Temperature-controlled spectrophotometry: a simultaneous analysis of phase transition, thermal degradation and optical properties of semi-transparent composites from 20 °C to 450 °C.

So far, optical and effective radiative properties of polymer matrix based composites were investigated at temperatures well below their degradation temperature. At the same time, polymers exhibit temperature dependent physical properties and may undergo structural changes as their temperature raises. In this work, we employ the "Temperature-Controlled Spectrophotometry", a new method enabling to identify simultaneously phase transitions, thermal degradation and radiative properties of semi-transparent composites over a large temperature range. The method consists of measuring simultaneously the normal-normal and the normal-hemispherical transmittances and reflectances of the sample subjected to a laser irradiation with tuneable wavelength while the temperature is rised from room temperature up to 450 °C by means of a CO2 laser. Physical changes of the sample are identified from the temperature variation of normal-normal transmittance and specular reflectance measurements. Most of the results here are presented at a specific wavelength of 1070 nm but the proposed method is suitable over the semi-transparency spectral domain of the material by changing the wavelength of the probe laser. An inverse method for parameter identification based on normal-hemispherical measurements is employed to determine the transport effective radiative properties of the sample, namely the transport extinction coefficient and the transport scattering albedo from room temperature to 325 °C.

Optical properties of oakwood in the near-infrared range of semi-transparency.

The spectral absorption and scattering properties of oakwood are retrieved from the measurements of both the normal-hemispherical reflectance and transmittance in the visible and near-infrared ranges of semi-transparency. We employ two alternative methods for the radiative transfer in wood samples: the modified two-flux approximation and the high-order discrete ordinate method. The modifications of both methods take into account the effect of total internal reflection at both surfaces of the wood samples. The analytical approximate solution of the first method gives very accurate results for the absorption coefficient, but the transport scattering coefficient of wood appeared to be systematically underestimated. Fortunately, this error is between 7% and 12%, and that is acceptable for the estimates. The oakwood samples of four different thicknesses were used in the experiments. The effect of the wood cell orientation appears to be insignificant and can be observed in the reflectance from optically thin samples only. There is a considerable decrease in the transport scattering coefficient of oakwood with the wavelength. This effect is explained by a predominant contribution of micron-sized longitudinal pores in oakwood. The latter is used to develop an approximate theoretical model of scattering based on the rigorous solution for arbitrary-oriented cylindrical pores. The model suggested is in good agreement with the experimental data.

Endocrine tumors associated with the vagus nerve.

The vagus nerve (cranial nerve X) is the main nerve of the parasympathetic division of the autonomic nervous system. Vagal paragangliomas (VPGLs) are a prime example of an endocrine tumor associated with the vagus nerve. This rare, neural crest tumor constitutes the second most common site of hereditary head and neck paragangliomas (HNPGLs), most often in relation to mutations in the succinate dehydrogenase complex subunit D (SDHD) gene. The treatment paradigm for VPGL has progressively shifted from surgery to abstention or therapeutic radiation with curative-like outcomes. Parathyroid tissue and parathyroid adenoma can also be found in close association with the vagus nerve in intra or paravagal situations. Vagal parathyroid adenoma can be identified with preoperative imaging or suspected intraoperatively by experienced surgeons. Vagal parathyroid adenomas located in the neck or superior mediastinum can be removed via initial cervicotomy, while those located in the aortopulmonary window require a thoracic approach. This review particularly emphasizes the embryology, molecular genetics, and modern imaging of these tumors.

(18)F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma.

