Preptin: A New Bone Metabolic Parameter?

Preptin is a 34-aminoacid peptide derived from the E-peptide of pro-insulin-like growth factor 2 (pro-IGF2) that is co-secreted with insulin and upregulates glucose-mediated insulin secretion. High serum preptin levels were described in conditions associated with insulin resistance, such as polycystic ovary syndrome and type 2 diabetes mellitus (T2M). Insulin and also IGF2 are known to be anabolic bone hormones. The "sweet bone" in T2M usually associates increased density, but altered microarchitecture. Therefore, preptin was proposed to be one of the energy regulatory hormones that positively impacts bone health. Experimental data demonstrate a beneficial impact of preptin upon the osteoblasts. Preptin also appears to regulate osteocalcin secretion, which in turn regulates insulin sensitivity. Preptin is greatly influenced by the glucose tolerance status and the level of physical exercise, both influencing the bone mass. Clinical studies describe low serum preptin concentrations in osteoporosis in both men and women, therefore opening the way towards considering preptin a potential bone anabolic therapy. The current review addresses the relationship between preptin and bone mass and metabolism in the experimental and clinical setting, also considering the effects of preptin on carbohydrate metabolism and the pancreatic-bone loop.

Cancer Predisposition Syndromes and Thyroid Cancer: Keys for a Short Two-Way Street.

Cancer predisposition syndromes are entities determined especially by germinal pathogenic variants, with most of them autosomal dominantly inherited. The risk of a form of cancer is variable throughout life and affects various organs, including the thyroid. Knowing the heterogeneous clinical picture and the existing genotype-phenotype correlations in some forms of thyroid cancer associated with these syndromes is important for adequate and early management of patients and families. This review synthesizes the current knowledge on genes and proteins involved in cancer predisposition syndromes with thyroid cancer and the phenomena of heterogeneity (locus, allelic, mutational, and clinical).

Thyroid, Gonadal and Adrenal Dysfunction in Kidney Transplant Recipients: A Review for the Clinician.

While chronic kidney disease-associated mineral and bone disorders (CKD-MBD) prevail in the endocrinological assessment of CKD patients, other endocrine abnormalities are usually overlooked. CKD is associated with significant thyroid, adrenal and gonadal dysfunction, while persistent and de novo endocrinological abnormalities are frequent among kidney transplant recipients (KTR). Low T3 levels prior to transplantation may help identify those at risk for delayed graft function and are often found in KTR. Thyroid surveillance after kidney transplantation should be considered due to structural anomalies that may occur. Despite the rapid recovery of gonadal hormonal secretion after renal transplantation, fertility is not completely restored. Testosterone may improve anemia and general symptoms in KTR with persistent hypogonadism. Female KTR may still experience abnormal uterine bleeding, for which estroprogestative administration may be beneficial. Glucocorticoid administration suppresses the hypothalamic-pituitary-adrenal axis in KTR, leading to metabolic syndrome. Patients should be informed about signs and symptoms of hypoadrenalism that may occur after glucocorticoid withdrawal, prompting adrenal function assessment. Clinicians should be more aware of the endocrine abnormalities experienced by their KTR patients, as these may significantly impact the quality of life. In clinical practice, awareness of the specific endocrine dysfunctions experienced by KTR patients ensures the correct management of these complications in a multidisciplinary team, while avoiding unnecessary treatment.

Management of malignant struma ovarii: is aggressive therapy justified? Case report and literature review.

BACKGROUND: Struma ovarii (SO) is a rare ovarian teratoma containing predominantly thyroid tissue. In rare situations SO may develop malignancy. Most cases of malignant struma ovarii (MSO) are diagnosed after surgical removal, based on histopathological examination. There are still controversies regarding the extent of surgery and postoperative management in MSO, due to its unpredictable behavior, possible risk of metastasis and relatively high rate of recurrence. CASE PRESENTATION: We present the case of a patient diagnosed with a right ovarian cyst discovered incidentally during routine ultrasound examination. Its rapid growth and pelvic MRI raised the suspicion of a neoplastic process. She underwent total hysterectomy and bilateral adnexectomy. The anatomopathological diagnosis was MSO with follicular variant of papillary thyroid carcinoma. Prophylactic total thyroidectomy was performed, followed by radioactive iodine ablation (RAI), and suppressive therapy with levothyroxine. At 1 year follow-up, the patient was disease free. CONCLUSIONS: Even if latest literature reports consider that completion of local surgery with total thyroidectomy and RAI might be too aggressive in cases of MSO without extraovarian extension, in our case it was decided to follow the protocol for primary thyroid carcinoma, in order to reduce the recurrence risk.

