Hyperparathyroidism Abstracts 1

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Secondary Hyperparathyroidism After Bariatric Surgery: Treatment Is With Calcium Carbonate Or Calcium Citrate
            (Baretta et al., 2015) Download
BACKGROUND:  Bariatric surgery, especially Roux-en-Y gastric bypass, can cause serious nutritional complications arising from poor absorption of essential nutrients. Secondary hyperparathyroidism is one such complications that leads to increased parathyroid hormone levels due to a decrease in calcium and vitamin D, which may compromise bone health. AIM:  To compare calcium carbonate and calcium citrate in the treatment of secondary hyperparathyroidism. METHOD:  Patients were selected on the basis of their abnormal biochemical test and treatment was randomly done with citrate or calcium carbonate. RESULTS:  After 60 days of supplementation, biochemical tests were repeated, showing improvement in both groups. CONCLUSION:  Supplementation with calcium (citrate or carbonate) and vitamin D is recommended after surgery for prevention of secondary hyperparathyroidism.

Clinical practice. Asymptomatic primary hyperparathyroidism.
            (Bilezikian and Silverberg, 2004) Download
A 60-year-old woman is noted incidentally to have a calcium level of 10.8 mg per deci- liter (2.70 mmol per liter; normal range, 8.4 to 10.2 mg per deciliter [2.10 to 2.55 mmol per liter]). The parathyroid hormone level, as measured on immunoradiometric assay, is 84 pg per milliliter (normal range, 10 to 65). She has never had a kidney stone or a fracture, and she feels well. Her urinary calcium excretion is normal. Her bone density is within 0.5 SD of the peak bone mass at the lumbar spine and the hip and is 1.0 SD below the peak bone mass at the forearm. How should her case be managed?

Lithium use and primary hyperparathyroidism.
            (Broome and Solorzano, 2011) Download
OBJECTIVE:  To review suspected causes of lithium-induced hyperparathyroidism, disease presentation, underlying pathology, and current recommendations and trends in medical and surgical treatment. METHODS:  Relevant literature was reviewed. RESULTS:  Lithium carbonate therapy has continued to be a mainstay of treatment for bipolar disease and schizoaffective disorder since its introduction into clinical use. Several metabolic consequences are associated with its long-term use, including hypercalcemia and hyperparathyroidism. CONCLUSIONS:  Until further data become available, the surgeon should remain vigilant for the presence of pathologically active glands that may manifest their function at different times during the disease course.

Administration of a supplement containing both calcium and vitamin D is more effective than calcium alone to reduce secondary hyperparathyroidism in postmenopausal women with low 25(OH)vitamin D circulating levels.
            (Deroisy et al., 2002) Download
BACKGROUND AND AIMS:  Supplementation of postmenopausal women with calcium alone or calcium-vitamin D association was suggested to have positive effects on bone turnover and bone density, as well as to lower fracture incidence. The beneficial effect appears to be mediated by a reduction in parathyroid hormone secretion. Our aim was to compare the respective efficacy of calcium and calcium-vitamin D supplements in reducing serum parathyroid hormone levels in postmenopausal women with prevalent low 25(OH)vitamin D levels. METHODS:  One hundred consecutive ambulatory postmenopausal women with serum 25(OH)vitamin D levels below 18 ng/mL were included in a randomized, prospective, open label study. For a duration of 90 days, the women were randomly assigned to a daily supplementation of either one tablet of calcium gluconolactate and carbonate (500 mg calcium), or one powder-pack of an association of calcium carbonate (500 mg calcium), citric acid (2.175 gr) and cholecalciferol (200 IU). Changes observed during the 90 days of the study in circulating PTH levels were the primary endpoint, while changes in serum 25(OH)D levels were assessed as secondary endpoint. RESULTS:  A significant difference was observed between the calcium-vitamin D (CaD) and the calcium (Ca) only groups for changes occurring during the 90 days of the study in PTH (-14.5+/-40% and +2.5+/-46%) (p=0.009) and 25(OH)D (+67+/-77% and +18+/-55%) (p<0.001) circulating levels. PTH changes between baseline and day 90 were significant in the CaD group, but not in the Ca group. The odds ratio for a patient in group Ca to experience an absolute (<12 ng/mL) deficiency in circulating 25(OH)vitamin D levels, compared to a group CaD patient was statistically increased (OR: 3.22, 95% CI: 1.33-7.80). CONCLUSIONS:  Our results support the recommendation of supplementing postmenopausal women with low circulating levels of 25(OH)vitamin D with a combination of calcium and vitamin D, rather than with calcium alone.

