Calcium Challenge to Confirm Secondary Hyperparathyroidism Caused by Decreased Calcium Intake

ObjectiveSecondary hyperparathyroidism commonly occurs in the setting of mid-to low-normal serum calcium levels, often in the setting of chronic kidney disease, phosphate loading, vitamin D deficiency, or insufficient calcium intake or absorption. In this article, we report 9 patients who had adequate kidney function (estimated glomerular filtration rate >60 mL/min/1.73 m²) and normal 25-hydroxy vitamin D level (≥30 ng/dL) and whose secondary hyperparathyroidism resolved after starting adequate oral calcium intake.MethodsOur retrospective case series included 8 women and 1 man; the mean age was 69.0 ± 12.2 years (mean ± standard deviation). The initial intact parathyroid hormone (iPTH) level was 80.6 ± 13.4 pg/mL (reference range [ref], 10-65 pg/mL), corrected serum calcium level was 9.2 ± 0.2 mg/dL (ref, 8.5-10.5 mg/dL), serum phosphate level was 3.6 ± 0.4 mg/dL (ref, 2.5-4.9 mg/dL), 25-hydroxy vitamin D level was 42.2 ± 10.5 mg/dL (ref, 20-50 ng/mL), and estimated glomerular filtration rate was 72.6 ± 14.4 mL/min/1.73 m². Patients were treated clinically with oral calcium 600 mg twice a day.ResultsiPTH was retested after a mean duration of 17.6 ± 12.7 days of calcium supplementation; the iPTH level decreased to 51.0 ± 10.6 pg/mL, with all patients achieving iPTH in the normal range with normocalcemia, consistent with hyperparathyroidism being because of insufficient calcium intake or absorption. All patients were normocalcemic after supplementation.ConclusionSecondary hyperparathyroidism can result from insufficient oral calcium intake. Calcium challenge is an efficacious and cost-effective tool for confirming and treating secondary hyperparathyroidism in the setting of normal vitamin D levels and kidney function.     

Calcium,Parathyroid Hormone,and Vitamin D in Patients with Primary Hyperparathyroidism: Normograms Developed from 10000 Cases

ObjectiveTo better define the typical and atypical biochemical profiles of patients with surgically proven primary hyperparathyroidism.MethodsIn this single-center, prospectively conducted study of consecutive patients with surgically proven primary hyperparathyroidism over a 7-year period, we analyzed serum calcium, parathyroid hormone, and 25-hydroxyvitamin D concentrations.ResultsA total of 10 000 patients were included, and more than 210 000 calcium, parathyroid hormone, and 25-hydroxyvitamin D values were evaluated. Both calcium and parathyroid hormone levels demonstrated a Gaussian distribution with the average calcium concentration being 10.9 ± 0.6 mg/dL and the average parathyroid hormone concentration being 105.8 ± 48 pg/mL. The average highest calcium and parathyroid hormone concentrations were 11.4 ± 0.7 mg/dL and 115.3 ± 50 pg/mL, respectively. At least 1 calcium value of 11.0 mg/dL was seen in 87% of patients, but only 21% had 1 or more calcium value above 11.5 mg/dL. Only 7% had a single serum calcium level reaching 12.0 mg/dL. Normocalcemic hyperparathyroidism was seen in just under 3% of patients who had identical findings at surgery. An average parathyroid hormone concentration less than 65 pg/mL was seen in 16%, with 10% of patients who had no high parathyroid hormone values. The average 25-hydroxyvitamin D concentration was 22.4 ± 9 ng/mL, with levels decreasing as calcium levels increased (P < .001); 36% had 25-hydroxyvitamin D levels below 20 ng/mL.ConclusionsPatients with PHPT present with a number of distinct biochemical profiles, but as a group, they present with a near-normal Gaussian distribution of both calcium and parathyroid hormone levels. Either serum calcium or parathyroid hormone remained normal in 13% of patients, yet the findings at surgery are similar to those of patients with elevated calcium or parathyroid hormone. Low 25-hydroxyvitamin D is an expected finding in patients with PHPT, decreasing as serum calcium levels increase. (Endocr Pract. 2011;17:384-394)     

