Parafollicular Research Articles

Expression of motilin and its precursor mRNA in normal parenchyma, benign and malignant tumors of human thyroid

To investigate the expression of motilin and its precursor mRNA in normal human thyroid. To compare the expression differences of motilin and it precursor mRNA between normal thyroid and intestines. To study the expression of motilin and its precursor mRNA in human thyroid tumors and their clinical implications. RT-PCR, Southern blot and molecular cloning were used to detect motilin transcript expression in human thyroid and mucous membrane of small intestine. Real-time PCR and immunohistochemical techniques were used to quantify motilin precursor mRNA and motilin peptide in thyroid tissue samples including adenoma, medullary carcinoma, follicular carcinoma, papillary carcinoma and nodular goiter. (1) The expression of motilin and its precursor mRNA in normal human thyroid was primarily in the thyroid C cells. (2) RT-PCR and Southern blot showed that motilin mRNA expressed in human thyroid was identical to that expressed in duodenum with identical sequence deposited in NCBI Genbank of America. (3) Immunohistochemistry, Western blot research and real-time PCR studies showed that motilin and its precursor mRNA were expressed in normal and tumor tissues of human thyroid. Thyroid tumors (acidophilic adenoma, medullary carcinoma, follicular carcinoma, papillary carcinoma and nodular goiter) showed intense and diffuse immunostaining for motilin peptide. Moreover, the expression of motilin and its precursor mRNA in thyroid medullar carcinoma and acidophilic adenoma were significantly higher than those of normal thyroid tissue (P < 0.05). The expression in thyroid follicular and papillary carcinomas were significantly lower than those of normal thyroid tissue (P < 0.05). There was no difference of the expression between nodular goiter and normal thyroid tissue (P > 0.05). Motilin peptide and its precursor mRNA are expressed in C cells of human thyroid. The sequence of motilin is identical to that expressed in duodenum from NCBI Genbank of America. The expressions of both motilin and its precursor mRNA in thyroid medullary carcinoma and acidophilic adenoma are significantly increased. In contrast, their expressions in thyroid follicular and papillary carcinomas are significantly decreased. Motilin may regulate physiological functions of the thyroid through parafollicular cells. Motilin may be involved in the pathogenesis of medullary carcinoma and acidophilic adenoma of the thyroid.

OPG, RANK and RANK ligand expression in thyroid lesions

Receptor activator of NF-κB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) play essential roles in bone metabolism. RANKL binds to RANK, which is expressed by osteoclasts whereas OPG acts as its decoy receptor blocking the RANK-RANKL interaction. OPG/RANK/RANKL are produced by variety of tissues including epithelial and mesenchymal cells. However, the role of RANKL/OPG in thyroid pathophysiology remains unclear. The aim of this study was to determine the expression pattern of RANK/RANKL/OPG in primary neoplastic thyroid lesions and in lymph node metastases. 27 specimens from total thyroidectomy were studied by immunohistochemistry: 9 papillary carcinomas (PC), 9 medullary carcinomas (MC), 9 macrovesicular adenomas (MA). Immunohistochemical evidence of RANKL was found in 30 % of MC, 22% of PC while RANKL has never been detected in PC. The expression of RANK is closely related to RANKL. OPG was restricted to the cytoplasm of epithelial in 1 MA and 1 MC. In contrast to pathological tissues, any expression of OPG/RANK/RANKL was detected in healthy thyroid tissue. This work reveals for the first time that OPG/RANK/RANKL are expressed in the pathological thyroid gland by follicular cells, by malignant parafollicular cells as well as in metastatic lymph node microenvironment. Thus OPG/RANK/RANKL molecular triad might play a role during pathogenesis of follicular and parafollicular tumors.

