Clinical profile of primary hyperparathyroidism in Northeast India: a single centre experience

Background: A retrospective study of the presentation of primary hyperparathyroidism was done at a tertiary care centre in northeast India and was compared with variable features in other parts in India and worldwide.Methods: The clinical presentation, biochemical parameters, radiological and histopathology findings of 27 subjects of primary hyperparathyroidism who presented to us over a period of 5 years were retrospectively analysed. Chi-square test, student t test and 'one way ANOVA' were used to compare different variables. Statistical significance was set at p<0.05.Results: The age distribution ranged from as young as 13 years to 72 years (39±16.7). The male:female ratio was 1:1.25. The duration of symptoms at presentation ranged from 2 to 72 months (21.7±20.3). The most common presentation was bone pain in 59.2% of cases, followed by proximal myopathy (48.1%), fatigue (44.4%), abdominal pain (44.4%), constipation (11.1%), hypertension (18.5%), palpable neck swelling (22.2%), limb deformity (22.2%) and fracture (14.8%). The mean serum calcium was 12.2±0.87mg/dl. Parathyroid adenoma was localized radiologically in all patients and single adenoma was the most common cause in 96.3%. Left inferior parathyroid adenoma was the most common site of involvement in 51.8%.Conclusions: Hyperparathyroidism at our centre in northeast India has a classic symptomatic presentation with severe bone and renal involvement and younger age at diagnosis, and equal gender distribution.

Frequency & predictors of pancreatitis in symptomatic primary hyperparathyroidism

Background & objectives: The frequency and predictors of pancreatitis in primary hyperparathyroidism (PHPT) are not well understood. The objective of the present study was to evaluate the frequency of pancreatitis in patients with PHPT and its association with clinical and biochemical parameters of the disease. Methods: In this retrospective study all consecutive patients with PHPT registered in the PHPT registry (www.indianphptregistry.com) from the year 2004 to 2013 were included. The clinical, biochemical and radiological parameters related to pancreatitis were evaluated in histologically proven PHPT patients. Results: A total of 218 patients (63 men; mean age: 40.6±14.4 yr) underwent surgery for PHPT during the study. Pancreatitis occurred in 35 [16%, 18 acute and 17 chronic pancreatitis (CP)] patients and male:female ratio was 1:0.94. Skeletal manifestations were seen less frequently in PHPT with pancreatitis as compared to that of PHPT without pancreatitis. PHPT with pancreatitis had significantly higher serum calcium (12.4±2.0 vs. 11.7±1.5 mg/dl, P <0.05) in comparison to PHPT without pancreatitis. PHPT with acute pancreatitis (AP) had higher serum calcium (P <0.05) and parathyroid hormone (PTH) (P <0.05) levels than PHPT with CP. Curative parathyroidectomy improved the symptoms associated with pancreatitis as there was no recurrence in AP group, whereas recurrence was observed only in about 10 per cent patients of the CP group. Interpretation & conclusions: Pancreatitis was observed in 16 per cent of PHPT patients with male predominance in the study population. No recurrence of AP was observed after curative surgery. It may be proposed that serum amylase with calcium and PTH should be measured in all patients of PHPT with pain abdomen to rule out pancreatitis.

Hipercalcemia maligna en pacientes con tumores neuroendocrinos. Reporte de 2 casos de tumores pancreáticos productores de péptido relacionado con hormona paratiroidea / Malignant hypercalcaemia in patients with neuroendocrine tumours. Report of 2 cases of parathyroid hormone-related peptide-secreting pancreatic tumours

Resumen La hipercalcemia maligna mediada por péptido relacionado con hormona paratiroidea (PR-PTH) es una manifestación poco común en tumores neuroendocrinos. Presentamos dos pacientes con tumores neuroendocrinos de páncreas con metástasis a hígado pero sin compromiso óseo en quienes se evidenció hipercalcemia maligna asociada a elevación de PR-PTH, con PTH suprimida. En ambos casos se logró normalizar temporalmente la calcemia con el uso de análogos de somatostatina, pero durante la evolución se requirió adición de bisfosfonatos en uno de ellos. Con la discusión de estos casos, la revisión de la literatura y de los casos similares publicados esperamos contribuir al mejor conocimiento de esta enfermedad.

Abstract Parathyroid hormone-related peptide-mediated hypercalcaemia (PTH-rp) is rare in patients with neuroendocrine tumours. The clinical cases are thus presented on two patients with pancreatic neuroendocrine tumours with liver metastases, but without bone involvement and with hypercalcaemia associated with elevated PTH-rp and with PTH suppressed. In both cases, it was possible to temporarily bring the calcium levels back to normal with the use of somatostatin analogues, but during the course of the disease, the addition of bisphosphonates was required in one of them. With the discussion of these cases and the review of the literature and similar published cases, it is hoped to contribute to provide better knowledge of this disease.