Estrogen replacement may be an alternative to parathyroid surgery for the treatment of osteoporosis in elderly postmenopausal women presenting with primary hyperparathyroidism: a preliminary report.
            (Diamond et al., 1996) Download
Parathyroid surgery is indicated in patients presenting with primary hyperparathyroidism (PHPT) and osteoporosis (defined as bone mineral density more than 2 standard deviations below normal). Many are elderly women with complex medical problems, either unwilling or considered unfit for surgery. Estrogen replacement therapy (ERT) may potentially be an alternative form of therapy in this group. We studied 15 consecutive postmenopausal women presenting with PHPT and osteoporosis. Group 1 comprised 5 women who elected to be treated with ERT (conjugated equine estrogen, 0.3-0.625 mg/day). The other 10 women underwent successful parathyroidectomy. These 10 patients were randomly subdivided into group 2 (5 patients who received calcitriol 0.25 micrograms b.i.d. for 12 months following surgery) and group 3 (5 patients who received elemental calcium 1 g/day for 12 months following surgery). Lumbar spine and femoral neck bone mineral density (BMD) were measured prior to and after 12 months of therapy, using a dual-energy X-ray absorptiometer (Lunar DPX-L). The three groups did not differ with respect to their ages (group mean 71.8 years), or baseline serum calcium (group mean 2.77 mmol/l), serum parathyroid hormone (group mean 11.0 pmol/l), lumbar spine BMD (group mean 0.93 g/cm2) and femoral neck BMD (group mean 0.73 g/cm2). Serum calcium normalized in all patients who underwent surgery and none developed hypoparathyroidism. A non-significant decrease in serum calcium was seen in patients treated with ERT only. Lumbar spine (+5.3% per year; 95% CI, 1.1% to 9.6%) and femoral neck BMD (+5.5% per year; 95% CI, -2.1% to 13.2%) increased significantly after 12 months of ERT (p < 0.001 compared with pre-therapy values). These increases in BMD did not differ significantly from those in patients who underwent successful parathyroidectomy followed by either calcitriol therapy or calcium replacement (lumbar spine BMD increase of +6.2% per year, 95% CI 3.1% to 9.4%; and femoral neck BMD increase of +3% per year, 95% CI 0 to 6%). In summary, increases in lumbar spine and femoral neck BMD occur following treatment of PHPT. ERT appeared as effective as parathyroidectomy (combined with either calcitriol or calcium supplements) for the treatment of osteoporosis in elderly postmenopausal women presenting with PHPT.

Hyperparathyroidism - Lancet
            (Fraser, 2009) Download
Hyperparathyroidism is due to increased activity of the parathyroid glands, either from an intrinsic abnormal change altering excretion of parathyroid hormone (primary or tertiary hyperparathyroidism) or from an extrinsic abnormal change affecting calcium homoeostasis stimulating production of parathyroid hormone (secondary hyperparathyroidism). Primary hyperparathyroidism is the third most common endocrine disorder, with the highest incidence in postmenopausal women. Asymptomatic disease is common, and severe disease with renal stones and metabolic bone disease arises less frequently now than it did 20-30 years ago. Primary hyperparathyroidism can be cured by surgical removal of an adenoma, increasingly by minimally invasive parathyroidectomy. Medical management of mild disease is possible with bisphosphonates, hormone replacement therapy, and calcimimetics. Vitamin D deficiency is a common cause of secondary hyperparathyroidism, particularly in elderly people. However, the biochemical definition of vitamin D deficiency and its treatment are subject to much debate. Secondary hyperparathyroidism as the result of chronic kidney disease is important in the genesis of renal bone disease, and several new treatments could help achieve the guidelines set out by the kidney disease outcomes quality initiative.

