Correlation of perioperative biochemical variables with single adenoma weight in patients with primary hyperparathyroidism.

BACKGROUND: Single parathyroid adenoma is the main cause of primary hyperparathyroidism (PHPT), with surgery remaining the gold standard for its treatment. The ability to preoperatively predict the parathyroid adenoma size and could facilitate the decision about the extent of surgical exploration. It is reasonable to hypothesize that the perioperative levels of PHPT-related variables (i.e. calcium, parathormone, phosphate) may predict the adenoma weight or/and demonstrate whether the adenoma is successfully removed or not. Aim of this study is to explore the relationship between perioperative biochemical values and adenoma weight. Secondarily, we investigated the relationship between adenoma weight and uni-/bilateral neck exploration. METHODS: Retrospective study of all patients undergone surgery for primary hyperparathyroidism due to single adenoma in a tertiary university hospital in Germany during a 6-year period. Following variables were analyzed: preoperative serum calcium, phosphorus and parathormone, intraoperative parathormone before and after adenoma excision, intraoperative PTH decrease, postoperative serum calcium and parathormone (PTHpostop-pg/ml), calcium and PTH decrease. Bivariate correlations were calculated by the Spearman's correlation test at the 95% significance level. RESULTS: A total of 339 patients were included in the study. The median age of the patients was 60 years (range 21-90) and 77% were females. The median adenoma weight was 1 g (range 0.1-11). Adenoma weight correlated strong with maximum adenoma diameter (r = 0.72, p < 0.05), moderate with preoperative parathormone (r = 0.44) and parathormone decrease (r = 0.27), whereas there was no correlation with the intraoperative PTH decrease (r = 0.02). There was also a borderline (moderate to weak) correlation with pre- and postoperative calcium levels (r = 0.21 and r = 0.23 respectively) and a negative borderline correlation with phosphorus (r = - 0.21). Patients who required bilateral neck exploration, had significantly lighter adenomas (median weight 0.8 g vs 1.1 g, p = 0.005). CONCLUSIONS: We conclude that preoperative PTH levels may only serve as an approximate guide to adenoma weight, as direct preoperative prediction is not possible. Serum calcium levels, PTH and calcium decrease correlate only weak with adenoma weight. Patients who require bilateral neck exploration, have significantly (20-25%) lighter adenomas.

Parathyroid Adenomas in Adults and Adolescents. Critical Appraisal and Surgical Strategy in 18 Cases.

Background: Our study underline scarcity of isolated case reports or small case series of parathyroid adenoma (PA) published in autochthonous medical literature,their variable clinical expression among the "historic" varieties but also the diagnostic difficulties and delays of diagnosis as well consecration of surgery as the golden therapeutic standard of this disorder. PATIENTS AND METHOD: Demographic, clinical presentations, laboratory and imaging data, operative findings and procedures together with pathology account and outcome from the case reports of 18 patients with documented PHP were retrospectively analyzed. Results: The male/female ratio was 1/5, with ages ranging from 16 to 58 (mean 46) years. Renal stones (n=9) and bone sufferings (n=6) were the most common modes of presentation. To these were added psychiatric and neuromuscular complaints, digestive disorders (pancreatitis and peptic ulcer) arterial hypertension and presence of a palpable nodule. Mean serum calcium and phospho-rus, alkaline phosphatase and PTH dosage together with parathyroid ultrasound and 99m Tc sestamibi scintigraphy are the most useful parameters for diagnosis. Eighteen adenomectomies were performed of which bilateral neck exploration was done in 16 patients and minimally invasive approach in the remaining two cases. In 9 situations concomitant thyroid exeresis for associated lesions or tactical purpose were done. Pathology revealed single adenoma consisting of main and oxyphil cells in 17 cases. In one case an atypical adenoma was identified and in another case three years after removal of a benign adenoma the subject presented a clinical ipsilateral recurrence which provided to be a carcinoma. Postoperative clinical and humoral outcome was favorable in all situations less the case of carcinoma which died after 14 months. Conclusions: Despite the rarity and difficulties of diagnosis in cases of PA, practitioners must be aware of potential existence of these lesions in order to apply as early and appropriate treatment where surgery is the gold standard.

Cinacalcet hydrochloride relieves hypercalcemia in Japanese patients with parathyroid cancer and intractable primary hyperparathyroidism.