Challenges in Parathyroid Cancers: A Review

@#Parathyroid carcinomas are rare neoplasms, with a reported incidence of less than 1% of cases of primary hyperparathyroidism. Diagnosis and treatment of parathyroid carcinoma remains a challenge, as many of the pathologic features are neither sensitive nor specific in differentiating from benign parathyroid lesions. The rule of 3’s (serum calcium of more than 3mmol/L and size of the adenoma being more than 3cm) is helpful in risk identifying a cancer. Ultrasound of the neck and Tc-99m pertechnetate/Tc-99m sestamibi (MIBI) scan remains the two main modalities of investigation of parathyroid disease. Although en-bloc treatment is recommended for parathyroid cancer, it is only performed in up to 12% of cases. This review illustrates the challenges in diagnosis and treatment of parathyroid carcinoma.

Perfil bioquímico en sangre de cordón en prematuros extremos y crecimiento fetal / Intrauterine growth and biochemical levels in cord blood samples in infants less than 31 weeks gestation

Introducción: Con mayor aporte de proteínas y energía en la primera semana se ha observado hipofosfemia en prematuros extremos. Los menores niveles de fósforo se han presentado en prematuros con antecedentes de restricción de crecimiento intrauterino. Objetivos: Caracterizar los niveles plasmáticos bioquímicos en el cordón de prematuros extremos, nacidos adecuados (AEG) y pequeños para edad gestacional (PEG) y la relación con calcemia y fosfemia en la primera semana de vida. Pacientes y método: Estudio clínico realizado en Neonatología del Hospital Doctor Sótero del Río, en los años 2013 y 2014. Se analiza el perfil bioquímico en el cordón y la calcemia y fosfemia en los primeros 7 días de vida, registrados en la ficha clínica según fueran AEG o PEG, según las curvas de Alarcón-Pittaluga. Análisis con significación de p < 0,05. Resultados: Los niveles de colesterol, transaminasas, albúmina y creatinina fueron similares para los PEG y AEG. Los niveles de pH, fósforo, calcio, y fosfatasas alcalinas fueron menores en los PEG. El nitrógeno ureico, el ácido úrico y los triglicéridos fueron mayores en los PEG. Los PEG muestran marcada reducción de fosfemia en la primera semana, la calcemia tiende a subir proporcionalmente al descenso de la fosfemia. Conclusiones: En prematuros extremos la desnutrición intrauterina se expresa en modificación de los niveles plasmáticos de calcio, fósforo, fosfatasas alcalinas, nitrógeno ureico, ácido úrico y triglicéridos. Posnatalmente, al recibir aporte nutricional, se manifiesta una disminución de la fosfemia y un aumento de calcemia, concordante con aportes insuficientes de fósforo durante el período.

Introduction: The use of greater amounts of protein and energy during the first week of life is associated with hypophosphataemia in extreme preterm babies. The lowest phosphorus levels are described in intrauterine growth restricted (IUGR) babies. Objectives: To describe biochemistry levels in cord blood plasma in extreme premature, adequate and small for gestational age babies (AGA/SGA) and their relationship with plasma calcium and phosphorus levels during the first week of life. Patients and method: A descriptive clinical study was performed in the Neonatology Service at Hospital Dr. Sótero del Río during 2013 and 2014. A biochemical analysis of cord blood was performed on 43 premature babies, as well as plasma calcium and phosphorus levels during the first week. The adequacy for gestational age was obtained using Alarcón- Pittaluga growth curves. Statistical significance was P < .05. Results: Cholesterol, transaminases, albumin and creatinine levels were similar for both AGA and SGA babies. Levels of pH, phosphorus, calcium and alkaline phosphatase were significantly lower in SGA babies. Urea nitrogen, uric acid and triglycerides levels were higher in SGA. The analysis during the first week showed a strong reduction in phosphorus levels, as well as an increase in calcium levels in proportion to the decrease in phosphorus in the SGA sub- group. Conclusions: Intrauterine malnutrition in preterm babies is expressed in the modulation of plasma levels of calcium, phosphorus, alkaline phosphatase, urea nitrogen, uric acid and triglycerides. During post-natal life, when nutritional intake begins, a decrease in phosphorus and an increase in calcium levels appear, consistent with insufficient phosphorus intake during this period.

