Glucose metabolism outcomes after pituitary surgery in patients with acromegaly.

AIM: To investigate the impact of pituitary surgery on glucose metabolism and to identify predictors of remission of diabetes after pituitary surgery in patients with acromegaly. METHODS: A national multicenter retrospective study of patients with acromegaly undergoing transsphenoidal surgery for the first time at 33 tertiary Spanish hospitals (ACRO-SPAIN study) was performed. Surgical remission of acromegaly was evaluated according to the 2000 and 2010 criteria. RESULTS: A total of 604 acromegaly patients were included in the study with a total median follow up of 91 months (interquartile range [IQR] 45-163). At the acromegaly diagnosis, 23.8% of the patients had diabetes mellitus (DM) with a median glycated hemoglobin (HbA1c) of 6.9% (IQR 6.4-7.9) [51.9 mmol/mol (IQR 46.4-62.8)]. In the multivariate analysis, older age (odds ratio [OR] 1.02, 95% CI 1.00-1.05), dyslipidemia (OR 5.25, 95% CI 2.81 to 9.79), arthropathy (OR 1.39, 95% CI 2.82 to 9.79), and higher IGF-I levels (OR 1.30, 95% CI 1.05 to 1.60) were associated with a greater prevalence of DM. At the last follow-up visit after surgery, 21.1% of the DM patients (56.7% of them with surgical remission of acromegaly) experienced diabetes remission. The cure rate of DM was more common in older patients (hazard ratio [HR] 1.77, 95% CI 1.31 to 2.43), when surgical cure was achieved (HR 2.10, 95% CI 1.01 to 4.37) and when anterior pituitary function was not affected after surgery (HR 3.38, 95% CI 1.17 to 9.75). CONCLUSION: Glucose metabolism improved in patients with acromegaly after surgery and 21% of the diabetic patients experienced diabetes remission; being more frequent in patients of older age, and those who experienced surgical cure and those with preserved anterior pituitary function after surgery.

Pegvisomant and pasireotide in PRL and GH co-secreting vs GH-secreting Pit-NETs.

The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) compared to their efficacy in patients with acromegaly caused by a GH-secreting pituitary neuroendocrine tumor (GH-Pit-NET). This is a multicenter retrospective study of patients with acromegaly on treatment with pasireotide and/or pegvisomant. Patients were classified in two groups: GH&PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC and GH-Pit-NETs when the previously mentioned criteria were not met. A total of 28 cases with GH&PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH&PRL-Pit-NETs presented at a younger age, caused hypopituitarism, and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide and with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs. All GH&PRL-Pit-NET cases treated with pasireotide (n = 6) and 82.6% (n = 19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH&PRL-Pit-NETs (84.9% vs 66.7%, P = 0.178). We conclude that despite the more aggressive behavior of GH&PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide were observed between both groups, and both drugs have shown to be effective treatments to control IGF-1 and PRL hypersecretion in these tumors.

Metabolic and Clinical Outcomes in Type 1 Diabetes in the COVID-19 Pre- and Post-Vaccination Periods in Spain: The COVID-SED1 Study.

Aims: To evaluate the metabolic and clinical outcomes in the Spanish type 1 diabetes mellitus (T1D) population before and after COVID-19 vaccination. Methods: A retrospective observational study was carried out in Spanish public hospitals previously enrolled in the SED1 study. Adults and children with T1D were included and their clinical electronic records were reviewed. Clinical, laboratory, and glucometric parameters from continuous glucose monitoring (CGM) data corresponding to the periods before and after administering the first COVID-19 vaccination were analyzed. Results: A total of 26 centers and 228 patients participated in this new phase of the SED1 study and 187 were finally evaluable (mean age 37.5 ± 15.6 years, 56.7% women). Overall, 94.6% of the sample was vaccinated, and this percentage increased with higher levels of education (p-value = 0.027). In the pre- and post-vaccination periods, respectively, the number of patients with acute hyperglycemic decompensation was 6/161 (3.7%) and 7/161 (4.3%) (p = 1) and with acute hypoglycemic decompensation was 6/161 (3.7%) and 6/161 (3.7%) (p = 1). The HbA1c level was lower in the post-vaccination period(mean ± SD, mg/dL): pre-vaccination 7.4 ± 0.9; post-vaccination 7.2 ± 1.0, (-0.19; p-value = 0.0006). A total of 31.9% of patients (95% CI: 24.7-39.7) in the pre-vaccination period and 45.0% (IC95%: 37.1-53.1) in the post-vaccine period had HbA1c < 7% (p-value < 0.001). Glucometrics from CGM data also showed numerical improvements post-vaccination. Conclusions: The COVID-19 vaccination was highly accepted in the Spanish T1D population, with hesitancy about the COVID-19 vaccine being higher in those with lower educational levels. A mildly better glycemic control was observed in the post-vaccination period.