Personalized Diagnosis in Differentiated Thyroid Cancers by Molecular and Functional Imaging Biomarkers: Present and Future.

Personalized diagnosis can save unnecessary thyroid surgeries, in cases of indeterminate thyroid nodules, when clinicians tend to aggressively treat all these patients. Personalized diagnosis benefits from a combination of imagery and molecular biomarkers, as well as artificial intelligence algorithms, which are used more and more in our timeline. Functional imaging diagnosis such as SPECT, PET, or fused images (SPECT/CT, PET/CT, PET/MRI), is exploited at maximum in thyroid nodules, with a long history in the past and a bright future with many suitable radiotracers that could properly contribute to diagnosing malignancy in thyroid nodules. In this way, patients will be spared surgery complications, and apparently more expensive diagnostic workouts will financially compensate each patient and also the healthcare system. In this review we will summarize essential available diagnostic tools for malignant and benignant thyroid nodules, beginning with functional imaging, molecular analysis, and combinations of these two and other future strategies, including AI or NIS targeted gene therapy for thyroid carcinoma diagnosis and treatment as well.

SHOX Deletion and Idiopathic Short Stature: What Does the Clinician Need to Know? Case Series Report.

Children diagnosticated with idiopathic short stature (ISS) are probably, in most cases, underdiagnosticated. The genetic causes of ISS may be mutations of genes involved in local regulation of the growth plate or genes involved in the GH-IGF1 axis physiology. We present a kindred of five children evaluated for short stature or low normal stature, initially diagnosticated as idiopathic short stature, familial short stature, or being small for gestational age. Clinical signs suggestive of SHOX deletion screening in a child with short stature are low arm span/height ratio, increased sitting height/height ratio, BMI > 50% percentile, Madelung deformity, cubitus valgus, bowing and shortening of the forearm, dislocation of the ulna (at the elbow), and the appearance of muscular hypertrophy. Radiological characteristics suggestive of SHOX deficiency are triangularisation of the distal radial epiphysis, an enlarged diaphysis of the radius plus bowing of the radius, the convexity of the distal radial metaphysis, short fourth and fifth metacarpals, pyramidalization of the carpal row. Treatment with rGH is approved for children with SHOX gene deficiency and short stature. This kindred is an example that familial short stature, idiopathic short stature, and short stature due to a small gestational age are not final diagnoses. Complex investigations are necessary to identify the precise cause, leading to optimal clinical management. Treatment with rGH is an option for some of them; for others, it has no therapeutic response and, in some cases, is even harmful.

Bone mineral density predictors in long-standing type 1 and type 2 diabetes mellitus.

BACKGROUND: Despite the increased fracture risk, bone mineral density (BMD) is variable in type 1 (T1D) and type 2 (T2D) diabetes mellitus. We aimed at comparing independent BMD predictors in T1D, T2D and control subjects, respectively. METHODS: Cross-sectional case-control study enrolling 30 T1D, 39 T2D and 69 age, sex and body mass index (BMI) - matched controls that underwent clinical examination, dual-energy X-ray absorptiometry (BMD at the lumbar spine and femoral neck) and serum determination of HbA1c and parameters of calcium and phosphate metabolism. RESULTS: T2D patients had similar BMD compared to T1D individuals (after adjusting for age, BMI and disease duration) and to matched controls, respectively. In multiple regression analysis, diabetes duration - but not HbA1c- negatively predicted femoral neck BMD in T1D (ß= -0.39, p = 0.014), while BMI was a positive predictor for lumbar spine (ß = 0.46, p = 0.006) and femoral neck BMD (ß = 0.44, p = 0.007) in T2D, besides gender influence. Age negatively predicted BMD in controls, but not in patients with diabetes. CONCLUSIONS: Long-standing diabetes and female gender particularly increase the risk for low bone mass in T1D. An increased body weight partially hinders BMD loss in T2D. The impact of age appears to be surpassed by that of other bone regulating factors in both T1D and T2D patients.

