Tratamiento del hipoparatiroidismo postquirúrgico permanente, servicio endocrinología, Centro Médico Nacional 20 de noviembre, México 2020 / Permanent post-surgical hypoparathyroidism treatment response, outpatient consultation Endocrinology Service, ISSSTE, 2020

El hipoparatiroidismo postquirúrgico se caracteriza por hipocalcemia, hiperfosfatemia, e hipercalciuria, secundarios a concentraciones bajas de la hormona paratiroidea. La prevalencia en Estados Unidos es 23-37 casos/100.000 años-persona. Tras la cirugía de cuello ocurre como complicación en 78% de los casos; 75% resuelve espontáneamente en los primeros 6 meses y en el 25% restante es permanente. El tratamiento requiere administrar calcio oral y análogos de vitamina D (calcitriol y alfacalcidol) de forma crónica; en casos complicados se puede emplear calcio intravenoso en el postquirúrgico inmediato y mediato; algunos pacientes no responden a la terapia estándar. Objetivo: describir las características clínicas y la respuesta al tratamiento médico en pacientes con hipoparatiroidismo postquirúrgico permanente. Material y métodos: estudio descriptivo, transversal, con componente analítico mediante revisión de expedientes clínicos de pacientes que asistieron a la consulta externa del Servicio de Endocrinología del Centro Médico Nacional 20 de Noviembre; universo 88 expedientes, muestra por conveniencia 55 expedientes. Resultados: 35(63.6%) pacientes alcanzaron control óptimo de tratamiento a dosis de calcio elemental de 5.7-9.79g/24h (p= 0.0001 chi cuadrado), mostrando calcio sérico promedio 8.36 0.55 mg/dl y calcitriol con mediana de 0.5µg/24 h. 15(27.2%) pacientes presentaron efectos secundarios al uso de calcio oral, 3 de ellos requirieron manejo con Hormona Paratiroidea Recombinante Humana para alcanzar control óptimo. Conclusión: el calcio elemental por vía oral continúa siendo la piedra angular en el tratamiento del hipoparatiroidismo post quirúrgico permanente, con pocos efectos adversos. Se recomiendan más estudios aleatorizados para identificar las características de los pacientes candidatos al manejo con Hormona Paratiroidea Recombinante Humana...(AU)

Tratamiento de hipoparatiroidismo con parathormona recombinante humana [rhPTH(1-84)] / Hypoparathyroidism treated with recombinant human parathyroid hormone [rhPTH(1-84)]

El hipoparatiroidismo (hipoPTH) es una enfermedad infrecuente caracterizada por hipocalcemia y niveles inapropiadamente bajos o ausentes de parathormona. Presentamos el caso de un hombre de 25 años, deportista de alto rendimiento, con antecedente de hipoPTH secundario a tiroidectomía total dos años antes por cáncer papilar multifocal bilateral tiroideo, estadificado como T3 N1b M0, derivado por hipocalcemia sintomática. Presentaba calcemias promedio de 7mg%, síntomas de hipocalcemia en reposo y múltiples internaciones. Inicialmente, se optimizó tratamiento convencional con aporte de calcio vía oral hasta 12g/día, vitamina D y calcitriol, sin mejoría clínica ni bioquímica. Se descartaron malabsorción y complicaciones crónicas de hipoPTH. Se evidenció a través de cuestionario de salud SF-36 disminución de la calidad de vida. Se indicó sustitución con parathormona recombinante humana [rhPTH(1-84)] 50μg/día subcutánea con posterior ascenso a 75μg y reducción progresiva de la medicación por vía oral. Actualmente se encuentra asintomático, sin requerimiento de calcio ni vitamina D, mantiene calcemias de 9mg%, realiza actividad deportiva y demuestra marcada mejoría en la calidad de vida según cuestionario SF-36 (36-Item Short Form Health Survey).

