Rise In Parathyroid Hormone Levels Research Articles

SAT-341 Hyperparathyroid Crisis Precipitated by Rapid Correction of Symptomatic Hypercalcemia in an Occult Ectopic Parathyroid Adenoma

Background: Parathyroid adenomas (PA) are typically benign, slow-growing tumors causing gradual increase in parathyroid hormone (PTH) and serum calcium (s.Ca) levels. Hyperparathyroid crisis is a rare and potentially fatal syndrome, which occurs due to rapid elevation of PTH and s.Ca levels (s.Ca >15mg/dL). This can potentiate severe metabolic derangements, manifesting as altered mental status (AMS), renal insufficiency and cardiac arrhythmias. We present a case of hyperparathyroid crisis in the setting of an occult ectopic parathyroid adenoma.Case: 75 year old female with a medical history of osteoporosis, hypertension and Parkinson’s disease, presented to our hospital with AMS and one week history of diarrhea. She was recently hospitalized for pneumonia and treated with antibiotics. Biochemical analysis revealed corrected s.Ca 15.4mg/dL (8.2- 9.6mg/dL; 7 days prior s.Ca was 9.7mg/dL), renal insufficiency (Cr 2.26mg/dL; baseline 1.2) with normal serum phosphorus, magnesium, 25-hydroxyvitamin D and alkaline phosphatase. PTH was found to be elevated at 75pg/mL (15-65pg/mL). She was treated with aggressive intravenous hydration and calcitonin 200mg BID for 3 days. Her s.Ca appropriately trended down. However, her PTH level continued to rise: 319pg/mL 12 hours later, 591pg/mL on day 2 and peaked to 1,242pg/mL on day 3. CT angiography neck showed an incidental finding of a heterogeneous, possibly necrotic, soft tissue nodule in the left paraesophageal region. Additional work-up with technetium 99 Sestamibi scan revealed persistent activity in the upper tracheoesophageal groove consistent with an ectopic PA. She underwent parathyroid exploration with excision of an enlarged ectopic left superior parathyroid adenoma, confirmed on histopathological analysis. The remaining parathyroid glands were normal. PTH declined to 34pg/mL postoperatively. Her mental status improved significantly returning to baseline within a few days with normal PTH and s.Ca levels.Discussion: Secretion of PTH is mediated by s.Ca via the calcium sensing receptors (CaSR). Studies have shown that patients with PA have decreased expression of the CaSR leading to an autonomous rise in PTH secretion and a higher PTH-calcium set point. In our case, the patient initially presented with a mildly elevated PTH level and symptomatic hypercalcemia. The rapid correction of s.Ca levels precipitated a remarkable rise in PTH levels. We postulate that this was caused by a possible upregulation mechanism in calcium sensing by adenomatous parathyroid tissue that is responsive to acute lowering of s.Ca levels, triggering a hyperparathyroid crisis.Reference: (1) Corbetta S., et al. Calcium-sensing receptor expression and signaling in human parathyroid adenomas and primary hyperplasia. Clinical Endocrinology. 2000; 52(3):339-48.

SUN-514 Severe Hypophosphatemia and Worsening Secondary Hyperparathyroidism Following Treatment with Denosumab

Introduction We present a case of a patient with osteoporosis and chronic kidney disease (CKD)-induced secondary hyperparathyroidism who developed severe hypophosphatemia and increasing parathyroid hormone (PTH) level after receiving Denosumab. Clinical Case 90-year-old male with CKD stage 3 presented for hyperparathyroidism evaluation in 2015. Baseline GFR was 39 - 47 ml/min/1.73 m2. PTH was 320 pg/ml (8 - 97 pg/ml) with normal calcium and low vitamin D (25-D) 14 ng/ml (30 - 100 ng/ml). Repeat PTH was 299 pg/ml; 25-D 23 ng/ml and 24-hr urine calcium was 8 mg (100 - 300 mg). Hyperparathyroidism was concluded to be due to CKD and Vitamin D deficiency. Vitamin D was replaced and PTH decreased to 262 pg/ml. With fragility fracture history, dual-energy X-ray absorptiometry (DXA) scan was obtained and resulted with a T-score of -2.8 SD at the femoral neck. Denosumab (60 mg) was started after 25-D normalized in 3/2016. Follow-up laboratory analysis in 8/2016 revealed PTH 512 pg/ml, calcium 8.9 mg/dl (8.5 - 10.1 mg/dl), 25-D 44.7 ng/ml and phosphate 1.3 mg/dl (2.5 - 4.5 mg/dl), previously 2.1 mg/dl. Alkaline phosphate 104 U/l (45 - 117 U/l), calcitriol 63.9 pg/ml (19.9 - 79.3 pg/ml) and fibroblast growth factor 23 (FGF-23) 188 RU/ml (44 - 215 RU/ml). 24-hr urine calcium was 27 mg and phosphate >90 mg/dl. Serum phosphate improved with supplementation and Cinacalcet started for high PTH. After the second Denosumab injection, low phosphate (1.2 mg/dl) recurred and PTH remained high (510 pg/ml). With recurrent effects, Denosumab was switched to bisphosphonate as GFR was stable >40 ml/min/1.73 m2. PTH normalized to 78 pg/ml and phosphate stable (2-2.4 mg/dl) on Cinacalcet and off Denosumab. Discussion Hypophosphatemia is a rare side effect of Denosumab, a monoclonal antibody to RANK-L. PTH mildly increase with Denosumab secondary to hypocalcemia. In our patient, there was a significant rise in PTH level and a decline in phosphate following Denosumab administration with no effect on calcium level. There are very few reports of these combined adverse events in the literature. The proposed mechanism is that the irreversible blockade by Denosumab results in low bone turnover which then causes increase in PTH and then increase urinary phosphate excretion. This mechanism can apply to CKD patients with secondary hyperparathyroidism when given a blocking agent like Denosumab, there is a further increase in PTH in the setting of low bone turnover. If not closely monitored, it can be detrimental. Elevated FGF-23 can downregulate 1-alpha-hydroxylase and increase urinary phosphate but unlikely in our patient given its normal level. Conclusion Severe hypophosphatemia may be a rare side effect of Denosumab, particularly in CKD patient with secondary hyperparathyroidism. Therefore, phosphate and PTH should be monitored closely after Denosumab administration to prevent adverse events.

