The results of surgery for mediastinal parathyroid tumors: a comparative study of 63 patients.

PURPOSE: Parathyroidectomy for ectopic mediastinal hyperfunctioning glands could be performed by transcervical approach, sternotomy, thoracotomy, and recently by thoracoscopic and mediastinoscopic approaches. This study was aimed to analyze the results of traditional and video-assisted parathyroidectomy for mediastinal benign hyperfunctioning glands. METHODS: Fifty-one upper mediastinal exploration by a conventional cervicotomy, 12 by video-assisted approaches (two thoracoscopy and 10 transcervical mediastinoscopy) and six by sternotomy were performed in 63 patients with primary hyperparathyroidism. RESULTS: Video-assisted and sternotomic parathyroid explorations achieved biochemical cure in all cases; following conventional transcervical mediastinal exploration, a persistent hyperparathyroidism occurred in 11.8% of patients, who were subsequently cured by sternotomic approach. No complications occurred after video-assisted parathyroidectomy, while an overall morbidity rate of 50% and 10% was found after sternotomic and conventional cervicotomic approaches. Postoperative pain and hospital stay were significantly increased following sternotomy; patient's subjective cosmetic satisfaction was significantly higher after video-assisted and conventional cervicotomic approaches. CONCLUSIONS: Conventional cervicotomic parathyroidectomy may achieve satisfactory results, especially for upper mediastinal glands. Sternotomic approaches are effective, but should be limited because of invasiveness and increased morbidity. In case of deep and lower hyperfunctioning mediastinal parathyroids, video-assisted approaches represent a less invasive, effective, and safe alternative and might be the technique of choice.

Hyperparathyroidism-jaw tumor syndrome: a report of three large kindred.

BACKGROUND: Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare autosomal disease caused by inactivating germ-line mutations of HRPT2 gene, with subsequent loss of Parafibromin expression. It is characterized by familial HPT, ossifying jaw tumors, and other associated neoplasms. METHODS: Clinical, histopathological, and genetic features of three large Italian unrelated HPT-JT kindred were assessed. RESULTS: Three different germ-line HRPT2 inactivating mutations were identified. Seventeen affected members and six healthy mutation carriers were found. HPT was diagnosed in virtually all affected patients, at a median age of 36.3 years (range 11-71). In all cases, a single parathyroid involvement was found at surgery, although a metachronous multiglandular involvement causing recurrence after selective parathyroidectomy occurred in 17.6% of cases, after a mean disease-free interval of 13.7 years (range 5-27). Parathyroid carcinoma, atypical parathyroid adenoma, and jaw tumor occurred in one case; uterine involvement in 61.5% of women; other associated neoplasms were thyroid carcinoma (two cases) and renal and colon carcinoma (one case). Immunohistochemistry confirmed the loss of Parafibromin as the distinctive feature of the disease both in parathyroid and uterine tumors. CONCLUSIONS: HPT-JT has a frequent single-gland parathyroid involvement and a relatively increased risk of parathyroid carcinoma. The penetrance of the disease is high but incomplete. Regardless of the denomination of the syndrome, jaw tumors occur rarely, while uterine involvement is frequently present. Selective parathyroidectomy may be an effective strategy, but a prolonged follow-up is required because of the risk of recurrences and malignancies. A systematic investigation is also required because of associated malignancies.

Clinical, genetic, and histopathologic investigation of CDC73-related familial hyperparathyroidism.

CDC73 (HRPT2) germline mutations are responsible for more than half of cases of hyperparathyroidism-jaw tumor syndrome (HPT-JT) and for a subset of familial isolated HPT (FIHP). We performed a clinical, genetic, and histopathologic study in three unrelated Italian kindreds with HPT-JT and FIHP. We identified three germline inactivating mutations of the CDC73 gene in the probands and affected patients of the three kindreds, but also in some asymptomatic subjects. HPT-JT and FIHP patients had similar laboratory, clinical, and demographic features and shared primary HPT and other neoplasms, the most common of which was uterine polyposis. Genetic analysis of tumor samples demonstrated a second somatic CDC73 mutation only in a parathyroid adenoma and no cases with the loss of the wild-type allele or methylation of the CDC73 promoter, even though immunohistochemical analysis demonstrated the loss of nuclear parafibromin expression in all tumors, including a uterine polyp. In conclusion, our results indicate that FIHP and HPT-JT associated with CDC73 mutations do not have distinct clinical, genetic, and histopathologic features, but may represent variants of the same genetic disease. This study also confirms that uterine involvement represents a clinical manifestation of the syndrome.

