Calcium-sensing receptor autoantibody-mediated hypoparathyroidism associated with immune checkpoint inhibitor therapy: diagnosis and long-term follow-up.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have produced significant survival benefit across many tumor types. However, immune-related adverse events are common including autoimmune responses against different endocrine organs. Here, a case of ICI-mediated hypoparathyroidism focusing on long-term follow-up and insights into its etiology is presented. CASE AND METHODS: A 73-year-old man developed severe symptomatic hypocalcemia after the initiation of ipilimumab and nivolumab for the treatment of metastatic melanoma. Hypoparathyroidism was diagnosed with undetectable intact parathyroid hormone (PTH). Immunoprecipitation assays, ELISAs, and cell-based functional assays were used to test the patient for antibodies against the calcium-sensing receptor (CaSR). NACHT leucine-rich repeat protein 5 (NALP5) and cytokine antibodies were measured in radioligand binding assays and ELISAs, respectively. RESULTS: The patient's symptoms improved with aggressive calcium and vitamin D supplementation. At 3 years and 3 months since the diagnosis of hypoparathyroidism, PTH was still inappropriately low at 7.6 pg/mL, and attempted discontinuation of calcium and calcitriol resulted in recurrent symptomatic hypocalcemia. Analysis for an autoimmune etiology of the patient's hypoparathyroidism indicated that CaSR antibodies were negative before treatment and detected at multiple time points afterwards, and corresponded to the patient's clinical course of hypoparathyroidism. CaSR antibodies purified from the patient's serum activated the human CaSR. The patient was seronegative for NALP5 and cytokine antibodies, indicating that their hypoparathyroidism was not a manifestation of autoimmune polyendocrine syndrome type 1. CONCLUSION: The etiology of hypocalcemia is likely autoimmune hypoparathyroidism caused by the development of CaSR-activating antibodies that might prevent PTH release from the parathyroid.

Early Calcium Supplementation After Total Thyroidectomy Can Prevent Symptomatic Hypocalcemia - Findings from a Retrospective Study.

INTRODUCTION: Thyroidectomy for thyroid cancers and central neck dissection are considered as independent predictors of postoperative hypocalcemia. Post-surgical hypocalcemia is the most common and often the most difficult long-term consequence of thyroid surgeries. Management of hypocalcemia is done with calcium supplementation, but there is no consensus on the timing and the amount of calcium supplementation. MATERIALS AND METHODS: A retrospective study of all thyroid cancer patients who underwent total thyroidectomy at our Centre, from August 2009 to August 2017 was done to evaluate the prevalence of symptomatic hypocalcemia. The patients were grouped into two based on the early and late supplementation of calcium in the form of intravenous calcium gluconate and oral calcium with calcitriol. RESULTS: There were 133 patients of which 109 had papillary carcinoma, 11 had follicular, 3 had hurthle cell and 10 had medullary carcinoma. Of these, 49.6% underwent total thyroidectomy alone and the rest with neck dissection. 38 patients (28.6%) had a unilateral neck dissection and 16 patients (12%) had a bilateral neck dissection. 14 out of the 67 patients (20.9%) who underwent neck dissection developed symptomatic hypocalcaemia, in contrast to only 2 patients out of the 66 (3%) without neck dissection. 31.7% of lateral neck dissection and 7.7% of central compartment dissection had symptomatic hypocalcaemia (p value = 0.0053). 22.5% of patients whose parathyroid were not identified had more symptomatic hypocalcaemia than in whom at least one parathyroid gland was seen (p value=0.0004). Eleven out of 73 patients (15.1%) who were treated late with calcium and calcitriol, and one out of 60 (1.7%) who had early calcium supplementation developed symptoms (p value=0.0073). CONCLUSION: Central compartment and lateral neck dissection were significantly associated with higher incidence of symptomatic hypocalcemia. Early intervention with calcium supplementation reduced the symptoms of hypocalcemia. Identification and preservation of parathyroid glands significantly reduces the hypocalcemia.

Cardiac, bone and growth plate manifestations in hypocalcemic infants: revealing the hidden body of the vitamin D deficiency iceberg.

