The multiple effects of thyroid disorders on bone and mineral metabolism / Os múltiplos efeitos das disfunções tireoidianas sobre o metabolismo osteomineral

Differently from most hormones, which commonly are specialized molecules able to influence other cells, tissues and systems, thyroid hormones (TH) are pleiotropic peptides, whose primordial function is difficult to identify. The complex action of TH on human economy can be easily witnessed by examining the diverse consequences of TH excess and deficiency during development and after maturity. In particular, different manifestations in bone modeling and remodeling reflect the circumstantial consequences of thyroid disturbances, which are age dependent. While hyperthyroidism during childhood enhances bone mineralization and accelerates epiphyseal maturation, in adults it induces bone loss by predominant activation of osteoclast activity. Furthermore, the syndrome of TH resistance is a multifaceted condition in which different sites exhibit signs of hormone excess or deficiency depending on the configuration of the TH receptor isoform. The investigation of the impact of TH resistance on the skeleton still remains to be elucidated. We present here a thorough review of the action of TH on bone and of the impact of thyroid disorders, including hyper- and hypothyroidism and the syndrome of TH resistance, on the skeleton.

Diferentemente da maioria dos hormônios, que usualmente são moléculas especializadas capazes de influenciar outras células, tecidos e sistemas, os hormônios da tireoide (HT) são peptídeos pleiotrópicos, cuja função primordial é difícil de identificar. A ação complexa dos HT na fisiologia humana pode ser facilmente reconhecida ao observar as diversas consequências do excesso e da deficiência de HT durante e após o pleno desenvolvimento. Em particular as diferentes manifestações na modelação e remodelação óssea refletem que as consequências esqueléticas das disfunções tireoidianas dependem das circunstâncias e variam com a idade. Enquanto o hipertireoidismo durante a infância aumenta a mineralização óssea e acelera a maturação epifisária, em adultos induz a perda óssea pela ativação predominante da ação osteoclástica. Além disso, a síndrome de resistência ao HT é uma condição multifacetada na qual diferentes tecidos apresentam sinais de excesso ou deficiência hormonal, dependendo da predominância da expressão das diversas isoformas do receptor de HT. O impacto da resistência ao HT sobre o esqueleto ainda é motivo de investigação. Apresentamos aqui uma revisão abrangente sobre as ações ósseas dos HT e o impacto no esqueleto dos distúrbios da tireoide, incluindo hipo e hipertireoidismo e síndrome de resistência ao HT.

Bone disease in thyrotoxicosis.

Thyrotoxicosis, a clinical syndrome characterized by manifestations of excess thyroid hormone, is one of the commonly-recognised conditions of the thyroid gland. Thyrotoxicosis causes acceleration of bone remodelling and though it is one of the known risk factors for osteoporosis, the metabolic effects of thyroxine on bone are not well discussed. Studies show that thyroid hormones have effects on bone, both in vitro and in vivo. Treatment of thyrotoxicosis leads to reversal of bone loss and metabolic alterations, and decreases the fracture risk. There are limited studies in India as to whether these changes are fully reversible. In this review we discuss about the effects of thyrotoxicosis (endogenous and exogenous) on bone and mineral metabolism, effects of subclinical thyrotoxicosis on bone and mineral metabolism and effects of various forms of treatment in improving the bone mineral density in thyrotoxicosis.

Avaliação da fosfatase alcalina óssea e hepática em gatos com tirotoxicose induzida / Evaluation of bone and liver alkaline phosphatase in cats with induced

A tirotoxicose é caracterizada pelas excessivas concentrações séricas dos hormônios tiroidianos, podendo desencadear graves alterações no metabolismo ósseo, sendo a elevação da fosfatase alcalina total uma alteração laboratorial freqüentemente observada no hipertiroidismo felino. O aumento global dos níveis séricos de fosfatase alcalina pode ser decorrente de diferentes isoenzimas e, no caso do hipertiroidismo em humanos, as isoenzimas de origem óssea e hepática apresentam-se comumente elevadas. A partir da avaliação da bioquímica sérica de oito gatos com tirotoxicose induzida e elevação da fosfatase alcalina associada, o presente trabalho demonstra um aumento significativamente maior dos níveis séricos da fosfatase alcalina de origem óssea quando comparado com a isoenzima de origem hepática. Conclui-se que as alterações no metabolismo ósseo foram as principais responsáveis pelo aumento da fosfatase alcalina nos gatos com tirotoxicose induzida