Updated Incidence of Thyroid Cancer in the North East Region of Romania after 35 Years of Chernobyl Fallout. Is There a Link between?

Thyroid cancer (TC) represents a worldwide problem, the consistent growth of the incidence increment issues about management of risk factors and curative treatment. Updated statistical data are not complete in the North East region of Romania and need to be improved. Therefore, through this study, we aim to renew the existing data on thyroid cancer. We conducted a retrospective study covering a period of 10 years. Data were collected from a hospital information system (InfoWorld) between 2009 and 2019. Patients' age groups were stratified in relation with the age at the moment of the Chernobyl event. A database was obtained (Microsoft Excel) and statistical correlations were applied. In the studied period, 1159 patients were diagnosed: 968 females and 191 males, distributed by region, with the highest addressability in Iasi (529), followed by neighboring counties. Age distribution displayed that most of the thyroid cancers were in the range 4060 years old (50.94%), followed by 60-80 years old (32.41%). Most patients were diagnosed with papillary carcinoma 63.10%, then follicular 14.7%, medullary 6.74% and undifferentiated 1.02%. Romania was in the vicinity of the radioactive cloud at Chernobyl fallout, so we must deliberate whether the increased incidence of thyroid cancer in the age group 40-60 years is associated with radiogenicity (iodine 131) given the fact that over has 35 years and the half-life of other radioisotopes like Caesium-137 and Strontium -90 is completed.

Primary solitary fibrous tumor of the thyroid gland: A review starting from a case report.

Primary solitary fibrous tumor (SFT) of the thyroid gland is a rare mesenchymal tumor with fibroblastic differentiation, ramified, thin-walled, enlarged (staghorn) vessels and specific NAB2-STAT6 gene fusion, which is more commonly found in pleura and peritoneum. This neoplasm can be located in a variety of anatomical sites outside pleura and peritoneum including bone, visceral organs and soft tissues, head and neck examples representing only 10-15% of the extra-pleural and extra-peritoneal tumors. Diagnosing this entity can be difficult, especially in thyroid gland, mainly because of the rarity of this neoplasm, but presence of characteristic microscopic features together with positivity for STAT6 and CD34 can confirm the diagnosis and exclude other differential diagnosis. Information about the diagnosis and treatment options of thyroid SFTs is limited but almost all primary thyroid SFTs have a good prognosis and indolent clinical course. Clinical surveillance is still necessary because some SFTs can be aggressive. Raising awareness regarding extra-pleural and extra-peritoneal location of this tumor in endocrine organs can help to better manage these patients. We report the case of a 34-year-old female with primary SFT of the thyroid gland. Additionally, we review the literature for the main clinical, paraclinical and pathological features of this neoplasm.

FGF23 Beyond the Kidney: A New Bone Mass Regulator in the General Population.

Clinical studies investigating the relationship between fibroblast growth factor 23 (FGF23) and bone mass are controversial, especially in the healthy renal population. Our study is one of the forefronts investigating the relationship between FGF23 and bone mass parameters in the general population, according to age, sex, menopausal, and nutritional status. Cross-sectional study enrolling 123 volunteers between 20-80 years of age without primary osteoporosis under treatment nor secondary osteoporosis, where bone mass (bone mineral density-BMD, bone mineral content-BMC; assessed by Dual X-Ray Absorptiometry-DXA), body composition (DXA evaluation), and also the serum levels of FGF23, parathormone (PTH), 25(OH)D, bone resorption marker C-terminal telopeptide of type I collagen (CTx) and leptin were determined. FGF23 was negatively and independently associated with BMD and/or BMC in all groups. FGF23 contributed to up to 10% (p <0.05) of femoral neck BMD variance in postmenopausal women, but was not an accurate discriminator of normal versus low bone mass (AUC=0.622±0.076). FGF23 did not correlate with 25(OH)D, CTx, body weight, body composition parameters or leptin. FGF23 was independently associated with PTH in premenopausal women and men only. FGF23 was negatively associated with bone mass parameters in both sexes, but was not a fine discriminator between normal bone mass and osteopenia/osteoporosis. The mechanism through which FGF23 acts upon the bone seems independent of the nutritional status, requiring further investigation.

