Antonella Picone

Minimally invasive, video-assisted parathyroid surgery for primary hyperparathyroidism

A new video-assisted surgical procedure for treatment of primary hyperparathyroidism combined with intraoperative quick PTH measurement was developed. This procedure was successfully used in 6 patients with a single parathyroid adenoma preoperatively localized by neck ultrasound examination.

Results of Video-assisted Parathyroidectomy: Single Institution’s Six-year Experience

Endoscopic surgery for primary hyperparathyroidism (PHPT) started in 1996 with a parathyroidectomy performed by Michel Gagner. The technique we propose and have been using for 6 years is based on a unique central access and external retraction. From February 1997 to October 2003, 370 of 520 patients affected with PHPT (71%) underwent minimally invasive video-assisted parathyroidectomy (MIVAP). There were 72 men and 298 women, with a mean age of 55.8 years. Twenty-four patients (6.5%) of the 370 in this series underwent MIVAP under loco-regional anesthesia, and the others had general anesthesia. Eleven patients were lost to follow-up. Surgical cure of PHPT was achieved in 353 patients (98,3%), as confirmed by a median follow-up of 35.1 months (range: 2–82 months). Video-assisted exploration was successfully performed in 350 patients (94%). The mean operative time was 36.2 minutes. In 21 cases (5.6%) a concomitant procedure was performed: a thyroid lobectomy in 14 cases and a total thyroidectomy in 7 cases. Patients were generally discharged the day after surgery. Most of the patients (91%) were satisfied with the cosmetic result 6 or more months after the procedure. Complications developed in 14 cases: 10 cases (2.7%) of transient hypoparathyroidism 3 cases (0.8%) of definitive palsies of the recurrent nerve, and 1 case of postoperative bleeding (0.27%). After 6 years of experience, MIVAP appears to be as safe and curative as traditional surgery, with better cosmetic results and better postoperative outcome.

No Evidence for Mutations in the Calcium‐Sensing Receptor Gene in Sporadic Parathyroid Adenomas

Inactivating mutations of the calcium‐sensing receptor gene (CaR) might explain abnormalities in the regulation of both parathyroid cell proliferation and parathyroid hormone secretion. In a previous study, using RNAse A protection assay, no mutations were identified in a series of parathyroid specimens from patients with primary and secondary hyperparathyroidism, but the analysis was incomplete, since part of exon 6 could not be analyzed. In the present study, we examined the presence of mutations in the CaR gene in 20 parathyroid adenomas using direct sequencing. The entire coding region of the CaR gene was successfully amplified by polymerase chain reaction and directly sequenced. This analysis did not identify CaR gene mutations in any tumors studied. A polymorphism that encoded a single amino acid change (Ala826Thr) was identified in 4 parathyroid adenomas and in 8 of 50 normal unrelated subjects. Loss of heterozygosity studies were also performed on adenomas using markers for the locus of the CaR gene on chromosome 3q. No allelic loss was demonstrated. In conclusion, our results extend previous observation and suggest that clonal somatic mutations of the CaR gene and allelic loss at the CaR locus on chromosome 3q do not play a major role in the pathogenesis of sporadic parathyroid tumors.

A reappraisal of the Rb1 gene abnormalities in the diagnosis of parathyroid cancer

objectives  Some histological features may suggest the malignant nature of a parathyroid tumour. However, the diagnosis of parathyroid cancer can only be definitively established in the presence of local invasion or metastases.

Limits and drawbacks of video-assisted parathyroidectomy†

Minimally invasive video‐assisted parathyroidectomy (MIVAP) is a novel minimally invasive approach to primary hyperparathyroidism (PHPT). It is a gasless operation characterized by a single central incision and external retraction. This paper describes the drawbacks and limitations of this procedure based on a 5‐year experience and 260 operations.

Calcium-sensing receptor gene polymorphisms in primary hyperparathyroidism

The calcium-sensing receptor (CaR) polymorphism A986S has been found to be associated with higher serum calcium levels in normal subjects, suggesting that this amino acid change might decrease the inhibitory activity of the mutated receptor, render the parathyroid cells more prone to proliferate, and eventually increase the risk of developing primary hyperparathyroidism (PHPT). The aim of the present study was to investigate the frequency of this and other 2 known CaR polymorphisms (R990G and Q1011E) in patients with PHPT and their effect on its phenotype. We studied 103 Italian patients with PHPT and 148 healthy Italian subjects and we compared the results in 50 pairs matched for sex, age and geographic provenience. A fragment of exon 7 of the CaR gene, containing the 3 polymorphic loci of interest (A986S, R990G, and Q1011E), was amplified by PCR and sequenced. Serum calcium and PTH levels, BMD and other biochemical and clinical parameters were evaluated. The frequency distribution of the A986S, R990G, and Q1011E polymorphisms in the 103 PHPT patients was 39.8%, 5.8%, and 2.0%, respectively. There was no difference in the frequency of the 3 CaR polymorphisms in the 50 matched pairs of patients and controls. We found no significant difference in several clinical and biochemical parameters between PHPT patients carrying or not the 986S allele. Finally, no relationship was observed between the 986S genotype and total and ionized serum calcium in control subjects. The A986S CaR polymorphism is the most common in Italian PHPT patients and the allotype AS does not appear to play a relevant role in the pathogenesis of PHPT and its severity. The A986S polymorphism does not correlate with serum calcium levels in normal Italian subjects.

