者,行甲状旁腺切除术,对患者术前、术后进行颈动脉彩超检查颈动脉钙化情况,并将患者术前、术后的血钙、血磷、钙磷乘积、PTH、C反应蛋白、血红蛋白、白蛋白等指标进行比较.结果:与术前比较,术后患者颈动脉钙化斑块有明显减少,血钙、血磷、钙磷乘积、PTH、C反应蛋白均明显降低,差异性有显著(P＜0.05);血红蛋白较术前明显升高(P＜0.05).结论:切除甲状旁腺(PTX)能安全有效的降低甲状旁腺素水平、改善钙磷代谢紊乱,并控制颈动脉钙化的进展.     

Intérêt de l’interprétation collégiale de l’échographie cervicale,de la scintigraphie 99mTc-MIBI et de la TEP-TDM à la 18-Fluorocholine dans l’hyperparathyroïdie primaire : expérience du service de médecine nucléaire de l’hôpital Cochin

ObjectivesThis study aims to assess performances of preoperative conventional imaging (99mTc-MIBI scintigraphy, cervical Ultrasonography) and 18F-fluorocholine PET/CT (FCH PET/CT) exams in the detection of hyperfunctioning parathyroid gland(s) in patients operated from primary hyperparathyroidism (pHPT).MethodsBefore surgery, 51 consecutive patients with biochemically confirmed pHPT had successively cervical ultrasonography (cUS), 99mTc-MIBI scintigraphy and FCH PET/CT, all performed in the same Nuclear Medicine Department. 99mTc-MIBI scintigraphy were performed immediatly after cUS and interpreted by same operators. FCH PET/CT exam were interpreted independently by two nuclear medicine physicians. An additional interpretation session integrating the three imaging modalities read in consensus as a combined imaging set was performed.ResultsAt surgery, 69 lesions were removed: 32 parathyroid adenoma and 37 parathyroid hyperplasia. 70% of patients had single-gland disease and 30% had multiglandular disease at histopathology analysis. In the patient-based analysis, sensitivity and accuracy in the detection of single gland disease) for FCH PET/CT, cUS and for 99mTc-MIBI scintigraphy were 86% [0.71–0.94] and 86% [0.70–0.95], 69% [0.52–0.81] and 69% [0.51–0.83], 40% [0.26–0.56] and 40% [0.24–0.58], respectively. Sensitivity and accuracy of the combined imaging set for the detection of single gland disease were 94% [0.81–0.99] and 94% [0.81–0.99].ConclusionOur results suggest that cUS/99mTc-MIBI scintigraphy and FCH PET/CT interpreted during a comprehensive session could be the ideal practice to precisely localize parathyroid lesion(s) in patients with pHPT before surgery.     

Medicine and surgery of amphibians

Amphibians are most notably characterized by their glandular skin, which they shed regularly and ingest routinely. It is advisable to handle amphibians only with protective gloves to avoid damaging their skin. These animals absorb water readily across the skin as a means of maintaining hydration. They also easily absorb drugs and anesthetics that are applied directly to the skin. Investigators commonly utilize cutaneous respiration in amphibians and evaluate skin abnormalities via wet mount preparations, skin scrapes, and biopsy. The examination of blood samples can be useful in evaluating the status of ill amphibians, although the similarity in function of amphibian blood cell types and those of other species is largely unknown. If surgery is required, it is necessary to fast the animals before surgery, and to monitor their hydration. The wet environment required for amphibian surgery makes sterile technique challenging, and it is advisable to institute prophylactic antibiotic therapy before the procedure. The anesthetic of choice for amphibian surgery is tricaine methanesulfonate (MS-222). Postoperative recommendations include fluids, nutritional support if necessary, and analgesia. If euthanasia is required, MS-222 overdose or pentobarbital injection are the preferred methods.     

