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.

Intra-individual variability in TSH levels of healthy women during the first half of pregnancy / Variabilidad intra-individual de los niveles TSH en mujeres sanas en primer trimestre de gestación

Objective: TSH is the parameter most widely accepted to assess thyroid function, especially in pregnant women. The aim of this current study was to analyze intra-individual changes in TSH during the first half of pregnancy in women with TSH levels higher than 2.5mIU/L in early pregnancy. Methods: An observational, prospective study was conducted on 243 healthy pregnant women in the first trimester of pregnancy. Thyroid function was assessed by testing TSH and free T4 levels. A subgroup of women with TSH levels >2.5mIU/L underwent additional tests (TSH, free T4, peroxidase antibodies). Information on dietary iodine intake and/or iodine supplements was also recorded. Results: Mean TSH level was 1.89mIU/L (range 0.024-6.48mIU/L), and mean FT4 level was 1.19ng/dL (range 0.80-1.90ng/dL). Fifty-eight women (23.8%) had TSH levels>2.5mIU/L in the first trimester of pregnancy, and additional thyroid function tests were performed in 27 women. TSH levels significantly decreased from the first to the second test (3.59±0.92mIU/L vs 2.81±1.06mIU/L respectively; p<0.01), and the decrease was significantly greater in pregnant women who used iodized salt as compared to those who did not (1.16±0.65mIU/L vs 0.19±0.93mIUI/L respectively; p<0.01). A positive correlation was found between the time elapsed to the second measurement (24.3±17.2 days; range 8-58) and the decrease in TSH levels (r=0.40; p=0.038). Conclusion: TSH levels showed a continuous, uniform decrease during the first half of pregnancy in women with values slightly above the normal range. Pregnant women who used iodized salt were more likely to have decreased TSH levels in a second test (AU)

Objetivo: La TSH es el parámetro más aceptado para evaluar la función tiroidea, especialmente en mujeres embarazadas. El objetivo del presente estudio fue analizar los cambios intraindividuales de TSH durante la primera mitad de la gestación, en aquellos casos en los que la TSH en las primeras etapas de la gestación fue superior a 2,5 mUI/L. Métodos: Estudio observacional prospectivo que incluyó a 243 mujeres embarazadas sanas en el primer trimestre de gestación. Se estudió función tiroidea mediante TSH y T4 libre. Un subgrupo de mujeres con TSH> 2,5 mUI/L fueron sometidas a un segundo análisis (TSH, T4 libre, anticuerpos antiperoxidasa). También se registró información sobre la ingesta de yodo con la dieta y/o suplementos. Resultados: La TSH media fue de 1,89 mUI/L (rango 0,024-6,48 mUI/L), y la T4 libre media fue de 1,19 ng/dL (rango 0,80-1,90ng/dL). El 23,8% (58 mujeres) presentaron TSH> 2,5 mUI/L en el primer trimestre de gestación, realizándose una segunda valoración en 27 pacientes. La TSH disminuyó significativamente del primer al segundo análisis (3,59±0,92 mUI/L vs. 2,81±1,06 mUI/L respectivamente, p <0,01). La TSH disminuyó significativamente más en aquellas mujeres embarazadas que consumieron sal yodada que en aquellas que no lo hicieron (1,16±0,65 mUI/L vs. 0,19±0,93 mUI/L respectivamente, p<0,01). Hubo una correlación positiva entre el tiempo transcurrido para una segunda determinación (24,3±17,2 días, rango 8-58 días), y la reducción en los niveles de TSH (r= 0,40; p=0,038). Conclusión: La disminución de los niveles de TSH con la edad gestacional es uniformemente continua a lo largo de la primera mitad de la gestación en aquellos casos con TSH ligeramente por encima del rango sugerido de normalidad. Las mujeres embarazadas que consumían sal yodada tenían más probabilidades de reducir los niveles de TSH en un segundo análisis (AU)

Intra-individual variability in TSH levels of healthy women during the first half of pregnancy.

OBJECTIVE: TSH is the parameter most widely accepted to assess thyroid function, especially in pregnant women. The aim of this current study was to analyze intra-individual changes in TSH during the first half of pregnancy in women with TSH levels higher than 2.5mIU/L in early pregnancy. METHODS: An observational, prospective study was conducted on 243 healthy pregnant women in the first trimester of pregnancy. Thyroid function was assessed by testing TSH and free T4 levels. A subgroup of women with TSH levels >2.5mIU/L underwent additional tests (TSH, free T4, peroxidase antibodies). Information on dietary iodine intake and/or iodine supplements was also recorded. RESULTS: Mean TSH level was 1.89mIU/L (range 0.024-6.48mIU/L), and mean FT4 level was 1.19ng/dL (range 0.80-1.90ng/dL). Fifty-eight women (23.8%) had TSH levels>2.5mIU/L in the first trimester of pregnancy, and additional thyroid function tests were performed in 27 women. TSH levels significantly decreased from the first to the second test (3.59±0.92mIU/L vs 2.81±1.06mIU/L respectively; p<0.01), and the decrease was significantly greater in pregnant women who used iodized salt as compared to those who did not (1.16±0.65mIU/L vs 0.19±0.93mIUI/L respectively; p<0.01). A positive correlation was found between the time elapsed to the second measurement (24.3±17.2 days; range 8-58) and the decrease in TSH levels (r=0.40; p=0.038). CONCLUSION: TSH levels showed a continuous, uniform decrease during the first half of pregnancy in women with values slightly above the normal range. Pregnant women who used iodized salt were more likely to have decreased TSH levels in a second test.