Hypoparathyroidism (HypoPT) is a rare disease characterized by low calcium and inappropriately low circulating parathormone levels. We present the case of a 25-year-old high-performance athlete male, with history of HypoPT after total thyroidectomy for papillary thyroid carcinoma (T3 N1b M0) two years before, who was referred to our clinic for symptomatic hypocalcemia. The patient reported serum calcium average levels of 7mg%, presented symptoms of hypocalcemia at rest and had multiple hospital admissions. First, standard treatment was optimized by calcium supplementation up to 12g/d and active vitamin D, not showing clinical or biochemical improvement. Malabsorption and complications of chronic HypoPT were ruled out. The 36-Item Short Form Health Survey (SF-36) demonstrated an impaired quality of life (QoL). Full-length recombinant human parathyroid hormone [rhPTH(1-84)] therapy was started with 50μg/d subcutaneous, and later adjusted to 75μg/d and the oral treatment gradually decreased. Currently, he is asymptomatic, with serum calcium levels above 9mg%, without receiving oral medication. He performs sports activity and shows marked improvement in quality of life according to SF-36 questionnaire.

Hipoparatiroidismo y calcificaciones cerebrales: reporte de caso / Hypoparathyroidism and brain calcifications: a case report

Introducción. El hipoparatiroidismo es una enfermedad caracterizada por la ausencia o concentraciones inadecuadamente bajas de hormona paratiroidea (PTH), que conduce a hipocalcemia, hiperfosfatemia y excreción fraccional elevada de calcio en la orina. Las calcificaciones del sistema nervioso central son un hallazgo frecuente en estos pacientes. Caso clínico. Mujer de 56 años con antecedente de hipotiroidismo, que ingresó por un cuadro de 6 días de evolución caracterizado por astenia, parestesias periorales y movimientos anormales de manos y pies. Las pruebas de laboratorio demostraron hipocalcemia, hiperfosfatemia y niveles bajos de hormona paratiroidea. Se realizó una tomografía computarizada de cráneo que mostró áreas bilaterales y simétricas de calcificaciones en hemisferios cerebelosos, ganglios basales y corona radiata. No se evidenciaron trastornos en el metabolismo del cobre y hierro. Se estableció el diagnóstico del síndrome de Fahr secundario a hipoparatiroidismo y se inició tratamiento con suplementos de calcio y vitamina D con evolución satisfactoria. Discusión. El síndrome de Fahr es un trastorno neurológico caracterizado por el depósito anormal de calcio en áreas del cerebro que controlan la actividad motora. Se asocia a varias enfermedades, especialmente, hipoparatiroidismo. La suplementación con calcio y vitamina D con el objetivo de normalizar los niveles plasmáticos de estos cationes es el tratamiento convencional. (AU)

Introduction. Hypoparathyroidism is a disease characterized by absence or inappropriately low concentrations of circulating parathyroid hormone, leading to hypocalcaemia, hyperphosphataemia and elevated fractional excretion of calcium in the urine. Central nervous system calcifications are a common finding in these patients. Case report. 56-year-old woman with a history of hypothyroidism who was admitted for a 6-day course of illness characterized by asthenia, perioral paresthesias, and abnormal movements of the hands and feet. Laboratory tests showed hypocalcemia, hyperphosphatemia, and low parathyroid hormone levels. A cranial computed tomography was performed. It showed bilateral and symmetrical areas of calcifications in the cerebellar hemispheres, basal ganglia, and radiata crown. No disorders of copper or iron metabolism were evident. The diagnosis of Fahr syndrome secondary to hypoparathyroidism was established and treatment with calcium and vitamin D supplements was started with satisfactory evolution. Discussion. Fahr's syndrome is a neurological disorder associated with abnormal calcium deposition in areas of the brain that control motor activity. It is associated with various diseases, especially hypoparathyroidism. The conventional treatment is supplementation with calcium and vitamin D, with the aim of normalizing their plasma levels. (AU)

Diagnosis and treatment of hypoparathyroidism: a position statement from the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Objective To present an update on the diagnosis and treatment of hypoparathyroidism based on the most recent scientific evidence. Materials and methods The Department of Bone and Mineral Metabolism of the Sociedade Brasileira de Endocrinologia e Metabologia (SBEM; Brazilian Society of Endocrinology and Metabolism) was invited to prepare a document following the rules set by the Guidelines Program of the Associação Médica Brasileira (AMB; Brazilian Medical Association). Relevant papers were retrieved from the databases MEDLINE/PubMed, LILACS, and SciELO, and the evidence derived from each article was classified into recommendation levels according to scientific strength and study type. Conclusion An update on the recent scientific literature addressing hypoparathyroidism is presented to serve as a basis for the diagnosis and treatment of this condition in Brazil.

