Renal complications and quality of life in postsurgical hypoparathyroidism: a case-control study.

PURPOSE: Conventional therapy (calcium and activated vitamin D) does not restore calcium homeostasis in patients with chronic hypoparathyroidism (HypoPT) and is associated with renal complications and reduced quality of life (QoL). The aim of this study was to evaluate in a case-control, cross-sectional study, the rate of renal complications and QoL in two sex- and age-matched cohort of patients with differentiated thyroid cancer with (n = 89) and without (n = 89) chronic post-operative HypoPT (PoHypoPT) and their relationship with the biochemical control of the disease. METHODS: Serum and urinary parameters, renal ultrasound and QoL were assessed by SF-36 and WHO-5 questionnaires. RESULTS: Forty-three (48.3%) PoHypoPT patients reported symptoms of hypocalcemia. Twenty-six (29.2%) patients were at target for all 6 parameters, 46 (51.6%) for 5. The most frequently unmet targets were gender-specific 24-h urinary calcium (44.9%) and serum calcium (37.1%). Serum phosphate, magnesium and 25(OH)D were in the normal range in > 90% of patients. Renal calcifications were found in 26 (29.2%) patients, with no correlation with 24-h urinary calcium. eGFR did not differ between patients and controls. Conversely, patients had a significant higher rate of renal calcifications and a lower SF-36, but not WHO-5, scores. SF-36 scores did not differ between PoHypoPT patients who were, or not, hypocalcemic. CONCLUSIONS: Our study shows that the rate of renal calcifications was higher in patients with PoHypoPT than in those without. This finding, together with the reduced QoL and the presence of hypocalcemic symptoms in about half patients, underscores that the treatment of chronic HypoPT with conventional therapy is suboptimal.

[Clinical characteristics of adult-onset primary hypoparathyroidism: a retrospective analysis of 200 cases].

Objective: To study the clinical characteristics of primary hypoparathyroidism in adults. Methods: The clinical data of 200 cases with adult-onset primary hypoparathyroidism in Peking Union Medical College Hospital during December 1987 to December 2015 were collected and analyzed retrospectively. Among them, 128 cases were followed up for a median period of 3 years. Results: The major manifestations at their first visits were tetany and numbness in the distal extremities(81.5%, 163/200 and 62.0%, 124/200). Thirty-two percent of the cases (62 cases) had history of seizures, and 60.9%(98/161) and 74.4%(96/129) of them were with intracerebral calcifications and cataracts, respectively.Most of subjects(155/200)had more than one year delay in diagnosis. Hypercalciuria occurred in 67.2%(86/128) of the cases during the follow-up. No significant differences in the clinical characteristics and biochemical markers between the hypercalciuria subjects and the non-hypercalciuria subjects. Renal nephrocalcinosis or stones were found in 6.5%(5/77) of the cases, and kidney function decreased in 6.6%(6/91) of the patients. Kidney function was negatively associated with age and duration of disease. Conclusions: The predominant manifestations of primary hypoparathyroidism in adults included tetany and numbness in the distal extremities and seizures. It is often misdiagnosed. Calcium supplement combined with vitamin D or its metabolites effectively relieve clinical symptoms and signs. The serum and urinary calcium levels should be monitored frequently to reduce renal complications.

Calcium and phosphor intake in preterm infants: sensitivity and specifity of 6-hour urine samples to detect deficiency.

Aim of the present study was to test whether six-hour (6 h) urine specimens predict the 24-hour (24 h) mineral homeostasis in individual infants born preterm. Urinary Calcium (Ca) and Phosphate (P) concentrations were studied in 60 stable infants; gestational age 34 (25-42) weeks. In 58 infants four 6 h urine specimens and in 2 infants all spot urine specimens obtained within 24 h were analyzed. In 39 infants born preterm coefficients of variation were 0.42 (SD 0.26) and 0.41 (SD 0.26) for Ca and P measurements in the four 6 h urine specimens obtained within 24 h, respectively, The mineral homeostasis of the infants was defined as Ca or P surplus homeostasis if the 24 h urinary concentrations were ≥1 mmol/l. The sensitivity, specificity, and PPV of a 6 h urinary specimen to predict Ca deficiency homeostasis (24 h urinary Ca <1 mmol/l) were 0.93 (0.77-0.98; 95%CI), 0.72 (0.43-0.90) and 0.90 (0.74-0.96). The sensitivity, specificity and PPV for urinary P were 0.8 (0.38-0.96), 0.97 (0.85-0.995), and 0.8 (0.38-0.96). In conclusion, in infants born preterm on regular 3 or 4 h feedings, 6 h urine sampling is sufficiently precise for prediction of Ca and P mineral deficiency homeostasis (PPV 0.92 and 0.83). However, measurements at regular intervals (twice weekly) are recommended not to miss any infant in mineral deficiency homeostasis.

