Accidental parathyroidectomy during total thyroidectomy and hypoparathyroidism in a large series of 766 patients: incidence and consequences in a referral center.

PURPOSE: Transient hypoparathyroidism is the most common complication after total thyroidectomy, and accidental parathyroidectomy (AP) may be a cause. The aim of this study was to investigate the incidence of AP and its impact on postoperative calcemia. MATERIALS AND METHODS: From February 2016 to May 2018, 766 patients undergoing total thyroidectomy were prospectively included. Surgical indications, hormonal status, definitive histology, and postoperative calcium and PTH levels were analyzed. RESULTS: 578/(75.45%) were women and 188/(24.55%) men with mean age of 53.4 years. Parathyroid tissue on the thyroid specimen was observed in 40 (5.2%) patients: 30 APs and 10 parathyroid fragments. Among the 30 APs, 12 glands were intrathyroid and 18 (2.3%) in eutopic location. 97 (12.6%) patients were treated for postoperative hypocalcemia: 90 (11.7%) had transient and 5 (0.6%) definitive hypoparathyroidism; 2 were lost in follow-up. 13/30 (43.3%) with AP had transient hypoparathyroidism. A strong correlation was found (p < 0.0001) between AP and postoperative hypocalcemia. 1/30 (3.3%) patient with APs had definitive hypoparathyroidism. Transient and persistent nerve palsies were found in 10 (1.3%) and 3 (0.4%) patients, respectively. DISCUSSION: A careful examination of the thyroid gland after resection help to identify an AP that could be autotransplanted. Surgeon and hospital activity volume per years seem to reduce the risk of hypoparathyroidism. CONCLUSION: Total thyroidectomy and intrathyroid localization of parathyroid glands are risk factors for the AP. The incidence of AP was 2.3%, and this remains low due to our longstanding experience in thyroid and parathyroid surgery.

Predicting risk factors of postoperative hypocalcemia after total thyroidectomy: is safe discharge without supplementation possible? A large cohort study.

PURPOSE: With increasing economic pressures to shorten the length of hospital stay, there has been much recent interest in studying risk factors for the development of postoperative hypocalcemia after total thyroidectomy. The aim of this study was to investigate whether serum calcium and/or PTH levels can predict post-thyroidectomy hypoparathyroidism. METHODS: From January to December 2014, 477 consecutive patients undergoing total thyroidectomy were included. Corrected calcemia and PTH were systematically performed on postoperative day 1/(POD1). Symptomatic patients were treated on POD1 or POD2 with calcium and vitamin D. RESULTS: Sixty-eight patients (14.25%) were treated for postoperative hypocalcemia. No patients with calcemia ≥ 2.16 mmol/l and PTH ≥ 1.9 pmol/l were supplemented and therefore were safely discharged on POD1 (specificity = 100%). All patients with calcemia ≤ 1.89 mmol/l were treated regardless the PTH values (n = 10) (specificity = 100%). For calcium value between 1.9 and 2.16 mmol/l with a PTH > 4.7 pmol/l, nobody was treated. With a calcemia between 1.9 and 2.16 mmol/l and a PTH > 1.9 pmol/l, 44 patients did not develop any symptom. ROC curve analysis showed that combination of Cac = 2.16 mmol/l and iPTH = 4.7 pmol/l provided a sensitivity of 97.06% and a specificity of 76.53% (p < 0.0001). We therefore propose an algorithm that would allow to 70% of patients could have been discharged on POD1 without risk of hypocalcemia or overtreatment. CONCLUSION: Combination of corrected calcemia and PTH on POD1 can efficiently predict hypocalcemia and be integrated into clinical practice for personalizing lengths of hospitalization and appropriate treatment. TRIAL REGISTRATION: ClinicalTrials.gov PRS. Unique Identifying number or registration ID: NCT04372225.

Surgical indications for pituitary tumors during pregnancy: a literature review.

