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Lymphoma infiltration to the pituitary is rare. It represents less than 0.5% of all reported pituitary metastases (PMs). Here we present a case series of 3 patients with PMs from a systemic lymphoma. Also, we performed a literature review of the cases reported. We identified additional 31 cases in which non-Hodgkin lymphoma (NHL) was the most common (n = 28, 90%), with large B-cell NHL the most frequent histological subtype (n = 14, 45%). Central hypothyroidism (n = 21, 67%) was the most frequent pituitary deficiency followed by adrenal insufficiency (n = 19, 61%) and diabetes insipidus (DI; n = 18, 58%). Full endocrine recovery was found in only 12% (n = 4) of patients after treatment, and magnetic resonance imaging showed tumor regression in 22% of them. In our series, 2 patients were diagnosed with diffuse large B-cell lymphoma, and 1 had mixed cellularity of classic Hodgkin lymphoma. The mean age was 54 ± 6.92 years. Hypopituitarism and DI were present in all of them, with 100% of mortality because of advanced systemic disease. more...

Background Extragonadal choriocarcinoma is rare and can be associated with hyperthyroidism when producing very high levels of human chorionic gonadotropin. Case presentation A 62-year-old Hispanic female presented with a 3-week history of shortness of breath, palpitations, extreme weakness, new-onset hot flashes, and right flank pain. Her physical examination was remarkable for tachycardia, hepatomegaly, hyperreflexia, and tremor; goiter was absent. Laboratory studies revealed increased lactate dehydrogenase, alkaline phosphatase, suppressed thyroid stimulating hormone, very elevated T4, and absent thyroid stimulating immunoglobulin. 18F-fluorodeoxyglucose positron emission tomography-computed tomography exhibited hepatomegaly with multiple large fluorodeoxyglucose-avid liver masses and a focus of fluorodeoxyglucose avidity in the stomach with no structural correlate. A thyroid scan (99mTcO 4 − ) showed diffusely increased tracer uptake. She was started on propranolol and methimazole. Upon stabilization of severe thyrotoxicosis, upper endoscopy was performed, showing a ~ 5 cm bleeding lesion in the greater stomach curvature body; biopsy was consistent with choriocarcinoma; beta-human chorionic gonadotropin hormone was 2,408,171 mIU/mL. The patient received methotrexate followed by etoposide and cisplatin. Methimazole was titrated down, and upon liver failure the medication was stopped. The thyrotoxicosis was effectively controlled with antithyroid drug and concurrent chemotherapy. At ~ 1.5 months after initial diagnosis, the patient died due to bleeding/acute liver failure with coagulation defects followed by multiple organ failure. Conclusions Severe thyrotoxicosis can represent an unusual initial presentation of metastatic choriocarcinoma in the setting of extreme elevation of beta-human chorionic gonadotropin. Primary gastric choriocarcinoma is an aggressive malignancy with very poor outcomes. The co-occurrence of severe thyrotoxicosis with advanced primary gastric choriocarcinoma and imminent liver failure complicates management options. more...

A 57-year-old man presented to the outpatient clinic with tremor, palpitations, weight loss and fatigue 1 week after receiving the first dose of the Oxford-AstraZeneca SARS-CoV-2 vaccine (ChAdOx1 nCoV-19). Laboratory studies showed a suppressed TSH with elevated total and free T4. Thyroid peroxidase and thyroglobulin antibodies were elevated but thyrotropin receptor autoantibodies were indeterminate. Thyroid scintigraphy with technetium Tc-99m pertechnetate revealed increased diffuse, symmetric uptake. The patient was treated with thiamazole 15 mg three times a day and propranolol with resolution of his symptoms and normalization of his thyroid function tests until discontinuation of the antithyroid drug 6 months after symptom onset.Thyroid autoimmunity triggered by SARS-CoV-2 vaccines is being increasingly recognized among patients with and without a history of autoimmune thyroid disease.Symptoms and signs of thyrotoxicosis, including fever and tachycardia, can be wrongly attributed to the systemic adverse events of these vaccines.Early recognition of this condition is mandatory to allow proper treatment with anti-thyroid medications and radioactive iodine when necessary. more...

