RESUMO
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) represents a heterogeneous group of rare endocrine disorders caused by (epi) genetic abnormalities affecting the GNAS locus. It is mainly characterized by resistance to PTH and TSH, and by peculiar clinical features such as short stature, obesity, cognitive impairment, subcutaneous ossifications and brachydactyly. Delayed puberty, GHRH and calcitonin resistances have also been described. The healthcare-pathway recently proposed by the Italian Society of Pediatric Endocrinology and Diabetology (ISPED) has provided a standardized clinical approach to these conditions. The purpose of the present study was to evaluate its application in clinical practice, and to collect data for setting future specific studies. METHODS: Through a semi-structured survey, based on the indications of the care-pathway, data on PHP clinical management were collected. The compilation of each data in the survey was read as an index of the adoption of the healthcare-pathway in clinical practice. RESULTS: In addition to the proposing Center, 4 Centers joined the study, thus obtaining a large collection of data on 48 PHP patients. Highest rates in the completion of data were obtained for diagnostic history, auxological measurements and subcutaneous ossifications evaluation. As expected, the availability of data for the other investigated fields was lower, coming from recent research studies. More information has been obtained on hormonal resistance classically involved in PHP (PTH, TSH, GHRH and GnRH) and on cognitive impairment, while a few data has been collected on bone mineral status, calcitonin levels and glucolipid metabolism. CONCLUSIONS: The presented data show that the ISPED healthcare-pathway could represent a valid tool both to confirm the clinical approach to PHP patients and to allow homogeneous data collection; however, it has not yet been fully adopted. The strengthening of the network among the major Italian Endocrine Centers will contribute to improve its application in clinical practice, optimizing the follow-up of these patients and increasing knowledge on PHP.
Assuntos
Procedimentos Clínicos , Padrões de Prática Médica/estatística & dados numéricos , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/terapia , Criança , Consenso , Feminino , Seguimentos , Humanos , Itália , Masculino , Pseudo-Hipoparatireoidismo/classificação , Inquéritos e QuestionáriosRESUMO
We describe symptomatic spinal cord compression associated with pseudohypoparathyroidism (PHP) in a young female patient and reviewed similar cases previously reported in the literature. The characteristics of these cases were analyzed from etiology, clinical subtypes, symptoms, treatment, and prognosis. Neurological examination revealed functional upper extremities with bilateral lower extremity paraplegia. Laboratory tests showed hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone; high-throughput sequencing showed a heterozygous GNAS mutation in exon 12, specifically c.1006C > T (p.R336W). Imaging findings showed multilevel spinal stenosis with significant spinal cord compression at the T2-T3 level. Seventeen cases with similar characteristics were reviewed. We found that the primary clinical manifestation of these patients was bilateral lower extremity spastic paraplegia. Multilevel spinal cord compression was commonly observed, especially at the lower cervical and upper thoracic spinal cord. Most of the patients had poor surgical treatment outcome and prognosis. Clinicians should be aware of paraplegia due to spinal cord compression as a rare neurological complication in patients with PHP. Early diagnosis and treatment of PHP is one basis for preventing severe spinal cord-related complications.