[The role of hypomagnesiuria in urolithiasis and renal colic: results from a prospective study of a metabolic evaluation protocola]. / Ruolo dell'ipomagnesuria nella colica renale da urolitiasi: risultati di uno studio prospettico sull'impiego di un protocollo di valutazione metabolica.

AIM: The stone disease of the urinary tract (urolithiasis) is a growing disease. The identification of metabolic disorders, treatable with prophylactic therapy, appears to be clinically important. The aim of this study was the analysis of metabolic disorders that promote and support the urolithiasis in a cohort of patients with renal colic at an Emergency Department. METHODS: In this prospective case series, we enrolled consecutive patients with renal colic treated at an Emergency Department within a Regional Teaching Hospital. We implemented a structured metabolic evaluation, which included blood chemistry studies, stone analysis and a 24-hour urine collection. We then evaluated the frequency of metabolic abnormalities alone or in combination. RESULTS: We enrolled 39 patients whit renal colic and a diagnosis of urolithiasis: 21 (54%) were males and the median age was 43.6 years (range 20-70). The most frequently observed type of stone was that of calcium oxalate (74%). Hypomagnesiuria was the most common metabolic abnormality found at the 24-hour urine collection (22/39, 56%), followed by hypocalciuria (31%), hypernatruria (20%), hyperuricuria (18%) and hyperoxaluria (15%). Among the associations of metabolic abnormalities, the hypocalciuria /hypomagnesuria was that observed with higher frequency (23%). CONCLUSION: We report an incidence of hypomagnesiuria (60%) in patients with renal colic higher than has ever been described in the literature. This result could be of importance in the knowledge of the pathogenesis of the urolithiasis and could have interesting implications in clinical practice.

Hypocalcemia in sepsis: analysis of the subcellular distribution of Ca2+ in septic rats and LPS/TNF-α-treated HUVECs.

INTRODUCTION: Hypocalcemia has been widely recognized in sepsis patients. However, the cause of hypocalcemia in sepsis is still not clear, and little is known about the subcellular distribution of Ca2+ in tissues during sepsis. METHODOLOGY: We measured the dynamic change in Ca2+ levels in body fluid and subcellular compartments, including the cytosol, endoplasmic reticulum and mitochondria, in major organs of cecal ligation and puncture (CLP)-operated rats, as well as the subcellular Ca2+ flux in HUVECs which treated by endotoxin and cytokines. RESULTS: In the model of CLP-induced sepsis, the blood and urinary Ca2+ concentrations decreased rapidly, while the Ca2+ concentration in ascites fluid increased. The Ca2+ concentrations in the cytosol, ER, and mitochondria were elevated nearly synchronously in major organs in our sepsis model. Moreover, the calcium overload in CLP-operated rats treated with calcium supplementation was more severe than that in the non-calcium-supplemented rats but was alleviated by treatment with the calcium channel blocker verapamil. Similar subcellular Ca2+ flux was found in vitro in HUVECs and was triggered by lipopolysaccharide (LPS)/TNF-α. CONCLUSIONS: Ca2+ influx from the blood into the intercellular space and Ca2+ release into ascites fluid may cause hypocalcemia in sepsis and that this process may be due to the synergistic effect of endotoxin and cytokines.

Continuous Subcutaneous Recombinant Parathyroid Hormone (1-34) Infusion in the Management of Childhood Hypoparathyroidism Associated with Malabsorption.

