ACTA ENDOCRINOLOGICA (BUC)

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Context. Pheochromocytomas are very rare but important and potentially life-threatening sources of ectopic ACTH secretion (EAS), and the diagnosis of Cushing’s syndrome due to adrenocorticotropic hormone (ACTH)- producing pheochromocytoma needs a high index of suspicion. Case presentation. Herein, we present a rare case of catastrophic Cushing ‘s syndrome due ACTH-producing pheochromocytoma in a 59-year-old woman, which was characterized by severe hypercortisolism, markedly elevated ACTH levels and rapidly progressed and persisting metabolic derangements, and complete resolution of symptoms and signs after adrenalectomy, despite no biochemical evidence of pheochromocytoma and the coexisting adrenal cortical adenoma. The timely recognition of findings sufficient to raise the suspicion of an ACTH-producing pheochromocytoma is crucial to plan surgical resection of the adrenal mass which is the only curative option enabling quick recovery with complete amelioration of symptoms and signs and restoration of organ functions. Conclusions. In this regard, our case highlights the likelihood of severe hypercortisolism even in the absence of typical Cushingoid features, and the consideration of suspected diagnosis of ACTH-releasing pheochromocytoma even in the absence of biochemical evidence on catecholamine hypersecretion when workup is suggestive of an ectopic source along with an adrenal mass on imaging.

5% of all cases of primary hyperparathyroidism and it is an exceedingly rare endocrine malignancy first described in 1933. Most experts recommend en bloc excision at initial surgery as the only chance for its cure. Both chemotherapy and radiotherapy have not been demonstrated to be beneficial in parathyroid carcinoma. Some patients have multiple recurrences or metastases. Therefore, new therapies are urgently needed. Inhibition of the interaction between Programmed Death Receptor 1 (PD-1) and Programmed Death Receptor Ligand 1 (PD-L1) enhances T-cell responses in vitro and mediates clinical antitumour activity. Aim. We analysed the expression of PD-L1 in parathyroid cancer to evaluate its potential as target for immunotherapeutic strategy. Subjects and methods. A cohort of 18 patients were diagnosed with primary or metastatic parathyroid cancer. Immunohistochemistry was performed in 18 formalin-fixed paraffin-embedded specimens using a rabbit monoclonal antibody. A 5% cut-off value was applied for PD-L1 positivity. Results. The anti PD-L1 antibody showed a predominantly membranous staining pattern in parathyroid cancer cells. Programmed Death Receptor Ligand-1 expression was found in 22.2% of all parathyroid carcinoma cases. There was no correlation between the expression of PD-L1 with lymph node metastasis, gender and age (P> 0.05). Conclusion. This expression of PD-L1 in human parathyroid cancer suggests that patients with parathyroid cancer could profit from immunotherapeutic strategies using anti-PDL1 antibodies.

Context. Thyroid cancer is the most common endocrine malignancy. Within various subtypes of thyroid neoplasms, those with follicular growth pattern usually make diagnostic problems. Objectives. To examine ck19 expression as a diagnostic marker in thyroid neoplasms with follicular growth pattern. Design. In this cross sectional study, 86 patients were enrolled. Subjects and Methods. Totally 22 follicular adenoma (FA), 18 well differentiated tumors with undetermined malignant potential (WT-UMP) and 46 follicular variants of papillary thyroid carcinoma (FV-PTC) were enrolled and examined for Ck19 expression by immunohistochemistry staining. Membranous/cytoplasmic staining patterns were considered as positive. Specimens without staining were considered as 0, < 5% positively stained cells as 1+, 5%-25% as 2+, 25%-75% as 3+ and >75% as 4+. Result. CK19 was negative in most cases of FA while positive in most WDT-UMP and FV-PTCs, p<0.001. Additionally, most cases with 2+ and 3+ staining patterns were FV-PTC (75% and 81%, respectively, p<0.001) and none of FAs showed 3+ positivity (p<0.001). Additionally, most of strongly positive results in patients > 45 y/o were PTC (p<0.001). Conclusion. Ck19 is a useful marker in differentiating FA from FV-PTC. We found diffuse and strong (3+) staining pattern in FV-PTC but none of FAs were so. We concluded that diffuse and strong staining for ck19 in a thyroid lesion with follicular pattern of growth, especially in a patient older than 45 y/o should raise the possibility of malignancy.

