Pheochromocytoma diagnosed during pregnancy: lessons learned from a series of ten patients.

BACKGROUND: Pheochromocytoma (PHEO) in pregnancy is a life-threatening condition. Its management is challenging with regards to the timing and type of surgery. METHODS: A retrospective review of the management of ten patients diagnosed with pheochromocytoma during pregnancy was performed. Data were collected on the initial diagnostic workup, symptoms, treatment, and follow-up. RESULTS: PHEO was diagnosed in ten patients who were between the 10th and the 29th weeks of pregnancy. Six patients had none to mild symptoms, while four had complications of paroxysmal hypertension. Imaging investigations consisted of MRI, CT scan and ultrasounds. All had urinary metanephrines, measured as part of their workup. Three patients had MEN 2A, one VHL syndrome, one suspected SDH mutation. All patients were treated either with α/ß blockers or calcium channel blockers to stabilize their clinical conditions. Seven patients underwent a laparoscopic adrenalectomy before delivery. Three out of these seven patients had a bilateral PHEO and underwent a unilateral adrenalectomy of the larger tumor during pregnancy, followed by a planned cesarean section and a subsequent contralateral adrenalectomy within a few months after delivery. Three patients had emergency surgery for maternal or fetal complications, with C-section followed by concomitant or delayed adrenalectomy. All newborns from the group of planned surgery were healthy, while two out three newborns within the emergency surgery group died shortly after delivery secondary to cardiac and pulmonary complications. CONCLUSIONS: PHEO in pregnancy is a rare condition. Maternal and fetal prognosis improved over the last decades, but still lethal consequences may be present if misdiagnosed or mistreated. A thorough multidisciplinary team approach should be tailored on an individual basis to better manage the pathology. Unilateral adrenalectomy in a pregnant patient with bilateral PHEO may be an option to avoid the risk of adrenal insufficiency after bilateral adrenalectomy.

Correction to: Pheochromocytoma diagnosed during pregnancy: lessons learned from a series of ten patients.

The original article was updated to correct the listing of A. Hamy's name; it is correct as displayed above.

Assessment of the Aldosteronona resolution score as a predictive resolution score of hypertension after adrenalectomy for aldosteronoma in French patients.

PURPOSE: Aldosteronoma Resolution Score (ARS) is a predictive score for cure of hypertension after adrenalectomy for hyperaldosteronism and has been validated in American patients. The aim of the study was to validate this score in a French population. METHOD: Data concerning patients operated from 2002 to 2015 in 7 French University Hospitals were retrospectively collected. Diagnosis of Aldosterone-producing adenoma (APA) was confirmed with clinical and biochemical hyperaldosteronism and adrenal nodule on CT scan. Adrenal venous sampling was performed when CT failed to identify laterality. ARS is based on four variables: female sex, BMI ≤25 kg/m2, duration of hypertension ≤6 years, number of antihypertensive medications ≤2. One point is attributed for the first three and 2 points for the last. Patients were considered as cured if they had no hypertension and no antihypertensive medications at least 6 months after surgery. Patients with bilateral adrenal hyperplasia were excluded. RESULTS: This multicenter study included 310 patients with APA. ARS and follow-up were obtained in 257 patients. 46.6% of patients were cured and potassium serum level was normalized in 97.7%. In multivariate analysis, odds ratio for female sex, BMI ≤25 kg/m2, duration of hypertension ≤6 years, and number of antihypertensive medications ≤2 were 1.60 (p = 0.09), 1.77 (p = 0.04), 1.28 (p = 0.4), 3.41 (p < 0.001), respectively. Cure rate were, respectively, 22.2, 41.4 and 74% for patients with a score ARS 0-1, 2-3, 4-5. The area under the curve (AUC) of ARS was 0.715. CONCLUSION: ARS is not a predictive score efficient enough in a French population maybe due to different metabolic data and genetic conditions.

Surgery for recurrent adrenocortical carcinoma: A multicenter retrospective study.

BACKGROUND: Adrenocortical carcinoma is a rare neoplasm with a high rate of recurrence. We studied the impact of surgery on the survival in recurrent adrenocortical carcinoma patients. METHODS: We performed a retrospective review of patients with recurrent adrenocortical carcinoma, managed in 5 French University Hospitals between 1980 and 2014. We compared surgery and medical management for ACC recurrence. RESULTS: Fifty-nine patients were included, 46 of whom had an initial R0 resection. Twenty-nine patients underwent reoperation for recurrence, while 30 had nonoperative treatments. Operated patients had a greater median overall survival after recurrence than nonoperated patients (91 vs 15 months; P < .001). Patients operated on for local or distant recurrence had similar overall survival (110 vs 91 months; P = .81). In nonoperated patients, types of medical managements did not impact survival. Surgery for recurrence (P = .037) and a disease-free interval between initial resection and recurrence >12 months (P = .059) were both prognostic factors for improved survival, whereas age, stage, and tumor size (P ≥ .2 each) were not. A Ki67 <25% tended to be associated with better overall survival (P = .051). CONCLUSION: Both surgery for recurrence and disease-free interval between the initial resection of an adrenocortical carcinoma and recurrence >12 months are associated with better overall survival.