BACKGROUND/AIMS: Hypoparathyroidism associated with malabsorption can be particularly challenging to manage due to limited and erratic intestinal absorption of calcium and vitamin D analogues, resulting in episodes of hypo- or hypercalcaemia. We evaluated the role of continuous subcutaneous recombinant parathyroid hormone (rhPTH 1-34) infusion (CSPI) in children with hypoparathyroidism associated with intestinal malabsorption resistant to conventional therapy. METHOD: Four patients (8-13 years of age), with symptomatic hypocalcaemia resistant to conventional therapy, were started on CSPI (follow-up 3-8 years) in two paediatric endocrinology units in Europe. RESULTS: Serum calcium normalized within 48 h of commencing treatment in all 4 patients. An average rhPTH 1-34 dose of 0.4 µg/kg/day resulted in a substantial reduction in symptomatic hypocalcaemia and hypo-/hypercalcaemia-related hospital admissions. An increased alkaline phosphatase activity was noted in the first 6 months on CSPI, indicating an increase in bone turnover. In 2 patients with elevated urinary calcium excretion before CSPI, this normalized in the first year on treatment. No significant side effects were noticed in the short or long term, with patient-reported preference of CSPI over conventional treatment. CONCLUSION: CSPI is a promising and effective treatment option for managing hypocalcaemia and hyperphosphataemia in children with hypoparathyroidism associated with intestinal malabsorption.

Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population.

CONTEXT: The autosomal dominantly inherited condition familial hypocalciuric hypercalcemia (FHH) is characterized by elevated plasma calcium levels, relative or absolute hypocalciuria, and normal to moderately elevated plasma PTH. The condition is difficult to distinguish clinically from primary hyperparathyroidism and is caused by inactivating mutations in the calcium sensing receptor (CASR) gene. OBJECTIVE: We sought to define the mutation spectrum of the CASR gene in a Danish FHH population and to establish genotype-phenotype relationships regarding the different mutations. DESIGN AND PARTICIPANTS: A total of 213 subjects clinically suspected to have FHH, and 121 subjects enrolled as part of a family-screening program were studied. Genotype-phenotype relationships were established in 66 mutation-positive index patients and family members. MAIN OUTCOME MEASURES: We determined CASR gene mutations, and correlating levels of plasma calcium (albumin corrected), ionized calcium (pH 7.4), and PTH were measured. RESULTS: We identified 22 different mutations in 39 FHH families. We evaluated data on circulating calcium and PTH for 11 different mutations, representing a spectrum of clinical phenotypes, ranging from calcium concentrations moderately above the upper reference limit, to calcium levels more than 20% above the upper reference limit. Furthermore, the mean plasma PTH concentration was within the normal range in eight of 11 studied mutations, but mild to moderately elevated in families with the mutations p.C582Y, p.C582F, and p.G553R. CONCLUSIONS: The present data add 19 novel mutations to the catalog of inactivating CASR mutations and illustrate a variety of biochemical phenotypes in patients with the molecular genetic diagnosis FHH.

Urinary cyclic AMP analyzed as a function of the serum calcium and parathyroid hormone in the idfferential diagnosis of hypercalcemia.

Urinary cyclic AMP (UcAMP) appropriate for the serum calcium concentration was determined in normal subjects during the base-line state and during alteration in their serum calcium concentrations by saline and calcium infusions. This was compared to the UcAMP in 76 patients with hypercalcemia and 5 patients with hypocalcemia. In 54 of 56 patients with primary hyperparathyroidism, the UcAMP was inappropriately high for their serum calcium concentration, the 2 exceptions having renal failure. In four patients with vitamin D intoxication, sarcoidosis, milkalkali syndrome, and thiazide-induced hypercalcemia and in five patients with hypocalcemia due to hypoparathyroidism, the UcAMP was appropriately low for their serum calcium concentration. In 16 patients with nonparathyroid neoplasms, 10 had UcAMP levels that were inappropriately high suggesting ectopic parathyroid hormone (PTH)-mediated hypercalcemia and 6 had UcAMP levels that were appropriately low suggesting that their hypercalcemia was due to osteolytic factors other than PTH. Correlations between UcAMP, serum calcium concentration, and carboxyl-terminal immunoreactive PTH suggest that random UcAMP is a sensitive accurate reflection of circulating biologically active PTH. If there is adequate renal function (serum creatinine concentration less than 2.0 mg/dl), a random UcAMP expressed as mumol/g creatinine and analyzed as a function of the serum calcium concentration completely separates patients with PTH and non-PTH-mediated hypercalcemia.

