Mild Hyperphosphatemia Research Articles

Impact of hyperphosphatemia on neutrophil-to-lymphocyte ratio and on the inflammatory state in patients with stage 5 chronic kidney disease under maintenance hemodialysis

Background Hyperphosphatemia can lead to detrimental effects such as cardiovascular calcification, renal osteodystrophy, secondary hyperparathyroidism, and increased mortality. The neutrophil-to-lymphocyte ratio (NLR) in chronic kidney disease (CKD) patients provides information on the inflammation status, used as a marker of poor prognosis in several disorders such as malignancies, CKD, and myocardial infarction. To study the impact of hyperphosphatemia on NLR and on the inflammatory state in patients with stage 5 CKD under maintenance hemodialysis. Patients and methods This observational cross-sectional study was carried out in Benha University Hospitals on 100 patients on maintenance hemodialysis who were recruited and subjected to careful history, clinical examination, and NLR; serum phosphorus was done with different inflammatory markers. Patients who had significant infection, malignancy, and who had undergone parathyroidectomy were excluded. Results The mean±SD age of the studied group was 61.28±13.7, 40% were males. There were two (2%) with hypophosphatemia, 44 (44%) with normal phosphate, 34 (34%) with mild hyperphosphatemia, and 20 (20%) with severe hyperphosphatemia. There was high statistically significant difference between categories of serum phosphate as regards white blood cell, neutrophil, NLR, and platelets. There was high statistically significant difference between categories of serum phosphate as regards erythrocyte sedimentation rate and C-reactive protein (CRP), and statistically significant difference as regards serum albumin and serum intact-parathyroid hormone. There was positive significant correlation between serum phosphorus and both CRP and NLR (P<0.001). Conclusion There is high prevalence of hyperphosphatemia in hemodialysis patients. Hyperphosphatemia was associated with higher intact-parathyroid hormone, white blood cell, neutrophil, NLR, CRP, and platelets.

Acromegaly and non\u2010parathyroid hormone\u2010dependent hypercalcemia: a case report and literature review

BackgroundHypercalcemia associated with acromegaly is mostly parathyroid hormone (PTH)-dependent, being caused by parathyroid hyperplasia or adenoma, which are common in individuals with multiple endocrine adenomatosis-1 (MEN-1). The rare occurrence of non-PTH-dependent hypercalcemia associated with acromegaly is attributable to complex factors involving increased intestinal calcium absorption, enhanced bone calcium release, and reduced urinary calcium elimination. Although patients with acromegaly often have mild hyperphosphatemia and hypercalciuria, clinically significant hypercalcemia is extremely rare.Case presentationHere we present a case of non-PTH-dependent hypercalcemia associated with a growth hormone- (GH) and prolactin- (PRL) co-secreting pituitary macroadenoma. A 37-year-old Chinese man presented with a 6-year history of increasing ring and shoe sizes and was referred to the West China Hospital of Sichuan University for treatment of acromegaly. Pituitary magnetic resonance imaging (MRI) showed a 2.0 × 1.7 × 1.9 cm macroadenoma. Laboratory examinations revealed high serum concentrations of GH and PRL with mild hypercalcemia, hyperphosphatemia, hypercalciuria, inhibited PTH concentration, and increased bone turnover markers. Administration of cabergoline together with somatostatin resulted in sharp decreases in his GH, PRL, and serum and urinary calcium concentrations. These values were further reduced 5 months later and his PTH and bone turnover markers gradually returned to within the normal range.ConclusionsMild hyperphosphatemia and hypercalciuria are common in individuals with acromegaly and deserve attention because they may contribute to osteoporosis and urolithiasis. However, overt hypercalcemia is rare in such individuals. It is usually attributable to a coexisting parathyroid hyperplasia or adenoma, rarely being non-PTH-dependent. In such cases, the hypercalcemia is attributable to excessive PRL and hypogonadism and reverses with remission of acromegaly.

