Therapy for persistent hypercalcemic hyperparathyroidism post-renal transplant: cinacalcet versus parathyroidectomy / Tratamento do hiperparatireoidismo hipercalcêmico persistente pós-transplante renal: cinacalcete versus paratireoidectomia

ABSTRACT Background: Persistent hyperparathyroidism post-transplant is associated with increases in the incidence of cardiovascular events, fractures, and deaths. The aim of this study was to compare both therapeutic options available: parathyroidectomy (PTX) and the calcimimetic agent cinacalcet. Methods: A single center retrospective study including adult renal transplant recipients who developed hypercalcemia due to persistent hyperparathyroidism. Inclusion criteria: PTH > 65 pg/mL with serum calcium > 11.5 mg/dL at any time after transplant or serum calcium persistently higher than 10.2 mg/dL one year after transplant. Patients treated with cinacalcet (n=46) were compared to patients treated with parathyroidectomy (n=30). Follow-up period was one year. Clinical and laboratory data were analyzed to compare efficacy and safety of both therapeutic modalities. Results: PTX controlled calcemia faster (month 1 x month 6) and reached significantly lower levels at month 12 (9.1±1.2 vs 9.7±0.8 mg/dL, p < 0.05); PTX patients showed significantly higher levels of serum phosphate (3.8±1.0 vs 2.9±0.5 mg/dL, p < 0.05) and returned PTH to normal levels (45±51 pg/mL). Cinacalcet, despite controlling calcium and phosphate in the long term, decreased but did not correct PTH (197±97 pg/mL). The proportion of patients that remained with PTH above normal range was 95% in the cinacalcet group and 22% in the PTX group. Patients treated with cinacalcet had better renal function (creatinine 1.2±0.3 vs 1.7±0.7 mg/dL, p < 0.05). Conclusions: Surgical treatment was superior to cinacalcet to correct the metabolic disorders of hyperparathyroidism despite being associated with worse renal function in the long term. Cinacalcet proved to be a safe and well tolerated drug.

RESUMO Introdução: O hiperparatireoidismo persistente pós-transplante está associado a aumento na incidência de eventos cardiovasculares, fraturas e óbitos. O objetivo deste estudo foi comparar as opções terapêuticas disponíveis: paratireoidectomia (PTX) e o agente calcimimético cinacalcete. Métodos: Estudo retrospectivo de um único centro incluiu pacientes transplantados renais adultos que desenvolveram hipercalcemia devido a hiperparatireoidismo persistente. Critérios de inclusão: PTH > 65 pg/mL com cálcio sérico > 11,5 mg/dL a qualquer momento após o transplante, ou cálcio sérico persistentemente superior a 10,2 mg/dL um ano após o transplante. Os pacientes tratados com cinacalcete (n = 46) foram comparados aos pacientes tratados com paratireoidectomia (n = 30). O período de acompanhamento foi de um ano. Dados clínicos e laboratoriais foram analisados para comparar a eficácia e a segurança de ambas as modalidades terapêuticas. Resultados: a PTX controlou a calcemia mais rapidamente (mês 1 x mês 6) e atingiu níveis significativamente mais baixos no mês 12 (9,1 ± 1,2 v.s. 9,7 ± 0,8 mg/dL, p < 0,05); pacientes submetidos à PTX apresentaram níveis significativamente mais altos de fósforo sérico (3,8 ± 1,0 v.s. 2,9 ± 0,5 mg/dL, p < 0,05) e retornaram aos níveis normais de PTH (45 ± 51 pg/mL). O cinacalcete, apesar de controlar o cálcio e o fósforo no longo prazo, diminuiu, mas não corrigiu o PTH (197 ± 97 pg/mL). A proporção de pacientes que permaneceram com PTH acima da faixa normal foi de 95% no grupo cinacalcete e 22% no grupo PTX. Os pacientes tratados com cinacalcete apresentaram melhor função renal (creatinina 1,2 ± 0,3 v.s. 1,7 ± 0,7 mg/dL, p < 0,05). Conclusões: O tratamento cirúrgico foi superior ao cinacalcete para corrigir os distúrbios metabólicos do hiperparatireoidismo, apesar de estar associado a pior função renal no longo prazo. Cinacalcete provou ser um medicamento seguro e bem tolerado.