Pharmacological treatment of hypercalcemia is essential for patients with parathyroid carcinoma and intractable primary hyperparathyroidism (PHPT). Use of the calcimimetic cinacalcet hydrochloride (cinacalcet) is an option to treat such patients. We investigated the efficacy and safety of cinacalcet in Japanese patients with parathyroid carcinoma and intractable PHPT. Five Japanese patients with parathyroid carcinoma and two with intractable PHPT were enrolled in an open-label, single-arm study consisting of titration and maintenance phases. Cinacalcet doses were titrated until the albumin-corrected serum calcium concentration decreased to 10.0 mg/dL or less or until dose escalation was considered not necessary or feasible. Serum calcium concentration at the baseline was 12.1 ± 1.3 mg/dL (mean ± standard deviation; range 10.4-14.6 mg/dL) and decreased to 10.1 ± 1.6 mg/dL (range 8.6-13.3 mg/dL) at the end of the titration phase with cinacalcet at a dosage of up to 75 mg three times a day. At the end of the titration phase, at least a 1 mg/dL reduction in serum calcium concentration from the baseline was observed in five patients (three with carcinoma and two with PHPT), and it decreased to the normocalcemic range in five patients (three with carcinoma and two with PHPT). Common adverse events were nausea and vomiting. One patient discontinued participation in the study because of an adverse event, liver disorder. Cinacalcet effectively relieved hypercalcemia in 60% of the Japanese patients with parathyroid carcinoma and might be effective in those with intractable PHPT. The drug might be tolerable and safe at a dosage of at most 75 mg three times a day.

Focused parathyroidectomy without intra-operative parathyroid hormone monitoring for primary hyperparathyroidism: results in a low-volume hospital.

BACKGROUND: The role of routine intra-operative parathyroid hormone monitoring for sporadic primary hyperparathyroidism is contentious. Satisfactory results can be achieved in high-volume centres. The results of low-volume hospitals are rarely studied. METHODS: A retrospective, non-comparative study was conducted. From November 2002 to October 2012, 105 patients with clinically sporadic primary hyperparathyroidism underwent focused parathyroidectomy without intra-operative parathyroid hormone monitoring. Single adenoma was localised on pre-operative ultrasonography or sestamibi scan. The cure rate, surgical complication rate and pathology findings were evaluated. RESULTS: Most of the operations (63.8 per cent) were performed under local anaesthesia. All but two patients (98.1 per cent) were cured after surgery. There was only one case of double adenomas. No recurrent hyperparathyroidism was observed after a mean follow up of 56.9 months. Surgical complications comprised two cases (1.9 per cent) of transient vocal fold palsy and one case (1.0 per cent) of permanent vocal fold palsy. Seven patients (6.7 per cent) suffered temporary hypocalcaemia. CONCLUSION: Satisfactory results of focused parathyroidectomy without routine intra-operative parathyroid hormone monitoring for appropriately selected primary hyperparathyroidism cases can be attained in a low-volume hospital.

Refractory hypercalcaemia secondary to parathyroid carcinoma: response to high-dose denosumab.

OBJECTIVE: Hypercalcaemia is an important cause of increased morbidity and mortality in patients with parathyroid carcinoma. Surgical resection is the mainstay of treatment but, equally, managing hypercalcaemia is of paramount importance. At present, few therapies have been shown to be effective in the most severe cases. This report describes the efficacy of denosumab in a patient with parathyroid carcinoma when conventional therapies had been shown to be relatively ineffective.SUBJECT, METHODS AND RESULTS: A 50-year-old man presented with symptomatic hypercalcaemia 1 year after the surgery for his parathyroid carcinoma. Investigations revealed raised serum calcium and parathyroid hormone concentrations consistent with the recurrence of the disease. Imaging failed to localise any surgically remediable foci. Medical management with loop diuretics, calcimimetics and bisphosphonates failed to provide a sustained response. Denosumab, as a monthly injection, led to a gradual decrement in his peak calcium concentrations with the values now persistently below 3 mmol/l. CONCLUSIONS: Denosumab, a fully human MAB that binds to the 'receptor activator of nuclear factor κB ligand (RANKL)', was shown to have a profound effect in modulating malignant hypercalcaemia. This medication should be considered as an effective option in patients with refractory hypercalcaemia secondary to parathyroid carcinoma.

