RESUMO
We describe a unique case of 27-year-old male with Gitelman syndrome (GS) co-exist with pseudohypoparathyroidism type 1B (PHP1B). The patient presented with a 5-year history of seizures, tetany, and numbness of the extremities. Further examinations showed recurrent hypokalemia, inappropriate kaliuresis, hypocalcemia, hyperphosphatemia, and elevated PTH levels. A novel variant of autosomal recessive GS (p.Val287Met SLC12A3) and a novel 492.3Kb deletion containing the whole of STX16, were discovered by a whole-exome sequencing. Following the diagnosis, calcitriol, calcium, and potassium supplements were started. Hematuria calcium and phosphorus levels, as well as blood potassium levels, have recovered and remained within normal ranges after 3 years of follow-up. Our findings have important consequences for supporting the idea that heterozygosity for variants have effects on the patients' clinical performance with autosomal recessive inheritance disorders. Further study is need for the putative effects of the variant. Likewise, further investigation with regards to the gene-gene interaction relations between GS and other electrolyte imbalance disorders is warranted.
Assuntos
Síndrome de Gitelman , Hipopotassemia , Pseudo-Hipoparatireoidismo , Desequilíbrio Hidroeletrolítico , Masculino , Humanos , Adulto , Síndrome de Gitelman/complicações , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/genética , Hipopotassemia/complicações , Cálcio , Membro 3 da Família 12 de Carreador de Soluto/genética , Pseudo-Hipoparatireoidismo/complicações , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/genética , Convulsões/etiologia , Convulsões/genética , Desequilíbrio Hidroeletrolítico/complicações , Cálcio da Dieta , Epigênese Genética , PotássioRESUMO
We report a 15-year-old Chinese girl who presented with intermittent seizure episodes and had been misdiagnosed as having idiopathic epilepsy 5 years previously. Laboratory testing revealed hypocalcemia, hyperphosphatemia, and a high parathyroid hormone (PTH) concentration. She was subsequently shown to have pseudohypoparathyroidism type Ib (PHPIb) based on the results of methylation analysis of the GNAS gene, which showed a loss of methylation of the differentially methylated regions (DMR) of GNAS-AS1, GNAS-XL, and GNAS-A/B; and a gain of methylation of the DMR of the GNAS-NESP55 region. We adjusted the patient's medication by prescribing calcium and calcitriol supplements, and gradually reduced the doses of antiepileptic drugs, until they had been completely discontinued. As a result, the patient did not experience any further seizures or epileptiform symptoms; and had normal plasma calcium, phosphorus, and 25-hydroxyvitamin D concentrations and 24-hour urinary calcium excretion. In addition, her PTH concentration gradually normalized over 12 months, and no urinary stones were found on ultrasonographic examination. In conclusion, the clinical presentation of PHP is complex, and the condition is often misdiagnosed. The diagnosis and follow-up of the present patient have provide valuable insights that should contribute to informed clinical decision-making and the implementation of appropriate treatment strategies.
Assuntos
Epilepsia , Pseudo-Hipoparatireoidismo , Humanos , Feminino , Adolescente , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Metilação de DNA , Cálcio , Seguimentos , Cromograninas/genética , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/genética , Hormônio Paratireóideo , Epilepsia/genética , Erros de DiagnósticoRESUMO
BACKGROUND AND OBJECTIVE: Parathyroid hormone (PTH) resistance, the main biochemical feature of a rare group of disorders known as Pseudohypoparathyroidism (PHP) is an uncommon cause of hypocalcaemia. In addition to the biochemical abnormalities, some individuals with PHP may have features of Albright Hereditary Osteodystrophy (AHO). Being a rare disorder with a significant level of variation and overlap in its clinical presentation, diagnosis of PHP may be challenging in some clinical settings. This case report highlights the diagnosis of this rare disorder. CASE REPORT: A 20-year-old Ghanaian female who had been involved in a road traffic accident (RTA) was referred to the endocrine clinic after a computer tomography (CT) scan of her head revealed an incidental finding of multiple basal ganglia calcifications. Investigations revealed hypocalcaemia, hyperphosphatemia, and elevated intact PTH in the presence of normal levels of 25-hydroxyvitamin D and magnesium, and a normal kidney function. She also had phenotypic features of AHO. Findings suggested a diagnosis of PHP, however, the type could not be identified due to the unavailability of further testing. CONCLUSION: This report of a Ghanaian female with PTH resistance and features of AHO diagnosed at the age of 20 years, is expected to add to the existing literature and assist in increasing the level of awareness and facilitate the diagnosis of this disorder in our setting.