Association between hypocalcemia and rivaroxaban in coagulation disorders: a case report / Associação entre hipocalcemia e rivaroxaban em distúrbios de coagulação: relato de caso

ABSTRACT We describe a patient with tertiary hyperparathyroidism with history of three episodes of deep vein thrombosis and on rivaroxaban. The patient underwent a subtotal parathyroidectomy, developing cervical hematoma with airway compression. Therefore, emergency surgical decompression was necessary. Later, on the ninth postoperative day, the serum ionized calcium levels were low. Medical team knowledge about preexisting diseases and their implication in the coagulation state are essential conditions to reduce morbidity and mortality of surgeries. However, no reports were found in literature about the association of hypocalcemia with the use of the new class of anticoagulants, which act as factor X inhibitors (Stuart-Prower factor), predisposing to increased bleeding in the immediate postoperative period.

RESUMO Descrevemos um paciente com hiperparatireoidismo terciário com história de três episódios de trombose venosa profunda e em uso de rivaroxabana. O paciente foi submetido a uma paratireoidectomia subtotal, desenvolvendo hematoma cervical com compressão das vias aéreas. Foi necessária descompressão cirúrgica de emergência. No nono dia de pós-operatório, os níveis séricos de cálcio iônico estavam baixos. O conhecimento da equipe médica sobre doenças preexistentes e de sua implicação no estado de coagulação é condição indispensável para a redução da morbimortalidade do procedimento cirúrgico. No entanto, não há relatos na literatura associando hipocalcemia com o uso da nova classe de anticoagulantes que atuam como inibidores do fator X (fator de Stuart-Prower), predispondo ao aumento do sangramento no pós-operatório imediato.

Vitamin d deficiency and paratohommonium increase in late postoperative gastric bypass in roux-en-y / Deficiência de vitamina d e elevação do paratohôrmonio no pós-operatório tardio de bypass gástrico em y-de- roux

ABSTRACT Background : Roux-en-Y gastric bypass patients can experience changes in calcium metabolism and hyperparathyroidism secondary to vitamin D deficiency. Aim : To evaluate nutritional deficiencies related to the calcium metabolism of patients undergoing gastric bypass with a 10-year follow-up. Method : This is a longitudinal retrospective study of patients submitted to Roux-en-Y gastric bypass at a multidisciplinary clinic located in the Brazilian southeast region. The study investigated the results of the following biochemical tests: serum calcium, ionized calcium, vitamin D, and parathormone (PTH). The generalized estimating equations (GEE) determined the nutritional deficiencies using a significance level of 5%. Results : Among the patients who finished the study (120 months), 82.86% (n=29) had vitamin D deficiency, and 41.94% (n=13) had high PTH. Postoperative time had a significant effect on PTH (p=0.0059). The percentages of patients with vitamin D, serum calcium, and ionized calcium deficiencies did not change significantly over time. Conclusion : One of the outcomes was vitamin D deficiency associated with secondary hyperparathyroidism. These findings reaffirm the importance of monitoring the bone metabolism of patients submitted to Roux-en-Y gastric bypass. HEADINGS: Calcium deficiency. Vitamin D deficiency. Secondary hyperparathyroidism.

Resumo Racional: Pacientes submetidos ao bypass gástrico em Y-de-Roux, podem apresentar alterações do metabolismo do cálcio e hiperparatireoidismo secundário à deficiência de vitamina D. Objetivo: Avaliar as deficiências nutricionais relacionadas ao metabolismo do cálcio de pacientes submetidos à bypass gástrico em Y-de-Roux, com seguimento de 10 anos. Método: Um estudo retrospectivo longitudinal foi conduzido com pacientes submetidos à bypass gástrico em Y-de-Roux, em uma Clínica Multidisciplinar no Sudeste do Brasil. Investigou-se a frequência do acompanhamento médico e nutricional e os exames bioquímicos de cálcio sérico, cálcio iônico, vitamina D e paratormônio (PTH). Para a análise das deficiências nutricionais, foram utilizadas as Equações de Estimativas Generalizadas (EEG), com nível de significância de 5%. Resultados: Dos pacientes que permaneceram no estudo até o final (120 meses), 82,86% (29), apresentaram níveis de deficiência de vitamina D e 41,94% (13) apresentaram PTH elevado. O efeito do tempo foi significativo para o PTH (p=0,0059). Para a vitamina D, cálcio sérico e cálcio iônico, o percentual de deficiência manteve-se constante ao longo do tempo, sem diferença significativa entre os tempos. Conclusão: A deficiência de vitamina D, associada ao hiperparatireoidismo secundário, foi um desfecho encontrado. Tais achados reafirmam a importância do cuidado com o metabolismo ósseo, em pacientes submetidos à bypass gástrico em Y-de-Roux.

