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In normal conditions follicle stimulating hormone receptors (FSHR) are expressed in zona granulosa cells of the ovary and Sertoli cells of the testis. However, the ectopic expression of FSHR was recently discovered in intra-tumoral blood vessels endothelia and/or in tumoral cells of many extra-gonadal human tumors (particularly in endocrine tumours). The paper reviews the data concerning the appearance of ectopic FSHR in particular human neoplasms. The possible involvement of FSHR in tumor progression and the use of FSHR examination for diagnostic purposes is also reviewed. Finally, the putative role of FSHR as a new target in oncological therapy is also discussed.
WięcejMilk-alkali syndrome (MAS), characterized by renal failure, metabolic alkalosis and hypercalcemia, is a severe and life-threatening complication of the treatment of hypoparathyroidism. The clinical course is often sudden and is not preceded by any prodromal symptoms. Occurrence does not depend on the duration of hypoparathyroidism treatment, although it is closely related to the applied therapy, especially the dose of calcium carbonate and active vitamin D preparations. Drugs influencing the glomerular filtration rate (angiotensin receptor blockers, sartans, aldosterone receptor antagonists, thiazide diuretics), lack of adequate routine control, changing the calcium carbonate supplementation, dehydration, a diet rich in pH-basic foods (i.e. vegetarian diet), pregnancy and other associated conditions are listed among the factors triggering MAS. A higher calcium carbonate dose is directly associated with an increased risk of milk-alkali syndrome. In case of a high calcium demand it is necessary to control renal function and monitor the level of calcium in the serum more frequently, aiming for the lower end of the reference range. If MAS has been confirmed or if there are alarming neurological symptoms suggestive of hypercalcemia, the patient must be sent to the hospital immediately. Treatment of MAS involves: discontinuation of calcium and vitamin D supplementation, and intravenous infusion of normal saline solution to eliminate volume deficiencies and to achieve forced diuresis while maintaining proper fluid balance. As soon as there is improvement in the patient’s clinical condition, it is necessary to begin the treatment of comorbidities increasing the risk of renal failure or alkalosis (i.e. vomiting, diarrhea).
WięcejBackground: Tumor induced osteomalacia (TIO) are extremely rare paraneoplastic syndrome with less than 300 reported cases. This report highlights the pitfalls and challenges in diagnosing and localizing TIO in patients with refractory and resistant osteomalacia. Patient and methods: 41- year gentleman with 4-year history of musculoskeletal weakness and pathologic fractures presented in wheelchair bound incapacitated state of 1-year duration. Investigations were significant for severe hypophosphatemia, severe phosphaturia, normal serum calcium, reduced 1,25-dihydroxy vitamin-D, elevated ALP, elevated intact parathyroid hormone (iPTH), and pseudo-fractures involving pelvis and bilateral femur. Whole body MRI and 99mTc methylene diphosphonate bone-scan were also normal. Whole body FDG-PET scan involving all 4 limbs revealed a small FDG avid lesion at lateral border of lower end of left femur (SUV max 3.9), which was well characterized on 3-dimensional CT reconstruction. Plasma C-terminal fibroblast growth factor (FGF)-23 was 698 RU/ mL (normal < 150 RU/ml). Wide surgical excision of the tumor was done. Histopathology confirmed mesenchymal tumor of mixed connective tissue variant. Serum phosphorous normalized post-surgery day-1. High dose oral calcium and vitamin-D was continued. FGF-23 normalized post surgery (73RU/ml). Physical strength improved significantly and now he is able to walk independently. Conclusion: TIO is frequently confused with normocalcemic hyperparathyroidism and vitamin-D resistant rickets/osteomalacia, which increases patient morbidity. Imaging for tumor localization should involve whole body from head to tip of digits, cause these tumors are notoriously small and frequently involve digits of hands and legs. Complete surgical removal of the localized tumor is key to good clinical outcomes.
WięcejThe differentiation of cystic lesions located in the sellar-suprasellar region is a significant problem in clinical practice because of the similarities in their clinical, radiological, and even histopathological picture. Arriving at the right diagnosis is vital for taking appropriate therapeutic decisions.