OR29-01 Long-Term Safety in Adults with X-Linked Hypophosphatemia (XLH) Treated with Burosumab, a Fully Human Monoclonal Antibody Against FGF23: Final Results of a Phase 3 Trial

Burosumab, a fully human IgG1 monoclonal antibody to FGF23, is approved in Canada and Brazil to treat XLH in patients ≥1 year of age and in the US to treat XLH in patients ≥6 months of age. Burosumab has also received conditional marketing authorization in Europe to treat XLH with radiographic evidence of bone disease in children ≥1 year of age and in adolescents with growing skeletons. Burosumab significantly improved serum phosphorus, fracture/pseudofracture healing, stiffness, and physical functioning in a phase 3, double-blind, multicenter study (CL303, NCT02526160). In this trial, subjects were randomized 1:1 to receive burosumab or placebo subcutaneously every 4 weeks. At Week 24, subjects in the placebo group crossed over to receive burosumab (total duration ≥96 weeks). Here, we report final long-term safety results from this trial. Most (119/134, 89%) subjects completed 96 weeks and received 1 mg/kg burosumab; protocol-specified dose reductions were required for 11/134 (8.2%) subjects to effectively manage hyperphosphatemia (all mild [Grade 1]). Mean (±SE) baseline serum phosphorus was 1.98 (±0.03) mg/dL and was 2.97 (±0.05) mg/dL at Week 94 (midpoint of dose interval). Mean (±SE) iPTH level was 96 (±3.8) pg/mL at baseline and progressively declined to 79 (±3.3) pg/mL at Week 96. Nephrocalcinosis score at Week 96 changed by 0 in 101 subjects, -1 in 9 subjects, +1 in 10 subjects (14 subjects not available). There were no meaningful changes in ectopic mineralization. There were no neutralizing antibodies. No treatment-emergent adverse events led to study or treatment withdrawal. Serum phosphorus was maintained with long-term burosumab treatment, with no evidence of loss of effect in adults with XLH. Burosumab dose reductions effectively managed mild hyperphosphatemia. Frequency, severity, and types of AEs reported were consistent with previous burosumab trials.

Moderate to severe hyperphosphataemia as an independent prognostic factor for 28-day mortality in adult patients with sepsis

BackgroundIschaemic tissue injury caused by tissue hypoperfusion is one of the major consequences of sepsis. Phosphate concentrations are elevated in ischaemic tissue injury. This study was performed to investigate the...

SUN-329 RETURN TO DIALYSIS AFTER KIDNEY TRANSPLANTATION : ABOUT 13 CASES

The return to dialysis after transplant loss is an emerging problem in dialysis centers. The objective of this study is to determine the conditions ofinitial treatment in dialysis of patients who have lost graft function. This study involved 13 renal transplant patients who started or restarted a chronic dialysis program in the renal nephrology and renal transplant department at Sahloul Hospital. We collected biological and epidemiological clinical data from all patients during the transplantation period and during dialysis. Thirteen (13) patients were enrolled: 8 men (61%) and 5 women (39%); all these patients were dialyzed before renal transplantation for an average duration of 39.5 months, 10 of whom were on hemodialysis (HD) and 3 peritoneal dialysis (DP). At the time of renal transplantation, patients were, on average 43 years old. The 13 recipients had a living donation, with a functional kidney transplant lasting 6 to 66 months, with an average of 28.5 months. Kidney transplant recipients, on average of 28 years old when they returned to dialysis. 9 patients were hypertensive, one patient had diabetes, one patient had kaposi sarcoma and 2 patients had heart disease. 10 patients started dialysis with HD. 9 patients started emergency dialysis with positioning of a central catheter. Dialysis in 7 patients and preexisting arterio-venous fistula in 2 patients. Mean serum creatinine pre-dialysis was 889 μmol /L. The average urea was 37 mmol /L. The mean hemoglobin, albumin levels were 7.4 g / dl and 32 g /L respectively. Serum calcium was 1.88 mmol/L and there was mild hyperkalemia and hyperphosphatemia. Four patients received between 3 and 4 treatments for hypertension, while 5 received 2 but did not allow normalization of blood pressure in the vast majority of cases. These data may provoke critical reflection among practitioners in charge of kidney transplant patients, as regards the management of the transition period from renal transplantation to dialysis.

In vivo evidence for an interplay of FGF23/Klotho/PTH axis on the phosphate handling in renal proximal tubules.