Simultaneous medullary and papillary thyroid cancer: two case reports

BackgroundPapillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) have always been considered different from each other; in their incidence, their cell origin and their histopathological features.Case presentationThis paper describes two rare cases of the simultaneous occurrence of MTC and PTC in the thyroid gland. Case 1 is unique for different reasons: (a) the patient was affected by both multicentric MTC and PTC; (b) a "composite thyroid carcinoma" with mixed feautures of MTC and PTC carcinomas was found in the istmus of the gland; and (c) these tumors were associated with diffuse lymphocytic-type thyroiditis (LT). Case 2 is notable for the long follow up: 16 years disease free.ConclusionThere are only 16 reports in the English medical literature describing a total of 20 cases of concurrent occurrence of both PTC and MTC in the same thyroid gland. We discuss whether the finding of another cancer in these patients was coincidental or from possible activation of a common tumorigenic pathway for both follicular and parafollicular thyroid cells.

The cyclic AMP-dependent protein kinase A pathway is involved in progesterone effects on calcitonin secretion from TT cells

It is well known that gonadal steroid hormones influence the level of plasma calcitonin (CT), but the mechanism by which progesterone affects CT secretion is not clear. Immortalized TT cells are a reliable model system for studying the endocrine function of human parafollicular cells. In the present study, the effects of progesterone on CT secretion were examined in TT cells. TT cells were incubated in medium containing vehicle (DMSO), progesterone or BSA-progesterone for 60 or 150 min, and then the levels of CT in the medium, progesterone receptors, cAMP accumulation and CT mRNA expression were measured. To study the correlation between progesterone effects and the cAMP-dependent protein kinase A (PKA) pathway, cell lysates or cells in 24-well plates were treated with either vehicle or progesterone plus RU486, SQ22536, KT5720, or 3-isobutyl-1-methylxanthine. Then, adenylyl cyclase and protein kinase A (PKA) activities were measured in the cell lysates, and the CT levels were measured in the medium from the 24-well plate. The activated cAMP response element binding protein (P-CREB) was also measured by immunofluorescence. Administration of 1 μM progesterone or 500 nM BSA-progesterone increased the secretion of CT by 381% and 100%, respectively. Progesterone receptors A and B were downregulated by progesterone treatment. The cAMP concentration, adenylyl cyclase and PKA activity, CT mRNA expression, and nuclear P-CREB concentrations all showed an increase after progesterone treatment. RU486, SQ22536 and KT5720 inhibited the progesterone-stimulated effects. These results suggest that a cAMP-dependent PKA pathway is involved in progesterone-stimulated effects on CT secretion from TT cells.

MEDULLARY THYROID CARCINOMA

Medullary thyroid carcinoma (MTC) represents 4–10 % of all thyroid carcinomas; MTCs arise from the parafollicular cells (C cells). Around 20–25 % of MTCs are part of inherited multiple endocrine neoplasia type 2 (MEN2) syndromes, while the rest are sporadic. Most are MEN2 syndromes that are divided in MEN2A and MEN2B. MEN2A represents 95 % of all MEN2 cases and is subdivided in 4 variants: classical MEN2A, MEN2A with cutaneous lichen amyloidosis (CLA), MEN2A with Hirschsprung’s disease (HD), and familial medullary thyroid carcinoma (FMTC). Codon 634 in exon 11 is found mutated in 80–93 % of MEN2A patients. MEN2B are 5 % of all patients with MEN2 syndromes. MEN2B is characterized by the presence of MTC, pheochromocytoma, ganglioneuromatosis of the intestine and oral mucosa, neuromas of the tongue, marfanoid habitus, and medullated corneal nerve fibers. The mutation M918T in exon 16 is found in 95–100 % of MEN2B cases. Two thirds of sporadic MTCs have somatic mutations in RET: M918T in exon 16, the most common mutation; 8–68 % of the RET mutation-negative cases have somatic mutations in HRAS and KRAS. RET germline mutations should be offered to all patients with C-cell hyperplasia, familial MTC, and apparently sporadic MTC. These molecular studies are very helpful in characterizing these tumors.