BACKGROUND: Whilst hypocalcemic complications from vitamin D deficiency are considered rare in high-income countries, they are highly prevalent among Black, Asian and Minority Ethnic (BAME) group with darker skin. To date, the extent of osteomalacia in such infants and their family members is unknown. Our aim was to investigate clinical, cardiac and bone histomorphometric characteristics, bone matrix mineralization in affected infants and to test family members for biochemical evidence of osteomalacia. CASE PRESENTATION: Three infants of BAME origin (aged 5-6 months) presented acutely in early-spring with cardiac arrest, respiratory arrest following seizure or severe respiratory distress, with profound hypocalcemia (serum calcium 1.22-1.96 mmol/L). All infants had dark skin and vitamin D supplementation had not been addressed during child surveillance visits. All three had severely dilated left ventricles (z-scores + 4.6 to + 6.5) with reduced ejection fraction (25-30%; normal 55-70), fractional shortening (7 to 15%; normal 29-40) and global hypokinesia, confirming hypocalcemic dilated cardiomyopathy. They all had low serum levels of 25 hydroxyvitamin D (25OHD < 15 nmol/L), and elevated parathyroid hormone (PTH; 219-482 ng/L) and alkaline phosphatase (ALP; 802-1123 IU/L), with undiagnosed rickets on radiographs. One infant died from cardiac arrest. At post-mortem examination, his growth plate showed a widened, irregular zone of hypertrophic chondrocytes. Histomorphometry and backscattered electron microscopy of a trans-iliac bone biopsy sample revealed increased osteoid thickness (+ 262% of normal) and osteoid volume/bone volume (+ 1573%), and extremely low bone mineralization density. Five of the nine tested family members had vitamin D deficiency (25OHD < 30 nmol/L), three had insufficiency (< 50 nmol/L) and 6/9 members had elevated PTH and ALP levels. CONCLUSIONS: The severe, hidden, cardiac and bone pathology described here exposes a failure of public health prevention programs, as complications from vitamin D deficiency are entirely preventable by routine supplementation. The family investigations demonstrate widespread deficiency and undiagnosed osteomalacia in ethnic risk groups and call for protective legislation.

Dietary Magnesium Alleviates Experimental Murine Colitis Through Upregulation of the Transient Receptor Potential Melastatin 6 Channel.

Background: Magnesium (Mg) is essential for human health and is absorbed mainly in the intestine. In view of the likely occurrence of an Mg deficit in inflammatory bowel disease (IBD) and the documented role of Mg in modulating inflammation, the present study addresses whether Mg availability can affect the onset and progression of intestinal inflammation. Methods: To study the correlation between Mg status and disease activity, we measured magnesemia by atomic absorption spectroscopy in a cohort of IBD patients. The effects of dietary Mg modulation were assessed in a murine model of dextran sodium sulfate (DSS)-induced colitis by monitoring magnesemia, weight, fecal occult blood, diarrhea, colon length, and histology. Expression of the transient receptor potential melastatin (TRPM) 6 channel was assessed by real-time reverse transcription polymerase chain reaction and immunohistochemistry in murine colon tissues. The effect of Mg on epithelial barrier formation/repair was evaluated in human colon cell lines. Results: Inflammatory bowel disease patients presented with a substantial Mg deficit, and serum Mg levels were inversely correlated with disease activity. In mice, an Mg-deficient diet caused hypomagnesemia and aggravated DSS-induced colitis. Colitis severely compromised intestinal Mg2+ absorption due to mucosal damage and reduction in TRPM6 expression, but Mg supplementation resulted in better restoration of mucosal integrity and channel expression. Conclusions: Our results highlight the importance of evaluating and correcting magnesemia in IBD patients. The murine model suggests that Mg supplementation may represent a safe and cost-effective strategy to reduce inflammation and restore normal mucosal function.

Endocrine Complications of Surgical Treatment of Thyroid Cancer: An Update.