Assuntos
Pseudo-Hipoparatireoidismo/complicações , Pseudo-Hipoparatireoidismo/diagnóstico , Compressão da Medula Espinal/complicações , Compressão da Medula Espinal/diagnóstico , Alelos , Biomarcadores , Cromograninas/genética , Análise Mutacional de DNA , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Heterozigoto , Humanos , Imageamento por Ressonância Magnética , Mutação , Pseudo-Hipoparatireoidismo/etiologia , Pseudo-Hipoparatireoidismo/terapia , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/terapia , Avaliação de SintomasRESUMO
BACKGROUND: Acroscyphodysplasia has been described as a phenotypic variant of acrodysostosis type 2 and pseudohypoparathyroidism. In acrodysostosis, skeletal features can include brachydactyly, facial hypoplasia, cone-shaped epiphyses, short stature, and advanced bone age. To date, reports on this disorder have focused on phenotypic findings, endocrine changes, and genetic variation. We present a 14-year overview of a patient, from birth to skeletal maturity, with acroscyphodysplasia, noting the significant orthopaedic challenges and the need for a multidisciplinary team, including specialists in genetics, orthopaedics, endocrinology, and otolaryngology, to optimize long-term outcomes. CASE PRESENTATION: The patient presented as a newborn with dysmorphic facial features, including severe midface hypoplasia, malar flattening, nasal stenosis, and feeding difficulties. Radiologic findings were initially subtle, and a skeletal survey performed at age 7 months was initially considered normal. Genetic evaluation revealed a variant in PDE4D and subsequent pseudohypoparathyroidism. The patient presented to the department of orthopaedics, at age 2 years 9 months with a leg length discrepancy, right knee contracture, and severely crouched gait. Radiographs demonstrated cone-shaped epiphyses of the right distal femur and proximal tibia, but no evidence of growth plate changes in the left leg. The child developed early posterior epiphyseal arrest on the right side and required multiple surgical interventions to achieve neutral extension. Her left distal femur developed late posterior physeal arrest and secondary contracture without evidence of schypho deformity, which improved with anterior screw epiphysiodesis. The child required numerous orthopaedic surgical interventions to achieve full knee extension bilaterally. At age 13 years 11 months, she was an independent ambulator with erect posture. The child underwent numerous otolaryngology procedures and will require significant ongoing care. She has moderate intellectual disability. DISCUSSION AND CONCLUSIONS: Key challenges in the management of this case included the subtle changes on initial skeletal survey and the marked asymmetry of her deformity. While cone-shaped epiphyses are a hallmark of acrodysostosis, posterior tethering/growth arrest of the posterior distal femur has not been previously reported. Correction of the secondary knee contracture was essential to improve ambulation. Children with acroscyphodysplasia require a multidisciplinary approach, including radiology, genetics, orthopaedics, otolaryngology, and endocrinology specialties.
Assuntos
Disostoses/terapia , Deficiência Intelectual/terapia , Comunicação Interdisciplinar , Osteocondrodisplasias/terapia , Equipe de Assistência ao Paciente , Pseudo-Hipoparatireoidismo/terapia , Osso e Ossos/anormalidades , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Disostoses/diagnóstico , Disostoses/genética , Seguimentos , Predisposição Genética para Doença/genética , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/genética , Radiografia/métodos , Fatores de TempoRESUMO
Patients affected by pseudohypoparathyroidism (PHP) or related disorders are characterized by physical findings that may include brachydactyly, a short stature, a stocky build, early-onset obesity, ectopic ossifications, and neurodevelopmental deficits, as well as hormonal resistance most prominently to parathyroid hormone (PTH). In addition to these alterations, patients may develop other hormonal resistances, leading to overt or subclinical hypothyroidism, hypogonadism and growth hormone (GH) deficiency, impaired growth without measurable evidence for hormonal abnormalities, type 2 diabetes, and skeletal issues with potentially severe limitation of mobility. PHP and related disorders are primarily clinical diagnoses. Given the variability of the clinical, radiological, and biochemical presentation, establishment of the molecular diagnosis is of critical importance for patients. It facilitates management, including prevention of complications, screening and treatment of endocrine deficits, supportive measures, and appropriate genetic counselling. Based on the first international consensus statement for these disorders, this article provides an updated and ready-to-use tool to help physicians and patients outlining relevant interventions and their timing. A life-long coordinated and multidisciplinary approach is recommended, starting as far as possible in early infancy and continuing throughout adulthood with an appropriate and timely transition from pediatric to adult care.