The usefulness of preoperative ultrasonographic identification of nonrecurrent inferior laryngeal nerve in neck surgery.

BACKGROUNDS AND AIMS: Nonrecurrent inferior laryngeal nerve (ILN) represents a risk factor for injury during neck surgery. It is associated to arterial abnormalities (absence of the brachiocephalic trunk and arteria lusoria) that can be identified by ultrasonography. The aim of the study was to verify the usefulness of preoperative ultrasonography in the research of nonrecurrent ILN by the means of identification of arterial abnormalities and the impact on ILN morbidity. PATIENTS AND METHODS: The study included 750 patients who underwent neck surgery with right-side ILN dissection. A preoperative ultrasonography aimed to identify arterial abnormalities associated to nonrecurrent ILN was performed in 400 patients (Group A) while no preoperative attempts were performed in the remaining patients (Group B). Patients' characteristics, time for intraoperative identification of the ILN, and morbidity were compared. RESULTS: Five and four nonrecurrent ILN were identified in groups A and B, respectively (p = NS). Preoperative ultrasonography correctly predicted nonrecurrent ILN in all cases (accuracy 100%). Nonrecurrent ILN palsy never occurred in group A, while three cases occurred in group B (p < 0.05). The mean time for intraoperative identification of both nonrecurrent and normally recurrent ILN was significantly shorter in group A (p < 0.01). CONCLUSIONS: Preoperative ultrasonography can correctly identify nonrecurrent ILN, allowing earlier nerve identification and prevention of injuries.

High risk of malignancy in patients with incidentally discovered adrenal masses: accuracy of adrenal imaging and image-guided fine-needle aspiration cytology.

AIMS AND BACKGROUND: The incidental finding of nonfunctioning adrenal masses (incidentalomas) is common, but no reliable criteria in differentiating between benign and malignant adrenal masses have been defined. The aim of this preliminary study was to assess the usefulness of adrenal imaging and image-guided fine-needle aspiration cytology in patients with nonfunctioning adrenal incidentalomas with the aim of excluding or confirming malignancy before surgery. METHODS: Forty-two consecutive patients (18 men and 24 women; median age, 54 years; range, 25-75 years) with incidentally discovered adrenal masses of 3 cm or more in the greatest diameter were prospectively enrolled in the study. All patients underwent helical computerized tomography scan and image-guided fine-needle aspiration cytology, 33 (78.6%) underwent magnetic resonance imaging, and 26 (61.9%) underwent norcholesterol scintigraphy before adrenalectomy. RESULTS: The revised final pathology showed 30 (71.4%) benign (26 adrenocortical adenomas, of which 3 were atypical, 2 ganglioneuromas, and 2 nonfunctioning benign pheochromocytomas) and 12 (28.6%, 95% CI = 15-42) adrenal malignancies (8 adrenocortical carcinomas and 4 unsuspected adrenal metastases). The definitive diagnosis of adrenocortical carcinoma was made according to Weiss criteria and confirmed on the basis of local invasion at surgery or metastases. The sensitivity, specificity and accuracy were 75%, 67% and 83% for computerized tomography scan, 92%, 95% and 94% for magnetic resonance imaging, 89%, 94% and 92% for norcholesterol scintigraphy, and 92%, 100% and 98% for fine-needle aspiration cytology. The sensitivity and accuracy of image-guided fine-needle aspiration cytology and magnetic resonance imaging together reached 100%. Immediate periprocedural complications of fine-needle aspiration cytology occurred in 2 (4.7%) patients: self-limited pneumothorax (n = 1), and severe pain (n = 1) requiring analgesic therapy. No postprocedural or late complications were observed. CONCLUSIONS: With the aim of selecting for surgery patients with a non-functioning adrenal incidentaloma of 3 cm or more in diameter, the combination of magnetic resonance imaging and fine-needle aspiration cytology should be considered the strategy of choice.

Adrenal ganglioneuroma: The Padua Endocrine Surgery Unit experience.