Vitamin D status in healthy black African adults at a tertiary hospital in Nairobi, Kenya: a cross sectional study

BackgroundVitamin D has been known since the twentieth Century for its benefits in bone health. Recent observational studies have demonstrated its benefits in infectious diseases such as tuberculosis and non-communicable diseases such as diabetes mellitus, cardiovascular diseases and cancer. This has led to a dramatic increase in testing among adults.The cut-offs for vitamin D deficiency have been debated for decades and the current cut off is derived from a Caucasian population. Studies done among black African adults in Africa are few with vitamin D deficiency ranging from 5 to 91%. A few cut- offs have correlated vitamin D deficiency to physiological markers such as parathyroid hormone (PTH), calcium and phosphate with varying results.MethodsThis was a cross sectional study carried out among blood donors at Aga Khan University hospital, Nairobi (AKUHN) from March to May 2015. Vitamin D (25(OH)D) levels were assayed and correlated with PTH, calcium and phosphate.ResultsA total of 253 individuals were included in the final analysis. The proportion of study participants who had a 25(OH) D level of < 20 ng/ml thus classified as vitamin D deficient was 17.4% (95% C.I 12.73–22.07). The 25(OH) D level that coincided with a significant increase in PTH was 30 ng/ml.Males were less likely to be vitamin D deficient (O.R 0.48 (C.I 0.233–0.993) p 0.04). Sunshine exposure for ≥3 h per day reduced the odds of being Vitamin D deficient though this was not statistically significant after multivariate regression analysis.ConclusionsWe found a much lower prevalence of Vitamin D deficiency compared to many similar studies carried out in sub-Saharan Africa possibly due to the recruitment of healthy individuals and the proximity of Nairobi to the equator which allows for considerable exposure to sunshine. Vitamin D levels below 30 ng/mL was associated with a significant rise in PTH levels, suggesting that this cut off could be appropriate for defining Vitamin D deficiency in the population served by our laboratory.

Gender specific association of parathyroid hormone and vitamin D with metabolic syndrome in population with preserved renal function

The association of parathyroid hormone (PTH) and vitamin D with Metabolic syndrome (MetS) was evaluated using representative data from the Korean population. Data from 7004 subjects aged 50 or older with preserved renal function (excluding chronic kidney disease stage 3b to 5) who were included in the Korean National Health and Nutrition Examination Survey between 2008 and 2010 were analysed. Higher PTH levels (pg/ml) were observed in subjects with MetS than in those without MetS among both genders (60.1 (58.6–61.6) vs. 62.4 (60.7–64.2) in males p = 0.018, 60.7 (59.4–62.1) vs. 63.9 (62.4–65.6) in females, p < 0.001). For females, PTH levels were significantly higher in subjects with MetS than in those without MetS after adjustment for possible covariates. Lower 25(OH)D levels were significantly associated with MetS only in male subjects (p = 0.004). As the number of MetS components increased, a significant rise in PTH levels (p for trend 0.005 in males and 0.024 in females) and a decrease in 25(OH)D levels (p for trend < 0.001 in males and 0.053 in females) were observed. In conclusion, among subjects with preserved renal function, PTH levels were possibly associated with MetS in females, whereas vitamin D levels exhibited a possible link to MetS in males.