CONTEXTE ET OBJECTIF: La résistance à l'hormone parathyroïdienne (PTH), principale caractéristique biochimique d'un groupe rare de troubles connus sous le nom de pseudohypoparathyroïdie (PHP), est une cause rare d'hypocalcémie. En plus des anomalies biochimiques, certaines personnes atteintes de PHP peuvent présenter des caractéristiques d'ostéodystrophie héréditaire d'Albright (AHO). Étant un trouble rare avec un niveau significatif de variation et de chevauchement dans sa présentation clinique, le diagnostic de PHP peut être difficile dans certains contextes cliniques. Ce rapport de cas met en lumière le diagnostic de cette maladie rare. RAPPORT DE CAS: Une femme ghanéenne de 20 ans qui avait été impliquée dans un accident de la circulation routière (RTA) a été référée à la clinique endocrinienne après qu'une tomodensitométrie (TDM) de sa tête a révélé la découverte fortuite de multiples calcifications des ganglions de la base. Les examens ont révélé une hypocalcémie, une hyperphosphatémie et une PTH intacte élevée en présence de taux normaux de 25 hydroxyvitamine D et de magnésium et d'une fonction rénale normale. Elle avait également des caractéristiques phénotypiques d'AHO. La découverte a suggéré un diagnostic de PHP, mais le type n'a pas pu être identifié en raison de l'indisponibilité de tests supplémentaires. CONCLUSION: Ce rapport d'une femme ghanéenne présentant une résistance à la PTH et des caractéristiques d'AHO diagnostiquée à l'âge de 20 ans, devrait s'ajouter à la littérature existante et aider à accroître le niveau de sensibilisation et à faciliter le diagnostic de ce trouble dans notre contexte. Mots-clés: Hypocalcémie, Hormone parathyroïdienne, Ghana.
Assuntos
Hipocalcemia , Pseudo-Hipoparatireoidismo , Feminino , Humanos , Adulto Jovem , Gana , Hipocalcemia/diagnóstico , Hipocalcemia/etiologia , Hormônio Paratireóideo , Pseudo-Hipoparatireoidismo/diagnósticoRESUMO
Objective: The serum calcium (Ca)-to-phosphorus (P) ratio has been proposed to identify patients with primary hyperparathyroidism and chronic hypoparathyroidism (HPT), but it has never been tested in pseudohypoparathyroidism (PHP). The aim of this study was to test the performance of Ca/P ratio in PHP diagnosis compared with that in healthy subjects and patients with HPT for differential diagnosis. Design: A retrospective, cross-sectional, and observational study was carried out. Methods: Serum Ca, P, creatinine, parathyroid hormone (PTH), and albumin were collected. Ca and P were expressed in mmol/L. Ca/P diagnostic performance was evaluated by receiver operating characteristic curve, sensitivity, specificity, and accuracy. Results: A total of 60 patients with PHP, 60 patients with HPT, and 120 controls were enrolled. The Ca/P ratio was lower in patients with PHP and HPT than that in controls (p < 0.0001). The cutoff of 1.78 (2.32 if Ca and P measured in mg/dL) for Ca/P ratio could identify patients with PHP and HPT among the entire cohort (sensitivity and specificity of 76%). No valid cutoff of Ca/P was found to distinguish patients with PHP from patients with HPT; in this case, PTH above 53.0 ng/dL identified patients with PHP (sensitivity and specificity of 100%). The index (Ca/P × PTH) above 116 ng/L recognized patients with PHP from controls (sensitivity of 84.7% and specificity of 87.4%), whereas (Ca/P × PTH) below 34 ng/L recognized patients with HPT from controls (sensitivity of 88.9% and specificity of 90.8%). Conclusions: The Ca/P ratio below 1.78 (2.32 CU) is highly accurate to identify patients with PHP and HPT, although it is not reliable to differentiate these two conditions. The index (Ca/P × PTH) is excellent to specifically recognize PHP or HPT from healthy subjects.