Regulation of the receptor-mediated cyclic AMP response of kidney to parathyroid hormone in the vitamin D-deficient rat

Rats fed a diet deficient in vitamin D were found to exhibit a refractory cyclic AMP response of kidney slices to parathyroid hormone and a marked decrease in membrane parathyroid hormone-dependent adenylate cyclase activity. Both the characteristic calcium deficiency (hypocalcemia) and secondary elevation of circulating parathyroid hormone appeared before the first noticeable decrease in hormone-dependent enzyme activity. After repletion of D-deficient rats with vitamin D₂, we found that serum calcium and parathyroid hormone were both restored to normal levels before the depressed enzyme response to the hormone was reversed. Moreover, infusion of parathyroid hormone into vitamin D-replete rats led to a marked reduction in parathyroid hormone-dependent adenylate cyclase activity, which was partly restored to control level 3 hours after discontinuing the hormone infusion. Taken as a whole, this study suggests that the elevated endogenous parathyroid hormone in the vitamin D-deficient rat is involved in the “down-regulation” of renal cyclic AMP responsiveness to the hormone. However, these experiments do not rule out the possibility that calcium deficiency and/or vitamin D per se participate in the regulation of the renal cyclic AMP response to parathyroid hormone.     

Feasibility and long-term results of focused radioguided parathyroidectomy using a &quot;low&quot; 37 MBq (1 mCi) <Superscript>99m</Superscript>Tc-sestamibi protocol

Aim of the present study was to investigate the feasibility and long-term results of focused radioguided parathyroidectomy using a "low" 37 MBq (1 mCi) ^99mTc-sestamibi dose protocol compared to conventional "high 740 MBq (20 mCi) ^99mTc-sestamibi dose protocol" in patients with primary hyperparathyroidism (PHPT). The data of focused radioguided surgery obtained in a group of 320 consecutive PHPT patients with high probability of the presence of a solitary parathyroid adenoma (PA) were studied. All patients underwent preoperative imaging work-up of double-tracer ^99mTc-pertechnetate/^99mTc-sestamibi subtraction parathyroid scintigraphy (Sestamibi scintigraphy) and high resolution neck ultrasound (US). In 301/320 patients (96.6%) focused minimally invasive radioguided surgery was successfully performed by administering a "low" 37 MBq (1 mCi) ^99mTc-sestamibi dose in the operating room 10 minutes before operation. No major intraoperative complications were recorded. Focused radioguided surgery required a mean time of 32 min and a mean hospital stay of 1.2 days. Local anesthesia was applied in 75 patients, 66 of whom (88%) were patients older than 65 years with comorbidities contraindicating general anesthesia. No case of persistent or recurrent PHPT was observed during post-surgical follow-up (range = 18–70 months; mean +/- SD = 15.3 +/- 9.1 months). Radiation exposure dose to the operating surgeon was 1.2 μSi/hour with the "low 37 MBq (1 mCi) ^99mTc-sestamibi dose", and less than 1.0 μSi/hour for the other operating-room personnel. Focused low dose radioguided parathyroidectomy is a safe and effective means to localize parathyroid adenomas in patients affected by solitary PA thus reducing by 20 fold the radiation exposure dose to the patients and operating room personnel.     

Intérêt de l’imagerie hybride TEMP/TDM dans la localisation des glandes parathyroïdes ectopiques : à propos de 3 cas

The presence of a parathyroid gland in ectopic position constitutes one of the leading causes of surgery failure. For this purpose, scintigraphy takes a major place in the anatomical localization of pathological parathyroid and so facilitates its treatment. The advent of hybrid cameras combining single photon emission tomography to CT (SPECT/CT) has further strengthened the contribution of this imaging modality in the precise localization of ectopic parathyroid and its anatomical relationships. The objective of our work is to illustrate the interest of hybrid imaging SPECT/CT, compared to planar scintigraphy and ultrasounds within the framework of primary hyperparathyroidism, particularly ectopic situation through three cases.