Evaluation of parathyroid function and mineral metabolism in psychiatric patients using lithium salts / Avaliação da função paratireoidiana e metabolismo mineral em pacientes psiquiátricos usuários de sais de lítio

Objective: To evaluate parathyroid function and mineral metabolism in psychiatric patients users of lithium salts. Materials and methods: We measured the serum levels of calcium, ionized calcium, inorganic phosphorus, alkaline phosphatase, albumin, parathyroid hormone (PTH), urea, creatinine, 25-hydroxy-vitamin D and lithium of 35 patients diagnosed with bipolar disorder in use of lithium carbonate (LC) for at least one year (Lithium Group – LG) and 35 healthy subjects (Control Group – CG). Results: The LG and CG were matched by sex and age. There was only statistic difference in relation to the levels of PTH and ionized calcium, with p < 0.004 and p < 0.03, respectively. Secondary form of hyperparathyroidism (HPT) was found in eight (22.8%) LG patients and in none of the CG. There was no correlation between lithemia, usage time and dosage of LC. Conclusion: Our data demonstrate that lithium may create an imbalance in the parathyroid axis, characterized by elevated levels of PTH. .

Objetivo: Avaliar a função paratireoidiana e o metabolismo mineral em pacientes psiquiátricos usuários de sais de lítio. Materiais e métodos: Foram avaliados os níveis séricos de cálcio total, cálcio iônico, fósforo inorgânico, fosfatase alcalina, albumina, paratormônio (PTH), ureia, creatinina, 25-hidroxivitamina D e lítio de 35 pacientes diagnosticados com transtorno afetivo bipolar usuários de carbonato de lítio (CL) há pelo menos um ano (Grupo Lítio – GL) e 35 indivíduos saudáveis (Grupo Controle – GC). Resultados: O GL e o GC foram pareados por sexo e idade. Somente se observou diferença estatística em relação aos níveis de PTH e cálcio iônico, com p < 0,004 e p < 0,03, respectivamente. Hiperparatireoidismo secundário foi encontrado em oito (22.8%) pacientes do GL e em nenhum do GC. No GL, não houve correlação entre litemia, tempo de uso e posologia do CL. Conclusão: Nossos dados demonstram que o lítio pode suscitar um desequilíbrio no eixo paratireoideano, caracterizado por níveis elevados de PTH. .

Endocrine disturbances related to the use of lithium / Distúrbios endocrinológicos relacionados ao uso de lítio

Despite recent advances in pharmacological treatment of psychiatric disorders, lithium salts remain frequently used, as they are effective and inexpensive alternatives, especially in the treatment of bipolar disorders. Their use is commonly associated with various endocrine disorders, mainly in thyroid and parathyroid function, and in mineral metabolism. This article aims at reviewing these potential endocrinopathies related to the use of lithium to make health care professionals aware and familiar with these possible complications when they follow up patients using this drug, and to make them able to monitor, identify and institute early and appropriate treatment.

Apesar dos recentes avanços farmacológicos no tratamento dos transtornos psiquiátricos, os sais de lítio permanecem como uma alternativa eficaz e de menor custo, sendo usados com frequência principalmente no tratamento dos transtornos bipolares. O seu uso é comumente relacionado com diversas alterações endocrinológicas, principalmente nas funções tiroidiana, paratiroidiana e do metabolismo iônico. Este artigo tem por objetivo fazer uma revisão dessas potenciais endocrinopatias relacionadas ao uso do lítio, para que, no seguimento de pacientes em uso dessa medicação, os profissionais de saúde estejam atentos e familiarizados com essas possíveis complicações, conseguindo identificar e instituir tratamento precocemente.

Responses of serum calcium and inorganic phosphate levels as well as parathyroid gland and calcitonin producing C cells of Rattus norvegicus to Mipcin administration.

Serum calcium (Ca) level of Rattus norvegicus ranged between 13.08 +/- 0.41 - 13.25 +/- 0.39 mg/100 ml whereas serum inorganic phosphate (Pi) concentration varied between 4.21 +/- 0.28 - 4.33 +/- 0.26 mg/100 ml. Sublethal (0.50 LD50 and 0.75 LD50) administration of Mipcin induced a progressive dose-dependent decline in serum Ca level in the rat which was statistically significant at 7 and 14 days. Serum inorganic phosphate level of the treated rats did not exhibit significant fluctuation during the entire course of investigation. Parathyroid chief cells of the experimental rats exhibited degranulation, vacuolation, loss of secretory (hormone) granules and lipid droplets, decreased chromatin in nuclei and damages in the endoplasmic reticulum as well as cristae of mitochondria at 14 days of the treatment. Not much of changes could be seen in the oxyphil cells of parathyroid as well as thyroid C cells of the Mipcin-treated rats.