PURPOSE: To evaluate the performance of (18)F-L-dihydroxyphenylalanine ((18)F-DOPA) PET/CT in the detection of locoregional and distant medullary thyroid carcinoma (MTC) metastases and to compare imaging findings with histological data. METHODS: We retrospectively evaluated 86 MTC patients with persistently high serum calcitonin levels after initial surgery who had undergone (18)F-DOPA PET/CT between January 2007 and December 2014 in two referral centres. They were followed up for at least 6 months after the PET/CT assessment. The results were compared with histological data or with the findings obtained during follow-up using a complementary imaging modality. RESULTS: (18)F-DOPA PET/CT was positive in 65 of the 86 patients, corresponding to a patient-based sensitivity of 75.6 %. Distant metastatic disease (M1) was seen in 29 patients including 11 with previously unknown metastases revealed only by PET/CT. Among the 36 patients without distant metastatic spread, 25 had nodal involvement limited to the neck, and 10 of these 25 patients underwent reoperation. The lymph node compartment-based sensitivity of (18)F-DOPA PET/CT was 100 % in the two institutions but lesion-based sensitivity was only 24 %. Preoperative and postoperative median calcitonin levels were 405 pg/mL (range 128 - 1,960 pg/mL) and 259 pg/mL (range 33 - 1,516 pg/mL), respectively. None of the patients achieved normalization of serum calcitonin after reoperation. CONCLUSION: (18)F-DOPA PET/CT enables early diagnosis of a significant number of patients with distant metastasis. It has a limited sensitivity in the detection of residual disease but provides high performance for regional analysis. A surgical compartment-oriented approach could be the approach of choice whatever the number of nodes revealed by (18)F-DOPA PET/CT.

The role of radionuclide imaging in the surgical management of primary hyperparathyroidism.

Primary hyperparathyroidism is a frequent and potentially debilitating endocrine disorder for which surgery is the only curative treatment. The modalities of parathyroid surgery have changed over the last 2 decades, as conventional bilateral neck exploration is no longer the only surgical approach. Parathyroid scintigraphy plays a major role in defining the surgical strategy, given its ability to orient a targeted (focused) parathyroidectomy and to recognize ectopic locations or multiglandular disease. This review, which represents a collaborative effort between nuclear physicians, endocrinologists, and endocrine surgeons, emphasizes the importance of performing imaging before any surgery for primary hyperparathyroidism, even in the case of conventional bilateral neck exploration. We discuss the advantages and drawbacks of targeted parathyroidectomy and the performance of various scintigraphic protocols to guide limited surgery. We also discuss the optimal strategy to localize the offending gland before reoperation for persistent or recurrent hyperparathyroidism. Finally, we describe the potential applications of novel PET tracers, with special emphasis on (18)F-fluorocholine.

Preoperative imaging for focused parathyroidectomy: making a good strategy even better.

OBJECTIVE: Surgical treatment for primary hyperparathyroidism (pHPT) has undergone a major paradigm shift during the last decades from bilateral cervicotomy with four-gland neck exploration to image-guided focused approaches. The primary objective of the present study was to compare the performances of parathyroid scintigraphy (PS), parathyroid ultrasonography (US), and the combination of both procedures for guiding a focused approach on the basis of modified interpretation criteria. METHODS: Data from 199 patients operated for apparent sporadic pHPT and evaluated with US and PS using dual-isotope (123)I/(99m)Tc-sestamibi planar pinhole and single-photon emission computed tomography (SPECT) acqusitions were evaluated. RESULTS: A total of 127 patients underwent a focused approach and the remainder had bilateral cervicotomy. In 42 cases, a focused approach was not performed due to the absence of concordant results between US and PS for a single-gland abnormality. Four patients had persistent disease and three had recurrent disease. A localizing preoperative PS had a sensitivity of 93.3%, positive predictive value of 85.8%, negative predictive value of 73.0%, and accuracy of 83.4% for predicting uniglandular disease. Additional SPECT images accurately localize posterior adenomas that are often missed by US. Compared with PS, US had a lower sensitivity (P<0.01). Our imaging protocol also enabled diagnosis of multiglandular disease in 60.6%. CONCLUSIONS: PS using a highly sensitive dual-tracer subtraction method is the most accurate technique for directing a focused approach. PS could be sufficient for directing a focused approach in the presence of a negative US in two major circumstances: posterior locations due to acquired ectopia that could be missed by US, and previous history of thyroidectomy due to interpretation difficulties.

Diagnosis and preoperative imaging of multiple endocrine neoplasia type 2: current status and future directions.