Protein expression of the transcriptional regulator MI-ER1 alpha in adult mouse tissues

MI-ER1 is a novel transcriptional regulator that plays a critical role in embryonic development and is differentially expressed in breast carcinoma. The MI-ER1 protein sequence is highly conserved among species, with 95% identity between mouse and humans and 72% between Xenopus and mouse. There are two major protein isoforms, MI-ER1alpha and MI-ER1beta, which differ in the sequence of their C-terminus. MI-ER1alpha is of particular interest because it contains a consensus LXXLL nuclear receptor interaction motif and the current study was undertaken to determine the expression pattern of MI-ER1alpha protein in adult mouse tissues. Immunohistochemical analysis of paraffin-embedded tissue using an MI-ER1alpha-specific antibody revealed that the majority of mouse adult tissues examined showed very weak or no immunoreactivity; these included tissues of the lung, liver, intestine, uterus, spleen, lymph node, bladder as well as skeletal muscle. Interestingly, a subset of endocrine tissues displayed intense staining for MI-ER1alpha. Specifically, the islets of Langerhans, the zona glomerulosa and medulla of the adrenal gland, the ovary and the hypothalamus were intensely stained. In addition, both anterior and posterior pituitary showed moderate immunoreactivity, as did the parafollicular cells of the thyroid gland and Leydig cells and spermatids in the testes. Negative endocrine tissues included follicular cells of the thyroid gland and the X zone of the adrenal cortex. A few non-endocrine tissues displayed moderate immunoreactivity; these included all tubules and collecting ducts in the kidney, myocardial and endocardial layers of the heart, the hippocampal formation, pyramidal neurons in the cortex and the ductal epithelium of the mammary gland. In all cases, MI-ER1alpha immunoreactivity was cytoplasmic. This study represents the first immunohistochemical analysis of MI-ER1alpha expression in mammals and our data suggest that this transcriptional regulator plays a role in specific endocrine pathways.

Medullary thyroid carcinoma: surgical treatment advances

Since medullary thyroid cancer (MTC) was first recognized as a distinct tumor in 1959, it became clear that MTC is more difficult to cure than papillary thyroid cancer and has higher rates of recurrence and mortality. MTC represents 5–8% of thyroid cancers. It derives from parafollicular cells of the ultimobranchial body derived from the neural crest. MTC secretes calcitonin and other hormonal peptides and is considered part of the amine precursor uptake and decarboxilation system. MTC may occur either as a hereditary or nonhereditary entity. Hereditary MTC can occur either alone as the familial MTC or as the thyroid manifestation of multiple endocrine neoplasia (MEN) type 2 syndromes (MEN 2A MEN 2B). Activating point mutations of the RET proto-oncogene have demonstrated to be causative of the familial form of medullary thyroid cancer, both isolated familial MTC and associated with MEN 2A and 2B. In the last 10 years, major improvements and new technologies have been proposed and applied in thyroid surgery; among these are molecular diagnosis with genetic screening and mini-invasive video-assisted thyroidectomy. The history of thyroid surgery starts with Billroth, Kocher and Halsted, who developed the technique for thyroidectomy between 1873 and 1910. Prophylactic surgery for patients carrying a positive RET proto-oncogene has proven to be highly effective in curing those likely to experience the development of MTC. Video-assisted procedures with central compartment dissection have proved feasible for patients carrying a positive RET proto-oncogene. This paper reviews relevant medical literature published in the English language on surgery of MTC in well-controlled trials. We discuss the particular ethical and legal issues that thyroid prophylactic surgery raises. Searches were last updated in February 2007.

Tissue expression and cellular localization of phospholipid hydroperoxide glutathione peroxidase (PHGPx) mRNA in male mice

Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is an ubiquitous antioxidant enzyme, but the exact expression pattern in mammalian tissues is still unknown. The expression and cellular localization of PHGPx mRNA were examined in male mice using real time-polymerase chain reaction and in situ hybridization techniques. The rank order of PHGPx mRNA expression across tissues exhibiting substantial levels of expression was:testes >> heart > cerebrum > or = ileum > stomach = liver = jejunum > or = epididymis. In testes, PHGPx mRNA was highly expressed in spermiogenic cells and Leydig cells. The signal was also expressed in the molecular layer, Purkinje cell layer, and white matter of cerebellum, the pituicytes of neurohypophysis, the parafollicular cells and follicular basement membrane of thyroid, the exocrine portion of pancreas, the tubular epithelium of kidney, the smooth muscle cells of arteries, and the red pulp of spleen. In the gastrointestinal tract, PHGPx mRNA expression was mainly observed in the keratinized surface epithelium of forestomach, the submucosal glands and serosa layers, and further the Paneth cells of intestines. PHGPx mRNA appeared to be ubiquitously expressed in the parenchyma of heart, liver, and lung. These results indicate that PHGPx exhibits a cell- and tissue-specific expression pattern in mice.

Tissue Distribution of Ca2+-dependent Activator Protein for Secretion Family Members CAPS1 and CAPS2 in Mice

The family of Ca2+-dependent activator proteins for secretion (CAPS) is involved in dense-core vesicle exocytosis. CAPS1/CADPS1 and CAPS2/CADPS2 have been identified in mammals. CAPS1 regulates catecholamine release from neuroendocrine cells, whereas CAPS2 is involved in the release of brain-derived neurotrophic factor and neurotrophin-3 from cerebellar granule cells. CAPS1 and CAPS2 are predominantly expressed in brain. Here we show the immunohistochemical localization of the CAPS family proteins in various mouse tissues. In the pituitary gland, CAPS1 and CAPS2 were localized to the pars nervosa and the pars intermedia, respectively. In non-neural tissues, CAPS1 was observed in the islets of Langerhans, minor cell types of the spleen and stomach, and medullary cells of the adrenal gland, whereas CAPS2 was present in bronchial epithelial cells, thyroid parafollicular cells, chief cells of the stomach, ductal epithelium of the salivary gland, kidney proximal tubules, and minor cell types of the thymus, spleen, and colon. These results suggest that secretion from distinct cell types in various tissues involves either or both members of the CAPS family.

Culture system for studying thyroid biology

Abstract. The thyroid is composed of many ball-like structures called thyroid follicles, which are supported by the interfollicular extracellular matrix and a dense network of fenestrated capillaries. The follicles consist of many thyrocytes and a few parafollicular cells (C cells). In this microenvironment, the component thyrocytes are highly integrated in their specific structural and functional polarization. In conventional monolayer and floating culture systems, thyrocytes are unable to organize themselves into the follicles with normal cellular polarity. By contrast, in three-dimensional collagen gel culture, thyrocytes easily form stable follicle structures with normal polarity. However, these culture systems cannot reconstruct follicle structures that consist of both thyrocytes and C cells. To overcome this issue, we developed a new organotypic culture system of thyroid tissue fragments, which contain the two cell types, using three-dimensional collagen gel culture with air–liquid interface. Our thyroid tissue-organotypic culture system retains three-dimensional follicle structures with both thyrocytes and C cells for a long term. In relation to our method, we propose a new approach to the cell type-specific culture systems on the basis of in vivo microenvironments of various cell types. We review here four culture systems above to study thyroid biology.

Somatostatinoma of the Vater's papilla in a patient with von Recklinghausen's disease

Somatostatinomas of the gastrointestinal tract secret hormon somatostatin which can cause "inhibitory syndrom" comprising diabetes mellitus, cholelithiasis and steatorrheic diarrhea. It is also secreted by the D cells of Langerhans's islands of the pancreas as well as endocrine cells of the stomack, small bowel, salivary glands and parafollicular cells of the thiroid gland. Somatostatinomas of the digestive tract appear within the pancreas and duodenum. Patients suffering from von Recklinghausens's disease are paticularly prone to the somatostatinomas of the duodenum. In this paper we presented a 51-year-old female patient with von Recklinghausen's disease in whom, during the investigation for obstructive jaundice, tumor of the Vater's papilla was found. The patient was submitted to Whipple's duodenopancreatectomy. Histology and immunohistochemistry discovered type B glandular carcinoid tumor with strong antisomatostatin and mild antigastrin immunoreactivity. The patient stayed symptom-free more than four years now. Patients with von Recklinghausen's disease should be examined for other tumors, particularly carcinoids of the duodenum and papilla, especially if the signs of cholestasis are present.