Background. The use of nutrient supplements along with medication to optimize the treatment of diseases yields desirable outcomes. Hypothyroidism causes abnormalities in cells, and organs, and induces gene expression changes. The use of salt supplements and vitamins considerably helps to treat hypothyroidism. Objectives. To evaluate the effect of a food supplement containing iron, iodine, and folic acid on thyroid hormones changes as well as the quality and quantity of hypothyroid female rat’s offspring. Materials and Methods. In the current experimental study, 40 female rats were divided into six experimental and two control groups. The study was conducted in three phases. In the first phase, the role of a combinatory supplement along with levothyroxine to treat hypothyroidism by assessing T3, T4, and TSH hormones was investigated. In the second phase, the dose-depended effects of a combinatory supplement were investigated. Additionally, in the third phase, the quality and quantity of the next generation were measured in the hypothyroid female rats receiving the salt supplement. Results. The plasma level of T3, T4 and TSH in hypothyroid rats receiving nutrient supplements indicated that the use of combinatory supplements along with levothyroxine could have desirable effects on the treatment of hypothyroidism to such an extent that the level of T3 and T4 hormones in the intervention group was significantly higher than that of the control group (P≤0.01). The second phase demonstrated that the desired effects of combinatory supplements on the serum levels of T3, T4, and TSH hormones were dose-dependent so that by increasing the dosage of supplementation, a significant decrease in the TSH level was observed (P <0.05), while T3 and T4 levels increased (P <0.01). The results of the third phase demonstrated that salt supplements could be effective in reducing the number of dead or preterm pups, and the use of mineral salts along with levothyroxine could promote a healthy birth. Conclusion. Salt supplements have considerable effects on the health status of the offspring of hypothyroid rats, resulting in the birth of more healthy pups and reducing the rate of abortion or preterm births.

Background. People chew betel nut (Areca catechu) for physical work and stress reduction, but it contains arecoline, which has both therapeutic value and untoward effects on endocrine and gonadal functions. Objective. Aim of the present study is to investigate its role on adrenal with its target in metabolic stress in mice. Materials and methods. Mice were deprived of water / food, each for 5 days / treated with arecoline (10 mg / kg body wt daily for 5 days) / arecoline after water or food deprivation, for 5 days each. Results. Water or food-deprivation caused adrenocortical hyperactivity, evident from abundance of enlarged mitochondria and smooth endoplasmic reticulum (SER) with elevation of corticosterone level (C: 68.31 ± 2.30, WD: 159.31 ± 4.10 / FD: 194.12 ± 3.40 μg/ mL). Arecoline treatment alone or in water deprivation (C: 68.31 ± 2.30, AR: 144.50 ± 4.33, AR+WD: 194.42 ± 3.35 μg/ mL) / food deprivation (AR + FD: 180.89 ± 4.51 μg/ mL) stress also stimulated adrenocortical activity as recorded in metabolic stress. In contrast, adrenomedullary activity was not altered following water/ food deprivation. Arecoline treatment alone or in metabolic stress suppressed adrenomedullary activity by showing depletion of chromaffin granules (E/NE?), epinephrine (E) and norepinephrine (NE) concentrations. Both the stress decreased blood glucose and liver glycogen levels. Arecoline treatment decreased blood glucose level, with a rise in liver glycogen level, but elevated blood glucose level in water deprivation unlike in starvation. Conclusion. Arecoline alone or in metabolic stress involves adrenal and probably other endocrine glands (pancreas, posterior pituitary and rennin-angiotensin system) to maintain homeostasis in metabolic stress in mice.

Background. Prevention of complications is widely considered as the main aim of diabetes control. And diabetes education is the cornerstone for type 2 diabetes (T2D) management. However, traditional lecture-based diabetes patient education activities have small and shortlasting efficacy. Therefore, technology-based initiatives for diabetes patient education are urgently required. Objective. To evaluate Guessing, a popular game, as tool in increasing complication awareness of patients with newly diagnosed T2D during diabetes care. Patients and Methods. In a cohort study, 103 patients were split into Guessing Game group and control group. The opinions of patients and educators in Guessing Game group were surveyed. Patient performance was evaluated by test scores and the attendance to diabetes complication screening clinic. Results. A majority of patients and all educators believed that Guessing Game enhanced complication awareness. Educatees achieved higher total scores and test scores in “Fill in the Gaps” (one of 2 types of test item), more actively attended complication screening clinic, after using Guessing Game as an education tool. Conclusion. Guessing Game is an attractive and effective educational intervention to increase complication awareness of T2D patients.