BACKGROUND: Adrenal ganglioneuroma (AGN) is a rare tumor that originates from the gangliar cells of the sympathetic nervous system. It represents less than 5% of all adrenal masses. AGN occurs as a large mass, with benign behavior and no relevant symptoms and hormonal secretion, but it is often misdiagnosed because the preoperative radiological diagnosis is generally challenging. The aim of the present paper is to report the experience of a tertiary referral academic center regarding the management of AGN and review the relevant literature. METHODS: The demographic, diagnostic, surgical, and pathological findings of 666 consecutive patients who were adrenalectomized at the Padua Endocrine Surgery Unit between 1990 and 2015 were retrospectively reviewed in order to focus on AGN. RESULTS: The pathology confirmed AGN in 10 patients (1.5% of cases; median age 35 years, range 19-73). The diagnosis was incidental and never available before surgery. Eight patients were asymptomatic, two presented lower back and abdominal pain. The mass was non-secreting in all cases. Preoperative imaging techniques were inconclusive about the nature of the mass in all cases. The median size of the tumor was 55 mm (range 30-80). The laparoscopic approach was performed in 60% of cases. No recurrences occurred after surgery at a median follow-up of 10 years (range 1.7-18.2). CONCLUSION: The diagnosis of AGN may be challenging and most often occurs after surgery, since it is frequently confirmed by histological examination. Radical excision may be achieved by laparoscopic adrenalectomy, with a subsequent definitive cure and excellent prognosis at long term follow up.

Familial nonsyndromic pheochromocytoma.

Judging from recent data, heritable forms account for 30-40% of pheochromocytomas. The molecular basis for the familial pheochromocytoma has been largely elucidated and the role of germline mutation of the VHL, RET, SDHB, and SDHD genes has been established. However, on genotyping a group of 172 sporadic or familial pheochromocytomas, we characterized four unrelated probands with familial pheochromocytomas without any sequence variants of RET (exons 8, 10, 11, 13, 14, 15, and 16) or the entire coding sequence of VHL, SDHB, SDHC, SDHD, and EGLN3 (exon-intron boundaries included). The proband of family 1 is a man who had a bilateral pheochromocytoma at the age of 32 and a local recurrence at the age of 48 years. His brother died of malignant pheochromocytoma and his nephew died suddenly of an undiagnosed pheochromocytoma. The proband of family 2 is a female who had a 5-cm benign adrenal pheochromocytoma at the age of 34 years, while her cousin (maternal branch) had a monolateral pheochromocytoma at the age of 42 years. No other tumors had been reported in either family. The proband of family 3 is a female who had a bilateral pheochromocytoma at the age of 66 years. Her sister had a bilateral pheochromocytoma and breast cancer at the age of 54 years. Several other tumors were recorded in this family, including laryngeal cancer, leukemia, and a case of medullary thyroid carcinoma (MTC) in one brother. MTC was naturally ruled out in the proband and her sister. In family 4, the proband was a female who had a bilateral pheochromocytoma at the age of 46 years and a local recurrence a few years later, with liver metastases from the pheochromocytoma. Her brother had a monolateral benign pheochromocytoma. The proband also had a melanoma and bilateral renal cysts. This case revealed a VHL sequence variant IVS2+43 A>G, which was also found in one other unrelated sporadic pheochromocytoma. VHL mRNA integrity is currently being evaluated. The proband had no cerebellar or spinal NMR findings or retinal alterations. In family 5, the proband was a female who had a right adrenal pheochromocytoma at the age of 50 years and a breast cancer at 49 years of age. Her mother had had a right adrenal pheochromocytoma at 61 years of age. Although other molecular mechanisms, such as particular variants in untranslated regions or partial gene deletions, cannot be ruled out, we think finding families with nonsyndromic pheochromocytoma without any RET, VHL, SDHB, SDHC, SDHD, or EGLN3 mutation may argue in favor of the presence of other pheochromocytoma susceptibility genes.

PCNA-LII, Ki-67 immunostaining, p53 activity and histopathological variables in predicting the clinical outcome in patients with parathyroid carcinoma.