PURPOSE: Surgical indications for pituitary tumors during pregnancy are rare, and are derived from a balance between expected benefits, particularly for maternal benefits, and anesthetic/surgical risks. METHODS: A literature review was performed to define the optimal surgical indications for pituitary adenomas (PA) and other pituitary tumors during pregnancy. RESULTS: Main benefits are expected in case of critical visual impairment and/or life-threatening endocrine disturbances. Multidisciplinary patient management is systematically required although nonobstetric surgery presents a reasonable risk during pregnancy. The risks of congenital malformation during the first trimester and those of premature birth during the third trimester make the second trimester the optimal period for surgery. In prolactin-secreting, nonsecreting, GH- and TSH-secreting PAs, transsphenoidal surgery (TS) is recommended in cases involving severe visual impairment, characterized by severe visual field deficit, visual acuity impairment, and abnormal optical coherence tomography findings, and when no other medical alternatives are possible and/or sufficient. Uncontrolled and severe Cushing's disease (CD) during pregnancy increases both maternal and fetal morbimortality, thus justifying TS or sometimes dopamine agonist therapy as a safer alternative. Finally, metyrapone, ketoconazole, or bilateral adrenalectomy could be recommended in certain cases after the failure of medical therapies and/or TS. Surgery is also required for suprasellar meningiomas, craniopharyngiomas, and pituitary cysts in the case of severe visual deficit. CONCLUSION: Surgical indications for pituitary tumors are rare during pregnancy; therefore, surgery should be avoided when possible. Further, the second trimester should be considered as the optimal surgical period. Severe visual disturbance and uncontrolled CD are the main surgical indications during pregnancy.

Gamma Knife radiosurgery for hypothalamic hamartoma preserves endocrine functions.

Gamma Knife radiosurgery (GK) is an effective treatment for hypothalamic hamartoma. No precise data are available on the risk of endocrine side effects of this treatment. In this study, 34 patients with hypothalamic hamartoma (HH) were followed prospectively at the Department of Endocrinology, La Timone Hospital, Marseille, France, for a mean follow-up of >2 years (mean ± standard deviation [SD] 3.6 ± 2 years). Initial pre- and post-GK radiosurgery evaluations were performed, including weight, body mass index (BMI), and a complete endocrinological workup. At diagnosis, eight patients presented with central precocious puberty at a mean age of 5.4 ± 2.4 years. At the time of GK (mean age 18.2 ± 11.1 years), two patients previously treated with surgery presented with luteinizing hormone/follicle-stimulating hormone (LH/FSH) deficiency. After GK, only one patient presented with a new thyrotropin-stimulating hormone (TSH) deficiency, 2 years after the procedure. The other pituitary axes remained normal in all but two patients (who had LH/FSH deficiency prior to GK). There was no significant difference between pre- and post-GK mean BMI (26.9 vs. 25.1 kg/m2 , p = 0.59). To conclude, in this group of 34 patients, GK did not induce major endocrinologic side effects reported with all the other surgical techniques in the literature. It is, thus, a safe and effective procedure in the treatment of hypothalamic hamartoma.

(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.

Prospective comparison of (68)Ga-DOTATATE and (18)F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases.

PURPOSE: Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors and recent studies have already shown excellent results in the localization of these tumors using (68)Ga-labeled somatostatin analogs ((68)Ga-DOTA-SSA), especially in patients with germline succinate dehydrogenase subunit B gene (SDHB) mutations and head and neck PGLs (HNPGLs). The value of (68)Ga-DOTA-SSA has to be established in sporadic cases, including PHEOs. Thus, the aim of this study was to compare (68)Ga-DOTATATE PET/CT, (18)F-FDOPA PET/CT, and conventional imaging in patients with various PHEOs/PGLs with a special emphasis on sporadic cases, including those located in the adrenal gland. DESIGN: (68)Ga-DOTATATE, (18)F-FDOPA PET/CT, and conventional imaging (contrast-enhanced CT and MRI with MR angiography sequences) were prospectively performed in 30 patients (8 with SDHD mutations, 1 with a MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis or relapse. RESULTS: The patient-based sensitivities were 93 % (28/30), 97 % (29/30), and 93 % (28/30) for (68)Ga-DOTATATE PET/CT, (18)F-FDOPA PET/CT, and conventional imaging, respectively. The lesion-based sensitivities were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for (68)Ga-DOTATATE PET/CT, (18)F-FDOPA PET/CT, and conventional imaging respectively (p = 0.042). (68)Ga-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) than (18)F-FDOPA PET/CT (26/30; p = 0.112) and conventional imaging (24/30; p = 0.024). (68)Ga-DOTATATE PET/CT missed two PHEOs of a few millimeters in size and a large recurrent PHEO. One lesion was considered false-positive on (68)Ga-DOTATATE PET/CT and corresponded to a typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions missed by conventional imaging, 7 were detected by conventional imaging with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent PHEO). CONCLUSION: (68)Ga-DOTATATE PET/CT is the most sensitive tool in the detection of HNPGLs, especially SDHD-related tumors, which may be very small and fail to concentrate sufficient (18)F-FDOPA. The present study further expands the use of (68)Ga-DOTATATE for all patients with HNPGLs, regardless of their genotype. (68)Ga-DOTATATE PET/CT may be inferior to (18)F-FDOPA PET/CT in the detection PHEOs.