Multiple endocrine neoplasia type 2 (MEN2) is a rare autosomal dominant syndrome caused by mutations in the RET protooncogene and is characterized by a strong penetrance of medullary thyroid carcinoma (all subtypes) and is often accompanied by pheochromocytoma (MEN2A/2B) and primary hyperparathyroidism (MEN2A). The evaluation and management of MEN2-related tumours is often different from that of sporadic counterparts. This review article provides an overview of clinical manifestations, diagnosis and surgical management of MEN2 patients. This review also presents applications of the most up-to-date imaging modalities to MEN2 patients that are tightly linked to the clinical management and aims to guide physicians towards a rationale for the use of imaging prior to prophylactic thyroidectomy, initial surgery and reoperations for persistent/recurrent disease. This review also concludes that, in the near future, it is expected that these patients will indeed benefit from newly developed positron emission tomography approaches which will target peptide receptors and protein kinases. Identification of MEN2-specific radiopharmaceuticals will also soon arise from molecular profiling studies. Furthermore, subtotal (cortical-sparing) adrenalectomy, which is a valid option in MEN2 for avoiding long-term steroid replacement, will benefit from an accurate estimation through imaging of differential adrenocortical function.

Quality of life is modestly improved in older patients with mild primary hyperparathyroidism postoperatively: results of a prospective multicenter study.

BACKGROUND: The objectives of this study were to evaluate, in mild primary hyperparathyroidism (pHPT) patients, the quality of life (QoL) using the SF-36 questionnaire before and after parathyroidectomy and to detect preoperatively patients who benefit the most from surgery. Most pHPT patients present a mild pHPT defined by calcemia ≤11.4 mg/dL. For these patients, there is debate about whether they should be managed with surveillance, medical therapy, or surgery. METHODS: A prospective multicenter study investigated QoL (SF-36) in patients with mild pHPT before and after parathyroidectomy in four university hospitals. Laboratory results and SF-36 scores were obtained preoperatively and postoperatively (3, 6, and 12 months). RESULTS: One hundred sixteen patients were included. After surgery, the biochemical cure rate was 98%. Preoperatively, the mental component summary and the physical component summary (PCS) were 38.69 of 100 and 39.53 of 100, respectively. At 1 year, the MCS and the PCS were 41.29 of 100 and 42.03 of 100. The subgroup analysis showed a more significant improvement in patients < 70 years and with calcemia ≥10.4 mg/dL. Postoperative PCS was correlated with age and preoperative PCS: variation = 32.11 - 0.21 × age - 0.4 × preoperative PCS. Men did not improve their MCS postoperatively. Only women with a preoperative MCS <43.6 of 100 showed postoperative improvement. CONCLUSIONS: This study showed, in patients with mild pHPT, an improvement of QoL 1 year after parathyroidectomy. Patients <70 years and with calcemia ≥10.4 mg/dL had a more significant improvement.

Contemporary review of large adrenal tumors in a tertiary referral center.

BACKGROUND: Large adrenal tumors (LATs, ≥6 cm) are uncommon and associated with malignancy in 25% of cases. Their surgical management remains debatable. The aim of the present report was to evaluate the current incidence, nature and management of LAT. PATIENTS AND METHODS: We carried out a retrospective review of LATs managed in a tertiary referral center (2002-2011). RESULTS: Eighty-one patients were included (out of a total of 750 with adrenal tumors, 11%). Nine patients had no surgical intervention (11%). Fifty-two LATs were malignant (64%): adrenocortical carcinoma (44%), metastasis (27%) and pheochromocytoma (21%). Patients with malignant tumors exhibited a poorer 5-year overall survival than those with benign tumors (53.4% versus 96.3%, p=0.001). Disease-related mortality was approximately 60%, 29% and 0% for those with metastasis, adrenal carcinoma and malignant pheochromocytoma, respectively. The recurrence rate was the same for the three malignant sub-groups (30%). CONCLUSION: LATs are rare and more frequently malignant than previously reported. Some are benign and do not require for surgical intervention. Surgical indication and approach should be tailored for each patient.

Surgery for 'asymptomatic' mild primary hyperparathyroidism improves some clinical symptoms postoperatively.