Parathyroid carcinoma is uncommon and no reliable histological markers are available for predicting the clinical outcome of patients. The aim of this study was to assess the correlation between survival, histopatological markers, proliferating cell nuclear antigen (PCNA), Ki-67 antigen and the expression of the p53 nuclear protein in patients with confirmed parathyroid carcinoma (PC). The routine histological specimens from 15 patients (11 men, 4-women, median age 65 years) with confirmed PC who had died of the disease were reviewed. New specimens were also stained with the streptavidin-biotin-peroxidase complex standard technique. The labelling index (LI) of PCNA was quantified by counting 1000 cells from multiple areas in a random fashion, while immunostaining of both Ki-67 and p53 was evaluated as the percentage of positive cells. The PCNA-LI, Ki-67 (%) and p53 (%) values were 14.9 +/- 4.1 (median 13, range 2-70), 13.9 +/- 3.9 (median 11%, range 3-65%) and 38.5 +/- 4.6 (median 29%, range 19-65%), respectively. There was an inverse correlation between age of the patients and p53 (R = -0.73, p = 0.002), but no correlation with both PCNA-LI (R = 0.07, p = 0.72) and Ki-67 (R = -0.07, p = 0.79). A significant relationship (R = 0.93, p < 0.01) between PCNA-LI and Ki-67 was found, while p53 did not correlate with either PCNA-LI (R = -0.11, p = 0.71) or Ki-67 (R = -0.05, p = 0.86). An inverse correlation (R = -0.63, p = 0.01) between survival and the presence of spindle cells and coagulation necrosis together in the standard slides was observed, but there was no correlation (p = NS) between survival and PCNA-LI (R = 0.05), Ki -67 (R = 0.05) or p53 (R = 0.25). In conclusion, none of the tested immunohistochemical markers were useful in predicting the clinical outcome of patients with PC. However, the presence of spindle cells and coagulation necrosis together in the standard specimens should be considered as a negative prognostic factor.

Are frozen sections useful and cost-effective in the era of intraoperative qPTH assays?

BACKGROUND: Since intraoperative quick parathormone (IOqPTH) assays are available, the role of frozen sections (FS) during parathyroid exploration has become questionable. This study compares the results of FS and IOqPTH in primary hyperparathyroidism (pHPT). METHODS: FS and IOqPTH assays were performed in 102 patients who underwent bilateral neck explorations or targeted parathyroidectomy for pHPT. The operation was considered complete when both an IOqPTH drop >50% and a FS diagnosis of parathyroid adenoma were obtained. RESULTS: Cure was achieved in all patients. Potential pitfalls for successful operation were encountered in 14 patients with multiglandular diseases and in 4 patients who had nonparathyroid tissue removed. FS correctly predicted the definitive histologic diagnosis with an accuracy of 81%. FS failures potentially misguided the operative therapy in 19% (14 insufficient explorations and 5 unnecessarily prolonged explorations), while IOqPTH identified all potential pitfalls and correctly guided the operative strategy, suggesting further exploration, in 100% of cases (P < .0001). After bilateral neck exploration, FS and IOqPTH correctly guided operative strategy in 86% and 100% of cases, respectively (P < .05), but both techniques were never indispensable, because potential pitfalls were already evident by macroscopic intraoperative appearance. The turnaround time and costs for IOqPTH were lower (P < .001). CONCLUSIONS: The role of FS should be reconsidered, since it can misguide the operative strategy. IOqPTH is indispensable for a focused approach and, although unnecessary in bilateral neck exploration, is more useful and cost-effective than FS.

Role and cost-effectiveness of adrenal imaging and image-guided FNA cytology in the management of incidentally discovered adrenal tumours.

Incidentally discovered adrenal masses (incidentalomas) are relatively frequent and unsuspected incidentalomas (AI) of more than 1 cm in size may be found in 1-5% of patients who have undergone abdominal or chest computed tomography (CT)-scan for unrelated reasons. Once an AI is detected, the two major questions are whether the patient has biochemical evidence of adrenal hyperfunction, and whether the mass is an adrenal metastasis or a malignant adrenal tumour. In most cases (>90%) AI are non-functioning, with a low (<10%) risk of being malignant, and an estimated cumulative risk of malignant transformation of less than 1:1000. However, all patients with non-functioning AI usually undergo several imaging studies, but the impact of imaging techniques and image-guided fine-needle aspiration cytology (FNAC) on the cost-effectiveness in the management of patients is not well established. A single test for disease probabilities is not always more cost-effective than two-test approaches and it has been shown that the cumulative sensitivity and accuracy of both FNAC + magnetic resonance imaging (MRI) and FNAC + norcholesterol adrenal scintigraphy reach 100%, at a similar cost-to-accuracy ratio (7.5 vs. 7.0), whilst the strategy CT-scan + MRI together is less sensitive at a lower cost-to-accuracy ratio. In conclusion, the significance of AI, as well as the optimal management approach to treatment, is still under discussion. However, image-guided FNAC in conjunction with MRI as the exclusive imaging test has the major role and cost-effectiveness in the management of patients with AL, and should be considered the strategy of choice in distinguishing between benign and malignant non-functioning adrenal masses of more than 2 cm in diameter.