The most frequent clinical manifestation of lesions located in the sellar-suprasellar region is headache. It often co-exists with symptoms of anterior pituitary gland insufficiency or hyperprolactinaemia caused by compression of the pituitary stalk. Diabetes insipidus, obesity, mental disorders, and circadian rhythm disorders may be associated with lesions penetrating the suprasellar space. It is extremely important to rule out the possible coexistence of pituitary microadenoma and Rathke’s cleft cyst, which became possible with the use of 11C-methionine positron emission tomography/computed tomography (C-MET PET/CT). Reports from literature indicate that pituitary microadenoma may coexist with Rathke’s cleft cyst in 10% of patients. Cystic lesions of the sellar-suprasellar region should also be differentiated from a cystic pituitary adenoma or abscess.
The first-choice therapy in symptomatic cystic lesions of the sellar-suprasellar region is neurosurgery, which usually relieves headache and improves vision impairment, while less frequently restores normal pituitary function. In suprasellar lesions, neurosurgery may trigger or aggravate pre-existing symptoms of damage to the hypothalamus. Patients undergoing neurosurgery for cystic lesions located in the sellar-suprasellar region should be monitored for a few years due to their high recurrence rate, potential malignant transformation of these lesions, and possible adenoma development through metaplasia. The advent of targeted therapy of the BRAF/MEK pathway is associated with new therapeutic opportunities for patients with craniopharyngiomas.
WięcejIntroduction: The distinction of papillary thyroid carcinomas from benign thyroid lesions has important implication for clinical management. Classification based on histopathological features can be supported by molecular biomarkers, including lipidomic signatures, identified with the use of high-throughput mass spectrometry techniques. Formalin fixation is a standard procedure for stabilization and preservation of tissue samples, therefore this type of samples constitute highly valuable source of clinical material for retrospective molecular studies. In this study we used mass spectrometry imaging to detect lipids discriminating papillary cancer from not cancerous thyroid directly in formalin-fixed tissue sections.
Material and methods: For this purpose imaging and profiling of lipids present in non-malignant and cancerous thyroid tissue specimens were conducted. High resolution MALDI-Q-Ion Mobility-TOF-MS technique was used for lipidomic analysis of formalin fixed thyroid tissue samples. Lipids were identified by the comparison of the exact molecular masses and fragmentation pathways of the protonated molecule ions, recorded during the MS/MS experiments, with LIPID MAPS database.
Results: Several phosphatidylcholines (32:0, 32:1, 34:1 and 36:3), sphingomyelins (34:1 and 36:1) and phosphatidic acids (36:2 and 36:3) were detected and their abundances were significantly higher in cancerous tissue compared to non-cancerous tissue. The same lipid species were detected in formalin-fixed as in fresh-frozen tissue, but [M + Na]+ ions were the most abundant in formalin fixed whereas [M + K]+ ions were predominant in fresh tissue.
Conclusions: Our results prove the viability of MALDI-MSI for analysis of lipid distribution directly in formalin-fixed tissue, and the potential for their use in the classification of thyroid diseases.
WięcejIntroduction: Platelet-derived growth factor BB (PDGF-BB) plays an important role in the development of GD (Graves’ disease). However, it is still unknown whether PDGF-BB is expressed in peripheral blood and whether the expression of PDGF-BB contributes to GD. We aim to study the expression of PDGF-BB, hypoxia inducible factor (HIF)-1α and C-C motif chemokine receptor (CCR)-2 in peripheral blood of patients with GD and explore its effect and potential mechanism in pathogenesis. Material and methods: 41 patients with GD (GD group) and forty-five healthy people (control group) were chosen. The concentration of PDGF-BB and HIF-1α in peripheral blood specimens were detected and compared between the two groups. The expression of CCR2 in macrophages in the peripheral blood specimens were examined using FCM (Flow Cytometry). Results: Both PDGF-BB and HIF-1α were expressed in human peripheral blood from the two groups. Compared with specimens from healthy people, there were statistically increased concentrations of PDGF-BB and HIF-1α in the GD group (P < 0.05). The proportion of CCR2-positive macrophages in peripheral blood in the GD group was significantly higher than that in the control group (P < 0.05). Conclusions: CCR2-positive macrophages may induce the expression of PDGF-BB through HIF-1α signal, and the high expression of PDGF-BB may be involved in the pathogenesis of GD.
WięcejIntroduction: Both overt and subclinical hypothyroidism are often accompanied by sexual dysfunction. Despite improving male sexual functioning, levothyroxine treatment does not always restore all its aspects. The aim of this study was to compare male sexual functioning and depressive symptoms between men with hypothyroidism receiving levothyroxine/liothyronine combination therapy and men receiving levothyroxine alone.
