Insulin autoimmune syndrome.

Not required for Clinical Vignette.

Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer.

Prior work has shown that heterozygosity G/C of single nucleotide polymorphism (SNP rs2910164) within the precursor of microRNA-146a predisposes to PTC (odds ratio = 1.62, P = 0.000007) although the mechanism was unclear. Here, we show that GC heterozygotes differ from both GG and CC homozygotes by producing 3 mature microRNAs: 1 from the leading strand (miR-146a), and 2 from the passenger strand (miR-146a*G and miR-146a*C), each with its distinct set of target genes. TaqMan analysis of paired tumor/normal samples revealed 1.5- to 2.6-fold overexpression of polymorphic miR-146a* in 7 of 8 tumors compared with the unaffected part of the same gland. The microarray data showed that widely different transcriptomes occurred in the tumors and in unaffected parts of the thyroid from GC and GG patients. The modulated genes are mainly involved in regulation of apoptosis leading to exaggerated DNA-damage response in heterozygotes potentially explaining the predisposition to cancer. We propose that contrary to previously held views transcripts from the passenger strand of miRs can profoundly affect the downstream effects. Heterozygosity for polymorphisms within the premiR sequence can cause epistasis through the production of additional mature miRs. We propose that mature miRs from the passenger strand may regulate many genetic processes.

Milk-alkali syndrome (MAS) as a complication of the treatment of hypoparathyroidism - a case study.

Milk-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).

Human breast cancer tissue expresses high level of type 1 5'-deiodinase.

Type 1 5'-deiodinase is one of two isoenzymes that participate in conversion of prohormone thyroxine into triiodothyronine (T3). A decrease in type 1 5'-deiodinase expression was observed in renal clear cell carcinoma, thyroid cancer, and lung cancer. The aim of this study was to evaluate type 1 5'-deiodinase activity and mRNA level in breast cancer tissue and non-cancerous surrounding breast tissue. Material was collected from 36 patients undergoing radical mastectomy or local tumor resection. In all non-cancerous breast tissues, type 1 50-deiodinase activity was found to be at a very low or immeasurable level, and type 1 5'-deiodinase mRNA was detected only in 2 out of the 36 samples. By contrast, 20 out of the 36 breast cancer tissues, mainly grades G1 and G2, expressed abundant type 1 5'-deiodinase activity and/or a high mRNA level. Our data demonstrated the presence of type 1 5'-deiodinase in well-differentiated breast cancer tissue. High enzymatic activity of type 1 50-deiodinase can potentially lead to an increase in the production of T3, which may affect target gene transcription, including genes responsible for energy expenditure, growth, differentiation, and proliferation.

Treatment of severe life threatening hypocalcemia with recombinant human teriparatide in patients with postoperative hypoparathyroidism - a case series.

INTRODUCTION: Hypocalcaemia is a common postoperative complication, both after the resection of parathyroid adenoma associated with primary hyperparathyroidism and after total thyroidectomy due to thyroid cancer or nodular goitre. For a few years, in patients with postoperative hypoparathyroidism and severe hypocalcaemia, who cannot discontinue intravenous calcium preparations even with the use of high vitamin D doses, attempts have been made to add recombinant human parathormone (rhPTH) to the treatment schedule. In this work, for the first time in Poland, we demonstrate the potential use of teriparatide for the treatment of severe hypocalcaemia based on three different cases of postoperative hypoparathyroidism. MATERIAL AND METHODS: Case 1. Female (52) with postoperative hypoparathyroidism, after total thyroidectomy and the removal of lower left parathyroid gland due to hyperparathyroidism, several weeks after the surgery still required intravenous calcium infusions because of tetany symptoms. Just one month of teriparatide treatment at 20 µg/0.08 mL given in daily subcutaneous injections proved sufficient to control calcium levels with oral calcium and vitamin D preparations during the next few days until total resolution of hypocalcaemia symptoms and the achievement and maintenance of laboratory normocalcaemia in the following weeks. CASE 2: Female (33) with hypoparathyroidism following total thyroidectomy in 1996 because of papillary thyroid cancer, with congenital tubulopathy associated with renal loss of calcium and magnesium, and the symptoms of tetany recurring since the day of surgery, requiring intravenous calcium administration every 2-3 days. Currently, the patient has been hospitalised because of venous port infection, the only venous access, which made intravenous therapy impossible. Because of the life-threatening condition of the patient, bridging teriparatide treatment was prepared (20 µg/0.08 mL). Complete resolution of clinical symptoms of hypocalcaemia was obtained with teriparatide doses given every 8-12 hours, which made dose reduction possible. Case 3. Female (52) after major oncological surgery because of laryngopharyngeal and cervical oesophageal cancer with the removal of parathyroid glands, fed through PEG, was admitted to hospital with the symptoms of tetany. Despite treatment intensification, the patient experienced a hypocalcaemic crisis during hospitalisation. Teriparatide treatment at 2 × 20 µg/day resulted in the resolution of tetany symptoms, with gradual normalisation of calcium-phosphate balance parameters during the following days. CONCLUSIONS: Based on the analysis of these cases, the conclusion was drawn that the use of recombinant human teriparatide allows for the control of severe hypocalcaemia requiring intravenous infusions of calcium in patients with postoperative hypoparathyroidism. (Endokrynol Pol 2016; 67 (4): 403-412).