Modifications in the spectrum of bone mass predictive factors with menopausal status.

PURPOSE: Fat mass (FM) is a source of adipocytokines, with both positive and negative bone consequences. We aimed to investigate the role of body composition and adipokines as predictive factors for bone mass in women. METHODOLOGY: This cross-sectional study included 93 women (38 premenopausal and 55 postmenopausal). Bone mineral density (BMD) and body composition were assessed by dual-energy X-ray absorptiometry. Serum levels of leptin, adiponectin, resistin, and also of the phosphocalcic markers parathormone and vitamin D were measured. RESULTS: Only lean mass (LM) was an independent predictor of BMD in premenopausal women (r2 = 0.381, p < 0.001 for femoral neck BMD, r2 = 0.2, p < 0.01 for whole-body BMD) in both unadjusted and age-adjusted models. The effect of total FM upon BMD became nonsignificant when LM was added to the models assessed. In postmenopausal women, although LM, trunk-to-leg fat ratio, and resistin were initially associated with BMD in unadjusted models, only the trunk-to-leg fat ratio independently predicted BMD at various sites (r2 = 0.171, p < 0.01 for lumbar BMD, r2 = 0.078, p < 0.05 for radius BMD, r2 = 0.094, p < 0.05 for whole-body BMD) after adjusting for age. CONCLUSIONS: While in premenopausal women the effect of LM upon bone is prevalent, after menopause, the fat distribution reflected by trunk-to-leg fat ratio is a major determinant of bone mass at different sites. Our study also stresses that the relationship between total FM and BMD is not mediated by adipokines in women irrespective of menopausal status and body composition, but it is largely mediated by LM only in young premenopausal women.

No definitive evidence for a connection between autoimmune thyroid diseases and stress in women.

The purpose of this literature review was to examine the available clinical studies performed during the last 15 years to identify if there is a causal relationship between the onset and course of autoimmune thyroid diseases (AITDs) and the hypothalamic-pituitary-adrenal (HPA) axis/sympathetic-adrenomedullary system (SAM) (dys)function in women. Using the PubMed, Web of Science and Scopus databases, a comprehensive search was performed, and 14 articles were finally identified. The majority of selected studies suggested a causal connection between Graves' Disease (GD) and stress, as well as between Hashimoto Thyroiditis (HT), with its variant postpartum thyroiditis, and stress. However, due to heterogeneity in the protocols, mainly based on the theoretical side effects of stress on the immune-neuroendocrine system, and the different modalities used to establish the impact of stress on individuals, no definitive conclusions could be reached to explain the mechanisms by which stress contributes to the onset of AITDs in women and to determine whether stress management could help in modifying the course of AITDs.

Effects of ghrelin in energy balance and body weight homeostasis.

Ghrelin is a gut peptide composed of 28 amino acids mostly secreted in the gastric fundus mucosa. It was isolated and described in 1999 by Kojima et al. and only three years later its specific receptor, GHSR1a, was also identified. Ghrelin, the endogenous ligand for the GH secretagogue receptor, is the only peripheral orexigenic hormone that activates the receptors to be found especially in the appetite center (hypothalamus and pituitary gland). Ghrelin is present in human plasma in two forms: an inactive form known as deacylated ghrelin, and an active form called acylated ghrelin synthesized under the action of ghrelin O-acyltransferase enzyme (GOAT). The literature even mentions an extremely complex ghrelin/GOAT/GHSR system involved in the regulation of human energy, metabolism and adaptation of energy homeostasis to environmental changes. In humans, there is a preprandial rise and a postprandial fall in plasma ghrelin levels, which strongly suggest that the peptide plays a physiological role in meal initiation and may be employed in determining the amount and quality of ingested food. Besides the stimulation of food intake, ghrelin determines a decrease in energy expenditure and promotes the storage of fatty acids in adipocytes. Thus, in the human body ghrelin induces a positive energy balance, an increased adiposity gain, as well as an increase in caloric storage, seen as an adaptive mechanism to caloric restriction conditions. In the current world context, when we are witnessing an increasing availability of food and a reduction of energy expenditure to a minimum level, these mechanisms have become pathogenic. As a consequence, the hypothesis that ghrelin is involved in the current obesity epidemic has been embraced by many scholars and researchers.

