[Long-term survival after small doses of radioiodine therapy for brain metastases of thyroid cancer]. / Supervivencia prolongada luego de pequeñas dosis de terapia con radioyodo en metástasis cerebral de cáncer de tiroides.

Differentiated thyroid cancer is generally accompanied by a long term survival. However, in some cases distant metastases can develop and among them, brain localizations are of poor prognosis. The aim of this presentation is to communicate the clinical case of a 65 year-old woman who consulted for diplopia in vertical gaze which had appeared one month earlier. MRI showed a big mass at the level of the occipital condyle. Diagnosis of primary brain tumor was made so she was operated twice with incomplete tumor resection. The pathological study was confirmatory of a metastatic lesion of thyroid carcinoma. A total thyroidectomy with resection of a papillary cancer of the follicular variant was performed. Then, she was successfully treated with small repetitive radioiodine amounts for a total accumulated dose of 325 mCi 131I, with a long-term survival.

El cáncer diferenciado de tiroides generalmente se acompaña de una supervivencia a largo plazo. Sin embargo, en algunos casos pueden desarrollarse metástasis a distancia y, entre ellas, las localizaciones cerebrales son de mal pronóstico. El objetivo de esta presentación es comunicar el caso clínico de una mujer de 65 años que consultó por diplopía en la mirada vertical que había aparecido un mes antes. La resonancia magnética mostró una gran masa a nivel del cóndilo occipital. Se realizó el diagnóstico de tumor cerebral primario, por lo que fue operada dos veces con resección tumoral incompleta. El estudio histopatológico confirmó una lesión metastásica de carcinoma de tiroides. Se realizó una tiroidectomía total con resección de un cáncer papilar de la variante folicular. Luego, fue tratada con éxito con pequeñas cantidades repetitivas de yodo radiactivo para una dosis total acumulada de 325 mCi 131I, con una supervivencia a largo plazo.

Supervivencia prolongada luego de pequeñas dosis de terapia con radioyodo en metástasis cerebral de cáncer de tiroides / Long-term survival after small doses of radioiodine therapy for brain metastases of thyroid cancer

Resumen El cáncer diferenciado de tiroides generalmente se acompaña de una supervivencia a largo plazo. Sin embargo, en algunos casos pueden desarrollarse metástasis a distancia y, entre ellas, las localizaciones cerebrales son de mal pronóstico. El objetivo de esta presentación es comunicar el caso clínico de una mujer de 65 años que consultó por diplopía en la mirada vertical que había aparecido un mes antes. La resonancia magnética mostró una gran masa a nivel del cóndilo occipital. Se realizó el diagnóstico de tumor cerebral primario, por lo que fue operada dos veces con resección tumoral incompleta. El estudio histopatológico confirmó una lesión metastásica de carcinoma de tiroides. Se realizó una tiroidectomía total con resección de un cáncer papilar de la variante folicular. Luego, fue tratada con éxito con pequeñas cantidades repetitivas de yodo radiactivo para una dosis total acumulada de 325 mCi 131I, con una supervivencia a largo plazo.

Abstract Differentiated thyroid cancer is generally accompanied by a long term survival. However,in some cases distant metastases can develop and among them, brain localizations are of poor prognosis. The aim of this presentation is to communicate the clinical case of a 65 year-old woman who consulted for diplopia in vertical gaze which had appeared one month earlier. MRI showed a big mass at the level of the occipital condyle. Diagnosis of primary brain tumor was made so she was operated twice with incomplete tumor resection. The pathological study was confirmatory of a metastatic lesion of thyroid carcinoma. A total thyroidectomy with resection of a papillary cancer of the follicular variant was performed. Then, she was successfully treated with small repetitive radioiodine amounts for a total accumulated dose of 325 mCi 131I, with a long-term survival.