An acromegalic patient with recurrent urolithiasis

A 52-year-old man with an acromegalic appearance of prolonged duration suffered abdominal colic attacks and hematuria during the middle of the course of the disease. The patient was diagnosed as having urolithiasis caused by increased urinary calcium. The calcium metabolic disorder was not considered to be due to hyperparathyroidism because serum calcium and PTH levels were within the normal range and no abnormality was observed in a parathyroidal scintigraph. The serum 1,25-dihydroxyvitamin D (1,25-(OH)2D) levels (55.0 and 73.0 pg/ml) were higher than the normal range (27.2-53.8 pg/ml). A selective adenomectomy by the transsphenoidal route (Hardy's method) was performed, resulting in an improvement in the hypercalciuria and urolithiasis, and a decrease in the levels of serum 1,25-(OH)2D (23.0 and 23.0 pg/ml). These findings suggest that GH may promote the activation of vitamin D in the kidney in acromegaly, resulting in an acceleration of calcium absorption in the intestine through the action of activated vitamin D and the induction of increased urinary calcium excretion by the urinary excretion of excessive blood calcium.     

Hypercalcemia and Acromegaly-Clarifying the Connections: A Case Report and Review of the Literature

ObjectiveHypercalcemia in patients with acromegaly is rare and usually due to co-existent primary hyperparathyroidism. The etiology of hypercalcemia directly related to acromegaly is debated.MethodsWe present a case report of 1,25(OH)2D3-mediated hypercalcemia in a patient with acromegaly and discuss potential pathophysiological mechanisms contributing to the development of hypercalcemia late in the course of the disease.ResultsA 67-year-old female presented with classical features of acromegaly. A review of her previous photographs suggested a disease duration of approximately 10 years, and her serum calcium (Ca) was normal during this period. A biochemical work up confirmed a combined growth hormone (GH-) and prolactin (PRL-) cosecreting tumor with a GH level of 92.03 ng/mL (normal 0-3.61), an insulin-like growth factor-1 (IGF-1) level of 1,498 ng/ mL (59-225), and a PRL level of 223.3 ng/mL (2-17.4). Magnetic resonance imaging (MRI) of the pituitary showed a 1.9-cm macroadenoma. Her preoperative work up revealed new onset hypercalcemia with a corrected serum Ca level of 10.7 mg/dL (8.5-10.5), an ionized Ca level of 1.37 mmol/L (1.08-1.30), a parathyroid hormone (PTH) level of 13.0 pg/mL (10-60), and a high 1,25(OH)2D3 level of 72.6 pg/mL (15-60). She underwent resection of the pituitary adenoma with normalization of GH and PRL levels, and her IGF-1 level decreased to 304 ng/mL. Her serum Ca (9.3 mg/dL), ionized Ca(1.22) and 1,25(OH)2D3 levels (38.6 pg/mL) normalized after surgery.ConclusionWhile overt hypercalcemia in acromegaly is rare, it tends to occur late in the disease course. The hypercalcemia is mediated by elevated 1,25(OH)2D3 levels rather than PTH. (Endocr Pract. 2014;20:e86-e90)     

Mediastinal parathyroid carcinoma: a case report

A 72 year-old woman with primary hyperparathyroidism was operated for parathyroid crisis. PTH serum level was 808 pg/mL. During the operation, only two superior parathyroid glands were found. One was normal, and hypertrophy was revealed in the other. After the surgical procedure, PTH serum level was 726.5 pg/mL. Helical computer tomography examination showed a heterogeneous mass in the anterior mediastinum. The tumour was removed via a sternotomy approach. Histopathological examination revealed parathyroid carcinoma. PTH level dropped to 5.74 pg/mL. Cytofluorometric examination revealed diploidy (DI = 1) in both the hypertrophic and the unchanged upper glands, whereas parathyroid cancer was aneuploid. After the initial operation, the woman was discharged from the hospital on the 27th postoperative day. One year after surgical procedures, she is well. She has to take calcium.     

A new, vitamin D-based, multidimensional nomogram for the diagnosis of primary hyperparathyroidism

ObjectiveTo refine the diagnostic criteria for primary hyperparathyroidism (1°HPT) to identify atypical patients, in whom serum calcium, parathyroid hormone (PTH), or both are within the “normal” range.MethodsTotal serum calcium, intact PTH, and 25-hydroxyvitamin D [25(OH)D] levels were measured in patients with 1°HPT and healthy patient groups. Multivariate analysis of healthy patient data first identified factors that significantly affected PTH levels and defined a new PTH reference range with a mathematical model. That nomogram was then validated for prediction of atypical 1°HPT in patients with surgically confirmed disease.ResultsOn multivariate analysis, calcium (P = .0002), 25(OH)D (P < .0001), and age (P = .015) independently affected PTH. With these variables, we created a 4-dimensional nomogram that distinguished normal patients from those with hyperparathyroid states. Mathematically, this nomogram predicts 1°HPT when the measured serum PTH value is higher than PTH calculated by the following formula: PTH (pg/mL) = 120-[6 × calcium (mg/dL)]-[0.52 × 25(OH)D (ng/mL)] + [0.26 × patient age (years)]. When applied to our surgical group of patients, this nomogram successfully identified 100% of patients (238 of 238) with classic 1°HPT, 84% (64 of 76) with normocalcemic 1°HPT, and 54% (20 of 37) with 1°HPT and normal PTH.ConclusionThis study uniquely defines a patientspecific upper limit of normal for PTH based on the readily available variables of serum calcium, 25(OH)D, and patient age. Our nomogram may allow for more rapid definitive diagnosis and treatment of 1°HPT in patients with atypical presentations. (Endocr Pract. 2012;18:124-131)     