Recomendações da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) para o diagnóstico e tratamento da hipovitaminose D / Recommendations of the Brazilian Society of Endocrinology and Metabology (SBEM) for the diagnosis and treatment of hypovitaminosis D

Objetivo Apresentar uma atualização sobre o diagnóstico e tratamento da hipovitaminose D baseada nas mais recentes evidências científicas. Materiais e métodos O Departamento de Metabolismo Ósseo e Mineral da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) foi convidado a conceber um documento seguindo as normas do Programa Diretrizes da Associação Médica Brasileira (AMB). A busca dos dados foi realizada por meio do PubMed, Lilacs e SciELO e foi feita uma classificação das evidências em níveis de recomendação, de acordo com a força científica por tipo de estudo. Conclusão Foi apresentada uma atualização científica a respeito da hipovitaminose D que servirá de base para o diagnóstico e tratamento dessa condição no Brasil. .

Objective The objective is to present an update on the diagnosis and treatment of hypovitaminosis D, based on the most recent scientific evidence. Materials and methods The Department of Bone and Mineral Metabolism of the Brazilian Society of Endocrinology and Metabology (SBEM) was invited to generate a document following the rules of the Brazilian Medical Association (AMB) Guidelines Program. Data search was performed using PubMed, Lilacs and SciELO and the evidence was classified in recommendation levels, according to the scientific strength and study type. Conclusion A scientific update regarding hypovitaminosis D was presented to serve as the basis for the diagnosis and treatment of this condition in Brazil. .

Diagnosis and management of primary hyperparathyroidism: a scientific statement from the Department of Bone Metabolism, the Brazilian Society for Endocrinology and Metabolism / Diagnóstico e manejo do hiperparatireoidismo primário: uma posição científica do Departamento de Metabolismo Ósseo, a Sociedade Brasileira de Endocrinologia e Metabolismo

OBJECTIVE: To conduct a literature review on the diagnosis and management of primary hyperparathyroidism including the classical hipercalcemic form as well as the normocalcemic variant. MATERIALS AND METHODS: This scientific statement was generated by a request from the Brazilian Medical Association (AMB) to the Brazilian Society for Endocrinology as part of its Clinical Practice Guidelines program. Articles were identified by searching in PubMed and Cochrane databases as well as abstracts presented at the Endocrine Society, Brazilian Society for Endocrinology Annual Meetings and the American Society for Bone and Mineral Research Annual Meeting during the last 5 years. Grading quality of evidence and strength of recommendation were adapted from the first report of the Oxford Centre for Evidence-based Medicine. All grades of recommendation, including "D", are based on scientific evidence. The differences between A, B, C and D, are due exclusively to the methods employed in generating evidence. CONCLUSION: We present a scientific statement on primary hyperparathyroidism providing the level of evidence and the degree of recommendation regarding causes, clinical presentation as well as surgical and medical treatment.

OBJETIVO: Conduzir uma atualização das últimas evidências científicas a respeito da apresentação, do diagnóstico e do manejo clínico e cirúrgico do hiperparatireoidismo primário clássico e normocalcêmico. MATERIAIS E MÉTODOS: Este documento foi concebido pelo Departamento de Metabolismo Ósseo da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) a partir daquele oriundo do Programa de Diretrizes da Associação Médica Brasileira (AMB) da SBEM. Realizamos uma revisão dos artigos mais relevantes obtidos nos bancos de dados PubMed e Cochrane, além de abstracts apresentados nos encontros anuais da Endocrine Society, da Sociedade Brasileira de Endocrinologia e da American Society for Bone and Mineral Research dos últimos cinco anos, e classificamos as evidências em níveis de recomendações de acordo com a força científica por tipo de estudo, adaptando o primeiro relato do "Oxford Centre for Evidence-based Medicine". Todos os graus de recomendação, incluindo-se o "D", foram basea-dos em evidência científica, sendo as diferenças entre o A, B, C e D devidas exclusivamente ao desenho empregado na geração da evidência. CONCLUSÃO: Apresentamos uma atualização científica a respeito do hiperparatireoidismo primário, classificando e graduando em níveis de recomendações as principais evidências científicas sobre as suas causas, as variadas formas de apresentação, seu diagnóstico e tratamento.