Effects of TNF Inhibitors on Parathyroid Hormone and Wnt Signaling Antagonists in Rheumatoid Arthritis.

Tumor necrosis factor α inhibitors (TNFi) are the major class of biologic drug used for the treatment of Rheumatoid arthritis (RA). Their effects on inflammation and disease control are well established, but this is not true also for bone metabolism, especially for key factors as parathyroid hormone and Wnt pathway. Those two pathways are gaining importance in the pathogenesis RA bone damage, both systemic and local, but how the new treatment affects them is still largely unknown. We studied 54 RA patients who were starting an anti-TNFα treatment due to the failure of the conventional synthetic disease-modifying antirheumatic drugs. Serum levels of Wnt/βcatenin pathway inhibitors (Dickkopf-related protein 1, Dkk1, and Sclerostin), Parathyroid hormone (PTH), vitamin D, and bone turnover markers were measured at baseline in the morning after fasting and after 6 months of therapy. We found a significant percentage increase in serum PTH (+32±55%; p=0.002) and a decrease in Dkk1 mean serum levels (-2.9±12.1; p=0.05). PTH percentage changes were positively correlated both with C-terminal telopeptide of type I collagen and Dkk1 percentage changes. Sclerostin serum levels showed no significant difference. TNFi treatment provokes in the short term a rise in PTH levels and a decrease in Dkk1 serum levels. The increase of PTH might promote bone resorption and blunt the normalization of Dkk1 serum levels in RA. Those data give a new insight into TNFi metabolic effects on bone and suggest new strategies to achieve better results in terms of prevention of bone erosions and osteoporosis with TNFi treatment in RA.

Hungry bone syndrome and normalisation of renal phosphorus threshold after total parathyroidectomy for tertiary hyperparathyroidism in X-linked hypophosphataemia: a case report.

IntroductionThis is the first report of which the authors are aware to describe this c.2166delinsGG mutation in X-linked hypophosphataemia and to describe normalisation of renal threshold for phosphate excretion after parathyroidectomy for tertiary hyperparathyroidism in X-linked hypophosphataemia.Case presentationWe present the case of a 34-year-old Caucasian woman with X-linked hypophosphataemia. She developed tertiary hyperparathyroidism with markedly high bone turnover requiring total parathyroidectomy and had prolonged requirement for intravenous calcium infusion after surgery. She had a novel mutation in her phosphate-regulating gene with homologies to endopeptidases on the X-chromosome and had an unusual degree of dependence on phosphate supplementation. Prior to operative intervention she had a trial of cinacalcet that improved bone turnover markers when used in isolation but which led to a paradoxical rise in parathyroid hormone levels when given with phosphate supplementation. After correction of hungry bone syndrome, the renal phosphorus threshold normalised as a manifestation of hypoparathyroid state despite marked elevation in level of fibroblast growth factor 23.ConclusionsThis case illustrates the risk of tertiary hyperparathyroidism as a complication of treatment for hypophosphataemia; it highlights the morbidity associated with hungry bone syndrome and provides novel insight into renal handling of phosphorus.

Development of Renal Calculi and Imatinib Therapy in CML: Is There an Association?.

Reports are accumulating regarding the altered bone and mineral metabolism caused by imatinib (IM) therapy (Berman E, et al 2006 NEJM). This probably occurs through in vivo inhibition of PDGF receptors. It has been proposed that prolonged use of IM may cause some potentially serious metabolic pathological disorders. Compensatory rise in parathyroid hormone level may cause renal pathologies in these patients. In this observational study we came across a few patients on imatinib therapy for CML who experienced prolonged dyspepsia, abdominal and bone pain (suggestive of groans, moans, bones and stones features) and abdominal ultrasonography revealed renal calculi. This has led to collection of clinical data. So far, no systematic evaluation with radiological or biochemical have been undertaken in our cohort of 177 of CML on imatinib therapy. At the time of this report we have noted development of renal calculi (all symptomatic) in 7 patients of CML on imatinib therapy. All these patients have been on imatinib therapy 400 mg daily for more than 1 month before symptoms developed. In all but one, no surgical intervention has been necessary so far. Biochemical evaluation for altered bone metabolism revealed hyperphosphatemia in one and normal in another. Analysis of renal stone in one showed a composition of calcium phosphate and oxalate. Imatinib was not discontinued but reduced to 300 mg in 3 patients. It is possible that prolonged use of IM may alter calcium and phosphate metabolism leading to renal calculi formation. The proposed mechanisms could be,i.interference with bone and mineral metabolism coupled with parathyroid dysfunction which in turn leads to renal tubular abnormalities orii.availability of excess oxalate for intestinal absorption brought about by low calcium ingestion.Well designed cohort studies may throw more light in this area.