Phosphate homeostasis is primarily maintained in the renal proximal tubules, where the expression of sodium/phosphate cotransporters (Npt2a and Npt2c) is modified by the endocrine actions of both fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH). However, the specific contribution of each regulatory pathway in the proximal tubules has not been fully elucidated in vivo. We have previously demonstrated that proximal tubule-specific deletion of the FGF23 coreceptor Klotho results in mild hyperphosphatemia with little to no change in serum levels of FGF23, 1,25(OH)2D3, and PTH. In the present study, we characterized mice in which the PTH receptor PTH1R was specifically deleted from the proximal tubules, either alone or in combination with Klotho ( PT-PTH1R-/- and PT-PTH1R/KL-/-, respectively). PT-PTH1R-/- mice showed significant increases in serum FGF23 and PTH levels, whereas serum phosphate levels were maintained in the normal range, and Npt2a and Npt2c expression in brush border membrane (BBM) did not change compared with control mice. In contrast, PT-PTH1R/KL-/- mice displayed hyperphosphatemia and an increased abundance of Npt2a and Npt2c in the renal BBM, along with increased circulating FGF23 levels. While serum calcium was normal, 1,25(OH)2D3 levels were significantly decreased, leading to extremely high levels of PTH. Collectively, mice with a deletion of PTH1R alone in proximal tubules results in only minor changes in phosphate regulation, whereas deletion of both PTH1R and Klotho leads to a severe disturbance, including hyperphosphatemia with increased sodium/phosphate cotransporter expression in BBM. These results suggest an important interplay between the PTH/PTH1R and FGF23/Klotho pathways to affect renal phosphate handling in the proximal tubules.

Hypophosphatemia is associated with poor prognosis of critically ill patients: a meta-analysis of 1 555 patients

To evaluate the relationship between hypophosphatemia and prognosis in critically ill patients. Some hypophosphatemia-associated prospective or retrospective clinical cohort studies were searched through CNKI, Wanfang Data, PubMed, Embase, Cochrane library, and Google Scholar English database respectively, with the guidance of these key words such as hypophosphatemia, intensive care, prognosis and fatality rate. The articles were concerned about the correlation between hypophosphatemia and the prognosis of patients in intensive care unit (ICU). The literatures collected were restricted from the creation of data base to April 2017. The mean value of < 0.8 mmol/L in serum phosphorus concentrations of the patients within the first 2 days of ICU admission would be treated as the diagnostic criteria of hypophosphatemia. Literature qualities were assessed by Newcastle-Ottawa scale (NOS). Meta-analysis was carried out by RevMan 5.3, and the sensitivity analysis was performed to test the stability of the meta-analysis. The existence of bias was analyzed by using the funnel graph analysis. Ten articles were ultimately included in the analysis, including 9 in Chinese and 1 in English, all of which were high qualities. 1 555 patients were involved in these clinical studies, of whom 606 patients had hypophosphatemia and other 949 were normal phosphatemia. Meta analysis results showed that patients with hypophosphatemia had higher acute physiology and chronic health evaluation II (APACHE II) score as compared with that of normal phosphatemia group [standardized mean difference (SMD) = 0.64, 95% confidence interval (95%CI) = 0.24-1.04, P = 0.002]. Subgroup analysis showed that APACHE II score increased in mild, moderate and severe hyperphosphatemia subgroups, and there were significant differences between any two subgroups (all P < 0.01). Longer duration of mechanical ventilation (SMD = 0.50, 95%CI = 0.23-0.78, P = 0.000 3) and the length of ICU stay (SMD = 0.36, 95%CI = 0.06-0.67, P = 0.02), and even higher ICU mortality [odds ratio (OR) = 2.99, 95%CI = 2.09-4.27, P < 0.000 01] were seen in patients with hypophosphatemia as compared with normal phosphatemia patients. However, serum creatinine (SCr) levels (SMD = -0.19, 95%CI = -2.76-2.39, P = 0.89) and serum albumin (Alb) level (SMD = -0.63, 95%CI = -1.54-0.27, P = 0.17) were all similar between hypophosphatemic group and normal phosphatemia group. Sensitivity analysis excluded the effect of heterogeneity on statistical results. The funnel graphics were basically symmetrical, which indicated that the included literatures were distributed well, and the publication bias was small. Occurrence of hypophosphatemia in ICU patients is associated with severity of illness, prolonged duration of MV and length of ICU stay, and higher mortalities. Levels of serum phosphorus may have certain clinical values for assessing prognosis of ICU patients.

