L'Hormona adrenocorticòtropa plasmàtica en el període postoperatori immediat com a índex predictor de la curació de la malaltia de Cushing

S'ha proposat que un valor de cortisol plasmàtic menor de 50 nmol/l en el període postoperatori immediat després de la cirurgia transesfenoïdal de la malatia de Cushing és un factor predictiu del seu guariment. No obstant això, les dades dels nivells de l'hormona adrenocorticòtropa (ACTH) en el període postoperatori immediat són minses. El propòsit d'aquest estudi fou establir si els nivells d'ACTH plasmàtica en el període postoperatori immediat després de la cirurgia transesfenoïdal de la malaltia de Cushing pot predir el guariment d'aquesta i comparar el seu valor pronòstic amb els del cortisol sèric. Vàrem analitzar tretze malalts amb malaltia de Cushing (edat mitjana de quaranta-tres anys) tractats amb cirurgia transesfenoïdal. Es varen prendre mostres per a cortisol sèric i ACTH plasmàtica en els set primers dies després de la cirurgia. El seguiment fou de dotze a cinquanta- cinc mesos (mitjana de trenta-quatre mesos). Durant aquest període per avaluar l'estat clínic hormonal es va mesurar de forma periòdica el cortisol sèric basal i després de l'estimulació amb 250 µg d'ACTH1-24, ACTH basal plasmàtic, cortisol lliure urinari i la prova de la frenació amb dexametasona a dosis baixes (0,5 mg/6 h durant dos dies). Dotze malalts (92,3 %) estaven en remissió durant el seguiment. El cortisol sèric en el període postoperatori immediat fou de 50 nmol/l en tan sols quatre de dotze malalts en remissió, mentre que els nivells d'ACTH plasmàtica foren de 2 pmol/l o menys en sis d'aquests malalts. Els valors normals d'ACTH es troben entre 2 i 12 pmol/l. Es conclou que els nivells d'ACTH plasmàtica mesurats en la primera setmana del període postoperatori no són un millor predictor que els nivells de cortisol sèric en el postoperatori immediat. Un valor d'ACTH plasmàtica molt baix no pot predir guariment.A plasma cortisol less than 50 nmol/l in the early postoperative stage after transsphenoidal surgery for Cushing’s disease has been proposed as predictive of cure. Data on postoperative plasma adrenocorticotropin (ACTH) are scarce. The purpose of this study was to establish whether plasma ACTH in the early postoperative period after transsphenoidal surgery for Cushing’s disease can predict cure and to compare its prognostic value with that of plasma cortisol. We analysed thirteen patients with Cushing’s disease (mean age forty-three years) treated with transsphenoidal surgery. Plasma cortisol andACTHsamples were taken in the first seven days after surgery. Follow-up was between twelve and fifty-five months (mean thirtyfour months). During this time samples for basal plasma cortisol and after stimulation with 250 µg of ACTH1-24, basal plasma ACTH, 24 hours free urinary cortisol and low-dose suppression with dexametasone (0,5 mg/6 h for two days) were taken periodically to evaluate their clinical status. Twelve patients (92,3 %) were in remission during follow-up. The early postoperative cortisol level was 50 nmol/l or less in only four of the twelve patients in remission, while the ACTH level was 2 pmol/l or less in six of these patients. Normal values for ACTH are between 2 and 12 pmol/l. The value of plasma ACTH levels measured in the first postoperative week is not a better predictor of cure than early postoperative plasma cortisol level. A very low plasma ACTH level can not predict cure

Adenoma hipofisiario no funcionante: estudio clínico y patológico

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Non-functioning pituitary adenoma underwent surgery: a multicenter retrospective study over the last four decades (1977–2015)

[Abstract] Objective. To assess clinical features, diagnostic procedures, therapies and outcomes in patients with clinically non-functioning pituitary adenomas (NFPAs) surgically treated over the last four decades. Design and methods. A multicenter retrospective study in NFPA patients periodically followed up in specialized neuroendocrinology units who underwent surgery in the period 1977–2015 was performed. Results. A total of 131 patients were studied [66 women (50.4%); mean age 52.6 ± 14.8 years (range, 15–82)]. Median diameter of the adenoma was 2.6 cm (interquartile range, 2.0–3.1). The most frequently type of surgery used was endoscopic endonasal surgery (58.5%) followed by microscopic transsphenoidal surgery (37.4%). Radiation therapy was used in 19 patients (14.5%). Ki-67 labeling index performed in 54 patients was ≤ 2% in 70% samples. After a median follow-up time of 57 months (25 to 128 months), tumor diameter significantly decreased to 0.9 cm (0–1.8 cm), p < 0.001. Multivariant analysis showed that endoscopic endonasal surgery (HR 2.74, 1.06–6.87, p = 0.036) and radiotherapy (HR 0.04, 0.02–0.65, p = 0.024) behaved as positive and negative predictors, respectively, of tumor absence in the follow-up. Endoscopic endonasal surgery (HR 6.71, 1.45–31.05, p = 0.015) was the only positive predictor for complete cure in the follow-up. Conclusion. NFPAs surgically treated in Spain are usually macroadenomas diagnosed around the sixth decade of life with no sex predilection. Type of surgery is associated with clinical outcome. Endoscopic endonasal surgery behaves as a positive predictor for the absence of tumor imaging and complete cure in the follow up