Is the 2-cm size cutoff relevant for small nonfunctioning pancreatic neuroendocrine tumors: A French multicenter study.

BACKGROUND: Nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are often discovered at a small size. No clear consensus exists on the management of NF-PNETs ≤ 2 cm. The aim of our study was to determine the prognostic value of indicators of malignancy in sporadic NF-PNETs ≤ 2 cm. METHODS: Eighty patients were evaluated retrospectively in 7 French University Hospital Centers. Patients were managed by operative resection (operative group [OG]) or observational follow-up (non-OG [NOG]). Pathologic characteristics and outcomes were analyzed. RESULTS: Sixty-six patients (58% women) were in the OG (mean age, 59 years; 95% CI, 56.0-62.3; mean tumor size, 1.6 cm; 95% CI, 1.5-1.7); 14 (72% women, n = 10) were in the NOG (mean age, 63 years; 95% CI, 56-70; mean tumor size, 1.4 cm; 95% CI, 1.0-1.7). All PNETs were ranked using the European Neuroendocrine Tumor Society grading system. Fifteen patients (19%) had malignant tumors defined by node or liver metastasis (synchronous or metachronous). The median disease-free survival was different between malignant and nonmalignant PNETs, respectively: 16 (range, 4-72) versus 30 months (range, 1-156; P = .03). On a receiver operating characteristic (ROC) curve, tumor size had a significant impact on malignancy (area under the curve [AUC], 0.75; P = .03), but not Ki-67 (AUC, 0.59; P = .31). A tumor size cutoff was found on the ROC curve at 1.7 cm (odd ratio, 10.8; 95% CI; 2.2-53.2; P = .003) with a sensitivity of 92% and a specificity of 75% to predict malignancy. CONCLUSION: Based on our retrospective study, the cutoff of 2 cm of malignancy used for small NF-PNETs could be decreased to 1.7 cm to select patients more accurately.

A novel mutation in the calcium-sensing receptor in a French family with familial hypocalciuric hypercalcaemia.

OBJECTIVE: The calcium-sensing receptor (CASR) has an important role in calcium homoeostasis by controlling PTH secretion and renal calcium handling. Inactivating mutations in the CASR gene (HGNC ID: 1514) cause familial hypocalciuric hypercalcaemia (FHH). We present a case of FHH patient to describe a novel mutation in the CASR. SUBJECTS AND METHODS: A 34-year-old patient was referred because of recurrent hypercalcaemia after resection of two hyperplastic parathyroids. Extensive evaluation found elevated PTH and low calcium/creatinine clearance ratio. One of her three children had high serum calcium concentrations. Genetic studies were performed by PCR amplification of CASR coding exons and direct sequencing of PCR products. Transient transfection of the wild-type (WT) CASR and the mutant CASR into COS-7 was performed to assess functional impact of the mutation and the capacity of either protein to mediate increases in cellular levels of inositol phosphates (IPs). RESULTS: CASR sequencing found a previously undescribed heterozygous base substitution, determining a change of threonine to isoleucine at codon 550 (p.T550I) in the sixth exon. In contrast to those transfected with WT CASR, which showed a five- to eightfold increase in total IPs at high levels of calcium, COS-7 cells transfected with the (p.T550I) mutant showed no increase confirming to the inactivating nature of the mutation. COS-7 cells co-transfected with the WT and the (p.T550I) mutant showed an intermediate response suggesting a possible dominant negative effect. CONCLUSION: This case report presents a not-yet-described mutation in the cysteine-rich region of the CASR extracellular domain, a mutation with a possible dominant negative effect.

[BRAF V600E mutation in papillary thyroid carcinoma: prevalence and detection in fine needle aspiration specimens]. / Mutation BRAF V600E et carcinomes papillaires de la thyroïde : prévalence et faisabilité de la détection sur produits de cytoponction.

UNLABELLED: BRAF V600E mutation in papillary thyroid carcinoma (PTC): prevalence and detection in fine needle aspiration (FNA) specimens. BACKGROUND AND OBJECTIVE: The activating mutation of the BRAF gene, T1799A, is the most common and specific genetic alteration in PTC. In the present study, our aims were to confirm these data and investigate the feasibility of BRAF mutation detection in FNA specimens. METHODS: In a retrospective study, we examined paraffin-embedded surgical samples of 57 PTC and 51 non-PTC thyroid tumors for the presence of BRAF mutation by dideoxy sequencing. We analyzed thyroid aspirates (drop and washed-out solution) and smears from 31 patients who underwent thyroidectomy, before intraoperative frozen sections, and 25 archival thyroid FNA smears. RESULTS: The BRAF mutation was present in 58 % of PTC. Among non-PTC thyroid tumors, only one medullary thyroid carcinoma contained the BRAF mutation. BRAF mutation was correctly detected from the FNA-derived materials. Considering the search of BRAF mutation in preoperative FNA smears, the diagnosis of PTC would have been affirmed in 31 % (4/13) of indeterminate and suspicious FNA. CONCLUSION: BRAF mutation detection in FNA specimens is feasible and could be used as an adjunct tool for preoperative diagnosis of PTC classified as indeterminate and suspicious with conventional cytology (categories 3, 4 and 5 according to NCI/Bethesda 2008 terminology).