Serum Phosphorus and Risk of Cardiovascular Disease, All-Cause Mortality, or Graft Failure in Kidney Transplant Recipients: An Ancillary Study of the FAVORIT Trial Cohort

Mild hyperphosphatemia is a putative risk factor for cardiovascular disease [CVD], loss of kidney function, and mortality. Very limited data are available from sizable multicenter kidney transplant recipient (KTR) cohorts assessing the potential relationships between serum phosphorus levels and the development of CVD outcomes, transplant failure, or all-cause mortality. Cohort study. The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial, a large, multicenter, multiethnic, controlled clinical trial that provided definitive evidence that high-dose vitamin B-based lowering of plasma homocysteine levels did not reduce CVD events, transplant failure, or total mortality in stable KTRs. Serum phosphorus levels were determined in 3,138 FAVORIT trial participants at randomization. During a median follow-up of 4.0 years, the cohort had 436 CVD events, 238 transplant failures, and 348 deaths. Proportional hazards modeling revealed that each 1-mg/dL higher serum phosphorus level was not associated with a significant increase in CVD risk (HR, 1.06; 95% CI, 0.92-1.22), but increased transplant failure (HR, 1.36; 95% CI, 1.15-1.62) and total mortality risk associations (HR, 1.21; 95% CI, 1.04-1.40) when adjusted for treatment allocation, traditional CVD risk factors, kidney measures, type of kidney transplant, transplant vintage, and use of calcineurin inhibitors, steroids, or lipid-lowering drugs. These associations were strengthened in models without kidney measures: CVD (HR, 1.14; 95% CI, 1.00-1.31), transplant failure (HR, 1.72; 95% CI, 1.46-2.01), and mortality (HR, 1.34; 95% CI, 1.15-1.54). We lacked data for concentrations of parathyroid hormone, fibroblast growth factor 23, or vitamin D metabolites. Serum phosphorus level is marginally associated with CVD and more strongly associated with transplant failure and total mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of phosphorus-lowering therapy on these hard outcomes may be warranted.

Management of Hyperphosphatemia

Serum phosphate levels, along with serum calcium and parathyroid hormone (PTH), are the most commonly used markers for the diagnosis, monitoring and treatment of chronic kidney disease (CKD)-mineral and bone disorder (MBD) abnormalities in patients affected by kidney failure. Hyperphosphatemia appears late in the course of CKD, but the consequences of phosphate retention, such as increased levels of FGF23 and hyperparathyroidism, can be appreciated much earlier. Clinical practice guidelines suggest aiming at phosphate levels that currently are reached by no more than 50% of patients, despite major efforts of nephrologists, nurses and dieticians in addressing the issue of dietary and pharmacological compliance. Thus, there are margins of improvement of phosphate management in CKD patients, which could be accomplished by dietary and/or pharmacological approaches aimed at improving patient compliance. Severe hyperphosphatemia is always associated with phosphate overload, but it should be kept in mind that even mild hyperphosphatemia can be linked to a positive phosphate balance and its deleterious consequences. In fact, hyperphosphatemia is associated with mortality and morbidity (including hyperparathyroidism, left ventricular hypertrophy, and vascular calcifications). Management of hyperphosphatemia should take into account the main rings of the therapeutic chain of phosphate control: defense of residual renal function, adequate dialysis, diet, and phosphate binders. Along with the traditional approaches to phosphate control, in this article new aspects of phosphate control are summarized, such as cooking tips, education regarding the presence of phosphate-based additives/preservatives in foods and even drugs, and the potential advantages of last-generation phosphate binders.