Clinical features and natural history of clinically non-functioning pituitary incidentalomas

ePoster presentation: pituitary and neuroendocrinologyDisclaimer: this is not the definitive version of record of this article. This manuscript has been accepted for publication in Endocrine Abstracts, but the version presented here has not yet been copy-edited, formatted or proofed. Consequently, Bioscientifica accepts no responsability for any errors or omissions it may contains. The definitive version in now freely avaliable at Endocrine Abstracts web page

Prevalence, clinical features, and natural history of incidental clinically non-functioning pituitary adenomas

[Abstract] The objective of the study was to assess the prevalence and clinical features of incidentally discovered clinically non-functioning pituitary adenoma (CNFPA) and to analyze its natural history. A multicenter retrospective study in patients diagnosed with incidental CNFPA periodically followed-up in 3 specialized neuroendocrinology units from 1992 to 2015 was performed. Out of a total of 189 CNFPA patients, 57 cases (30.1%; 29 women; age at diagnosis 55.8±16.7 years) were incidental. Most patients (n=55, 96.5%) were diagnosed by magnetic resonance imaging (MRI). A sum of 71.9% (n=41) were macroadenomas; 2 of them (3.5%) were giant adenomas (≥4 cm). Patients with macroadenomas were older than those with microadenomas (59.5±16.7 vs. 46.4±18.1 years, p=0.007). Macroadenomas were more common in men (85.7% vs. 58.6%, p=0.023). Twenty-eight patients (49.1%) showed suprasellar extension; of these, 19 were accompanied by chiasmatic compression. Hypopituitarism was present in 14 (24.6%) patients; which was partial in 13 patients (22.8%) and complete in one patient (1.8%). The gonadal axis was the most frequently affected (n=13, 22.8%). Twenty four patients (42.1%) underwent surgery. Of the non-operated patients, 26 patients could be evaluated morphologically after a median follow-up of 15.5 months (interquartile range, 5.7–32.7 months). No significant changes were found in the maximum tumor diameter at the end of follow-up (1.2±0.6 vs 1.2±0.7 cm). The majority of CNFPAs evaluated (n=23, 88.5%) did not show any changes in size. In 2 cases (7.7%) tumor size decreased, and in one patient (3.8%) increased. In our series of CNFPA patients, approximately one-third were incidental. These tumors were diagnosed by MRI preferably from the 5th decade of life without sex predilection. Most of them were macroadenomas, more commonly diagnosed in men and at an older age, compared to microadenomas. The suprasellar extension with chiasmatic compression and hypopituitarism were frequent at diagnosis. Most of the non-operated incidental CNFPAs remain with stable tumor size over time, growth being an unusual event.Insituto de Salud Carlos III; PI16/0088

Transient hypothyroidism after iodine-131 therapy for Grave's disease

We studied 355 patients with Grave's disease to characterize transient hypothyroidism and its prognostic value following 131I therapy. Methods: the patients received therapeutic 131I treatment as follows: 333 received a dose 10 mCi (12.8 +/- 2.9 mCi). Diagnosis of transient hypothyroidism was based on low T4, regardless of TSH within the first year after 131I followed by recovery of T4 and normal TSH. Results: after administration of 10 mCi) of 131I. Iodine-131 uptake > 70% at 2 hr before treatment was a risk factor for developing transient hypothyroidism (Odds ratio 2.8, 95% confidence interval 0.9-9.4). At diagnosis of transient hypothyroidism, basal TSH levels were high (51%), normal (35%) or low (14%); therefore, the transient hypothyroidism was not centralized. If hypothyroidism developed during the first 6 mo after basal TSH > 45 mU/liter ruled out transient hypothyroidism. Conclusion: the development of transient hypothyroidism and its hormonal pattern did not influence long-term thyroid function. Since no prognostic factors reliably predicted transient hypothyroidism before 131I or at the time of diagnosis, if hypothyroidism appears within the first months after 131I, the reevaluation of thyroid function later is warranted to avoid unnecessary chronic replacement therapy