Postoperative hypoparathyroidism (HypoPT) and hypothyroidism (HypoT) are the main endocrine complications after the surgical treatment for thyroid cancer. Postsurgical HypoPT can be transient, protracted or permanent. Its frequency varies according to the underlying cervical pathology, surgical technique, and mainly the experience of the surgeon. Risk factors for HypoPT include aggressiveness of the tumor, extent of surgery, the presence of parathyroid gland in the pathologic specimen, and surgeon experience. Clinical manifestations of postsurgical HypoPT can be acute or chronic. An adequate surgical technique that minimizes trauma and preserve the vascularization of the parathyroid glands is the better procedure to reduce the risk of postoperative HypoPT. Acute hypocalcemia may be managed with intravenous or oral calcium supplements, according to the level of serum calcium and the presence of signs and symptoms. Patients with permanent HypoPT require lifelong calcium and vitamin D supplementation. Calcitriol is the vitamin D metabolite of preference because of its high activity and short half-life. Both PTH (1-34) and intact PTH (1-84) have demonstrated to be attractive options in hypoparathyroid patients who cannot maintain stable serum and urinary calcium levels with calcium and vitamin D supplementation. However, the long-term safety of these preparations has not been established. Postsurgical HypoT is an unavoidable consequence of total or near-total thyroidectomy for thyroid cancer. Replacement and suppressive therapy are necessary in these patients. Thyroid hormone suppression therapy has shown to be accompanied by a decreased risk of disease progression and recurrence; however, it may also be associated with increased risk of dysrhythmia and loss of bone mass. Therefore, the intensity of TSH suppression must be established in a personalized way after balancing risk and benefits, according to the severity of the thyroid cancer, the response to therapy, and the individual risk factors for adverse events.

Novel calcium-sensing receptor cytoplasmic tail deletion mutation causing autosomal dominant hypocalcemia: molecular and clinical study.

OBJECTIVE: Autosomal dominant hypocalcemia (ADH) is a rare disorder caused by activating mutations of the calcium-sensing receptor (CASR). The treatment of ADH patients with 1α-hydroxylated vitamin D derivatives can cause hypercalciuria leading to nephrocalcinosis. DESIGN AND METHODS: We studied a girl who presented with hypoparathyroidism and asymptomatic hypocalcemia at age 2.5 years. Mutations of CASR were investigated by DNA sequencing. Functional analyses of mutant and WT CASRs were done in transiently transfected human embryonic kidney (HEK293) cells. RESULTS: The proband and her father are heterozygous for an eight-nucleotide deletion c.2703_2710delCCTTGGAG in the CASR encoding the intracellular domain of the protein. Transient expression of CASR constructs in kidney cells in vitro suggested greater cell surface expression of the mutant receptor with a left-shifted extracellular calcium dose-response curve relative to that of the WT receptor consistent with gain of function. Initial treatment of the patient with calcitriol led to increased urinary calcium excretion. Evaluation for mosaicism in the paternal grandparents of the proband was negative. CONCLUSIONS: We describe a novel naturally occurring deletion mutation within the CASR that apparently arose de novo in the father of the ADH proband. Functional analysis suggests that the cytoplasmic tail of the CASR contains determinants that regulate the attenuation of signal transduction. Early molecular analysis of the CASR gene in patients with isolated idiopathic hypoparathyroidism is recommended because of its relevance to clinical outcome and treatment choice. In ADH patients, calcium supplementation and low-dose cholecalciferol avoids hypocalcemic symptoms without compromising renal function.

Vitamin D Metabolites and Their Association with Calcium, Phosphorus, and PTH Concentrations, Severity of Illness, and Mortality in Hospitalized Equine Neonates.

BACKGROUND: Hypocalcemia is a frequent abnormality that has been associated with disease severity and outcome in hospitalized foals. However, the pathogenesis of equine neonatal hypocalcemia is poorly understood. Hypovitaminosis D in critically ill people has been linked to hypocalcemia and mortality; however, information on vitamin D metabolites and their association with clinical findings and outcome in critically ill foals is lacking. The goal of this study was to determine the prevalence of vitamin D deficiency (hypovitaminosis D) and its association with serum calcium, phosphorus, and parathyroid hormone (PTH) concentrations, disease severity, and mortality in hospitalized newborn foals. METHODS AND RESULTS: One hundred newborn foals ≤72 hours old divided into hospitalized (n = 83; 59 septic, 24 sick non-septic [SNS]) and healthy (n = 17) groups were included. Blood samples were collected on admission to measure serum 25-hydroxyvitamin D3 [25(OH)D3], 1,25-dihydroxyvitamin D3 [1,25(OH) 2D3], and PTH concentrations. Data were analyzed by nonparametric methods and univariate logistic regression. The prevalence of hypovitaminosis D [defined as 25(OH)D3 <9.51 ng/mL] was 63% for hospitalized, 64% for septic, and 63% for SNS foals. Serum 25(OH)D3 and 1,25(OH) 2D3 concentrations were significantly lower in septic and SNS compared to healthy foals (P<0.0001; P = 0.037). Septic foals had significantly lower calcium and higher phosphorus and PTH concentrations than healthy and SNS foals (P<0.05). In hospitalized and septic foals, low 1,25(OH)2D3 concentrations were associated with increased PTH but not with calcium or phosphorus concentrations. Septic foals with 25(OH)D3 <9.51 ng/mL and 1,25(OH) 2D3 <7.09 pmol/L were more likely to die (OR=3.62; 95% CI = 1.1-12.40; OR = 5.41; 95% CI = 1.19-24.52, respectively). CONCLUSIONS: Low 25(OH)D3 and 1,25(OH)2D3 concentrations are associated with disease severity and mortality in hospitalized foals. Vitamin D deficiency may contribute to a pro-inflammatory state in equine perinatal diseases. Hypocalcemia and hyperphosphatemia together with decreased 1,25(OH)2D3 but increased PTH concentrations in septic foals indicates that PTH resistance may be associated with the development of these abnormalities.

