[Effect of surgical treatment of thyroid nodules in older patients the likelihood of developing osteoporosis, the role of low levels of calcitonin].

In the article describes the role of deficiency of calcitonin, which originate after surgical operations on the thyroid gland, in headway of osteoporosis. Regarded significance such factors as age, level of parathyroid hormone, volume of the operational intervention in the development of osteoporosis. In elder people with thyroid nodular pathology bone metabolism is influenced by the amount of thyroid residue after resection. After thyroidectomy thyrocalcitonin is not produced, but the function of parathyroid glands remains normal, and this contributes to the progression of osteoporosis. In case of limited thyroid resection minimal changes can be observed in bone metabolism.

Cómo convencer al jefe de servicio y al gerente de la importancia de las unidades/consultas especializadas de cefaleas / How to convince the head of department and managing director of the importance of specialised headache clinics

A pesar de que la cefalea es, con diferencia, el principal motivo neurológico de consulta, y de la complejidad diagnóstica y terapéutica de algunos pacientes, el número de consultas monográficas de cefalea (CC) y de unidades de cefalea (UC) es muy reducido en nuestro país. En este artículo pasaremos revista a los principales argumentos que nos permitan, como neurólogos, defender la necesidad de la implementación de una CC/UC, dependiendo de la población que se debe atender, en todos nuestros servicios de neurología. Para ello deberemos, en primer lugar, vencer las reticencias internas, que hacen que la cefalea sea aún poco apreciada y atractiva dentro de nuestra especialidad. El hecho de que la cefalea justifique más de un cuarto de las consultas a un servicio de neurología estándar de nuestro país y de que existan más de 200 cefaleas diferentes, algunas de ellas realmente invalidantes, y las nuevas opciones de tratamiento para pacientes crónicos, como la OnabotulinumtoxinA para la migraña crónica o las técnicas de neuromodulación, obligan a introducir dentro de nuestras carteras de servicios la asistencia especializada en cefaleas. Aunque no disponemos de datos incontrovertibles, existen ya datos suficientes en la literatura que indican que esta atención es eficiente en pacientes con cefaleas crónicas no sólo en términos de salud, sino también desde el punto de vista económico (AU)

In spite that headache is, by far, the most frequent reason for neurological consultation and that the diagnosis and treatment of some patients with headache is difficult, the number of headache clinics is scarce in our country. In this paper the main arguments which should allow us, as neurologists, to defend the necessity of implementing headache clinics are reviewed. To get this aim we should first overcome our internal reluctances, which still make headache as scarcely appreciated within our specialty. The facts that more than a quarter of consultations to our Neurology Services are due to headache, that there are more than 200 different headaches, some of them actually invalidating, and the new therapeutic options for chronic patients, such as OnabotulinumtoxinA or neuromodulation techniques, oblige us to introduce specialised headache attendance in our current neurological offer. Even though there are no definite data, available results indicate that headache clinics are efficient in patients with chronic headaches, not only in terms of health benefit but also from an economical point of view (AU)

Oral administration of soluble guanylate cyclase agonists to rats results in osteoclastic bone resorption and remodeling with new bone formation in the appendicular and axial skeleton.

Orally administered small molecule agonists of soluble guanylate cyclase (sGC) induced increased numbers of osteoclasts, multifocal bone resorption, increased porosity, and new bone formation in the appendicular and axial skeleton of Sprague-Dawley rats. Similar histopathological bone changes were observed in both young (7- to 9-week-old) and aged (42- to 46-week-old) rats when dosed by oral gavage with 3 different heme-dependent sGC agonist (sGCa) compounds or 1 structurally distinct heme-independent sGCa compound. In a 7-day time course study in 7- to 9-week-old rats, bone changes were observed as early as 2 to 3 days following once daily compound administration. Bone changes were mostly reversed following a 14-day recovery period, with complete reversal after 35 days. The mechanism responsible for the bone changes was investigated in the thyroparathyroidectomized rat model that creates a low state of bone modeling and remodeling due to deprivation of thyroid hormone, calcitonin (CT), and parathyroid hormone (PTH). The sGCa compounds tested increased both bone resorption and formation, thereby increasing bone remodeling independent of calciotropic hormones PTH and CT. Based on these studies, we conclude that the bone changes in rats were likely caused by increased sGC activity.

Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis.

BACKGROUND: Periprosthetic osteolysis is a major cause of aseptic loosening in joint arthroplasty. This study investigates the impact of CT (calcitonin) deficiency and CT substitution under in-vivo circumstances on particle-induced osteolysis in Calca -/- mice. METHODS: We used the murine calvarial osteolysis model based on ultra-high molecular weight polyethylene (UHMWPE) particles in 10 C57BL/6J wild-type (WT) mice and twenty Calca -/- mice. The mice were divided into six groups: WT without UHMWPE particles (Group 1), WT with UHMWPE particles (Group 2), Calca -/- mice without UHMWPE particles (Group 3), Calca -/- mice with UHMWPE particles (Group 4), Calca -/- mice without UHMWPE particles and calcitonin substitution (Group 5), and Calca -/- mice with UHMWPE particle implantation and calcitonin substitution (Group 6). Analytes were extracted from serum and urine. Bone resorption was measured by bone histomorphometry. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase (TRACP) + cells. RESULTS: Bone resorption was significantly increased in Calca -/- mice compared with their corresponding WT. The eroded surface in Calca -/- mice with particle implantation was reduced by 20.6% after CT substitution. Osteoclast numbers were significantly increased in Calca -/- mice after particle implantation. Serum OPG (osteoprotegerin) increased significantly after CT substitution. CONCLUSIONS: As anticipated, Calca -/- mice show extensive osteolysis compared with wild-type mice, and CT substitution reduces particle-induced osteolysis.

Marcadores de remodelação e densidade mineral óssea em pacientes com deficiência de calcitonina / Markers of bone remodeling and bone mineral density in patients with calcitonin deficiency

Objetivo: Este estudo avaliou marcadores de remodelação e densidade mineral óssea (DMO) em mulheres pré-menopausadas com deficiência de calcitonina. Metodologia (pacientes e métodos): Um total de 12 pacientes tireoidectomizadas por doença benigna, mantidas em terapia de reposição com levotiroxina e com calcitonina sérica indetectável foram comparadas a 15 pacientes controles (semelhantes em relação a: idade, IMC, níveis de TSH). Elas não apresentavam co-morbidades associadas. Resultados: Cálcio, PTH e 1,25 (OH)2 vitamina D não diferenciaram nos dois grupos. Houve tendência a mais baixos valores séricos de fosfatase alcalina óssea e osteocalcina naquelas com deficiência de calcitonina e o N-telopeptídeo urinário foi significativamente mais alto neste grupo. A densidade mineral óssea foi significativamente mais baixa nas pacientes tireoidectomizadas, tanto em coluna lombar quanto em colo de fêmur. Conclusão: A deficiéncia de calcitonina pode estar associada a aumento da reabsorção óssea e redução da DMO em mulheres antes da menopausa.

Calcitonin deficiency in mice progressively results in high bone turnover.