Postoperative follow-up of Cushing's disease using cortisol, desmopressin and coupled dexamethasone-desmopressin tests: a head-to-head comparison.

OBJECTIVE: Predicting the outcome of patients operated on for Cushing's disease (CD) is a challenging task. Our objective was to assess the accuracy of immediate postsurgical plasma cortisol, desmopressin test and the coupled dexamethasone-desmopressin test (CDDT) as predictors of outcome. DESIGN AND PATIENTS: Sixty-seven patients with initial remission and a minimal postsurgical follow-up greater than 18 months were included in this retrospective bicentre study. MEASUREMENTS: Follow-up included 3-6 months followed by yearly 24-h urinary-free cortisol, ACTH and cortisol plasmatic levels, a 1-mg overnight dexamethasone suppression test (1-mg DST), desmopressin test and the CDDT. ROC curves were performed to define the optimal threshold of immediate postsurgical cortisol level and 3- to 6-month desmopressin test and CDDT, as predictors of final outcome in comparison with classical biological markers of recurrence. RESULTS: Eleven patients presented recurrence. The patient's median follow-up was 52 months (range, 18-180). As early predictors of outcome, immediate postsurgical plasma cortisol level <35 nmol/l predicted the lack of recurrence with 93% negative predictive value (NPV), whereas predictive positive value (PPV) was 25%. During the follow-up, the CDDT was more precise than the desmopressin test in predicting the lack of recurrence (100% NPV) when performed in the first 3 years after surgery. Positivity of the CDDT was defined based on ROC curves by ACTH and cortisol increments >50%. The CDDT was highly reproducible, as the same response was observed every year in 91% of the patients. CONCLUSIONS: Adding the CDDT the first 3 years after surgery to immediate postsurgical cortisol evaluation should allow obtaining an optimal follow-up management of patients operated for Cushing's disease.

Beyond MEN1, When to Think About MEN4? Retrospective Study on 5600 Patients in the French Population and Literature Review.

CONTEXT: Germline CDKN1B variants predispose patients to multiple endocrine neoplasia type 4 (MEN4), a rare MEN1-like syndrome, with <100 reported cases since its discovery in 2006. Although CDKN1B mutations are frequently suggested to explain cases of genetically negative MEN1, the prevalence and phenotype of MEN4 patients is poorly known, and genetic counseling is unclear. OBJECTIVE: To evaluate the prevalence of MEN4 in MEN1-suspected patients and characterize the phenotype of MEN4 patients. DESIGN: Retrospective observational nationwide study. Narrative review of literature and variant class reassessment. PATIENTS: We included all adult patients with class 3/4/5 CDKN1B variants identified by the laboratories from the French Oncogenetic Network on Neuroendocrine Tumors network between 2015 and 2022 through germline genetic testing for MEN1 suspicion. After class reassessment, we compared the phenotype of symptomatic patients with class 4/5 CDKN1B variants (ie, with genetically confirmed MEN4 diagnosis) in our series and in literature with 66 matched MEN1 patients from the UMD-MEN1 database. RESULTS: From 5600 MEN1-suspected patients analyzed, 4 with class 4/5 CDKN1B variant were found (0.07%). They presented with multiple duodenal NET, primary hyperparathyroidism (PHPT) and adrenal nodule, isolated PHPT, PHPT, and pancreatic neuroendocrine tumor. We listed 29 patients with CDKN1B class 4/5 variants from the literature. Compared with matched MEN1 patients, MEN4 patients presented lower NET incidence and older age at PHPT diagnosis. CONCLUSION: The prevalence of MEN4 is low. PHPT and pituitary adenoma represent the main associated lesions, NETs are rare. Our results suggest a milder and later phenotype than in MEN1. Our observations will help to improve genetic counseling and management of MEN4 families.

