3P association (3PAs): Pituitary adenoma and pheochromocytoma/paraganglioma. A heterogeneous clinical syndrome associated with different gene mutations.

BACKGROUND: Pituitary adenomas (PA) associated with pheochromocytomas/paragangliomas (Pheo/PGL), also known as "the three P association" or "3PAs" could be the results of coincidence, but new evidence supports a common pathogenic mechanism in some patients. Our aim is to report the clinical data, surgical outcome, genetic findings of a large case series and review the current knowledge on this topic. METHODS AND RESULTS: In a retrospective multicentre study, we compiled 10 patients with PAs (6 new unreported cases). Six patients were female with mean age of 51.6 ±â€¯18.0 years. PA were: 6 acromegaly, 3 prolactinoma and 1 non-functioning PA (NFPA). Among the Pheo/PGL, 7 patients had a single tumour (4 Pheo and 3 PGL) and 3 patients had multiple or bilateral disease (2 PGL and 1 Pheo). Patients with GH-secreting PA and NFPA underwent surgery, while patients with prolactinoma received medical treatment (one patient required surgery). Unilateral adrenalectomy was carried out in all single Pheo and a bilateral procedure was performed in the patient with bilateral tumour. A single tumour was resected in two patients with multiple PGL. We found 3 germline pathogenic mutations: 2 in SDHB (c.166-170delCCTCA and a gross deletion involving exon 1) and 1 SDHD (p.P81L exon 3). Two variants of uncertain significance: 1 in MEN1 (c.1618C > T; p.Pro540Ser) and 1 in RET (c.2556C > G, p.Ile852Met), and finally a RETM918T somatic mutation in a Pheo tissue. CONCLUSION: We actively suggest considering the possibility of hereditary disease in all cases with 3PA and performing a complete genetic study.

ACROSTART: A retrospective study of the time to achieve hormonal control with lanreotide Autogel treatment in Spanish patients with acromegaly / ACROSTART: Estudio retrospectivo del período de tiempo para lograr el control hormonal con lanreótida Autogel en pacientes con acromegalia en la práctica clínica española

Objectives: The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline(R) Autogel(R)). Methods: From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels <2.5ng/ml and/or normalized IGF-I levels in ≥2 measurements) were analyzed. The primary objective was to determine the time from start of lanreotide treatment to hormonal normalization. Results: Median patient age was 64 years, 21 patients were male, 39 patients had undergone surgery, and 14 patients had received radiotherapy. Median hormonal values at start of lanreotide treatment were: GH, 2.6ng/ml; IGF-I, 1.6×ULN. The most common starting dose of lanreotide was 120mg (29 patients). The main initial regimens were 60mg/4 weeks (n=13), 90mg/4 weeks (n=6), 120mg/4 weeks (n=13), 120mg/6 weeks (n=6), and 120mg/8 weeks (n=9). An initial treatment regimen with a long interval (≥6 weeks) was administered in 25 patients. Mean duration of lanreotide treatment was 68 months (7-205). Median time to achieve hormonal control was 4.9 months. Injections were managed without healthcare assistance in 13 patients. Median number of visits to endocrinologists until hormonal control was achieved was 3. Fifty-one patients were "satisfied"/"very satisfied" with treatment and 49 patients did not miss any dose. Conclusions: Real-life treatment with lanreotide Autogel resulted in early hormonal control in responding patients, with high treatment adherence and satisfaction despite disparity in starting doses and dosing intervals

