An intricate case of sporadic pseudohypoparathyroidism type 1B with a review of literature

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.

Seudohipoparatiroidismo 1b / Pseudohypoparathyroidism 1b

RESUMEN El seudohipoparatiroidismo 1b se caracteriza por resistencia aislada a la parathormona, en ausencia de las manifestaciones típicas de la osteodisfrofia hereditaria de Albright; debido a alteraciones epigenéticas del locus GNAS. Puede presentarse de forma esporádica, o heredado de manera autosómico dominante por vía materna. Se presenta paciente masculino de 31 años, con antecedentes de tumores óseos y calcificaciones cerebrales diagnosticados a los 14 años; que se consulta por presentar mareo intenso, rigidez del cuello y la boca, dificultad para hablar y tragar, desorientación y trastornos de percepción; con fenotipo y somatometría normales, y signos de tetania latente (Chvostek y Trouseau positivos). Los estudios realizados mostraron: hipocalcemia, hiperfosfatemia, aumento de niveles de parathormona y múltiples calcificaciones en cerebro y cerebelo. Con tales hallazgos se emite el diagnóstico de seudohipoparatiroidismo 1b, el cual se confirma mediante pruebas moleculares con alteración en el patrón de metilación en el locus GNAS. No presentó alteraciones en el estudio de secuenciación de los 13 exones codificantes del GNAS. Se concluyó como un caso esporádico ante la ausencia de historia familiar de hipocalcemia, combinado con amplia pérdida de metilación del gen GNAS y la no evidencia de deleciones. Se presenta el primer reporte de esta enfermedad en Cuba con estudio molecular(AU)

ABSTRACT Pseudohypoparathyroidism 1b is characterized by isolated resistance to parathormone, in the absence of the typical manifestations of hereditary Albright osteodysphrophy; due to epigenetic alterations of the GNAS locus. It can occur sporadically, or inherited in an autosomal dominant way through the mother. We report the case of a 31-year-old male patient, with history of bone tumors and cerebral calcifications diagnosed at age 14. She came to consultation due to severe dizziness, stiff neck and mouth, difficulty speaking and swallowing, disorientation and perception disorders; he showed normal phenotype and somatometry, and signs of latent tetany (positive Chvostek and Trouseau). Studies have shown hypocalcaemia, hyperphosphatemia, increased levels of parathormone and multiple calcifications in the brain and cerebellum. These findings, pseudohypoparathyroidism 1b is diagnosed confirmed by molecular tests showing alteration in the methylation pattern in the GNAS locus. There were no alterations in the sequencing study of the 13 exons coding for GNAS. It was concluded as a sporadic case in the absence of a family history of hypocalcemia, combined with extensive loss of GNAS gene methylation and no evidence of deletions. This is the first report this disease with molecular study in Cuba(AU)

Coexistence of glucocorticoid resistance and pseudohypoparathyroidism / Coexistencia de la resistencia a glucocorticoides y el pseudohipoparatiroidismo

We report for the first time the case of a young man who developed both glucocorticoid resistance and resistance to parathyroid hormone. Treatment with high doses of dexamethasone together with administration of calcium and calcitriol resulted in a significant improvement in the patient's condition. In this paper, we discuss in detail diagnostic and treatment strategies used on the patient and the impact on the course and outcome of both disorders. We associate the development of both these disorders with a possible inherited defect in the signal pathways common to glucocorticoid and parathyroid hormone receptors.

Por primera vez se reporta el caso de un joven que desarrolló resistencia a glucocorticoides y resistencia a la hormona paratiroidea. El tratamiento con altas dosis de dexametasona, junto con la administración de calcio y calcitriol, trajo como resultado una mejoría significativa de la condición del paciente. En este papel, se analiza en detalle el diagnóstico así como las estrategias de tratamiento del paciente, y su impacto en el curso y resultado de ambos trastornos. Se concluye que el desarrollo de ambos trastornos se halla asociado a un posible defecto hereditario en las vías de transducción de señales comunes a los receptores de las hormonas glucocorticoides y las hormonas paratiroideas.

Hipocalcemia asociada a hiperfosfemia y PTH elevada: caso clínico / Hypocalcemia, vitamin D deficiency and elevated PTH levels in a patient with celiac disease: report of one case

We report a 56 years old woman that presented a severe hypocalcemia, with a serum calcium of 4.7 mg/dl, after the intake of bisphosphonates. Laboratory examination showed elevated PTH levels (167 pg/ml), hyperphosphatemia, hypomagnesemia and normal phosphate tubular reabsorption. Therefore, the diagnosis of pseudohypoparathyroidism was considered (PHP). However, further studies showed low levels of 25 OH Vitamin D (13.6 ng /ml), osteoporosis, positive anti endomysium antibodies and an endoscopic biopsy, that confirmed the presence of a celiac disease.