Outcome of multimodal therapy in operated acromegalic patients, a study in 115 patients.

INTRODUCTION: Given the new therapeutic options in acromegaly, it seemed important to evaluate the outcome of operated acromegalic patients today. OBJECTIVE: To analyse the characteristics and short- and long-term surgical outcome of patients who underwent transsphenoidal surgery for a growth hormone (GH)-secreting adenoma in our centre and to determine predictive factors of remission. DESIGN AND PATIENTS: This retrospective 10-year study included 115 newly diagnosed acromegalic patients operated on at Timone University Hospital, Marseille, France, between 1997 and 2007. MEASUREMENTS: Initial and long-term outcomes were evaluated using stringent and current remission criteria, associating GH nadir after oral glucose tolerance test <0·4 µg/l and normal insulin-like growth factor-1 (IGF-1) at 3 months, and a normal IGF-1 at the end of follow-up (52·4 ± 36·8 months, median 41 months, range 6·7-135·4 months, n = 99). RESULTS: At the end of follow-up, 90·9% of patients had controlled disease. Overall, 49·5% of patients were in long-term remission after surgery alone, and only 2·0% of patients experienced recurrent disease. Multivariate predictors of 3-month remission included mean GH at diagnosis (P = 0·033), tumour invasion (P = 0·013) and surgeon report of incomplete or uncertain macroscopic resection (P = 0·003 and P = 0·047, respectively). Multivariate predictors at diagnosis of long-term remission included mean GH level (P = 0·048), adenoma size (P = 0·007) and absence of pituitary deficit (P = 0·026). CONCLUSIONS: In long-term follow-up after surgery of acromegaly, half of the patients achieved remission after surgery alone and more than 90% had their disease controlled. With stringent 3-month remission criteria, recurrence was rare.

Functional characterization of nonmetastatic paraganglioma and pheochromocytoma by (18) F-FDOPA PET: focus on missed lesions.

AIMS AND METHODS: To evaluate the clinical value of (18) F-fluorodihydroxyphenylalanine ((18) F-FDOPA) PET in relation to tumour localization and the patient's genetic status in a large series of pheochromocytoma/paraganglioma (PHEO/PGL) patients and to discuss in detail false-negative results. A retrospective study of PGL patients who were investigated with (18) F-FDOPA PET or PET/CT imaging in two academic endocrine tumour centres was conducted (La Timone University Hospital, Marseilles, France and National Institutes of Health (NIH), Bethesda, MD, USA). RESULTS: One hundred sixteen patients (39·7% harbouring germline mutations in known disease susceptibility genes) were evaluated for a total of 195 PHEO/PGL foci. (18) F-FDOPA PET correctly detected 179 lesions (91·8%) in 107 patients (92·2%). Lesion-based sensitivities for parasympathetic PGLs (head, neck, or anterior/middle thoracic ones), PHEOs, and extra-adrenal sympathetic (abdominal or posterior thoracic) PGLs were 98·2% [96·5% for Timone and 100% for NIH], 93·9% [93·8 and 93·9%] and 70·3% [47·1 and 90%] respectively (P < 0·001). Sympathetic (adrenal and extra-adrenal) SDHx-related PGLs were at a higher risk for negative (18) F-FDOPA PET than non-SDHx-related PGLs (14/24 vs 0/62, respectively, P < 0·001). In contrast, the risk of negative (18) F-FDOPA PET was lower for parasympathetic PGLs regardless of the genetic background (1/90 in SDHx vs 1/19 in non-SDHx tumours, P = 0·32). (18) F-FDOPA PET failed to detect two head and neck PGLs (HNPGL), likely due to their small size, whereas most missed sympathetic PGL were larger and may have exhibited a specific (18) F-FDOPA-negative imaging phenotype. (18) F-FDG PET detected all the missed sympathetic lesions. CONCLUSIONS: (18) F-FDOPA PET appears to be a very sensitive functional imaging tool for HNPGL regardless of the genetic status of the tumours. Patients with false-negative tumours on (18) F-FDOPA PET should be tested for SDHx mutations.

Hormonal therapy is associated with better self-esteem, mood, and quality of life in transsexuals.

