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Bone mineral density Z scores for L2-L4 and femoral neck of controls (C), of patients with thyroid dysgenesis (TD), and of patients with hypothyroidism due to disorders of hormonal synthesis and Hashimoto's thyroiditis (OH).
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The objective of the present study was to determine the effect of chronic calcitonin deficiency on bone mass development. The results of 11 patients with thyroid dysgenesis (TD) were compared to those of 17 normal individuals (C) and of 9 patients with other forms of hypothyroidism (OH): 4 with hypothyroidism due to inborn errors of thyroid hormone...
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While there is a general agreement that patient education is essential for compliance, no objective tools exist to assess knowledge of children and parents of children with endocrine disorders. We aimed to design and validate a Pediatric Endocrine Knowledge Assessment Questionnaire (PEKAQ) for congenital hypothyroidism, Hashimoto's thyr...
The mechanisms underlying the early steps of thyroid development are largely unknown. In search for novel candidate genes implicated in thyroid function, we performed a gene expression analysis on thyroid cells revealing that TSH regulates the expression of several elements of the Notch pathway, including the ligand Jagged1. Because the Notch pathw...
Thyroid transcription factor 2 (TTF2) also known as FOXE1 is one of the candidate genes thought to has been involved in thyroid development. Impairment in this gene has been reported in a few cases of patients with congenital hypothyroidism resulting from thyroid dysgenesis (TD). In this study we analyzed the entire coding-region of TTF2 genes in 5...
Considering the higher prevalence of congenital hypothyroidism (CH) in Iran and the importance of determination of the etiology of CH for assessing appropriate treatment strategies, understanding the pathogenesis of CH and the implications of its inheritance and prognosis, the aim of this study was to determine the etiology of CH 7 years after init...
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Citations
... Osteoporosis is attributed to an imbalance between bone formation and resorption, followed by bone mass loss and microarchitectural deterioration, leading to increased bone fragility and fracture risk [66,67]. Several studies have shown that NOS inhibitors have abolished the protective effect of estrogen on bone ovariectomized rats, whereas treatments with NO donors were almost effective as estrogen in prevention of ovariectomy-induced bone loss [47,57,68,69]. ...
... The clinical assessment of the calcium-phosphate balance in subjects with thyroid dysgenesis has only occasionally been studied. Daripa et al. demonstrated that subjects with congenital hypothyroidism due to thyroid dysgenesis present comparable basal concentrations of calcium, parathormon and calcitonin, but the calcium-stimulated calcitonin response is blunted[9]. This corresponds to the results of our study, performed on the group of patients with TH, where no significant differences in these parameters were observed compared to normal subjects. ...
Thyroid hemiagenesis (TH) is characterized by the congenital absence of one thyroid lobe. The aim of this study was to evaluate the calcium-phosphate balance in TH. Twenty patients with TH and 20 controls with a bilobed thyroid were studied. Serum concentrations of total calcium, parathormon and calcitonin were measured. Additionally, the immunohistochemical expression of calcitonin, chromogranin A (chA), neuron-specific enolase (NSE) and calcitonin gene-related peptide (CGRP) was evaluated in surgical specimens from patients with TH and controls. There were no significant differences in biochemical parameters between TH and controls. Positive staining for calcitonin was demonstrated in 3/8 thyroid sections from three patients with TH, but only in 2/33 sections from four controls (p < 0.005). All sections from patients with TH positive for calcitonin also expressed chA, NSE and CGRP. Two sections from controls positive for calcitonin presented an additionally positive reaction for chA, and one of them also for NSE. None presented positive staining for CGRP. Of three TH sections, in one, hyperplasia of C cells of medium grade, and in another hyperplasia of C cells of high grade, could be detected. In the controls, hyperplasia of C cells of low and medium grade was observed. TH was associated with slightly enhanced C cells hyperplasia compared to controls, which might indicate compensatory proliferation. However, the calcium-phosphate balance does not seem to be significantly affected.