Assuntos
Hipoparatireoidismo , Pseudo-Hipoparatireoidismo , Humanos , Cálcio , Estudos Retrospectivos , Estudos Transversais , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/metabolismo , Hormônio Paratireóideo , FósforoRESUMO
Pseudohypoparathyroidism (PHP) is a spectrum of diseases characterized by insensitivity of target tissues to the action of parathyroid hormone and, consequently, by the presence of hyperphosphatemia and hypocalcaemia of varying severity. Early-onset obesity is a feature of PHP type 1A. This article discusses the need to establish uniform criteria to guide the nutritional management of patients with PHP. A decrease in energy expenditure calls for an adjustment of the energy content of the diet. Reducing the intake of foods rich in inorganic phosphorus helps to manage hyperphosphataemia. Targeted nutrition should be part of the treatment plan of children and adolescents with PHP, since it contributes to modulating the calcium and phosphorus metabolism imbalances characteristic of these patients.
Assuntos
Pseudo-Hipoparatireoidismo , Adolescente , Criança , Humanos , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/terapia , Hormônio Paratireóideo , Estado Nutricional , FósforoRESUMO
BACKGROUND: Pseudohypoparathyroidism (PHP) encompasses a highly heterogenous group of disorders, characterized by parathyroid hormone (PTH) resistance caused by mutations in the GNAS gene or other upstream targets. Here, we investigate the characteristics of a female patient diagnosed with PHP complicated with hypokalemia, and her family members. CASE PRESENTATION AND GENE ANALYSIS: A 27-year-old female patient occasionally exhibited asymptomatic hypocalcemia and hypokalemia during her pregnancy 1 year ago. Seven months after delivery, she experienced tetany and dysphonia with diarrhea. Tetany symptoms were relieved after intravenous calcium gluconate supplementation and she was then transferred to our Hospital. Laboratory assessments of the patient revealed hypokalemia, hypocalcemia and hyperphosphatemia despite elevated PTH levels. CT scanning of the brain revealed globus pallidus calcification. Possible mutations in GNAS and hypokalemia related genes were identified using WES, exon copies of STX16 were analized by MLPA and the methylation status of GNAS in three differential methylated regions (DMRs) was analyzed by methylation-specific polymerase chain reaction, followed by confirmation with gene sequencing. The patient was clinically diagnosed with PHP-1b. Loss of methylation in the A/B region and hypermethylation in the NESP55 region were detected. No other mutations in GNAS or hypokalemia related genes and no deletions of STX16 exons were detected. A negative family history and abnormal DMRs in GNAS led to a diagnosis of sporadic PHP-1b of the patient. CONCLUSIONS: Hypokalemia is a rare disorder associated with PHP-1b. Analysis of genetic and epigenetic mutations can aid in the diagnosis and accurate subtyping of PHP.
Assuntos
Hipocalcemia , Hipopotassemia , Pseudo-Hipoparatireoidismo , Tetania , Adulto , Cromograninas/genética , Feminino , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Hipocalcemia/genética , Hipopotassemia/genética , Pseudo-Hipoparatireoidismo/complicações , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/genéticaRESUMO
SUMMARY Pseudohypoparathyroidism comprehends an assorted group of genetically rare disorders that share end-organ resistance to parathyroid hormone. Genetic and epigenetic modifications on guanine nucleotide-binding protein alpha-stimulating gene locus are the most common underlying mechanisms associated with pseudohypoparathyroidism. Biochemical and molecular analysis stratify pseudohypoparathyroidism into types 1A, 1B, 1C, and 2. We describe an unusual case of sporadic pseudohypoparathyroidism type 1B. A 34-year-old Caucasian woman was admitted to the emergency department, with persistent asthenia, limb paresthesias, and tactile hyposensitivity. Her physical examination, previous personal and family histories were unsuspicious, except for mild, intermittent and self-limited complaints of paresthesia during her two pregnancies, but no detailed workup was done. No typical features of Albright hereditary osteodystrophy were observed. The initial laboratory investigation showed elevated parathyroid hormone level (311.2 pg/mL), hypocalcemia (albumin-corrected serum calcium 4.3 mg/dL), hypocalciuria, hyperphosphatemia, hypophosphaturia, and vitamin D deficiency. Combined calcium, vitamin D, and magnesium supplementation was commenced, with symptomatic and analytical improvement. Albeit resolution of vitamin D deficiency, the patient relapsed with mild and intermittent lower limb paresthesias. Pseudohypoparathyroidism was confirmed by molecular identification of the 3-kb STX16 deletion. The treatment was readjusted, and one year later, symptomatic remission was attained. Clinical and biochemical features, and their respective course, along with lack of distinctive features of Albright hereditary osteodystrophy pointed to pseudohypoparathyroidism type 1B. A careful follow-up is needed to avoid complications and recurrence. Once correction of hypocalcemia and hyperphosphatemia is achieved, with no reported complications and recurrence, a good prognosis is anticipated, comparable to the general population.