Few studies have assessed the role of cross-sex hormones on psychological outcomes during the period of hormonal therapy preceding sex reassignment surgery in transsexuals. The objective of this study was to assess the relationship between hormonal therapy, self-esteem, depression, quality of life (QoL), and global functioning. This study incorporated a cross-sectional design. The inclusion criteria were diagnosis of gender identity disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) and inclusion in a standardized sex reassignment procedure. The outcome measures were self-esteem (Social Self-Esteem Inventory), mood (Beck Depression Inventory), QoL (Subjective Quality of Life Analysis), and global functioning (Global Assessment of Functioning). Sixty-seven consecutive individuals agreed to participate. Seventy-three percent received hormonal therapy. Hormonal therapy was an independent factor in greater self-esteem, less severe depression symptoms, and greater "psychological-like" dimensions of QoL. These findings should provide pertinent information for health care providers who consider this period as a crucial part of the global sex reassignment procedure.

Pituitary carcinomas and aggressive pituitary tumours: merits and pitfalls of temozolomide treatment.

Pituitary carcinomas are rare, accounting for about 0.2% of all pituitary tumours. They represent a challenge to clinical practice in both diagnosis and treatment. They may present initially as typical pituitary adenomas, with a delayed appearance of aggressive signs, or as aggressive tumours from the outset. Predicting the pituitary tumour behaviour remains difficult: increased mitotic, Ki-67 and P53 indices might be associated with tumour aggression. The treatment of pituitary carcinomas and aggressive pituitary tumours includes surgery, adjuvant medical treatment, external beam radiotherapy and chemotherapy. Until recently, the treatment of pituitary carcinomas was mainly palliative and did not seem to increase overall survival. Recent case reports have detailed the successful use of temozolomide, an orally administered alkylating agent used to treat malignant gliomas, in the management of pituitary carcinomas and aggressive pituitary tumours. The outcome of treatment might depend on the expression of O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme that potentially interferes with drug efficacy. This review describes the clinical presentation and response to temozolomide in 44 patients with pituitary carcinomas or aggressive pituitary tumours reported in the literature. The results suggest that temozolomide should be considered a drug of major importance in the therapeutic algorithm of aggressive pituitary tumours and pituitary carcinomas. Because of the inconsistency of published data, MGMT expression should probably not be taken as a reason to deny these patients the potential benefit of temozolomide treatment, taking into account the paucity of other available treatments.

Is hormonal therapy associated with better quality of life in transsexuals? A cross-sectional study.

INTRODUCTION: Although the impact of sex reassignment surgery on the self-reported outcomes of transsexuals has been largely described, the data available regarding the impact of hormone therapy on the daily lives of these individuals are scarce. AIMS: The objectives of this study were to assess the relationship between hormonal therapy and the self-reported quality of life (QoL) in transsexuals while taking into account the key confounding factors and to compare the QoL levels between transsexuals who have, vs. those who have not, undergone cross-sex hormone therapy as well as between transsexuals and the general population (French age- and sex-matched controls). METHODS: This study incorporated a cross-sectional design that was conducted in three psychiatric departments of public university teaching hospitals in France. The inclusion criteria were as follows: 18 years or older, diagnosis of gender identity disorder (302.85) according to the Diagnostic and Statistical Manual, fourth edition text revision (DSM-IV TR), inclusion in a standardized sex reassignment procedure following the agreement of a multidisciplinary team, and pre-sex reassignment surgery. MAIN OUTCOME MEASURE: QoL was assessed using the Short Form 36 (SF-36). RESULTS: The mean age of the total sample was 34.7 years, and the sex ratio was 1:1. Forty-four (72.1%) of the participants received hormonal therapy. Hormonal therapy and depression were independent predictive factors of the SF-36 mental composite score. Hormonal therapy was significantly associated with a higher QoL, while depression was significantly associated with a lower QoL. Transsexuals' QoL, independently of hormonal status, did not differ from the French age- and sex-matched controls except for two subscales of the SF-36 questionnaire: role physical (lower scores in transsexuals) and general health (lower scores in controls). CONCLUSION: The present study suggests a positive effect of hormone therapy on transsexuals' QoL after accounting for confounding factors. These results will be useful for healthcare providers of transgender persons but should be confirmed with larger samples using a prospective study design.

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.

The risks of medical treatment of prolactinoma.