OBJECTIVE AND BACKGROUND: Most primary hyperparathyroidism (pHPT) patients do not conform to the guidelines for parathyroidectomy established by an international panel of specialists and have a mild pHPT. This group is typically defined as 'asymptomatic'. The primary aim of this study was to determine symptom improvement in this 'asymptomatic' group after parathyroidectomy. Secondly, we aimed to create a preoperative clinical score predicting postoperative symptom resolution. DESIGN: A prospective nonrandomized study included patients with mild pHPT. METHODS: A questionnaire (22 items) was given to 'asymptomatic' patients preoperatively and at 3, 6, and 12 postoperative months. A logistic regression was performed to create a preoperative clinical score. RESULTS: One hundred and sixteen patients were included. Postoperatively, HPT was resolved in 98% of patients. Twelve of 22 nonspecific symptoms were improved at 1 year. Subgroups analysis showed a greater improvement in patients <70 years and those with a serum calcium level ≥2.6 mmol/l preoperatively. A clinical score, based on age and five symptoms, was established to predict the clinical improvement after surgery in mild pHPT patients with a positive predictive value of 81%. CONCLUSION: Patients with asymptomatic pHPT have clinical improvement of their symptoms postoperatively even after 1 year. Younger patients and those with higher preoperative calcium levels show the best improvement.

Parathyroid scintigraphy in renal hyperparathyroidism: the added diagnostic value of SPECT and SPECT/CT.

Secondary hyperparathyroidism (sHPT) is a major complication for patients with end-stage renal disease on long-term hemodialysis or peritoneal dialysis. When the disease is resistant to medical treatment, patients with severe sHPT are typically referred for parathyroidectomy (PTx), which usually improves biological parameters as well as clinical signs and symptoms. Unfortunately, early surgical failure with persistent disease may occur in 5%-10% of patients and recurrence reaches 20%-30% at 5 years. Presently, the use of parathyroid scintigraphy in sHPT is usually limited to the management of surgical failures after initial PTx. This review describes the strengths and limitations of typical (99m)Tc-sestamibi imaging protocols, and highlights the potential benefits of using parathyroid scintigraphy in the initial workup of surgical patients.

Ectopic hormone-secreting pheochromocytoma: a francophone observational study.

BACKGROUND: Ectopic hormone-secreting pheochromocytomas are rare; only case reports exist in the literature. This condition has been linked with increased malignancy, familial syndromes, and ACTH secretion. We wanted to test these hypotheses and shed light on the nature of ectopic hormone-secreting pheochromocytomas. METHODS: This is a multicenter (francophone) observational study. Inclusion was based upon abnormal preoperative hormone tests in patients with pheochromocytoma that normalized after removal of the tumor. Where possible, immunohistochemistry was performed to confirm that ectopic secretion came from the tumor. RESULTS: Sixteen cases were found: nine female and seven male patients. Median age was 50.5 (range 31-89) years. Most presented with hypertension, diabetes, or cushingoid features. Ten patients had specific symptoms from the ectopic hormone secretion. Two had a familial syndrome. Of eight patients with excess cortisol secretion, three died as a result of the tumor resection: two had pheochromocytomas >15 cm and their associated cortisol hypersecretion complicated their postoperative course. The other died from a torn subhepatic vein. The 13 survivors did not develop any evidence of malignancy during follow-up (median 50 months). Symptoms from the ectopic secretion resolved after removal of the tumor. Immunohistochemistry was performed and was positive in eight tumors: five ACTH, three calcitonins, and one VIP. CONCLUSIONS: Most pheochromocytomas with ectopic secretion are neither malignant nor familial. Most ectopic hormone-secreting pheochromocytoma cause hypercortisolemia. Patients with a pheochromocytoma should be worked up for ectopic hormones, because removal of the pheochromocytoma resolves those symptoms. Associated cortisol secretion needs careful attention.

Preoperative 18F-FDG uptake is strongly correlated with malignancy, Weiss score, and molecular markers of aggressiveness in adrenal cortical tumors.