Clinical, biochemical and genetic spectrum of low alkaline phosphatase levels in adults

BackgroundLow serum levels of alkaline phosphatase (ALP) are a hallmark of hypophosphatasia. However, the clinical significance and the underlying genetics of low ALP in unselected populations are unclear. MethodsIn order to clarify this issue, we performed a clinical, biochemical and genetic study of 42 individuals (age range 20–77yr) with unexplained low ALP levels. ResultsNine had mild hyperphosphatemia and three had mild hypercalcemia. ALP levels were inversely correlated with serum calcium (r=−0.38, p=0.012), pyridoxal phosphate (PLP; r=−0.51, p=0.001) and urine phosphoethanolamine (PEA; r=−0.49, p=0.001). Although many subjects experienced minor complaints, such as mild musculoskeletal pain, none had major health problems. Mutations in ALPL were found in 21 subjects (50%), including six novel mutations. All but one, were heterozygous mutations. Missense mutations were the most common (present in 18 subjects; 86%) and the majority were predicted to have a damaging effect on protein activity. The presence of a mutated allele was associated with tooth loss (48% versus 12%; p=0.04), slightly lower levels of serum ALP (p=0.002), higher levels of PLP (p<0.0001) and PEA (p<0.0001), as well as mildly increased serum phosphate (p=0.03). Ten individuals (24%) had PLP levels above the reference range; all carried a mutated allele. ConclusionOne-half of adult individuals with unexplained low serum ALP carried an ALPL mutation. Although the associated clinical manifestations are usually mild, in approximately 50% of the cases, enzyme activity is low enough to cause substrate accumulation and may predispose to defects in calcified tissues.

Tenosinovitis with psammomatous calcification – a case report

Tenosynovitis with psammomatous calcification, described in 1983 by Gravanis and Gaffney, is poorly recognized by pathologists. Recently, tenosynovitis with psammomatous calcification differ from those of typical idiopathic calcifying tenosynovitis/calcific tendinitis and tumoral calcinosis, were reported based on the analysis of 6 cases. We report a 36-year-old man with tenosynovitis with psammomarous calcification involving the palmar side of the proximal interphalangeal (PIP) joint at left middle finger. He had been suffered from a slow growing painful mass at left finger for three weeks. He had not a history of persistent mild trauma and hyperphosphatemia. X-ray examination revealed ill-demarcated calcifying mass 5mm in diameter. The lesion, treated by surgical excision, was elastic soft and white-yellow mass on the volar plate of the PIP joint extending to the intraarticular space. Histologically, the lesion was centered in the tendon or peritendinous soft tissue and composed of a mixed fibroblastic and histiocytic proliferation with the formation of distinctive psammoma body-like spheroidal bodies.

Rasamsonia argillacea mycosis in a dog: first case in Europe

The fungus Rasamsonia argillacea was first described in 1969 (Stolk and others 1969). Its optimal growth temperature is between 37°C and 40°C (Houbraken and others 2012). It has been found...

Rasamsonia argillacea mycosis in a dog: first case in Europe

The fungus Rasamsonia argillacea was first described in 1969 (Stolk and others 1969). Its optimal growth temperature is between 37°C and 40°C (Houbraken and others 2012). It has been found...

Biochemical Effects of Phosphate-Containing Replacement Fluid for Continuous Venovenous Hemofiltration

Aims: To examine biochemical effects of phosphate-containing replacement fluid (Phoxilium®) for continuous venovenous hemofiltration (CVVH). Methods: Retrospective comparison of respective serum biochemistry with sequential use of Accusol™ and Phoxilium, each over 48 h of CVVH. Results: We studied 15 critically ill patients. Accusol was switched to Phoxilium after 5 (4–8) days of CVVH. Respective serum biochemistry after 36–42 h of Accusol versus Phoxilium were: phosphate 1.02 (0.82–1.15) versus 1.44 (1.23–1.78) mmol/l, ionized calcium 1.28 (1.22–1.32) versus 1.12 (1.06–1.21) mmol/l, bicarbonate 24 (23–25) versus 20 (19–22) mmol/l, base excess 0 (–2 to 1) versus –4 (–6 to –3) mmol/l (p < 0.001). Cumulative phosphate intakes during respective periods were 69.6 (56.6–76.6) versus 67.2 (46.6–79.0) mmol (p = 0.45). Plasma strong ion differences were narrower with Phoxilium (p < 0.05), with similar strong ion gaps. No additional intravenous phosphate was given during Phoxilium use. Seven patients had serum phosphate >1.44 mmol/l. Conclusions: Phoxilium versus Accusol use during CVVH effectively prevented hypophosphatemia but contributed to mild hyperphosphatemia, and is associated with relative hypocalcemia and metabolic acidosis.