First-line treatment of prolactinoma is usually medical, based on dopamine agonists receptors, mainly cabergoline. The classical side-effects of cabergoline (low blood pressure and nausea) have been well known since it was first introduced. Other side-effects, however, are more controversial or simply less frequent, but need to be considered during monitoring. This review will focus on these side-effects: cardiac valvular fibrosis, pleural, pericardial and retroperitoneal fibrosis, addictive/compulsive behaviors, and risks secondary to significantly decreased tumor volume. We will also describe how such side-effects should be monitored and managed. In our opinion, the low prevalence of these side-effects should not cast doubt on the role of cabergoline in the therapeutic algorithm of prolactinoma.

Acromegaly in remission: a view from the partner.

OBJECTIVE: A relative can be an asset in dealing with chronic illnesses, such as acromegaly, where quality of life (QoL) is altered even after remission. However, it has been shown that quality of life of caregivers can also be impacted. Our main objective was to compare the perception of acromegaly in remission in the patient-relative dyad. METHODS: In this observational study, 27 patients in remission and relatives were first asked to complete QoL, anxiety/depression and coping strategy questionnaires. Then, the patient's body image and self-esteem were evaluated from both the patient's and the relative's point of view using the same questionnaires with modified instructions. RESULTS: Relatives had overall an accurate estimation of patient body image using the Figure Rating Scale by Stunkard. However, there were wide variations between the patient's and the relative's responses regarding self-esteem and body perception. The QoL of relatives was not altered and was significantly higher in the social domain than for the patient. CONCLUSIONS: Our results show that relatives require education concerning all the steps involved in the management of acromegaly, as they likely do not fully understand the sequelae of acromegaly.

Role of growth hormone in hepatic and intestinal triglyceride-rich lipoprotein metabolism.

BACKGROUND: Elevated plasma concentrations of hepatic- and intestinally-derived triglyceride-rich lipoproteins (TRL) are implicated in the pathogenesis of atherosclerotic cardiovascular disease and all-cause mortality. Excess of TRL is the driving cause of atherogenic dyslipidemia commonly occurring in insulin-resistant individuals such as patients with obesity, type 2 diabetes and metabolic syndrome. Interestingly, growth hormone (GH)-deficient individuals display similar atherogenic dyslipidemia, suggesting an important role of GH and GH deficiency in the regulation of TRL metabolism. OBJECTIVE: We aimed to examine the direct and/or indirect role of GH on TRL metabolism. METHODS: We investigated the effect on fasting and postprandial hepatic-TRL and intestinal-TRL metabolism of short-term (one month) withdrawal of GH in 10 GH-deficient adults. RESULTS: After GH withdrawal, we found a reduction in fasting plasma TRL concentration (significant decrease in TRL-TG, TRL-cholesterol, TRL-apoB-100, TRL-apoC-III and TRL-apoC-II) but not in postprandial TRL response. This reduction was due to fewer fasting TRL particles without a change in TG per particle and was not accompanied by a change in postprandial TRL-apoB-48 response. Individual reductions in TRL correlated strongly with increases in insulin sensitivity and decreases in TRL-apoC-III. CONCLUSION: In this relatively short term 'loss of function' human experimental model, we have shown an unanticipated reduction of hepatic-TRL particles despite increase in total body fat mass and reduction in lean mass. These findings contrast with the atherogenic dyslipidemia previously described in chronic GH deficient states, providing a new perspective for the role of GH in lipoprotein metabolism.

Lack of delayed neurocognitive side effects of Gamma Knife radiosurgery in acromegaly: the Later-Ac study.

INTRODUCTION: Persistent growth hormone hypersecretion can be observed in roughly 50% of patients operated for somatotroph adenomas, requiring additional treatments. Despite its proven antisecretory efficacy, the use of Gamma Knife radiosurgery (GK) is limited probably due to the lack of data on long-term side effects, including potential cognitive consequences. METHODS: The LATe Effects of Radiosurgery in Acromegaly study was a cross-sectional exposed/unexposed non-randomized study. The primary objective was to determine the long-term neurocognitive effects of GK focusing on memory, executive functions, and calculation ability. Exposed patients had been treated by GK for acromegaly at least 5 years before inclusion. Unexposed patients (paired for age) had to be cured or controlled at last follow-up without any radiation technique. Patients of both groups were cured or controlled at the last follow-up. RESULTS: Sixty-four patients were evaluated (27 exposed and 37 unexposed). Mean follow-up after GK was 13 ± 6 years (including 24 patients followed for at least 10 years). While up to 23.8% of the patients of the whole cohort presented at least one abnormal cognitive test, we did not observe any significant difference in neurocognitive function between both groups. During the follow-up, 11 patients presented at least one new pituitary deficiency (P = 0.009 for thyroid-stimulating hormone deficiency with a higher rate in exposed patients), two presented a stroke (1 in each group), and one presented a meningioma (12 years after GK). CONCLUSIONS: While GK exposes patients to a well-known risk of pituitary deficiency, it does not seem to induce long-term cognitive consequences in patients treated for acromegaly.