Assuntos
Diabetes Mellitus Tipo 2 , Nanismo Hipofisário , Hipotireoidismo , Pseudo-Hipoparatireoidismo , Transição para Assistência do Adulto , Adulto , Criança , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Nanismo Hipofisário/diagnóstico , Nanismo Hipofisário/terapia , Humanos , Hipotireoidismo/diagnóstico , Hipotireoidismo/terapia , Guias de Prática Clínica como Assunto , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/terapiaAssuntos
Humanos , Lactente , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/genética , Pseudo-Hipoparatireoidismo/terapia , Displasia Fibrosa Poliostótica/complicações , Displasia Fibrosa Poliostótica/diagnóstico , Displasia Fibrosa Poliostótica/terapia , Diagnóstico Diferencial , Obesidade Infantil/etiologia , Hipocalcemia/etiologiaRESUMO
Hypocalcemia is a potentially fatal electrolyte imbalance with complications that include seizures, tetany, prolonged QT interval, cardiomyopathy, and congestive heart failure. In chi dren, persistent hypocalcemia can also be detrimental to bone growth and health. Therefore, it is important to recognize the many ways this electrolyte imbalance may present and determine its etiology. This article provides a framework for assessing hypocalcemia and describes in detail a case with a rare cause of refractory hypocalcemia. [Pediatr Ann. 2019;48(5):e208-e211.].
Assuntos
Hipocalcemia , Criança , Feminino , Humanos , Hipocalcemia/diagnóstico , Hipocalcemia/etiologia , Hipocalcemia/terapia , Pseudo-Hipoparatireoidismo/complicações , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/terapiaRESUMO
Pseudohypoparathyroidism (PHP), pseudo-PHP, acrodysostosis, and progressive osseous heteroplasia are heterogeneous disorders characterized by physical findings, differently associated in each subtype, including short bones, short stature, a stocky build, ectopic ossifications (features associated with Albright's hereditary osteodystrophy), as well as laboratory abnormalities consistent with hormone resistance, such as hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH) and thyroid-stimulating hormone levels. All these disorders are caused by impairments in the cAMP-mediated signal transduction pathway and, in particular, in the PTH/PTHrP signaling pathway: the main subtypes of PHP and related disorders are caused by de novo or autosomal dominantly inherited inactivating genetic mutations, and/or epigenetic, sporadic, or genetic-based alterations within or upstream of GNAS, PRKAR1A, PDE4D, and PDE3A. Here we will review the impressive progress that has been made over the past 30 years on the pathophysiology of these diseases and will describe the recently proposed novel nomenclature and classification. The new term "inactivating PTH/PTHrP signaling disorder," iPPSD: (1) defines the common mechanism responsible for all diseases, (2) does not require a confirmed genetic defect, (3) avoids ambiguous terms like "pseudo," and (4) eliminates the clinical or molecular overlap between diseases.
Assuntos
Doenças Ósseas Metabólicas , Disostoses , Deficiência Intelectual , Ossificação Heterotópica , Osteocondrodisplasias , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Hormônio Paratireóideo/metabolismo , Pseudo-Hipoparatireoidismo , Transdução de Sinais/fisiologia , Dermatopatias Genéticas , Doenças Ósseas Metabólicas/classificação , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/metabolismo , Doenças Ósseas Metabólicas/terapia , Disostoses/classificação , Disostoses/diagnóstico , Disostoses/metabolismo , Disostoses/terapia , Humanos , Deficiência Intelectual/classificação , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/metabolismo , Deficiência Intelectual/terapia , Ossificação Heterotópica/classificação , Ossificação Heterotópica/diagnóstico , Ossificação Heterotópica/metabolismo , Ossificação Heterotópica/terapia , Osteocondrodisplasias/classificação , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/metabolismo , Osteocondrodisplasias/terapia , Pseudo-Hipoparatireoidismo/classificação , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/metabolismo , Pseudo-Hipoparatireoidismo/terapia , Dermatopatias Genéticas/classificação , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/metabolismo , Dermatopatias Genéticas/terapiaRESUMO
Since Albright and co-workers described pseudohypoparathyroidism in 1942 as the combined presence of hypocalcaemia and hyperphosphataemia associated with the existence of tissue resistance to parathyroid hormone (PTH) action upon normal renal function, great advances have been made in the clinical and genetic profile of patients affected by this condition. Furthermore, not only have genetic bases of pseudohypoparathyroidism been unravelled, but also variants in other genes involved in the PTH/PTHrP signalling pathway through Gsα, have been identified as the cause of diseases that share clinical features with pseudohypoparathyroidism. In the paediatric setting, the first symptoms suggesting the impairment of this signalling pathway are the presence of subcutaneous ossifications, brachydactyly and/or early onset obesity, followed by the possible development of PTH resistance. This clinical suspicion should be confirmed by an accurate molecular diagnosis to allow for coordinated multidisciplinary clinical management. Among the features of this group of disorders, physicians should pay attention to evaluation of PTH and/or thyrotropin (TSH) resistance at diagnosis and throughout follow-up, as well as growth hormone deficiency, hypogonadism, skeletal deformities, dental impairment, obesity, insulin resistance, impaired glucose tolerance or type2 diabetes mellitus and hypertension, as well as ectopic ossifications (either subcutaneous or affecting deeper tissues) and impairment of neurocognitive development.