BACKGROUND: Adrenal incidentaloma are frequent in the general population. It can be difficult to diagnose adrenocortical carcinomas among them, even with the progress of imaging techniques. We studied the results of PET-FDG in the diagnosis of such tumours. METHODS: We studied patients referred to the Department of Endocrine Surgery at La Timone Hospital, Marseilles, France, between June 2006 and October 2010 for adrenal tumours. All patients underwent a complete work-up (biological tests and imagery), completed with PET-FDG. We compared the results of PET-FDG and molecular analysis with Weiss score and clinical follow-up. We calculated correlations with the Pearson test. RESULTS: A total of 51 patients were studied. We found that PET-FDG had a sensitivity of 95% and specificity of 97% for the diagnosis of adrenocortical carcinoma. The correlation between PET-FDG and Weiss score was 77% (P ≤ 0.0001). Molecular analyses were correlated as well with Weiss score and malignancy (P < 0.05). CONCLUSIONS: The nature of atypical adrenal masses can be difficult to define during preoperative investigations. For undetermined tumours smaller than 6 cm, characterization with PET-FDG can be one more diagnostic argument pointing to malignancy. It could potentially change the therapeutic strategy and surgical management. In our experience, molecular analyses are available after surgery and have less impact on the therapeutic strategy than PET-FDG. Preoperative PET-FDG can be an asset in the management of adrenal incidentaloma and adrenocortical carcinoma.

Lithium-associated hyperparathyroidism: surgical strategies in the era of minimally invasive parathyroidectomy.

BACKGROUND: Lithium remains an effective treatment of bipolar affective disorder. The long-term use of lithium is associated with an alteration in parathyroid function that may culminate in hyperparathyroidism. The long-term effects of lithium use are variable due to its complex effects on calcium homeostasis and bone metabolism, and as a consequence the indications for surgery remain poorly defined. The optimal surgical strategy for lithium-associated hyperparathyroidism in the era of minimally invasive surgery is also the subject of debate. The aim of the present study was to evaluate the variable findings of lithium-associated parathyroid disease. METHODS: A retrospective review was performed of patients undergoing parathyroid surgery presenting with lithium-associated hyperparathyroidism from July 1999 until July 2009 at the university hospital La Timone, Marseille, and from October 2005 to July 2009 at Hammersmith Hospital, Imperial College, London. Fifteen patients underwent surgery for lithium-associated hyperparathyroidism. Clinical data including patient demographics, duration of lithium use, clinical manifestations of hyperparathyroidism, indications for surgery, and biochemical parameters preoperatively and postoperatively were reviewed. Preoperative imaging, the surgical procedure performed, operative findings, and histopathology were also analyzed. RESULTS: All 15 patients had preoperative imaging: sestamibi scanning showed that 10 patients had localized single-gland disease, 1 had multiple hot spots, and 4 had a negative scan. Ultrasonography demonstrated a single abnormal gland in 8 patients and multiple enlarged glands in 1 patient; the test was negative in 6. As a consequence of concordant preoperative imaging a minimally invasive approach (endoscopic or a focused lateral approach) was adopted in 3 patients. Focused surgery demonstrated an enlarged hyperplastic gland in 3 cases and resulted in normocalcemia in the immediate postoperative period. However, one patient has a serum calcium at the upper limit of normal and elevated parathyroid hormone (PTH) levels, suggestive of possible recurrence of disease at 15 months follow-up. One patient has permanent hypoparathyroidism. In those patients who had open procedures, final histology showed hyperplastic multiglandular disease in 10 patients (83.3%) of patients and single-gland disease in 2 patients (16.7%). None of these patients show evidence of recurrence at follow-up. CONCLUSIONS: Lithium hyperparathyroidism is predominantly a multiglandular disease characterized by asymmetrical hyperplasia that is frequently associated with misleading or discordant localization studies. Bilateral neck exploration is therefore recommended in order to minimize the risk of disease recurrence.

Radiation doses to cohabitants of patients undergoing radioiodine ablation for thyroid cancer: poor compliance with radiation protection guidelines but low radiation exposure.