Biochemical Dynamics of Untreated Primary Hyperparathyroidism: an Observational Study

Objective: The natural biochemical history of untreated primary hyperparathyroidism (PHPT) is poorly understood. The purpose of this study was to determine the extent of biochemical fluctuations in patients with PHPT.Methods: Retrospective cohort study from January 1, 1995, to December 31, 2014. Serum calcium and parathyroid hormone (PTH) levels in patients with classic (Ca >10.5 mg/dL, PTH >65 pg/mL) and nonclassic (Ca >10.5 mg/dL, PTH 40 to 65 pg/mL) PHPT were followed longitudinally at 1, 2, and 5 years. Biochemical profiles in follow-up were ranked in descending biochemical severity as classic PHPT, nonclassic PHPT, normal calcium with elevated PTH (Ca <10.5 mg/dL, PTH >65 pg/mL), possible PHPT (Ca >10.5 mg/dL, PTH 21 to 40 pg/mL), or absent PHPT (Ca >10.5 mg/dL, PTH <21 pg/mL or Ca <10.5 mg/dL, PTH <65 pg/mL).Results: Of 10,598 patients, 1,570 were treated with parathyroidectomy (n = 1,433) or medications (n = 137), and 4,367 were censored due to study closure, disenrollment, or death. In the remaining 4,661 untreated patients with 5 years of follow-up, 235 (5.0%) progressed to a state of increased biochemical severity, whereas 972 (20.8%) remained the same, and 3,454 (74.1%) regressed to milder biochemical states. In 2,522 untreated patients with classic PHPT, patients most frequently transitioned to the normal calcium with elevated PTH group (n = 1,257, 49.8%). In 2,139 untreated patients with nonclassic PHPT, patients most frequently transitioned to the absent PHPT group (n = 1,354, 63.3%).Conclusion: PHPT is a biochemically dynamic disease with significant numbers of patients exhibiting both increases and decreases in biochemical severity.Abbreviations: IQR = interquartile range; KPSC = Kaiser Permanente Southern California; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; PTx = parathyroidectomy     

Unusual Case of Calciphylaxis Associated with Primary Hyperparathyroidism Without Coexistent Renal Failure

ObjectiveTo report a case of calciphylaxis in a patient with primary hyperparathyroidism without coexistent renal failure.MethodsThe clinical, laboratory, and radiographic details of this case are reviewed, and the pathogenesis of calciphylaxis and the associated prognosis are discussed.ResultsA 52-year-old woman had progressive fatigue, cachexia, severe osteoporosis, and necrotizing skin lesions. Her serum calcium level was 16 mg/dL, serum phosphorus level was 2.13 mg/dL, and parathyroid hormone level was 2,257 pg/mL (reference range, 15 to 65). On physical examination, gangrenous skin lesions with black crusts were noted on her legs, abdomen, and gluteal region. A mass lesion was detected in the parathyroid region by both ultrasonography and a parathyroid scan. The patient underwent a bilateral neck exploration, and a parathyroid adenoma measuring 3.5 by 1.5 by 1.2 cm was found on pathologic examination. After the operation, biochemical findings normalized, and the skin lesions progressively improved.ConclusionSevere primary hyperparathyroidism may be a factor leading to calciphylaxis, even in the absence of renal failure and a high calcium-phosphate product. This potentially life-threatening condition should not be left untreated if the levels of serum calcium and parathyroid hormone are severely elevated. (Endocr Pract. 2008;14:368-372)     