Objetivos: El objetivo del estudio ACROSTART era determinar el período de tiempo para lograr la normalización hormonal (GH e IGF-I) en pacientes con acromegalia respondedores al tratamiento considerando los regímenes de lanreótida Autogel (Somatuline(R) Autogel(R)) utilizados en la práctica clínica. Métodos: Desde marzo de 2013 hasta octubre de 2013, en 17 hospitales españoles se analizaron los datos clínicos de 57 pacientes con acromegalia activa tratados con lanreótida durante ≥4 meses que lograron control hormonal (niveles de GH <2,5ng/ml y/o IGF-I normalizado en ≥2 evaluaciones). El objetivo principal fue determinar el período de tiempo desde el inicio del tratamiento con lanreótida hasta la normalización hormonal. Resultados: La mediana de edad de los pacientes fue 64 años, 21 pacientes eran hombres, 39 pacientes habían recibido cirugía, 14 pacientes habían recibido radioterapia. Los valores hormonales medianos al inicio del tratamiento con lanreótida fueron GH: 2,6ng/ml, IGF-I: 1,6×LSN. La dosis inicial más frecuente de lanreótida fue de 120mg (29 pacientes). Los principales regímenes iniciales fueron 60mg/4 semanas (n=13), 90mg/4 semanas (n=6), 120mg/4 semanas (n=13), 120mg/6 semanas (n=6), 120mg/8 semanas (n=9). Se administró un régimen de intervalo prolongado (≥6 semanas) en 25 pacientes. La duración media del tratamiento con lanreótida fue de 68 meses (7-205). El tiempo medio hasta lograr el control hormonal fue de 4,9 meses. Las inyecciones se manejaron sin asistencia médica en 13 pacientes. La mediana del número de visitas al endocrinólogo hasta el control hormonal fue 3. Cincuenta y un pacientes estaban "satisfechos"/"muy satisfechos" con el tratamiento y 49 pacientes no olvidaron ninguna dosis. Conclusiones: El tratamiento en la vida real con lanreótida Autogel condujo a un control hormonal temprano en pacientes que respondieron, con una alta adherencia al tratamiento y satisfacción con el tratamiento, a pesar de la disparidad de las dosis iniciales y los intervalos de dosificación

ACROSTART: A retrospective study of the time to achieve hormonal control with lanreotide Autogel treatment in Spanish patients with acromegaly.

OBJECTIVES: The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline® Autogel®). METHODS: From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels <2.5ng/ml and/or normalized IGF-I levels in ≥2 measurements) were analyzed. The primary objective was to determine the time from start of lanreotide treatment to hormonal normalization. RESULTS: Median patient age was 64 years, 21 patients were male, 39 patients had undergone surgery, and 14 patients had received radiotherapy. Median hormonal values at start of lanreotide treatment were: GH, 2.6ng/ml; IGF-I, 1.6×ULN. The most common starting dose of lanreotide was 120mg (29 patients). The main initial regimens were 60mg/4 weeks (n=13), 90mg/4 weeks (n=6), 120mg/4 weeks (n=13), 120mg/6 weeks (n=6), and 120mg/8 weeks (n=9). An initial treatment regimen with a long interval (≥6 weeks) was administered in 25 patients. Mean duration of lanreotide treatment was 68 months (7-205). Median time to achieve hormonal control was 4.9 months. Injections were managed without healthcare assistance in 13 patients. Median number of visits to endocrinologists until hormonal control was achieved was 3. Fifty-one patients were "satisfied"/"very satisfied" with treatment and 49 patients did not miss any dose. CONCLUSIONS: Real-life treatment with lanreotide Autogel resulted in early hormonal control in responding patients, with high treatment adherence and satisfaction despite disparity in starting doses and dosing intervals.

Estudio retrospectivo para evaluar la eficacia y la seguridad de la radiocirugía en enfermedad de Cushing: 24 casos y revisión / Retrospective analysis to evaluate efficacy and safety of stereotactic radiosurgery in Cushing's disease: 24 cases and a review

Introducción: En los últimos años la radiocirugía (RC) se ha postulado como una buena alternativa terapéutica, por lo general de segunda línea, en el manejo de los adenomas hipofisarios productores de ACTH. Se realiza un estudio retrospectivo para evaluar la eficacia y la seguridad de dicho tratamiento en estos pacientes. Material y métodos: Se recogieron datos de los pacientes tratados mediante RC por adenoma hipofisario productor de ACTH entre 1996 y 2008, con al menos un año de seguimiento, analizando la tasa de normalización hormonal y mejoría clínica (estigmas del síndrome de Cushing, hipertensión arterial), así como la aparición de efectos adversos y de recidiva. Se consideró normalización hormonal -y por tanto curación- como una tasa normal de cortisol libre urinario (CLU) en 24 h (< 100 μg/día). Resultados: Treinta pacientes fueron tratados, de los que 24 entraron en el estudio. Todos ellos tenían cifras elevadas de CLU previamente al tratamiento con RC. La curación se consiguió en 12 (50%), en un promedio de 28meses, y en otros 3 pacientes se normalizaron las cifras de CLU con tratamiento con ketoconazol posterior. En todos mejoraron los estigmas de Cushing, y en 13 (de 14) mejoró la HTA. No se evidenció ningún caso de recidiva una vez instaurada la curación. Entre las complicaciones destacan 9 déficits hormonales nuevos (siendo el más frecuente el hipotiroidismo), una radionecrosis y un empeoramiento de la campimetría previa. No se encontró ningún caso de tumor radioinducido. Conclusiones: La RC es un tratamiento efectivo para aquellos pacientes con adenoma productor de ACTH en que la cirugía ha fallado o que no son candidatos a la misma, consiguiéndose buenas tasas de normalización hormonal y de control clínico de la enfermedad, con un bajo porcentaje de efectos adversos

