Water-clear cell adenoma: A rare form of hyperparathyroidism

INTRODUCTIONPrimary hyperparathyroidism is a common endocrine disorder, with an incidence of 21.6 per 100,000 person-years. Asymptomatic elevated serum calcium levels on routine biochemical investigations accounts for 80% of newly diagnosed primary hyperparathyroidism. Solitary adenoma is the commonest cause of primary hyperparathyroidism and can be treated by excision of a single gland.PRESENTATION OF CASEWe present a case of primary hyperparathyroidism in a 74-year-old female was referred to our surgery endocrine outpatients for assessment of a persistently elevated calcium level, lower abdominal pain and constipation. Biochemical analysis revealed corrected serum calcium of 3.13 mmol/L (reference range 2.17–2.51 mmol/L) and an intact parathyroid hormone level (iPTH) of 488.9 ng/L (reference range 15–65 ng/L). Sestamibi scan localised a persistent increased area of activity inferior to the lower pole of the left lobe of thyroid gland.DISCUSSIONThe patient underwent a minimally invasive parathyroidectomy using a 3 cm incision with intra-op radionucliotide localisation. At surgery a single large parathyroid gland measuring 5.5 cm was excised without complication. Grossly the parathyroid gland was an encapsulated tan mass measuring 5.5 cm × 2.5 cm × 2 cm and weight 13 g and histological assessment revealed a water-clear cell (WCC) adenoma. She made an uneventful post op recovery with normalisation of her serum calcium.CONCLUSIONWCC adenomas have a “low endocrinological activity” in which serum calcium levels do not elevate until the adenoma has reached considerable size. Our case supports this hypothesis and aids to the understanding of these rare tumours.     

Incremento de la densidad mineral ósea en pacientes con hiperparatiroidismo terciario tras paratiroidectomía total y autotrasplante de glándula paratiroides

IntroductionChanges in bone metabolism and bone mineral density are observed in renal transplant patients with tertiary hyperparathyroidism. The objective of this work was to analyse the increase in bone mineral density, as well the laboratory results, after total parathyroidectomy and autotransplantation in renal transplant patients with tertiary hyperparathyroidism.Material and methodsA retrospective study was conducted in which the bone mineral density values at femoral and lumbar level were analysed, together with the serum levels of calcium, phosphorous, parathyroid hormone (PTH), and alkaline phosphatase in 13 renal transplant patients with tertiary hyperparathyroidism before and after total parathyroidectomy and autotransplantation of the parathyroid glands.ResultsParathyroidectomy is associated with an increase in bone mineral density at femoral and lumbar level, with an increase of 8.6 ± 6.7% at lumbar level, and 4 ± 16.1% at femoral level. The decrease in calcium after the parathyroidectomy was 2.8 mg/dL (95% CI; 1.9-4). The decrease in PTH was 172 pg/mL (95% CI; 98-354) and the decrease in alkaline phosphatase was 229 U/L (95% CI; 70-371).ConclusionsTotal parathyroidectomy and autotransplantation of the parathyroid glands in renal transplant patients with tertiary hyperparathyroidism increases the bone mineral density. Furthermore, the calcium, PTH and alkaline phosphatase returned to normal in the long-term.     

Factores que condicionan la sensibilidad de la ecografía y la gammagrafía en la localización del adenoma paratiroideo

IntroductionThe treatment of choice for primary hyperparathyroidism (PHPT) when there is proper preoperative localization of the adenoma is minimally invasive parathyroidectomy. However, imaging techniques are not always able to provide the exact location. The objective is to identify potential factors that might influence the sensitivity and concordance of ultrasound (US) and 99mTc-methoxy-isonitrile parathyroid scintigraphy (MIBI-PS) and the actual location of the adenoma.MethodsWe reviewed the data of patients who underwent parathyroidectomies for PHPT. All patients had undergone ultrasound and 99mTc-MIBI scintigraphy as a preoperative location study. Multiple endocrine neoplasms, other hyperplasias and non-cervical ectopic adenomas were excluded. The sensitivity, PPV and concordance have been estimated for the location of the gland in both tests compared with the intraoperative location, using a multivariable analysis of the factors that might influence their localization capacity.Results139 patients (82% women) have been analysed. The US sensitivity was 56.7%, concordance (Kappa index) 0.387 and PPV 96.3%. The MIBI-PS sensitivity was 81.6%, the concordance (Kappa index) 0.669 and the PPV 97.4%. The factor that improved localization of the glands by US in the multivariable analysis was the absence of a concomitant thyroid pathology. The factor that improved the MIBI-PS results was a gland weight greater than 600 mg.ConclusionsUS sensitivity improves when there is no concomitant thyroid pathology. MIBI-PS sensitivity improves when the gland weight is greater than 600 mg.     