Necrosis grasa subcutánea con hipercalcemia persistente en un neonato tratado con hipotermia terapéutica: Reporte de un caso / Subcutaneous fat necrosis and persistent hypercalcaemia in a newborn treated with therapeutic neonatal hypothermia: A case report

La hipotermia terapéutica constituye el tratamiento de elección para los recién nacidos con encefalopatía hipóxico-isquémica moderada-grave, que cambia el pronóstico de estos niños y se acepta como una técnica segura y con escasas complicaciones secundarias considerando su beneficio. Un posible efecto adverso es la necrosis grasa subcutánea, una paniculitis transitoria aguda de presentación durante las primeras semanas de vida. Se presenta un caso de un recién nacido a término afecto de encefalopatía hipóxico-isquémica con lesiones cutáneas en forma de eritema multiforme generalizado y placas eritematosas firmes e induradas en la espalda, los glúteos y las extremidades a los 12 días de vida, tras el tratamiento con hipotermia. El estudio histopatológico, tras la biopsia cutánea, confirmó la sospecha de necrosis grasa subcutánea. Al mes de vida, presentó cifras elevadas de calcio sérico, que precisaron tratamiento con hidratación intravenosa y diuréticos. La calcemia descendió hasta normalizarse a los 3 meses, con desaparición progresiva de las lesiones cutáneas.

Therapeutic hypothermia is the current standard treatment in newborns with moderate to severe hypoxic-ischemic encephalopathy, changing the outcome of these children. It is considered a safe technique with almost no side effects. A possible adverse side event is subcutaneous fat necrosis, which is an acute self-limiting panniculitis that develops during the first weeks of life. We report a case of a newborn at term suffering hypoxic-ischemic encephalopathy with a generalized multiform erythematous rash and firm and indurated plaques over the back, buttocks and extremities on his 12th day of life after being treated with therapeutic hypothermia. Histopathological study after skin punchbiopsy confirmed the suspicion of subcutaneous fat necrosis. The infant developed asymptomatic moderate hypercalcaemia within the first month of life, which was treated with intravenous fluids and diuretics. Serum calcium levels decreased and normalized in 3 months, with progressive disappearance of skin lesions.

Parathyroid Hormone Secreting Metaplastic Breast Carcinoma: A Case Report of Paraneoplastic Syndrome

Paraneoplastic syndrome (PNS) is a distant neurological manifestation of an underlying tumour. Humoral hypercalcaemia of malignancy is a form of paraneoplastic syndrome where there is an increased in calcium levels. In this article we report a 48 year old lady, with no known medical illness and presented with symptomatic hypercalcaemia. She presented to our institution complaining of a fungating and ulcerating mass over the right breast, measuring 11 X 15 cm and associated with gradual paraxial body weakness. Further investigations revealed the lesion to be an invasive breast carcinoma with metaplastic features. Computed tomography (CT) scan showed a locally advanced breast carcinoma with right axillary node metastasis, without evidence of distant metastasis. Serum calcium, i-PTH together with SPECT has confirmed the patient to have a humoral hypercalcaemia malignancy with elevated ectopic parathyroid hormone level. Bone scan did not reveal any evidence of metastasis. High volume intake and loop diuretics were employed in the management of hypercalcaemia, which was eventually resolved following mastectomy with axillary clearance of the ipsilateral side. Currently she’s she is under oncologist’s follow up for further management.

Ovarian small cell carcinoma hypercalcemic type with acute renal dysfunction / 临床与实验病理学杂志

Purpose To investigate the clinicopathlogical characteristics, diagnosis and differential diagnosis of ovarian small cell car-cinoma hypercalcemic type ( OSCCHT) associated with acute renal dysfunction. Methods A case of OSCCHT associated with acute renal dysfunction was reported. The clinical and pathologic data, treatment and pathological examinations were analyzed and the related literatures were reviewed. Results A 29-year-olds women was presented to hospital with inappetence and significant weight loss for 2 months. The laboratory examination showed abnormal renal function, and pelvic cavity mass, possibly coming from adnexa of the uterus was seen by radiography. Serum levels showed significantly increased serum calcium with acute renal dysfunction. An emergency opera-tion was performed just after renal function partially recovered by 2 times hemodialysis. During surgery, right ovary tumor with a size of 12 cm × 10 cm × 10 cm was inspected. Microscopically, the tumor cells were arranged in a diffuse solid pattern, mutiple nodules were separated by fibrous tissue. some small folliculars and pseudoglandular cavities with acidophilia secretion within nodules could been ob-served. Tumor cells were medium to large with eosinophilic cytoplasm, round or oval vesicular nucleus, increased karyoplasmic ratio and pathologic mitosis. Immunohistochemistry revealed that the tumor cells expressed EMA, CKpan, C-erbB-2 ( +) , CA125 ( focal+) and Ki-67 proliferation index was about 60%, while ER, PR, Syn, CgA, PTH, Inhibin, CD99, AFP, PLAP, CD30 and CD20 were not expressed. Conclusion Ovarian small cell carcinoma hypercalcemic type with acute renal dysfunction is a very rare with a rapidly progressive and highly malignant tumor. The final diagnosis mainly lies on clinical information ( hypercalcaemia) , morphology and immunohistochemistry, combined with electron microscopy and molecular biological detection when necessary.