A case of hypocalcemia

Hypocalcemia is a common disorder in the elderly, affecting 10% of the elderly population as a whole, 18% of those in hospital and 36% of those in long-term care [1, 2]. Many conditions can lead to hypocalcemia in adults young and old, e.g. primary hypoparathyroidism, chronic renal failure, gastrointestinal diseases (such as celiac disease or Crohn’s disease), drugs (particularly diuretics, bisphosphonates and antiepileptics), acute pancreatitis and thyroid surgery. Rare causes of hypocalcemia include isolated vitamin 1.25(OH)D3 deficiency or vitamin 1.25(OH)D3 resistance. Another, often neglected cause of hypocalcemia relating to functional parathyroid deficiency is hypomagnesemia. Magnesium and parathyroid hormone (PTH) are closely related, since the latter promotes magnesium reabsorption in the kidney, while mild hypomagnesemia (Mg [ 1.2 mg/dl) induces PTH secretion via a protein called CaSR (G protein) expressed particularly by the parathyroid glands. On the other hand, if blood magnesium levels drop below 1.2 mg/dl, the alpha subunit of the G protein is activated, and this leads to a decline in PTH secretion. This process is called a ‘‘paradoxical block’’ [3]. We report on a case of severe hypocalcemia in a 76-year old woman with hypomagnesemia and normal PTH levels. She was hospitalized at the Geriatric Department of the University of Padua for biliary colic: on admission the calcium level was 4.0 mg/dl. Cardiovascular examination showed a normal jugular venous pressure and normal heart sounds, with no murmurs or pericardial friction rub. Respiratory examination identified some crackling, compatible with mild cardiac failure, probably emphasized by the patient’s hypocalcemic state. Abdominal examination revealed nothing of note, with no Murphy or Blumberg signs. The patient was also negative for Trousseau’s and Chvostek’s signs. An electrocardiogram obtained on admission showed chronic atrial fibrillation with a mean rate of 78 bpm and an abnormal QTc interval (520 ms), with a severe risk of torsades de pointes. The patient had undergone total hip replacement for coxarthrosis in 2008, and had been on anticoagulant therapy for chronic atrial fibrillation since 2008. Her medical history was negative for any use of hypocalcemia-inducing medication (e.g. diuretics or bisphosphonates). Dietary assessment based on a modified version of the diet history questionnaire [4] indicated a low calorie intake (about 943 kcal), with a daily intake of 600 mg of calcium, 130 mg of magnesium and 54 IU of vitamin D3. After several episodes of lower back pain, she had undergone a computed imaging (CT scan) of the spine in 2006, which revealed osteopenia and major signs of arthrosis. Given the radiological evidence of osteopenia, she also had performed a DEXA (the T score was 2 for the lumbar spine and 1 for the total hip) and lumbosacral spine X-ray study with morphometry, which ruled out any collapse of the vertebrae. As shown in Table 1, on admission the patient had severe hypocalcemia (total calcium 4.0 mg/dl; free calcium 2.00 mg/dl), mild hyperphosphatemia, hypocalciuria and hypophosphaturia, with severe hypomagnesemia (1.4 mg/ dl), low vitamin 25(OH)D3 (\4 ng/ml) and normal PTH levels (60 ng/l). N. Veronese F. Bolzetta M. Mosele E. Manzato G. Sergi Department of Medical and Surgical Sciences, Division of Geriatrics, University of Padova, Via Giustiniani 2, 35128 Padova, Italy

Extended-Release Niacin/Laropiprant Lowers Serum Phosphorus Concentrations in Patients with Type 2 Diabetes and Mild Hyperphosphatemia

Extended-Release Niacin/Laropiprant Lowers Serum Phosphorus Concentrations in Patients with Type 2 Diabetes and Mild Hyperphosphatemia

Oral calcium supplementation reverses the biochemical pattern of parathyroid hormone resistance in underprivileged Indian toddlers

Background:Toddlers in Pune, India, accustomed to low dietary calcium intake but vitamin D replete have low serum ionised calcium and inappropriately raised serum inorganic phosphorus concentrations together with elevated serum...