Assuntos
Humanos , Feminino , Pseudo-Hipoparatireoidismo , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/genética , Deficiência de Vitamina D , Hipocalcemia , Hipocalcemia/genética , Hormônio ParatireóideoRESUMO
Pseudohypoparathyroidism comprehends an assorted group of genetically rare disorders that share end-organ resistance to parathyroid hormone. Genetic and epigenetic modifications on guanine nucleotide-binding protein alpha-stimulating gene locus are the most common underlying mechanisms associated with pseudohypoparathyroidism. Biochemical and molecular analysis stratify pseudohypoparathyroidism into types 1A, 1B, 1C, and 2. We describe an unusual case of sporadic pseudohypoparathyroidism type 1B. A 34-year-old Caucasian woman was admitted to the emergency department, with persistent asthenia, limb paresthesias, and tactile hyposensitivity. Her physical examination, previous personal and family histories were unsuspicious, except for mild, intermittent and self-limited complaints of paresthesia during her two pregnancies, but no detailed workup was done. No typical features of Albright hereditary osteodystrophy were observed. The initial laboratory investigation showed elevated parathyroid hormone level (311.2 pg/mL), hypocalcemia (albumin-corrected serum calcium 4.3 mg/dL), hypocalciuria, hyperphosphatemia, hypophosphaturia, and vitamin D deficiency. Combined calcium, vitamin D, and magnesium supplementation was commenced, with symptomatic and analytical improvement. Albeit resolution of vitamin D deficiency, the patient relapsed with mild and intermittent lower limb paresthesias. Pseudohypoparathyroidism was confirmed by molecular identification of the 3-kb STX16 deletion. The treatment was readjusted, and one year later, symptomatic remission was attained. Clinical and biochemical features, and their respective course, along with lack of distinctive features of Albright hereditary osteodystrophy pointed to pseudohypoparathyroidism type 1B. A careful follow-up is needed to avoid complications and recurrence. Once correction of hypocalcemia and hyperphosphatemia is achieved, with no reported complications and recurrence, a good prognosis is anticipated, comparable to the general population.
Assuntos
Hipocalcemia , Pseudo-Hipoparatireoidismo , Deficiência de Vitamina D , Adulto , Feminino , Humanos , Hipocalcemia/genética , Hormônio Paratireóideo , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/genética , Pseudo-HipoparatireoidismoRESUMO
BACKGROUND: Pseudohypoparathyroidism(PHP) is a heterogeneous group of disorders due to impaired activation of c AMP dependant pathways following binding of parathyroid hormone (PTH) to its receptor. In PHP end organ resistance to PTH results in hypocalcaemia, hyperphosphataemia and high PTH levels. CASE PRESENTATION: A 59 year old male presented with a history of progressive impairment of speech and unsteadiness of gait for 1 week and acute onset altered behavior for 1 day and one episode of generalized seizure. His muscle power was grade four according to MRC (medical research council) scale in all limbs and Chovstek's and Trousseau's signs were positive. Urgent non contrast computed tomography scan of the brain revealed extensive bilateral cerebral and cerebellar calcifications. A markedly low ionized calcium level of 0.5 mmol/l, an elevated phosphate level of 9.5 mg/dl (reference range: 2.7-4.5 mg/dl) and an elevated intact PTH of 76.3 pg/l were noted. His renal functions were normal. His hypocalcemia was accentuated by the presence of hypomagnesaemia. His 25 hydroxy vitamin D level was only marginally low which could not account for severe hypocalcaemia. A diagnosis of pseudohypoparathyroidism without phenotypic defects, was made due to hypocalcaemia and increased parathyroid hormone levels with cerebral calcifications. The patient was treated initially with parenteral calcium which was later converted to oral calcium supplements. His coexisting Vitamin D deficiency was corrected with 1αcholecalciferol escalating doses. His hypomagnesaemia was corrected with magnesium sulphate parenteral infusions initially and later with oral preparations. With treatment there was a significant clinical and biochemical response. CONCLUSION: Pseudohypoparathyroidism can present for the first time in elderly resulting in extensive cerebral calcifications. Identification and early correction of the deficit will result in both symptomatic and biochemical response.