Malignant lymphoma of the pituitary gland is extremely rare. The most common form of CNS involvement in lymphoma is leptomeningeal metastases, but it can also affect the spine or the cerebral parenchyma. Pituitary involvement usually presents as diabetes insipidus but can also present as hypopituitarism if there is adenohypophyseal destruction and may also present as bitemporal hemianopsia. (1)We present a case series of four patients with metastatic lymphomas to the pituitary gland that presented with diabetes insipidus to a tertiary center in Mexico City. Our investigation identified 4 patients with a previous diagnosis of lymphoma (3 B cell non-Hodgkin and 1 Hodgkin lymphoma) that were admitted into the endocrinology clinic with evidence of pituitary involvement and metastases to the pituitary gland. The average age of the cases was 54.5 years. 1 of the 4 patients had a diagnosis of HIV infections prior to the diagnosis of the lymphoma. Diabetes insipidus was present in 100% of the patients, while headache (75%) and visual field defects (50%) were the most common findings at presentation. Two of the patients also had involvement of the adenohypophysis and had hypocortisolism and central hypothyroidism that required hormone replacement therapy. All cases were documented by a lesion in the contrast enhancing lesion on MRI. Lymphoma involving the pituitary gland is particularly rare. In our series, involvement of the posterior pituitary was the most common form of presentation in contrast to the reported in other series, but the clinical presentation can be heterogenous, hence, it is important to perform an extensive endocrinological examination when pituitary involvement is suspected.1. Mathiasen RA, Jarrahy R, Cha ST, et al. Pituitary lymphoma: a case report and literature review. Pituitary. 2000;2(4): 283-287. doi: 10.1023/a: 1009969417380 Presentation: No date and time listed more...

Immune checkpoint inhibitors (ICI) are a group of drugs that have been used in recent years for the treatment of advanced malignancies such as melanoma, non-small cell lung cancer and other tumors, significantly increasing survival. However, the use of ICI has been associated with an increased risk of autoimmune diseases, with endocrine organs, specifically the thyroid, being highly susceptible to this phenomenon.To describe the incidence and clinical characteristics of patients treated with ICI who develop thyroid disease.The medical records of all patients who received ICI treatment within the last three years were retrospectively reviewed, with those who developed thyroid abnormalities being identified.The prevalence of thyroiditis was 7 %, with an incidence of 21.4 % of patients-month. Median time for the development of thyroiditis was 63 days. Most patients had mild or moderate symptoms and did not require hospitalization, although all but one developed permanent hypothyroidism and required hormone replacement therapy with levothyroxine.Thyroid dysfunction secondary to immunotherapy is a common entity in our population. Clinical presentation is usually mild and does not require treatment discontinuation; however, due to the high incidence of these adverse events, non-oncology specialists must be familiar with the diagnosis and treatment of these alterations in order to provide multidisciplinary management.Los inhibidores del punto de control inmunológico (IPCi) son utilizados en los últimos años en el tratamiento de neoplasias malignas avanzadas, con ellos se ha logrado un aumento significativo de la supervivencia; sin embargo, su uso se ha asociado a incremento del riesgo de enfermedades autoinmunes.Describir la incidencia y las características clínicas de los pacientes tratados con IPCi que desarrollaron tiroidopatía.Se revisaron retrospectivamente los expedientes de todos los pacientes que recibieron IPCi en los últimos tres años y se identificaron aquellos que desarrollaron anomalías tiroideas.La prevalencia de tiroiditis fue de 7 %, con una incidencia de 21.4 % pacientes/mes. La mediana del tiempo para el desarrollo de tiroiditis fue de 63 días. La mayoría de los pacientes presentó síntomas leves o moderados y no requirió hospitalización, si bien todos menos uno desarrollaron hipotiroidismo permanente y requirieron terapia de reemplazo hormonal con levotiroxina.La disfunción tiroidea secundaria a inmunoterapia es una entidad común en nuestra población. El cuadro clínico suele ser leve y no requiere suspender el tratamiento; sin embargo, debido a la alta incidencia de este evento adverso, los médicos no oncólogos deben estar familiarizados con su diagnóstico y tratamiento, para brindar un manejo multidisciplinario. more...