Surgical treatment of children with hyperparathyroidism: Single centre experience

BackgroundHyperparathyroidism (HPT) in children is rare and surgical management is supported only by limited evidence.MethodsRetrospective case series of all children under the age of 16 years who underwent parathyroidectomy (PTx) between 1978 and 2012.ResultsWe identified 29 children who had surgery for HPT. Six were neonates with neonatal severe hyperparathyroidism (NSHPT) and 23 older children (age range 7–16 years) with sporadic (16) or familial (7) HPT and 93% were symptomatic. Accuracy of ultrasound and MIbi in localising solitary parathyroid adenomas was 96%, but less helpful in hyperplasia and neonates.Children with NSHPT underwent 5 curative total and 1 subtotal PTx (no reoperations). Children with familial HPT underwent 3 total and 4 subtotal PTx. One child with subtotal PTx required a reoperation. Children with sporadic HPT underwent subtotal PTx prior to 1980 (2), exploration and removal of enlarged glands 1980–2002 (5) and minimally invasive PTx since 2002 (9) and all cured by the first operation.ConclusionsOur study documents that HPT in children is predominantly symptomatic on presentation and genetically determined in 46% of cases. Imaging is accurate in localising parathyroid adenomas, but not hyperplasias. Total PTx for familial HPT was curative and minimally invasive PTx is the operation of choice for older children with sporadic HPT.     

Health-related quality of life improvement following surgical treatment of primary hyperparathyroidism in a United Kingdom population

ObjectiveThe aim of this study was to determine if parathyroidectomy for primary hyperparathyroidism produces improvement in health-related quality of life in a United Kingdom population.MethodsSince October 2002, patients undergoing parathyroidectomy for primary hyperparathyroidism were asked to complete the SF-36 questionnaire, a validated self assessment tool prior to surgery and at six months post surgery. The questionnaires were either mailed to the patients or given at the time of outpatient follow up.Results24 out of 29 patients completed the questionnaire pre- and postoperatively. Compared to the national average, the median pre-operative scores were worse in all 8 domains. At 6 months post surgery, there were significant improvements in six out of eight domains (p < 0.05); physical and social functioning, physical and emotional role limitations, energy and mental health. The median physical component summary score (PCS) and the mental component summary score (MCS) were also significantly improved postoperatively [Preop vs. Postop (PCS) = 28.16 vs. 35.40 (P = 0.03)] and Preop vs. Postop (MCS) = 41.50 vs. 56.23 (P = 0.005)]. The post-operative MCS was comparable with the national average.ConclusionThis study shows that parathyroidectomy for primary hyperparathyroidism improves health-related quality of life in a United Kingdom population.     

