Rare Thyroid Diseases Mimicking or Concealing Primitive Thyroid Neoplasms: A Call for a "Check and Double-Check" Clinical Mindset.

Clinical endocrinologists encounter in their practice patients with thyroid diseases on a daily basis. Still, diagnosis of rare structural thyroid disorders can be quite challenging. In some instances, they do not only impersonate but can also conceal, other conditions such as thyroid carcinomas. We describe a series of patients with structural thyroid disorders including 1) anaplastic thyroid carcinoma initially presenting with features of thyroid abscess; 2) unicentric hyaline vascular Castleman's disease of the thyroid embedded in a stroma of papillary thyroid carcinoma; and 3) primary thyroid lymphoma with a rapid and fulminant evolution. The common challenge in the diagnosis of these cases lies in both their low incidence and their complex presentation. We use the presentation of these cases to raise the attention related to their identification. We highlight the need for precision diagnosis to enable a patient-tailored management approach and improve patient outcomes.

Lymphadenopathy after COVID-19 vaccination in patients with endocrine cancer: two case reports.

Summary: The Covid-19 vaccination has been rapidly implemented among patients with cancer. We present two cases of patients with endocrine tumours who developed lymphadenopathy following a Covid-19 vaccination. In the case of a patient with multiple endocrine neoplasia (MEN) 1 syndrome, an 18-fluorodeoxyglucose (18FDG)-PET/CT showed positive axillary lymph nodes. Further work-up with fine needle aspiration showed a reactive pattern following a Covid-19 vaccination in the ipsilateral arm shortly before the 18FDG-PET/CT. A second patient, in follow-up for thyroid cancer, developed clinical supraclavicular lymphadenopathy after a Covid-19 vaccination. Follow-up ultrasound proved the lesion to be transient. These cases demonstrate lymphadenopathy in response to a Covid-19 vaccination in two patients susceptible to endocrine tumours and metastatic disease. With growing evidence about the pattern and occurrence of lymphadenopathy after mRNA Covid-19 vaccination, recommendations for scheduling and interpretation of imaging among cancer patients should be implemented to reduce equivocal findings, overdiagnosis, and overtreatment, while maintaining a good standard of care in oncological follow-up. Learning points: Reactive lymphadenopathy is very common after an mRNA vaccination against Covid-19 and should be part of the differential diagnosis in patients with endocrine tumours who recently received a Covid-19 mRNA vaccination and present with an ipsilateral lymphadenopathy. A good vaccine history is essential in assessing the risk for lymphadenopathy and if possible, screening imaging in patients with endocrine tumours should be postponed at least 6 weeks after the previous vaccination. For now, a multidisciplinary care approach is recommended to determine the necessary steps in the diagnostic evaluation of lymphadenopathy in the proximity of a Covid-19 vaccination.

Pituitary carcinoma - case series and review of the literature.

Although pituitary adenomas (PAs) account for 15% of intracranial tumors, pituitary carcinomas (PCs) are a rare entity. Most commonly, PCs evolve from aggressive PAs invading the surrounding structures and eventually leading to metastatic lesions. Due to the low incidence, the diagnosis and treatment remains challenging. We report a case series of five patients with pituitary carcinoma (PC) treated in our center. At first diagnosis 3 patients had an ACTH-producing adenoma, 1 a prolactinoma and 1 a double secreting adenoma (GH and prolactin). The mean time interval from initial diagnosis to diagnosis of PC was 10.7 years (range 5-20 years). All patients underwent multiple surgical resections and radiotherapy. Four patients were treated with temozolomide for metastatic disease. One patient with concomitant radiochemotherapy for local recurrence. Temozolomide led to a stable disease in 2 patients. One patient had a progressive disease after 9 cycles of temozolomide. In absence of standard treatment, immunotherapy was initiated, resulting in a stable disease. We report five cases of PCs. Three patients obtained a stable disease after tailored multidisciplinary treatment. Additionally, one patient was treated with immunotherapy, opening a new treatment option in PCs. Overall, PCs are rare intracranial neoplasms occurring several years after the initial diagnosis of aggressive PAs. Currently, the absence of predictive factors for an aggressive clinical course, provokes a challenging management.

COVID-19 and Cushing's disease in a patient with ACTH-secreting pituitary carcinoma.

