Background Alpha-blockade is the standard management preoperatively to prevent intraoperative hemodynamic instability (IHD) during resection of a pheochromocytoma. Calcium channel blockers also have ...been shown to lessen the risk of IHD. We aim to determine differences between these classes of antihypertensive agents in minimizing IHD. Methods This was a retrospective analysis from a tri-institutional database. Inclusion criteria were unilateral transabdominal adrenalectomy for pheochromocytomas between 2002 and 2012. IHD was defined as at least one systolic blood pressure (SBP) measurement >160 mm Hg and at least one episode of mean arterial pressure 60 mm Hg. Results A total of 155 patients were included: 110 receiving calcium channel blockers, 41 alpha-blockade, and 4 no medication. Intraoperatively, mean maximal SBP was less after alpha-blockade ( P < .0001) as well as the incidence and duration of episodes of SBP >200 mm Hg ( P < .01); however, severe hypotensive episodes (MAP <60 mm Hg) were more frequent ( P < .001) and longer ( P < .0001) with alpha-blockade. Consequently, intraoperative vasoactive drugs were used more frequently ( P = .03), and mean fluid volume infused was larger ( P < .001). Fifty-four patients had IHD, but these were independent of type of preoperative medication used. Familial disease was the only independent predictor of IHD. Conclusion IHD was independent of type of preoperative medical management but was dependent on familial disease. These findings broaden options for clinicians in the preoperative management of pheochromocytoma.
Immune control point (ICI) inhibitors represent a significant advance in the management and survival of cancers such as melanoma or non-small cell bronchial carcinoma. However, they induce unusual ...side effects, such as hypophysitis, which are rarely described elsewhere. This nationwide retrospective study describes the characteristics of hypophysitis reported in the French pharmacovigilance database (FPVD). We requested for all cases of ICI-related hypophysitis registered in the FPVD before May 2018. An endocrinologist and a pharmacologist reviewed all cases. About 94 pituitary cases were selected, involving 49 females and 45 men. Ipilimumab alone or in combination was the most represented ICI (56%). Most cases (61%) were grade 3 severity and the majority (90%) were corticotropic deficiency cases. Cases with thyroid and/or gonadotropic involvement were 21% and 1% respectively. Five patients (8%) had panhypopituitarism. Pituitary MRI, when performed, was in favor of hypophysitis in 50%. No patient recovered his previous hormonal function. The mean time of onset was significantly shorter with ipilimumab than other ICIs. ICI-related hypophysitis generate deficits that do not spontaneously recover, even at a distance from the event, unlike thyroiditis. Patients must then benefit from long-term coordinated onco-endocrinological management, adapted to their own specific deficits.
Current histoprognostic parameters and prognostic scores used in paragangliomas and pheochromocytomas do not adequately predict the risk of metastastic progression and survival. Here, using a series ...of 147 cases of paraganglioma and pheochromocytoma, we designed and evaluated the potential of a new score, the COPPS (COmposite Pheochromocytoma/paraganglioma Prognostic Score), by taking into consideration three clinico-pathological features (including tumor size, necrosis, and vascular invasion), and the losses of PS100 and SDHB immunostain to predict the risk of metastasis. We compared also the performance of the COPPS with several presently used histoprognostic parameters in risk assessment of these tumors. A PASS score (Pheochromocytoma of the Adrenal gland Scaled Score) ≥ 6 was significantly associated with the occurrence of metastases (
P
< 0.0001) and shorter PFS (
P
= 0.013). In addition, both MCM6 and Ki-67 LI correlated with worse PFS (
P
= 0.004 and
P
< 0.0001, respectively), and MCM6, but not Ki-67, was significantly higher in metastatic group (
P
= 0.0004). Loss of PS100 staining correlated with the occurrence of metastasis (
P
< 0.0001) and shorter PFS (
P
< 0.0001). At a value of greater or equal to 3, the COPPS correlated with shorter PFS (
P
< 0.0001), and predicted reproducibly (weighted Kappa coefficient, 0.863) the occurrence of metastases with a sensitivity of 100.0% and specificity of 94.7%. It thus surpassed those found for either PASS, SDHB, MCM6, or Ki-67 alone. In conclusion, while validation is still necessary in independent confirmatory cohorts, COPPS could be of great potential for the risk assessment of metastasis and progression in paragangliomas and pheochromocytomas.
Vitamin D-dependent rickets type 1B (VDDR1B) is an autosomal semidominant genetic disorder caused by a deficiency in
CYP2R1,
which encodes vitamin D 25-hydroxylase, an enzyme that plays a crucial ...role in the conversion of vitamin D to 25-dihydroxyvitamin D
3
. VDDR1B is a severe form of rickets that occurs during infancy and which is responsive to 25-OH vitamin D supplementation. We studied three adult patients from a multi-consanguineous family with VDDR1B. They have been diagnosed with pseudo-nutritional rickets and treated during their adolescence with 25-OH vitamin D. These patients stopped their treatments at the end of adolescence and were contacted 14 to 17 years later when VDDR1B diagnosis was carried out in their niece and nephews. These three patients had undetectable 25-OH vitamin D, but normal levels of plasma 1–25(OH)
2
vitamin D. All patients had a hip bone mineral density and a normal vertebral despite osteoarthritis degenerative lesions which may impact BMD evaluation. These findings show that vitamin D supplementation has a questionable effect, if any, for osteoporosis prevention in adulthood in contrast to its crucial importance during infancy and adolescence.