Long-term results of adrenalectomy in patients with aldosterone-producing adenomas: multivariate analysis of factors affecting unresolved hypertension and review of the literature.

The long-term surgical cure rate of patients with primary aldosteronism varies widely, and causes of persistent hypertension are not completely established. We reviewed retrospectively charts from 98 patients (range, 19-70 years old) with aldosterone-producing adenomas who underwent unilateral adrenalectomy. At a median follow-up of 81 months (range, 18-186 months), the mean blood pressure values improved in 95 out of 98 (96.9%) patients, although hypertension was cured only in 71 out of 98 (72.4%) patients. Multivariate analysis using a logistic regression model adjusted for duration of follow-up showed that only age of the patients and duration of the disease independently correlated with unresolved hypertension. The cumulative odds ratio (OR), obtained using the logistic regression function, was 5.38 (95% CI 1.78-16.22), and the OR of single variables were 1.32 (95% CI 0.36-19.83) and 4.56 (95% CI 1.41-14.78), respectively. By using discriminant analysis to derive a classification function for the prediction of unresolved hypertension, a maximum predictive power of 75 per cent was achieved. In conclusion, in patients with an aldosterone-producing adenoma undergoing surgery, the combination of age and duration of hypertension gave the best predictive power of a linear classification function and represented the main independent risk factors affecting hypertension cure rate.

Adrenalectomy may improve cardiovascular and metabolic impairment and ameliorate quality of life in patients with adrenal incidentalomas and subclinical Cushing's syndrome.

BACKGROUND: Adrenalectomy represents the definitive treatment in clinically evident Cushing's syndrome; however, the most appropriate treatment for patients with subclinical Cushing's syndrome (SCS) with an adrenal incidentaloma remains controversial. This study was aimed to assess whether adrenalectomy may improve cardiovascular and metabolic impairment and quality of life compared with conservative management. METHODS: Twenty patients with adrenal incidentaloma underwent laparoscopic adrenalectomy for SCS, whereas 15 were managed conservatively. Hormonal laboratory parameters of corticosteroid secretion, arterial blood pressure (BP), glycometabolic profile, and quality of life (by the SF-36 questionnaire) were compared at baseline and the end of follow-up. RESULTS: The 2 groups were equivalent concerning all the examined parameters at baseline. In the operative group, laboratory corticosteroid parameters normalized in all patients but not in the conservative-management group (P < .001). In operated patients, a decrease in BP occurred in 53% of patients, glycometabolic control improved in 50%, and body mass index decreased; in contrast, no improvement or some worsening occurred in the conservative-management group (P < .01). SF-36 evaluation improved in the operative group (P < .05). CONCLUSION: Adrenalectomy can be more beneficial than conservative management in SCS and may achieve remission of laboratory hormonal abnormalities and improve BP, glycemic control, body mass index, and quality of life.

Unilateral adrenal hyperplasia: a novel cause of surgically correctable primary hyperaldosteronism.

BACKGROUND: Primary hyperaldosteronism may be caused by an aldosterone-producing adenoma (APA), which is correctable by unilateral adrenalectomy or by idiopathic adrenal hyperplasia, a bilateral disease without any indication for surgery. This study sought to assess the prevalence and the results of surgery in unilateral adrenal hyperplasia (UAH). METHODS: The study included 35 patients who underwent unilateral adrenalectomy because of primary hyperaldosteronism after unequivocal successful lateralization by adrenal venous sampling. Demographics, biochemical evaluation, and blood pressure were assessed pre- and postoperatively. Pathology was categorized as APA (isolated adenoma), nodular (multiple micromacronodules), and diffuse UAH (gland thickening without nodules). RESULTS: Pathology revealed 9 APAs and 23 nodular and 3 diffuse UAHs. Patients with APAs and UAHs were statistically similar regarding demographics and preoperative blood pressure levels. Bilateral adrenal involvement was evident at imaging in 10 patients (11% in APA versus 35% in UAH, P = NS). After surgery, biochemical cure of the disease was achieved in all patients; blood pressure levels normalized in 66.6% of patients and ameliorated in 22.2% in APA versus 34.6% and 50% in patients with UAH (P = NS). At a long-term follow-up, only 1 patient with nodular UAH experienced a biochemical recurrence of disease. CONCLUSION: UAH is not rare, sharing the same features of APA. When disease lateralization is confirmed by adrenal venous sampling, unilateral adrenalectomy achieves excellent long-term results.