Hiperparatiroidismo primario y crisis hipercalcémica aguda tóxica

ObjectivesTo describe the clinical characteristics and surgical treatment of patients with acute hypercalcaemia due to primary hyperparathyroidism (PHPT) and compare them with other patients with PHPT without associated acute hypercalcaemia.Material and methodsA prospective, observational study (1998-2010) was conducted on 158 patients with PHPT treated by parathyroidectomy. Those with acute hypercalcaemia (>14 mg/dl -3.5 mmol/L- or >3 mmol/L with symptoms of calcium toxicity) were evaluated by recording their clinical and treatment characteristics, and comparing them, using the Mann-Whitney U test and the Fisher test, with the 146 PHPT patients without hypercalcaemic crisis.ResultsTwelve patients (7.6%) had acute hypercalcaemia with symptoms of calcium toxicity and other symptoms of chronicity. The preoperative calcium and PTH values were 14.5 ± 1.3 mg/dL and 648.2 ± 542 pg/dL, respectively. There were 10 adenomas, 1 hyperplasia and 1 carcinoma. The mean weight of the surgical pieces was 4.075 ± 2.918 mg, with a diameter greater than 27 ± 14 mm. The gradients of PTH at 10 and 25 minutes were 79 ± 18% and 92 ± 6%, respectively. Post-operative calcium values on discharge and at 6 months were 8.2 ± 0.7 mg/dL and 9.1 ± 0.9 mg/dL, respectively. The plasma concentrations of calcium, PTH, and the size of the surgical pieces were higher in patients with hypercalcaemic crisis (P<0.001). There were no differences in the other parameters studied or in the cure rate.ConclusionsHypercalcaemic crises were caused by larger and heavier tumours that led to higher plasma Ca and PTH plasma concentrations. All patients had long-standing symptoms and parathyroidectomy led to cure of the disease.     

Evolution of secondary hyperparathyroidism in patients following return to hemodialysis after kidney transplant failure

IntroductionSevere uncontrolled secondary hyperparathyroidism and kidney transplantation history are both risk factors for fractures in hemodialyzed patients. Moreover, patients who return to dialysis after transplant failure have more severe infections/anemia and higher mortality risk than transplant-naive patients starting dialysis with native kidneys. In this context, our aim was to test the hypothesis that transplant failure patients have more secondary hyperparathyroidism than transplant-naive patients.MethodsWe retrospectively compared 29 transplant failure patients to 58 transplant-naive patients matched for age, sex, chronic kidney disease duration and diabetes condition (1 transplant failure/2 transplant-naive ratio), who started dialysis between 2010 and 2014. Clinical and biological data were collected at baseline, 6 and 12 months.FindingsAt baseline, neither serum parathyroid hormone (transplant-naive: 386 ± 286 pg/mL; transplant failure: 547 ± 652 pg/mL) nor serum 25-hydroxyvitamin D (transplant-naive: 27.8 ± 17.0 μg/L, transplant failure: 31.1 ± 14.9 μg/L) differed between groups. However, serum parathyroid hormone at 12 months and the proportion of patients with uncontrolled secondary hyperparathyroidism (parathyroid hormone > 540 pg/mL, KDIGO criteria) were significantly higher in transplant failure than in transplant-naive (parathyroid hormone: 286 ± 205 vs. 462 ± 449, P < 0.01; uncontrolled secondary hyperparathyroidism: 30% vs. 13%, P < 0.01, respectively). Within the transplant failure group, patients with uncontrolled secondary hyperparathyroidism at 12 months were younger than patients with normal or low parathyroid hormone.DiscussionThis retrospective and monocentric study suggests that transplant failure patients are more likely to develop secondary hyperparathyroidism. Thus, finding high serum parathyroid hormone in young transplant failure patients, who are expected to undergo further transplantations, should incite physicians to treat early and more aggressively this complication.     

A case report on acute severe hyponatraemia following parathyroid surgery for primary hyperparathyroidism—A rare but life threatening complication

IntroductionParathyroidectomy is a common operation, which is well tolerated and associated with low morbidity. Patients are usually discharged within 24 hours of surgery. Severe postoperative hyponatraemia is a rare complication which can cause significant morbidity including seizure, coma, respiratory arrest and even death.Presentation of caseWe present two patients with clinically significant hyponatremia resulting in seizures and collapse within 24 hours after parathyroidectomy, an unreported complication following surgery for primary hyperparathyroidism. One patient required support on the High Dependency Unit and both were treated with fluid restriction which resulted in correction of their electrolyte balance.DiscussionWe believe this was caused by the relative inability to secrete a water load after surgery and non-psychogenic polydipsia. Preoperatively, neither patient was prescribed any routine medications nor did they have any risk factors for hyponatremia. Both had normal preoperative sodium levels.It is usual practice is to advise patients to increase oral water intake when they are hypercalcaemic. The aim of parathyroidectomy is to treat hypercalcaemia by stopping excess PTH secretion from abnormal parathyroid glands. These patients continued to follow this advice after surgery when they were eucalcaemic after their operation and because they were thirsty. The patients drank several litres of water in 12–24 hours after surgery. We believe that this may have contributed to this complication.ConclusionHealthcare professionals need to be aware of this complication and patients should be advised to restrict intake of free water after surgery.     