Assuntos
Calcinose/etiologia , Pseudo-Hipoparatireoidismo/complicações , Doenças da Coluna Vertebral/etiologia , Calcinose/sangue , Calcinose/diagnóstico , Calcinose/tratamento farmacológico , Cálcio/administração & dosagem , Cálcio/sangue , Humanos , Deficiência de Magnésio/sangue , Deficiência de Magnésio/complicações , Deficiência de Magnésio/diagnóstico , Deficiência de Magnésio/tratamento farmacológico , Sulfato de Magnésio/administração & dosagem , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Pseudo-Hipoparatireoidismo/sangue , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/tratamento farmacológico , Doenças da Coluna Vertebral/sangue , Doenças da Coluna Vertebral/diagnóstico , Doenças da Coluna Vertebral/tratamento farmacológico , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/tratamento farmacológicoAssuntos
Doenças Ósseas Metabólicas/patologia , Calcitriol/administração & dosagem , Suplementos Nutricionais , Predisposição Genética para Doença , Ossificação Heterotópica/patologia , Pseudo-Hipoparatireoidismo/patologia , Dermatopatias Genéticas/patologia , Adolescente , Biópsia por Agulha , Doenças Ósseas Metabólicas/complicações , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/genética , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Ossificação Heterotópica/complicações , Ossificação Heterotópica/diagnóstico , Ossificação Heterotópica/genética , Dor/diagnóstico , Dor/etiologia , Pseudo-Hipoparatireoidismo/complicações , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/genética , Doenças Raras , Medição de Risco , Índice de Gravidade de Doença , Pele/patologia , Dermatopatias Genéticas/complicações , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/genéticaRESUMO
RATIONALE: It is rare to find 22q11.2 deletion syndrome with pseudohypoparathyroidism in children. Furthermore, the phenotypic spectrum of this disorder varies widely. PATIENT CONCERNS: A patient was diagnosed with pseudohypoparathyroidism at age 14 years because of convulsions, hypocalcemia, hyperphosphatemia, normal parathyroid hormone levels, and basal ganglia calcifications. Thereafter, the child presented with symptoms of nephrotic syndrome; subsequently, he was diagnosed with nephrotic syndrome at the local hospital. DIAGNOSIS: At our hospital, multiplex ligation-dependent probe amplification confirmed that the patient had 22q11.2 deletion syndrome. INTERVENTIONS: The patient continued to be treated with calcium supplements. OUTCOMES: Seizure activity and proteinuria ceased. LESSONS: Signs of this syndrome include delayed speech development due to velofacial dysfunction, recurrent croup attacks during early childhood due to latent hypocalcemia, and mild dysmorphic features. The findings of this patient indicated that 22q11.2 deletion syndrome may include a wide spectrum of clinical findings and that this diagnosis needs to be considered for all patients presenting with hypocalcemia, regardless of age.