Inhibition of growth hormone secretion in mild primary hyperparathyroidism

INTRODUCTION: Impairment in growth hormone (GH) secretion has been reported to occur in primary hyperparathyroidism (PHP) with strikingly elevated (>150 pg/ml) plasma PTH and free Ca levels. Patients with these characteristics are relatively few, whereas the great majority of patients with biochemically diagnosed PHP are asymptomatic and show borderline or slightly elevated plasma PTH and Ca levels. We wondered whether also patients in these latter conditions show a defective GH secretory pattern. METHODS: In order to answer this question, 8 female subjects (mean age +/- SE: 44 +/- 1.3 years) were selected at the time of a checkup examination from a larger population of persons in fairly good clinical condition. Inclusion criteria were plasma PTH values slightly above the normal range (up to 50% higher than the maximum limit) with free Ca levels in the upper normal range or slightly higher (experimental group). Normal values in our laboratory are ionized calcium: 1.22-1.42 mmol/ml and plasma PTH: 12-72 pg/ml. A group of 15 age-matched healthy women with plasma PTH and Ca levels in the middle normal range and significantly lower than values found in the experimental group was also selected and used as control. Experimental and control groups were tested with arginine [0.5 mg/kg body weight (BW)] infused intravenously over 30 min and arginine plus GH-releasing hormone (GHRH; 1 microg/kg BW in an intravenous bolus injection). The GH responses to these challenging stimulations were compared between groups. RESULTS: Basal serum GH values were similar in all subjects. Both arginine and arginine plus GHRH induced a significant GH rise in both groups; however, the GH responses were significantly lower in the experimental than in the control group. Mean GH peak was 27.7 and 14.6 times higher than baseline after arginine and 57.5 and 26.6 times higher than baseline after arginine plus GHRH in the control and experimental group, respectively. No significant correlation was observed between PTH or Ca levels and the GH responses to challenging stimuli in any group. CONCLUSION: These data show that impairment in GH secretion is associated with slightly elevated levels of PTH in the presence of serum Ca values in the upper normal range. GH responses to stimulations were reduced by about 50% in our hyperparathyroid subjects. A long-time duration of this relatively small decline of GH secretory activity may be supposed to contribute to age-related catabolic processes in a large number of patients with mild primary hyperparathyroidism.     

Unusual Recurrence of Hypercalcemia Due to Concurrent Parathyroid Adenoma and Parathyroid Sarcoidosis with Lymph Node Involvement

ObjectiveTo describe a patient presenting with the rare findings of synchronous parathyroid adenoma and parathyroid sarcoidosis.MethodsWe describe the clinical history, physical examination findings, laboratory values, imaging findings, and pathologic data of a man who developed recurrent se- vere hypercalcemia after successful parathyroidectomy.ResultsA 67-year-old man had the following initial blood test results: calcium, 11.1 mg/dL (reference range, 8.5-10.6 mg/dL); albumin 4.0 g/dL (reference range, 3.2-5.2 g/dL); intact parathyroid hormone, 166 pg/mL (refer- ence range, 10-69 pg/mL); creatinine, 1.9 mg/dL; 25-hy- droxyvitamin D, 15 ng/mL (reference range, 30-80 ng/ mL); and 1, 25-dihydroxyvitamin D, 44 pg/mL (reference range, 16-72 pg/mL). Chest x-ray was normal, and delayed images from a technetium Tc 99m sestamibi scan showed increased activity in the right lower pole of the thyroid. Two months after successful parathyroidectomy, the pa- tient was admitted to the hospital with a serum calcium concentration of 17 mg/dL. Pathologic examination of the resected gland confirmed the diagnosis of parathyroid ad- enoma, and subsequent review disclosed the presence of noncaseating granulomas within the adenoma.ConclusionsSarcoidosis with parathyroid involve- ment causing severe hypercalcemia is unique to this case.Recurrent hypercalcemia after successful resection of a parathyroid adenoma may require consideration of poten- tial causes other than the initial diagnosis. (Endocr Pract. 2010;16:463-467)     

Optimizing efficacy of quick parathyroid hormone determination in the operating theater

The usefulness of intraoperative parathyroid hormone (PTH) monitoring has been extensively documented in primary hyperparathyroidism (HPT), whereas few data have been published on its use in reoperations or in secondary and tertiary HPT. We report our initial experience with a rapid (12 min response) PTH immunochemiluminometric assay performed in the operating room during surgery in 12 patients with primary HPT, 16 end-stage renal disease patients with secondary HPT and five kidney transplanted subjects with tertiary HPT. Blood samples were taken at baseline, within 10 min after resection and subsequently at various intervals whenever needed. The mean PTH levels before and after parathyroidectomy were 230.5 pg/mL (range 69-842) and 47.3 pg/mL (range 5-184), respectively, in primary HPT, 855.0 pg/mL (416-1655) and 202.2 pg/mL (53-440) in secondary HPT, and 205.6 pg/mL (116-301) and 45.4 pg/mL (18-97) in tertiary HPT. All patients but one had a significant percentage decline from pre-excision values (mean 76.9%, 76.0%, and 76.1% in primary, secondary and tertiary HPT, respectively). While a reduction of more than 50% was observed in 30 out of 33 patients after the first intraoperative sampling, additional measurements were performed in 10 cases. On-site PTH monitoring with this user-friendly and reliable system has proved helpful in targeting PTH tests to give the surgeon a rapid and accurate assessment of the intervention. The development of optimal PTH sequence strategies with decision-focused analytical and clinical limits will improve the efficacy of "point-of-care" PTH assay and resource utilization.     