Early and Severe Hyperparathyroidism Associated with Hypercalcemia After Renal Transplant Treated with Cinacalcet

Bone disease is a common clinical problem following renal transplantation. In renal transplant recipients, multiple underlying factors determine the extent of bone loss and the subsequent risk of fractures. In addition to the well-recognized risk to bone disease posed by steroids, calcineurin inhibitors and pre-existing bone disease, persistent hyperparathyroidism (HPT) contributes to post-transplant bone loss. HPT is usually treated with vitamin D supplements combined with calcium. Patients whose HPT is associated with hypercalcemia pose a difficult therapeutic dilemma which often requires parathyroidectomy. Cinacalcet, a calcium mimetic agent, offers a unique pharmacologic approach to the treatment of patients with post-transplant hypercalcemia and HPT. In this paper, we describe the clinical course and biochemical changes in 10 renal transplant recipients with hypercalcemia and severe HPT early after renal transplantation treated with cinacalcet. Cinacalcet therapy corrected hypercalcemia and decreased parathyroid hormone (PTH) levels in all cases. A transient rise in the level of alkaline phosphatase was noted following initiation of cinacalcet therapy. In this patient population, correction of HPT was not permanent as discontinuing cinacalcet therapy led to a rapid rise in PTH level.

Circulating intact parathyroid hormone levels in acute pancreatitis.

Serum levels of parathyroid hormone (PTH), calcium and albumin were measured daily for 5 days in 41 selected patients with moderate to severe acute pancreatitis. The PTH level was measured by means of a two-site immunoradiometric assay specific for the intact polypeptide. A rise in PTH level was observed more commonly in patients with a complicated or fatal outcome than in those with an uncomplicated course (14 of 16 versus six of 25 patients, P < 0.001). Although PTH levels were variable in the presence of hypocalcaemia, raised concentrations were found more frequently in patients with complications (seven of eight versus two of seven without complications, P = 0.035). This study confirms that an appropriate rise in PTH level occurs in response to the hypocalcaemic stimulus in patients with acute pancreatitis.

On the mechanisms responsible for the phosphaturia of bicarbonate administration.

Experiments were carried out in normal dogs to characterize the mechanisms by which sodium bicarbonate administration results in increased excretion of phosphate. Infusion of sodium bicarbonate alone increased fractional phosphate excretion from 0.8 to 29.3%. During bicarbonate administration, ionized calcium fell and mean parathyroid hormone values increased from 59.6 to 230.4 muleq/ml. In the same group of dogs, administration of sodium bicarbonate plus calcium prevented the fall in ionized calcium, and parathyroid hormone levels remained unchanged. In these dogs fractional phosphate excretion increased from 2.4 to only 4.9%. Similar results were obtained in thyroparathyroidectomized dogs receiving sodium bicarbonate. In these dogs fractional excretion of phosphate increased from 0.6 to 4.5%. Under all three experimental conditions no differences were observed in sodium or bicarbonate excretion or in urinary or plasma pH. Administration of hydrochloric acid, after phosphaturia had been induced by the infusion of bicarbonate, resulted in a decrease in plasma bicarbonate and an acid urine; however, the phosphaturia persisted even in the presence of an acid urine pH. In five thyroparathyroidectomized dogs infused with parathyroid hormone throughout, administration of identical amounts of sodium as either NaCl or NaHCO3 resulted in a similar degree of phosphaturia despite significant differences in urine pH. These experiments suggest that a rise in parathyroid hormone levels, resulting from a fall in ionized calcium, is the major mechanism by which bicarbonate administration produces phosphaturia. An increased natriuresis per nephron, as a consequence of extracellular fluid volume expansion, contributes to the phosphaturia. On the other hand, alkalinization of the urine does not play a significant role in the phosphaturia seen after bicarbonate administration.

Calcium, Phosphorus, and Bone in Renal Disease and Transplantation

Calcium-phosphate-bone interrelationships become disrupted progressively in advancing renal disease. Parathyroid hormone (PTH) release, normally attuned to calcium homeostasis requirements, becomes dominated by alterations in phosphate balance. With each wave of nephron destruction, there is believed to occur transient hyperphosphatemia, transient hypocalcemia, and a step-wise rise in PTH levels. When the glomerular filtration rate falls below 25 to 30 ml per minute, hyperphosphatemia persists, hypocalcemia tends to persist, and the stimulus to PTH release is exaggerated. Vitamin D resistance contributes both to hypocalcemia (thus to accelerated PTH secretion) and to osteomalacia. In patients receiving long-term hemodialysis, if hyperphosphatemia and hypocalcemia persist, PTH levels may remain high and osteitis fibrosa may progress. Successful renal transplantation typically leads to regression of hyperparathyroidism and restoration of vitamin D sensitivity; however, hyperparathyroidism may regress slowly, and severe hypercalcemia must be guarded against. True autonomy of PTH release apparently occurs rarely in chronic renal disease.