Adrenal incidentaloma in adults - management recommendations by the Polish Society of Endocrinology.

INTRODUCTION: A wide use of imaging techniques results in more frequent diagnosis of adrenal incidenataloma. AIM: To analyse the current state of knowledge on adrenal incidentaloma in adults in order to prepare practical management recommendations. METHODS: Following a discussion, the Polish Society of Endocrinology expert working group have analysed the available data and summarised the analysis results in the form of recommendations. IMAGING AND HORMONAL ASSESSMENT: Unenhanced adrenal computed tomography (CT) may be recommended as an initial assessment examination helpful in the differentiation between adenomas and "non-adenomatous" lesions. In the case of density > 10 Hounsfield units, CT with contrast medium washout assessment or MRI are recommended. However, in all patients with adrenal incidentaloma, hormonal assessment is recommended in order to exclude pheochromocytoma and hypercortisolism, notwithstanding the clinical picture or concomitant diseases. In addition, examination to exclude primary hyperaldosteronism is suggested in patients with diagnosed hypertension or hypokalaemia. TREATMENT: Surgical treatment should be recommended in patients with adrenal incidentaloma, where imaging examinations suggest a malignant lesion (oncological indication) or with confirmed hormonal activity (endocrinological indication). The basis of the surgical treatment is laparoscopic adrenalectomy. Patients with suspected pheochromocytoma must be pharmacologically prepared prior to surgery. In patients not qualified for surgery, control examinations (imaging and laboratory tests) should be established individually, taking into consideration such features as the size, image, and growth dynamics of the tumour, clinical symptoms, hormonal tests results, and concomitant diseases.

Disturbed expression of type 1 and type 2 iodothyronine deiodinase as well as titf1/nkx2-1 and pax-8 transcription factor genes in papillary thyroid cancer.

Type 1 and type 2 iodothyronine 5' deiodinases (D1 and D2, respectively) catalyze the conversion of thyroxine (T(4)) to triiodothyronine (T(3)). Similar to other genes crucial for T(3) generation, D1 and D2 expression might be disturbed in papillary thyroid cancer (PTC) possible as a result of impairments in thyroid transcription factors Titf1/Nkx2-1 and Pax-8. The aim of the study was to investigate changes in the expression of D1 and D2 in PTC compared to changes in the expression of Titf1/Nkx2-1 and Pax-8. Although D1 and D2 activities were decreased in tumor samples (PTC) compared to control C samples (tissues from a nontumorous part of the gland), the differences were not statistically significant. Contrary to that, their mRNA levels were significantly decreased in PTC samples compared to C samples (p = 0.017 and p = 0.012, respectively). Interestingly there was clear discrepancy between enzymatic activity and mRNA level of both deiodinases. There was a statistically significant correlation between D1 and Pax-8 (r = 0.464, p = 0.039), D2 and Pax-8 (r = 0.461, p = 0.041), D2 and Titf1/Nkx2-1 mRNA levels (r = 0.526, p = 0.017). Our results show that changes in D1 and D2 expression in PTC, including the discrepancy between deiodinases activity and mRNA level, might possibly related to impaired Titf1/Nkx2-1 and Pax-8 action.

Thyroid sialyltransferase mRNA level and activity are increased in Graves' disease.