Six novel MEN1 gene mutations in sporadic parathyroid tumors

We report nine mutations of the multiple endocrine neoplasia type 1 (MEN1) gene in sporadic parathyroid adenomas. Six of them have not previously been described: E60X, P32R, 261delA, 934+2T→G, S443P, and 1593insC. The tissue samples were initially submitted to LOH analysis at 11q13 followed by SSCP screening of LOH‐positive samples. Mutations were identified by direct sequencing and subcloning. Three (E60X, P32R, and 261delA) were in exon 2, one (934+2bp) in the splice junction of exon 5, one (S443P) in exon 9, and one (1593insC) in exon 10. The 3 mutations in exon 2 were associated with loss and/or creation of a restriction site. The corresponding germline sequence of the MEN1 gene was normal. Most mutations would likely result in a nonfunctional menin protein, and therefore in the loss of a tumor suppressor protein.

The impact of thyroidectomy on parathyroid glands: A biochemical and clinical profile

Introduction: An evaluation of PTH levels during thyroid surgery may reflect the functional status of the parathyroids and be useful in identifying patients at risk for hypocalcemia. This study aims to monitor the parathyroid function during total thyroidectomy through intra-operative serial samples for calcium and PTH. Materials and methods: Forty-seven patients undergoing total thyroidectomy for different diseases were selected for the study. Patients underwent serum PTH and calcium sampling at the induction of anesthesia (T0) and after the first (T1) and the second (T2) lobectomy. Serum calcium was also drafted 24 h after the operation. Results: Mean PTH at T0, T1, and T2 was, respectively: 32.1 pg/ml, 19.6 pg/ml, and 11.5 pg/ml. PTH was significantly higher at T0 when compared to T1 (p<0.0001). It was also significantly higher at T1 than at T2 (p<0.0001). At T1 PTH levels were below the normal range in 20/47 cases (42.5%) and at T2 in 31/47 cases (66%). Twenty-four h after surgery, 8 patients (17%) demonstrated a biochemical hypocalcemia. A PTH value at T0 in the upper (>70 pg/ml) or in the lower (<20 pg/ml) limits of the normal range was statistically related to post-operative hypocalcemia (p=0.017). Discussion: The study seems to confirm that serum PTH during thyroidectomy does not represent a sensitive tool in precociously identifying hypocalcemic patients. Nevertheless, before surgery, a PTH concentration at the higher or lower normal limit may help to identify patients “at risk” of developing hypocalcemia.

High-intensity focused ultrasound as an alternative to the surgical approach in primary hyperparathyroidism: a preliminary experience

Background: Surgery is the therapy of choice in primary hyperparathyroidism (PHPT), although other less invasive techniques have been used in the attempt to cure the disease. Recently, high-intensity focused ultrasound (HIFU), a totally non-invasive technique, has become available to cure solid tumors. Aim: The aim of this pilot study has been to assess the safety and efficacy of HIFU in symptomatic patients with PHPT. Material and methods: Four out of 31 patients with surgical indications within a cohort of 47-screened patients with PHPT were considered eligible for the study. All patients accepted to participate and were submitted to HIFU treatment in a single session. One patient was submitted to surgery after HIFU treatment. Patients were followed-up for 12 months after the procedure. Results: A persistent or a partial remission of the disease, respectively, were obtained in 2 patients (50%), including the one who underwent surgery after HIFU treatment. Safety was assessed performing laryngoscopy in all patients after HIFU procedure. A transient vocal cord paralysis was observed in all patients treated by HIFU only. No permanent side effects were observed in the long term. Conclusions: HIFU might be a promising technique in treating PHPT, provided that further development of the software decreases the rate of side effects and improves the short- and long-term efficacy.

Six novel MEN1 gene mutations in sporadic parathyroid tumors Communicated by: Richard G.H. Cotton Online Citation: Human Mutation, Mutation in Brief #373 (2000) Online http://journals.wiley.com/1059-7794/pdf/mutation/373.pdf

We report nine mutations of the multiple endocrine neoplasia type 1 (MEN1) gene in sporadic parathyroid adenomas. Six of them have not previously been described: E60X, P32R, 261delA, 934+2T-->G, S443P, and 1593insC. The tissue samples were initially submitted to LOH analysis at 11q13 followed by SSCP screening of LOH-positive samples. Mutations were identified by direct sequencing and subcloning. Three (E60X, P32R, and 261delA) were in exon 2, one (934+2bp) in the splice junction of exon 5, one (S443P) in exon 9, and one (1593insC) in exon 10. The 3 mutations in exon 2 were associated with loss and/or creation of a restriction site. The corresponding germline sequence of the MEN1 gene was normal. Most mutations would likely result in a nonfunctional menin protein, and therefore in the loss of a tumor suppressor protein.