Assuntos
Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/terapia , Criança , Diagnóstico Diferencial , Marcadores Genéticos , Humanos , Pediatria , Pseudo-Hipoparatireoidismo/etiologia , Pseudo-Hipoparatireoidismo/fisiopatologiaRESUMO
Pseudohypoparathyroidism (PHP) refers to a heterogeneous group of uncommon, yet related metabolic disorders that are characterized by impaired activation of the Gsα/cAMP/PKA signaling pathway by parathyroid hormone (PTH) and other hormones that interact with Gsa-coupled receptors. Proximal renal tubular resistance to PTH and thus hypocalcemia and hyperphosphatemia, frequently in presence of brachydactyly, ectopic ossification, early-onset obesity, or short stature are common features of PHP. Registries and large cohorts of patients are needed to conduct clinical and genetic research, to improve the still limited knowledge regarding the underlying disease mechanisms, and allow the development of novel therapies.
Assuntos
Pseudo-Hipoparatireoidismo/terapia , Adulto , Doenças Ósseas/etiologia , Doenças Ósseas/prevenção & controle , Criança , Resistência a Medicamentos , Humanos , Hormônio Paratireóideo/uso terapêutico , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/patologia , Pseudo-Hipoparatireoidismo/fisiopatologiaRESUMO
This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders.
Assuntos
Diagnóstico Tardio/efeitos adversos , Hormônio Paratireóideo/uso terapêutico , Guias de Prática Clínica como Assunto , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/terapia , Consenso , Resistência a Medicamentos , Feminino , Predisposição Genética para Doença , Humanos , Recém-Nascido , Masculino , Triagem Neonatal/organização & administração , Prognóstico , Desenvolvimento de Programas , Pseudo-Hipoparatireoidismo/genética , Medição de RiscoRESUMO
The term pseudohypoparathyroidism (PHP) refers to a spectrum of rare disorders of mineral metabolism, characterized by features due to end-organ resistance to PTH. The phenotypes of Albright hereditary osteodystrophy (AHO), originally described as associated to the disease, and progressive osseous heteroplasia, can be associated to the endocrine manifestations of hormonal resistance. Genetic or epigenetic alterations in the complex imprinted GNAS locus, encoding the alpha-subunit of the stimulatory G protein (GSα) and several other transcripts, give rise to the different forms oh PHP, which can be differentiated according to the phenotype, the response to PTH infusion and in vitro assays testing Gsα activity. Since PHP-related phenotypes are overlapping and other non GNAS-dependent disorders mimicking AHO, such as acrodysostosis, have been genetically characterized, the term PHP is today considered obsolete and better referred to the more comprehensive "inactivating PTH/PTHrP signaling disorder (iPPSD)" as proposed in a recent classification. This broad term include all the congenital rare disorders due to impaired PTH/PTHrP cAMP pathway. Genetic and epigenetic analyses, although not necessary for diagnosis made on the basis of major and minor criteria according to clinical and biochemical signs, will let to differentiate among the different forms for proper therapeutic planning, counseling and follow-up.