Objective: Describe the demographic, clinical, and biochemical characteristics of overweight or obese people with severe COVID-19 pneumonia and evaluate its association with mechanical ventilation requirements in a Mexican cohort. Subjects and methods: Data were obtained from medical electronic records. Patients were divided in three groups according to the World Health Organization (WHO) classification of body mass index (BMI): lean, overweight and obese. Baseline characteristics and clinical course were compared among these 3 groups. Results: The study included a total of 355 patients with confirmed COVID-19 diagnoses. Patients with obesity and overweigh, according to the WHO classification, had no significantly increased risk of requiring intubation and invasive mechanical ventilation (IMV) compared to lean subjects, with an odds ratio (OR) of 1.82 (95% CI, 0.94-3.53). A post hoc and multivariate analysis using a BMI > 35 kg/m2 to define obesity revealed that subjects above this cut off had as significantly increased risk of requiring IMV after with an OR of 2.86 (95% CI, 1.09-7.05). Conclusion: We found no higher risk of requiring IMV in patients with overweight or obesity while using conventional BMI cutoffs. According to our sensitivity analyses, the risk of IMV increases in patients with a BMI over 35 kg/m2. more...

Invasive pulmonary aspergillosis (IPA) is a severe infection caused by aspergillus sp. that usually develops in patients with severe immunosuppression. IPA has been recently described in critically ill COVID-19 patients (termed as COVID-associated pulmonary aspergillosis, or CAPA) that are otherwise immunocompetent. In order to describe the characteristics of patients with CAPA, we conducted a retrospective cohort study in a tertiary care center in Mexico City. We included all patients with confirmed COVID-19 admitted to the intensive care unit that had serum or bronchoalveolar lavage galactomannan measurements. We used the criteria proposed by Koehler et al. to establish the diagnosis of CAPA. Main outcomes were the need for invasive mechanical ventilation (IMV) and in-hospital mortality. Out of a total of 83 hospitalized patients with COVID-19 in the ICU, 16 (19.3%) met the criteria for CAPA. All patients diagnosed with CAPA required IMV whereas only 84% of the patients in the non-IPA group needed this intervention (P = 0.09). In the IPA group, 31% (n = 5) of the patients died, compared to 13% (n = 9) in the non-CAPA group (P = 0.08). We conclude that CAPA is a frequent co-infection in critically ill COVID-19 patients and is associated with a high mortality rate. The timely diagnosis and treatment of IPA in these patients is likely to improve their outcome. Lay Summary We studied the characteristics of patients with COVID-19-associated invasive pulmonary aspergillosis (CAPA). Patients with CAPA tended to need invasive mechanical ventilation more frequently and to have a higher mortality rate. Adequate resources for its management can improve their outcome more...

Background Coronavirus disease 2019 (COVID-19) is a systemic disease that can rapidly progress into acute respiratory failure and death. Timely identification of these patients is crucial for a proper administration of health-care resources. Objective To develop a predictive score that estimates the risk of invasive mechanical ventilation (IMV) among patients with COVID-19. Study design Retrospective cohort study of 401 COVID-19 patients diagnosed from March 12, to August 10, 2020. The score development cohort comprised 211 patients (52.62% of total sample) whereas the validation cohort included 190 patients (47.38% of total sample). We divided participants according to the need of invasive mechanical ventilation (IMV) and looked for potential predictive variables. Results We developed two predictive scores, one based on Interleukin-6 (IL-6) and the other one on the Neutrophil/Lymphocyte ratio (NLR), using the following variables: respiratory rate, SpO2/FiO2 ratio and lactic dehydrogenase (LDH). The area under the curve (AUC) in the development cohort was 0.877 (0.823–0.931) using the NLR based score and 0.891 (0.843–0.939) using the IL-6 based score. When compared with other similar scores developed for the prediction of adverse outcomes in COVID-19, the COVID-IRS scores proved to be superior in the prediction of IMV. Conclusion The COVID-IRS scores accurately predict the need for mechanical ventilation in COVID-19 patients using readily available variables taken upon admission. More studies testing the applicability of COVID-IRS in other centers and populations, as well as its performance as a triage tool for COVID-19 patients are needed. more...