Thyrotoxicosis, characterized by excessive serum levels of thyroidhormones, can cause serious effects in bone metabolism, elevating the total alkaline phosphatase, which is a frequent laboratorial alteration observed in feline hyperthyroidism. A rise in total serum levels of alkaline phosphatase can be caused by different isoenzymes, and in human hyperthyroidism, bone and hepatic isoenzymes are commonly increased. After serum biochemical evaluation of eight cats with induced thyrotoxicosis and associated elevation of alkaline phosphatase, the present paper shows a significant elevation of bone isoenzyme serum levels when compared with hepatic isoenzyme. It was possible to conclude that bone metabolism alterations were the main responsible for the increase of serum alkaline phosphatase in cats with induced thyrotoxicosis.

Water and creatinine clearance in thyrotoxicosis

In thyrotoxicosis, changes in urine output and serum creatinine [Cr] concentration has been related to increased glomerular filtration rate [GFR]. The aim of this study is to clarify the mechanism of these changes. Forty-one thyrotoxic patients, 9 male and 32 female with the age range of 16-62 years were selected and body weight, 24-h urine output, serum and urine Cr concentration, and GFR were measured in the thyrotoxic state and two months after treatment. The data was analyzed by student 't' test and paired 't' test. The following parameters were measured and are compared in thyrotoxic and euthyroid states respectively. Body weight: 58.4 +/- 10.6 Kg and 61.6 +/- 10.4 Kg after receiving anti-thyroid therapy [p<0.001]. 24-h urine output: 1430 +/- 420 ml, and 1165 +/- 450 ml [p <0.001]. Serum creatinine concentration: 0.7 +/- 0.11 mg/dl, and 0.84 +/- 0.13 mg/dl [p<0.001]. 24-h urine creatinine concentration: 906 +/- 225 mg/l and 1081 +/- 285 mg/l [p<0.001]. The change in GFR was not statistically significant, being 90.1 ml/min before therapy and 89.5 ml/min in the euthyroid state. Increased urine output and decreased serum creatinine concentration in thyrotoxicosis is not GFR related

Nifedipine induced modulations of intra-thyroidal radio-iodine turnover kinetics in euthyroid and thyrotoxic patients.

Nifedipine induced modulations of intrathyroidal radioiodine turnover kinetics has been studied in euthyroid and thyrotoxicosis individuals. Nifedipine has been found to suppress Amax significantly (p < 0.001), while transit kinetics k1 and k2 are not significantly affected. On the contrary, in the patients with thyrotoxicosis post-nifedipine Amax was not significantly different from pre-nifedipine study, while k1 was slightly suppressed (p < 0.05) and k2 was significantly elevated (p < 0.01). Apparently different Ca+2 dependent control mechanisms are operative in euthyroid and thyrotoxic states. Clinical implications of these observations have been discussed.

Antipyrine and doxycycline pharmacokinetics in patients with thyroid disorders.

Pathological conditions are known to affect pharmacokinetics of many drugs. Antipyrine half-life is used as a marker of liver microsomal enzyme function. Antipyrine pharmacokinetics, therefore, was investigated in 23 thyrotoxic and 11 euthyroid goitre patients. Of these, 11 thyrotoxic and 9 euthyroid goitre patients also participated in doxycycline bioavailability studies. In thyrotoxic patients, antipyrine half-life and AUCo infinity and doxycycline Cpmax and AUCo infinity were found to be reduced as compared to those of healthy euthyroid normal subjects. Following treatment of thyrotoxicosis, the antipyrine half-life and AUCo infinity returned to normal. Doxycycline AUCo infinity returned to near normal range but Cpmax did not.