Hypoparathyroidism and pseudohypoparathyroidism: etiology, laboratory features and complications

ABSTRACT Objectives To identify a clinical profile and laboratory findings of a cohort of hypoparathyroidism patients and determine the prevalence and predictors for renal abnormalities. Materials and methods Data from medical records of five different visits were obtained, focusing on therapeutic doses of calcium and vitamin D, on laboratory tests and renal ultrasonography (USG). Results Fifty-five patients were identified, 42 females and 13 males; mean age of 44.5 and average time of the disease of 11.2 years. The most frequent etiology was post-surgical. Levels of serum calcium and creatinine increased between the first and last visits (p < 0.001 and p < 0.05, respectively); and serum levels of phosphate decreased during the same period (p < 0.001). Out of the 55 patients, 40 had USG, and 10 (25%) presented with kidney calcifications. There was no significant difference in the amount of calcium and vitamin D doses among patients with kidney calcifications and others. No correlation between serum and urinary levels of calcium and the presence of calcification was found. Urinary calcium excretion in 24h was significantly higher in patients with kidney calcification (3.3 mg/kg/d) than in those without calcification (1.8 mg/kg/d) (p < 0.05). Conclusions The reduction of hypocalcemia and hyperphosphatemia suggest an effectiveness of the treatment, and the increase in serum creatinine demonstrates an impairment of renal function during follow-up. Kidney calcifications were prevalent in this cohort, and higher urinary calcium excretion, even if still within the normal range, was associated with development of calcification. These findings suggest that lower rates of urinary calcium excretion should be aimed for in the management of hypoparathyroidism.

Hipoparatiroidismo primario de presentación tardía asociado a patologías autoinmunes / Late onset primary hypoparathyroidism associated with autoimmune disorders

Se presenta una paciente que, en la sexta década de su vida, debuta con episodios de espasmo carpopedal espontáneo. Los valores bajos de calcemia (6,1 mg/dl) y de PTH (8 pg/ml) confirmaron el diagnóstico de hipoparatiroidismo. No había sido sometida a cirugías de cuello ni radioterapia. No existían antecedentes familiares vinculantes. Durante 11 años de seguimiento, la paciente presenta asociación con otras patologías que permiten sospechar la etiología autoinmune del hipoparatiroidismo: candidiasis de piel y uñas, hipotiroidismo por tiroiditis de Hashimoto, penfigoide y psoriasis. Finalmente fallece por una neumonía adquirida en la comunidad, complicada. (AU)

A patient who develops hypoparathyroidism during her sixth decade of life is reported. It was detected due to spontaneous carpopedal spasms. Low calcium (6.1 mg/dl) and PTH (8 pg/ml) levels confirmed the diagnosis. She had not undergone neck surgery or irradiation. There was no relevant family history. Throughout the 11 years follow up she presented association of other pathologies that allow the suspicion of autoimmune etiology of hypoparathyroidism: candidiasis of skin and nails, autoimmune thyroiditis, pemphigoid and psoriasis. She eventually died of complicated community-acquired pneumonia. (AU)

Severe isolated primary hypoparathyroidism in an adult

A man aged 42 years, presented with 3 years history of paraesthesias in hands and feet and muscle cramps off and on, progressing to severe carpopedal spasm, a couple of times, relieved by intravenous calcium gluconate at the emergency reception of the hospital. On examination, Trousseau's sign and Chvostek's sign were positive. Thyroid gland was not enlarged. Right eye showed mature cataract. Total serum calcium, corrected serum calcium, serum phosphate, ionized serum calcium, serum alkaline phosphatase, serum parathormone [PTH] level were deranged favouring hypoparathyroidism. He was diagnosed to be suffering from isolated primary hypoparathyroidism and put on alfacalcidol and oral calcium carbonate, with which he is asymptomatic now