Assuntos
Pseudo-Hipoparatireoidismo/terapia , Humanos , Hipocalcemia/etiologia , Hormônio Paratireóideo/fisiologia , Pseudo-Hipoparatireoidismo/sangue , Pseudo-Hipoparatireoidismo/complicaçõesAssuntos
Cesárea/métodos , Cromograninas/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Hipotireoidismo , Complicações na Gravidez , Pseudo-Hipoparatireoidismo , Tiroxina/administração & dosagem , Adulto , Apresentação Pélvica/cirurgia , Cálcio/sangue , Metilação de DNA , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/genética , Hipotireoidismo/terapia , Recém-Nascido , Hormônio Paratireóideo/sangue , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/genética , Complicações na Gravidez/terapia , Resultado da Gravidez , Pseudo-Hipoparatireoidismo/sangue , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/genética , Pseudo-Hipoparatireoidismo/terapia , Testes de Função Tireóidea/métodosRESUMO
Hypocalcaemia is one of the commonest disorders of mineral metabolism seen in children and may be a consequence of several different aetiologies. These include a lack of secretion or function of parathyroid hormone, disorders of vitamin D metabolism and abnormal function of the calcium-sensing receptor. A practical approach to the investigation, diagnosis and subsequent management of hypocalcaemic disorders is presented.
Assuntos
Cálcio/metabolismo , Hipocalcemia/diagnóstico , Hipoparatireoidismo/diagnóstico , Hormônio Paratireóideo/metabolismo , Insuficiência Renal/diagnóstico , Deficiência de Vitamina D/diagnóstico , Vitamina D/metabolismo , Criança , Síndrome de DiGeorge/complicações , Síndrome de DiGeorge/diagnóstico , Humanos , Hipercalciúria/complicações , Hipercalciúria/diagnóstico , Hipercalciúria/terapia , Hipocalcemia/etiologia , Hipocalcemia/terapia , Hipoparatireoidismo/complicações , Hipoparatireoidismo/terapia , Nefrocalcinose/complicações , Nefrocalcinose/diagnóstico , Nefrocalcinose/terapia , Osteopetrose/complicações , Osteopetrose/diagnóstico , Osteopetrose/terapia , Pseudo-Hipoparatireoidismo/complicações , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/terapia , Insuficiência Renal/complicações , Erros Inatos do Transporte Tubular Renal/complicações , Erros Inatos do Transporte Tubular Renal/diagnóstico , Erros Inatos do Transporte Tubular Renal/terapia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/terapiaRESUMO
Molecular alterations of cAMP-mediated signaling affect primarily the signaling of the PTH/PTHrp receptor, and, with different severities the signaling of other hormones, including TSH. The identification of PTH and other hormonal resistances implies to look for the genetic disorder supporting the metabolic disorder.
Assuntos
Doenças das Paratireoides/terapia , Hormônio Paratireóideo/fisiologia , Humanos , Doenças das Paratireoides/diagnóstico , Doenças das Paratireoides/fisiopatologia , Pseudo-Hipoparatireoidismo/genética , Pseudo-Hipoparatireoidismo/terapia , Receptores de Hormônios Paratireóideos/genética , Receptores de Hormônios Paratireóideos/metabolismo , Tireotropina/fisiologiaRESUMO
UNLABELLED: Hypothyroidism is a particular condition observed in pseudohypoparathyroidism (PHP), a rare disorder characterized by parathyroid (PTH) resistance leading to hypocalcemia and hyperphosphatemia associated with a GNAS (guanine nucleotide-binding protein α-subunit) mutation (PHP1A) or epimutation (PHP1B). To determine the presence of hypothyroidism at birth we conducted a retrospective study in our cohort of patients presenting with either PHP1A (n = 116) or PHP1B (n = 99). We also investigated patients presenting at birth with congenital hypothyroidism (CH) and a eutopic thyroid gland for phosphocalcium abnormalities suggesting PTH resistance and PHP. Our study reveals CH as the earliest diagnostic clue for PHP1A, but not for PHP1B. We estimated the frequency of CH at birth to be between 8 and 34% in patients presenting with PHP1A. The elevation of phosphatemia and PTH concentration precedes hypocalcemia in PHP1A. Conversely, the frequency of PHP1A in patients presenting CH is dramatically low. This may be due to the low prevalence of PHP1A which remains unknown. CONCLUSIONS: Subclinical and overt hypothyroidism can occur in PHP1A patients at birth many years before PTH resistance becomes clinically apparent. Although such cases appear to be rare, some pediatric patients with unexplained CH are likely to benefit from measuring calcium, phosphorus, and PTH for extended periods of time.