Background: In the past few years, stereotactic radiosurgery (SRS) has been suggested as a good alternative, second line therapy for the management of patients with ACTH-secreting pituitary adenomas. A retrospective study has been conducted in order to evaluate the efficacy and safety of this treatment in these patients. Material and methods: Data were collected on all patients treated with SRS for an ACTH-secreting pituitary adenoma between 1996 and 2008, and with at least one year of follow-up. An analysis was carried out by analysing the return to normal of the hormone levels and clinical improvement rates (including Cushing signs, arterial hypertension), as well as adverse effects, and disease relapse. A return to normal of the 24hour urinary free cortisol (24-UFC) levels (<100μg/day) without any ACTH-secretion suppressor drug treatment, was considered as cure or improvement. Results: A total of 30 patients were treated with SRS, of which 24 were included in the analysis. They all had high 24-UFC levels before the treatment. Cure was achieved in 12 (50%) in a mean of 28months, and in other 3 patients 24-UFC levels returned to normal with treatment with ketoconazole after the SRS. Cushing signs improved in all cases, as well as arterial hypertension in 13 out of 14 cases. There were relapses after cure consolidation. As far as adverse effects, it should be mentioned that there were 9 cases of new pituitary hormonal dysfunction (the most frequent being hypothyroidism), one radionecrosis, and one case of visual field defect impairment. Radiation-related neoplasm was not detected in any of the cases. Conclusions: SRS is an effective treatment for those patients with ACTH-secreting pituitary adenoma in whom surgery has failed, or in those that are not good candidates for it. It showed good rates of hormone levels returning to normal, as well as clinical disease control and a low level of adverse effects

[Retrospective analysis to evaluate efficacy and safety of stereotactic radiosurgery in Cushing's disease: 24 cases and a review]. / Estudio retrospectivo para evaluar la eficacia y la seguridad de la radiocirugía en enfermedad de Cushing: 24 casos y revisión.

BACKGROUND: In the past few years, stereotactic radiosurgery (SRS) has been suggested as a good alternative, second line therapy for the management of patients with ACTH-secreting pituitary adenomas. A retrospective study has been conducted in order to evaluate the efficacy and safety of this treatment in these patients. MATERIAL AND METHODS: Data were collected on all patients treated with SRS for an ACTH-secreting pituitary adenoma between 1996 and 2008, and with at least one year of follow-up. An analysis was carried out by analysing the return to normal of the hormone levels and clinical improvement rates (including Cushing signs, arterial hypertension), as well as adverse effects, and disease relapse. A return to normal of the 24 hour urinary free cortisol (24-UFC) levels (<100 µg/day) without any ACTH-secretion suppressor drug treatment, was considered as cure or improvement. RESULTS: A total of 30 patients were treated with SRS, of which 24 were included in the analysis. They all had high 24-UFC levels before the treatment. Cure was achieved in 12 (50%) in a mean of 28 months, and in other 3 patients 24-UFC levels returned to normal with treatment with ketoconazole after the SRS. Cushing signs improved in all cases, as well as arterial hypertension in 13 out of 14 cases. There were relapses after cure consolidation. As far as adverse effects, it should be mentioned that there were 9 cases of new pituitary hormonal dysfunction (the most frequent being hypothyroidism), one radionecrosis, and one case of visual field defect impairment. Radiation-related neoplasm was not detected in any of the cases. CONCLUSIONS: SRS is an effective treatment for those patients with ACTH-secreting pituitary adenoma in whom surgery has failed, or in those that are not good candidates for it. It showed good rates of hormone levels returning to normal, as well as clinical disease control and a low level of adverse effects.