Supernumerary parathyroid glands in hyperparathyroidism associated with multiple endocrine neoplasia type 1 / Paratireoides supranumerárias em hiperparatireoidismo primário associado a neoplasia endócrina múltipla tipo 1

OBJECTIVE: To evaluate frequency, anatomic presentation, and quantities of supernumerary parathyroids glands in patients with primary hyperparathyroidism (HPT1) associated with multiple endocrine neoplasia type 1 (MEN1), as well as the importance of thymectomy, and the benefits of localizing examinations for those glands. METHODS: Forty-one patients with hyperparathyroidism associated with MEN1 who underwent parathyroidectomy between 1997 and 2007 were retrospectively studied. The location and number of supernumerary parathyroids were reviewed, as well as whether cervical ultrasound and parathyroid SESTAMIBI scan (MIBI) were useful diagnostic tools. RESULTS: In five patients (12.2%) a supernumerary gland was identified. In three of these cases (40%), the glands were near the thyroid gland and were found during the procedure. None of the imaging examinations were able to detect supernumerary parathyroids. In one case, only the pathologic examination could find a microscopic fifth gland in the thymus. In the last case, the supernumerary gland was resected through a sternotomy after a recurrence of hyperparathyroidism, ten years after the initial four-gland parathyroidectomy without thymectomy. MIBI was capable of detecting this gland, but only in the recurrent setting. Cervical ultrasound did not detect any supernumerary glands. CONCLUSION: The frequency of supernumerary parathyroid gland in the HPT1/MEN1 patients studied (12.2%) was significant. Surgeons should be aware of the need to search for supernumerary glands during neck exploration, besides the thymus. Imaging examinations were not useful in the pre-surgical location of these glands, and one case presented a recurrence of hyperparathyroidism.

OBJETIVO: Avaliação da frequência, da localização anatômica e do número de paratireoides extranumerárias em pacientes com hiperparatireoidismo primário (HPT1) associado a neoplasia endócrina múltipla tipo 1(NEM1), além da avaliação da importância da timectomia e da utilidade dos exames radiológicos para localização destes. MÉTODOS: Foram avaliados de forma retrospectiva 41 pacientes portadores de NEM1 com HPT1 submetidos a paratireoidectomia entre 1997 e 2007. O número de glândulas supranumerárias encontradas e a sua localização foram revisados, assim como a utilidade do ultrassom cervical e do SESTAMIBI (MIBI) de paratireoide como ferramentas diagnósticas. RESULTADOS: Em cinco pacientes (12,2%) foram identificadas glândulas supranumerárias. Em três destes (40%), as glândulas estavam próximas à glândula tireoide e foram encontradas durante a exploração cirúrgica. Os exames de imagem não foram úteis para a localização destas glândulas. Em um caso, apenas o exame anatomopatológico foi capaz de encontrar uma glândula extranumerária microscópica localizada no timo. No último caso, uma quinta glândula foi ressecada por meio de esternotomia após a recidiva do hiperparatireoidismo, cerca de 10 anos após a paratireoidectomia realizada sem timectomia na ocasião. Neste caso o MIBI detectou esta paratireoide apenas após a recidiva da doença. Em nenhum dos casos o ultrassom cervical foi capaz de detectar glândulas extranumerárias. CONCLUSÃO: A frequência de paratireoides supranumerárias em nossa casuística foi significativa (12,2%). Durante a exploração cervical, o cirurgião deve estar atento para localizar glândulas extranumerárias além do timo. Exames de imagem não foram úteis na localização préoperatória dessas glândulas, e em um caso houve recidiva do hiperparatireoidismo.

Utilidad de la PTH intraoperatoria como predictor de curación quirúrgica en hiperparatiroidismo primario / Usefulness of intraoperative parathormone measurement to predict surgical cure in primary hyperparathyroidism