Fluctuation analysis of postoperative secretory status in patients operated for acromegaly.

OBJECTIVE: The aim of this study was to describe endocrinological outcome in patients operated on for acromegaly. METHODS: A retrospective study included 167 patients. Patients were assessed in the early postoperative period (EPP), at 3 months (M3), at 1 year (Y1), and then annually. They were classified as grade I (IGF-1 level normal-for-age and positive GH response on oral glucose tolerance test [nadir <0.4ng/L]); grade II (discordant); or grade III or IV (acromegaly, controlled or uncontrolled under medical therapy, respectively). RESULTS: Taking all patients with all grades, 35% changed grades between EPP and M3, 26% between M3 and Y1 and 9% after Y1. In grade I, respectively 22%, 15% and 2% of patients changed grades between EPP and M3, between M3 and Y1, and after Y1, compared to 31%, 6% and 6% in grade IV. Respectively 57%, 67%, and 47% of grade II patients changed grades between EPP and M3, between M3 and Y1, and after Y1; between EPP or M3 and last follow-up (>1 year), respectively 74% and 75% of grade II patients changed grades. Knosp category, resection quality and abnormal GH response (vs. abnormal IGF-1) significantly impacted grade II patients' outcome. CONCLUSIONS: Whereas outcome in grades I and III-IV seems to be determined by 1 year, grade II discordant patients' outcome remains uncertain even after 1 year.

18F-FDG avidity of pheochromocytomas and paragangliomas: a new molecular imaging signature?

UNLABELLED: Our objective was to evaluate (18)F-FDG PET uptake in patients with nonmetastatic and metastatic chromaffin-derived tumors. METHODS: Twenty-eight consecutive unrelated patients with chromaffin tumors, including 9 patients with genetically determined disease, were studied. A combination of preoperative imaging work-up, surgical findings, and pathologic analyses was used to classify the patients into 2 groups: those with nonmetastatic disease (presumed benign, n = 18) and those with metastatic tumors (n = 10). (18)F-FDG PET was performed in all cases. Visual and quantitative analyses were individually graded for each tumor. Somatic mutations of the succinate dehydrogenase subunits B and D and Von-Hippel Lindau genes were also evaluated in 6 benign sporadic tumor samples. RESULTS: All but 2 patients showed significantly increased (18)F-FDG uptake on visual analysis. The maximum standardized uptake value (SUVmax) ranged from 1.9 to 42 (mean +/- SD, 8.2 +/- 9.7; median, 4.6) in nonmetastatic tumors and 2.3 to 29.3 (mean +/- SD, 9.7 +/- 8.4; median, 7.4) in metastatic tumors. No statistical difference was observed between the groups (P = 0.44), but succinate dehydrogenase-related tumors were notable in being the most (18)F-FDG-avid tumors (SUVmax, 42, 29.3, 21, 17, and 5.3). Succinate dehydrogenase and Von-Hippel Lindau-related tumors had a significantly higher SUVmax than did neurofibromatosis type 1 and multiple endocrine neoplasia type 2A syndrome-related tumors (P = 0.02). (18)F-FDG PET was superior to (131)I-metaiodobenzylguanidine in all metastatic patients but one. By contrast, (18)F-FDG PET underestimated the extent of the disease, compared with 6-(18)F-fluorodopa PET, in 5 patients with metastatic pheochromocytoma. However, succinate dehydrogenase mutations (germline and somatic) and functional dedifferentiation do not adequately explain (18)F-FDG uptake since most tumors were highly avid for (18)F-FDG. CONCLUSION: (18)F-FDG PET positivity is almost a constant feature of pheochromocytomas and paragangliomas. It may be considered a molecular signature of such tumors, although which aspect of the plethora of molecular changes associated with dedifferentiation, germline genetic defects, or the adaptive response to hypoxia is responsible for this characteristic requires further elucidation.