UNLABELLED: Although the pharmacological action of calcitonin (CT) as an inhibitor of bone resorption is well established, there is still some controversy regarding its physiological function. Unexpectedly, Calca-deficient mice lacking CT and alpha-calcitonin gene-related peptide (alphaCGRP) were described to have a high bone mass phenotype caused by increased bone formation with normal bone resorption. Here we show that these mice develop a phenotype of high bone turnover with age, suggesting that CT is a physiological inhibitor of bone remodeling. INTRODUCTION: The absence of significant changes in bone mineral density caused by decline or overproduction of CT in humans has raised the question, whether the pharmacological action of CT as an inhibitor of bone resorption is also of physiological relevance. To study the physiological role of mammalian CT, we have analyzed the age-dependent bone phenotype of two mouse models, one lacking CT and alphaCGRP (Calca-/-), the other one lacking only alphaCGRP (alphaCGRP-/-). MATERIALS AND METHODS: Bones from wildtype, Calca-/- -mice and alphaCGRP-/- -mice were analyzed at the ages of 6, 12 and 18 months using undecalcified histology. Differences of bone remodeling were quantified by static and dynamic histomorphometry as well as by measuring the urinary collagen degradation products. To rule out secondary mechanisms underlying the observed phenotype, we determined serum concentrations of relevant hormones using commercially available antibody-based detection kits. RESULTS: Whereas alphaCGRP-/- -mice display an osteopenia at all ages analyzed, the Calca-/- -mice develop a phenotype of high bone turnover with age. Histomorphometric analysis performed at the age of 12 months revealed significant increases of bone formation and bone resorption specifically in the Calca-/- -mice. This severe phenotype that can result in hyperostotic lesions, can not be explained by obvious endocrine abnormalities other than the absence of CT. CONCLUSIONS: In addition to the previously described increase of bone formation in the Calca-deficient mice, we have observed that there is also an increase of bone resorption with age. This suggests that CT has a dual action as an inhibitor of bone remodeling, which may explain why alterations of CT serum levels in humans do not result in major changes of bone mineral density.

The predominant CD44 splice variant in prostate cancer binds fibronectin, and calcitonin stimulates its expression.

BACKGROUND: Prostate cancer (PC) consistently overexpresses variant the (v) isoform of the cell adhesion protein CD44, and loses expression of the standard (s) isoform. MATERIALS AND METHODS: We re-expressed CD44 full-length (exons 1-20) or standard (exons 1-5 + 16-20) or enforced stable RNAi against CD44v, and the examined functional effects on PC. The effect of stable knockout of calcitonin, a paracrine factor, or its receptor, on CD44 was assessed. RESULTS: Re-expression of full-length CD44 or CD44s increased the total CD44 mRNA and CD44s protein while suppressing CD44v. These approaches, and RNAi to CD44v, decreased invasion. In adhesion assays, benign prostate cells bound mainly to hyaluronan, whereas PC lost affinity for hyaluronan but bound more strongly to fibronectin. Re-expressing CD44s restored predominant hyaluronan binding. Knockout of the calcitonin receptor in PC-3 derived cells caused marked loss of CD44v expression and reversion to CD44s expression. CONCLUSION: Calcitonin influenced PC's balance between CD44s and CD44v. CD44v controlled invasiveness, altered ligand binding, and provides a target for therapeutic intervention.

Calcitonin plays a critical role in regulating skeletal mineral metabolism during lactation.

The maternal skeleton rapidly demineralizes during lactation to provide calcium to milk, responding to the stimuli of estrogen deficiency and mammary-secreted PTH-related protein. We used calcitonin/calcitonin gene-related peptide-alpha (Ctcgrp) null mice to determine whether calcitonin also modulates lactational mineral metabolism. During 21 d of lactation, spine bone mineral content dropped 53.6% in Ctcgrp nulls vs. 23.6% in wild-type (WT) siblings (P < 0.0002). After weaning, bone mineral content returned fully to baseline in 18.1 d in Ctcgrp null vs. 13.1 d in WT (P < 0.01) mice. Daily treatment with salmon calcitonin from the onset of lactation normalized the losses in Ctcgrp null mice, whereas calcitonin gene-related peptide-alpha or vehicle was without effect. Compared with WT, Ctcgrp null mice had increased circulating levels of PTH and up-regulation of mammary gland PTH-related protein mRNA. In addition, lactation caused the Ctcgrp null skeleton to undergo more trabecular thinning and increased trabecular separation compared with WT. Our studies confirm that an important physiological role of calcitonin is to protect the maternal skeleton against excessive resorption and attendant fragility during lactation and reveal that the postweaning skeleton has the remarkable ability to rapidly recover even from losses of over 50% of skeletal mineral content.

[Bone density and mineral metabolism in calcitonin-deficiency patients]. / Densità ossea e metabolismo calcico in pazienti calcitonino-privi.