Hypocalciuria in patients with Gitelman syndrome: role of blood volume.

BACKGROUND: Hypocalciuria is common in patients with Gitelman syndrome (GS), and its cause primarily is enhanced renal reabsorption of calcium in the proximal tubule in response to hypovolemia, judged by recent studies in animals. STUDY DESIGN: Uncontrolled trial in cases and controls to evaluate the effect of acute reexpansion of extracellular fluid volume (ECFV) on urine calcium excretion in patients with GS. SETTING & PARTICIPANTS: 8 patients with GS and 8 sex- and age-matched healthy control subjects (CSs) were enrolled in an academic medical center. PREDICTOR: ECFV expansion with isotonic saline at 1 L/h for 3 hours. OUTCOMES & MEASUREMENTS: Urinary calcium excretion was measured hourly for 6 hours, and subsequent 18-hour urine was analyzed as a single collection; hormones and electrolytes were measured. RESULTS: Patients with GS had hypokalemia, metabolic alkalosis, hypomagnesemia, severe hypocalciuria (urine calcium-creatinine ratio, 0.006 +/- 0.002 versus 0.08 +/- 0.02 mg/mg [0.02 +/- 0.01 versus 0.22 +/- 0.05 mmol/mmol]; P < 0.005), and a mild degree of ECFV contraction. Sodium excretion and creatinine clearance rates were similar to those in CSs. In patients with GS, saline infusion increased ECFV, which caused a significantly greater sodium excretion rate, but there was only a small increase in calcium excretion rate, in both the first 6 hours (0.04 +/- 0.02 mg/min [1.0 +/- 0.6 micromol/min]) and subsequent 18-hour period (0.02 +/- 0.01 mg/min [0.4 +/- 0.2 micromol/min]), as in CSs. Notwithstanding, their calcium excretion rate was still much less than that in CSs before volume repletion (0.13 +/- 0.04 mg/min [3.2 +/- 1.0 micromol/min]). LIMITATION: Patients with GS did not become euvolemic on a long-term sodium chloride supplementation because they excreted sodium chloride so rapidly. CONCLUSION: Hypovolemia is not the sole cause of hypocalciuria in patients with GS.

Dilated cardiomyopathy and adipic aciduria in nutritional rickets.

Hypocalcemia secondary to nutritional rickets is a rare cause of dilated cardiomyopathy. It is also not a recognized cause of dicarboxylic aciduria. We report the first case of adipic aciduria, presenting with dilated cardiomyopathy, secondary to hypocalcemia.

Hyperphosphatemia, hypocalcemia and increased serum potassium concentration as distinctive features of early hypomagnesemia in magnesium-deprived mice.

Magnesium-deficient patients show dysfunctional calcium (Ca(2+)) metabolism due to defective parathyroid hormone (PTH) secretion. In mice and rats, long-term magnesium (Mg(2+)) deprivation causes hyperphosphaturia and increases fibroblast growth factor 23 (FGF23) secretion, despite normal serum phosphate (Pi) and Ca(2+). Electrolyte disturbances during early hypomagnesemia may explain the response of mice to long-term Mg(2+) deprivation, but our knowledge of electrolyte homeostasis during this stage is limited. This study compares the effect of both short- and long-term Mg(2+) restriction on the electrolyte balance in mice. Mice were fed control or Mg(2+)-deficient diets for one to three days, one week, or three weeks. Prior to killing the mice, urine was collected over 24 h using metabolic cages. Within 24 h of Mg(2+) deprivation, hypomagnesemia, hypocalcemia and hyperphosphatemia developed, and after three days of Mg(2+) deprivation, serum potassium (K(+)) was increased. These changes were accompanied by a reduction in urinary volume, hyperphosphaturia, hypocalciuria and decreased Mg(2+), sodium (Na(+)) and K(+) excretion. Surprisingly, after one week of Mg(2+) deprivation, serum K(+), Pi and Ca(2+) had normalized, showing that mineral homeostasis is most affected during early hypomagnesemia. Serum Pi and K(+) are known to stimulate secretion of FGF23 and aldosterone, which are usually elevated during Mg(2+) deficiency. Thus, the hyperphosphatemia and increased serum K(+) concentration observed during short-term Mg(2+) deprivation may help our understanding of adaptation to chronic Mg(2+) deficiency.

Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia.

The calcium-sensing receptor (CASR) is a plasma membrane G protein coupled receptor that is expressed in the parathyroid hormone (PTH) producing chief cells of the parathyroid gland and the cells lining the kidney tubule. By virtue of its ability to sense small changes in circulating calcium concentration ([Ca(2+)](o)) and to couple this information to intracellular signaling pathways that modify PTH secretion or renal cation handling, the CASR plays an essential role in maintaining mineral ion homeostasis. Inherited abnormalities of the CASR gene located on chromosome 3p13.3-21 can cause either hypercalcemia or hypocalcemia depending upon whether they are inactivating or activating, respectively. Heterozygous loss-of-function mutations give rise to familial (benign) hypocalciuric hypercalcemia (FHH) in which the lifelong hypercalcemia is asymptomatic. The homozygous condition manifests itself as neonatal severe hyperparathyroidism (NSHPT), a rare disorder characterized by extreme hypercalcemia and the bony changes of hyperparathyroidism which occur in infancy. The disorder autosomal dominant hypocalcemia (ADH) is due to gain-of-function mutations in the CASR gene. ADH may be asymptomatic or present with neonatal or childhood seizures. A common polymorphism in the intracellular tail of the CASR, Ala to Ser at position 986, has a modest effect on the serum calcium concentration in healthy individuals.

Comparison of hypocalcemic hypercalciuria between patients with idiopathic hypoparathyroidism and those with gain-of-function mutations in the calcium-sensing receptor: is it possible to differentiate the two disorders?

Gain-of-function mutations in the calcium ion-sensing receptor (CaR) cause hypocalcemia with low PTH levels. It is stated that patients with activating CaR mutations generally show milder degree of hypocalcemia before treatment and more profound hypercalciuria during treatment than those with idiopathic hypoparathyroidism (IHP). To test this validity we analyzed the data of serum and urinary calcium collected from 85 patients with IHP and 15 with activating CaR mutations. The mean (+/-SEM) serum calcium concentration before treatment was significantly higher (P: < 0.001) in patients with activating CaR mutations (1.76 +/- 0.05 mmol/L; n = 15) than in those with IHP (1.41 +/- 0.03; n = 58), but there was a substantial overlap in the range of hypocalcemia between the two groups (1.25-2. 05 vs. 0.90-1.95). The mean urinary calcium/creatinine ratio (Ca/Cr) in patients with activating CaR mutations before treatment (0.362 +/- 0.045 mmol/mmol; n = 9) was almost equal to that in normocalcemic controls (0.331 +/- 0.022; n = 56) and markedly higher (P: < 0.001) than in patients with IHP (0.093 +/- 0.008; n = 57). The overlap of pretreatment urinary Ca/Cr between the 2 disorders was relatively small; subnormal urinary Ca/Cr was observed in only 1 of 9 patients with CaR mutations and in the majority (49 of 57) of patients with IHP. In contrast to pretreatment findings, the degree of hypercalciuria during treatment was not different between the 2 disorders. The data points of urinary Ca/Cr plotted as a function of the serum calcium concentration were not separable between patients with CaR mutations (n = 8) and those with IHP (n = 40). Comparison of urinary Ca/Cr between 2 patients with a CaR mutation and 7 with IHP over a wide range of serum calcium concentrations measured during 4-8 yr of treatment also indicated that the 2 disorders were inseparable. These results suggested that inappropriately normal urinary Ca/Cr in patients with untreated hypocalcemia, mostly of mild degree, might be a better biochemical clue than the development of severe hypercalciuria during treatment to suspect gain-of-function mutations in the CaR.

Dosing time-dependent variation in the hypocalcemic effect of calcitonin in rat.

Dosing time-dependent variation in the hypocalcemic effect of salmon calcitonin was examined in rats under a 12-h light-dark cycle. In both a single-dosing study with normal rats and a repeated-dosing study with hypercalcemic rats (induced by chronic vitamin-D dosing), we consistently observed that the hypocalcemic effect of calcitonin was greater when the drug was given at 14 h after lights on than that at 2 h after lights on. The reduction in urinary deoxypyridinoline excretion, a marker of bone resorption, was also greater when calcitonin was given at 14 h after lights on. Urinary excretion of Ca was not affected by the drug. Pharmacokinetic profiles of calcitonin after a single dosing did not differ between the two trials. These results indicate that the hypocalcemic effect of calcitonin is greater after dosing in the early dark phase (14 h after lights on) than after dosing in the early light phase (2 h after lights on). A time-dependent variation in the sensitivity to the drug of osteoclasts, but not renal tissues, may be involved in the mechanism of this event.