MYTHS AND CONTROVERSIES IN HYPOGONADISM TREATMENT OF AGING MALES.

Low T is an independent risk factor for metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) development; patients with these clinical conditions should be screened for hypogonadism. Testosterone replacement therapy (TRT) ameliorates libido, improves bone mass, improves insulin resistance, reduces fat mass and increases lean body mass with no change in body weight. There are no evidences that testosterone therapy increases the risk of prostate cancer but it is certain that testosterone stimulates growth of metastatic prostate cancer. TRT has an antiarrhythmic and a vasodilator effect, independent of the nitric oxide effect. Patients with heart failure have low levels of testosterone, and TRT improves exercise capacity. Men with low testosterone have risk for premature death. Cardiovascular adverse effects of testosterone therapy are under discussion. We need large prospective placebo-controlled randomized trials to determine definitively the cardiovascular risks of TRT.

Electrocardiographic changes in the most frequent endocrine disorders associated with cardiovascular diseases. Review of the literature.

Car- diovascular abnormalities associated with endocrine diseases are often frequent and due to complex relationships between endocrine glands (with internal secretion) and cardiovascular system (heart and vessels). Certain hormones secreted by the endocrine glands (particularly the thyroid and pituitary gland) excesses or deficiencies, are involved in morphogenesis, growth processes and activity regulation of cardiovascular system, most often in connection with the autonomic nervous system. There are also a lot of electrocardiographic changes caused by hormonal disorders that requires differential diagnosis and represents the source of erroneous diagnosis. Endocrine pathology occurred later than a heart disease, may worse heart function. Ignoring the cardiovascular events that may occur in the evolution of endo- crine diseases, may induce increased mortality due to cardiovascular complications.

Thyroid fine-needle biopsy: aspiration versus capillary.

UNLABELLED: Thyroid nodules are a common pathology of the thyroid gland. Thyroid fine-needle biopsy (FNB) is a technique used as the first step in the assessment of thyroid nodules. Some au- thors have demonstrated the superiority of nonaspiration compared with aspiration biopsy. AIM: The objective was to assess whether there are significant differences between the two thyroid biopsy techniques. MATERIAL AND METHODS: The study group comprised 309 patients with thyroid nodules admitted to the Endocrinology Clinic of the Iasi "St. Spiridon "Hospital between 2005 and 2008 in which fine-needle nonaspiration or aspiration biopsy was performed. The slides were read by one pathologist. The smears were stained using the May-Grunwald-Giemsa method (MGG). The quality of smears obtained by the two sampling techniques was evaluated by using the scoring system developed by Mair. RESULTS AND DISCUSSION: No differences in smear quality between the two sampling techniques in terms of blood contamination, amount of cellular material, degree of cellular degeneration, degree of cellular trauma, and preservation of appropriate architecture were found. CONCLUSION: The results of this study show that the sensitivity and specificity of both techniques allow their use as standard screening methods for thyroid nodular lesions.

Vitamin D status in patients admitted in a clinic of endocrinology.

UNLABELLED: Vitamin D deficiency has been known as a global health problem and there were reported moderate to strong inverse associations between 25(OH) D concentrations and cardiovascular diseases, serum lipid concentrations, inflammation, glucose metabolism disorders, weight gain, infectious diseases, multiple sclerosis, mood disorders, declining cognitive function, impaired physical functioning, and all-cause mortality. In Romania there are only a few published reports on vitamin D status among adult population. AIM: To evaluate vitamin D status in 440 patients those were admitted in our clinic for various endocrine pathology. MATERIAL AND METHOD: Serum 25-hydroxy vitamin D was measured using chemiluminescence assay. We categorized the vitamin D levels in 3 subgroups (deficiency, insufficiency and sufficiency). RESULTS: In our study there was a high prevalence of both vitamin D deficiency and insufficiency, while optimal level was observed only in a very small number of patients. CONCLUSIONS: We demonstrated a high frequency of vitamin D deficiency in general population, especially in elderly and children. There are still many controversies regarding the optimal vitamin D status and the supplementation dosage, so long-term large scale studies are needed regarding efficacy and safety.