Background. Arecoline, a plant alkaloid of betel nut, is consumed by millions of people, for increased capacity of work. It causes immunosuppression, hepatotoxicity, and disturbance in antioxidant production, but it stimulates HPA axis and induces thyroid dysfunction.\r\nAim. To investigate the role of arecoline on adrenal activity, glycemia and glycogen profile in mice.\r\nMaterials and methods. Arecoline was injected intraperitoneally at a dose of 10 mg/kg body wt for 20-60 min for acute administration. In chronic administration the same dose was used daily for 15 days. Corticosterone, epinephrine, norepinephrine, blood glucose and liver glycogen profiles were measured after 20, 40 and 60 min, in acute administration and after 15 days in chronic administration.\r\nResults. Arecoline in acute administration increased corticosterone, norepinephrine and epinephrine levels and induced hyperglycemia with depletions of liver glycogen. But\r\nchronic arecoline administration with the same dose for 15 days caused ultrastructural degenerations of adrenal cortex and medulla with the elevation of corticosterone, and\r\ndepletions of norepinephrine and epinephrine levels. Arecoline also caused hypoglycemia and elevated liver glycogen. Atropine (arecoline receptor antagonist) prevented arecoline action on adrenal activity or blood glucose ? liver glycogen interaction.\r\nConclusion. The findings indicate that arecoline initially stimulates adrenal activity, but subsequently inhibits it with alterations of glycemic and glycogen profiles. Arecoline action is mediated by arecoline receptor in mice. Arecoline may have immunological action via adrenal hormonal suppression in mice.

Context. Regulatory T cells (Tregs) have critical roles in preventing autoimmune diseases such as Hashimoto’s thyroiditis (HT). Forkhead box P3 (Foxp3), the master transcription factor of Tregs, plays a pivotal role in Treg function. Objective. Herein, we investigated the association of two single nucleotide polymorphisms (SNPs) of the Foxp3 gene with HT development. Methods and study design. A total of 129 HT patients and 127 healthy subjects were genotyped for rs3761548 (-3279 A/C) and rs3761549 (-2383 C/T) in the Foxp3 gene, using polymerase chain reaction-restriction fragment length polymorphism. Results. Genotypic and allelic distribution of rs3761548 SNP showed a significant association with HT. The CC genotype was observed in 37.2% of patients versus 22.1% of the controls [P<0.008, odds ratio (OR): 2.1; 95% confidence interval (CI): 1.2-3.6] and the AC genotype in 41.1% of patients compared to 54.3% of the controls (P<0.025, OR: 2.1; CI: 1.2-3.6). In addition, higher frequency of C allele in patients compared to controls (P=0.05, OR: 1.4; 95% CI: 0.9-2) suggested that patients with the CC genotype and C allele had increased susceptibility to HT. There were significantly higher serum levels of anti-thyroid peroxidase (ATPO) antibody in patients with the rs3761548 CC genotype (1156±163 IU/mL) compared to the other genotypes (≈582-656 IU/mL; P<0.004). We observed a greater frequency of the AC genotype in patients who had decreased ATPO antibody levels (P=0.02). Conclusions. The association of the rs3761548 SNP with risk of HT and its influence on ATPO antibody levels suggested an important role for Foxp3 in the biology and pathogenesis of HT.

Context. The grey mullet, Mugil cephalus, is an edible fish of high economic importance. Breeding biology with reference to hormonal/growth factor regulation of oocyte maturation needs to be known for its commercial production. Objective. The present study was conducted to examine the potency of maturation inducing hormones, chorionic gonadotropin (hCG), bovine-insulin, and insulin like growth factor1 (h-IGF-1) I on ovarian steroidogenesis and oocyte maturation. Design. The role of hormones and growth factors on steroidogenesis and oocyte maturation was investigated using specific inhibitors, Wortmannin for phosphatidylinositol-3 (PI3) kinase, trilostane for 3β-hydroxysteroid dehydrogenase, 1-octanol and 1-heptanol for gap junctions, actinomycin D for transcription and cycloheximide for translation of signal molecules. Methods. Actions of hormonal and growth factors were examined for steroidogenesis, by radioimmunoassay and oocyte maturation by germinal vesicle breakdown (GVBD). Specific inhibitors were used to determine the cell signaling pathways, PI3 kinase. Results. All the inhibitors attenuated the hCGinduced oocyte maturation (GVBD%), steroidogenesis including transcription, translation, gap junctions and PI3 kinase signaling. These inhibitors failed to inhibit h-IGF-I and b-insulin-induced oocyte maturation, steroidogenesis, translation and PI3 kinase signaling. Conclusion. hCG induces oocyte maturation via steroid dependent pathway involving gap junctions, transcription, translation and PI3 kinase signaling, unlike h-IGF-I and b-insulin in the mullet.