Increased Parathyroid Hormone Research Articles

Hyperparathyroidism and Peripheral Arterial Disease.

Primary hyperparathyroidism (PHPT) is presented in various forms, including classic PHPT, characterised by increased parathyroid hormone (PTH) secretion, normohormonal PHPT, and normocalcaemic PHPT. Secondary hyperparathyroidism is characterised by increased PTH secretion triggered by factors such as vitamin D deficiency and kidney failure. This review aims to discuss the involvement of hyperparathyroidism (HPT) in atherosclerosis, including peripheral arterial disease (PAD). The increased level of PTH is involved in developing subclinical and overt vascular diseases, encompassing endothelial dysfunction, vascular stiffness, hypertension, and coronary and peripheral arterial diseases. It has been consistently associated with an augmented risk of cardiovascular morbidity and mortality, independent of classical risk factors for atherosclerosis. Chronic hypercalcemia associated with increased levels of PTH contributes to the development of calcification of vessel walls and atherosclerotic plaques. Vascular calcification can occur in the intima or media of the arterial wall and is associated with stiffness of peripheral arteries, which the formation of atherosclerotic plaques and narrowing of the vessel lumen can follow. For treating hyperparathyroidism, particularly SHPT, calcimimetics, novel phosphorus binders and novel vitamin D receptor activators are used. However, they are ineffective in severe PHPT. Therefore, parathyroidectomy remains the primary therapeutic option of PHPT.

Hypovitaminosis D and hyperparathyroidism: a 5-year postoperative follow-up of 30,458 gastric bypass and sleeve gastrectomy patients

BackgroundBariatric procedures are associated with nutrient deficiencies. Studies show an association between gastric bypass (Roux-en-Y gastric bypass [RYGB]) and hypovitaminosis D as well as hyperparathyroidism, yet few compare RYGB to sleeve gastrectomy (SG), and large long-term analyses are scarce. ObjectiveEvaluate trends of vitamin D and parathyroid hormone (PTH) levels in RYGB and SG. SettingNational quality register. MethodThe Scandinavian Obesity Surgery Registry records all bariatric surgeries in Sweden. Data from 2008 to 2021 on primary RYGB or SG with reported 25-hydroxy vitamin D (25-OH-D) and/or PTH levels were included. Individuals with an estimated glomerular filtration rate of <60 mL/min/1.73 m2 were excluded, leaving a study population of 25,385 RYGB and 5073 SG patients. ResultsA decrease in 25-OH-D, mirrored by an increase in PTH, was observed after the first year for both procedures, but more pronounced in RYGB. At 5 years, 25-OH-D levels were still higher than at baseline. Regular supplementation resulted in better 25-OH-D and PTH levels. Linear regression found that procedure type (RYGB versus SG), 25-OH-D levels, and time since surgery were significant factors in predicting PTH levels. The risk of pathologic PTH levels (>7 pmol/L) at 2 and 5 years postoperatively was roughly three times higher in RYGB (odds ratios = 3.41 and 2.84, respectively). ConclusionsPrevious studies alongside these results suggest that RYGB, more so than SG, may cause hypovitaminosis D and thereby hyperparathyroidism, which could lead to osteopenia. The threshold for 25-OH-D should be >75 nmol/L, and despite higher levels, current vitamin D supplementation may not be sufficient. Follow-up should include screening for hyperparathyroidism and hypovitaminosis D.

Clinical characteristics and treatment modalities in uremic and non uremic calciphylaxis - a dermatological single-center experience