Case report of a large lactating adenoma with rapid antepartum enlargement

IntroductionLactating adenomas are rare benign breast tumors, most commonly found during pregnancy and lactation. They are usually slow growing and smaller than 3 cm in maximal diameter. Rare cases of giant lactating adenomas and rapid postpartum enlargement have been reported, but none have shown a giant lactating adenoma with rapid antepartum enlargement or antepartum surgical management.Case presentationA 27 year-old pregnant woman presented at 28 weeks gestation with a 5 cm left breast mass that doubled to 10 cm within six weeks and was increasingly tender. Histopathologic examination of a core biopsy was consistent with a lactating adenoma. The mass was excised at 31 weeks gestation with no complications.DiscussionLactating adenomas are common during pregnancy and need to be distinguished from breast cancer, a commonly diagnosed malignancy in pregnancy. They can be distinguished from carcinoma and other benign tumors like fibroadenoma under histopathologic examination. Rare cases of giant lactating adenomas with rapid postpartum enlargement that were managed by postpartum excision have been reported. However, a giant lactating adenoma with rapid antepartum enlargement, managed by excision in the third trimester of pregnancy, has not been reported.ConclusionExcision of a large, rapidly enlarging lactating adenoma in the third trimester of pregnancy is a safe and feasible management option.     

Parathyroidectomy for patients with secondary hyperparathyroidism in a changing landscape for the management of end-stage renal disease

BackgroundThe landscape of patients with end-stage renal disease is changing with the increasing availability of kidney transplantation. In the near future, a less aggressive approach to treat secondary hyperparathyroidism might be beneficial. We report outcomes of parathyroidectomy for end-stage renal disease–related hyperparathyroidism comparing the outcomes of limited, subtotal, and total parathyroidectomy.MethodsWe performed a retrospective analysis of prospectively collected data. Patients were divided into 3 parathyroidectomy subgroups: limited (<3 glands removed), subtotal (3–3.5 glands), and total (4 glands) parathyroidectomy. Primary outcome was serum levels of parathyroid hormone. Secondary endpoints were serum levels of calcium, phosphate, and alkaline phosphatase, postoperative complications, and persistent or recurrent disease rates.ResultsIn total, 195 patients were included for analysis of whom 13.8% underwent limited parathyroidectomy, 46.7% subtotal parathyroidectomy, and 39.5% total parathyroidectomy. Preoperative parathyroid hormone levels (pg/mL) were 471 (210–868), 1,087 (627–1,795), and 1,070 (475–1,632) for the limited, subtotal, and total parathyroidectomy groups, respectively (P < .001). A decrease in serum parathyroid hormone was seen in all groups; however, postoperative levels remained greater in the limited parathyroidectomy group compared to the subtotal and total parathyroidectomy groups (P < .001). Serum calcium, phosphate, and alkaline phosphatase levels decreased in all groups to within the reference range. In the limited parathyroidectomy group, persistent disease and recurrence occurred more frequently (P = .02 and P = .07, respectively).ConclusionSubtotal parathyroidectomy is the optimal strategy in an era with an increasing availability of kidney transplantation and improved regimens of dialysis. In this changing practice, the approach to parathyroid surgery, however, might shift to a less aggressive and patient-tailored approach.     