A Novel Mutation Causing Pseudohypoparathyroidism 1A with Congenital Hypothyroidism and Osteoma Cutis

Various inactivating mutations in guanine nucleotide−binding protein, alpha−stimulating activity polypeptide1 (GNAS1) gene have been described with poor phenotype correlation. Pseudohypoparathyroidism type 1a (PHP1a) results from an inactivating mutation in the GNAS1 gene. Hormone resistance occurs not only to parathyroid hormone (PTH), but typically also to other hormones which signal via G protein coupled receptors including thyroid stimulating hormone (TSH), gonadotropins, and growth hormone releasing hormone. In addition, the phenotype of Albright hereditary osteodystrophy (AHO) is observed, which may include short stature, round facies, brachydactyly, obesity, ectopic soft tissue or dermal ossification (osteoma cutis) and psychomotor retardation with variable expression. We present a 2−year−old boy with PHP 1A who initially presented at age 3 weeks with congenital hypothyroidism. By 17 months of age, he manifested osteoma cutis, psychomotor retardation, obesity, brachydactyly and resistance to PTH with normocalcemia and mild hyperphosphatemia. Genetic analysis revealed a novel mutation in exon 13 of GNAS1 in our patient. This mutation, c.1100_1101insA, resulted in a frameshift and premature truncation of bases downstream. This mutation was also found in the mother of this patient who was also noted to have short stature, obesity, brachydactyly and non progressive osteoma cutis, but no hormone resistance.We report a novel heterozygous mutation causing PHP1A with PTH and TSH resistance and AHO which has not been described previously. PHP1A is also a rare presentation of congenital hypothyroidism.Conflict of interest:None declared.

Interpreting observational studies of disordered mineral metabolism and mortality in patients on hemodialysis

This Practice Point commentary discusses the findings and limitations of a cohort study reported by Wald and colleagues of mineral metabolism in patients on hemodialysis. The investigators' observational analysis utilized data from the 1,846 patients in the randomized, controlled Hemodialysis (HEMO) Study. Wald et al.'s advantages include the well-characterized dataset, particularly with regard to comorbid conditions. However, the authors found it impossible to analyze the potentially confounding effect of concomitant medications. Furthermore, the relatively small dataset, especially compared with those of previous studies, limits the power of this study. In summary, Wald et al.'s findings support earlier studies confirming the importance of mineral metabolism as a risk factor for mortality in patients on hemodialysis. However, because of its low statistical power, its lack of analysis of potentially important confounders, and its observational design, the study cannot provide appropriate targets and should not serve as a justification for tolerating mild hyperphosphatemia or hypercalcemia or for overlooking the importance of preventing secondary hyperparathyroidism.

Goitrous hypothyroidism associated with treatment with trimethoprim-sulfamethoxazole in a young dog

A 16-week-old female Boxer that had been treated for 5 weeks with trimethoprim-sulfamethoxazole and chloramphenicol because of aspiration pneumonia was evaluated for bilaterally symmetric masses in the subcutaneous tissues of the ventral neck, in the region of the larynx. Fine-needle aspirates were obtained from the neck masses; cytologic examination revealed well-differentiated thyroid epithelial tissue. A blood sample was collected for serum biochemical and thyroid function analyses. Mild hyperphosphatemia, severe hypercholesterolemia, mild hyperkalemia, and a mild increase in creatine kinase activity were identified. Serum concentration of total thyroxine was less than the lower reference limit, and that of thyroid-stimulating hormone was greater than the upper reference limit. Findings were consistent with a diagnosis of clinical hypothyroidism in a skeletally immature dog. Treatment with trimethoprim-sulfamethoxazole was discontinued. The dog was reevaluated 3 weeks later, at which time the neck masses were markedly decreased in size. Serum concentrations of cholesterol and potassium were lower; serum concentrations of total thyroxine and thyroid-stimulating hormone were near or within respective reference ranges. Age-appropriate increases in serum phosphorus concentration and serum alkaline phosphatase activity were also detected. To the authors' knowledge, this is the first report of antimicrobial-induced goiter in a dog. Cytologic examination of fine-needle aspirates and interpretation of data from serum biochemical and thyroid function analyses were needed to obtain a definitive diagnosis. Practitioners should include goiter among the differential diagnoses for ventral neck swellings in young dogs receiving potentiated sulfonamide antimicrobials.