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.

[AIP mutations in familial and sporadic pituitary adenomas: local experience and review of the literature]. / Mutaciones de AIP en adenomas hipofisarios familiares y esporádicos: experiencia local y revisión de la literatura.

Clinically relevant pituitary adenomas occur 3-5 times more frequently than previously thought. The majority are isolated cases, but their presentation can be familial in the setting of known syndromes such as multiple endocrine neoplasia (MEN)-1 and Carney complex. When 2 or more cases of pituitary adenomas occur in the same family in the absence of the above-mentioned syndromes, a diagnosis of FIPA (familial isolated pituitary adenomas) is made, which accounts for 1-2% of all pituitary adenomas. Mutations of the gene AIP (aryl hydrocarbon receptor-interacting protein) may account for 15% of FIPA families (50% of familial acromegaly), and as such the genetic causes continue to be studied. Also mutations in AIP can be detected in sporadic adenomas among young populations (< 30 years of age). We describe the characteristics of FIPA, detailing the study of a spanish family, in this case AIP mutation negative. Also, the reported findings in sporadic adenomas in the young population are detailed, accompanied by the description of a 19- year old patient with an intronic AIP mutation. Multicenter studies have provided understanding of aspects such as mutations in AIP; however, further studies are necessary to identify other genes involved in FIPA and sporadic pituitary adenomas occurring at a young age.

Mutaciones de AIP en adenomas hipofisarios familiares y esporádicos: experiencia local y revisión de la literatura / AIP mutations in familial and sporadic pituitary adenomas: local experience and review of the literature

Los adenomas hipofisarios clínicamente relevantes son 3-5 veces más frecuentes de lo que inicialmente se pensaba. La mayoría son casos esporádicos, pero su presentación puede ser familiar dentro de síndromes conocidos: neoplasia endocrina múltiple (MEN) 1 y complejo de Carney. Cuando se expresan dos o más casos en la misma familia en ausencia de los síndromes anteriores, hablamos de adenomas hipofisarios familiares aislados (familial isolated pituitary adenomas [FIPA]), que suponen un 1-2% de todos los adenomas hipofisarios. Las mutaciones del gen AIP (aryl hydrocarbon receptor-interacting protein) pueden justificar el 15% de las familias con FIPA (el 50% de acromegalia familiar), pero su base genética continúa en estudio. Además, estas mutaciones de AIP se detectan en adenomas aislados en población joven (< 30 años). Se describen las características descritas en los FIPA detallando el estudio de una familia española, en este caso AIP negativa. También se detallan los hallazgos descritos en adenomas esporádicos en población joven con la presentación de una paciente de 19 años acromegálica con mutación de AIP intrónica. Los estudios multicéntricos han permitido conocer aspectos como las mutaciones de AIP, pero continúan siendo necesarios para conocer otros genes involucrados en los FIPA y los adenomas esporádicos que se presentan en edades tempranas (AU)

Clinically relevant pituitary adenomas occur 3-5 times more frequently than previously thought. The majority are isolated cases, but their presentation can be familial in the setting of known syndromes such as multiple endocrine neoplasia (MEN)-1 and Carney complex. When 2 or more cases of pituitary adenomas occur in the same family in the absence of the above-mentioned syndromes, a diagnosis of FIPA (familial isolated pituitary adenomas) is made, which accounts for 1-2% of all pituitary adenomas. Mutations of the gene AIP (aryl hydrocarbon receptor-interacting protein) may account for 15% of FIPA families (50% of familial acromegaly), and as such the genetic causes continue to be studied. Also mutations in AIP can be detected in sporadic adenomas among young populations (< 30 years of age). We describe the characteristics of FIPA, detailing the study of a spanish family, in this case AIP mutation negative. Also, the reported findings in sporadic adenomas in the young population are detailed, accompanied by the description of a 19-year old patient with an intronic AIP mutation. Multicenter studies have provided understanding of aspects such as mutations in AIP; however, further studies are necessary to identify other genes involved in FIPA and sporadic pituitary adenomas occurring at a young age (AU)