Is Preoperative Vitamin D Deficiency a Risk Factor for Postoperative Symptomatic Hypocalcemia in Thyroid Cancer Patients Undergoing Total Thyroidectomy Plus Central Compartment Neck Dissection?

BACKGROUND: Although some studies have reported that preoperative vitamin D deficiency (VDD) is a risk factor for hypocalcemia after total thyroidectomy (TT) in patients with nontoxic multinodular goiter or Graves' disease, the association between VDD and postoperative hypocalcemia in thyroid cancer patients undergoing TT plus central compartment neck dissection (CCND) remains unclear. This study evaluated whether preoperative VDD was associated with postoperative symptomatic hypocalcemia. MATERIALS AND METHODS: Data were collected prospectively between September 2012 and May 2013. A total of 267 consecutive thyroid cancer patients who underwent TT with CCND were analyzed. Patients were divided into two groups--VDD or non-VDD--by preoperative vitamin D level of <10 or ≥10 ng/mL. Symptomatic hypocalcemia was defined as serum calcium <8.2 mg/dL and symptoms or signs of hypocalcemia. The rates of postoperative symptomatic hypocalcemia and clinicopathological features were compared between the two patient groups. RESULTS: The rate of postoperative symptomatic hypocalcemia was higher in the VDD group than in the non-VDD group (43.8% vs. 30.4%, p=0.043). By logistic regression analysis, predictive factors for postoperative symptomatic hypocalcemia included a preoperative vitamin D level of <10 ng/mL (p=0.007; odds ratio=3.00). In patients who had postoperative intact parathyroid hormone (iPTH) levels <15 pg/mL, symptomatic hypocalcemia was more common in the VDD group than in the non-VDD group (77.5% vs. 53.2%, p=0.008). The findings show that a preoperative vitamin D threshold level of >20 ng/mL reduced the risk of symptomatic hypocalcemia by 72% when compared with patients with VDD (p=0.003). CONCLUSION: VDD is significantly associated with postoperative symptomatic hypocalcemia in thyroid cancer patients undergoing TT plus CCND. VDD was predictive for symptomatic hypocalcemia when patients had postoperative serum iPTH levels <15 pg/mL. Thus, preoperative supplementation with oral vitamin D should be considered to minimize postoperative symptomatic hypocalcemia.

Disorders of mineral metabolism in the newborn.

Disorders of calcium and phosphorus homeostasis present both acute and chronic clinical consequences for newborns. The etiologies responsible range from iatrogenic, idiopathic, and inherited metabolic abnormalities. Maintenance of physiologically normal serum calcium and phosphorus requires complex interactions between the kidneys, gastrointestinal tract, and bone. Calciotropic hormones such as vitamin D and parathyroid hormone, as well as hormones controlling phosphorus homeostasis, such as fibroblast growth factor-23 (FGF-23), are essential in controlling these interactions. In newborns, calcium and phosphorus balance must necessarily be positive in order to provide the requisite building blocks for growth and maturation. Renal tubular handling of these minerals is a key control point in regulating the overall body balance in calcium and phosphorus. Adaptive changes in renal calcium and phosphorus reabsorption in newborns explain how a net positive total body balance of these minerals is achieved. Monogenetic disorders leading to abnormal renal handling of calcium and/or phosphorus have immediate clinical consequences in terms of complications associated with high or low levels of these minerals. Perhaps more importantly, chronic abnormalities of calcium and/or phosphorus, without treatment, may have serious consequences for growth and development of the growing skeleton. This article serves to review calcium and phosphorus regulation in the human body, describe differences in handling of these minerals by the newborn, and review the conditions, both acquired and congenital, that may present with abnormalities in calcium and/or phosphorus in the newborn period.