Background: The aim of the surgical treatment of primary hyperparathyroidism (PHPT) is to achieve its complete cure, evidenced by normal serum calcium in the postoperative period. Measurement of intraoperative serum parathormone (PTH) can be useful to predict complete cure of the disease. Aim: To assess the usefulness of intraoperative PTH measurement to predict complete cure of PHPT Material and methods: Serum PTH was measured to all patients operated for PHPT between 2003 and 2008, before and five and ten minutes after the excision of the parathyroid gland causing the disease. The criteria for complete cure were normal serum calcium at 24 hours and 6 months after surgery and the pathological confirmation of parathyroid gland excision. Results: Eighty-eight operated patients, aged 58±15 years (72 females) were studied. Sixty four percent were asymptomatic and their preoperative serum calcium was 11.6± 1.2 mg/dl. A normal serum calcium was achieved in 86 patients (98 percent) at 24 hours and 50 of 52 patients followed for six months (96 percent). The pathological study disclosed an adenoma in 69 (78 percent), and multiglandular disease in 16 (18 percent), a parathyroid cancer in one and a normal gland in one patient. Intraoperative PTH predicted early and definitive cure in 97 percent and 100 percent of patients with a single adenoma, respectively. Among patients with multiglandular disease, the predictive figures were 94 percent and 100 percent, respectively. Conclusions: Intraoperative PTH measurement efficiently predicts early and definitive surgical cure of PHPT.

Hiperparatiroidismo normocalcémico asociado a hipovitaminosis D, hipercalciuria renal y nódulo paratiroideo: caso clínico / Normocalcemic hyperparathyroidism secondary to vitamin D deficiency and renal hypercalciuria: report of one case

We report a 77 years old woman with osteoporosis in whom a hyperparathyroidism secondary vitaminD deficiency and renal hypercalciuria was diagnosed. Serum calcium was normal. During the diagnostic work up, a parathyroid nodule was discovered and subjected to a fine needle aspiration biopsy, that showed normal parathyroid cells. The patient was treated with calcitriol, cholecalciferol, hydrochlorothiazide and intravenous zolendronic acid. There was a reduction in urinary calcium and serum PTH levels and improvement of serum 25 hydroxy vitamin D levels.

Parathyroid lipoadenoma: case report and review of the literature.

Parathyroid lipoadenoma is a rare variant of parathyroid adenoma showing intermingling of chief/ oxyphil cells with abundant mature adipose cells, the latter comprising 20-90% of the tumour. Approximately thirty-five cases have been reported previously. We report a case of 41-year old woman who presented with clinical manifestations of primary hyperparathyroidism. She had elevated serum calcium and parathyroid hormone levels. Radiological investigations suggested presence of adenoma. Intra-operatively, parathyroid adenoma was found in the neck in an ectopic location behind the carotid sheath and extending into the superior mediastinum. Clinicopathological findings of this rare tumour are discussed.

Primary hyperparathyroidism due to parathyroid adenoma

To evaluate the clinical characteristics and outcome of patients with parathyroid adenoma. We diagnosed and operated 54 patients with primary hyperparathyroidism in the Faculty of Medicine, Gazi University, Turkey from January 2000 to December 2004. In this study, 52 [96.2%] of these patients who had parathyroid adenoma were retrospectively evaluated. There were 46 female, and 6 male patients with a median age of 54.5 years [range, 18-87 years] at diagnosis. Preoperative mean serum level of calcium was 11.09 +/- 0.9 mg/dL, while phosphorus was 2.3 +/- 0.5 mg/mL, and parathyroid hormone [PTH] was 338.99 +/- 416.43 pg/ml. Ultrasound imaging revealed parathyroid adenoma in 38 of the 52 patients [73%], while 27% of the patients were normal. In 29 [69%] of the 42 patients who had sestamibi scanning, results revealed parathyroid adenoma and in the others [31%], sestamibi scanning was normal. On the postoperative period, the mean serum calcium level was 9.2 +/- 0.74 mg/dL [p=0.0001 compared to preoperative level], phosphorus was 2.7 +/- 0.39 mg/mL [p=0.07 compared to preoperative level], and PTH level was 41.01 +/- 43.03 pg/ml [p=0.0001 compared to preoperative level]. All patients were cured after operation, as determined by normalization in serum calcium levels in the postoperative period. Parathyroid adenoma is the most common cause of primary hyperparathyroidism. Preoperative serum calcium and PTH levels are the most useful parameters for diagnosis. Preoperative screening methods and operative findings are not always correlated so the patients with high serum calcium and PTH should be planned for surgery, independent of radiological results. All patients were cured after operation, as determined by normalization in serum calcium levels in the postoperative period

Hiperparatiroidismo primario con compromiso esquelético grave: Un caso de carcinoma paratiroideo / Primary hyperparathyroidism with severe skeletal involvement in one patient with parathyroid carcinoma

Parathyroid carcinoma is an uncommon cause of primary hyperparathyroidism; however, when this condition is severe, cancer must be suspected. We report on a 28-year-old male with severe hypercalcemia, cachexia, acute pancreatitis, urolithiasis, anemia and a severe skelletal involvement with multiple fractures. The patient had a 4-cm parathyroid tumor, that was surgically excised, along with the ipsilateral thyroid lobe. During the postoperative period, he had a severe and prolonged hungry bone syndrome, with a slow recovery of fractures, with functional and anatomical sequelae in the extremities. PTH levels were adequate for the serum calcium during the 16 months of follow-up.