The influence of bariatric surgery on calcium homeostasis and biochemical markers of bone turnover in patients with morbid obesity

INTRODUCTION: Obese patients may have abnormal calcium homeostasis because of unbalanced diet and decreased sun exposure. Bariatric surgery itself may lead to disturbances in calcium homeostasis (and in consequence changes in bone mass) or increase preexisting metabolic derangements. The aim of the study was: 1. To assess calcium homeostasis and biochemical markers of bone turnover in patients with morbid obesity. 2. To determine the impact of bariatric surgery on parameters mentioned above. 3. To establish recommendations for supplementation with calcium and vitamin D in morbidly obese patients after bariatric surgery. MATERIAL AND METHODS: Serum calcium, parathormone (PTH), vitamin D (25(OH)D), biochemical markers of bone turnover (beta-CrossLaps as a marker of bone resorption and osteocalcin as a marker of bone formation) and urine calcium as well as fat mass, lean mass and bone mineral content (by DXA) were measured before bariatric surgery of the stomach (VBG or GBP) in 57 morbidly obese patients (48 women, 9 men; mean age 35.9 y). The same procedures were repeated six months after operation in 28 of them (24 women, 4 men). Daily calcium intake was also determined based on food questionnaire. RESULTS: Biochemical findings in the group of patients before bariatric surgery were as follows: serum calcium, beta-CrossLaps and urine calcium were within normal range, PTH concentration was increased to 81.0 pg/ml and 25(OH)D as well as osteocalcin concentration decreased (4.9 ng/ml and 13.6 ng/ml, respectively). Six months after bariatric surgery there was no change in serum and urine calcium, PTH concentration decreased to normal level (46.8 pg/ml), 25(OH)D concentration increased to 6.5 ng/ml (not significant) and still remained below normal range. Markers of bone turnover--both resorption and formation--increased (beta-CrossLaps over normal range to 0.594 ng/ml, osteocalcin to normal range 26.8 ng/ml). Daily calcium intake was below RDA before and after bariatric procedure. CONCLUSIONS: 1. Patients with morbid obesity have secondary hyperparathyroidism and deficiency of vitamin D. 2. Abrupt weight loss after bariatric surgery is accompanied by the regression of secondary hyperparathyroidism, decrease of the deficiency of vitamin D and increase in bone turnover. 3. Supplementation with vitamin D and calcium is recommended for patients with morbid obesity after bariatric surgery.     

Evaluation of the parathyroid function in six patients with hypophosphatemic osteomalacia,including a case of tertiary hyperparathyroidism developing during combined oral phosphate and vitamin D therapy

AIM: To describe a case of tertiary hyperparathyroidism after long-term phosphate and vitamin D therapy and the retrospective evaluation of parathyroid function in 6 patients with hypophosphatemic osteomalaica. METHODS: We evaluated the parathyroid function by measuring iPTH before and during treatment and divided the patients into normal and elevated serum iPTH groups. RESULTS: In the normal serum iPTH group, the 4 patients were all males, whereas the 2 patients in the elevated serum iPTH group were females. Clinical characteristics and biochemical results showed no differences between the two groups. One of the women with an elevated iPTH level (224 pg/ml) had a normal serum calcium level and no evidence of increasing parathyroid uptake by (99m)Tc-MIBI scan 52 months after treatment. The other woman also had an elevated iPTH level (483 pg/ml) and a normal serum calcium level 56 months after treatment. However, in this latter case both her iPTH (1,447 pg/ml) and serum calcium (11.3 mg/dl) levels were elevated 113 months after treatment, when a (99m)Tc-MIBI scan showed increased uptake in all four parathyroid glands during early and delayed phases of the scan. Parathyroidectomy was performed after the diagnosis of tertiary hyperparathyroidism was made, and the histological findings showed adenomatous hyperplasia. CONCLUSIONS: Our findings indicate that even with vitamin D therapy, long-term phosphate therapy may lead to the development of secondary or tertiary hyperparathyroidism in hypophosphatemic osteomalacia and, therefore, suggest that it is important to carefully monitor the parathyroid function during therapy in those with hypophosphatemic osteomalacia.     