Guía para el diagnóstico y tratamiento de la insuficiencia suprarrenal en el adulto / Guidelines for the diagnosis and treatment of adrenal insufficiency in the adult

La insuficiencia suprarrenal (IA) es un trastorno que se caracteriza por un déficit de glucocorticoides, al que se asocia en ocasiones un déficit de mineralocorticoides y/o andrógenos adrenales. Puede ser consecuencia de enfermedades intrínsecas del córtex adrenal (IA primaria), de procesos hipofisarios que afecten a la secreción de corticotropina (IA secundaria) o de trastornos hipotalámicos que afecten la secreción de la hormona liberadora de corticotropina (IA terciaria). Se trata de una entidad de baja prevalencia pero con elevado impacto sobre la salud individual, dado que entraña riesgo vital en ausencia de tratamiento y efectos deletéreos para la salud en caso de tratamiento inadecuado. En la actualidad no hay ninguna guía de práctica clínica para el manejo de esta enfermedad, por este motivo, a partir de una propuesta de la junta directiva de la Sociedad Española de Endocrinología y Nutrición (SEEN), se constituyó un grupo de trabajo dependiente del Área de Conocimiento de Neuroendocrinología de la SEEN, al que se encomendó la tarea de actualizar el diagnóstico y tratamiento de la IA del adulto. En cumplimiento de esta labor, el grupo de trabajo ha elaborado la presente guía, que, basándose en una revisión exhaustiva de la bibliografía, pretende dar respuesta a los interrogantes que se platean en el manejo de esta enfermedad. Se trata, por tanto, de un documento de carácter eminentemente práctico, cuya intención principal es servir de guía a los profesionales que se dedican al cuidado de los pacientes con IA

Adrenal insufficiency (AI) is a disease characterized by a deficient production or action of glucocorticoids, with or without deficiency in mineralcorticoids and/or adrenal androgens. It can result from disease intrinsic to the adrenal cortex (primary AI), from pituitary diseases that hamper the release of corticotropin (secondary AI) or from hypothalamic disorders that impair the secretion of the corticotropin-releasing hormone (tertiary AI). It is a disease with a low prevalence but its impact on the affected individual is very high as it can be life-threathening if not treated or lead to health problems if inadequately treated. However, currently there are no specific guidelines for the management of this disease. Therefore, at the proposal of the Spanish Society of Endocrinology and Nutrition (SEEN) board, a task-force under the Neuroendocrinology Knowledge Area of the SEEN was established, with the mandate of updating the diagnosis and treatment of AI. In fulfilment of this mandate the task-force has elaborated the present guide that, based on a comprehensive review of literature, is intended to provide an answer to questions related to the management of this disease. It is, therefore, an essentially practical document, mainly aimed at guiding the health professionals involved in the care of IA patients

Neurocognitive function in acromegaly after surgical resection of GH-secreting adenoma versus naïve acromegaly.

Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH) and insulin-like growth factor (IGF-I) hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients) with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA) solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with better neurocognitive state. Overall, this data suggests that the effects of chronic exposure to GH/IGF-I hypersecretion could have long-term effects on brain functions.

Eventos adversos perinatales y anomalías neuroanatómicas en pacientes con hipopituitarismo idiopático / Perinatal adverse events and neuroanatomical abnormalities in patients with idiopathic hypopituitarism

Objetivo El objetivo de nuestro trabajo fue analizar las posibles causas del déficit de hormona de crecimiento (DGH) aislado o en combinación con otras deficiencias hipofisarias, catalogado como idiopático. Pacientes y métodos Estudiamos a los pacientes con DGH idiopático incluidos en el protocolo de tratamiento con GH sintética para adultos en seguimiento por el Servicio de Endocrinología y Nutrición del Hospital Universitario San Cecilio. Se evaluaron de forma retrospectiva los antecedentes de la historia perinatal, los hallazgos en la resonancia magnética (RM) hipotálamo-hipofisaria y el diagnóstico de DGH y otros déficits hormonales. Resultados Se revisaron las historias de 17 pacientes: 14 varones y 3 mujeres con una edad media al diagnóstico de 8,4±7,3 años. Se presentaron eventos adversos perinatales en 12 pacientes (69,2%). El análisis de las imágenes de RM mostró silla turca vacía (2 pacientes), hipoplasia hipofisaria o ausencia del tallo hipofisario (7 pacientes) e hipoplasia hipofisaria con neurohipófisis ectópica (6 pacientes); en los 2 restantes no se pudo acceder a estos datos. En todos ellos se había establecido el diagnóstico de DGH, en 15 (88,2%) déficit de gonadotropinas, en 9 (52,9%) déficit de corticotropina y en 8 (47,1%) déficit de tirotropina. Conclusiones En nuestros pacientes, los eventos adversos durante la gestación o en la historia perinatal y la presencia de alteraciones anatómicas identificadas por RM suponen un marcador de disfunción hipofisaria y pueden ser importantes en la patogenia de esta entidad. El espectro de la enfermedad es variable desde el DGH aislado hasta múltiples déficits hormonales (AU)