Sialylation of cell components is an important immunomodulating mechanism affecting cell response to hormones and adhesion molecules. To study alterations in sialic acid metabolism in Graves' disease (GD) we measured the following parameters in various human thyroid tissues: lipid-bound sialic acid (LBSA) content, ganglioside profile, total sialyltransferase activity, and the two major sialyltransferase mRNAs for sialyltransferase-1 (ST6Gal I) and for sialyltransferase-4A (ST3Gal I). Fragments of toxic thyroid nodules (TN), nontoxic thyroid nodules (NN) and nontumorous tissue from patients with nodular goiter or thyroid cancer were used as a control (C). The LBSA content and sialyltransferase activity were the highest in the GD group (164 +/- 4.44 versus 120 +/- 2.00 nmoL/g, p = 0.005 and 1625 +/- 283.5 versus 324 +/- 54.2 cpm/mg of protein, p < 0.005 compared to control group C). Ganglioside profile in the GD group was similar to that in control tissues. Sialyltransferase- 1 mRNA and sialyltransferase-4A mRNA levels were significantly higher in the GD group than in the control group (12.52 +/- 6.90 versus 2.54 +/- 1.24 arbitrary units, p < 0.005 and 2,49 +/- 1.16 versus 1.23 +/- 0.46 arbitrary units, p < 0.05, respectively). There was a positive correlation between the increased sialyltransferase-1 mRNA level and the TSH-receptor antibody titer determined by the TRAK test. These results indicate that sialyltransferases expression and activity are increased in GD. Exact mechanism of this upregulation remains unknown, though one of possible explanations is the activation of the thyrotropin (TSH) receptor.

Laparoscopic treatment of adrenal cysts--own research and literature review.

MATERIAL AND METHODS: Over the last 18 months we operated on six patients with large adrenal gland cysts in our centre. This consisted of 8.2% of all patients treated in said period due to adrenal gland pathologies. On ruling out malignancy or parasitic nature of the lesions, all patients were surgically treated in order to excise the cysts while leaving the gland untouched. In five patients the cysts were resected but the adrenal gland was spared. However, in one patient the adrenal gland coated the entire cystic mass, which imposed performance of adrenalectomy in addition to cystectomy. During surgeries we tried not to clip the suprarenal vein, which we managed to do in four out of six cases. RESULTS: A one-year remote follow-up period revealed no cyst recurrence in ultrasound or CT, and it was possible to visualise the remaining part of the adrenal gland in all cases. CONCLUSION: Thus, in our opinion resection of benign cysts is well justified and recommendable.

Ontogenic redistribution of type 2 deiodinase messenger ribonucleic acid in the brain of chicken.

Thyroid hormone is essential for brain development. T(4) has to be converted to T(3) for efficient binding to thyroid hormone receptors. Type 2 deiodinase (D2) is the key enzyme that allows T(3) generation in the brain. To elucidate the onset and localization of T(3) production in the brain, we studied the changes of D2 activity, mRNA content, and the distribution of D2 mRNA in the brain of chicken embryos before and after the onset of thyroid function. D2 activity was detectable in the brain at all stages studied from embryonic day (E)7 to E15 and increased significantly with time. The wild-type chicken D2 transcript was detectable at all those stages by RT-PCR. The amount of D2 mRNA in the brain increased approximately 14-fold from E10 to E17 as assessed by Northern blot. Week D2 hybridization signal could be detected by in situ hybridization at E8 in cell clusters throughout the brain, and its intensity markedly increased to E15. Interestingly, no D2 expression was detected in hypothalamic tanycytes at these embryonic stages. However, D2 hybridization signal was observed in the wall of the third ventricle of adult chicken posterior to the rostral pole of the median eminence in the location typical for tanycytes, whereas D2 signal in other localizations was decreased throughout the brain. Our data suggest that D2 contributes to T(3) content of the developing chicken brain even before the onset of thyroid function. Furthermore, redistribution of D2 mRNA expression was observed during the development of the chicken brain.

Pax-8 expression correlates with type II 5' deiodinase expression in thyroids from patients with Graves' disease.

Transcription factors TTF-1 and Pax-8 control the expression of thyroid-specific genes crucial for thyroid function. It has been postulated that they may play a role in thyrotropin (TSH)-mediated augmentation of gene expression observed in some thyroid diseases including Grave's hyperthyroidism. Recently, we and others described the expression of two genes participating in thyroid hormone metabolism type I and type II deiodinase (D1 and D2, respectively) that are upregulated by TSH, although the mechanisms responsible for this effect are likely to be different. The aim of this study was to investigate whether there is a correlation between TTF-1 and Pax-8 mRNA levels and type I or type II 5' deiodinases expression in Graves' disease. D1 activity and mRNA level, as well as D2 activity and mRNA level, were significantly increased in Graves' disease in comparison to control tissues. D1, but not D2, activity correlated with its mRNA level in Graves' disease and toxic multinodular goitre. The TTF-1 mRNA level was not different between Graves' disease and control thyroids and no correlation between TTF-1 mRNA level and either D1 or D2 mRNA levels were found. The Pax-8 mRNA level was significantly increased in Graves' disease in comparison to control tissues and correlated with D2, but not D1, mRNA levels among all investigated groups of tissues. Our data suggest that transcription factor Pax-8 could be involved in the upregulation of D2 expression in the thyroid of Graves' patients.