Assuntos
Síndrome de DiGeorge/diagnóstico , Pseudo-Hipoparatireoidismo/diagnóstico , Adolescente , Síndrome de DiGeorge/genética , Humanos , Hiperfosfatemia/etiologia , Hipocalcemia/etiologia , Masculino , Reação em Cadeia da Polimerase Multiplex/métodos , Pseudo-Hipoparatireoidismo/complicações , Pseudo-Hipoparatireoidismo/genética , Convulsões/etiologiaAssuntos
Obstrução das Vias Respiratórias/psicologia , Deglutição , Medo , Hipocalcemia/diagnóstico , Pseudo-Hipoparatireoidismo/diagnóstico , Adolescente , Cálcio/uso terapêutico , Metilação de DNA , Diagnóstico Diferencial , Humanos , Hipocalcemia/tratamento farmacológico , Hipocalcemia/etiologia , Masculino , Fósforo/sangue , Pseudo-Hipoparatireoidismo/complicações , Pseudo-Hipoparatireoidismo/genética , Pseudo-Hipoparatireoidismo/psicologia , Tireotropina/sangue , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Pseudo-HipoparatireoidismoRESUMO
BACKGROUND: In patients with pseudohypoparathyroidism type 1b (PHP1b) due to a tissue-specific imprinting defect in the G-protein α-subunit, skeletal disorders can arise from the bones being sensitive to parathyroid hormone (PTH) while the kidneys remain resistant to this hormone. CASE-DIAGNOSIS/TREATMENT: We report a 4.8-year-old girl with PHP1b who presented with an abnormal gait, severe skeletal changes and elevated levels of serum PTH (2844 pg/ml), phosphate (7.2 mg/dl) and bone turnover markers. Traditional treatment with calcium and calcitriol failed to suppress PTH secretion, which was still elevated at 2877 pg/ml after 14 months of therapy, nor did it correct the other clinical, biochemical and radiographic abnormalities. The addition of cinacalcet to the treatment regimen over the subsequent 32 months resulted in normalization of serum PTH (58 ng/ml), phosphate (4.9 mg/dl) and bone turnover markers, and resolution of the radiographic changes, with no adverse effects noted. CONCLUSIONS: Due to its ease of administration, we recommend the addition of cinacalcet into the armamentarium of medications available to treat children with PHP1b.
Assuntos
Remodelação Óssea/efeitos dos fármacos , Calcimiméticos/uso terapêutico , Cinacalcete/uso terapêutico , Pseudo-Hipoparatireoidismo/tratamento farmacológico , Biomarcadores/sangue , Calcitriol/uso terapêutico , Cálcio/sangue , Cálcio/uso terapêutico , Pré-Escolar , Cromograninas/genética , Metilação de DNA , Suplementos Nutricionais , Éxons , Feminino , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Predisposição Genética para Doença , Humanos , Hormônio Paratireóideo/sangue , Fenótipo , Fosfatos/sangue , Pseudo-Hipoparatireoidismo/sangue , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/genética , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Pseudo-HipoparatireoidismoRESUMO
OBJECTIVE: To report the case of an individual with PHP, Turner syndrome and Hashimoto's thyroiditis. CASE: A 16-year-old girl was referred to our hospital with chief complaint of short stature. She presented with round chubby facies, short neck, obesity and short stature. Radiography indicated short metatarsals and metacarpals, which mainly affected the second, third and fourth digits. Biochemistry revealed hyperphosphatemia, increased serum concentrations of parathyroid hormone and thyroid stimulating hormone, elevated levels of follicular-stimulating hormone and prolactin, and increased thyroid peroxidase antibody and thyroglobulin antibody. Radiographic examination revealed delayed bone age and pelvic ultrasonography demonstrated an immature uterus. Karyotype analysis showed 46,X,i(Xq10), while molecular analysis revealed a same sense mutation in exon 5 of GNAS (ATC â ATT, Ile).The specific diagnosis was made of Turner syndrome in the presence of Hashimoto's thyroiditis and PHP. She was treated with calcium supplementation, calcitriol and thyroxine. CONCLUSIONS: This is the first case report to describe a combination of Turner syndrome with these other clinical entities, and their co-existence should be considered and further investigated.