Hiperparatireoidismo primário em paciente com lúpus eritematoso sistêmico / Primary hyperparathyroidism in a patient with systemic lupus erythematosus

O hiperparatireoidismo primário (HPP) é uma doença metabólica que resulta da secreção anormal do hormônio da paratireóide (PTH), sendo uma das causas mais comuns de hipercalcemia na população geral. Apresentamos o caso de uma paciente de 47 anos, com diagnóstico prévio de lúpus eritematoso sistêmico (LES) há dois anos, que apresentou manifestações clínicas (dor óssea difusa, labilidade emocional, tumoração em ramo mandibular esquerdo) e laboratoriais (cálcio sérico= 13,5mg/dL, fosfato= 1,8mg/dL, fosfatase alcalina= 3.028U/L, PTH intacto= 1472pg/dL) que culminaram com o diagnóstico de HPP, complementado pelo estudo anátomo-patológico, que evidenciou adenoma de paratireóide. Após o tratamento com calcitonina nasal 400UI/dia, pamidronato 90mg IV/semana e, por fim, a paratireoidectomia subtotal, a paciente apresentou melhora do quadro clínico e normalização dos exames laboratoriais. A presente descrição se constitui no segundo caso relatado na literatura, com tal associação de doenças. Embora os mecanismos etiopatogênicos do HPP em LES não estejam ainda definidos, essa associação deve ser sempre lembrada, uma vez que a estratégia terapêutica tende a mudar completamente.

Water-clear cell adenoma of the parathyroid gland: a rare entity.

Water-clear cell hyperplasia is a rare but well-documented cause of primary hyperparathyroidism. Parathyroid adenomas of water-clear cell type are exceptionally rare, and only five case reports are available at present in the medical literature. We report an additional case of water-clear cell adenoma of the parathyroid gland, and the differential diagnoses are discussed.

Brown tumor of the femur associated with double parathyroid adenomas

Severe parathyroid bone disease is a rare clinical presentation of primary hyperparathyroidism. Double parathyroid adenomas are even more rare cause of primary hyperparathyroidism. The authors present a case of double parathyroid adenomas in a 48-year-old man, who presented with painful left lower limb swelling, which was slowly growing in size in the last 20 years. Magnetic resonance imaging revealed a cystic bony lesion and coincidentally, a urinary bladder calculus. Biopsy of the mass revealed giant cell lesion. Laboratory investigations showed hypercalcemia and hypophosphatemia with elevated parathyroid hormone level. A computerized tomography scan of the neck delineated an adenoma of the left superior parathyroid gland, which was surgically removed. The left inferior parathyroid was also enlarged and was removed. Histological diagnosis confirmed double parathyroid adenomas. The rarity and the interesting clinical presentation of such association are discussed

Compensatory hyperparathyroidism following high fluoride ingestion - a clinico - biochemical correlation.

OBJECTIVE: To evaluate the effect of varying ingestion of drinking water containing high fluorides and its effect on serum parathyroid hormone. DESIGN: Cross sectional clinical study. SETTING: S.M.S. Medical College, Jaipur. SUBJECT: 200 children were selected from four areas (50 from each area) consuming water containing 2.4, 4.6, 5.6 and 13.5 mg/l of fluoride. All children were in an age group of 6 to 12 years. METHODS: All children were graded for clinical, radiological and dental fluorosis and biochemical estimations were made for serum calcium, serum and urinary fluoride and serum parathyroid hormone. RESULTS: Serum calcium levels were well within normal range in the patients of all areas but an increase in serum parathyroid levels (S. PTH) was noted. The increased S. PTH was well correlated with increase in fluoride ingestion. The severity of clinical and skeletal fluorosis was observed to increase with increase in S. PTH concentration. CONCLUSIONS: High Fluoride ingestion has a definite relationship with increased parathyroid hormone secretion, which may be responsible for maintaining serum calcium levels and may have a role in toxic manifestations of fluorosis.