Circulating angiogenic cytokines in multiple myeloma and related disorders

We investigated the serum concentrations of selected angiogenic cytokines including: vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGF-beta1) and basic fibroblast growth factor (bFGF) in 162 patients with multiple myeloma (MM), 5 patients with Waldenstr m's macroglobulinaemia (WM), and 31 healthy controls. Among the MM patients there were 2 cases of primary plasma cell leukemia (PCL) and one case of extramedullary plasmacytoma. The levels of measured cytokines were correlated with the phase and stage of the disease as well as the most important clinical and laboratory parameters associated with disease activity (haemoglobin, creatinine, albumins, calcium, M-component, CRP,beta2m, LDH and bone involvement). We have found correlations between serum levels of angiogenic cytokines and some parameters depicting the disease activity and advancement. The serum level of VEGF in MM patients (median 244.5 pg/mL) correlated with serum concentrations of beta-2-microglobulin (beta2m) greater than 2.5 mg/L (p = 0.0005) and abnormal values of lactate dehydrogenase (> 425 U/L, median 329.0 pg/mL and < 210 U/L, median 426.6 pg/mL, p = 0.004 and p = 0.04 respectively). MM patients in stage III had higher serum levels of HGF (median 1 411.3 pg/mL) than those in stage I (median 1 219 pg/mL) (p = 0.01) according to Durie and Salmon staging, and those in phase I (at diagnosis) (median 1 555.6 pg/mL) and phase III (in progression) (median 1 309.7 pg/mL) had higher levels than those in phase II (plateau phase) (median 1 047.9 pg/mL) (p = 0.002 and p = 0.02 respectively). Significantly elevated values of HGF were found in MM patients with anaemia (median 1 962.0 pg/mL) and hypercalcaemia (median 2 085.6 pg/mL) (p = 0.00001 and 0.04 respectively). TGF-beta1 (median 33.9 ng/mL) correlated positively with highbeta2m values (> 2.5 mg/L) (p = 0.04) and was significantly higher in phase I (median 40.1 ng/mL) than in phase II (median 30.9 ng/mL) (p = 0.03) of the disease. The concentration of bFGF was significantly higher in stage III of MM (median 3.1 pg/mL) than in stage I (median 1.2 pg/mL) (p = 0.04). We found that the survival probability was statistically higher for newly diagnosed MM patients with a concentration of VEGF lower than the median value for this cytokine. The concentrations of the cytokines analyzed in patients with Waldenstr m's macroglobulinaemia (WM), primary plasma cell leukaemia (PCL) and non-secretory (NS) myeloma were not distinguishable from those found in MM patients. We also studied the relationship between the levels of cytokines analyzed and found positive correlations between bFGF and TGF-beta1 (rh? = 0.183, p < 0.02), as well as VEGF and TGF-beta 1 (rh? = 0.537, p < 0.001) and VEGF and bFGF (rh? = 0.197, p < 0.02). In conclusion, our data indicate a strong relationship between angiogenic cytokine serum levels and clinical course as well as selected laboratory parameters of patients with MM.     

Low serum reverse T3 levels in patients with primary hyperparathyroidism

Although patients with primary hyperparathyroidism (1 degree HPT) were euthyroid, we measured serum thyroid hormone levels in 16 patients with 1 degree HPT together with 17 patients with hypercalcemia due to malignant diseases (HCM). In patients with 1 degree HPT, serum levels of T3, T4 and T3U were within normal range, but serum rT3 (reverse T3) levels (205 +/- 37 pg/ml, mean +/- SD) were significantly decreased as compared with those in normal controls (276 +/- 44 pg/ml, P less than 0.01). A significant inverse correlation was observed between the serum levels of rT3 and parathyroid hormone (PTH) (r = 0.54, P less than 0.05). After parathyroidectomy, serum rT3 levels were significantly elevated (240 +/- 56 pg/ml) compared to preoperative levels (P less than 0.01). Low levels of serum rT3 seemed to be attributed to the high levels of serum PTH. On the other hand, serum levels of T3 and T4 were low and serum rT3 levels were high in patients with HCM. Low serum rT3 allows for the differentiation of patients with 1 degree HPT from those with HCM.     