AIM: Calcitonin is a hormone secreted by thyroid C-cells. Its primary effect seems to be a direct inhibition of bone degradation, but the physiological function of calcitonin in humans is still uncertain. The role of this hormone in the development of osteoporosis is unknown, but few authors have shown bone mass reduction in thyroidectomy patients. METHODS: To investigate the influence of calcitonin deficiency on bone turnover, 9 males (age 31 to 66 years) submitted to total thyroidectomy in 1996 for non-toxic goitre have been studied. These patients received thyroxine treatment at individual dose but never with suppressed TSH levels. Moreover 8 sex-, age- and Body Mass Index-matched normal subjects have also been studied as control group. RESULTS: Calcitonin was undetectable in thyroidectomized patients, while the mean value was 7.1+/-3.2 pg/ml in the control group. At bone ultrasonography 50% of patients showed osteopenia, while only 1 subject showed osteopenia in the control group. The mean calcium serum level of patients was significant lower than in the control group (p<0.001). Calcium urinary level was increased in patients than controls. PTH serum levels were statistically decreased (p<0.001) in patients more than in controls. Osteocalcin showed a significantly (p<0.05) lower bone formation in patients than in controls, while the markers of resorption, deoxypyridinoline and N-terminal telopeptide of type I collagen, suggested an increased bone turnover in calcitonin-deficiency patients. CONCLUSION: The results of this study show that the chronic lack of calcitonin in total thyroidectomized patients may play a role in increased bone degradation and osteopenia with a higher risk of bone fracture.

Pathophysiology of bone loss in patients receiving anticonvulsant therapy.

Many studies have shown that patients taking antiepileptic drugs (AEDs) are at increased risk for metabolic bone disease and low bone mineral density. Although early reports of bone disease in patients with epilepsy often involved institutionalized patients, who may be at risk because of lack of physical activity, reduced sunlight exposure, and poor nutrition, low bone density has also been reported in well-nourished, ambulatory outpatients with epilepsy. Traditionally, attention to the problem of AED-induced bone loss has been focused on those drugs that induce the hepatic cytochrome P450 enzyme system, thereby increasing the metabolism of vitamin D. However, the mechanisms of AED-induced bone loss appear to be multiple, and all types of AEDs are potentially implicated. Besides hepatic enzyme induction, mechanisms may include direct effects of AEDs on bone cells, resistance to parathyroid hormone, inhibition of calcitonin secretion, and impaired calcium absorption. An understanding of bone biology and the pathophysiology of bone loss can aid in the identification and monitoring of patients at risk and in the planning of appropriate prophylactic and therapeutic measures, by which most of the morbidity associated with AED-induced bone loss can be prevented.

Physiological studies in heterozygous calcium sensing receptor (CaSR) gene-ablated mice confirm that the CaSR regulates calcitonin release in vivo.

BACKGROUND: The calcium sensing receptor (CaSR) regulates serum calcium by suppressing secretion of parathyroid hormone; it also regulates renal tubular calcium excretion. Inactivating mutations of CaSR raise serum calcium and reduce urine calcium excretion. Thyroid C-cells (which make calcitonin) express CaSR and may, therefore, be regulated by it. Since calcium stimulates release of calcitonin, the higher blood calcium caused by inactivation of CaSR should increase serum calcitonin, unless CaSR mutations alter the responsiveness of calcitonin to calcium. To demonstrate regulatory effects of CaSR on calcitonin release, we studied calcitonin responsiveness to calcium in normal and CaSR heterozygous-ablated (Casr+/-) mice. Casr+/- mice have hypercalcemia and hypocalciuria, and live normal life spans. Each mouse received either 500 microl of normal saline or one of two doses of elemental calcium (500 micromol/kg or 5 mmol/kg) by intraperitoneal injection. Ionized calcium was measured at baseline and 10 minutes, and serum calcitonin was measured on the 10 minute sample. RESULTS: At baseline, Casr+/- mice had a higher blood calcium, and in response to the two doses of elemental calcium, had greater increments and peak levels of ionized calcium than their wild type littermates. Despite significantly higher ionized calcium levels, the calcitonin levels of Casr+/- mice were consistently lower than wild type at any ionized calcium level, indicating that the dose-response curve of calcitonin to increases in ionized calcium had been significantly blunted or shifted to the right in Casr+/- mice. CONCLUSIONS: These results confirm that the CaSR is a physiological regulator of calcitonin; therefore, in response to increases in ionized calcium, the CaSR inhibits parathyroid hormone secretion and stimulates calcitonin secretion.