Expression of sex steroid hormone receptors in C cell hyperplasia and medullary thyroid carcinoma.

Previous studies have shown that C cells are twice as numerous in male than in female thyroids and that C cell hyperplasia (CCH) is much more frequent in men. These findings suggest regulation involving sex steroid hormones through the expression of sex steroid hormone receptors on C cells. To investigate this hypothesis, we performed an immunohistochemical study of estrogen receptors alpha (ER alpha) and beta (ER beta), progesterone receptors (PR), and androgen receptors (AR) on specimens from a series of 40 patients operated on for a medullary thyroid carcinoma (MTC; n=28; female 18, male 10) and/or CCH (n=19; female 6, male 13). ER beta was the only receptor to be consistently expressed in CCH (100%) and MTC (96.5%), whereas ER alpha was never expressed. PR and AR were rarely expressed in MTC (7 and 14%, respectively). AR was expressed in half the CCH cases (53%), with a trend to male predominance (61% in men vs 33% in women). Our study is the first to describe ER beta expression in CCH. In addition, our findings suggest that CCH, and possibly MTC, might be influenced by sex steroid hormones, namely, estrogens and androgens, through the expression of ER beta and AR on C cells.

Acute diverticulitis in very young patients: a frequent surgical management.

PURPOSE: The natural history of sigmoid diverticulitis in terms of the virulence and management in young patients is an ongoing controversy. This retrospective study was designed to assess the severity and early management of acute diverticulitis according to age. METHODS: From 2000 to 2004, 284 patients were admitted for acute diverticulitis. Fifty-two patients (18 percent) were aged 50 years or younger and were divided in two groups: aged 40 years or younger (Group 1, n = 20), and patients older than aged 40 years (Group 2, n = 32). The diagnosis was confirmed by computed tomography in 49 patients (94 percent). RESULTS: Radiologic findings showed that the rate of complicated lesions (i.e., diverticular perforation and/or abscess) was significantly higher for patients younger than aged 40 years than patients older, respectively 72 and 35 percent (P = 0.02). The risk of requiring immediate surgical treatment was significantly more frequent in Group 1 than Group 2 (40 vs.13 percent; P = 0.04). There was a trend toward a higher risk of "major surgery" (i.e., Hartmann's procedure) in Group 1 than Group 2 (15 vs. 0 percent; P = 0.05). CONCLUSIONS: Diverticulitis in patients younger than aged 40 years seems to have a particularly aggressive and fulminant course and requires early surgical procedures for complications (associated abscess, colonic perforation) in 40 percent of cases. The use of "major procedure" (i.e., stoma) is more frequent in these patients.

Management and prognosis of metastases to the thyroid gland.

BACKGROUND: Intrathyroid metastases (ITM) of extrathyroid cancer are rare and have a poor prognosis. The aim of this work was to identify the sites of primary cancers and the treatment and prognosis of these lesions. STUDY DESIGN: This retrospective study was carried out on patients treated between 1982 and 2002 in the surgical departments of the University hospitals of Poitiers, Limoges, Tours, and Nantes, France. All diagnoses were confirmed by cytology or histologic examination. RESULTS: Twenty-nine patients (41 to 78 years) had ITM. Primary cancers were renal cell in 16 patients, lung in 4, digestive in 4, sarcoma in 1, melanoma in 1, neuroendocrine in 1, and of unknown origin in 1 patient. For 10 patients, diagnoses of primary cancer and ITM were synchronous. For 19 patients, delay between diagnosis of the primary cancer and ITM was 6.8 years (2 months to 16 years). Diagnosis was confirmed with fine-needle aspiration 3 times and with histologic examination of the thyroid 26 times. Twenty-seven patients had thyroidectomy; two were not operated on. After treatment of ITM, 13 patients had new metastatic sites. Mean followup for all patients was 2.3 years. Seven patients (24%) (6 with renal cancer) were disease free (followup 4.5 years). Four patients were alive with disease (followup 1.4 years). Eighteen patients (62%) died of their disease at a mean delay of 1.4 years. CONCLUSIONS: ITM are rare but the diagnosis should be borne in mind when patients have a history of cancer (mainly renal cancer). Preoperative diagnosis and complete evaluation could avoid unnecessary thyroidectomy because numerous patients had diffuse metastases.