Differences between GH and PRL co-secreting and GH-secreting pituitary adenomas. A series of 604 cases.

PURPOSE: To evaluate differences in clinical presentation and in surgical outcomes between growth hormone-secreting pituitary adenomas (GH-PAs) and GH and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). METHODS: Multicenter retrospective study of 604 patients with acromegaly submitted to pituitary surgery. Patients were classified into two groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal and IHC for GH and PRL was positive or PRL levels were >100ng/and PRL IHC was not available (n=130) and b) GH-PAs who did not meet the previously mentioned criteria (n=474). RESULTS: GH&PRL-PAs represented 21.5% (n=130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P<0.001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs. 77.4%, P=0.001) and tended to be more invasive (33.6% vs. 24.7%, P=0.057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (OR 2.8, 95% CI 1.83-4.38). IGF-1 upper limit of normality (ULN) levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [IQR 1.73-3.29] vs. 2.7 [IQR 1.91-3.67], P=0.023). There were no differences in the immediate (41.1% vs 43.3%, P=0.659) or long-term post-surgical acromegaly biochemical cure rate (53.5% vs. 53.1%, P=0.936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs. 2.4%, P=0.011) in GH&PRL-PAs patients. CONCLUSIONS: GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently.

Thymic Hyperplasia and Graves Disease: A Nonincidental Association.

We present 2 cases referred for evaluation of Graves disease (GD) associated with an incidental mediastinal mass. Chest computed tomography (CT) scans showed a 1.2 × 2.4 × 4.3 cm and a 5.7 × 2.6 × 7 cm thymic enlargement, respectively, consistent with thymic hyperplasia (TH) in the 2 patients. Patient 1 had been assessed by thoracic surgery for the mediastinal mass, and thymectomy had been performed to exclude thymoma, with an anatomopathological diagnosis consistent with thymic hyperplasia. Patient 2 was treated with methimazole. CT scan was repeated after he maintained a euthyroid state, which revealed total regression of the mass. There is a well-documented association between these 2 entities, but it is often underdiagnosed and unrecognized in routine clinal practice. The benign evolution, as evidenced by regression of thymic hyperplasia after resolution of the hyperthyroidism, is characteristic. These cases highlight the importance of recognizing the association of GD and TH and warrant a conservative approach, preventing unnecessary thymic evaluation and surgery.

Percutaneous ethanol injection therapy as the first line of treatment of symptomatic thyroid cysts.

BACKGROUND: Our aim was to evaluate the efficacy and security of ultrasound-guided percutaneous ethanol injection therapy (US-PEIT) for the treatment of recurrent symptomatic thyroid cysts in two high-resolution consultations of thyroid nodule in the Valencian Community. PATIENTS AND METHODS: The study comprised thirty-three consecutive patients (51 ±â€¯12 years, 76% women) with symptomatic benign thyroid cysts relapsed after drainage and benign cytology prior to treatment. Through ultrasound, maximum cyst diameter and volume were determined, and the content of the cyst was drained. We then instilled between 2 and 4 ml of ethanol (according to initial volume). We followed up with ultrasound at one, 3, 6 and 12 months and we calculated the total volume and the Volume Reduction Rate (VRR). We evaluated the perceived pain using a visual analog scale. RESULTS: The initial median cyst volume was 11.6 ml (8.5-16.5) A single session of US-PEIT was required in 22 patients (67%), two in 8 (24%) and three in 3 (9%). During PEIT, 49% of the patients experienced virtually no pain, 39% mild pain and 12% moderate pain. There were no complications. After 6 months of follow up the median VRR was 93% (84-98). All the patients achieved a volume reduction of more than 50%, 94% of more than 70% and 56% of more than 90%. Twenty-four patients completed a year of follow-up, achieving a VRR of 97% (93-98). CONCLUSIONS: In our experience US-PEIT has proven to be an effective, safe treatment of symptomatic thyroid cysts. For this reason it can be considered as the first line of treatment and included in the portfolio of services of a high-resolution consultation.