Analysis of parathyroid graft rejection suggests alloantigen-specific production of nitric oxide by iNOS-positive intragraft macrophages

BackgroundDuring acute rejection of organ or tissue allografts T cells and macrophages are dominant infiltrating cells. CD4-positive T cells are important for the induction of allograft rejection and macrophages are important effector cells mediating cytotoxicity via production of nitric oxide (NO) by the inducible NO-synthase (iNOS). In the present study we analysed whether the destruction of primarily nonvascularised parathyroid allografts is also mediated by iNOS-positive macrophages.MethodsHypocalcaemic Lewis rats received parathyroid isografts (from Lewis donors) and allografts (from Wistar Furth donors), respectively, under the kidney capsule. Levels of serum calcium above 2 mmol/L correlated with normal parathyroid function and below 2 mmol/L with parathyroid rejection. Accelerated parathyroid allograft rejection was induced by immunisation of Lewis recipients with the allogeneic peptide P1.ResultsDetermination of serum calcium levels is a useful parameter to control parathyroid graft function, and therefore to determine allograft rejection. Macrophages positive for both major histocompatibility complex (MHC) class II molecules and costimulatory molecules accumulated in iso- and allografts, but iNOS-positive macrophages were only detectable in allografts in the presence of activated CD4-positive T cells. These results confirm a cooperation between activated T cells and intragraft macrophages to induce macrophage iNOS expression. Recipients immunised with the allogeneic peptide P1 demonstrated accelerated rejection of allografts (mean ± SD: 9.2 ± 0.9 days) in contrast to nonimmunised animals (mean ± SD: 15.8 ± 1.8 days). Allografts of P1-immunised animals were infiltrated faster by activated CD4-positve T cells and, in addition, the infiltrates of iNOS-positive macrophages were stronger than those in allografts of nonimmunised animals.ConclusionsIntragraft iNOS-positive macrophages seem to be able to produce cytotoxic NO involved in the killing of allogeneic cells during the alloimmune response against primarily nonvascularised parathyroid organ grafts. Infiltrates of iNOS-negative macrophages found in parathyroid isografts were caused by antigen-independent inflammation triggered by surgically induced injury. The absence of activated T cells in isografts and their presence in allografts underlines their importance in inducing macrophage iNOS expression.     

Mortality associated with primary hyperparathyroidism

561 patients with primary hyperparathyroidism were followed between 1961 and 1994. Relative survival was compared to that of the Australian population studied during the same time interval. Mortality was significantly greater in the hyperparathyroid population (P < 0.001). Mortality was not greater in the patients with serum calcium levels > 3.00 mmol/L compared to those with a serum calcium levels < 3.00 mmol/L.113 patients did not have parathyroid surgery. Their relative survival was not significantly different from those who had surgery but their mean serum calcium and parathyroid hormone (PTH) levels were significantly lower than those who had surgery.A re-analysis of the 453 patients followed between 1972 and 2011 was carried out and a 20-year survival analysis made of those diagnosed between 1972 and 1981 and those diagnosed between 1982 and 1991. The latter group had significantly worse relative mortality than the former group (P < 0.001) but was significantly older at the time of diagnosis (56.94 ± 14.83 vs 52.01 ± 13.58, P < 0.001). The serum calcium and serum PTH levels were not significantly different between these two groups.     

Bone mineral density changes following discontinuation of ronacaleret treatment: Off-treatment extension of a randomized,dose-finding phase II trial