Ablation of calcitonin/calcitonin gene-related peptide-alpha impairs fetal magnesium but not calcium homeostasis.

We used the calcitonin/calcitonin gene-related peptide (CGRP)-alpha gene knockout model (Ct/Cgrp null) to determine whether calcitonin and CGRPalpha are required for normal fetal mineral homeostasis and placental calcium transfer. Heterozygous (Ct/Cgrp(+/-)) and Ct/Cgrp null females were mated to Ct/Cgrp(+/-) males. One or two days before term, blood was collected from mothers and fetuses and analyzed for ionized Ca, Mg, P, parathyroid hormone (PTH), and calcitonin. Amniotic fluid was collected for Ca, Mg, and P. To quantify skeletal mineral content, fetuses were reduced to ash, dissolved in nitric acid, and analyzed by atomic absorption spectroscopy for total Ca and Mg. Placental transfer of (45)Ca at 5 min was assessed. Ct/Cgrp null mothers had significantly fewer viable fetuses in utero compared with Ct/Cgrp(+/-) and wild-type mothers. Fetal serum Ca, P, and PTH did not differ by genotype, but serum Mg was significantly reduced in null fetuses. Placental transfer of (45)Ca at 5 min was normal. The calcium content of the fetal skeleton was normal; however, total Mg content was reduced in Ct/Cgrp null skeletons obtained from Ct/Cgrp null mothers. In summary, maternal absence of calcitonin and CGRPalpha reduced the number of viable fetuses. Fetal absence of calcitonin and CGRPalpha selectively reduced serum and skeletal magnesium content but did not alter ionized calcium, placental calcium transfer, and skeletal calcium content. These findings indicate that calcitonin and CGRPalpha are not needed for normal fetal calcium metabolism but may regulate aspects of fetal Mg metabolism.

Impact of congenital calcitonin deficiency due to dysgenetic hypothyroidism on bone mineral density.

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 synthesis and 5 with Hashimoto's thyroiditis. The subjects received an intravenous calcium stimulus and blood was collected for the determination of ionized calcium (Ca2+), calcitonin, and intact parathyroid hormone. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry. After calcium administration the levels of Ca2+ in the two groups of hypothyroidism were significantly higher than in the normal control group (10 min after starting calcium infusion: C=1.29 +/- 0.08 vs TD=1.34 +/- 0.03 vs OH=1.34 +/- 0.02 mmol/l; P<0.05), and only the TD group showed no calcitonin response (5 min after starting calcium infusion: C = 27.9 5.8 vs TD = 6.6 0.3 vs OH = 43.0 13.4 ng/l). BMD values did not differ significantly between groups (L2-L4: C=1.116 +/- 0.02 vs TD=1.109 +/- 0.03 vs OH=1.050 +/- 0.04 g/cm2). These results indicate that early deficiency of calcitonin secretion has no detrimental effect on bone mass development. Furthermore, the increased calcitonin secretion observed in patients with inborn errors of thyroid hormone biosynthesis does not confer any advantage in terms of BMD.

Influencia de la tiroidectomía sobre la pérdida de masa ósea en relación con el déficit de calcitonina y el tratamiento con tiroxina / Influence of thyroidectomy and thyroxin treatment on bone mass loss and calcitonin deficit