The effectiveness of low-dose versus high-dose 99mTc MIBI protocols for radioguided surgery in patients with primary hyperparathyroidism.

OBJECTIVE: The aim of this study was to compare the efficacy of low-dose and high-dose (99m)Tc methoxy isobutyl isonitrile (MIBI) protocols in intraoperative localization of parathyroid adenomas by means of a gamma probe in patients with primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: The study included 62 patients with PHPT who were divided into two groups. Group 1 consisted of 32 patients who were injected with a low dose (1 mCi) of (99m)Tc MIBI in the surgical suite 10 min before incision. Group 2 included 30 patients who were intravenously administered a high dose (15 mCi) of (99m)Tc MIBI 2 h before surgery. With the aid of a gamma probe, intraoperative localization of parathyroid adenomas was performed in both groups of patients who underwent minimally invasive parathyroidectomy. All lesions thought to be parathyroid adenomas were excised and subsequently evaluated histopathologically. RESULTS: All parathyroid adenomas in both groups were localized and excised by means of an intraoperative gamma probe. The sensitivity, specificity, and accuracy of low-dose and high-dose (99m)Tc MIBI protocols in the intraoperative localization of adenomas in patients with PHPT were 100%. CONCLUSION: In the light of these findings, we conclude that low-dose (99m)Tc MIBI may be preferred to intraoperative identification of parathyroid adenomas by means of a gamma probe in PHPT patients because it appears to be as effective as high-dose (99m)Tc MIBI. Moreover, the low-dose protocol does not have the disadvantages of high-dose protocol.

Evaluating real-world use of cinacalcet and biochemical response to therapy in US hemodialysis patients.

BACKGROUND/AIMS: Data describing real-world use and effectiveness of cinacalcet are limited. We aimed to characterize predictors of treatment and changes in secondary hyperparathyroidism (SHPT) biochemistry after cinacalcet initiation. METHODS: We studied 25,250 in-center hemodialysis patients from a large dialysis provider, alive through November 2004, with no prior cinacalcet prescription. Patients were followed until initiation of cinacalcet, censoring, death, or July 31, 2007. Initiators were further followed for dose titration and discontinuation. Predictors of these events were evaluated using Cox proportional hazards modeling. Biochemical parameters and other SHPT medication use were compared between baseline, pre-initiation, and post-initiation time points. RESULTS: Over an average of 1.25 years of follow-up, 30% of patients initiated cinacalcet therapy. Between baseline and initiation (mean of 386 days), parathyroid hormone (PTH) and phosphorus levels increased 78 and 7%, respectively, in these patients. After adjustment, cinacalcet initiation was associated with higher SHPT severity, younger age, African-American race, higher phosphorus levels, and more comorbidity. Within 1 month of initiation, median PTH was reduced by 15-30% and phosphorus by 3-5%. Reductions were sustained or increased over 12 months, depending on initiating PTH level and whether dose up-titration occurred. Discontinuation was common, although many patients reinitiated. CONCLUSIONS: A substantial proportion of patients experienced SHPT progression and initiated cinacalcet treatment. Reductions in biochemistry varied by disease severity and whether doses were titrated.

Parathyroid carcinosarcoma: a rare form of parathyroid carcinoma with normal parathyroid hormone levels.

Parathyroid carcinosarcoma was first described by Nacamuli et al in 2002. We present the second case of this rare disease. This rare carcinosarmoca presented as a parathyroid carcinoma with uncharacteristically normal parathyroid hormone levels. The patient is a 57-year-old woman with long-standing right-sided vocal cord paralysis presented with a progressive 3 × 2 × 3 cm mass in the right neck. She had previously undergone a total thyroidectomy revealing benign pathology. Parathyroid hormone and calcium blood levels were within normal limits. The mass was removed with negative surgical margins. Histopathology and immunohistochemical analysis showed a biphasic pattern, with positive for chromogranin and vimentin, consistent with carcinoma and sarcoma. The disease in our patient, as in the previously reported case, has shown systemic progression despite aggressive surgical resection and adjuvant therapy.

Parathyroid Carcinoma Presenting as a Hyperparathyroid Crisis

No abstract available.