ContextParathyroidectomy in patients with hyperparathyroidism can produce subsequent increases in bone mineral density (BMD). Ronacaleret, a selective calcium-sensing receptor antagonist that stimulates endogenous parathyroid hormone release, induced mild hyperparathyroidism.ObjectiveThe aim of this study is to evaluate whether BMD changes after cessation of ronacaleret treatment.DesignObservational, off-treatment, extension of a randomized, placebo-controlled, dose-ranging phase II trial.SettingFifteen academic centers in seven countries.PatientsPostmenopausal women with low BMD; 171 out of 569 women in the parent study were enrolled in the extension study.InterventionsSubjects were treated with ronacaleret 100 mg (n = 16), 200 mg (n = 38), 300 mg (n = 35), or 400 mg (n = 32) once daily, alendronate 70 mg (n = 17) once weekly, or matching placebo (n = 33) for 10–12 months; BMD was measured after discontinuation of ronacaleret or alendronate treatment.Main outcome measureMean percent change in lumbar spine areal BMD by dual-energy X-ray absorptiometry at 6–12 months after discontinuing ronacaleret or alendronate compared with the 10- to 12-month BMD measurement of the parent study.ResultsAt the lumbar spine, all doses of ronacaleret resulted in gains in BMD while on treatment. These increases in BMD were maintained or increased after discontinuation of ronacaleret. All doses of ronacaleret caused bone loss at the total hip while on active treatment. However, there was an attenuation of this loss in the off-treatment extension study.ConclusionThe gain in BMD at the lumbar spine was maintained post-treatment and the loss of BMD at the total hip was attenuated. We hypothesize that there may have been some bone remineralization after cessation of ronacaleret.     

Identificación de adenomas ocultos en hiperparatiroidismo primario con PET-TC 18F-fluorocolina

IntroductionSingle parathyroid adenomas are the most common cause of primary hyperparathyroidism (PHP) in our population. Parathyroidectomy is still the only potentially curative treatment and requires preoperative localization imaging studies to perform selective surgery. In patients with negative results on conventional tests, PET/CT has demonstrated higher sensitivity rates.MethodsA prospective cohort study was designed, including 34 patients diagnosed with PHP between 2017 and 2019, candidates for surgery with negative preoperative localization tests with scintigraphy and MIBI SPECT/CT. All patients underwent PET/CT with 18F-Fluorocholine. The clinical, biochemical and postoperative outcome results were compared with a control group of 30 patients with positive standard tests.ResultsHyperfunctional parathyroid tissue was detected in 85% of the patients that had undergone choline PET/CT. The selective resection of the adenoma identified in these patients achieved curative criteria in 87% of the cases without undergoing bilateral cervical surgical exploration. The preoperative levels of PTH, calcemia and gland weight were significantly lower in this group compared to the control group. No differences were identified in cure criteria or approach between the 2 groups.ConclusionIn our study, choline PET/CT showed higher detection rates compared to the gold standard. The increase provides the opportunity to perform unilateral selected adenoma resection, especially in patients with smaller adenomas associated with lower calcemia and PTH levels and patients with previous cervical surgery.     

Seasonal changes in serum calcium,PTH and vitamin D levels in patients with primary hyperparathyroidism

BackgroundSeasonal variations of 25-hydroxyvitamin D, PTH and calcium levels are not well characterized in primary hyperparathyroidism (PHPT). Our objectives were to characterize seasonal changes in these parameters in PHPT patients, and to assess whether these seasonal changes affect clinical decision making.MethodsThis is a retrospective study based on the electronic medical records of Clalit Health service in the south of Israel between 2000 and 2012. Patients 18 years and older with PHPT (PTH > upper limit of norm (ULN) and serum calcium > 10.5 mg%) were included. Patients with renal failure or on Thiazide diuretics were excluded. All serum levels of calcium, PTH and 25-hydroxyvitamin D were collected and then stratified according to season.Results792 patients were classified as PHPT (72.2% female) and had a total of 2659 PTH tests, 1395 25-hydroxyvitamin D tests and 7426 calcium test. Fifty six percent of 25-hydroxyvitamin D levels were < 50 nmol/L. Seasonality was demonstrated in all three parameters: mean 25-hydroxyvitamin D was 13% higher in the summer compared to the winter (P < 0.001), median PTH values showed opposite trend with a fall of about 8.4% in summer compared to winter (P < 0.001). Calcium levels were higher during the autumn with a rise of about 0.2 mg/dL in the mean calcium levels compared to spring and summer (P < 0.001). The odds ratio of calcium level above 11.5 mg/dL is highest in the autumn (OR = 1.275, P = 0.018).ConclusionWe show seasonal variation in serum 25-hydroxyvitamin D, PTH, and calcium levels in patients with PHPT. These seasonal variations cause transition to pathological values that may influence diagnosis and treatment of PHPT patients.     