Long-term outcome after bilateral adrenalectomy in Cushing's disease with focus on Nelson's syndrome

ABSTRACT Objective We analyzed the clinical, biochemical, and imaging findings of adrenalectomized patients with Cushing's disease (CD) in order to compare the characteristics of those who developed Nelson's syndrome (NS) versus those who did not develop this complication (NNS), aiming to identify possible predictive factors for its occurrence. Subjects and methods We performed a retrospective review of the clinical records of a group of patients with CD who underwent TBA between 1974 and 2011. Results Out of 179 patients with CD, 13 (7.3%) underwent TBA. NS occurred in 6 of them (46%) after a mean of 24 months from the total bilateral adrenalectomy (TBA). Age at diagnosis, duration of Cushing's syndrome (CS) until TBA, and steroid replacement doses were similar in both groups. Initial urinary cortisol levels (24-hour urinary free cortisol [UFC]) were significantly higher in the NS group than in the NNS group (p = 0.009). Four patients in the NS group and three of those in the NNS group received radiotherapy before TBA (p = 0.26). Three patients in the NS group presented residual tumors before TBA, compared with none in the NNS group (p = 0.04). At 1 year after TBA, the median ACTH level was 476 ng/L (240-1500 ng/L) in the NS group and 81 ng/L (48-330 ng/L) in the NNS group (p = 0.0007). Conclusion In conclusion, a residual tumor before TBA, higher 24-hour UFC at diagnosis, and increasing ACTH levels within 1 year after TBA emerged as predictive factors of development of NS.

Pegvisomant in acromegaly: a multicenter real-life study in Argentina.

OBJECTIVE: To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. SUBJECTS AND METHODS: We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. RESULTS: Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). CONCLUSION: this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7.

Pegvisomant in acromegaly: a multicenter real-life study in Argentina

ABSTRACT Objective To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. Subjects and methods We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. Results Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). Conclusion this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7

Long-term outcome after bilateral adrenalectomy in Cushing's disease with focus on Nelson's syndrome.

OBJECTIVE: We analyzed the clinical, biochemical, and imaging findings of adrenalectomized patients with Cushing's disease (CD) in order to compare the characteristics of those who developed Nelson's syndrome (NS) versus those who did not develop this complication (NNS), aiming to identify possible predictive factors for its occurrence. SUBJECTS AND METHODS: We performed a retrospective review of the clinical records of a group of patients with CD who underwent TBA between 1974 and 2011. RESULTS: Out of 179 patients with CD, 13 (7.3%) underwent TBA. NS occurred in 6 of them (46%) after a mean of 24 months from the total bilateral adrenalectomy (TBA). Age at diagnosis, duration of Cushing's syndrome (CS) until TBA, and steroid replacement doses were similar in both groups. Initial urinary cortisol levels (24-hour urinary free cortisol [UFC]) were significantly higher in the NS group than in the NNS group (p = 0.009). Four patients in the NS group and three of those in the NNS group received radiotherapy before TBA (p = 0.26). Three patients in the NS group presented residual tumors before TBA, compared with none in the NNS group (p = 0.04). At 1 year after TBA, the median ACTH level was 476 ng/L (240-1500 ng/L) in the NS group and 81 ng/L (48-330 ng/L) in the NNS group (p = 0.0007). CONCLUSION: In conclusion, a residual tumor before TBA, higher 24-hour UFC at diagnosis, and increasing ACTH levels within 1 year after TBA emerged as predictive factors of development of NS.

Akt/p27kip1 Pathway Is Not Involved in Human Insulinoma Tumorigenesis.

Insulinomas are pancreatic neuroendocrine tumors (pNET), usually benign. Akt/p27kip1 is an intracellular pathway overexpressed in many pNET. There are no data regarding its expression in human insulinomas. We aimed to investigate the expression of Akt and p27kip1 in 24 human insulinomas and to compare them to their expression in normal surrounding islets. Staining was performed on embedded paraffin tissue using polyclonal antibodies against total Akt, p-Akt, p27kip1, and pp27kip1. p-Akt was the predominant form in insulinomas; they presented lower Akt and p-Akt expression than normal islets in 83.3% and 87.5% of tumors, respectively. p27kip1 and pp27kip1 were mainly cytoplasmic in both insulinomas and normal tissue. Cytoplasmic pp27kip1 staining was higher in insulinomas and surprisingly nearly half of the insulinomas also presented nuclear p27kip1 (p = 0.029). No differences were observed in the subcellular localization of p27kip1 and activation of Akt between benign and malignant insulinomas. The low expression of Akt seen in insulinomas might explain the usual benign behavior of this type of pNET. Cytoplasmic p27kip1 in both insulinomas and normal islet cells could reflect the low rate of replication of beta cells, while nuclear p27kip1 would seem to indicate stabilization and nuclear anchoring of the cyclin D-Cdk4 complex. Our data seem to suggest that the Akt pathway is not involved in human insulinoma tumorigenesis.