Calciphylaxis in A Morbidly Obese Woman with Rheumatoid Arthritis Presenting with Severe Weight Loss and Vitamin D Deficiency

ObjectiveTo present an unusual case of calciphylaxis in an obese patient with inactive rheumatoid arthritis and normal renal function.MethodsWe describe a 46-year-old morbidly obese Caucasian woman who had previously weighed 200 kg and presented with painful leg ulcers following a rapid weight loss of 102 kg in 1 year.ResultsThe subject was admitted with a 6-week history of painful leg ulcers that progressed to her thighs. Vasculitis and active rheumatoid arthritis were excluded clinically and biochemically. A skin biopsy confirmed calciphylaxis in the context of normal renal function. Serum 25-hydroxyvitamin D was low at 14 ng/mL (reference range, 20 to 200 ng/mL), with an elevated serum parathyroid hormone level of 241 pg/mL (reference range, 10 to 65 pg/mL), but normal serum calcium and phosphorus levels. The skin lesions persisted despite local wound care, daily hyperbaric oxygen, and parenteral sodium thiosulfate therapies. After normalizing the serum vitamin D level through oral supplementation, she responded well to pamidronate infusion with complete healing of the ulcers and regained 13% of her premorbid weight.ConclusionThis is the first case of calciphylaxis preceded by weight loss of greater than 100 kg in a patient with hypovitaminosis D who responded to pamidronate therapy. (Endocr Pract. 2011;17:e104-e108)     

Safety of Vitamin D Replacement in Patients with Primary Hyperparathyroidism and Concomitant Vitamin D Deficiency

ObjectiveTo evaluate the safety of vitamin D replacement in patients with vitamin D deficiency and primary hyperparathyroidism.MethodsRetrospective chart review of 35 patients from our endocrine clinic, age 22 to 89 years, diagnosed with primary hyperparathyroidism and vitamin D deficiency, and treated with either 1,000 to 2,000 international units (IU) of vitamin D daily or 50,000 IU of vitamin D weekly for 5 months. Data were collected before and after treatment on serum calcium, 25-hydroxyvitamin D (25-OH D), intact parathyroid hormone (iPTH), phosphorus, alkaline phosphatase, nephrolithiasis, fractures, and osteoporosis.Results25-OH D increased significantly, from a baseline of 14.65 ± 6.57 ng/mL to 42.17 ± 12.98 ng/ mL after weekly treatment with 50,000 IU of vitamin D (P<.0001), and from 22.42 ± 5.47 ng/mL to 33.33 ± 6.39 ng/mL following daily treatment with 1,000 to 2,000 IU of vitamin D (P<.0001). Pre- and posttreatment unadjusted serum calcium remained stable in the high-dose group (10.80 ± 0.43 mg/dL vs. 10.72 ± 0.67 mg/dL; P = .47), but decreased slightly in the low-dose group (10.76 ± 0.58 mg/dL vs. 10.11 ± 0.54 mg/dL; P = .0007). After adjusting for age, sex, vitamin D, and PTH levels, the small calcium difference in the low-dose group became statistically insignificant. Treatment with either high or low doses of vitamin D did not significantly change iPTH levels. Creatinine remained stable in all patients, and no new cases of nephrolithiasis were reported.ConclusionReplacing vitamin D in mild primary hyperparathyroidism is safe, effective, and does not increase calcium to dangerous levels. (Endocr Pract. 2013;19:420-425)     

Hypothyroidism as A Cause of Hyponatremia: Fact or Fiction?

ObjectiveTo illustrate that severe primary hypothyroidism alone may not be enough to cause hyponatremia in the otherwise healthy ambulatory patient.Methods:A retrospective chart review was conducted using an academic health center enterprise-wide electronic health record to identify 10 patients with primary hypo thyroidism and same-day serum thyroid-stimulating hormone (TSH), sodium, creatinine, and calculated glomerular filtration rate (GFR). Same-day free triiodothyronine or free thyroxine was also recorded if tested. Patients were included in our case series if they met the following inclusion criteria: TSH level > 100 μU/mL and same-day sodium and creatinine levels. All laboratory tests were collected on an outpatient basis.ResultsThe 10 subjects (2 men and 8 women) were ages 19 to 97 years (median, 51.5 years). Median TSH was 193 μU/mL (range, 104.2 to 515.6 μU/mL; normal, 0.40 to 5.50 μU/mL) with median sodium of 138 mmol/L (range, 136 to 142 mmol/L; normal, 135 to 146 mmol/L). The lowest sodium was 136 mmol/L with concurrent TSH of 469.7 μU/mL, free triiodothyronine of 1.0 pg/mL (normal, 1.8 to 4.6 pg/mL), and free thyroxine of 0.2 ng/ dL (normal, 0.7 to 1.8 ng/dL). Median GFR was 67.5 mL/ min/1.73 m² (range, 44 to 114 mL/min/1.73 m²; normal, 90 to 120 mL/min/1.73 m²).ConclusionIn our small series of patients with extreme TSH elevations, none had a serum sodium level below normal (< 135 mmol/L), even in the presence of a reduced GFR. Hyponatremia can be a common occurrence in hospitalized and/or chronically ill patients; however, in an otherwise relatively healthy ambulatory patient, hypothyroidism, even when severely undertreated, may be a less clinically relevant cause of hyponatremia. (Endocr Pract. 2012;18:894-897)     