Prognostic usefulness of ACTH in the postoperative period of Cushing's disease.

OBJECTIVES: To analyze the usefulness of plasma ACTH in predicting CD remission after surgery and to evaluate the prognostic usefulness of ACTH measurement after the cortisol and ACTH nadir (48 h prior to discharge). DESIGN: A prospective study was made of 65 patients with CD operated upon between 2005 and 2016. METHODS: Postsurgery plasma ACTH and cortisol were measured every 6 h, in the absence of corticosteroid coverage. Hydrocortisone was started in the presence of adrenal insufficiency or cortisol <55.2 nmol/L. Plasma ACTH was again determined before discharge. MAIN OUTCOME MEASURE: Usefulness of plasma ACTH in predicting CD remission. RESULTS: Remission at 3 months of CD was achieved in 56 of 65 cases, with late recurrence in 18 of 58 cases. Following resection, the ACTH nadir was significantly lower referred to late remission (2.8 vs 6.5 pmol/L; P = 0.031) and higher for recurrence (2.1 vs 4.8 pmol/L; P < 0.001), and identical results were obtained for the ACTH values before discharge. In the analysis of the ROC curves, nadir and before discharge ACTH values <1.9 pmol/L and <2.6 pmol/L were respectively indicative of early remission (AUC 0.827; P < 0.001); <6.2 pmol/L of remission at 3 months (AUC 0.847; P = 0.001) and >3.2 pmol/L of recurrence (AUC 0.810; P < 0.001) in both ACTH values. A time to ACTH nadir <46 h was indicative of early remission (AUC 0.751; P = 0.001), while a time >39 h was indicative of recurrence (AUC 0.773; P = 0.001). CONCLUSIONS: We propose an ACTH value <3.3 pmol/L as a good long-term prognostic marker in the postoperative period of CD. Reaching the ACTH nadir in less time is associated to a lesser recurrence rate.

Factores pronósticos de remisión a largo plazo tras cirugía transesfenoidal en la enfermedad de Cushing / Predictors of long-term remission after transsphenoidal surgery in Cushing's disease

En el manejo de la enfermedad de Cushing (EC) no existe un consenso sobre los criterios de remisión ni sobre la definición de recurrencia en la literatura, por lo que las seriesno son comparables. Se ha descrito que la tasa de recurrencia en la EC oscila entre 5-25% en el seguimiento a largo plazo. Dentro de los factores pronósticos de remisión a largo plazo podemos diferenciar: 1) factores dependientes del adenoma (agresividad, tamaño, identificación preoperatoria por técnicas de imagen); 2) factores dependientes de la cirugía, donde destaca por su importancia la experiencia del neurocirujano; 3) factores clínicos, siendo la dependencia del tratamiento glucocorticoideo y su duración los más demostrados; y 4) factores bioquímicos. Dentro de estos últimos queda bien documentado en la literatura que un nadir indetectable de cortisol, al menos inferior a 2 mcg/dL, en el postoperatorio predice la remisión de la enfermedad pero, incluso en estos casos, no puede excluirse la recidiva, lo que obliga al seguimiento de por vida en estos pacientes. Presentamos los resultados preliminares de los primeros 20 pacientes intervenidos en el Hospital Universitario de la Ribera utilizando el nadir de cortisol inferior a 2 mcg/dL

There is no consensus on the remission criteria for Cushing's disease or on the definition of disease recurrence after transsphenoidal surgery, and comparison of the different published series is therefore difficult. A long-term recurrence rate of Cushing's disease ranging from 2%-25% has been reported. Predictors of long-term remission reported include: 1) adenoma-related factors (aggressiveness, size, preoperative identification in MRI), 2) surgery-related factors, mainly neurosurgeon experience, 3) clinical factors, of which dependence on and duration of glucocorticoid treatment are most important, and 4) biochemical factors. Among the latter, low postoperative cortisol levels, less than 2 mcg/dL predict for disease remission. However, even when undetectable plasma cortisol levels are present, long-term recurrence may still occur and lifetime follow-up is required. We report the preliminary results of the first 20 patients with Cushing's disease operated on at our hospital using nadir cortisol levels less than 2 mcg/dl as remission criterion

[Predictors of long-term remission after transsphenoidal surgery in Cushing's disease]. / Factores pronósticos de remisión a largo plazo tras cirugía transesfenoidal en la enfermedad de Cushing.