Acromegaly: A rare disease?

Acromegaly is generally considered a benign and uncommon disease. However, some recent data bring support to the idea that it is more frequent than previously thought. Besides, acromegaly can significantly shorten the length of life due to its cardiovascular and metabolic complications. Since its clinical signs are insidiously progressive for many years, there is a considerable delay in its detection. Usually, many different specialists have been consulted before reaching diagnosis of acromegaly. Those specialists include cardiologists, pulmonologists, dentists, rheumatologists, and diabetes specialists. Possible means to achieve earlier detection are based on increasing awareness of doctors and the public in general. In this paper, the author analyzes the factors related to delayed diagnosis and the potential ways to ameliorate awareness of the disease with particular attention to screening procedures.

Acromegaly: a rare disease?

Acromegaly is generally considered a benign and uncommon disease. However, some recent data bring support to the idea that it is more frequent than previously thought. Besides, acromegaly can significantly shorten the length of life due to its cardiovascular and metabolic complications. Since its clinical signs are insidiously progressive for many years, there is a considerable delay in its detection. Usually, many different specialists have been consulted before reaching diagnosis of acromegaly. Those specialists include cardiologists, pulmonologists, dentists, rheumatologists, and diabetes specialists. Possible means to achieve earlier detection are based on increasing awareness of doctors and the public in general. In this paper, the author analyzes the factors related to delayed diagnosis and the potential ways to ameliorate awareness of the disease with particular attention to screening procedures.

Existe la idea generalizada de que la acromegalia es una enfermedad benigna e infrecuente. Sin embargo, el paciente acromegálico ve comprometida su vida a causa de complicaciones cardiovasculares y metabólicas. Por otra parte, trabajos recientes muestran que su frecuencia parece mucho mayor que lo supuesto previamente. Dado que los signos y síntomas de la enfermedad se instalan lenta e insidiosamente, existe una demora considerable en su diagnóstico. Habitualmente, los pacientes han consultado diversos especialistas antes de que el trastorno sea detectado. Los mismos incluyen cardiólogos, neumonólogos, odontólogos, reumatólogos y diabetólogos. Un camino posible para lograr una detección temprana es el incremento del grado de concientización de los médicos y de la comunidad. En este artículo se analizan los factores vinculados al retraso diagnóstico y los medios posibles para mejorar el conocimiento y detección precoz de la enfermedad.

[Myxedema coma]. / Coma mixedematoso.

Hypothyroidism is a frequently diagnosed and simply treated disease. If not recognised, however, in time it may develop into the most severe manifestation of hypothyroidism known as myxedema coma. The term "myxedema coma" is generally seen as misleading since most patients do not initially present in a coma. The typical progression is lethargy evolving into stupor and, eventually, into coma with respiratory failure and hypothermia. It mainly affects elderly women, often occurring in winter and is relatively rare. It can be considered a form of decompensated hypothyroidism often triggered by a variety of non-thyroid conditions or diseases provoking an extremely severe condition of multiple system failure with lethal consequences unless an early diagnosis is made and an aggressive treatment is administered.

Coma mixedematoso / Myxedema coma

El hipotiroidismo es una enfermedad frecuente, de diagnóstico y tratamiento simples. Si no es detectada a tiempo puede progresar a la forma más grave conocida como coma mixedematoso. El término "coma mixedematoso" es considerado generalmente engañoso, ya que la mayoría de los pacientes no se presenta inicialmente en estado de coma. La progresión típica es la letargia, evolucionando al estupor y eventualmente al coma, con insuficiencia respiratoria e hipotermia. Es relativamente infrecuente, afecta fundamentalmente a mujeres ancianas, y a menudo ocurre en invierno. Esta entidad debe ser considerada una forma de hipotiroidismo descompensado, desencadenada a partir de una variedad de enfermedades o condiciones no tiroideas que provocan un compromiso sistémico generalizado de extrema gravedad, con desenlace fatal de no mediar un diagnóstico precoz y un tratamiento intensivo.