Pseudohipoparatiroidismo en niños, Manifestaciones clínicas e implicancias del tratamiento / Pseudohypoparathyroidism in childhood. Clinical manifestations and implications of treatment

El pseudohipoparatiroidismo es una enfermedad hereditaria caracterizada por presentar resistencia a la hormona paratiroidea que se manifiesta por hipocalcemia, hiperfosfatemia y niveles elevados de PTH. Los pacientes pueden presentar características fenotípicas de osteodistrofia hereditaria de Albright y tener asociadas otras resistencias hormonales. En este trabajo se analizan las características clínicas y bioquímicas de 13 niños afectados de la enfermedad, como así también la implicancia del tratamiento. El diagnóstico temprano, la detección oportuna de resistencias hormonales asociadas y el control periódico de los pacientes, son de relevancia para promover el crecimiento y disminuir las secuelas de la hipocalcemia (AU)

Pseudohypoparathyroidism is an hereditary disease characterized by hypocalcemia, hyperphosphatemia due to parathyroid hormone resistance. Patients may have the association of other endocrine resistances and physical characteristics termed Albright's hereditary osteodystrophy. We present here 13 patients with PHP, their clinic and biological signs, and the implication of the treatment. Early diagnosis, the study of other hormone resistances, and periodic control of the patients, are mandatory to promote a correct growth and decrease the consequences of hypocalcemia in these patients (AU)

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.

¿Pseudohipoparatiroidismo o déficit de vitamina D? / Pseudohypoparathyroidism or vitamin D deficiency? Report of one case

Pseudohypoparathyroidism is characterized by a resistance to parathormone, with variable phenotypical and biochemical manifestations. Its diagnosis is difficult. We report a 28 years old male presenting with a hypokalemic periodic paralysis. His serum PTH was elevated to 1,343 and 1,101 pg/ml with concomitant hypocalcemia of 7.9 and 6.7 mg/dl. Twenty four hour urinary calcium and serum 25 hydroxy vitamin D were normal. Bone mineral density was normal. The patient was managed with calcitriol in doses of 1 to 2 µg/d, associated to calcium 2 g/day. Serum calcium levels and PTH normalized after two months and six months of treatment respectively.

Vitamin D deficiency masquerading as pseudohypoparathyroidism type 2.

A case of antiepileptic-induced vitamin D deficiency, who presented with hypocalcemia, hyperphosphatemia with increased tubular reabsorption of phosphate mimicking pseudohypoparathyroidism type 2, is reported. He showed remarkable improvement with calcium and vitamin D treatment with normalisation of serum calcium and phosphate with reestablishment of phosphaturic response.

Psoríase e pseudo-hipoparatireoidismo / Psoriasis and pseudohypoparathyroidism

Relato de caso clínico de paciente do sexo masculino, de 24 anos de idade, com psoríase pustulosa havia dois meses. Apresentava antecedentes de crises convulsivas e retardo do desenvolvimento neuropsicomotor. Ao exame físico o sinal de Trousseau foi positivo, e a dosagem de cálcio no soro estava acentuadamente diminuída. O diagnóstico foi de psoríase pustulosa generalisada associada a pseudo-hipoparatireoidismo. Inicialmente o paciente foi tratado com etretinato, sem controle do quadro; porém, com detecçäo da hipocalcemia e a reposiçäo do cálcio, houve melhora acentuada das lesöes cutâneas. A remissäo completa foi obtida com a correçäo da hipocalcemia. Esses resultados indicam que a hipocalcemia estava diretamente relacionada com a manutençäo das lesöes de psoríase pustulosa generalizada e pseudo-hipoparatireoidismo

Pseudohypoparathyroidism-Albright hereditary osteodystrophy.

A 13 year old girl with short stature, and retarded mental growth with coarse facies and deranged thyroid function test was initially suspected as a case of hypothyroidism and was started on thyroxine. Lack of response to treatment and on further investigations it was diagnosed as a case of pseudohypoparathyroidism. High index of suspicion and careful evaluation is important to diagnose such an entity.

Aspectos clínicos e neurorradiológicos do pseudo-hipoparatireoidismo: relato de caso / Clinical and neuroradiologic aspects of pseudohypoparathyreoidism: case report

Os autores relatam o caso de um paciente do sexo masculino, de 18 anos, com baixa estatura, epilepsia e deficiencia mental, alem de calcificacoes dos glanglios da base. Os achados clinicos e laboratorias sugeriram psdeudo-hipoparatireoidismo. Trata-se de patologia rara, de base genetica, secundaria a resistencia periferica ao hormonio da paratireoide e que evolui com excitabilidade neuromuscular, baixa estatura e calcificacoes dos glanglios da base, entre outros achados. Sao discutidas as formas de diagnosticas e a terapeutica empregada, seguidas de preve revisao da literatura sobre calcificacao dos glanglios da base.