Therapeutic particularities in amiodarone induced thyroid disorder in patients with underlying cardiac condition.

AIM: the analysis of therapeutic approach in patients with basic heart condition and amiodarone induced thyroid dysfunction--correlations with the evolution and prognosis. MATERIAL AND METHODS: The study included 215 patients, 90 men and 125 women aged between 35 and 87, with different cardiac pathologies hospitalized in the Cardiology Clinic between 2004-2014, who received amiodarone treatment, in most cases for prophylaxis of various arrhythmias, both supraventricular and ventricular. During the evolution, these patients have developed amiodarone-induced thyroid dysfunction (hypo- or hyper function). RESULTS AND DISCUSSION: The evaluation of thyroid function after starting treatment was performed in 187 patients (86.97%). Diagnosis of amiodarone-induced thyroid dysfunction was based on hormonal dosages of TSH, FT4 and FT3, endocrinological examination and thyroid ultrasound. Thyroid dysfunction treatment was initiated, depending on the situation, in all patients during the hospitalization. Treatment included anti thyroid drugs or hormones substitution and in some cases a minimal dose of prednisone. CONCLUSIONS: Thyroid dysfunction regardless of the type (with hypo- or hyper function) requires continuous changes of the cardiovascular treatment, and association, where appropriate, with thyroid dysfunction medication. In some cases the latter determines cardiovascular side effects, for instance corticotheraphy may become a factor of imbalance for the hemodynamic status of the patient (by fluid retention, increased blood pressure, hyper glycemia).

Jod-Basedow effect due to prolonged use of lugol solution-case report.

Graves' disease is the most common form of hyperthyroidism, accounting for 60-80% of all cases of thyrotoxicosis. If left untreated, it may lead to severe thyrotoxicosis with cardiovascular, ocular, psychiatric complication, and in extreme cases thyrotoxic crisis with a high mortality rate. We present the case of a 50-years-old woman diagnosed in another service with Graves' disease and treated for many years with antithyroid drugs (ATDs), admitted to our service for a relapse due to treatment discontinuation. The surgical treatment was planned and the preoperative preparation with Lugol solution was initiated. Due to a misunderstanding, the administration of iodine solution was extended for a period of about 30 days, thus generating the so-called Jod-Basedow effect, with the exacerbation of the manifestations of thyrotoxicosis and risk of thyroid storm. The patient received treatment with high ATDs doses, glucocorticoids, and beta-blockers, resulting in the progressive improvement of symptoms. She was discharged from hospital and given the risk of thyrotoxic crisis the surgery was postponed. After a month, the patient underwent thyroidectomy without preoperative preparation with iodine solution. The operative and postoperative courses were uneventful.

[Clinical profile of thyroid nodules in Iasi, Department of Endocrinology, St. Spiridon Hospital, between 2005-2009]. / Profilul clinic al nodulilor tiroidieni in Clinica de Endocrinologie a spitalului "Sf. Spiridon" Iasi in perioada 2005-2009.

UNLABELLED: Thyroid nodules are common, with up to 50% of the adult population having palpable nodules. With the use of ultrasound, up to 10 times more nodules are likely to be detected. Given this we decided to evaluate by retrospective study the incidence of thyroid nodule in the North-Eastern Region of Romania (Moldavia) between 2005-2009. MATERIAL AND METHOD: We reviewed the records of patients admitted in the Department of Endocrinology, St. Spiridon Hospital Iasi between 1.01.2005-31.12. 2009 (4712 patients) and with selected the cases with nodular goiter. RESULTS: A total of 3105 cases of nodular goiter were identified. The women were most affected and highest prevalence was noticed for the patients with ages between 51-60 years. Most of the nodules were found in the right thyroidian lobe and the majority of the patients were euthyroid . The peak of incidence of nodular hyperthyroidism was different from that of diffuse hyperthyroidism. CONCLUSIONS: Thyroid nodules are the most common endocrine problem and the increasingly frequent detection of nonpalpable thyroid nodules in asymptomatic patients requires new approaches for their management.