Objective To analyze the possible causes of growth hormone (GH) deficiency, whether isolated (GHD) or in combination with other pituitary deficiencies classified as idiopathic. Patients and methods We studied patients with idiopathic GHD included in a protocol of recombinant GH treatment in adults attending the outpatient clinic of the Endocrinology and Nutrition Service of the San Cecilio University Hospital. Perinatal history, findings on magnetic resonance imaging (MRI) of the hypothalamic-pituitary axis and diagnosis of GHD and other deficiencies were retrospectively evaluated. Results A total of 17 patients were included: 14 men and 3 women with a mean age at diagnosis of 8.4±7.3 years. Perinatal adverse events occurred in 12 patients (69.2%). MRI showed empty sella (2 patients), pituitary hypoplasia or absence of the pituitary stalk (7 patients) and pituitary hypoplasia with ectopic posterior pituitary gland (6 patients); in the remaining 2 patients these data were not available. All had an established diagnosis of GHD: 15 with (88.2%) gonadotropin deficiency, 9 (52.9%) with adrenocorticotropic hormone (ACTH) deficiency and 8 (47.1%) with thyroid-stimulating hormone (TSH) deficiency. Conclusions In our patients, adverse events during pregnancy or the perinatal period and the presence of anatomical abnormalities identified by MRI are a marker of pituitary dysfunction and may be important in the pathogenesis of this entity. The clinical spectrum of disease varies from isolated GH deficiency to multiple pituitary hormone deficiencies (AU)

Evidence of cognitive and neurophysiological impairment in patients with untreated naive acromegaly.

CONTEXT: Recent studies have suggested that long-term exposure to high levels of GH and IGF-I affect brain and cognitive functions. However, very few human studies have challenged this hypothesis. OBJECTIVE: The aim of this study is to explore whether GH/IGF-I excess in naive patients with acromegaly alters cognitive functions, particularly memory, and whether these alterations are accompanied by neurophysiological correlates. DESIGN: We conducted a comprehensive neuropsychological and neurophysiological exam on 16 naive acromegaly patients and 16 strictly matched healthy controls. Comparative analyses were carried out on major neurocognitive domains (executive functions, visual/verbal memory, attention, visuoconstructive abilities, and verbal fluency) and on quantitative electroencephalogram and low-resolution brain electromagnetic tomography sources. Results were correlated with GH and IGF-I hormone concentrations. RESULTS: Short- and long-term memory were the most severely impaired cognitive functions. Moreover, memory performance correlated negatively with GH and IGF-I concentrations. No association was detected between depression and memory impairment, and only a marginal association was found with quality of life. Finally, acromegaly patients showed power attenuation in fast frequency electroencephalogram bands, as well as decreased activity in prefrontal and middle temporal cortices, that was associated to cognitive performance. CONCLUSIONS: Results provide evidence of cognitive and neurophysiological impairment, characterized by moderate-to-severe memory impairment and decreased neural activity in specific brain areas. High levels of GH and IGF-I in acromegaly patients could be the basis for these findings.

[Perinatal adverse events and neuroanatomical abnormalities in patients with idiopathic hypopituitarism]. / Eventos adversos perinatales y anomalías neuroanatómicas en pacientes con hipopituitarismo idiopático.