Computed tomography of the parathyroids: the value of density measurements to distinguish between parathyroid adenomas of the lymph nodes and the thyroid parenchyma

PurposeTo compare the densities of parathyroid adenomas, lymph nodes and the thyroid parenchyma during multi-phase cervico-thoracic computed tomography to determine the differentiating threshold values.Materials and methodsThis study comprises 30 patients operated for a parathyroid adenoma after computed tomography without injection and then 45 and 70 seconds after the injection of an iodine based contrast product (350 mgI/mL, 150 mL, 3 mL/s). The density of the adenomas, lymph nodes and thyroid was measured during the three phases (D0, D45, D70). The relative enhancement (RE) at 45 seconds was calculated: RE = (D45 – D0) / D0.ResultsA significant difference was found in the spontaneous density of the parathyroid adenomas of the thyroid (P < 0.01) with a threshold value of 75 HU. A significant difference is found in the enhancement after injection of the adenomas and lymph nodes (P < 0.01). The adenomas present an enhancement peak at 45 seconds while the maximum enhancement of the lymph nodes is at 70 seconds. At 45 seconds, a threshold value of 114 HU and an RE 125% allows them to be distinguished (sensitivity and specificity 0.96).ConclusionMeasurement of the densities can differentiate between the parathyroid adenomas, lymph nodes and thyroid.     

Relationship between vitamin D deficiency and bone fragility in sickle cell disease: A cohort study of 56 adults

BackgroundRecent studies suggest that patients with sickle cell disease (SCD) have profound vitamin D (VD) deficiency. Limited data exist on the effect of VD deficiency on bone fragility in these patients.ObjectivesTo assess the prevalence of VD deficiency in adults with SCD and its consequences on bone metabolism and fragility.MethodsThis prospective study included 56 SCD adult patients (mean age 29.8 ± 9.5 years), in a clinically steady state. Clinical and laboratory data were recorded. Bone mineral density (BMD) was measured using dual X-ray absorptiometry. Fracture history, BMD, avascular osteonecrosis, H-shaped vertebra and markers of mineral metabolism were compared between two groups of patients presenting very low (≤ 6 ng/mL, n = 26) (group 1) and low (> 6 ng/mL, n = 26) (group 2) 25(OH)D concentration, respectively.ResultsMedian 25(OH)D concentration was 6 ng/mL. VD deficiency (25(OH)D < 10 ng/mL) was found in 42 out of 56 patients (75%) and secondary hyperparathyroidism in 40 (71.4%). History of fracture was documented in 17 patients (30.3%), osteopenia and/or osteoporosis in 39.6% of patients. Overall, patients of group 1 were more likely to have sustained a fracture (42.8%) compared to patients of group 2 (17.8%) (p = 0.04). These patients had also lower body mass index and significantly higher parathyroid hormone, C-terminal telopeptides of type I-collagen and bone-specific alkaline phosphatase serum levels. There was no difference between group for BMD, avascular osteonecrosis history, H-shaped vertebra, and disease severity markers.ConclusionThis study suggests that VD deficiency is a key feature in SCD-bone disease. It is highly prevalent and associated with hyperparathyroidism, bone resorption markers, and history of fracture. The optimal supplementation regimen remains to be determined.     

Novel homozygous inactivating mutation of the calcium-sensing receptor gene (CASR) in neonatal severe hyperparathyroidism—lack of effect of cinacalcet