Giant non-functioning pituitary adenoma: clinical characteristics and therapeutic outcomes

[Abstract] Background: Giant pituitary adenoma (≥4 cm) is a rare tumor whose clinical features and prognosis are not well known. Aim: To evaluate the clinical characteristics and therapeutic outcomes of giant non-functioning PA (gNFPA). Patients and methods: A retrospective multicenter study of gNFPA patients diagnosed in a 12-year period was performed. In each patient, clinical data and therapeutic outcomes were registered. Results: Forty patients (24 men, age 54.2 ± 16.2 years) were studied. The maximum tumor diameter [median (interquartile range)] was 4.6 cm (4.1-5.1). Women had larger tumors [4.8 cm (4.2-5.4) vs. 4.5 cm (4.0-4.9); p=0.048]. Hypopituitarism [partial (n=22, 55%) or complete (n=9, 22.5%)] at diagnosis was present in 77.5% of the patients. Visual field defects were found in 90.9%. The most used surgical technique was endoscopic endonasal transsphenoidal (EET) surgery (n=31, 77.5%). Radiotherapy was used in 11 (27.5%) patients (median dose 50.4 Gy, range 50-54). Thirty-seven patients were followed for 36 months (10-67 months). Although more than half of these patients showed tumor persistence (n=25, 67.6%), tumor size was significantly reduced [0.8 cm (0-2.5); p<0.001]. At last visit, 12 patients (32.4%) showed absence of tumor on MRI. Hypopituitarism rate was similar (75.0%), although with significant changes (p<0.001) in the distribution of the type of hypopituitarism. The absence of tumor at the last visit was positively associated with positive immunohistochemical staining for FSH (p=0.01) and LH (p=0.006) and negatively with female sex (p=0.011), cavernous sinus invasion (p=0.005) and the presence of Knosp grade 4 (p=0.013). Conclusion: gNFPAs are more frequent in men but tumors are larger in women. Surgical treatment is followed by a complete tumor resection rate of approximately 30%. Positive immunostaining for gonadotropins is associated with tumor absence at last revision, while female sex and invasion of the cavernous sinuses with tumor persistence

Adenomas hipofisarios no funcionantes: valoración de la invasión, persistencia, recurrencia y del índice de proliferación celular Ki-67

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Fluorescent "turn-Off" detection of fluoride and cyanide ions using zwitterionic spirocyclic meisenheimer compounds

Stable zwitterionic spirocyclic Meisenheimer compounds were synthesized using a one-step reaction between picric acid and diisopropyl (ZW1) or dicyclohexyl (ZW3) carbodiimide. A solution of these compounds displays intense orange fluorescence upon UV or visible light excitation, which can be quenched or "turned-off" by adding a mole equivalent amount of F⁻ or CN⁻ ions in acetonitrile.Fluorescence is not quenched in the presence of other ions such as Cl⁻, Br⁻, I⁻, NO₂⁻ , NO₃⁻ , or H₂PO₄⁻ These compounds can therefore be utilized as practical colorimetric and fluorescent probes for monitoring the presence of F⁻ or CN⁻ anions

Therapeutic Management and Long-Term Outcome of Hy-Perthyroidism in Patients with Antithyroid-Induced Agranu-Locytosis: A Retrospective, Multicenter Study

Background: Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/mu L) is a rare but serious complication in the treatment of hyperthyroidism. Methodology: Adult patients with AIA who were followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The etiology of hyperthyroidism was distributed as follows: Graves' disease (n = 21), amiodarone-induced thyrotoxicosis (n = 7), and hyperfunctioning multinodular goiter (n = 1). Twenty-one patients were treated with methimazole, as well as six patients with carbimazole and two patients with propylthiouracil. Results: The median (IQR) time to development of agranulocytosis was 6.0 (4.0-11.5) weeks. The most common presenting sign was fever accompanied by odynophagia. All of the patients required admission, reverse isolation, and broad-spectrum antibiotics; moreover, G-CSF was administered to 26 patients (89.7%). Twenty-one patients received definitive treatment, thirteen patients received surgery, nine patients received radioiodine, and one of the patients required both treatments. Spontaneous normalization of thyroid hormone values occurred in six patients (four patients with amiodarone-induced thyrotoxicosis and two patients with Graves' disease), and two patients died of septic shock secondary to AIA. Conclusions: AIA is a potentially lethal complication that usually appears around 6 weeks after the initiation of antithyroid therapy. Multiple drugs are required to control hyperthyroidism before definitive treatment; additionally, in a significant percentage of patients (mainly in those treated with amiodarone), hyperthyroidism resolved spontaneously