Abstract Objectives To update the recommendations on the prevention and treatment of glucocorticoid-induced osteoporosis issued in 2003 by the French National Authority for Health (HAS). This update ...was performed under the aegis of the Bone Section of the French Society for Rheumatology (SFR) and Osteoporosis Research and Information Group (GRIO), in collaboration with four French learned societies (primary-care, gastroenterology, internal medicine, and nephrology). Methods A task force composed of members of the medical specialties involved in managing patients with glucocorticoid-induced osteoporosis conducted a systematic literature review according to the method developed by the HAS then used the results to develop updated recommendations. Results These recommendations are intended for all physicians involved in the management of patients who are scheduled to start, or are taking, long-term glucocorticoid therapy (≥ 3 months) in any dose and for any reason. In postmenopausal women and men older than 50 years of age, treatment is warranted in the presence of any of the following risk factors for fracture: history of bone frailty fracture after 50 years of age, bone mineral density T-score ≤ −2.5 at one or more sites, age ≥ 70 years, and dosage ≥ 7.5 mg/d prednisone-equivalent for longer than 3 months. Bisphosphonates can be used in all these situations; teriparatide can be given as first-line therapy in patients at high fracture risk but is reimbursed by the French statutory health insurance system only in patients having two or more prevalent vertebral fractures. The fracture risk is lower in nonmenopausal women and in men younger than 50 years of age, in whom treatment decisions should rest on a case-by-case evaluation. Conclusion These recommendations are intended to clarify the pharmacological management of glucocorticoid-induced osteoporosis.
Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The ...expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking.
To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes.
This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes.
Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized.
Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female 65.0% and 340 male 35.0%; age range, 8-80; mean SD age, 41.0 13.3 years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation carriers (48%) and in 23 of 29 SDHA mutation carriers (79%), particularly with head and neck paraganglioma. MAX disease occurred almost exclusively in the adrenal glands with frequently bilateral tumors. Penetrance in the largest subset, SDHA carriers, was 39% at 40 years of age and is statistically different in index patients (45%) vs mutation-carrying relatives (13%; P < .001).
The SDHA, TMEM127, MAX, and SDHAF2 genes may contribute to hereditary pheochromocytoma and paraganglioma. Genetic testing is recommended in patients at clinically high risk if the classic genes are mutation negative. Gene-specific prevention and/or early detection requires regular, systematic whole-body investigation.
Abstract Background This study evaluates the perioperative outcomes of robotic-assisted adrenalectomy (RA) compared with lateral transperitoneal laparoscopic adrenalectomy (LA). Methods Prospective ...evaluation of 50 patients who underwent unilateral RA versus 59 patients who underwent unilateral LA. Results RA was associated with lower blood loss (49 mL) but longer operative times (104 minutes) ( P <.001). However, the difference in operative time was not significant after the learning curve of 20 cases. In patients with body mass index (BMI) ≥30 kg/m2 , mean operative time was longer in the LA group (90 vs 78 minutes, P = .03) but not in the RA group. In patients with large tumors (≥55 mm), mean operative time was longer in the LA group (100 vs 80 minutes, P = .009) but not in the RA group. Conversion rate, morbidity, and hospital stay were similar in both groups. Conclusions After a learning curve of 20 cases, RA has similar perioperative outcomes compared to lateral transperitoneal LA. Several criteria (previous laparoscopic expertise, first assistant’s skill and tumor side) remain determinative on RA operative time.
Abstract Denosumab is an anti-RANK ligand (RANKL) monoclonal antibody approved for the treatment of postmenopausal osteoporosis and prevention of skeletal metastasis complications. Administered ...subcutaneously every 6 months, it reduces the risk of vertebral fracture by 70% and of hip fracture by 40%. Its safety profile is acceptable. Denosumab may be used to treat patients with moderate to severe renal insufficiency. It has anti-fracture activity equivalent to that of zoledronic acid, but no residual effect, and no action at all beyond 6 months. In France, denosumab is reimbursed as a second-line treatment after a first attempt with bisphosphonate.
Purpose
Thyrotropin-secreting pituitary adenomas (TSHomas) represent a rare subtype of pituitary tumors. Neurosurgery (NCH) is still considered the first-line therapy. In this study we aimed to ...investigate the outcome of different treatment modalities, including first line somatostatin analogs (SSA) treatment, with a specific focus on neurosurgery-related complications.
Methods
We retrospectively evaluated thirteen patients diagnosed for TSHomas (9 M; age range 27–61). Ten patients had a magnetic resonance evidence of macroadenoma, three with slight visual field impairment. In the majority of patients, thyroid ultrasonography showed the presence of goiter and/or increased gland vascularization. Median TSH value at diagnosis was 3.29 mU/L (normal ranges 0.2–4.2 mIU/L), with median fT4 2.52 ng/dL (0.9–1.7 ng/dL).
Results
Three patients (two microadenoma) were primarily treated with NCH and achieved disease remission, whereas ten patients (nine macroadenomas) were initially treated with SSA. Despite the optimal biochemical response observed during medical treatment in most patients (mean TSH decrease −72 %), only two stayed on medical therapy alone, achieving stable biochemical control at the end of the follow-up. The remaining patients (n = 7) underwent NCH later on during their clinical history, followed by radiotherapy or adjuvant SSA treatment in two cases. Noteworthy, five of them developed hypopituitarism. All patients reached a biochemical control, after a multimodal therapeutic approach.
Conclusions
Neurosurgery ultimately led to complete disease remission or to biochemical control in majority of patients, whereas resulting in a considerable percentage of post-operative complications (mainly hypopituitarism, 50 %). In the light of the optimal results unanimously reported for medical treatment with SSA, our experience suggests that a careful evaluation of risk/benefit ratio should be taken into consideration when directing the treatment approach in patients with TSHoma.
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