SUMMARY: The pandemic caused by severe acute respiratory syndrome coronavirus 2 is of an unprecedented magnitude and has made it challenging to properly treat patients with urgent or rare endocrine disorders. Little is known about the risk of coronavirus disease 2019 (COVID-19) in patients with rare endocrine malignancies, such as pituitary carcinoma. We describe the case of a 43-year-old patient with adrenocorticotrophic hormone-secreting pituitary carcinoma who developed a severe COVID-19 infection. He had stabilized Cushing's disease after multiple lines of treatment and was currently receiving maintenance immunotherapy with nivolumab (240 mg every 2 weeks) and steroidogenesis inhibition with ketoconazole (800 mg daily). On admission, he was urgently intubated for respiratory exhaustion. Supplementation of corticosteroid requirements consisted of high-dose dexamethasone, in analogy with the RECOVERY trial, followed by the reintroduction of ketoconazole under the coverage of a hydrocortisone stress regimen, which was continued at a dose depending on the current level of stress. He had a prolonged and complicated stay at the intensive care unit but was eventually discharged and able to continue his rehabilitation. The case points out that multiple risk factors for severe COVID-19 are present in patients with Cushing's syndrome. 'Block-replacement' therapy with suppression of endogenous steroidogenesis and supplementation of corticosteroid requirements might be preferred in this patient population. LEARNING POINTS: Comorbidities for severe coronavirus disease 2019 (COVID-19) are frequently present in patients with Cushing's syndrome. 'Block-replacement' with suppression of endogenous steroidogenesis and supplementation of corticosteroid requirements might be preferred to reduce the need for biochemical monitoring and avoid adrenal insufficiency. The optimal corticosteroid dose/choice for COVID-19 is unclear, especially in patients with endogenous glucocorticoid excess. First-line surgery vs initial disease control with steroidogenesis inhibitors for Cushing's disease should be discussed depending on the current healthcare situation.

A focused 35-minute whole body MRI screening protocol for patients with von Hippel-Lindau disease.

BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited tumor syndrome. Affected patients develop central nervous system hemangioblastomas and abdominal tumors, among other lesions. Patients undergo an annual clinical screening program including separate magnetic resonance imaging (MRI) of the brain, whole spine and abdomen. Consequently, patients are repeatedly subjected to time-consuming and expensive MRI scans, performed with cumulative Gadolinium injections. We report our experience with a 35-min whole body MRI screening protocol, specifically designed for detection of VHL-associated lesions. METHODS: We designed an MRI protocol dedicated to the typical characteristics of VHL-associated lesions in different imaging sequences, within the time frame of 35 min. Blank imaging of the abdomen is carried out first, followed by abdominal sequences with Gadolinium contrast. Next, the full spine is examined, followed by imaging of the brain. A single dose of contrast used for abdominal imaging is sufficient for further highlighting of spine- and brain lesions, thus limiting the Gadolinium dosage. We used 1.5 Tesla equipment, dealing with fewer artifacts compared to a 3 Tesla system for spine- and abdominal imaging, while preserving acceptable quality for central nervous system images. In addition, imaging on a 1.5 Tesla scanner is slightly faster. RESULTS: From January 2016 to November 2018, we performed 38 whole body screening MRIs in 18 VHL patients; looking for the most common types of VHL lesions in the abdomen, spine, and brain, both for new lesions and follow-up. The one-step approach MRI examinations lead to 6 surgical interventions for clinically significant or symptomatic hemangioblastomas in the brain and spine. One renal cell carcinoma was treated with radiofrequency ablation. In comparison with previous conventional MRI scans of the same patients, all lesions were visible with the focused protocol. CONCLUSIONS: Annual screening in VHL disease can be done in a rapid, safe and sensitive way by using a dedicated whole body MRI protocol; saving MRI examination time and limiting Gadolinium dose.

Endocochlear potential depends on Cl- channels: mechanism underlying deafness in Bartter syndrome IV.

Human Bartter syndrome IV is an autosomal recessive disorder characterized by congenital deafness and severe renal salt and fluid loss. It is caused by mutations in BSND, which encodes barttin, a beta-subunit of ClC-Ka and ClC-Kb chloride channels. Inner-ear-specific disruption of Bsnd in mice now reveals that the positive potential, but not the high potassium concentration, of the scala media depends on the presence of these channels in the epithelium of the stria vascularis. The reduced driving force for K(+)-entry through mechanosensitive channels into sensory hair cells entails a profound congenital hearing loss and subtle vestibular symptoms. Although retaining all cell types and intact tight junctions, the thickness of the stria is reduced early on. Cochlear outer hair cells degenerate over several months. A collapse of endolymphatic space was seen when mice had additionally renal salt and fluid loss due to partial barttin deletion in the kidney. Bsnd(-/-) mice thus demonstrate a novel function of Cl(-) channels in generating the endocochlear potential and reveal the mechanism leading to deafness in human Bartter syndrome IV.