Vitamin D and hyperparathyroidism in obesity.
            (Grethen et al., 2011) Download
BACKGROUND:  Low vitamin D status and hyperparathyroidism occur in obesity and may be involved in pathogenesis of obesity-associated comorbid conditions. AIMS:  Our aims were to determine in obesity whether there was vitamin D insufficiency, assessed by serum 25-hydroxyvitamin D (s25D) and serum PTH (sPTH) and whether it related to comorbid conditions. METHODS:  We conducted a case-control study of 48 women having bariatric surgery and 50 healthy women frequency matched for race, age, year, and season of study. Height, weight, s25D, sPTH, serum 1,25-dihydroxyvitamin D (s1,25D), serum bone alkaline phosphatase, serum cross-linked N-telopeptides of type 1 collagen, and serum calcium, phosphate, creatinine, glucose, and insulin were measured, and comorbid conditions were documented from patient files. RESULTS:  Weight (140 vs. 76 kg, P < 0.001), sPTH (44.4 vs. 25.6 pg/ml, P < 0.001), s1,25D (39 vs. 24 pg/ml, P < 0.001), serum bone alkaline phosphatase (19 vs. 12 ng/ml, P < 0.001), serum cross-linked N-telopeptides of type 1 collagen (9.6 vs. 7.9 nm bone collagen equivalents, P = 0.007), serum phosphate (3.45 vs. 3.24 mg/dl, P = 0.043), and serum creatinine (1.05 vs. 0.87 mg/dl, P < 0.001) were higher, and s25D (16 vs. 23 ng/ml, P <.001) was lower in bariatric-surgery women than control women. s25D was lower in bariatric-surgery women than controls in summer (17 vs. 26 ng/ml, P < 0.0001) but not winter (15 vs. 18 ng/ml, P > 0.2). Multiple regression analysis demonstrated that weight predicted s25D (P < 0.001) and sPTH (P = 0.001), but s25D did not predict sPTH or the presence of comorbid conditions except for osteoarthritis. CONCLUSION:  Women having bariatric surgery had lower s25D and higher sPTH. The major determinant of s25D and sPTH was weight. Hyperparathyroidism in obesity did not indicate vitamin D insufficiency. Low s25D was not associated with comorbid conditions, apart from osteoarthritis.

Lithium-associated hypercalcemia and hyperparathyroidism in the elderly: what do we know
            (Lehmann and Lee, 2013) Download
BACKGROUND:  Lithium has been reported to induce hypercalcemia and hyperparathyroidism, yet few studies have examined the impact on older patients. We therefore undertook this review and report our findings. METHOD:  We undertook a systematic review of articles on lithium-associated hypercalcemia and/or hyperparathyroidism that were identified via electronic English language database searches through PubMed. RESULTS:  Among reported cases and case series of lithium-associated hyperparathyroidism in which ages of specific subjects were provided, 40% of affected individuals were over age 60. Mean serum calcium levels are reported to be higher in lithium treated patients over age 60 compared with younger patients. While many patients who develop lithium-associated hypercalcemia and hyperparathyroidism are asymptomatic, symptomatic complications may be more of a concern in older patients, especially in those with co-morbid renal disease. LIMITATIONS:  To date, all cross-sectional studies of lithium-associated hypercalcemia and hyperparathyroidism are of mixed age group cohorts and more specific studies focused on older patients have yet to be performed. CONCLUSIONS:  Lithium-induced hypercalcemia and hyperparathyroidism are under-recognized potential complications of lithium therapy which may occur more frequently in older patients. Psychiatrists should be vigilant in screening for hypercalcemia and hyperparathyroidism in their older patients receiving lithium, both prior to starting treatment and at least annually thereafter.

Primary hyperparathyroidism: an overview.
            (Mackenzie-Feder et al., 2011) Download
Primary hyperparathyroidism is a common condition that affects 0.3% of the general population. Primary and tertiary care specialists can encounter patients with primary hyperparathyroidism, and prompt recognition and treatment can greatly reduce morbidity and mortality from this disease. In this paper we will review the basic physiology of calcium homeostasis and then consider genetic associations as well as common etiologies and presentations of primary hyperparathyroidism. We will consider emerging trends in detection and measurement of parathyroid hormone as well as available imaging modalities for the parathyroid glands. Surgical indications and approach will be reviewed as well as medical management of primary hyperparathyroidism with bisphosphonates and calcimimetics.