Assuntos
Doença de Hashimoto/diagnóstico , Pseudo-Hipoparatireoidismo/diagnóstico , Síndrome de Turner/diagnóstico , Adolescente , Comorbidade , Feminino , Doença de Hashimoto/epidemiologia , Humanos , Pseudo-Hipoparatireoidismo/epidemiologia , Síndrome de Turner/epidemiologiaRESUMO
We report on an infant presenting with acute cardiogenic shock. She was eventually diagnosed with pseudohypoparathyroidism, which is a heterogeneous group of disorders characterized by severe hypocalcemia, hyperphosphatemia, and increased parathyroid hormone. The patient responded dramatically to calcium and vitamin D supplementation; left ventricular systolic function was normalized within days of treatment. Although the diagnosis of pseudohypoparathyroidism is rare, this case is a reminder of the importance of obtaining calcium levels in patients presenting in acute cardiogenic shock.
Assuntos
Insuficiência Cardíaca/etiologia , Pseudo-Hipoparatireoidismo/complicações , Choque Cardiogênico/etiologia , Calcitriol/uso terapêutico , Cálcio/sangue , Gluconato de Cálcio/uso terapêutico , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/etiologia , Cardiotônicos/uso terapêutico , Terapia Combinada , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/terapia , Humanos , Hipocalcemia/tratamento farmacológico , Hipocalcemia/etiologia , Lactente , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Pseudo-Hipoparatireoidismo/sangue , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/tratamento farmacológico , Indução de Remissão , Respiração Artificial , Choque Cardiogênico/sangue , Choque Cardiogênico/terapia , Disfunção Ventricular Esquerda/etiologiaRESUMO
OBJECTIVE: To analyze the clinical characteristics, diagnosis and treatment of pseudohypoparathyroidism (PHP). METHODS: The clinical data of 15 patients with pseudohypoparathyroidism (including 9 male and 6 female patients) admitted in our hospital between January, 1990 and July, 2011 were reviewed. RESULTS: The disease course of the patients ranged from 3 days to 21 years, and such symptoms of tetany and fatigue were found in all the patients. Most of the patients had a history of seizures. Laboratory tests suggested commonly low serum calcium, hyperphosphatemia, and parathyroid hormone (PTH) elevation. Head CT indicated multiple intracranial calcifications in 9 cases, and abnormal thyroid function was found in 4 cases. No specific treatment was available for this disease, and life-long calcium and vitamin D supplementation was advised to prevent acute attacks and disease progression. CONCLUSION: PHP is a rare genetic disease with a high rate of misdiagnosis in initial diagnosis. For repeated tetany and epileptic attacks and children with congenital developmental defects, examinations of blood calcium, phosphorus, and PTH and brain CT should be ordered as soon as possible. Long-term calcium and vitamin D supplementation is suggested for the treatment, and the presence of concomitant thyroid dysfunction or hypogonadism necessitates corresponding treatments.
Assuntos
Pseudo-Hipoparatireoidismo , Adolescente , Adulto , Criança , Erros de Diagnóstico , Feminino , Humanos , Masculino , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/fisiopatologia , Pseudo-Hipoparatireoidismo/terapia , Estudos Retrospectivos , Adulto JovemAssuntos
Doenças dos Gânglios da Base/diagnóstico , Calcinose/diagnóstico , Transtornos Cognitivos/etiologia , Disartria/etiologia , Pseudo-Hipoparatireoidismo/diagnóstico , Ataxia/diagnóstico , Ataxia/etiologia , Criança , Transtornos Cognitivos/diagnóstico , Diagnóstico Diferencial , Dominância Cerebral/fisiologia , Disartria/diagnóstico , Feminino , Humanos , Hipocalcemia/diagnóstico , Exame Neurológico , Hormônio Paratireóideo/sangue , Fonética , Fósforo/sangue , Síndrome , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The term hypoparathyroidism refers to a group of disorders in which a relative or absolute deficiency of PTH leads to hypocalcemia and hyperphosphatemia. THE AIM OF THE STUDY: Was to evaluate clinical symptoms in patients with hypoparathyroidism during normocalcemic period and to try to establish its etiology (electrolyte imbalance, organic central nervous system lesions, coincidence of tetany and epilepsy). MATERIAL AND METHODS: The analysis included a group of 14 patients with hypoparathyroidism: 3 boys and 11 girls, aged from 12 months to 31 years (median 16.11 years), with duration of the disease 12 months to 26 years (median 