Hypoparathyroidism: clinical features, skeletal microstructure and parathyroid hormone replacement / Hipoparatiroidismo: aspectos clínicos, microestrutura esquelética e reposição do paratormônio

OBJECTIVE: Hypoparathyroidism is a disorder in which parathyroid hormone is deficient in the circulation due most often to immunological destruction of the parathyroids or to their surgical removal. The objective of this work was to define the abnormalities in skeletal microstructure as well as to establish the potential efficacy of PTH(1-84) replacement in this disorder. SUBJECTS AND METHODS: Standard histomorphometric and µCT analyses were performed on iliac crest bone biopsies obtained from patients with hypoparathyroidism. Participants were treated with PTH(1-84) for two years. RESULTS: Bone density was increased and skeletal features reflected the low turnover state with greater BV/TV, Tb. Wi and Ct. Wi as well as suppressed MS and BFR/BS as compared to controls. With PTH(1-84), bone turnover and bone mineral density increased in the lumbar spine. Requirements for calcium and vitamin D fell while serum and urinary calcium concentrations did not change. CONCLUSION: Abnormal microstructure of the skeleton in hypoparathyroidism reflects the absence of PTH. Replacement therapy with PTH has the potential to correct these abnormalities as well as to reduce the requirements for calcium and vitamin D.

OBJETIVO: O hipoparatiroidismo é uma doença em que há diminuição dos níveis circulantes do paratormônio, em geral, causada por destruição autoimune ou exerese cirúrgica. O objetivo deste estudo foi descrever as anormalidades microestrutrurais esqueléticas, como também o potencial terapêutico do uso do PTH(1-84). SUJEITOS E MÉTODOS: Histomorfometria padrão e análise de micro-CT foram realizadas em biópsias de crista ilíaca de indivíduos com hipoparatiroidismo. Os participantes foram tratados com PTH(1-84) por dois anos. RESULTADOS: A densidade óssea aumentou e os achados esqueléticos refletiram o estado de baixa remodelação óssea com maior BV/TV, Tb Wi e CT Wi, como também supressão de MS e BFR/BS quando comparado com o grupo controle. Com o uso de PTH(1-84), a remodelação óssea aumentou e a densidade óssea aumentou na coluna lombar. As necessidades de cálcio e vitamina D diminuíram e a calciúria não mudou. CONCLUSÃO: A microestrutura esquelética anormal no hipoparatiroidismo reflete a ausência do PTH. A terapia de reposição com PTH tem o potencial de reverter essas anormalidades, como também reduzir as necessidades de cálcio e vitamina D.

Miocardiopatía por hipocalcemia / Hypocalcemic cardiomyopathy

Se presenta el caso de un varón de 56 años, portador de Miocardiopatía dilatada, considerada, en algún momento, como terminal. Se comprobó que presentaba de base una hipocalcemia crónica secundaria a hipoparatiroidismo. Se discute su notable respuesta a administración de calcio e infusión de levosimendan IV fármaco inotropo positivo que actúa sensibilizando al calcio.

Hypoparathyroidism and pseudohypoparathyroidism / Hipoparatiroidismo e pseudohipoparatiroidismo

The principal function of the parathyroid hormone (PTH) is maintenance of calcium plasmatic levels, withdrawing the calcium from bone tissue, reabsorbing it from the glomerular filtrate, and indirectly increasing its intestinal absorption by stimulating active vitamin D (calcitriol) production. Additionally, the PTH prompts an increase in urinary excretion of phosphorus and bicarbonate, seeking a larger quantity of free calcium available in circulation. Two mechanisms may alter its function, limiting its control on calcium: insufficient PTH production by the parathyroids (hypoparathyroidism), or a resistance against its action in target tissues (pseudohypoparathyroidism). In both cases, there are significantly reduced levels of plasmatic calcium associated with hyperphosphatemia. Clinical cases are characterized by nervous hyperexcitability, with paresthesia, cramps, tetany, hyperreflexia, convulsions, and tetanic crisis. Abnormalities such as cataracts and basal ganglia calcification are also typical of these diseases. Treatment consists of oral calcium supplementation associated with increased doses of vitamin D derivatives.