Role of postoperative vitamin D and/or calcium routine supplementation in preventing hypocalcemia after thyroidectomy: a systematic review and meta-analysis.

BACKGROUND: Transient hypocalcemia is a frequent complication after total thyroidectomy. Routine postoperative administration of vitamin D and calcium can reduce the incidence of symptomatic postoperative hypocalcemia. We performed a systematic review to assess the effectiveness of this intervention. The primary aim was to evaluate the efficacy of routine postoperative oral calcium and vitamin D supplementation in preventing symptomatic post-thyroidectomy hypocalcemia. The second aim was to draw clear guidelines regarding prophylactic calcium and/or vitamin D therapy for patients after thyroidectomy. METHODS: We identified randomized controlled trials comparing the administration of vitamin D or its metabolites to calcium or no treatment in adult patients after thyroidectomy. The search was performed in PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Google Scholar, and Web of Knowledge databases. Patients with a history of previous neck surgery, calcium supplementation, or renal impairment were excluded. RESULTS: Nine studies with 2,285 patients were included: 22 in the vitamin D group, 580 in the calcium group, 792 in the vitamin D and calcium group, and 891 in the no intervention group, with symptomatic hypocalcemia incidences of 4.6%, 14%, 14%, and 20.5%, respectively. Subcomparisons demonstrated that the incidences of postoperative hypocalcemia were 10.1% versus 18.8% for calcium versus no intervention and 6.8% versus 25.9% for vitamin D and calcium versus no intervention. The studies showed a significant range of variability in patients' characteristics. CONCLUSIONS: A significant decrease in postoperative hypocalcemia was identified in patients who received routine supplementation of oral calcium or vitamin D. The incidence decreased even more with the combined administration of both supplements. Based on this analysis, we recommend oral calcium for all patients following thyroidectomy, with the addition of vitamin D for high-risk individuals.

Persistent hypocalcemia associated with therapeutic plasma exchange performed to reduce HLA antibody levels in cardiac transplant recipients.

BACKGROUND: Patients who receive heart transplants may undergo therapeutic plasma exchange to reduce high levels of HLA antibodies which may increase the risk of allograft rejection. Plasma exchange may predispose to hypocalcemia because of chelation of calcium by sodium citrate, used as an anticoagulant both during the procedure and in thawed fresh frozen plasma often used for replacement. METHODS: We report three adults with dilated cardiomyopathy who underwent cardiac transplantation and serial plasma exchange for high levels of HLA antibodies. We followed these patients' pre-exchange serum calcium levels and the quantity of calcium supplementation they received. Further, we examined myocardial tissue sections post-transplantation for calcium deposition. RESULTS: Our patients' serum calcium levels were initially normal, but, despite aggressive calcium repletion, remained low (nadirs for pre-exchange ionized calcium in two patients 4.48 and 3.8mg/dL, respectively, reference range 4.6-5.4mg/dL). For patient 3, pre-exchange total calcium on day 2 was 7.9mg/dL (reference range 8.4-10.2mg/dL). Two patients had intermittent symptoms of hypocalcemia. Studies of cardiac tissue sections (available only from these two patients) were consistent with the presence of calcium deposition post transplantation. In comparison, six patients who underwent lung transplantation and plasma exchange for high levels of HLA antibodies did not manifest significant hypocalcemia. CONCLUSIONS: We emphasize the need for prompt and sufficient calcium replacement, monitored by serum ionized calcium levels, in the early post-cardiac transplantation period when plasma exchange is performed with thawed fresh frozen plasma replacement. The persistently low serum calcium levels we observed post heart transplantation were possibly contributed to by increased myocardial calcium influx.

Calcinosis cutis complicated by compartment syndrome following extravasation of calcium gluconate in a neonate: a case report.