A case of diabetes mellitus and hypercalcaemia / Journal of the ASEAN Federation of Endocrine Societies

@#We report a case of diabetes mellitus in a middle-aged female who subsequently developed primary hyperparathyroidism and underwent parathyroidectomy. Prior to surgery, she was hospitalized several times since 1988 for vomiting, pain abdomen and dehydration. On none of these occasions hypercalcaemia could be documented. Yet she developed pancreatic calcification and diabetes in 1991 and was diagnosed as fibrocalculous pancreatic diabetes (FCPD) and treated with insulin. Nephrolithiasis developed in 2003. Hypercalcaemia with high PTH was detected in 2004 and a solitary right parathyroid adenoma was identified and surgically removed. Following surgery, gastrointestinal symptoms disappeared but diabetes remained unaltered on follow up for 8 years. The cause of multi-organ calcification which started well before development of hypercalcaemia is not known.

Hypercalcaemia secondary to Hypervitaminosis A in a patient with chronic renal failure / Hipercalcemia secundaria a la Hipervitaminosis A en un paciente con insuficiencia renal crónica

Vitamin A toxicity is a well-described medical condition with a multitude of potential presenting signs and symptoms. It can be divided into acute and chronic toxicity. Serum vitamin A concentrations are raised in chronic renal failure even with ingestion of less than the usual toxic doses. Hypercalcaemia can occasionally be associated with high levels of vitamin A but it is rare. In this report, we describe a 67-year old female patient with chronic kidney disease who was taking vitamin A supplements for approximately 10 years. The patient had worsening of her chronic kidney disease over the last years and developed chronic hypercalcaemia. Her vitamin A level was elevated with a daily intake of 7000 IU. The vitamin A supplement was stopped. A few months later, vitamin A level diminished substantially and serum calcium levels returned to normal.

La toxicidad de la vitamina A es una condición médica bien descrita que presenta un sinnúmero de potenciales signos y síntomas. Puede ser dividida en toxicidad aguda y crónica. Las concentraciones séricas de vitamina A se elevan con la insuficiencia renal crónica, incluso con la ingestión de dosis tóxicas por debajo de lo habitual. En ocasiones, la hipercalcemia puede estar asociada con altos niveles de vitamina A, pero esto raramente ocurre. En este informe, describimos a una paciente de 67 años de edad con enfermedad renal crónica, que estuvo tomando suplementos de vitamina A por aproximadamente 10 años. La paciente sufrió un empeoramiento de su enfermedad renal crónica en los últimos años, y desarrolló hipercalcemia crónica. Su nivel de vitamina A se elevó con una ingesta diaria de 7000 UI. El suplemento de vitamina A fue suspendido. Unos meses más tarde, el nivel de vitamina A nivel disminuyó sustancialmente, y los niveles de calcio sérico volvieron a la normalidad.

Late onset systemic lupus erythematosus with severe hypercalcaemia / Lupus eritematoso sistémico de inicio tardío con hipercalcemia severa

We report a case of a 76-year old female presenting with symptomatic severe hypercalcaemia, and subsequently diagnosed with late onset SLE due to the presence of anaemia, leucopenia, antibodies of antinuclear (ANA), anti-dsDNA, and also kidney impairment. Serum levels of FGF23 and intact-parathyroid hormone (iPTH) were low in this patient. Serum calcium, FGF23 and iPTH levels responded to steroids, which occurred simultaneously with disease activity. On follow-up, the faster increase in FGF23 than in parathyroid hormone suggested that FGF23 might be involved in the pathogenesis of hypercalcaemia in SLE.

Se reporta el caso de una mujer de 76 años de edad que se presentó con hipercalcemia sintomática severa, y a la que posteriormente le fuera diagnosticada LES de inicio tardío con presencia de anemia, leucopenia, anticuerpos antinucleares (ANA), anti-dsDNA, e insuficiencia del riñón. Los niveles séricos del factor de crecimiento fibroblástico 23 (FGF23) y la hormona paratiroidea intacta (iPTH) fueron bajos en este paciente. Los niveles de calcio séricos, FGF23 e iPTH respondieron a los esteroides, que ocurrieron simultáneamente con la actividad de la enfermedad. En el seguimiento, el hecho de que el factor FGF23 aumentara más rápidamente que la hormona paratiroidea, sugiere que el FGF23 podría estar involucrado en la patogénesis de la hipercalcemia en LES.