Estradiol improves cerebellar memory formation by activating estrogen receptor beta.

Learning motor skills is critical for motor abilities such as driving a car or playing piano. The speed at which we learn those skills is subject to many factors. Yet, it is not known to what extent gonadal hormones can affect the achievement of accurate movements in time and space. Here we demonstrate via different lines of evidence that estradiol promotes plasticity in the cerebellar cortex underlying motor learning. First, we show that estradiol enhances induction of long-term potentiation at the parallel fiber to Purkinje cell synapse, whereas it does not affect long-term depression; second, we show that estradiol activation of estrogen receptor beta receptors in Purkinje cells significantly improves gain-decrease adaptation of the vestibulo-ocular reflex, whereas it does not affect general eye movement performance; and third, we show that estradiol increases the density of parallel fiber to Purkinje cell synapses, whereas it does not affect the density of climbing fiber synapses. We conclude that estradiol can improve motor skills by potentiating cerebellar plasticity and synapse formation. These processes may be advantageous during periods of high estradiol levels of the estrous cycle or pregnancy.

Otolith deprivation induces optokinetic compensation.

According to the multisensory integration theory vestibular, optokinetic and proprioceptive inputs act in concert to maintain a stable retinal image of the visual world. Yet, it remains elusive to what extent the otolith organs contribute to this process and whether a specific loss of otolith input is compensated for. Here we investigated the compensatory eye movements in tilted mice, which lack otoconia because of a mutation in otopetrin 1. Tilted mice showed very small displacements of the eyes in the orbit during static roll paradigms, suggesting the absence of functional otolith organs. Independent of head position with respect to gravity, the gain and phase lead of angular vestibuloocular reflex of tilted mice were decreased and increased, respectively (frequencies 0.2 to 1 Hz and peak accelerations 8 to 197 degrees /s2, respectively). Furthermore, lack of otolith input increases the dependency of the vestibular system on stimulus frequency. In contrast, the gain of optokinetic reflex in tilted mice was significantly higher in the low-frequency range than in control mice, regardless of the position of the mice in space or the plane of the eye movements. To explain these results, a simple model was used in which a multisensory integration unit was embedded. With this model, we were able to simulate all the behaviors observed. Thus our data and the model support the presence of the multisensory integration system and revealed a compensatory enhanced optokinetic reflex in tilted mice, indicating an adaptive synergism in the processing of otolith and visually driven signals.

A behavioral and histological study of the effects of long-term exposure of adult rats to aluminum.

Aluminum (Al) has been etiologically and epidemiologically related to several neurologic conditions, including Alzheimer's disease (AD). The effects of Al long-term exposure were investigated to describe the associated behavioral and brain modifications. Adult rats were intraperitoneally injected three times a week for 6 months with ecological doses of Al gluconate (0.85 mg/kg). The Al overload was confirmed by the significantly increased level of Al in serum. We assessed fear conditioning, spatial memory and emotional reactivity by shuttle-box task, Morris water maze, and open-field, respectively. The performance of the experimental animals at the shuttle-box task was significantly lower (p <.01) compared to that of control. The experimental animals had impaired spatial memory, with lower and more fluctuant performance at Morris water maze. The noxious-driven behavior of the experimental animals was also altered, with significantly lower activity scores (p <.05), and high emotionality scores (p <.01) at the open-field. We recovered and processed the brain for aluminum and amyloid deposits. The brains of experimental animals, studied by optical microscopy, displayed a massive cellular depletion in the hippocampal formation, particularly, the CAl field, and also in the temporal and parietal cortex. We observed numerous ghost-like neurons with cytoplasmic and nuclear vacuolations, and with Al deposits. The hippocampus contained extracellular accumulations of Al and amyloid surrounded by nuclei of degenerating cells, which we interpreted as neuritic plaques. The cerebrovasculature was distorted, with a significant thickening of the wall of capillaries, associated with amyloid deposits. These behavioral and neuropathological modifications associated with long-term exposure to Al are reminiscent of those observed in AD.