Introducción. Durante las últimas décadas se ha intentado valorar si la tiroidectomía y el tratamiento con tiroxina tienen un efecto negativo sobre la masa ósea. Los resultados publicados presentan discrepancias, faltan, además, estudios en pacientes con tratamiento sustitutivo. Material y métodos. Se realiza un estudio de casos y controles, comparando a mujeres tiroidectomizadas (n = 60) con mujeres sin enfermedad tiroidea, de la misma situación estrogénica y edad, peso y talla similares. Se determinan T3, T4, TSH, PTH, vitamina D, calcitonina basal e inducida, densitometría ósea lumbar y femoral (AXD) y marcadores de la actividad ósea (osteocalcina, FATR, hidroxiprolina y deoxipiridinolina), así como las dosis de tiroxina y el tiempo de tratamiento en cada paciente. Resultados. La comparación entre casos y controles no presentó diferencias en edad, peso, talla, PTH y vitamina D. No se hallaron diferencias densitométricas globales ni aumento de pérdida de densidad ósea en los subgrupos estrogénicos de las tiroidectomizadas. Tampoco se apreciaron diferencias en la osteocalcina y en la deoxipiridinolina. La calcitonina basal fue de 6,9 ñ 4,4 pg/ml en los controles y de 4,6 ñ 1,9 pg/ml en los casos (p < 0,01). No hubo respuesta al estímulo en las tiroidectomías totales, que presentó un incremento mínimo a los 5 minutos en las subtotales. Conclusiones. No existe aumento de pérdida de mineral óseo en mujeres tiroidectomizadas por enfermedad benigna no hipertiroidea tratadas con tiroxina. Éstas presentan valores de calcitonina inferiores a los controles con incapacidad de respuesta al estímulo con calcio (AU)

Possible effect of calcitonin deficiency on bone mass after subtotal thyroidectomy.

Bone mass is purportedly reduced by an excess of endogenous or exogenous thyroid hormone or perhaps by calcitonin deficiency. Patients who have undergone thyroidectomy could be subject to all of these effects. In the present study we tried to demonstrate, whether lack of calcitonin following thyroidectomy has a significant influence on bone density. We measured thyroid hormone levels, TSH and calcitonin and assessed the bone mass in the hip and lumbar spine of 55 patients (32 f, 23 m), who had undergone a subtotal thyroidectomy between 1938 and 1996 on the reason of a non-toxic goitre. TSH levels were suppressed in 16 patients. Serum concentration of total calcium, intact PTH, osteocalcin were normal in all subjects. The mean fasting calcitonin level was in the patient group 2.09 +/- 0.7 pg/ml and in the control group, age matched healthy volunteers, 2.8 +/- 1.2 pg/ml. However, the serum level of calcitonin was not significantly lower than in the control group. 43 patients had an osteopenia or osteoporosis. The interpretation of the results in this study is hampered by the fact, that in women results may be influenced by involutional osteoporosis. Therefore we focus on the potential for osteoporosis among the 23 men. The results of our study indicates, that there is a significant reduction in bone mass in male after thyroidectomy, no matter whether T4 therapy is given or not, and whether TSH is suppressed or in a normal range.

Calcitonin deficiency in early stages of chronic autoimmune thyroiditis.

OBJECTIVES: Although calcitonin (Ct) deficiency has been described in chronic autoimmune thyroiditis (CAT) it is unclear at what stage in the disease it develops. We have analysed the Ct secretory responses of patients in two different evolutionary stages of CAT, namely the goitrous and atrophic phases. DESIGN: We studied the Ct response to combined calcium (2 mg/kg) and pentagastrin (0.5 microgram/kg) intravenous infusion in 27 patients with CAT and 30 normal adult controls. The cases were divided into two groups. The first comprised eleven women with CAT and goitrous subclinical hypothyroidism (GH), aged 28.6 +/- 10.1 years--at diagnosis they had increased thyroid autoantibody titres and cytological features compatible with stages 1 and 2 of Hashimoto's thyroiditis. The second comprised 16 females with CAT and an atrophic thyroid confirmed by ultrasound scan, aged 38.0 +/- 9.2 years--these patients were severely hypothyroid at diagnosis and were termed AH (atrophic hypothyroidism). Both groups (GH and AH) received replacement doses of thyroxine sufficient to restore euthyroidism for at least six months before the stimulation tests. Control group (C) consisted of 20 healthy women (A), aged 30.0 +/- 9.6 years, and 10 healthy men (B), aged 34.7 +/- 8.0 years. Serum Ct was measured by IRMA. The Ct secretory response was related to thyroid size and cytological data, when available. RESULTS: Basal Ct concentrations in groups GH (0.08 ng/l, median) and AH (0.07 ng/l, median) were significantly lower than those of female controls (0.58 ng/l, median). Stimulated Ct peak values in groups GH (0.08 ng/l, median) and AH (0.19 ng/l, median) were significantly lower than those of female controls (13.61 ng/l, median). Also, both basal (2.72 ng/l, median) and stimulated Ct levels (35.73 ng/l, median) in male controls were significantly higher than in female controls given already. A positive correlation between the Ct secretory reserve and thyroid dimensions, evaluated by ultrasound scan, was found only in patients with thyroid atrophy (AH; rs = 0.61, P < 0.05). CONCLUSIONS: We have found low basal and stimulated calcitonin values in patients with chronic autoimmune thyroiditis and thyroid enlargement, which represents an early phase of chronic autoimmune thyroiditis. Our data have also confirmed previous findings of deficient calcitonin secretion in advanced stages of chronic autoimmune thyroiditis in which thyroid atrophy is usually found. These findings may be associated with C-cell destruction following progressive, nonspecific follicular cell damage caused by lymphocytic infiltration and fibrosis of the gland.

