Relationship between endocrine changes and bone markers in pediatric thalassemic patients after hematopoietic stem cell transplantation.

BACKGROUND: Beta thalassemia major and its treatment by hematopoietic stem cell transplantation can have deleterious effects on bone integrity and a main part of such effects is due to their deleterious effects on endocrine systems. So, we assessed the effects of endocrine changes during HSCT (Hematopoietic Stem Cell Transplantation) on growing bones of pediatric thalassemic patients. METHODS: Bone-specific alkaline phosphatase and osteocalcin (bone formation markers), N-terminal telopeptide (NTX, bone resorption marker), calcium (Ca), phosphorus (P), alkaline phosphatase (Alk ph), parathyroid hormone (PTH), vitamin D (vit D), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), insulin-like growth factor 1 (IGF-1), testosterone (in males) or estradiol (in females), measured in 20 major thalassemic patients with mean age of 10.8±3.9 years. Parameters at the baseline (before HSCT), and 1 month and 3 months after HSCT. RESULTS: After stem cell transplantation, changes of mean serum levels of NTX, osteocalcin, prolactin, LH, T4, IGF-1, testosterone (in males), Ca, Alk ph, PTH, and vit D were not significant, but bone specific Alk ph, P, T3, TSH, FSH and estradiol changed significantly (P=0.013, P=0.001, P=0.48, P=0.02, P=0.04 and P=0.001, respectively). After one month, there was a significant positive relationship between osteocalcine and T3 (p= 0.009). After 3 months, also, there was a significant positive relationship between osteocalcine and T3 and T4 as well as a negative one with IGF-1 (P<0.001, P<0.02 and P<0.03, respectively). CONCLUSIONS: Endocrine disorders do not appear to have an overall positive or negative effect on bone metabolism (anabolism or catabolism) in HSCT pediatric thalassemic patients in short term (three months).

The Importance of Precision Medicine in Type 2 Diabetes Mellitus (T2DM): From Pharmacogenetic and Pharmacoepigenetic Aspects.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a worldwide disorder as the most important challenges of health-care systems. Controlling the normal glycaemia greatly profit long-term prognosis and gives explanation for early, effective, constant, and safe intervention. MATERIAL AND METHODS: Finding the main genetic and epigenetic profile of T2DM and the exact molecular targets of T2DM medications can shed light on its personalized management. The comprehensive information of T2DM was earned through the genome-wide association study (GWAS) studies. In the current review, we represent the most important candidate genes of T2DM like CAPN10, TCF7L2, PPAR-γ, IRSs, KCNJ11, WFS1, and HNF homeoboxes. Different genetic variations of a candidate gene can predict the efficacy of T2DM personalized strategy medication. RESULTS: SLCs and AMPK variations are considered for metformin, CYP2C9, KATP channel, CDKAL1, CDKN2A/2B and KCNQ1 for sulphonylureas, OATP1B, and KCNQ1 for repaglinide and the last but not the least ADIPOQ, PPAR-γ, SLC, CYP2C8, and SLCO1B1 for thiazolidinediones response prediction. CONCLUSION: Taken everything into consideration, there is an extreme need to determine the genetic status of T2DM patients in some known genetic region before planning the medication strategies.

Decreased apolipoprotein A4 and increased complement component 3 as potential markers for papillary thyroid carcinoma: A proteomic study.

BACKGROUND:: Thyroid carcinomas have comprised the fastest rising incidence of cancer in the past decade. Currently, the diagnosis of thyroid tumors is performed by the fine-needle aspiration biopsy (FNAB) method, which still holds some challenges and limitations, mostly in discriminating malignant and benign lesions. Therefore, the development of molecular markers to distinguish between these lesion types are in progress. METHODS:: A 2D-PAGE separation of proteins was performed followed by tandem mass spectrometry with the aim of discovering potential serum protein markers for papillary thyroid carcinoma and multinodular goiter. Protein-protein interaction network analysis revealed the most important pathways involved in the progression of papillary thyroid cancer. The enzyme-linked immunosorbent assay method was used to confirm a part of the results. RESULTS:: The significantly altered proteins included C3, C4A, GC, HP, TTR, APOA4, APOH, ORM2, KRT10, AHSG, IGKV3-20, and IGKC. We also confirmed that increased complement component 3 and decreased apolipoprotein A4 occurred in papillary thyroid cancer. Network investigations demonstrated that complement activation cascades and PPAR signaling might play a role in the pathogenesis of thyroid cancer. CONCLUSION:: The results demonstrated that serum proteomics could serve as a viable method for proposing novel potential markers for thyroid tumors. Surely, further research must be performed in larger cohorts to validate the results.

Correlation between criteria of diagnosis of low bone mineral density in adult and pediatric thalassemic patients: a prospective study.