The Thyroid Gland in Bottlenose Dolphins (Tursiops truncatus) from the Texas Coast of the Gulf of Mexico: Normal Structure and Pathological Changes

Fresh thyroid glands (n=60) from Atlantic bottlenose dolphins that died after stranding along the Texas coast between 1991 and 2005 were examined. Organ weight ranged from 11 g in a neonate (length 109 cm) to 58 g in a large (249 cm) male. More typical weights were 25-45 g (mean=30.6 g). Glands tended to be larger in pregnant and lactating females (mean 37.4 g; n=5) than in non-pregnant animals of comparable size. In infancy, the gland tended to be compact, relatively homogeneous, and sometimes partly lobular, but with advancing age it became more lobular, the lobules being defined by fibrous bands. In one 8-year-old female (233 cm), and in a large male (295 cm) aged>25 years the gland was represented by a cluster of lobules. Lobulation was not necessarily accompanied by increased weight, distinguishing it from hyperplasia. With age, variation in follicle size and colloid density tended to increase. Two animals (3%) had adenomas and five (8%) had discrete hyperplastic nodules, not to be confused with lobulation. Five (8%) had macroscopically identifiable colloid-filled cysts (1-4 mm in diameter). Nine animals (15%) had squamous cysts (4-15 mm) containing creamy white fluid. Other abnormalities included patchy or diffuse interstitial fibrosis (six cases, 10%) amyloidosis (two cases), thyroiditis (one case) and vasculitis (one case). No malignant neoplasms were found. Cells presumed to be C cells (light cells, parafollicular cells) were identified immunohistochemically with synaptophysin antibody.

Pathology of the thyroid in severe acute respiratory syndrome

The severe acute respiratory syndrome (SARS) epidemic started in November 2002 and spread worldwide. The pathological changes in several human organs of patients with SARS have been extensively described. However, to date, little has been reported about the effects of this infection on the thyroid gland. Femoral head necrosis and low serum triiodothyronine and thyroxine levels, commonly found in patients with SARS, raise the possibility of thyroid dysfunction. We have undertaken this study to evaluate for any potential injury to the thyroid gland caused by SARS on tissue samples obtained from 5 SARS autopsies. The terminal deoxynucleotidyl transferase-mediated dUPT nick end–labeling assay was performed to identify apoptotic cells. The follicular epithelium was found to be damaged with large numbers of cells exfoliated into the follicle. The terminal deoxynucleotidyl transferase-mediated dUPT nick end–labeling assay demonstrated many cells undergoing apoptosis. Follicular architecture was altered and showed distortion, dilatation, and collapse. No distinct calcitonin-positive cells were detectable in the SARS thyroids. In conclusion, both parafollicular and follicular cells were injured. This may provide an explanation both for low serum triiodothyronine and thyroxine levels and the osteonecrosis of the femoral head associated with patients with SARS. Apoptosis may play a role in the pathogenesis of SARS associated coronavirus infection in the thyroid gland.

Identification and localization of procalcitonin-like immunoreactivity in the rat hypothalamus

Procalcitonin (PCT) is a 116-amino acid polypeptide physiologically produced, as the precursor protein of calcitonin (CT), in the parafollicular cells of the thyroid gland, but physiological functions and other major sources of PCT remains unclear. The distribution of PCT-like immunoreactivity (PCT-LI) in the rat hypothalamus was examined by immunohistochemistry using a monoclonal antibody raised against the mid-region of human PCT (60–77-amino acid fragment). This antibody cross-reacts well with rat PCT and immature CT, but it cross-react poorly with free mature CT. Abundant expression of PCT-LI was found in zones at the interface between brain and cerebrospinal fluid (CSF) such as the ependymal layer and ventral glia limitans (VGL). Double labeling of PCT and glial fibrillary acidic protein (GFAP) identified this population of small cells as astrocytes, possibly tanycytes, a type of specialized glial cell that interacts in neuroendocrine functional dynamics. The fibers of these cells extend to circumventricular organs (CVOs) and to astrocytes located inside the parenchyma of key autonomic regulatory hypothalamic areas, with highest densities in the supraoptic nucleus (SO), arcuate nucleus (Arc), area postrema (AP), median eminence (ME), medial preoptic nucleus, tuber cinereum, and accessory neurosecretory nuclei. No strongly labeled cells were found in the paraventricular nucleus. The wide distribution of PCT-LI in the hypothalamus, in close correspondence with previous mapping of CT receptors in the rat brain, suggests that PCT may influence a multitude of biological activities associated with the hypothalamic-pituitary axis.