BACKGROUND: The drive to reduce hospital stay after radioiodine remnant ablation in patients with thyroid cancer may increase the risk of radiation exposure to family members. The aim of this study was to evaluate the key determinants of dose exposure to familial members, with particular reference to the degree of adherence to current radiation safety guidelines. METHODS: All participants prospectively received our standard departmental oral and written safety instructions, with a mandatory 3-day restriction period. The postmicturition radiation levels of treated patients were measured (at 1-m distance) at the time of discharge using a portable radiometer. The radiation exposure of cohabitants was assessed with an optically stimulated luminescence-based personal dosimeter during the 3 days after hospital discharge. A questionnaire was used to assess the adherence of relatives/cohabitants to radiation safety guidelines. RESULTS: A total of 38 patients with thyroid cancer and 48 household members were included. At 48 h post therapy, the patient's median emission at 1-m distance was 13.4 µSv/h. The mean cumulative cohabitant exposure was 102 µSv (<50-1000). A positive correlation between cohabitant radiation exposure and the radiation level of the patient was observed (P=0.016). This correlation was absent when the recommended guidelines were followed (P=0.56). Only 17 household members (35.4%) strictly followed the recommended guidelines, but dose exposures exceeded 0.3 mSv in only four cases, in which a mean of between 5.8 and 9.5 h were spent in close proximity to the patient in the first 3 days, including sleeping with treated patients in half of the cases. CONCLUSION: Despite poor compliance with safety guidelines, a short-stay protocol respects current legislation, and is applicable to most patients treated with 3.7 GBq for radioiodine remnant ablation.

Heath-related quality of life in thyroid cancer patients following radioiodine ablation.

BACKGROUND: There is limited information about the medium to long-term health-related quality of life (QOL) in thyroid cancer patients after initial therapy and the existing studies suffer from limitations. The aim of the study was to assess the determinants of medium-term QOL after the initial therapy. METHODS: Following a total thyroidectomy, 88 thyroid cancer patients received either rhTSH or hypothyroid-assisted radioiodine ablation (RRA) using 3.7 GBq (100 mCi) of radioiodine. QOL evaluation of the patients using the validated Functional Assessment of Chronic Illness & Therapy (FACIT) was performed at the time of inclusion (t0) and later at the 9-month post-RRA (t1). RESULTS: 83 patients were eligible for the final evaluation. Medium-term FACIT scores were not statistically different between t0 and t1 patients. All but one domain of the QOL score was similar between t0 and t1. Using a multivariate analysis, only age and immediate postoperative QOL scores were found to be determinants of the overall medium term 9-month QOL scores. Analysis showed that 'high QOL levels' (baseline and 9-month) and 'no depression', 'low anxiety levels', were associated with '<45 yrs', 'men', 'partner', and 'rhTSH stimulation'. CONCLUSIONS: The use of radioiodine ablation does not seem to affect the medium term QOL scores of patients. Medium-term QOL is mainly determined by pre-ablation QOL. The assessment of baseline QOL might be interesting to evaluate in order to adapt the treatment protocols, the preventive strategies, and medical information to patients for potentially improving their outcomes.

Adrenal venous sampling is crucial before an adrenalectomy whatever the adrenal-nodule size on computed tomography.

OBJECTIVE: To assess the additional value of adrenal venous sampling (AVS) to diagnose primary aldosteronism sub-types in patients who have a unilateral nodule detected by computed tomography (CT scan) and who should undergo an adrenalectomy. METHODS: A retrospective study to assess consecutive patients with primary aldosteronism undergoing an adrenal CT scan and AVS. Criterion for selective cannulation was an equal or higher cortisol level in the adrenal vein compared to the inferior vena cava. An adrenal-vein aldosterone-to-cortisol ratio of at least two times higher than the other side defined lateralization of aldosterone production. RESULTS: Sixty-seven patients (mean age 52 years, 39 men) underwent a CT scan and AVS. In nine patients (13%), cannulation of the right adrenal vein led to a technical failure. Both procedures led to diagnosis of 29 patients with adenoma-producing aldosterone (APA; 50%), 23 bilateral adrenal hyperplasias (40%), and six unilateral adrenal hyperplasias (10%). Of the 45 patients with a nodule detected by CT, subsequent AVS showed bilateral secretion in 16 patients (36%). Compared to the strategy of coupling CT scans with AVS to diagnosis APA, a CT scan alone had an accuracy of 72.4% (P < 0.001). Among patients with a macronodule detected by CT, 13 (37%) had bilateral secretion as assessed by AVS. The patients with a macronodule detected by CT alone had the same risk of a discrepancy as those with a small nodule (P = 0.99). CONCLUSION: AVS is essential to diagnose the unilateral hypersecretion of aldosterone, even in patients in whom a unilateral macronodule is detected by CT, to avoid unnecessary surgery.