Hiperparatiroidismo primario con normocalcemia, una asociación de diagnóstico complejo: a propósito de un caso clínico / Normocalcemic hyperparathyroidism: report of one case

We report a 59 years old female with a history of nephrolithiasis and progressive worsening of her bone mineral density. High serum PTH levels were detected, with normal serum calcium. Causes of secondary hyperparathyroidism were discarded. The patient was followed during six years, period in which she maintained elevated serum PTH and normal serum calcium. During the second year of follow up, hydrochlorothiazide was indicated. Serum calcium raised progressively and after six years, it became abnormally high. The patient was subjected to a total left lobe and subtotal right lobe thyroidectomy. The surgeon found a 1.6 mm diameter left parathyroid nodule. After surgery the patient is asymptomatic and is receiving levothyroxine supplementation.

[Maxilla-mandibular brown tumors as a first sign of parathyroid adenoma]. / Tumeurs brunes maxillomandibulaires révélant un adénome parathyroïdien.

OBJECTIVES: Through a novel observation of parathyroid adenoma revealed by brown tumors of the jaws and a review of the literature, the authors describe this rare mode of primary hyperparathyroidism discovery. MATERIAL AND METHODS: The patient was a 23-year-old woman who consulted for a recurrent tumefaction of the maxillary; histology showed reparative giant cell granuloma. RESULTS: The clinical examination found an osseous tumefaction in continuity with the zygomatic bone and a gingival tumefaction on the mandible symphysis. The radiological findings showed two osteophytic lesions: mandibular and maxillary. The phosphocalcic metabolism was disturbed and the parathormone rate was high. The etiologic search consisted of a MRI of the neck, which showed a mass behind the thyroid gland, suggesting a parathyroid adenoma. The diagnosis was confirmed at surgical exploration. After removal of this tumor, the blood calcium rate dropped sharply and the bone tumefaction progressively regressed. CONCLUSION: Brown tumors are a rare mode of parathyroid adenoma discovery, and the jaw location is exceptional. The diagnosis is based on the parathormone rate, and radiological exams generally find the etiology. Treatment is based on surgery of the parathyroid adenoma.

Predictors of intra-operative parathyroid hormone decline in subjects operated for primary hyperparathyroidism by minimally invasive parathyroidectomy.

BACKGROUND: The predictors of intra-operative PTH (IOPTH) decline during minimally invasive parathyroidectomy (MIP) for primary hyperparathyroidism have been but poorly studied. MATERIALS AND METHODS: This retrospective study included 108 patients who underwent MIP for a single adenoma. Serum calcium and phosphorus were measured before surgery and 1 day post-operatively. IOPTH was measured before (intra-operative preincision or PTHt0) and 10 min after removal of the adenoma (PTHt10). The Modification of Diet in Renal Disease (MDRD) equation was used to estimate the glomerular filtration rate. The weight of the adenoma was assessed in all the subjects. RESULTS: The sex ratio female/male was 5.37 with a mean age of 57.3 yr. The mean pre- and postoperative values were for calcium 2.80 and 2.19 mmol/l, respectively (p<0.0001) and for phosphorus 0.90 and 1.16 mmol/l, respectively (p<0.0001). The PTH dropped from a mean value of 184.8 to 50.8 pg/ml 10 min after adenoma resection with a mean drop of 69.7%. Thirteen patients (12%) did not achieve a PTH fall of more than 50%. In a bivariate analysis, age, an MDRD<60 ml/min and weight of adenoma were inversely associated with IOPTH fall (p=0.009, p=0.004, and p<0.001, respectively) while gender, body mass index, hypertension, diabetes, pre-operative phosphorus and calcium had no significant effects. In the multivariate analysis, age, weight of adenoma, and MDRD were still independent negative predictors of the IOPTH fall (p=0.01, p=0.018, and p<0.001, respectively). CONCLUSION: Our results suggest that during MIP the presence of a parathyroid adenoma with a high weight, in an elderly subject or in a subject with altered renal function, will result in a lesser degree of IOPTH fall.

Parathyroid glands: combination of sestamibi-(99m)Tc scintigraphy and ultrasonography for demonstration of hyperplasic parathyroid glands.