Estradiol and testosterone concentrations increase with fasting in weaned pups of the northern elephant seal (Mirounga angustirostris)

Although neonatal development is generally associated with increased levels of circulating testosterone (T) and estradiol (E2), food deprivation may inhibit steroidogenesis. Therefore, these potentially conflicting stimuli were examined in fasting weaned northern elephant seal (Mirounga angustirostris) pups by measuring serum concentrations of T, E2, progesterone (P4), and luteinizing hormone (LH) by either radioimmunoassay (P4, LH) or enzymeimmunoassay (T, E2). Blood samples were obtained from 20 male and 20 female pups at both early (<1 wk postweaning) and late (6-8 wk postweaning) periods during their natural postweaning fast. T in males (early: 2.9 +/- 0.4 ng/mL; late: 16 +/- 2 ng/mL; P < 0.0001) and E2 in females (early: 42 +/- 6 pg/mL; late: 67 +/- 5 pg/mL; P < 0.01) increased between the two measurement periods, while P4 (early: 2.5 +/- 0.3 ng/mL; late: 2.1 +/- 0.3 ng/mL; P > 0.05) did not. LH increased (early: 46 +/- 4 pg/mL; late: 65 +/- 6 pg/mL; P < 0.05) in males but not in females (early: 69 +/- 9 pg/mL; late: 65 +/- 6 pg/mL; P > 0.05). Increases in LH and T suggest that LH may stimulate T secretion. Alternatively, relatively low concentrations of LH in both males and females may reflect negative feedback inhibition imposed by elevated T and E2 concentrations. Despite the inherent postweaning fast, concentrations of T and E2 increased, suggesting that they may be critical for the continued development of pups. Therefore, compensatory mechanisms may exist that alleviate the fasting-induced inhibition of gonadal steroidogenesis during neonatal development in elephant seal pups.     

Suppressibility of Parathyroid Hormone in Primary Hyperparathyroidism

ObjectiveTo describe an unusual case of pathologically confirmed primary hyperparathyroidism in a patient presenting with severe hypercalcemia and an undetectable parathyroid hormone (PTH) level.MethodsWe present a detailed case report and outline the serial laboratory findings. In addition, the possible causes of low serum PTH levels in the setting of primary hyperparathyroidism are discussed.ResultsA 16-year-old female patient presented with severe epigastric pain, found to be attributable to acute pancreatitis. At hospital admission, her serum calcium concentration was high (14.0 mg/dL); the patient also had a normal serum phosphorus level of 3.6 mg/dL and an undetectable PTH level (< 0.2 pmol/L). An evaluation for non-PTH-mediated causes of hypercalcemia revealed a partially suppressed thyroid-stimulating hormone concentration and a below normal 1,25-dihydroxyvitamin D level, consistent with her suppressed PTH. One week after the patient was dismissed from the hospital, repeated laboratory studies showed a serum calcium value of 11.1 mg/dL, a serum phosphorus level of 2.8 mg/dL, and an elevated PTH concentration of 11.0 pmol/L, consistent with primary hyperparathyroidism. A repeated 1,25-dihy-droxyvitamin D measurement was elevated. A parathyroid scan showed a parathyroid adenoma in the left lower neck area, and she subsequently underwent successful surgical resection of a pathologically confirmed parathyroid adenoma.ConclusionThis case demonstrates that the serum PTH level can be suppressed in patients with primary hyperparathyroidism. Moreover, it emphasizes the need for careful evaluation of the clinical context in which the PTH measurement is determined. Consideration should be given to repeating measurement of PTH and serum calcium levels when the initial laboratory evaluation of hypercalcemia is unclear because dynamic changes in calcium metabolism may occur in the presence of secondary contributing factors. (Endocr Pract. 2007;13:785-789)