Given the lipolytic effect of GH and its potential role in determining adipose tissue distribution, we evaluated the expression of the GH hormone receptor (GHR) isoforms in patients with morbid obesity seeking associations with metabolic parameters. 262 morbidly obese subjects (mean age 42.5 ± 11 years, 75% women) underwent PCR-genotyping of the exon 3 GHR polymorphism. In 17 of these subjects, who proved to be heterozygous for the exon 3 genotype (+3/−3), subcutaneous and visceral adipose tissue was obtained during bariatric surgery; total RNA was extracted, reversely transcribed, and the different isoforms of the GHR (exon 3 containing and lacking flGHR as well as the trGHR) were PCR-amplified using specific primers. 27% were +3/+3 homozygous, 20% −3/−3 homozygous and 53% were +3/−3 heterozygous. Compared to subjects homozygous for the +3 genotype, homozygous and heterozygous carriers of the −3 genotype were significantly heavier and tended to have a higher HOMA 2-IR. Expression of the flGHR and trGHR mRNA was demonstrated in all evaluated samples of subcutaneous and visceral adipose tissue from the 17 patients. The exon 3+ isoform was expressed in all adipose tissue samples, whereas only six subjects expressed the 3− isoform as well. The only distinctive feature of these six patients was a higher HbA1c. The heterozygous GHR +3/−3 genotype is more prevalent in subjects with morbid obesity. Patients expressing the exon +3 and exon −3 isoforms in adipose tissue had a higher HbA1c, than those expressing only the exon −3 isoform. more...

Clinically non-functioning pituitary adenomas (NFPAs) are among the most common tumors in the sellar region. These lesions do not cause a hormonal hypersecretion syndrome, and are therefore found incidentally (particularly microadenomas) or diagnosed based on compressive symptoms such as headache and visual field defects, as well as clinical signs of pituitary hormone deficiencies. Immunohistochemically, more than 45% of these adenomas stain for gonadotropins or their subunits and are therefore called gonadotropinomas, while 30% of them show no immunostaining for any hormone and are known as null cell adenomas. The diagnostic approach to NFPAs should include visual field examination, an assessment of the integrity of all anterior pituitary hormone systems, and magnetic resonance imaging of the sellar region to define tumor size and extension. The treatment of choice is transsphenoidal resection of the adenoma, which in many instances cannot be completely accomplished. The recurrence rate after surgery may be up to 30%. Persistent or recurrent adenomas are usually treated with radiation therapy. In a small proportion of these cases, drug treatment with dopamine agonists and, to a lesser extent, somatostatin analogs may achieve reduction or at least stabilization of the tumor. more...

Mexico has been one of the most affected countries by COVID-19, with case rate of 1195.32 per 100,000 patients and one of the highest mortality rates worldwide. Diabetes has been found a major risk factor for severe COVID-19. Mexico has a high prevalence of diabetes, estimated around 10.3%. On top of this, recent estimates suggest that 4.1% of the population has diabetes but does not have a proper diagnosis. We conducted a retrospective study in patients hospitalized for COVID-19 in tertiary private hospital in Mexico City from March 15th to July 10th, 2020. We classified patients as having diabetes or prediabetes if it was registered in the electronical medical record. Patients were classified as newly diagnosed diabetes if they had an HbA1c on admission greater or equal than 6.5%. A total of 144 measurements of HbA1c were done on non-diabetic patients. Eighteen patients (12.5%) had a level of HbA1c equal or higher than 6.5%, while 70 (48.6%) patients had a level between 5.7% and 6.5%. Of the patients with HbA1c levels suggesting prior diabetes, 9 (50%) of them did not have hyperglycemia (>140 mg/dl) on admission. Our findings suggest that Mexican patients with COVID-19 might need HbA1c measurements regardless of glucose levels on admission since unknown diabetes is frequent and might modify in-hospital glucose management and discharge follow up and treatment. more...