Is genetic screening indicated in apparently sporadic pheochromocytomas and paragangliomas?

BACKGROUND: Pheochromocytoma (Pheo) is usually considered a sporadic disease. Recently, an increasing rate of genetically based tumors has been reported. However, the need for systematic screening of unsuspected germline mutations in apparently sporadic forms is still debated. This study aimed to assess the effective rate of germline mutations causing Pheo and Paraganglioma (PGL), and the role of systematic genetic screening. METHODS: Demographics, clinical, and genetic evaluation were performed in a series of 71 patients with Pheo and/or PGL. RESULTS: Twelve patients had evident inherited/familial disease at presentation: NF1 (n = 4); MEN2 (n = 4), and familial Pheo/PGL (n = 4). Among 59 patients with apparently sporadic disease, unsuspected germline mutations occurred in 8 cases: TMEM127 (n = 4), SDHB (n = 2), VHL (n = 1), SDHC (n = 1). No differences were found between hereditary and sporadic disease concerning age, sex, and tumor size; bilateral Pheo and/or PGL and recurrences occurred most often in hereditary disease. CONCLUSION: Hereditary Pheo and/or PGL are frequent (28.2%). Inheritance is evident at presentation only in 16.9% of cases; 13.6% of apparently sporadic variants are genetically determined. Despite increased costs, systematic genetic screening might be useful because it might lead to a stricter follow-up, early diagnosis of recurrences in index cases and presymptomatic detection of disease in relatives.

The role of unilateral adrenalectomy in ACTH-independent macronodular adrenal hyperplasia (AIMAH).

BACKGROUND: ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing's syndrome. Bilateral adrenalectomy is considered the treatment of choice, with subsequent lifetime steroid replacement, but unilateral adrenalectomy has been recently proposed to reduce the secreting tissue. This prospective study was designed to evaluate the long-term results of unilateral adrenalectomy in AIMAH concerning the main laboratory and clinical abnormalities and the patient's quality of life. METHODS: Seven consecutive patients with confirmed AIMAH underwent unilateral adrenalectomy of the largest gland. ACTH and cortisol levels, arterial blood pressure (BP), glycometabolic parameters, and patient's subjective perception of health-related quality of life (by the SF-36 questionnaire) were measured preoperatively and postoperatively. RESULTS: No surgery-related morbidity occurred. One patient with a large contralateral adrenal enlargement required a completion adrenalectomy after 7 months because of persistent hypercortisolism. At a median follow-up of 53 (range, 27-68) months, the remaining six patients were cured, because serum and urinary free cortisol levels significantly decreased and ACTH increased, thus regaining the normal range. Both systolic and diastolic BP levels significantly reduced: 50% of patients definitively became normotensive, and the remaining patients reduced the need for antihypertensive treatment; 40% of patients suffering from preoperative diabetes were cured, whereas 40% reduced the need for hypoglycemizing drug. SF-36 evaluation of the health-related quality of life confirmed a significant amelioration. CONCLUSIONS: Unilateral adrenalectomy of the largest gland can be an effective and safe treatment for AIMAH in case of asymmetric involvement. It may achieve long-term remission of Cushing's syndrome and improve BP values, glycemic control, and patient's quality of life.

Parafibromin expression, single-gland involvement, and limited parathyroidectomy in familial isolated hyperparathyroidism.