Calcitonina: fisiologia e deficiência / Calcitonin: physiology and defficiency

O desenvolvimento e o aprimoramento das técnicas de dosagem da calcitonina sérica (CT) (radioimunoensaio e ensaios imunométricos), os avanços da biologia molecular, abriram novas e interessantes perspectivas, permitindo amplicar o conhecimento acerca da CT, este hormônio tantas vezes dito "sem funçao". Nesta revisao, sao discutidos aspectos históricos, estruturais e moleculares da CT, os métodos de dosagem, a importância e utilidade dos testes provocativos, sobretudo no diagnóstico do câncer medular da tireóide. Além disso, sao abordados os principais aspectos fisiológicos conhecidos, bem como as condiçoes caracterizadas por deficiente reserva secretóia de CT como no hipotireoidismo congênito, na tireoidite crônica autoimune, em pacientes tireoidectomizados e em mulheres no período pós-menopausa.

Endogenous calcitonin attenuates parathyroid hormone-induced cancellous bone loss in the rat.

Although calcitonin (CT) treatment has been shown to prevent bone loss in estrogen-deficient states, the function of endogenous CT in bone metabolism is not clearly established. To test the hypothesis that endogenous CT has a role in bone conservation, we compared the bone-resorbing effect of exogenous PTH between CT-deficient [thyroparathyroidectomized (TPTX)] and CT-sufficient [parathyroidectomized (PTX)] rats. Studies were carried out with two doses (30 and 40 pmol/h) of bovine PTH-(1-34) to examine dose responsiveness and with or without T4 replacement in TPTX rats to exclude the influence of thyroid function on the results. Sham-operated control rats received vehicle. At comparable hypercalcemia (mean +/- SEM, 13.6 +/- 0.8 vs. 12.7 +/- 1.0 mg/dl) after 3 days of sc infusion of 30 pmol/h PTH, serum CT levels were significantly (P < 0.05) higher in PTX rats (66.0 +/- 8.0 pg/ml) than in TPTX rats (17.7 +/- 4.3). CT-deficient TPTX rats showed a significant cancellous bone loss in the proximal tibia [bone volume (BV/TV), 4.2 +/- 1.0%] compared with control rats 10.4 +/- 1.2%) In contrast, there was no bone loss in CT-sufficient PTX rats (BV/TV, 10.9 +/- 0.5%). A similar difference in the serum CT level and more marked difference in BV/TV (0.9 +/- 0.3% vs. 8.1 +/- 1.3%) were observed between TPTX and PTX rats infused with 40 pmol/h PTH. The magnitude of bone loss in TPTX rats was not different between T4-supplemented and nonsupplemented groups. Unlike cancellous bone, the PTH-induced decrease in the cortical thickness of the tibia was comparable in TPTX and PTX rats. The extent of increase in serum osteocalcin after PTH infusion was not different between TPTX and PTX groups. These results indicate that in the rat, endogenous CT has a protective effect against PTH-stimulated cancellous bone loss, but not cortical bone loss.