Background An elevated incidence of invasive pulmonary aspergillosis (IPA) in patients with COVID-19 without traditional risk factors for IPA has been recently reported around the world. This co-infection has been described in patients requiring treatment in an intensive care unit. The risk factors for its development are still unclear. Methods We conducted a nested case-control study using the COVID-19 registry of the ARMII study group, based in the Centro Médico ABC, a private hospital in Mexico City. We included all patients that required admission to the intensive care unit (ICU) from March 12 to June 15, 2020, and excluded patients without serum galactomannan measurements or bronchial secretion cultures. We used the modified definition of IPA proposed by Schauwvlieghe et al for IPA in influenza patients. The control group was formed by patients with ruled-out IPA (negative galactomannan and secretion cultures). We compared both groups to identify risk factors for IPA using the chi-squared test or the Mann-Whitney U test as applicable. Results Out of a total 239 patients, 54 met the inclusion criteria. We identified 13 patients with IPA (24.07%) that met the definition of IPA (2 with positive cultures and 11 with positive galactomannan) and 41 without IPA. Only three patients with IPA had important comorbidities (COPD, chronic kidney disease, and HIV). Patients with IPA tended to have a higher median age (64.6 vs 53.59, p=0.075) and a higher serum glucose at their arrival (145 vs 119, p=0.028). All patients with IPA presented to the hospital with ARDS (100% vs 72.5%, p=0.034), but ultimately did not have a higher requirement for mechanical ventilation (100% vs 82.93%, p=0.110). There were no statistical significant differences in use of Tocilizumab, use of glucocorticoids, mortality (23.07% vs 17.50%, p=0.563) or length of stay. Conclusion It has been previously described that patients with acute respiratory disease syndrome triggered by viral infection, like the influenza virus, are prone to invasive aspergillosis even in the absence of underlying immunodeficiency. The use of antifungals to prevent aspergillosis in COVID-19 patients should be assessed because of the gravity presented in the patients with this co-infection. Disclosures All Authors: No reported disclosures more...

Struma ovarii is a rare monodermal variant of ovarian teratoma that contains at least 50% thyroid tissue. Less than 8% of struma ovarii cases present with clinical and biochemical evidence of thyrotoxicosis due to ectopic production of thyroid hormone and only 5% undergo malignant transformation into a papillary thyroid carcinoma. Only isolated cases of hormonally active papillary thyroid carcinoma developing within a struma ovarii have been reported in the literature. We report the case of a 36-year-old woman who presented with clinical signs and symptoms of hyperthyroidism as well as a left adnexal mass, which proved to be a thyroid hormone-producing, malignant struma ovarii. more...