Material and methods: The study population consisted of 21 young levothyroxine-treated men with clinical symptoms of hypothyroidism, in whom serum thyrotropin and thyroid hormone levels were within the normal limits. In 11 of these patients, levothyroxine was replaced with levothyroxine/liothyronine combination therapy, while the remaining ones (n = 10) continued levothyroxine treatment. Beyond measuring serum levels of thyrotropin, free thyroxine, free triiodothyronine, and prolactin, before the beginning of the study and six months later, all enrolled patients completed questionnaires evaluating male sexual function (International Index of Erectile Function-15: IIEF-15) and assessing the presence and severity of depressive symptoms (Beck Depression Inventory-Second Edition — BDI-II).
Results: The study included 10 patients from each group. At baseline, erectile function, intercourse satisfaction, orgasmic function, sexual desire and overall satisfaction, as well as the total BDI-II score did not differ between both groups. With the exception of an improvement in sexual desire, replacing levothyroxine with levothyroxine/liothyronine combination therapy did not affect sexual functioning and depressive symptoms.
Conclusions: The obtained results suggest that levothyroxine/liothyronine combination therapy has a relatively mild effect on sexual functioning in levothyroxine-treated men with normal thyrotropin and thyroid hormone levels experiencing clinical symptoms of hypothyroidism.
WięcejIntroduction: Distant metastases of papillary thyroid carcinoma (PTC) may lack the ability to concentrate radioiodine. In such cases, positive somatostatin receptor scintigraphy might be useful in demonstrating the expression of somatostatin receptors that are potential therapeutic targets. To date, only a few cerebellar metastases from PTC have been reported in the literature.
Patient findings: We present an 82-year-old female, in whom an asymptomatic cerebellar metastasis from PTC was diagnosed by means of Tc-99m-EDDA/HYNIC-TOC scintigraphy four years after the initial diagnosis. She was previously treated with total thyroidectomy and regional lymph node dissection, followed by three cycles of radioiodine therapy. Despite persistently elevated thyroglobulin, no specific radioiodine accumulation was found in the whole body post-treatment scan. Tc-99m-EDDA/HYNIC-TOC scintiscan revealed foci of increased tracer uptake in the lungs, cervical lymph nodes, and a single focus in the head. Thus, therapy with octreotide LAR was initiated. The patient died four months later due to disseminated PTC.
Summary: In this paper, a patient with asymptomatic previously unknown non-iodine avid cerebellar metastasis of PTC diagnosed by means of scintigraphy using somatostatin analogue Tc-99m-EDDA/HYNIC-TOC is reported.
Conclusions: Somatostatin receptor scintigraphy might be useful in the visualisation of non-iodine avid PTC metastases and demonstrating the expression of somatostatin receptors that are potential therapeutic targets.
WięcejIntroduction: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies and constitutes approximately 1.6–5% of the malignant neoplasms of the thyroid gland. ATC usually manifests itself with the local symptoms due to a rapidly enlarging thyroid mass, and as other thyroid cancers, has only seldom been reported to cause thyrotoxicosis. Up to now only 9 cases of ATC with concomitant thyrotoxicosis have been described.
Case report: We report a rare case of a 66-year-old woman, who had had the preexisting large, euthyroid multinodular goiter for almost 50 years. She was consulted by a doctor because of a 4-week history of thyrotoxicosis, symptoms of the congestive heart failure and a rapid increase in the size of the goiter. Thyroid hormone levels were consistent with a hyperthyroid state. The fine-needle aspiration biopsy confirmed a diagnosis of the anaplastic thyroid carcinoma, the small cells variant. The 99m Tc-pertechnetate scintigraphy visualized non-homogenous tracer distribution with hot nodules.
She was given a doxorubicin (20 mg/week) and required the continuous antithyroid treatment. The patient died a one year after the first symptoms of the disease occurred.
Discussion: The association between ATC and a thyrotoxic state is very rare. In most cases, thyrotoxicosis concomitant with ATC was thought to be a result of the destruction of the thyroid follicles by the rapid infiltration with malignant cells, resulting in the leakage of preformed hormones to the circulation. In that case the most probable cause of thyrotoxicosis was the multinodular goiter coexisting with ATC. A simultaneous onset of tumor growth, thyrotoxicosis and a relatively long survival time of our patient is worth to notice and discuss.
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