Hypothyroidism is a frequently diagnosed and simply treated disease. If not recognised, however, in time it may develop into the most severe manifestation of hypothyroidism known as myxedema coma. The term "myxedema coma" is generally seen as misleading since most patients do not initially present in a coma. The typical progression is lethargy evolving into stupor and, eventually, into coma with respiratory failure and hypothermia. It mainly affects elderly women, often occurring in winter and is relatively rare. It can be considered a form of decompensated hypothyroidism often triggered by a variety of non-thyroid conditions or diseases provoking an extremely severe condition of multiple system failure with lethal consequences unless an early diagnosis is made and an aggressive treatment is administered.

Macroprolactinoma appearing after resolution of hydrocephalus.

SUMMARY: The role of mechanical forces influencing the growth of a pituitary adenoma is poorly understood. In this paper we report the case of a young man with hyperprolactinaemia and an empty sella secondary to hydrocephalia, who developed a macroprolactinoma following the relief of high intraventricular pressure. LEARNING POINTS: The volume of a pituitary tumour may be influenced not only by molecular but also by local mechanical factors.Intratumoural pressure, resistance of the sellar diaphragm and intracranial liquid pressure may play a role in the final size of a pituitary adenoma.The presence of hydrocephalus may hide a pituitary macroadenoma.

Implementing a screening program for acromegaly in Latin America: necessity versus feasibility.

INTRODUCTION: Acromegaly is a rare disease with a large burden due its associated comorbidities and the life-long management required. Since the occurrence and severity of associated complications are related to length of exposure to the excess growth hormone seen in acromegaly, early diagnosis is imperative. The delay in diagnosis, however, can be long, and may be the result of a lack of disease awareness and screening programs. Since acromegaly is an uncommon disease, finding ways to increase recognition and diagnosis that would permit early detection in a logical and cost-effective manner could be a challenge. METHODS: We conducted a retrospective literature review for information relating to the screening and diagnosis of acromegaly using PubMed. The aim was to assess whether an acromegaly-screening program in Latin America (and elsewhere) would be both of use and be feasible. FINDINGS AND CONCLUSIONS: An earlier diagnosis allows earlier initiation of treatment, such as surgery and/or drugs, which leads to more successful disease management (biochemical control) and better outcomes. Since the delay in diagnosis can be long, we believe that clear opportunities exist for earlier (and increased) detection of acromegaly. This can be achieved by increasing disease awareness for earlier recognition of symptoms and by using targeted screening (rather than mass screening) programs.

The 10:00-11:00 pm urine cortisol/creatinine ratio. An alternative to late-night salivary cortisol for the diagnosis of Cushing's syndrome.

The aim of this study was to investigate interchangeability of two tests to diagnose Cushing's syndrome. We compared 10:00-11:00 PM urinary free cortisol/creatinine ratio (UFC/Cr) with late night 11:00 PM salivary cortisol (LNSC) in normal and obese controls vs. patients with Cushing's syndrome. Mean UFC/Cr did not differ between 69 normal and 62 obese controls (9.9 ± 7.9 vs. 9.7 ± 9.3) whereas 116 Cushing's patients had significantly higher values (277.0 ± 318.0; z: -11.1 and -10.2, respectively; p < 0.001). LNSC was 1.9 ± 1.2 nmol/l in 44 normal and 2.5 ± 1.6 in 45 obese subjects with no differences between them, but was significantly higher in 47 Cushing's patients (24.8 ± 23.3; z: -7.22 and -6.96, respectively, p < 0.001). Comparison of UFC/Cr and LNSC in samples obtained simultaneously showed that UFC/Cr was 12.0 ± 8.7 ng cortisol/mg creatinine in 34 normal, 12.3 ± 8.9 in 40 obese and 319.5 ± 333.4 in 35 CS subjects (p < 0.001 vs. normal and obese), whereas LNSC was 1.8 ± 1.2 nmol/l in normal, 2.6 ± 1.7 in obese and 24.6 ± 17.4 in CS patients (p < 0.001 vs. normal and obese); ROC curves showed comparable high sensitivity and specificity figures for the diagnosis of CS. We concluded that UFC/Cr test is easy to perform, readily available in routine laboratories, has high sensitivity and specificity, and offers a valuable alternative to LNSC in the study of Cushing's syndrome.