Comparison of serum parathyroid hormone and ionized calcium and magnesium concentrations and fractional urinary clearance of calcium and phosphorus in healthy horses and horses with enterocolitis.

OBJECTIVE: To evaluate calcium balance and parathyroid gland function in healthy horses and horses with enterocolitis and compare results of an immunochemiluminometric assay (ICMA) with those of an immunoradiometric assay (IRMA) for determination of serum intact parathyroid hormone (PTH) concentrations in horses. ANIMALS: 64 horses with enterocolitis and 62 healthy horses. PROCEDURES: Blood and urine samples were collected for determination of serum total calcium, ionized calcium (Ca2+) and magnesium (Mg2+), phosphorus, BUN, total protein, creatinine, albumin, and PTH concentrations, venous blood gases, and fractional urinary clearance of calcium (FCa) and phosphorus (FP). Serum concentrations of PTH were measured in 40 horses by use of both the IRMA and ICMA. RESULTS: Most (48/64; 75%) horses with enterocolitis had decreased serum total calcium, Ca2+, and Mg2+ concentrations and increased phosphorus concentrations, compared with healthy horses. Serum PTH concentration was increased in most (36/51; 70.6%) horses with hypocalcemia. In addition, FCa was significantly decreased and FP significantly increased in horses with enterocolitis, compared with healthy horses. Results of ICMA were in agreement with results of IRMA. CONCLUSIONS AND CLINICAL RELEVANCE: Enterocolitis in horses is often associated with hypocalcemia; 79.7% of affected horses had ionized hypocalcemia. Because FCa was low, it is unlikely that renal calcium loss was the cause of hypocalcemia. Serum PTH concentrations varied in horses with enterocolitis and concomitant hypocalcemia. However, we believe low PTH concentration in some hypocalcemic horses may be the result of impaired parathyroid gland function.

Effects of elevated carbon dioxide environment on calcium metabolism in humans.

BACKGROUND: Chronic respiratory acidosis induced by an elevated carbon dioxide (CO2) environment should provoke hypercalciuria with related total body and subsequent bone calcium losses. We examined this hypothesis in four healthy male volunteers, who were exposed during a 25-d period to an 0.7% CO2 environment within a deep diving isolation chamber. Three months later the same subjects were reexamined during a second campaign being exposed to a 1.2% CO2 atmosphere. METHODS: The subjects received a constant calcium intake (1.4 g.d-1) and vitamin D supplement (1000 IU.d-1) during both campaigns. Calcium balance (oral calcium intake minus urinary and fecal calcium output) was evaluated. Serum calcium concentrations and biomarkers of bone metabolism were measured, in order to evaluate bone turnover. Additionally, the response to an acute oral calcium load was examined as a sensitive measure of changes in calcium metabolism. RESULTS: Both, urinary calcium excretion (from 245 +/- 38 to 199 +/- 31 mg.d-1; mean +/- SE, 0.7% and 1.2%, respectively) and fecal calcium losses (from 1229 +/- 128 to 996 +/- 62 mg.d-1) were significantly reduced in the higher (1.2%) CO2 atmosphere. Although more calcium was retained in the body during the 1.2% than during the 0.7% CO2 campaign, serum calcium concentrations and biomarkers of bone formation were significantly lower in the higher CO2 campaign. Furthermore, bone resorption was slightly increased in the 1.2% experiment. CONCLUSION: Elevated CO2 atmosphere may dose-dependently preserve body calcium without a parallel improvement of bone substance.