Hypocalcemia most frequently occurs in premature neonates. It is usually treated by intravenous (iv) calcium supplementation. However, complications caused by extravasation of iv calcium gluconate include localized soft tissue calcification, necrosis, cellulitis, osteomyelitis, and even compartment syndrome. We present a rare case of iatrogenic calcinosis cutis complicated by compartment syndrome secondary to extravasation of iv calcium gluconate in a neonate. Emergent fasciotomy was performed twice for decompression of compartment syndrome. Histologic findings revealed necrosis and calcification. Appropriate antibiotics were administered to control secondary infection. To the best of our knowledge, there were no previous case reports of calcinosis cutis with compartment syndrome in infants. Although iatrogenic calcinosis cutis is generally a benign entity, the early recognition of the presentation of extravasation of calcium gluconate is important to avoid severe complications and possible medical malpractice disputes. This report aims to raise doctors' awareness of the presentation, course, and management of this relatively rare iatrogenic complication.

A pilot study of addition of amifostine to melphalan, carboplatin, etoposide, and cyclophosphamide with autologous hematopoietic stem cell transplantation in pediatric solid tumors-A pediatric blood and marrow transplant consortium study.

Limited information is available regarding the use of amifostine in pediatric hematopoietic stem cell transplant (HSCT) patients. Melphalan, carboplatin, etoposide +/- cyclophosphamide is a commonly used preparatory regimen in pediatric solid tumor HSCT. Therefore, we decided to determine the feasibility of the addition of amifostine (750 mg/m b.i.d. x 4 d) to melphalan (200 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) (level 1) and escalating doses of cyclophosphamide (3000 mg/m and 3800 mg/m, levels 2 and 3, respectively) followed by autologous HSCT. Thirty-two patients with a variety of pediatric solid tumors were studied. Seventeen patients were accrued at level 1, 9 at level 2, and 6 at level 3. Major toxicities during the administration of the preparatory regimen were hypocalcemia, emesis, and hypotension. Hypocalcemia required aggressive calcium supplementation during the conditioning phase. No dose limiting toxicities were encountered at level 3. Amifostine at 750 mg/m b.i.d. for 4 days can be administered with a double alkylator regimen consisting of melphalan (200 mg/m), cyclophosphamide (up to 3800 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) with manageable toxicities.

Idiopathic hypoparathyroidism presenting with severe hypocalcemia and asymptomatic basal ganglia calcification followed by acute intracerebral bleed.

OBJECTIVE: To report a case of idiopathic hypoparathyroidism presenting with severe hypocalcemia and intracerebral calcifications that resulted in a spontaneous intracerebral bleed. METHODS: We present the clinical, laboratory, and radiologic findings in a woman with idiopathic hypoparathyroidism who developed spontaneous intracerebral bleed in the setting of chronic intracerebral calcifications. RESULTS: A 37-year-old woman presented with vague symptoms of hypocalcemia. Clinical evaluation revealed brisk deep tendon reflexes and positive Chvostek's and Trousseau's signs. The serum calcium level was 3.7 mg/dL (reference range, 8.0 to 10.6 mg/dL) and the phosphorus level was 8.2 mg/dL (reference range, 2.3 to 5.0 mg/dL). Serum intact parathyroid hormone was undetectable. Computed tomography of the head showed extensive bilateral symmetrical calcification of basal ganglia and dentate nucleus in the cerebellum and centrum semiovale. Fluid and electrolytes were replaced appropriately, and calcium and calcitriol were prescribed. While in the hospital, the patient developed an acute intracerebral bleed confirmed by computed tomography. The patient recovered without neurologic sequelae and was discharged from the hospital on calcium supplementation and calcitriol. Repeated computed tomography of the head 3 years later demonstrated complete resolution of the bleed. CONCLUSION: This case suggests that patients with severe hypoparathyroidism and intracerebral calcification may be at risk for spontaneous intracerebral bleed and should be monitored accordingly.

Hypocalcemic heart failure in thalassemic patients.

Hypocalcemic cardiomyopathy in primary or secondary hypoparathyroidism is usually refractory to conventional treatment of cardiac failure. We report the case of a thalassemic patient with severe cardiac failure that might have been attributed to several factors, such as hemosiderosis, hypomagnesemia, and hypocalcemia, refractory to conventional cardiac therapy. Cardiac echocardiography showed impaired biventricular performance, and laboratory analyses revealed hypoparathyroidism due to hemosiderosis. When concomitant treatment of heart failure and calcium supplementation was initiated, correction of hypocalcemia resulted in clinical and laboratory improvement, providing strong evidence in support of our hypothesis about hypocalcemic myocardiopathy.