OBJECTIVE: To analyze the possible causes of growth hormone (GH) deficiency, whether isolated (GHD) or in combination with other pituitary deficiencies classified as idiopathic. PATIENTS AND METHODS: We studied patients with idiopathic GHD included in a protocol of recombinant GH treatment in adults attending the outpatient clinic of the Endocrinology and Nutrition Service of the San Cecilio University Hospital. Perinatal history, findings on magnetic resonance imaging (MRI) of the hypothalamic-pituitary axis and diagnosis of GHD and other deficiencies were retrospectively evaluated. RESULTS: A total of 17 patients were included: 14 men and 3 women with a mean age at diagnosis of 8.4+/-7.3 years. Perinatal adverse events occurred in 12 patients (69.2%). MRI showed empty sella (2 patients), pituitary hypoplasia or absence of the pituitary stalk (7 patients) and pituitary hypoplasia with ectopic posterior pituitary gland (6 patients); in the remaining 2 patients these data were not available. All had an established diagnosis of GHD: 15 with (88.2%) gonadotropin deficiency, 9 (52.9%) with adrenocorticotropic hormone (ACTH) deficiency and 8 (47.1%) with thyroid-stimulating hormone (TSH) deficiency. CONCLUSIONS: In our patients, adverse events during pregnancy or the perinatal period and the presence of anatomical abnormalities identified by MRI are a marker of pituitary dysfunction and may be important in the pathogenesis of this entity. The clinical spectrum of disease varies from isolated GH deficiency to multiple pituitary hormone deficiencies.

Acromegalia y prolactinomas / No disponible

No disponible

Lipoatrophy in GH deficient patients treated with a long-acting pegylated GH.

OBJECTIVE: Changes observed during adult GH deficiency (GHD) are most often reversed with the administration of recombinant human GH (rhGH). To avoid daily injections, a long-acting GH molecule has been obtained by covalent binding of polyethylene glycol (PEG) with rhGH (PEG-GH), allowing weekly s.c. injections. This study was designed to assess its efficacy and safety, in adult GHD subjects. DESIGN AND METHODS: This was a randomized, double-blind, placebo-controlled, multiple-dose, parallel group study. Subjects were recruited from 34 centers. A total of 105 subjects with GHD were assigned a treatment. They received 6 weekly injections of either PEG-GH or placebo. Subjects were randomized into one out of four treatment groups (Groups A-D) or placebo (Group E). Groups A, B, and C received 1, 3, and 4 mg PEG-GH respectively, for the first 3 weeks followed by 2, 6, and 8 mg PEG-GH respectively, for the remaining 3 weeks. Group D received 4 mg PEG-GH for 6 weeks. Group E received placebo. The study was suspended because of the development of lipoatrophy in certain subjects and restarted with an injection rotation plan, before being terminated due to further subjects developing lipoatrophy. RESULTS: A total of 13 cases of injection-site lipoatrophy were reported, of which ten were in females and three occurred after the first injection; all cases were independent of PEG-GH dose or IGF1 levels, either basal or under treatment. CONCLUSION: The unpredictable occurrence of injection-site lipoatrophy with weekly long-acting pegylated GH molecules may be a limiting factor for their development.

Alteración de la función gonadal en las enfermedades crónicas / No disponible

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Clinical practice guideline for hypotalamic-pituitary disturbances in pregnancy and the postpartum period.

During pregnancy, the body undergoes a major adaptation process as a result of the interaction between mother, placenta and fetus. Major anatomical and histological changes are produced in the pituitary, with an increase of up to 40% in the size of the gland. There are wide variations in the function of the hypothalamus-pituitary-thyroid axis that effect iodine balance, the overall activity of the gland, as well as transport of thyroid hormones in plasma and peripheral metabolism of thyroid hormones. The incidence of goiter and thyroid nodules increases throughout pregnancy. The management of differentiated thyroid carcinoma should be individually tailored according to tumoral type and pregnancy stage. Given the effects of hypothyroidism on fetal development, both the diagnosis and appropriate therapeutic management of thyroid hypofunction are essential. The most important modification to the hypothalamus-pituitary-adrenal axis during pregnancy is the rise in serum cortisol levels due to an increase in cortisol-binding proteins. Although Cushing's syndrome during pregnancy is infrequent, both diagnosis and treatment of this disorder are especially difficult. Adrenal insufficiency during pregnancy does not substantially differ from that occurring outside pregnancy. However, postpartum pituitary necrosis (Sheehan's syndrome) is a well-known complication that occurs after delivery and, together with lymphocytic hypophysitis, constitutes the most frequent cause of adrenal insufficiency. The management of prolactinoma during pregnancy requires suppression of dopaminergic agonists and their reintroduction if there is tumoral growth. Notable among the neuropituitary disorders that can occur throughout pregnancy is diabetes insipidus, which occurs as a consequence of increased vasopressinase activity.