BackgroundNSHPT is a life-threatening disorder caused by homozygous inactivating calcium-sensing receptor (CASR) mutations. In some cases, the CaSR allosteric activator, cinacalcet, may reduce serum PTH and calcium levels, but surgery is the treatment of choice.ObjectiveTo describe a case of NSHPT unresponsive to cinacalcet.Patient and ResultsA 23-day-old girl was admitted with hypercalcemia, hypotonia, bell-shaped chest and respiratory distress. The parents were first-degree cousins once removed. Serum Ca was 4.75 mmol/l (N: 2.10–2.62), P: 0.83 mmol/l (1.55–2.64), PTH: 1096 pg/ml (9–52) and urinary Ca/Cr ratio: 0.5 mg/mg. First, calcitonin was given (10 IU/kg × 4/day), and then 2 days later, pamidronate (0.5 mg/kg) for 2 days. Doses of cinacalcet were given daily from day 28 of life starting at 30 mg/m² and increasing to 90 mg/m² on day 43. On day 33, 6 days after pamidronate, serum Ca levels had fallen to 2.5 mmol/l but, thereafter, rose to 5 mmol/l despite the cinacalcet. Total parathyroidectomy was performed at day 45. Hungry bone disease after surgery required daily Ca replacement and calcitriol for 18 days. At 3 months, the girl was mildly hypercalcemic, with no supplementation, and at 6 months, she developed hypocalcemia and has since been maintained on Ca and calcitriol. By CASR mutation analysis, the infant was homozygous and both parents heterozygous for a deletion–frameshift mutation.ConclusionThe predicted nonfunctional CaSR is consistent with lack of response to cinacalcet, but total parathyroidectomy was successful. An empiric trial of the drug and/or prompt mutation testing should help minimize the period of unnecessary pharmacotherapy.     

Regulation of PTH secretion by 25-hydroxyvitamin D and ionized calcium depends on vitamin D status: A study in a large cohort of healthy subjects

IntroductionPrevious papers investigating vitamin D status have often outlined the significant relationships between serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD), but the influence of ionized calcium levels has not been concomitantly considered.DesignCross-sectional.Materials and methodsIn 1050 healthy men (547) and women (503), serum ionized calcium (iCa), creatinine (Cr), albumin, 25OHD, and PTH were measured. After conventional analysis, a regression tree was fitted on the data set.Results25OHD and PTH values showed significant opposite seasonal changes. 25OHD levels negatively correlated with PTH, which in turn negatively correlated with iCa. A regression tree was fitted to the whole data set using PTH as the response variable and 25OHD and iCa as covariates. PTH concentration depended on that of iCa only in subjects with 25OHD levels > 16.35 ng/mL, while for 25OHD <16.35 ng/mL it depended on 25OHD values.ConclusionsOur results indicated that PTH levels were highly conditioned by those of 25OHD in subjects with 25OHD values lower than 16.35 ng/mL and by those of iCa only for higher 25OHD concentration.     

Secular trends in the incidence of primary hyperparathyroidism over five decades (1965–2010)

Introduction of automated serum calcium measurements in the 1970s resulted in a sharp rise in primary hyperparathyroidism (PHPT) incidence. However, recent investigations suggest a significant rise in PHPT incidence for unclear reasons. Our objective was to update our population-based secular trends in PHPT incidence, to determine if there has been a significant rise in PHPT incidence as suggested by others, and, if possible, to identify changes in clinical practice that might be responsible. Rochester, Minnesota, residents who met the criteria for PHPT from 2002 through 2010 were identified through the medical records-linkage system of the Rochester Epidemiology Project and added to the historical cohort beginning in 1965. Incidence rates were adjusted to the 2010 US white population. Altogether, 1142 Rochester residents have been diagnosed with PHPT since 1965, including 341 in 2002–2010. Over time, two periods of increased PHPT incidence occurred, one beginning in 1974 (121.7 per 100,000 person-years) and a second peak (86.2 per 100,000 person-years) starting in 1998. The median age of PHPT subjects has increased significantly from 55 years in 1985–1997 to 60 years of age in 1998–2010 and more patients (36%) had a parathyroidectomy in 1998–2010. Although serum calcium measurement has declined since 1996, there was a progressive increase in parathyroid hormone testing between 1994 and 2008. There was also a rise in orders for bone mineral density measurements in women since 1998, which peaked in 2003–2004. A second sharp rise in PHPT incidence occurred in our community in 1998, simultaneously with the introduction of national osteoporosis screening guidelines, Medicare coverage for bone density measurement, and new medications for the treatment of osteoporosis. Case ascertainment bias from targeted PHPT screening in patients being evaluated for osteoporosis is the most likely explanation.