... Therefore, the animals present with a unilateral thyroid, devoid of parafollicular cells and parathyroid glands, associated with a lack of ultimobranchial bodies formation [7,8]. The bioavailability of parafollicular cells in subjects with TH is unknown, although it has been hypothesized that their survival or activity might be deteriorated [9]. To the best of our knowledge, neither the function of parafollicular cells nor that of parathyroid glands in humans with TH has yet to be systematically evaluated. ...
... The clinical assessment of the calcium-phosphate balance in subjects with thyroid dysgenesis has only occasionally been studied. Daripa et al. demonstrated that subjects with congenital hypothyroidism due to thyroid dysgenesis present comparable basal concentrations of calcium, parathormon and calcitonin, but the calcium-stimulated calcitonin response is blunted [9]. This corresponds to the results of our study, performed on the group of patients with TH, where no significant differences in these parameters were observed compared to normal subjects. ...
Thyroid hemiagenesis (TH) is characterized by the congenital absence of one thyroid lobe. The aim of this study was to evaluate the calcium-phosphate balance in TH. Twenty patients with TH and 20 controls with a bilobed thyroid were studied. Serum concentrations of total calcium, parathormon and calcitonin were measured. Additionally, the immunohistochemical expression of calcitonin, chromogranin A (chA), neuron-specific enolase (NSE) and calcitonin gene-related peptide (CGRP) was evaluated in surgical specimens from patients with TH and controls. There were no significant differences in biochemical parameters between TH and controls. Positive staining for calcitonin was demonstrated in 3/8 thyroid sections from three patients with TH, but only in 2/33 sections from four controls (p < 0.005). All sections from patients with TH positive for calcitonin also expressed chA, NSE and CGRP. Two sections from controls positive for calcitonin presented an additionally positive reaction for chA, and one of them also for NSE. None presented positive staining for CGRP. Of three TH sections, in one, hyperplasia of C cells of medium grade, and in another hyperplasia of C cells of high grade, could be detected. In the controls, hyperplasia of C cells of low and medium grade was observed. TH was associated with slightly enhanced C cells hyperplasia compared to controls, which might indicate compensatory proliferation. However, the calcium-phosphate balance does not seem to be significantly affected. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 299–305)
... Outros fatores que também estão relacionados à diminuição acentuada de massa óssea são os nutricionais, ambientais, desordens hormonais e a falta de atividade física regular. 7,8 A osteoporose torna o osso menos resistente a diferentes estímulos relacionados a cargas, devido à diminuição na quantidade de tecido, o que leva a amplos canais internos de reabsorção. Porém, a concentração de cálcio é normal na matriz orgânica. ...
Objective: the aim of this study was the evaluation of the sinvastatin effect on the bone
tissue biomechanical parameters in ovariectomized rats, emphasizing the evaluation of
the bone resistance. Matherial and Methods: four month Wistar rats previously submitted to ovariectomia (ovx) were used. The animals have been divided into four groups:
1) intact, 2) intact + sinvastatin, 3) ovx + sinvastatin, 4) ovx + saline. A 5 mg/kg/day
sinvastatin dose has been given through gavage, six days a week for eight weeks. 0,1
mL/100g saline dose has been given . Corporal weight, bone rigidity, bone physical
properties and femur biomechanical properties were analyzed through the three-pointflexion test. Results: There was significant differences for the maximum load (in Newtons)
between the groups ovx + sinvastatin (115,08±2,49) and intact + sinvastatin (114,67±2,22)
in comparison with the group intact ones (89,68±3,06) and between the groups ovx +
sinvastatin and ovx + saline (95,5±1,22). Regarding bone rigidity (N/mm), the groups ovx
+ sinvastatin (87,88±8,48) and intact + sinvastatin (91,56±6,30) have presented values
significantly higher than those of the intact ones group (61,93±5,87). The group ovx +
sinvastatin (145,00±2,49) put on higher corporal mass (g) comparing with the intact rats
group (113,00±3,06) and with the ovx + saline (120,33±1,21) group. Conclusion: thus it is inferred that the sinvastatin has protected the animals bone tissue concerning resistance loss due to osteopenia.