Uso inapropiado de diuréticos: Algunas características no tan conocidas / Diuretic misuse: Some not so well known characteristics

Entre las situaciones asociadas al uso inapropiado de diuréticos se encuentran los intentos por descencer rápidamente de peso, comunes en los desordenes de la alimentación, y los intentos por enmascarar el consumo de otras sustancias, en el caso de las competencias deportivas. El uso sin indicación ni supervisión médica de estos fármacos genera un desbalance electrolítico, que puede manifestarse con hiponatremia, hipocalemia, hipocalcemia e hipomagnesemia, hipercalemia, entre otras alteraciones. El objetivo de este trabajo fue investigar las caracteríscas del uso inapropiado de diuréticos a partir de la casuística del CENATOXA. Se realizó un estudio descriptivo restrospectivo sobre los análisis ingresados al CENATOXA con solicitud de investigación cualitativa de diuréticos en orina, entre los años 2002 y 2016. En dicho período ingresaron al CENATOXA 138 casos, de los cuales el 56 % resultó positivo para algún diurético. Del total de casos con resultado positivo, el 93,5 % fueron mujeres entre 25 y 55 años de edad y predominó la etiología intencional. Los diuréticos mayoritariamente encontrados fueron hidroclorotiazida y furosemida. El perfil de diuréticos hasta el año 2008 (hidroclorotiazida = 68% de los casos positivos) se diferenció del hallado entre 2009 y 2016 (furosemida + hidroclorotiazida = 60% de los casos positivos). Se observó recurrencia en el uso inapropiado en el 8% de los casos. El uso simultáneo de más de un diurético y la recurrencia son factores que pueden contribuir a la aparición de toxicidad. Estos resultados sugieren que el uso inapropiado de diuréticos es una situación que debería ser ob­servada más atentamente para establecer mejor su alcance y sus riesgos.

Among the situations associated with diuretics misuse are the attempts to lose weight fast, frequently observed in eating disorders, and the attempts to mask the consumption of other substances, in the case of sports competitions. The use of these drugs with no medical indication or supervision generates an electrolyte imbalance, leading to hyponatremia, hypokalemia, hypocalcemia and hypomagnesemia, hyperkalemia, among other alterations. The objective of this work was to investigate the characteristics of diuretics misuse from the CENATOXA database, where the qualitative investigation of diuretics in urine is per­formed. A descriptive retrospective study was conducted on the cases admitted to the CENATOXA with a request for qualitative diuretic investigation, between 2002 and 2016. During this period, 138 urine samples were received at the CENATOXA and 56% were positive for at least one diuretic. Of all cases with positive results, 93.5% were women between 25 and 55 years of age, and intentional etiology predominated. The most detected diuretics were hydrochlorothiazide and furosemide. The diuretic misuse pattern detected up to 2008 (hydrochlorothiazide = 68% of positive cases) differed from that detected between 2009 and 2016 (furosemide + hydrochlorothiazide = 60% of positive cases). Recurrence in misuse was observed in 8% of the cases. The simul­taneous misuse of more than one diuretic and the recurrence are factors that can contribute to the onset of toxicity. These results suggest that diuretic misuse is a situation that should be observed more closely to better assess its consequences and its risks.

Screening for parathyroid hormone resistance in patients with nonphenotypically evident pseudohypoparathyroidism.

OBJECTIVE: Hypocalcemia and hyperphosphatemia in the setting of elevated parathyroid hormone (PTH) and normal vitamin D metabolites, raises the possibility of PTH resistance. The idiopathic and inherited forms of PTH resistance are referred to as pseudohypoparathyroidism. Nonphenotypically evident pseudohypoparathyroidism can go undiagnosed for decades. We have designed a new test to diagnose PTH resistance and confirmed its clinical utility in the diagnosis of pseudohypoparathyroidism. METHODS: Our test consists of a subcutaneous injection of commercially available recombinant PTH and concomitant measurement of cyclic adenosine monophosphate in urine. We implemented the test in 2 patients with recalcitrant hypocalcemia and a healthy control subject. RESULTS: Our test unequivocally demonstrated PTH resistance in both patients. One of the patients had phenotypically evident pseudohypoparathyroidism type-1a hence, PTH resistance was suspected. The other patient with nonphenotypically evident disease, also showed PTH resistance and was later demonstrated to have pseudohypoparathyroidism type-1b at the genomic level and confirmed to be of familial type. CONCLUSION: Our results show for the first time the implementation of a simple new diagnostic tool designed to check for PTH resistance. This new test has already proven to be useful in few occasions at our institution. Larger populations, however, should be tested before implementation of such a test is considered a standard of care.