Calcitonin and bone mass status in congenital hypothyroidism

Abstract

Calcitonin (CT) deficiency and its possible repercussions on bone mass were studied in a group of 9 adult patients (7 females, 2 males) with congenital hypothyroidism of dysgenetic origin. Using a new extraction method (exCT) which considerably improves the sensitivity and the specificity of the assay for CT-monomer, we measured CT levels before and after a short calcium (Ca) stimulation test (2 mg Ca/kg over 5 minutes) to evaluate C-cell secretory reserve. Mean basal plasma CT concentrations were lower in the hypothyroid women (mean +/- SEM: 0.6 +/- 0.1 pg/ml) than in 30 normal female controls (1.7 +/- 0.2 pg/ml, P less than 0.001). Serum calcium increased similarly in the two groups, but postinfusion CT levels were lower in the hypothyroid women, (1.7 +/- 0.2 pg/ml) than in normal women (16.8 +/- 2.9 pg/ml), P less than 0.001. Hypothyroid women showed a 10% reduction in bone mineral content at the diaphyseal site in the radius, 0.840 +/- 0.037 g/cm, compared with normal age-matched controls, 0.930 +/- 0.020 g/cm, (P less than 0.05). Our study demonstrates the existence of a profound CT-monomer deficiency in adult patients with thyroid agenesis or dysgenesis. Both calcitonin deficiency and thyroid hormone treatment could play a role in the observed bone loss. Attention should therefore be paid to bone metabolism during treatment of congenital hypothyroidism to avoid further bone loss.

The immunohistochemical demonstration of parafollicular cells and evaluation of calcium-phosphate balance in patients with thyroid hemiagenesis

“…However, one limitation of the study is that provocative tests, with assessment of calcitonin level followed by administration of calcium or pentagastrin, were not performed. On the other hand, Demeester-Mirkine et al evaluated the basal and calcium-stimulated calcitonin concentration in subjects with congenital hypothyroidism and found that the basal concentration of calcitonin, as well as the secretory reserve of parafollicular cells, were decreased [38]. Similar findings were obtained by Carey et al who demonstrated calcitonin deficiency, as well as altered calcitonin response, to calcium or pentagastrin infusion in children with non-goitrous cretinism [41].…”

“…This hypothesis was confirmed in a study of chick embryos, in which neural crest ablation led to thyroid agenesis or hemiagenesis [37]. On the other hand, Demeester-Mirkine et al hypothesized that proper development of parafollicular cells requires the presence of factors secreted by follicular cells, while cells which did not migrate adequately would not present a proper function [38]. In a study of SHH knock-out mice, the expression of calcitonin in the unilateral thyroid was not evaluated [36].…”

Densidade mineral óssea de crianças e adolescentes com hipotireoidismo congênito

“…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), fê-mur (12,14,15) e falanges proximais (16).…”

“…Por sua vez, Demeester-Mirkine e cols. (10) encontraram conteúdo e densidade mineral na diáfise do rádio mais baixos nas sete mulheres com HC quando comparadas aos controles de mesmo sexo e idade (10% de redução no CMO e 7% na DMO). Como os mesmos autores (11) encontraram baixos níveis de CT (basal e estimulada), quando comparados ao grupo controle, sugeriu-se que a deficiência de CT precoce no HC teria prejudicado o desenvolvimento esquelético e teria contribuído para a diminuição da massa óssea.…”

“…No entanto, Demeester-Mirkine e cols. (10) não dispunham dos valores de T 4 e TSH durante todo o período de tratamento, não sendo possível determinar se a perda de massa óssea teria sido induzida pelo excesso de HT.…”