Key words: Bone and Bones/drug effect; Bone Diseases, Metabolic; Simvastatin; Ovariectomy
... Estudos demonstraram deficiência de calcitonina (CT), tanto basal quanto após estímulo (cálcio, pentagastrina), em pacientes com HC, em relação ao grupo controle, sugerindo que fatores tróficos secretados pelas células foliculares são necessários para o desenvolvimento adequado das células C (8)(9)(10)(11). Entretanto, até o momento, poucos autores estudaram a massa óssea em crianças e adolescentes com HC, e os estudos existentes mostram DMO normal e semelhante à dos controles na coluna lombar (12)(13)(14)(15)(16), fêmur (12,14,15) e falanges proximais (16). Estes autores concluíram que o tratamento prolongado e cuidadosamente monitorizado com altas doses de l-T 4 não causariam a diminuição da massa óssea na infância e, se houvesse um efeito deletério sobre o esqueleto, o crescimento longitudinal teria reparado o dano com sucesso até a idade dos pacientes destes estudos (12)(13)(14)(15)(16). Por sua vez, Demeester-Mirkine e cols. ...
... Estudos demonstraram deficiência de calcitonina (CT), tanto basal quanto após estímulo (cálcio, pentagastrina), em pacientes com HC, em relação ao grupo controle, sugerindo que fatores tróficos secretados pelas células foliculares são necessários para o desenvolvimento adequado das células C (8)(9)(10)(11). Entretanto, até o momento, poucos autores estudaram a massa óssea em crianças e adolescentes com HC, e os estudos existentes mostram DMO normal e semelhante à dos controles na coluna lombar (12)(13)(14)(15)(16), fêmur (12,14,15) e falanges proximais (16). Estes autores concluíram que o tratamento prolongado e cuidadosamente monitorizado com altas doses de l-T 4 não causariam a diminuição da massa óssea na infância e, se houvesse um efeito deletério sobre o esqueleto, o crescimento longitudinal teria reparado o dano com sucesso até a idade dos pacientes destes estudos (12)(13)(14)(15)(16). Por sua vez, Demeester-Mirkine e cols. ...
... Entretanto, até o momento, poucos autores estudaram a massa óssea em crianças e adolescentes com HC, e os estudos existentes mostram DMO normal e semelhante à dos controles na coluna lombar (12)(13)(14)(15)(16), fêmur (12,14,15) e falanges proximais (16). Estes autores concluíram que o tratamento prolongado e cuidadosamente monitorizado com altas doses de l-T 4 não causariam a diminuição da massa óssea na infância e, se houvesse um efeito deletério sobre o esqueleto, o crescimento longitudinal teria reparado o dano com sucesso até a idade dos pacientes destes estudos (12)(13)(14)(15)(16). Por sua vez, Demeester-Mirkine e cols. ...
A cross sectional study was made on 60 patients (9.9 ± 1.8 yr-old) with congenital hypothyroidism (CH) (group A): 40 girls (23 prepubertal) and 20 boys (18 prepubertal). Control group (group B) was constituted of 28 healthy children (10.4 ± 2.1 yr-old): 18 girls (8 prepubertal) and 10 boys (9 prepubertal). AIMS: To evaluate bone mineral density (BMD) and content (BMC) and to correlate them with chronological and bone age (BA), sex, sexual maturation, l-T4 dose, TSH, TT4, FT4, and CH etiology. BA, total body BMD, and BMC (DXA) were obtained of both groups. TSH, TT4, and FT4 were measured in patients only. BMD was lower in group A (0.795 ± 0.075 g/cm² vs. 0.832 ± 0.092; p = 0.04) and higher in pubertal than in prepubertal girls (p = 0.004). There was no significant difference between BMD and BMC related to sex and CH etiology. Our data demonstrated that BMD was significantly lower in children with CH, different from what has been published in the literature.