An unusual case of generalized soft-tissue mineralization in a suckling foal.

An atypical case of severe soft-tissue mineralization in a 3-week-old foal from a herd of Andalusian horses is described. The herd clinical history and the laboratory findings were compatible with a diagnosis of secondary hyperparathyroidism due to a mineral imbalance in the diet (low calcium and high phosphorus intake). Mares showed a marked increase in serum parathyroid hormone (PTH) approximately 10 times normal levels. Serum PTH was marginally elevated in foals. Clinical signs (unthriftiness, painful joints, lameness in one or more limbs, and stiff gait) were more pronounced in foals than in mares. Two foals died and necropsy of one of them revealed extensive soft-tissue mineralization of arterial walls and pulmonary parenchyma. Clinical signs in mares and foals resolved by 4 weeks after diet adjustment.

The course of selected bone resorption marker concentrations in response to short-term hypocalcemia experimentally induced with disodium EDTA infusions in dairy cows.

The collagen metabolites hydroxyproline (HYP), deoxypyridinoline (DPD), and the carboxyterminal telopeptide of type I collagen (ICTP) are suitable markers for bone resorption in humans and several animal species. The purpose of this study was to describe the course of bone resorption markers during short-term hypocalcemia induced with disodium ethylenediaminetetraacetic acid (Na2EDTA) and to investigate whether bone resorption is increased in dairy cows under these conditions. EDTA infusions have been used as a model for periparturient paresis in dairy cows and to estimate the calcium mobilization rate from body reserves in ruminants. In this study, hypocalcemia was induced by means of a 5% Na2EDTA infusion (0.55 mg/kg/min Na2EDTA for 5 h = total dose of 100.6 g). Two experiments were conducted: (1) Six 4-11 years-old Brown Swiss cows were infused intravenously with EDTA for 5 h. Blood and urine samples were taken repeatedly from 1 day before until 10 days after infusion. (2) Towards the end of the lactation, the experiment was repeated with the same animals after a 14-day-period of feeding a low calcium diet (26 g/animal per day). The EDTA-infusion induced hypocalcemia and hypophosphatemia. The HYP-, DPD- and ICTP-concentration remained mainly unaffected during both infusions. Only DPD showed an increase during infusion and HYP an increase 2 days after the infusion. In conclusion, the EDTA infusion had little effect on the concentrations of the measured bone markers, which may be due to the fact that the serum calcium pool was refilled by increased absorption of Ca via the gastrointestinal tract. From these results, it can be concluded that bone resorption was not influenced by EDTA infusion.

The effects of hypocalcemia/hypophosphatemia on porcine bone and dental hard tissues in an inherited form of type 1 pseudo-vitamin D deficiency rickets.

The effects of Vitamin D deficiency rickets on the formation of mineralized dental tissues were studied in a breed of pigs which had moderate and marked hypocalcemia because of an inherited defect in the renal production of the biologically-active Vitamin D metabolites. Affected piglets developed classical symptoms of rickets which were fatal unless Vitamin D supplements were given. The dissected mandibles of homozygous (rickets) and heterozygous (normal) pigs were photographed and radiographed. Compared with those of normal pigs, the mandibles of homozygous pigs demonstrated slowed development/eruption of permanent teeth, under-mineralized bone, underdeveloped dentin (enlarged pulp chambers), interglobular dentin, and enamel hypoplasia. Enamel defects in rachitic pig teeth were difficult to observe radiographically, but could be detected visually and by SDS-PAGE analysis of the enamel protein components of developing and maturing enamel. There was significant retention of amelogenins in the enamel maturation zones of developing molars taken from rachitic pigs, but there was no obvious difference in the patterns of amelogenin processing.

[Hyperparathyroidism in endocrinology and nephrology]. / L'iperparatiroidismo in endocrinologia e in nefrologia.

The literature on primary and secondary hyperparathyroidism is surveyed in the presentation of an account of the present positon. Reference is also made to personal clinical experience, particularly in secondary cases. The physiopathology of parathormone, calcitonin and vitamin D is described; the last, in fact, has proved useful in the treatment of secondary forms. The usual symptomatological tests of performance are explained, together with their diagnostic value. The clinical symptoms and their physiopathological significance are also illustrated. Stress is laid on the importance of conservative management in secondary forms. Good results now enable parathyroidectomy to be avoided or delayed in many cases.