Hyperprolactinemia is a frequent neuroendocrinological condition that should be approached in an orderly and integral fashion, starting with a complete clinical history. Once physiological causes such as pregnancy, systemic disorders such as primary hypothyroidism and the use of drugs with dopamine antagonistic actions such as metochlopramide have been ruled out, the most common cause of hyperprolactinemia is a PRL-secreting pituitary adenoma or prolactinoma. Prolactinomas are usually classified as microprolactinomas (less than 1 cm) or macroprolactinomas (larger than 1 cm), which can either be confined or invasive. The hormonal consequence of hypeprolactinemia is hypogonadism; in women, this is manifested as amenorrhea/oligomenorreha, anovulation and galactorrhea, whereas in men the main complaints are a diminished libido and erectile dysfunction. Macroprolactinomas can also present with symptoms and signs resulting form mass effect of the tumor, such as headaches and visual field defects. Other structural causes of hyperprolactinemia include non-functioning pituitary adenomas and infiltrative disorders, which can interrupt the inhibitory, descending dopaminergic tone. The primary treatment of prolactinomas is pharmacological with dopamine agonists such as cabergoline.La hiperprolactinemia es uno de los trastornos neuroendocrinológicos más frecuentes y su abordaje debe hacerse de manera ordenada e integral, partiendo de una historia clínica completa. Una vez excluidas las causas fisiológicas, como el embarazo, enfermedades sistémicas (como el hipotiroidismo primario) y el uso de fármacos con acción antidopaminérgica (como la metoclopramida), la causa más común de la hiperprolactinemia es la presencia de un adenoma hipofisario productor de prolactina (PRL) o prolactinoma. Los prolactinomas se clasifican por su tamaño en microprolactinomas (menores de 1 cm) y macroprolactinomas (mayores de 1 cm), los cuales a su vez pueden ser intraselares o invasivos. La consecuencia hormonal de la hiperprolactinemia es el hipogonadismo; en la mujer, esto se manifiesta como amenorrea/oligomenorrea, anovulación y galactorrea, mientras que en el hombre la manifestación consiste en la disminución de la libido y disfunción eréctil. En el caso de los macroprolactinomas, no es infrecuente encontrar síntomas y signos de efecto de masa como cefalea y alteraciones en los campos visuales. Otras causas estructurales de hiperprolactinemia son los adenomas no funcionantes y las enfermedades infiltrativas de la hipófisis, las cuales interrumpen el tono dopaminérgico descendente. El tratamiento primario de los prolactinomas es farmacológico, a base de agonistas dopaminérgicos, como la cabergolina. more...

Acromegaly is a rare condition characterized by the excessive secretion of growth hormone (GH), usually by a pituitary adenoma. The clinical manifestations of acromegaly include enlarged hands, feet and face, headaches, arthralgias, fatigue and hyperhydrosis. This condition is also associated with comorbidities such as hypertension and diabetes in a significant proportion of patients and frequently compromises life quality and life expectancy. The biochemical diagnosis of acromegaly rests on the demonstration of an autonomous secretion of GH by means of the measurement of glucose-suppressed GH levels and the serum concentration of insulin like growth factor type 1 (IGF-1). The localizing method of choice is magnetic resonance image of the selar area, which in 70 % of the cases reveals the presence of a macroadenoma. Even though the primary treatment is usually the transsphenoidal resection of the adenoma, the majority of patients require a multimodal intervention that includes radiotherapy, as well as pharmacological therapy with somatostatin analogs and dopamine agonists. The latter approach has resulted in a significant reduction in mortality and in an improvement in the quality of life.La acromegalia es una entidad rara que se caracteriza por un incremento en la secreción de hormona de crecimiento (GH), generalmente resultado de un adenoma hipofisiario. Las manifestaciones clínicas incluyen acrocrecimiento de manos, pies y cara, cefalea, artralgias, fatiga e hiperhidrosis. Esta condición se asocia a comorbilidades como la hipertensión y la diabetes en una proporción importante de pacientes y resulta en una disminución en la esperanza y la calidad de vida. El diagnóstico bioquímico se basa en la demostración de una hipersecreción autónoma de GH mediante la prueba de supresión con glucosa y en la presencia de niveles elevados de factor de crecimiento insulinoide tipo 1 (IGF-1). El método de imagen de elección es la resonancia magnética nuclear (RMN) de silla turca, la cual muestra un macroadenoma en el 7 % de los casos. Si bien el tratamiento de elección es la cirugía transefenoidal, la mayoría de los pacientes requiere de un abordaje multimodal, que incluye radioterapia y manejo farmacológico con agonistas dopaminérgicos y análogos de la somatostatina. Este abordaje multimodal, aunado al tratamiento específico de las distintas comorbilidades ha resultado en una disminución significativa en la mortalidad y en una importante mejoría en la calidad de vida de estos pacientes. more...