This chapter addresses the normal biology and pathophysiology of parathyroid hormone (PTH), PTH-related protein, and calcitonin, three important calcium-regulating factors that are each regulated by vitamin D. The chapter discusses the regulation of gene expression and protein secretion for each peptide and then addresses their biological function, involvement in human disease, and clinical applications. It provides the reader with a sound initial understanding of the normal biology and pathophysiology of each of these hormones and lays the foundation required to fully appreciate the functions of these factors in normal mineral and bone metabolism and in metabolic bone diseases as discussed in more depth in other chapters of this text and elsewhere.
This chapter provides information on mechanism, structure, and function of parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP), and Calcitonin. The observations that intermittent administration of PTH induces anabolic responses in the skeleton have led to the development of PTH analogs for the treatment of osteoporosis. Like many growth factors or cytokines, PTHrP has been suggested to have many functions, such as in the skeleton, mammary gland, placenta, smooth muscle and the cardiovascular system, teeth, and bone homeostatis. Finally, as far as calcitonin is concerned, it is a convenient serum tumor marker for medullary thyroid carcinoma, and can be used in longitudinal monitoring of patients for signs of recurrence or progression after surgery. There is considerable variability in the ability of individual medullary thyroid cancers to produce calcitonin, so baseline levels drawn prior to surgery are needed to interpret results. The effects of calcitonin on the osteoclast have made it a useful agent in treatment of bone and calcium disorders.
The thyroid parafollicular cell, or commonly named "C-cell," functions in serum calcium homeostasis. Elevations in serum calcium trigger release of calcitonin from the C-cell, which in turn functions to inhibit absorption of calcium by the intestine, resorption of bone by the osteoclast, and reabsorption of calcium by renal tubular cells. Oncogenic transformation of the thyroid C-cell is thought to progress through a hyperplastic process prior to malignancy with increasing levels of serum calcitonin serving as a biomarker for tumor burden. The discovery that multiple endocrine neoplasia type 2 is caused by activating mutations of the RET gene serves to highlight the RET-RAS-MAPK signaling pathway in both initiation and progression of medullary thyroid carcinoma (MTC). Thyroid C-cells are known to express RET at high levels relative to most cell types; therefore, aberrant activation of this receptor is targeted primarily to the C-cell, providing one possible cause of tissue-specific oncogenesis. The role of RET signaling in normal C-cell function is unknown though calcitonin gene transcription appears to be sensitive to RET activation. Beyond RET, the modeling of oncogenesis in animals and screening of human tumors for candidate gene mutations have uncovered mutation of RAS family members and inactivation of Rb1 regulatory pathway as potential mediators of C-cell transformation. A growing understanding of how RET interacts with these pathways, both in normal C-cell function and during oncogenic transformation, will help in the development of novel molecular-targeted therapies.
This review reflects on the past, present, and future of translational research on calcitropic hormones and bone metabolism. Calcitonin (CT) and parathormone (PTH) are complementary hormones involved in the acquisition and maintenance of bone mass and regulation of calcium metabolism. Early research demonstrated that these hormones could have an important role in the treatment of osteoporosis. Calcitonin was approved for this indication by the FDA more than two decades ago, and PTH gained regulatory approval for the treatment of osteoporosis nearly ten years ago. Unfortunately, basic research underlying the mechanism of action of these agents has lagged behind drug approval, and the role of these hormones in bone remodeling is still not firmly established. Moreover, research in bone biology shifted from these hormones to smaller molecules and paracrine regulators of skeletal remodeling. Although important, this development was somewhat unfortunate because without a clearer understanding of how calcitropic hormones work, we cannot be sure that they are being used optimally in the management of osteoporosis. In this review, we look at what is known about CT and PTH and the cells that they target, namely osteoblasts, osteoclasts, and osteocytes. We then identify gaps in knowledge and the research needed to fill them. The conduct of mechanistic studies may point to important factors, such as diurnal variation and dose responsiveness that would lead to improved treatment regimens. By reopening lines of basic and clinical investigation and applying those findings at the bedside, we hope to restart the cycle of translational research in this area.