Temozolomide Therapy for Aggressive Pituitary Tumors: Results in a Small Series of Patients from Argentina.

We evaluated results of temozolomide (TMZ) therapy in six patients, aged 34-78 years, presenting aggressive pituitary tumors. In all the patients tested O(6)-methylguanine-DNA methyltransferase (MGMT) immunoexpression in surgical specimens was absent. Patients received temozolomide 140-320 mg/day for 5 days monthly for at least 3 months. In two patients minimum time for evaluation could not be reached because of death in a 76-year-old man with a malignant prolactinoma and of severe neutro-thrombopenia in a 47-year-old woman with nonfunctioning pituitary adenoma. In two patients (a 34-year-old acromegalic woman and a 39-year-old woman with Nelson's syndrome) no response was observed after 4 and 6 months, respectively, and the treatment was stopped. Conversely, two 52- and 42-year-old women with Cushing's disease had long-term total clinical and radiological remissions which persisted after stopping temozolomide. We conclude that TMZ therapy may be of variable efficacy depending on-until now-incompletely understood factors. Cooperative work on a greater number of cases of aggressive pituitary tumors should be crucial to establish the indications, doses, and duration of temozolomide administration.

Tiroiditis no-autoinmunes / Non-autoimmune thyroiditis

El término tiroiditis comprende un grupo de enfermedades de la glándula tiroides caracterizado por la presencia de inflamación, abarcando entidades autoinmunes y no-autoinmunes. Pueden manifestarse como enfermedades agudas con dolor tiroideo severo (tiroiditis subaguda y tiroiditis infecciosas), y condiciones en las cuales la inflamación no es clínicamente evidente, cursando sin dolor y presentando disfunción tiroidea y/o bocio (tiroiditis inducida por fármacos y tiroiditis de Riedel). El objetivo de esta revisión es aportar un enfoque actualizado sobre las tiroiditis no-autoinmunes cubriendo sus aspectos clínicos, diagnósticos y terapéuticos.

The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.

[Female hyperandrogenemia and normal serum levels of testosterone and sex hormone binding globulin]. / Hiperandrogenemia femenina y niveles séricos normales de testosterona y globulina ligadora de esteroides sexuales.

It is well known that the reference values usually employed for endocrine biochemical measurements are those suggested by the suppliers of commercial kits despite their advice that each laboratory should set its own reference values. Our objectives were to (i) determine reference ranges for serum testosterone (T) and sex hormone binding globulin (SHBG) appropriate to our laboratory and population, and (ii) to analyze their influence on evaluating hyperandrogenemia. SHBG and T were measured, and free and bioavailable testosterone calculated, in (a) 30 selected non-hyperandrogenic women, (b) 87 non-selected healthy female blood donors, (c) 53 women with hyperandrogenism, and (d) 38 women with hyperandrogenic disorders but without biochemical hyperandrogenemia according to normal ranges suggested by the kit manufacturer. Mean serum SHBG concentrations were significantly different among all four groups. SHBG levels were significantly higher in selected normal women (group a). Using our results for this selected control group as new reference values, 12 out of 38 (31.6%) women with hyperandrogenic disorders without apparent hyperandrogenemia (group d) were recategorized as hyperandrogenemic. Similarly, 4 out of 63 (6.4%) non-selected, normal weight, women (group b), were recategorized as hyperandrogenic. Therefore, the diagnosis of hyperandrogenemia would improve accuracy by using customized reference SHBG values instead of those suggested by the suppliers.