Cellular expression of Noc2, a Rab effector protein, in endocrine and exocrine tissues in the mouse

Noc2 is a Rab effector which participates in regulated exocytosis. It is expressed abundantly in endocrine cells but at low levels in exocrine tissues. Noc2-deficient mice, however, exhibit marked accumulation of secretory granules in exocrine cells rather than endocrine cells. In the present study, we investigated localization of Noc2 immunohistochemically in various endocrine and exocrine tissues in normal mice. Western blotting detected a Noc2-immunoreactive band of 38 kDa in isolated pancreatic islets, the adrenal gland, pituitary gland, and thyroid gland. Immunostaining for Noc2 labeled endocrine cells in the adrenal medulla and adenohypophysis, pancreatic islet cells, thyroid parafollicular cells, and gut endocrine cells, supporting the notion that Noc2 is a Rab effector protein shared by amine/peptide-secreting endocrine cells. Besides endocrine tissues, granular ducts in salivary glands contained Noc2. Although immunostaining failed to detect Noc2 in acinar cells of all exocrine glands examined, reverse transcriptase-polymerase chain reaction analysis detected the mRNA expression in exocrine pancreas. Ultrastructurally, Noc2 immunoreactivity was associated with the limiting membrane of granules in both pancreatic endocrine and salivary duct exocrine cells. The cellular and subcellular localizations of Noc2 should yield key information on its functional significance as well as account for the phenotype in Noc2-deficient mice.

Distant regulatory elements in a Sox10‐βGEO BAC transgene are required for expression of Sox10 in the enteric nervous system and other neural crest‐derived tissues

Sox10 is an essential transcription factor required for development of neural crest-derived melanocytes, peripheral glia, and enteric ganglia. Multiple transcriptional targets regulated by Sox10 have been identified; however, little is known regarding regulation of Sox10. High sequence conservation surrounding 5' exons 1 through 3 suggests these regions might contain functional regulatory elements. However, we observed that these Sox10 genomic sequences do not confer appropriate cell-specific transcription in vitro when linked to a heterologous reporter. To identify elements required for expression of Sox10 in vivo, we modified bacterial artificial chromosomes (BACs) to generate a Sox10betaGeoBAC transgene. Our approach leaves endogenous Sox10 loci unaltered, circumventing haploinsufficiency issues that arise from gene targeting. Sox10betaGeoBAC expression closely approximates Sox10 expression in vivo, resulting in expression in anterior dorsal neural tube at embryonic day (E) 8.5 and in cranial ganglia, otic vesicle, and developing dorsal root ganglia at E10.5. Characterization of Sox10betaGeoBAC expression confirms the presence of essential regulatory regions and additionally identifies previously unreported expression in thyroid parafollicular cells, thymus, salivary, adrenal, and lacrimal glands. Fortuitous deletions in independent Sox10betaGeoBAC lines result in loss of transgene expression in peripheral nervous system lineages and coincide with evolutionarily conserved regions. Our analysis indicates that Sox10 expression requires the presence of distant cis-acting regulatory elements. The Sox10betaGeoBAC transgene offers one avenue for specifically testing the role of individual conserved regions in regulation of Sox10 and makes possible analysis of Sox10+ derivatives in the context of normal neural crest development.