There is no consensus on the remission criteria for Cushing's disease or on the definition of disease recurrence after transsphenoidal surgery, and comparison of the different published series is therefore difficult. A long-term recurrence rate of Cushing's disease ranging from 2%-25% has been reported. Predictors of long-term remission reported include: 1) adenoma-related factors (aggressiveness, size, preoperative identification in MRI), 2) surgery-related factors, mainly neurosurgeon experience, 3) clinical factors, of which dependence on and duration of glucocorticoid treatment are most important, and 4) biochemical factors. Among the latter, low postoperative cortisol levels, less than 2 mcg/dL predict for disease remission. However, even when undetectable plasma cortisol levels are present, long-term recurrence may still occur and lifetime follow-up is required. We report the preliminary results of the first 20 patients with Cushing's disease operated on at our hospital using nadir cortisol levels less than 2 mcg/dl as remission criterion.

[Pegylated-interferon alpha plus ribavirin-induced subacute thyroiditis in chronic hepatitis C]. / Tiroiditis subaguda inducida por el tratamiento con interferón alfa pegilado y ribavirina en un caso de hepatitis crónica por virus C.

Chronic hepatitis C virus infection may be associated with extrahepatic manifestations. Thyroid disease related to chronic hepatitis C virus infection has been associated with interferon-alpha treatment. We present the case of a 40-year-old woman with chronic hepatitis C virus infection, who developed subacute thyroiditis during treatment with pegylated interferon-alpha plus ribavirin.

Tiroiditis subaguda inducida por el tratamiento con interferón alfa pegilado y ribavirina en un caso de hepatitis crónica por virus C / Pegylated-interferon alpha plus ribavirin-induced subacute thyroiditis in chronic hepatitis C

La infección crónica por el virus de la hepatitis C puede acompañarse de manifestaciones extrahepáticas. En especial se ha relacionado la enfermedad tiroidea con el tratamiento con interferón alfa. Se presenta el caso de una mujer de 40 años con infección por el virus de la hepatitis C, que desarrolló un cuadro de tiroiditis subaguda durante el tratamiento con interferón alfa pegilado y ribavirina (AU)

Chronic hepatitis C virus infection may be associated with extrahepatic manifestations. Thyroid disease related to chronic hepatitis C virus infection has been associated with interferon-alpha treatment. We present the case of a 40-year-old woman with chronic hepatitis C virus infection, who developed subacute thyroiditis during treatment with pegylated interferon-alpha plus ribavirin (AU)

Desnutrición caloricoproteínica grave tras bypass gástrico / Severe protein-calorie malnutrition after gastric bypass

La cirugía bariátrica da lugar a una pérdida de peso que perdura y mejora las comorbilidades de la obesidad mórbida. Pueden darse complicaciones tras ella, la mayoría nutricionales y de carácter leve, pero en algunos casos pueden ser graves y comprometer la vida del paciente. Se presenta el caso de una mujer de 50 años en quien se desarrolló desnutrición caloricoproteínica grave tras cirugía bariátrica y que precisó que se revirtiera la intervención. Se discuten los factores que dieron lugar a la desnutrición y las opciones de tratamiento (AU)

Bariatric surgery achieves lasting weight loss and improves the comorbidities associated with morbid obesity. After surgery, patients can develop complications, mainly mild nutritional alterations. However, in some patients, complications can be serious and life-threatening. We present the case of a 50-year-old woman who developed severe protein-calorie malnutrition after bariatric surgery, which required surgical reversion. The factors leading to malnutrition in this patient and the treatment options are discussed (AU)

Severe protein-calorie malnutrition after gastric bypass.

Bariatric surgery achieves lasting weight loss and improves the comorbidities associated with morbid obesity. After surgery, patients can develop complications, mainly mild nutritional alterations. However, in some patients, complications can be serious and lifethreatening. We present the case of a 50-year-old woman who developed severe protein-calorie malnutrition after bariatric surgery, which required surgical reversion. The factors leading to malnutrition in this patient and the treatment options are discussed.