Chronic autoimmune atrophic gastritis associated with primary hyperparathyroidism: a transversal prospective study.
            (Massironi et al., 2013) Download
DESIGN:  The coexistence of chronic autoimmune atrophic gastritis (CAAG) and primary hyperparathyroidism (PHPT) has been described previously, even if its extent and underlying mechanisms remain poorly understood. We therefore prospectively evaluated this association in two series of patients, one with CAAG and the other with sporadic PHPT. METHODS:  From January 2005 to March 2012, 107 histologically confirmed CAAG patients and 149 PHPT patients were consecutively enrolled. Routine laboratory assays included serum calcium, parathyroid hormone (PTH), plasma gastrin and chromogranin A (CgA). In CAAG patients with high PTH levels, ionized calcium and 25(OH)-vitamin D were evaluated. All CAAG and hypergastrinemic PHPT patients received an upper gastrointestinal endoscopy. Exclusion criteria were familial PHPT, MEN1 syndrome, treatment with proton pump inhibitor drugs, Helicobacter pylori infection and renal failure. RESULTS:  Of the 107 CAAG patients, nine (8.4%) had PHPT and 13 (12.1%) had secondary hyperparathyroidism stemming from vitamin D deficiency. Among the 149 PHPT patients, 11 (7.4%) had CAAG. Gastrin and CgA levels were similar in the CAAG patients with vs those without hyperparathyroidism (either primary or secondary), and calcium and PTH levels were similar in the PHPT patients with vs those without CAAG. CONCLUSIONS:  This study confirms a non-casual association between PHPT and CAAG. The prevalence of PHPT in CAAG patients is threefold that of the general population (8.4 vs 1-3%), and the prevalence of CAAG in PHPT patients is fourfold that of the general population (7.4 vs 2%). The mechanisms underlying this association remain unknown, but a potential role for autoimmunity is suggested.

Surgical cure of primary hyperparathyroidism ameliorates gastroesophageal reflux symptoms.
            (Norman et al., 2015) Download
OBJECTIVE:  Gastroesophageal reflux disease (GERD) symptoms are commonly reported in primary hyperparathyroidism (pHPT). Although a calcium-mediated cause-and-effect relationship has been suggested, it remains unknown if parathyroidectomy improves GERD symptoms. METHODS:  Over a 22-month period, 1,175 (39%) of 3,000 consecutive adult patients with pHPT and symptomatic GERD (on prescription reflux medications daily for ≥2 years) undergoing parathyroidectomy were entered into a prospective study. Standardized Frequency Scale for Symptoms of GERD (FSSG) questionnaire was used to assess symptoms before, 1 and 2 years after parathyroidectomy. RESULTS:  Daily prescription medication was used by 81%, while 19% used daily non-prescription drugs, both for a mean of 2.9 ± 0.7 years. GERD symptoms improved (26%) or resolved completely (36%) in 62% of patients (p < 0.0001 vs. preoperative baseline) 1 year after parathyroidectomy. Prescription medications for GERD decreased from 81% of enrolled patients to 26% (p < 0.0001) 12 months postoperatively, with 39% having complete symptom relief and taking no medications (p < 0.0001). Daily use of prescription GERD medications decreased to occasional over-the-counter drug use in 35% after parathyroidectomy (p < 0.0001). Mean FSSG scores decreased significantly postoperatively (pre-op: 18.0 ± 8.0 vs. post-op: 10.0 ± 5.0; p < 0.0001), with significant improvements in all 12 FSSG categories, including motility (pre-op: 7.3 ± 3.0 vs. post-op: 4.4 ± 3.0; p < 0.0001) and acid reflux symptoms (pre-op: 10.8 ± 5.0 vs. post-op: 5.9 ± 4.0; p < 0.0001). Symptomatic improvements were durable 2 years after parathyroidectomy. CONCLUSION:  Symptomatic GERD is common in pHPT. Parathyroidectomy provides significant, durable relief of both motility and acid reflux symptoms allowing discontinuation of prescription drug use for GERD in most (74%) patients providing yet another indication for parathyroidectomy in pHPT.

Hyperparathyroidism Resulting From Lithium Treatment Remains Underrecognized
            (Pomerantz, 2010) Download
Lithium continues to be the gold standard for the treatment of bipolar disorder. It is also helpful for related diagnoses, such as schizoaffective disorder and cyclic major depression. In addition to watching out for the well-known complications of lithium treatment—hypothyroidism and decreased renal function—health care providers should be aware of hyperparathyroidism.