BACKGROUND: Finding the correlation between criteria for low bone mineral density (BMD) in adulthood and childhood is a matter of interest. This study aimed to find how many of thalassemic patients with Z-Score ≤-2 during childhood, will be found with T-Score ≤-2.5 or Z-Score ≤-2.0 in adulthood. METHODS: The results of BMDs (one in childhood and one in adulthood) of 30 patients with beta thalassemia major (12 males and 18 females) with mean age of 17.63 y/o in childhood and 20.67 y/o in adulthood were studied, retrospectively. A Norland XR-46 device was used for measuring BMD. RESULTS: Z-Score ≤-2 was found in 33% of children and T-Score ≤-2.5 and Z-Score ≤-2.0 was found in 43 and 66% of adults, respectively. Correlation of pediatric Z-scores was good with adult T-scores and Z-scores (0.699-0.833). Relation of low BMD diagnosis in pediatric and adults was significant, and Kappa showed a moderate to good correlation between criteria for low BMD in childhood and adulthood, both with special significance in femoral region (8.10-14.47 and 0.258-0.703, respectively). Z-score ≤-2 significantly increased risk of low BMD in adulthood only when T-Score ≤-2.5 was used as low BMD criteria in adulthood (6.2-15.7). More patients dropped to poorer diagnosis group when Z-Score ≤-2.0 was used as low BMD criteria in adulthood. CONCLUSIONS: There is a moderate to good agreement of these criteria, at least in femoral region but using T-Score ≤-2.5 as low BMD criteria in adulthood caused a better prediction power for Z-Score ≤-2 of childhood.

A survey of clinical practice patterns in diagnosis and management of Cushing's disease in Iran.

BACKGROUND: Cushing's disease is the most prevalent cause of endogenous adrenocorticotrophic hormone hypersecretion. The aim of this study was to document the current clinical practice pattern in the management of Cushing's disease by Iranian Endocrinologists to determine their opinions and compare them with the current clinical practice guidelines. METHODS: An eight-item questionnaire dealing with diagnosis, treatment and follow up of patients with Cushing's disease was developed, piloted, and sent to the members of Iranian Endocrinology Society. RESULTS: Among 90 endocrinologists invited to participate in the survey, 76 replied. Most respondents selected overnight dexamethasone suppression test (ONDST) and assessment of 24-hour urinary free cortisol (UFC) as the best screening tests followed by midnight serum cortisol and midnight salivary cortisol. Classic high dose dexamethasone suppression test and measurement of serum ACTH were selected for localization of the primary lesion by 64.5%. The primary choice of treatment was trans-sphenoidal pituitary surgery (86.8%). For the recurrence of Cushing's disease, the preferred treatment modality was medical therapy followed by bilateral adrenalectomy, and pituitary re-surgery. In case of treatment failure after the first pituitary surgery and ketoconazole treatment, 51% chose bilateral adrenalectomy, while36.8% selected pasireotide only. CONCLUSION: ONDST and UFC are two most common tests used to screen an index case with signs and symptoms of hypercortisolism. The primary choice of treatment in Cushing's disease is pituitary surgery. However, medical treatment by ketokonazol is preferred for the recurrences. Pasireotide is the second alternative after bilateral adrenalectomy in case of treatment failure after pituitary surgery and ketoconazole.

The comparison of muscle strength and short-term endurance in the different periods of type 2 diabetes.

BACKGROUND: Patients with type 2 diabetes (T2DM) are subjected to reduction in the quality and oxidative capacity of muscles. The effect of duration of diabetes on the muscle endurance response is not clear and strength as well. OBJECTIVE: The aim of this study was the assessment of strength and endurance of knee extensor and flexor in the patients with T2DM < 10 and T2DM > 10 years in comparison with age, sex, BMI, ABI and PAI-matched health control subjects. METHODS: Isometric maximal peak torque (MPT) of knee extensor and flexor before and after 40 isokinetic repetitions with velocity of 150 degree/s were recorded in 18 patients with T2DM < 10 Y , 12 patients with T2DM > 10 Y and 20 matched health control (HC) groups. RESULTS: Both diabetic patient groups had significant lower isometric and isotonic knee extensor and flexor strength than HC. The endurance indices indicated that whereas the isometric MPT of flexor movement was reduced after isokinetic protocol in the both patient groups in comparison with HC, the less decline was seen in the isotonic torque and work during isokinetic protocol in the T2DM > 10 Y group in comparison with two other groups. The HbA1c and FPG were significantly correlated with strength not with endurance indices. CONCLUSIONS: It seems the progression of diabetes accompanied with vascular, neural and muscular deficits activate, some adaptive and compensatory processes which can maintain muscle performance.