Expression of somatostatin receptors, dopamine D2 receptors, noradrenaline transporters, and vesicular monoamine transporters in 52 pheochromocytomas and paragangliomas.

While somatostatin receptors (sst), through somatostatin-radiolabeled analogs, are used, mainly in second line, in the diagnosis and treatment of pheochromocytomas (PCC) and paragangliomas (PGL), the clinical significance of dopamine receptor subtype 2 (D2) in PCC/PGL is unknown. Indeed, radiolabeled dopamine (DA) analogs such as fluorine 18 ((18)F)-DA, used for positron emission tomography in PCC localization, are mainly correlated to the presence of noradrenaline transporter (NAT) and vesicular monoamine transporters (VMAT) but not to D2. The aim of this study was to quantitate D2 and sst expression in 52 PCC/PGL and to compare it with that of 35 gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Quantitative RT-PCR of sst(1-3) and sst5, D2, NAT, VMAT1/2 was performed in all tumors, while immunohistochemistry analysis of sst2 and D2 was performed in seven tumors. D2 mRNA was expressed in all PCC/PGL. Mean expression was significantly higher in PCC/PGL than in GEP-NETs (4.8 vs 0.5 copy/copy ß-glucuronidase (Gus)). sst2 and sst(1) were expressed in most PCC/PGL, with sst(2)-dominant expression (mean mRNA: 1.6 vs 0.4 copy/copy ß-Gus). sst2 expression level was similar to that of GEP-NETs, whereas sst5 expression level was significantly lower (0.12 vs 0.78 copy/copy ß-Gus). Our study evidenced strong D2 mRNA expression in PCC and for the first time in PGL. PCC/PGL express sst2 mRNA at levels similar to those of GEP-NETs. New drugs can target ssts and D2 more efficiently than current somatostatin analogs. Moreover, transporters like NAT and VMAT1/2, could be co-targeted with sst, as a basis of new radionuclide compounds in the imaging and treatment of these tumors.

Should routine analysis of the MEN1 gene be performed in all patients with primary hyperparathyroidism under 40 years of age?

BACKGROUND: Familial hyperparathyroidism, especially Multiple Endocrine Neoplasia Type 1, is more likely to present with primary hyperparathyroidism (1 degrees HPT) at a young age, mandating bilateral exploration of the parathyroid glands. However, the majority of young patients will not be gene carriers or have a family history. Recent evidence suggests that young adults under 40, in whom there is no suspicion of family history, can be managed with the same pre- and perioperative strategy as used for sporadic primary HPT of any age. Our aim was to evaluate the prevalence of mutations in the MEN1 gene in young adults under 40 who present with apparent sporadic 1 degrees HPT. METHODS: A retrospective review was undertaken of all patients who underwent surgery for 1 degrees HPT between 1993 and 2004. From a total of 1253 patients, 87 (6.2%) were under the age of 40. Thirty-three patients provided informed consent to a detailed personal and family history, physical examination, and genetic analysis of the MEN1 gene. Twelve patients were subsequently excluded as they were known gene carriers prior to surgery (10 MEN1 and 2 MEN2A patients). Twenty-one patients underwent genetic analysis. RESULTS: Of the 21 patients who consented to genetic analysis, the mean age was 30.8 years (range = 18-39 years with 43% younger than 30). These patients had no suspicious family or personal histories suggestive of a MEN phenotype. Fifteen patients presented with symptomatic hypercalcemia. All 21 patients underwent parathyroid surgery by conventional cervicotomy (12) or endoscopic parathyroidectomy in cases (9) where the parathyroid gland was localized preoperatively. Nineteen patients (91%) had uniglandular disease. Surgical cure was achieved in all patients. Of the 21 patients, only one patient (4.7%) was found to have a MEN1 gene mutation (exon 3, at codon 190, c;680_681delGGinsC). This patient was found to have double adenomas at surgery with subsequent histological confirmation. The overall prevalence of MEN1 mutation in all patients under 40 was 13%. CONCLUSION: Although young age is often the only criterion to suspect MEN1, our results do not support routine MEN1 analysis in patients under 40. We propose that these patients be managed with the same preoperative and surgical approach as those presenting with sporadic 1 degrees HPT of any age.