10.9 years). In all the patients, the diagnosis was confirmed based on history, physical examination, results of biochemical and hormonal laboratory tests, radiological and neurological examinations. All the patients were followed by endocrinology specialists. Low phosphorus diet, calcium, magnesium, active vitamin D supplementation and management of other endocrine disorders were employed. RESULTS: In 9 patients, pseudo-hypoparathyrodism was diagnosed; of this number, in 8 children, type Ia Albright syndrome was confirmed. Five patients were diagnosed as true hypoparathyroidism, two girls in this group were found to have autoimmune hypoparathyroidism as a component of the autoimmune polyglandular syndrome type 1, 2 others were diagnosed in infancy as congenital hypoparathyroidism and 1 girl had true hypoparathyroidism as a component of Kearns-Sayre syndrome. Five patients were referred to neurological department with epilepsy suspicion. In the medical history, 9 patients had generalized epileptic seizures, moreover, 1 girl manifested absence attack and balance disturbances. In 3 patients, EEG demonstrated changes typical of generalized seizure activity. In 5 patients on anti-epileptic management, additional calcium and active vitamin D treatment was initiated, allowing for achieving seizure remission. CT of the head and pituitary gland showed calcification foci in the central nervous system in 9 patients. Five patients of the eight individuals with Albright syndrome showed mild or moderate mental retardation confirmed by psychological testing. CONCLUSIONS: 1. Hypoparathyroidism leads to functional and morphological CNS changes. 2. Restoring metabolic balance through administration of calcium and active vitamin D preparations may obliterate the need for anti-epileptic treatment. 3. Calcification foci in the central nervous system seem to be associated with the duration of hypoparathyroidism. 4. No correlation has been observed between the extent and location of calcification foci and neurological abnormalities. 5. Hypoparathyroid patients with calcification foci in CSN require long-term multidisciplinary medical management and neurophysiological, imaging and neuropsychological monitoring.
Assuntos
Encefalopatias/etiologia , Calcinose/etiologia , Hipoparatireoidismo/complicações , Hipoparatireoidismo/diagnóstico , Adolescente , Adulto , Encefalopatias/diagnóstico , Cálcio/uso terapêutico , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Hipoparatireoidismo/tratamento farmacológico , Lactente , Masculino , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/etiologia , Vitamina D/uso terapêutico , Adulto JovemRESUMO
BACKGROUND/PURPOSE: Transient pseudohypoparathyroidism is a rare cause of late-onset hypocalcemia in neonates and infants. The purpose of this study was to investigate the clinical presentation and natural course of transient pseudohypoparathyroidism in neonates and infants. METHODS: From 1995 to 2006, 21 patients under 3 months of age were admitted to our department because of late-onset neonatal hypocalcemia. Among these, five were noted to have transient hypocalcemia, hyperphosphatemia and elevated serum parathyroid hormone levels. Their clinical data, biochemical findings and natural course were thoroughly analyzed. RESULTS: All five patients were boys with increased neuromuscular irritability as their initial clinical manifestation. Initial biochemical data showed calcium 1.5 +/- 0.16 mmol/L, phosphorus 9.6 +/- 1.5 mg/dL, intact parathyroid hormone 182 +/- 93 pg/mL and tubular reabsorption of phosphorus 94.8 +/- 3.7%. Two of the patients had magnesium deficiency. After reduction of phosphorus intake and supplementation with calcium and/or magnesium as indicated, the biochemical derangements resolved in 28 +/- 3 days. CONCLUSION: Neuromuscular irritability is usually the initial clinical presentation of transient pseudohypoparathyroidism. Aside from delayed renal maturation, pseudohypoparathyroidism is also caused by magnesium deficiency. Such a disturbance usually resolves before 3 months of age.
Assuntos
Hipocalcemia/etiologia , Pseudo-Hipoparatireoidismo/complicações , Pseudo-Hipoparatireoidismo/diagnóstico , Fatores Etários , Estudos de Coortes , Humanos , Hipocalcemia/diagnóstico , Hipocalcemia/terapia , Lactente , Recém-Nascido , Masculino , Pseudo-Hipoparatireoidismo/terapia , Estudos Retrospectivos , Fatores de RiscoRESUMO
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.