A principal função do paratormônio (PTH) é a manutenção dos níveis plasmáticos de cálcio, retirando-o do tecido ósseo, reabsorvendo-o do filtrado glomerular e, indiretamente, aumentando sua absorção intestinal através do estímulo para a produção de vitamina D ativa (calcitriol). Além disso, o PTH promove um aumento na excreção urinária de fósforo e bicarbonato, objetivando uma maior quantidade de cálcio livre disponível na circulação. Dois mecanismos podem alterar sua função, limitando seu controle sobre o cálcio: produção insuficiente de PTH pelas paratiróides (hipoparatiroidismo), ou uma resistência à sua ação nos órgãos-alvo (pseudohipoparatiroidismo). Em ambos os casos, ocorre uma redução significativa dos níveis plasmáticos de cálcio em associação com hiperfosfatemia. Manifestações clínicas características são: hiperexcitabilidade nervosa, com parestesia, cãimbras, tetania, hiperreflexia, convulsões e crise tetânica. Catarata e calcificação dos gânglios basais são anormalidades típicas dessas doenças. O tratamento consiste da suplementação oral de cálcio, associada com doses elevadas de derivados da vitamina D.

Extracellular calcium-sensing receptor: structural and functional features and association with diseases

The recently cloned extracellular calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays an essential role in the regulation of extracellular calcium homeostasis. This receptor is expressed in all tissues related to this control (parathyroid glands, thyroid C-cells, kidneys, intestine and bones) and also in tissues with apparently no role in the maintenance of extracellular calcium levels, such as brain, skin and pancreas. The CaR amino acid sequence is compatible with three major domains: a long and hydrophilic aminoterminal extracellular domain, where most of the activating and inactivating mutations described to date are located and where the dimerization process occurs, and the agonist-binding site is located, a hydrophobic transmembrane domain involved in the signal transduction mechanism from the extracellular domain to its respective G protein, and a carboxyterminal intracellular tail, with a well-established role for cell surface CaR expression and for signal transduction. CaR cloning was immediately followed by the association of genetic human diseases with inactivating and activating CaR mutations: familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism are caused by CaR-inactivating mutations, whereas autosomal dominant hypoparathyroidism is secondary to CaR-activating mutations. Finally, we will comment on the development of drugs that modulate CaR function by either activating (calcimimetic drugs) or antagonizing it (calcilytic drugs), and on their potential therapeutic implications, such as medical control of specific cases of primary and uremic hyperparathyroidism with calcimimetic drugs and a potential treatment for osteoporosis with a calcilytic drug

Pseudohipoparatiroidismo Tipo I

El pseudohipoparatiroidismo es una entidad infrecuente y heterogénea causada por la pérdida heterocigótica de aproximadamente el 50 por ciento de la proteína Gs alfa, caracterizada por losvalores séricos de calcio bajos, grados de fosfatemia variable elevada y resistencia variable de la PTH, con hallazgos clínicos dismórficos y en algunos casos (tipo I) asociado a retardo mental. La alteración descrita es el resultado de la disfunción de la proteína Gs alfa miembro de la superfamilia de proteínas heterotriméricas transductoras de señales intracelulares estimuladoras de la adenil ciclasa intracelular. Se revisan dos casos con el tipo pseudohipo-hiperparatiroidismo y uno de tipo I.

Ensayo terapéutico con 1-25 dihidroxicolecalciferol en el hipoparatiroidismo posquirúrgico / Therapeutical assay with 1-25 dihydroxycholecalciferol in postsurgical hypoparathyroidism

Se presentan los resultados preliminares del empleo (no reportado) del 1-25 dihidroxicolecalciferol como coadyuvante en el tratamiento de hipoparatiroidismo posquirúrgico. En los seis pacientes estudiados se logró restaurar los niveles séricos de calcio (1,85 pre vs 2,25 nmol/L postratamiento) con disminución de la calciuria. Ningún caso mostró reacción adversa al medicamento, aunque en uno hubo manifestaciones clínicas de hipercalemia. Se sugiere emplear el medicamento en aquellos pacientes en los que la terapéutica convencional no sea eficaz