Assuntos
Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/terapia , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/terapia , Gêmeos Monozigóticos , Criança , Pré-Escolar , Cromograninas , Hipotireoidismo Congênito/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Lactente , Masculino , Mutação , Pseudo-Hipoparatireoidismo/genéticaRESUMO
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 JovemRESUMO
El seudohipoparatiroidismo neonatal transitorio es un cuadro escasamente descrito, que cursa con hipocalcemia neonatal tardía, hiperfosfatemia y niveles elevados de hormona paratiroidea (PTH), lo que refleja resistencia periférica a su acción. Es una causa infrecuente de hipocalcemia neonatal tardía, y el defecto bioquímico parece residir en una inmadurez funcional de los receptores renales de la PTH. Para su corrección, se precisan aportes elevados de calcio y análogos de vitamina D. Su carácter autolimitado lo diferencia de otros seudohipoparatiroidismos persistentes. Exponemos el caso de una recién nacida pretérmino, con crecimiento intrauterino retardado, que presentó esta patología. Analizaremos los hallazgos clínicos y bioquímicos, así como el diagnóstico diferencial y el manejo de este raro trastorno(AU)
Transient neonatal pseudohypoparathyroidism is an uncommon pathology that causes late neonatal hypocalcemia, hyperphosphatemia and high levels of parathyroid hormone (PTH),which reflects peripheral resistance to its action. It is a rare cause of late neonatal hypocalcemia and the biochemical defect appears to lie in a functional immaturity of renal PTH receptors. High doses of calcium and vitamin D are necesary for its correction. Its self-limited evolution differences it with other persistent pseudohypoparathyroidism. We report a case of a premature newborn with intrauterine growth retardation who presented this pathology. We analyze the clinical and biochemical findings and differential diagnosis and management of this rare disorder(AU)
Assuntos
Humanos , Feminino , Recém-Nascido , Pseudo-Hipoparatireoidismo/diagnóstico , Pseudo-Hipoparatireoidismo/terapia , Pseudo-Hipoparatireoidismo/fisiopatologia , Hipocalcemia/sangue , Mutação/genética , Recém-Nascido Prematuro , Índice de Apgar , AMP Cíclico/fisiologiaRESUMO
We describe clinical, biochemical, radiological profile, and treatment outcome in 97 patients with idiopathic hypoparathyroidism seen over a period of 18 years. Of the 97 patients, 78 (80%) had idiopathic hypoparathyroidism and 19 (20%) had pseudohypoparathyroidism. The mean age±standard deviation (SD) at presentation was 28.7±14.1 years. There were 52 males, the mean lag time from first reported symptom to diagnosis was 5.9±5.2 years and the mean (±SD) follow-up was 1.8±0.4 years. The most common presenting manifestation was carpopedal spasm in 68 (70%) patients, followed by paresthesia and seizures in 52 (54%) patients. The mean (±SD) serum calcium and inorganic phosphate concentrations were 6.1±1.5 mg/dl and 6.3±1.5 mg/dl, respectively. The most common imaging abnormality noted was basal ganglia calcification followed by cerebral cortex and cerebellum calcification. More than one-third of patients were on various antiepileptic drugs including phenytoin. In addition to oral calcium and active vitamin D (calcitriol), twenty-six patients (27%) also required hydrochlorothiazide. The important finding in our study was long lag time from the first reported symptom to diagnosis. Phenytoin was the drug in almost one- third of our patients with seizures. Practicing clinicians should have high index of suspicion of diagnosis hypoparathyroidism in the appropriate clinical states to avoid the morbidity associated with hypoparathyroidism. Phenytoin should be avoided in patients with hypoparathyroidism and seizures.