BACKGROUND: Familial isolated hyperparathyroidism (FIHPT) is a rare syndrome linked to HRPT2 mutations, with a variable extent of parathyroid involvement. Extensive parathyroidectomy is usually indicated, but single-gland involvement is often reported. Recently, loss of parafibromin expression (caused by HRPT2 inactivating mutations) has been suggested as a distinguishing feature of FIHPT. This study aimed to evaluate the extent of parathyroid involvement and parafibromin expression in FIHPT. METHODS: Twelve patients from 3 FIHPT families underwent bilateral neck exploration, selective excision of macroscopically enlarged parathyroids, and biopsy of the remaining glands. Parafibromin expression was evaluated and compared with that in normal parathyroids and in adenomas arising in sporadic hyperparathyroidism. RESULTS: Pathology confirmed single-gland involvement in all cases (11 adenomas and 1 carcinoma). Limited parathyroidectomy achieved a cure in 91.6% (1 persistent case of parathyroid carcinoma). After a mean follow-up of 9.4 years, all remaining patients are disease free, although 3 underwent successful reoperation for single-gland long-term recurrence. Parafibromin expression was absent in all macroscopically affected glands from FIHPT patients, but present in normal parathyroids and in adenomas arising in sporadic hyperparathyroidism. CONCLUSIONS: Loss of parafibromin expression is a distinguishing marker of parathyroid involvement in FIHPT. Single-gland involvement often occurs; limited parathyroidectomy is effective and achieves long disease-free periods.

Results of iterative surgery for persistent and recurrent parathyroid carcinoma.

BACKGROUND AND AIMS: Parathyroid carcinoma (PC) is a rare cause of primary hyperparathyroidism. Surgery is the only effective treatment; re-operations are often required, because recurrences occur in most of the cases. The aim of this retrospective study was to analyse the rate of biochemical cure, clinical relief, sensitivity of localizing studies and morbidity after re-operations. PATIENTS AND METHODS: From January 1980 to December 2000, 19 patients underwent surgery for PC. PC persisted or recurred in all cases. Fourteen re-operations were performed in six patients. RESULTS: Twelve re-operations at loco-regional site and two pulmonary metastasectomies were performed. Iterative surgery achieved a symptomatic relief in 86% of cases and a transient biochemical remission only in one patient, but significantly reduced parathormone and calcemia. The sensitivity of scintigraphy, CT and ultrasonography was 86, 79 and 100%, respectively. CONCLUSION: When recurrences occur, complete cure of PC is unlikely, despite re-operations. Iterative surgery is associated with some morbidity and never achieves a definitive cure, but provides significant clinical and biochemical palliation. Localizing studies are mandatory but do not detect all recurrences.

Up-to-date on parathyroid carcinoma: analysis of an experience of 19 cases.

BACKGROUND AND OBJECTIVES: Parathyroid carcinoma (PC) is a rare disease; experience with its management is limited. The aim of this retrospective study was to evaluate a relatively large series of patients suffering from PC. METHODS: Since 1980, PC was diagnosed in the 4.7% of cases of primary hyperparathyroidism (HPT) (19 patients). Clinical and biochemical features, and surgical outcome were analyzed. RESULTS: In patients with PC, the mean serum calcium was 3.34 mmol/L; the tumor size 30.5 mm. Malignancy was never diagnosed preoperatively. Thirty-two operations were performed; six patients underwent repeated surgery. Recurrence of HPT was observed in 100% of patients. The median disease-free interval was 15 months (range 2-74 months). Fifteen patients died because of the disease; median survival was 29 months (range 20-146 months). A significant correlation was found between late recurrences and prolonged survival; less advanced age and higher preoperative calcium levels predicted early recurrences. CONCLUSIONS: Preoperative diagnosis of PC is difficult. Preoperative severe hypercalcemia should alert the surgeon. En bloc resection of the PC and the adjacent structures is the treatment of choice. Unfortunately, recurrences are common and long-term survival rate is low.

High prevalence of thyroid ultrasonographic abnormalities in primary aldosteronism.

The study was performed to evaluate the prevalence of thyroid abnormalities detected by ultrasonography and, in particular, of multinodular nontoxic goiter in primary aldosteronism. We analyzed 80 consecutive of patients with primary hyperaldosteronism (40 with unilateral adenoma and 40 with idiopathic hyperaldosteronism) and 80 normotensive healthy controls, comparable for age, sex, iodine intake, and geographical area. Blood pressure, thyroid palpation, thyroid function, and ultrasonography were evaluated. The prevalence of ultrasonographic thyroid abnormalities was 60% in primary aldosteronism and 27% in controls (p < 0.0001). There was a statistically significant difference in prevalence of these abnormalities in unilateral adenoma and idiopathic hyperaldosteronism with respect to controls (p < 0.05 and p < 0.0001, respectively). The prevalence of multinodular nontoxic goiter in idiopathic hyperaldosteronism was higher than in controls (p < 0.001) and, in particular, in female patients. From these data it seems to be worth considering the existence of primary hyperaldosteronism in patients with multinodular goiter and hypertension.