The relationship between serum 25(OH)D and parathyroid hormone levels.
            (Saliba et al., 2011) Download
OBJECTIVE:  Low 25(OH)D levels are associated with increased parathyroid hormone levels leading to progressive bone loss. The serum levels of 25(OH)D sufficient to keep the parathyroid hormone level at a range that will prevent bone loss are still unclear. The current study was aimed at evaluating the relationship between 25(OH)D levels and concomitant parathyroid hormone levels. METHODS:  The computerized laboratory database of Clalit Health Services, a not-for-profit health maintenance organization covering more than half of the Israeli population, was searched for all 25(OH)D and parathyroid hormone tests performed in 2009. Concomitant tests of parathyroid hormone and 25(OH)D were identified in 19,172 people. RESULTS:  Serum parathyroid hormone levels were inversely correlated with 25(OH)D levels (r = -0.176, P < .001); 25(OH)D levels less than 50 nmol/L were associated with a steep increase in parathyroid hormone levels and hyperparathyroidism, which decreased with increasing 25(OH)D levels and reached a plateau at 25(OH)D levels of 75 to 85 nmol/L. The quadratic fit with plateau model showed that parathyroid hormone stabilizes at 25(OH)D level of 78.9 nmol/L. However, after excluding 5449 people with hypercalcemia or renal failure, the parathyroid hormone plateau was attained at a significantly lower 25(OH)D cut point of 46.2 nmol/L. CONCLUSION:  Our data suggest that a 25(OH)D threshold of 50 nmol/L is sufficient for parathyroid hormone suppression and prevention of secondary hyperparathyroidism in persons with normal renal function. 25(OH)D levels greater than 75 nmol/L do not seem to be associated with additional change in parathyroid hormone levels.

 


References

Baretta, GA, et al. (2015), ‘Secondary Hyperparathyroidism After Bariatric Surgery: Treatment Is With Calcium Carbonate Or Calcium Citrate’, Arq Bras Cir Dig, 28 Suppl 1 43-45. PubMed: 26537273
Bilezikian, JP and SJ Silverberg (2004), ‘Clinical practice. Asymptomatic primary hyperparathyroidism.’, N Engl J Med, 350 (17), 1746-51. PubMed: 15103001
Broome, JT and CC Solorzano (2011), ‘Lithium use and primary hyperparathyroidism.’, Endocr Pract, 17 Suppl 1 31-35. PubMed: 21247849
Deroisy, R, et al. (2002), ‘Administration of a supplement containing both calcium and vitamin D is more effective than calcium alone to reduce secondary hyperparathyroidism in postmenopausal women with low 25(OH)vitamin D circulating levels.’, Aging Clin Exp Res, 14 (1), 13-17. PubMed: 12027147
Diamond, T, et al. (1996), ‘Estrogen replacement may be an alternative to parathyroid surgery for the treatment of osteoporosis in elderly postmenopausal women presenting with primary hyperparathyroidism: a preliminary report.’, Osteoporos Int, 6 (4), 329-33. PubMed: 8883124
Fraser, WD (2009), ‘Hyperparathyroidism.’, Lancet, 374 (9684), 145-58. PubMed: 19595349
Grethen, E, et al. (2011), ‘Vitamin D and hyperparathyroidism in obesity.’, J Clin Endocrinol Metab, 96 (5), 1320-26. PubMed: 21325456
Lehmann, SW and J Lee (2013), ‘Lithium-associated hypercalcemia and hyperparathyroidism in the elderly: what do we know’, J Affect Disord, 146 (2), 151-57. PubMed: 22985484
Mackenzie-Feder, J, et al. (2011), ‘Primary hyperparathyroidism: an overview.’, Int J Endocrinol, 2011 251410. PubMed: 21747852
Massironi, S, et al. (2013), ‘Chronic autoimmune atrophic gastritis associated with primary hyperparathyroidism: a transversal prospective study.’, Eur J Endocrinol, 168 (5), 755-61. PubMed: 23447517
Norman, J, et al. (2015), ‘Surgical cure of primary hyperparathyroidism ameliorates gastroesophageal reflux symptoms.’, World J Surg, 39 (3), 706-12. PubMed: 25409840
Pomerantz, JM (2010), ‘Hyperparathyroidism Resulting From Lithium Treatment Remains Underrecognized’, Drug Benefit Trends, 22 62-63. PubMed:
Saliba, W, et al. (2011), ‘The relationship between serum 25(OH)D and parathyroid hormone levels.’, Am J Med, 124 (12), 1165-70. PubMed: 22114830