OBJECTIVE: To determine the frequency of the types of parathyroid gland hyperplasia and the sensitivity of sestamibi-(99m)Tc (MIBI) scintigraphy and ultrasonography (US) of patients with secondary hyperparathyroidism (SHPT) due to chronic renal failure. MATERIAL AND METHODS: We studied 43 patients with SHPT (26 females and 17 males with age range of 27-75 years). Blood tests were performed to determine intact parathyroid hormone (PTH), calcium and phosphorus concentration and parathyroid MIBI scintigraphy and US examinations were done, to evaluate each glandular function and structure. Nineteen of the 43 patients underwent total parathyroidectomy and 69 abnormal glands were removed at operation. The 69 abnormal and 4 normal glands from patients that underwent total thyroidectomy were studied by light microscopy. The results were compared and correlation was calculated to: weight, MIBI uptake and US results. RESULTS: All 43 patients had elevated serum PTH ranged from 400 to 4,075 pg/ml (1,868.0 +/- 975.9 and normal range 10-75 pg/ml). Serum calcium and phosphorus concentration were 10.13 +/- 2.02 mg/dl and 5.28 +/- 2.07 mg/dl respectively. Fifty eight of 69 glands from surgical resection were MIBI positive and 11 were negative, but their cellular composition and presentation were similar. Hyperplasic glands had increased number of all cell types considered (chief, oxyphil and clear) compared to the normal gland. Chief cell hyperplasia was the most frequent type (81 %) followed by oxyphil (9 %), clear (6 %) and adenomatous type (4 %). False negative results of 10 % to US and 4.6 % to scintigraphy were found. The correlation of gland weight and MIBI uptake were not significant (p = 0.09). The sensitivity of MIBI scintigraphy was 84 % and US was 72.5 %. CONCLUSIONS: The MIBI scintigraphy is a very sensitive tool for pre-operative localization of hyperplasic parathyroid gland and should be used as the first imaging method. The association of MIBI and US is recommended because increases the sensitivity for preoperative hyperplasic parathyroid glands identification.

25-hydroxyvitamin D deficiency is a risk factor for symptoms of postoperative hypocalcemia and secondary hyperparathyroidism after minimally invasive parathyroidectomy.

BACKGROUND: Patients with primary hyperparathyroidism who undergo minimally invasive parathyroidectomy (MIP) may have postoperative symptoms of hypocalcemia or secondary hyperparathyroidism. This study sought to identify factors predictive of these events. METHODS: Between 1998 and 2004, 190 patients with primary hyperparathyroidism underwent MIP with excision of a single adenoma. Age, gender, race, prior head and neck surgery, use of preoperative thyroid hormone or calcium-channel blockers, preoperative levels of calcium, 25-hydroxyvitamin D (25[OH]D) and intact parathyroid hormone (iPTH), the presence of osteopenia or osteoporosis, intraoperative iPTH levels, and adenoma weight were evaluated by univariate analysis as predictors of postoperative symptoms of hypocalcemia and secondary hyperparathyroidism. RESULTS: None of the following were predictors of postoperative symptoms of hypocalcemia: age, gender, race, prior head and neck surgery, preoperative medications, preoperative calcium and iPTH levels, osteopenia or osteoporosis, intraoperative iPTH levels, or adenoma weight. However, patients with postoperative symptoms of hypocalcemia had significantly lower preoperative 25[OH]D levels (P = .01). Further, higher preoperative iPTH levels (P < .01) and lower preoperative 25[OH]D levels (P = .05) were associated with secondary hyperparathyroidism postoperatively. CONCLUSIONS: A low preoperative 25[OH]D level is associated with postoperative symptoms of hypocalcemia and secondary hyperparathyroidism in patients undergoing MIP. One might consider instituting empiric calcium supplementation postoperatively in patients with low 25[OH]D levels.

[New directions in the surgical treatment of primary hyperparathyroidism]. / Orientations nouvelles dans le traitement chirurgical de l'hyperparathyroïdisme primaire.