Effects of diazinon on serum calcium and inorganic phosphate levels as well as ultrastructures of parathyroid and calcitonin cells of Rattus norvegicus.

Daily intramuscular administration of two doses--0.50 LD550 (150 mg/kg b w) and 0.75 LD50 (225 mg/kg b w) of diazinon for 14 days induced progressive hypocalcemia without altering serum inorganic phosphate value in Rattus norvegicus. Hypocalcemic response of the pesticide was dose- as well as time-dependent. Parathyroid chief cells of the experimental rats exhibited degranulation, vacuolation, loss of secretory granules and lipid droplets, decreased chromatin, and degenerative changes in endoplasmic reticulum, Golgi complex as well as cristae of the mitochondria. Not much of ultrastructural changes could be seen in the C cells of the rats treated with diazinon.

Cresimiento y metabolismo del calcio en ratas sometidas a intoxicación crónica con hidróxido de aluminio / Growth and metabolism of calcio in rats chronically poisoned with aluminium hydroxide

Se estudiaron los efectos del aluminio sobre el crecimiento y desarrollo corporal, entre la 3 y 26 semanas de edad, en ratas intoxicadas crónicamente con hidróxido de aluminio (80 mg/kg peso ûi.p.- 3 veces por semana) y en ratas controles. El crecimiento fue evaluado de acuerdo a la teorfa de Parks de alimentación y crecimiento. El metabolismo del calcio al finalizar el perfodo de intoxicación, se estudió a través de un balance de calcio y la determinación de la velocidad de deposición y resorción ósea con ayuda de (45)Ca. Se examinó la función de la glándula paratiroides por un método indirecto. Se observó una disminución del peso corporal, sin afectarse la ingesta de alimento. El grupo tratado con aluminio se carcterizó por una reducción en la eficiencia inicial de conversión de alimento en biomasa. El aluminio no afectó la velocidad de crecimiento, ni el tiempo necesario para alcanzar la madurez. El balance de calcio en las ratas tratadas fue significativamente menor que en el grupo control. Esto fue acompañado de un aumento significativo del calcio excretado por heces, causado quizás por una menor absorción intestinal. Se observaron depósitos importantes de aluminio en la superficie del hueso trabecular y una disminución en la masa de calcio óseo en las ratas tratadas, no obstante no existen diferencias de esta última al ser expresada por 100 gr de peso corporal. La velocidad de deposición de Ca++ óseo disminuyó por efecto del aluminio, sin existir modificaciones en la velocidad de resorción ósea. La reducción del turnover óseo, reflejado por la disminución de Vo+/Vo-, fue acompañado por una menor velocidad en la recuperación de la calcemia, dato vinculado indirectamente a la respuesta de la glándula paratiroides a la hipocalcemia. En el modelo estudiado, la reducción del turnover óseo podrfa estar originado por los depósitos de aluminio en hueso, no obstante podrfan existir factores asociados como una disfunción en la secreción de PTH, o bien disminución de la afinidad en sus receptores a nivel óseo.

Swelling of the vesicle is prerequisite for PTH secretion

Unlike most secretory cells, high extra cellular calcium inhibits rather than stimulates hormonal secretion in several cells such as parathyroid cells, Juxtaglomerular cells and osteoclast. To gain further insight into the common but unique stimulus-secretion coupling mechanism in these cells, bovine parathyroid slices were incubated in various conditions of Krebs-Ringer (KR) solution containing essential amino acids. Parathyroid cells showed the inverse dependency of secretion on extra cellular calcium concentration as we expected. Ammonium acetate overcame the inhibitory effect of 2.5 mM of calcium and the maximum effect was as much as the five times of the basal value, while there was a little additive effect under 0 mM CaCl2. PTH secretion was biphasic according to the change of extra cellular osmolarity and the lowest response was observed at 300 mOsm/l. In Na-rich KR solution, high concentration of nigericin (> 10(-4)M) completely overcame the inhibitory effect of 2.5 mM CaCl2 and the maximum stimulatory effect was 8 times greater whereas it was only 2 times greater without CaCl2. In K-rich KR solution that abolished the K-gradient between the extra cellular solution and the cytoplasm, the rate of PTH secretion increased, and furthermore the addition of nigericin increased the rate of secretion significantly. The results above suggested that the osmotic swelling of the secretory vesicle in parathyroid cells might promote exocytosis as in Juxtaglomerular cells. We propose that the swelling of the vesicle is also prerequisite for secretion in several cells inhibited paradoxically by Ca++, whatever the signal transduction pathway for swelling of the secretory granules induced by the lowering of Ca++ in cytoplasm are.