The effect of surgical treatment of phaeochromocytoma on concomitant arterial hypertension and diabetes mellitus in a single-centre retrospective study.

INTRODUCTION: Phaeochromocytoma is one of the numerous causes of secondary hypertension. Furthermore, phaeochromocytoma may first present with type 2 diabetes mellitus. The objective of our study was to evaluate the effects of adrenalectomy on patient recovery with regards to normotension and well-controlled glycaemia. MATERIAL AND METHODS: The retrospective analysis involved 67 patients with phaeochromocytoma operated between 2006 and mid-2012. The pre-operative diagnoses were made in the departments of internal medicine and endocrinology. Based on laboratory tests and diagnostic imaging, we were able to confirm the diagnosis of phaeochromocytoma in 42 (62.7%) patients. We verified the influence of adrenalectomy on the level of patient recovery, with regards to normotension and glycaemic control: arterial pressure and fasting glycaemia levels were obtained on the day of hospital discharge, at follow-up 3 months post-operatively and 1 year after surgical intervention. RESULTS: Of the 67 patients operated for phaeochromocytoma, 48 (71.6%) were treated laparoscopically, whereas 19 (28.4%) underwent open adrenalectomy. Arterial hypertension was recorded in 53 (79.1%) cases. Furthermore, among this group, diabetes mellitus coexisted in 21 (31.3%) cases. Postoperatively, 70% of cases of arterial hypertension and 90% of type 2 diabetes mellitus were cured. Additionally, a high rate of patients reported a quantitative reduced use of antihypertensive medicines. CONCLUSIONS: In the majority of patients, surgical treatment of symptomatic phaeochromocytoma leads to a regression of arterial hypertension, or a reduction of the number or doses of medicines taken in one's treatment, and glucose-intolerance symptoms.

Thyroid hormone receptor beta (THRB) is a major target gene for microRNAs deregulated in papillary thyroid carcinoma (PTC).

CONTEXT: Loss of the thyroid hormone receptor is common in tumors. In mouse models, a truncated THRB gene leads to thyroid cancer. Previously, we observed up-regulation of the expression of eight microRNAs (miRs) in papillary thyroid carcinoma (PTC) tumors. OBJECTIVE: Our objective was to determine whether THRB might be inhibited by miRs up-regulated in PTC. DESIGN: The potential binding of miR to the 3'-untranslated region of THRB was analyzed in silico. Direct inhibition by miRs binding to the cloned 3'-untranslated region of THRB was evaluated using luciferase assays. Inhibition of endogenous THRB and its target genes (DIO1 and APP) was examined in cell lines transfected by pre-miRs. The impact on thyroid hormone response element (TRE) was evaluated in promoter assays. Correlations between the expression of THRB and miRs was evaluated in 13 PTC tumor/normal tissue pairs. RESULTS: THRB contains binding sites for the top seven miRs up-regulated in PTC (P = 0.0000002). Direct interaction with THRB was shown for miR-21 and miR-146a. We observed lower levels of THRB transcripts in cell lines transfected with miR-21, -146a, and -221 (down-regulation of 37-48%; P < 0.0001), but not with miR-181a. THRB protein was suppressed down to 10-28% by each of four miRs. Concomitant expression of DIO1 and APP was affected (down-regulation of 32-66%, P < 0.0034 and up-regulation of 48-57%, P < 0.0002, respectively). All four miRs affected TRE activity in promoter assays. Down-regulation of luciferase occurred after transfection with pTRE-TK-Luc construct and each of four miRs. The analysis of tumor/normal tissue pairs revealed down-regulation of THRB in 11 of 13 pairs (1.3- to 9.1-fold), and up-regulation of miR-21, -146a, -181a, and -221 in almost all pairs. CONCLUSIONS: MiRs up-regulated in PTC tumors directly inhibit the expression of THRB, an important tumor suppressor gene.

Suppurative thyroiditis caused by Salmonella enteritidis.

Bacterial thyroiditis is a rare disease, and one of which the clinical symptoms and signs are frequently misleading. On the other hand, prompt diagnosis is crucial for successful treatment. We report the case of an 82 year-old man with diabetes mellitus type 2 and a history of steroid treatment who presented with severe odynophagia and dysphagia associated with fever, chills, sore throat and right ear pain. Based on the clinical picture, radiological studies, thyroid cytology, blood and thyroid aspirate culture, suppurative thyroiditis caused by Salmonella enteritidis was diagnosed. The patient was successfully treated with antibiotics and surgical drainage.