For a long time, bilateral cervicotomy with a scrupulous exploration of the sites of the parathyroid glands was the technique of choice in the treatment of primary hyperparathyroidism. Recently new less invasive surgical techniques appeared: unilateral approach under local anaesthesia (UA LA) and video endoscopic parathyroidectomy (VEP), which could be used in 50% of patients after elimination of contraindications. Three factors support these new techniques: HPT I is in 85% of the patients related to a solitary adenoma. Ultrasonography or scintigraphy isolated or associated can detect the adenoma. Peroperative monitoring of the PTH can control the success of surgery. In our experience, 95 to 98 per cent of patients are cured of their HPTI.... In our opinion, UALA, technically simpler, with long term good results, is the technique of choice.

Revision parathyroidectomy guided by intraoperative radionuclide imaging.

BACKGROUND: Technetium-99m sestamibi scintigraphy has become one of the most popular techniques for localization of the parathyroid gland after failure of primary neck exploration. OBJECTIVE: To examine the efficacy of sestamibi with the hand-held gamma ray detecting probe for the identification of parathyroid adenomas during revision parathyroidectomy. METHODS: We reviewed six cases of probe-assisted neck exploration for parathyroid lesions following unsuccessful primary exploration. RESULTS: In all cases the pathologic glands were successfully detected and removed. CONCLUSIONS: With careful planning, a gamma ray detecting probe can be used optimally 2-3 hours after technetium-99m sestamibi injection. The probe is efficient, easy and convenient to use.

Elevated serum parathormone level after "concise parathyroidectomy" for primary sporadic hyperparathyroidism.

BACKGROUND: Cure after parathyroid exploration is traditionally assessed by serum calcium concentration 6 months postoperatively. Postoperative normocalcemic elevation of serum parathormone (PTH) level has been described but is of unclear significance. METHODS: In a 6-year prospective study of outcomes in 380 patients undergoing initial parathyroidectomy for primary sporadic hyperparathyroidism, we measured intact serum PTH and calcium levels at more than 5 months. Those with normocalcemic high PTH levels were begun on oral calcium + vitamin supplements and monitored. RESULTS: At more than 5 months postoperatively, normocalcemic elevation in serum PTH level occurred in 28% of patients, was more common after resection of double adenomas (P =.01), and predated the onset of recurrent hypercalcemia in 3 of 3 patients with unrecognized multiglandular disease. Although delayed treatment with calcium and vitamin supplements produced no clear benefit, patients who took such supplements from the date of surgery were much less likely to have an elevated serum PTH level more than 5 months later (P =.0005). CONCLUSIONS: After successful parathyroid surgery, compensatory normocalcemic elevation in serum PTH level is frequent and may arise from dietary deficiency. Monitored supplemental intake of calcium and vitamin D appears to prevent or to normalize the condition in most patients. Patients with normocalcemic elevation in serum PTH level should receive evaluation for dietary deficiencies as well as follow-up for possible residual disease.

[Diagnostic and surgical strategy for parathyroid adenoma]. / Stratégie diagnostique et chirurgicale de l'adénome parathyroïdien.

From a retrospective study carrying on 8 patients operated for sporadic parathyroid adenoma, we underline the place of medical imagery which allowed the detection of parathyroid adenoma in 7 cases. For all our patients the exploration of thyroid space was bilateral, seeking parathyroid glands. The authors discuss the stages and the various processes of the surgical strategy for parathyroid glands' exploration.

[Effects of octreotide on serum and urine electrolytes in a patient with parathyroid carcinoma: clinical case]. / Efectos del octreotide sobre los electrolitos en suero y orina de un paciente con carcinoma de paratiroides: caso clínico.

Parathyroid carcinoma (PC) is a rare endocrine tumor whose management is difficult whenever surgery does not achieve complete en bloc resection or recurrence is detected. Medical options (mainly bisphosphonates) are scanty and often associated with toxic side-effects. We present a case report of a patient with recurrent PC after two surgical interventions who was treated with octreotide (SMS-201) taken into account the positive somatostatin staining of the specimen obtained during the last surgery. Short term effects (-2 weeks-) included a decrease in urinary calcium excretion paired with a simultaneous increase in urinary phosphorus excretion. Later on, continuous subcutaneous octreotide administration kept urinary calcium excretion at low levels and this effect was completely reversible/reinducible upon discontinuation/reintroduction of the drug. Neither iPTH nor total serum calcium were modified at short or long term basis. The lack of clear-cut therapeutic effects make this findings a pure clinical observation. Thus, octreotide cannot be recommended for the treatment of parathyroid carcinoma.