Prognostic Factors for Sporadic Medullary Thyroid Carcinoma

Medullary thyroid carcinoma (MTC) originates from the thyroid parafollicular cells and accounts for 3% to 10% of all thyroid malignancies. Approximately 84% of cases are sporadic. The aim of this study was to evaluate the outcomes of treatment for sporadic medullary thyroid carcinoma (SMTC) and define the prognostic factors for overall survival. The records of 32 SMTC patients treated at Ankara Oncology Education and Research Hospital between September 1993 and April 2003 were retrospectively evaluated. The effects of age, gender, tumor localization, extent of the primary surgical resection, tumor size, capsule invasion, lymph node metastasis, extranodal extension, tumor stage, local recurrence, and distant metastasis on the overall survival rate were evaluated by univariate and multivariate analyses. There were 32 patients (19 females, 13 males) with a median age of 45 years (21-76 years). Altogether, 22 patients had undergone complete resection and 10 patients incomplete resection. The median follow-up was 48 months (9-111 months), and the overall 5-year survival rate was 51%. Based on the univariate analysis, the extent of primary surgical resection, pathologic tumor size, capsule invasion, lymph node invasion, extranodal extension, tumor stage, local recurrence, and distant metastasis were factors that significantly affected survival. In the multivariate analysis, however, only the extent of the primary surgical resection, capsule invasion, and distant metastasis were found to be statistically significant factors. The extent of the primary surgical resection significantly influences the survival of patients with SMTC. Capsule invasion and distant metastasis were additional factors affecting the prognosis.

Simultaneous Medullary and Papillary Thyroid Carcinoma with Lymph Node Metastasis in the Same Patient: Case Report and Review of the Literature

We report a rare case of simultaneous medullary thyroid carcinoma on the left thyroid lobe with lymph node metastasis and papillary thyroid cancer on the right thyroid lobe. The 55-year-old woman was diagnosed with medullary thyroid carcinoma after left hemithyroidectomy for goitre. Completion thyroidectomy, central neck dissection and left modified neck dissection revealed the presence of papillary carcinoma on the right side. The extreme rarity and interesting pathological features are discussed and we raise the question of whether the finding of another thyroid cancer on the opposite side was coincidental or from possible activation of a common tumorigenic pathway for both follicular and parafollicular thyroid cells.

The effect of extremely low-frequency electromagnetic fields on skin and thyroid amine- and peptide-containing cells in rats: An immunohistochemical and morphometrical study

The aim of this study was to investigate the influence of extremely low-frequency electromagnetic fields (ELF-EMFs) on mast cells (MCs), parafollicular cells, and nerve fibers in rat skin and thyroid gland. The experiment was performed on 24 2-month-old Wistar male rats exposed for 4 h a day, 7 days a week for 1 month to EMFs (50 Hz, 100–300 μT, 54–160 V/m). After sacrifice, samples of skin and thyroid were processed for indirect immunohistochemistry or toluidine blue staining and then were analyzed using the methods of stereology. The antibody markers to serotonin, substance P, calcitonin gene-related peptide (CGRP), and protein gene product 9.5 (PGP) were applied to skin sections and PGP, CGRP, and neuropeptide Y (NPY) markers to the thyroid. A significantly increased number of serotonin-positive MCs in the skin and NPY-containing nerve fibers in the thyroid of rats exposed to ELF-EMF was found compared to controls, indicating a possible EMF effect on skin and thyroid vasculature.

Overexpression and Purification of Recombinant Eel Calcitonin and Its Phylogenetic Analysis

Calcitonin (CT), a peptide hormone that is widely used for the treatment of osteoporosis, Paget's disease, hypercalcemic shock and chronic pain in terminal cancer patients, is produced by the para-follicular cells of the thyroid gland in mammals and by the ultimobranchial gland of birds and fish. Fish calcitonin, like eel calcitonin (eCT), is more potent and longer lasting than human CT and is one of the many bioactive peptides that require C-terminal amidation for full biological activity. In this study we describe the over-expression and over-production of C-terminal amidated eCT in recombinant Streptomyces avermitilis. A phylogenetic analysis was performed with all the known CT amino acid sequences.