Calciphylaxis (CP) is a serious, potentially life-threatening disease that presents with medial calcification of small-sized vessels and painful ischemic ulcerations. Although calciphylaxis is frequently seen in patients with end-stage kidney disease on dialysis (calcific uremic arteriolopathy, CUA), there are reported cases of nonuremic calciphylaxis (NUC), which often remain undiagnosed. We conducted a retrospective chart review at our dermatological hospital and evaluated data concerning the epidemiology, comorbidities, medication, laboratory abnormalities, and therapeutic approaches of 60 patients diagnosed with calciphylaxis between 01/2012 and 12/2022. We identified 21 patients diagnosed with NUC and 39 with kidney disease. The predilection sites of skin lesions were the lower legs in 88% (n = 53), followed by the thigh and gluteal regions in 7% (n = 4). Significant differences were identified in comorbidities, such as atrial fibrillation (p < 0.001) and hyperparathyroidism (p < 0.01) accounting for CUA patients. Medication with vitamin K antagonists (p < 0.001), phosphate binders (p < 0.001), and loop diuretics (p < 0.01) was found to be associated with the onset of calciphylaxis. Hyperphosphatemia (p < 0.001), increased parathyroid hormone (p < 0.01) and triglyceride levels (p < 0.01), hypoalbuminemia (p < 0.01) and decreased hemoglobin values (p < 0.001) in the CUA cohort were significantly different from those in the NUC group. All patients with CUA received systemic medication. In contrast, only 38% (n = 8) of patients with NUC received systemic treatment. Striking discrepancies in the treatment of both cohorts were detected. In particular, NUC remains a disease pattern that is still poorly understood and differs from CUA in several important parameters.

Association of parathyroid hormone with risk of hypertension and type 2 diabetes: a dose-response meta-analysis

BackgroundDespite an increase in parathyroid hormone (PTH) has been reported to be associated with a higher risk of hypertension and type 2 diabetes (T2D), the comprehensive evaluation of the dose-response relationship between PTH and hypertension and T2D remains ambiguous. Therefore, a dose-response meta-analysis was performed to quantitatively investigate this association.MethodsPubMed, Web of Science, and Embase were systematically searched up to May 2023. Random-effect models were used to estimate the summary odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were used to model the dose-response association.ResultsTen articles (including 13 studies) were identified, with a total of 11,878 cases and 51,234 participants in the meta-analysis. Of these studies, eight (five cohort and three cross-sectional) studies investigated the association of PTH with hypertension; five (two cohort and three cross-sectional) studies assessed the association of PTH with T2D. The results showed a positive relationship between PTH and the risk of hypertension (OR,1.24, 95% CI: 1.16–1.33). We found a linear association between PTH and hypertension (Pnon−linearity= 0.222). In the dose-response analysis, the risk of hypertension increased 5% for every 10 pg/ml increase in PTH (OR,1.05, 95% CI: 1.02–1.08). The pooled OR of T2D risk for a 10 pg/ml increase in PTH was 1.00 (95% CI: 0.98–1.02).ConclusionsElevated PTH is associated with an increased risk of hypertension. However, the evidence of the association between PTH and T2D is limited, and more well-designed studies need to be explored.

Parathyroid carcinoma case-report in a patient with multinodular goiter and chronic kidney disease: difficulties in diagnosis and treatment (observation from practice)

We would like to present a clinical case of severe primary hyperparathyroidism due to a parathyroid carcinoma of atypical location in a patient with chronic kidney disease of complex etiology and multinodular goiter. Patient S., 59 years old, was followed-up for a long time in tertiary referral hospitals for “chronic tubulointerstitial nephritis with nephrosclerosis”, secondary hyperparathyroidism due to chronic kidney disease (CKD) G3–4, osteoporosis, and a multinodular euthyroid colloid goiter. In July 2021 she was referred to the Endocrinology Research Centre in order to clarify the diagnosis because of the persistence of an extremely high level of parathyroid hormone (PTH) despite cinacalcet treatment. During examination, primary hyperparathyroidism, a left parathyroid gland lesion, multinodular goiter with subclinical thyrotoxicosis, and vitamin D deficiency were diagnosed. After the removal of the left parathyroid gland lesion (histologically confirmed parathyroid carcinoma) and a left-sided hemithyroidectomy, hypocalcemia («hungry bone syndrome») developed, but the level of parathyroid hormone remained elevated. After 3–18 months after surgery, no data for relapse of primary hyperparathyroidism was obtained. The persistent moderate increase in PTH was regarded as secondary hyperparathyroidism in CKD and hypocalcemia. Complex therapy of osteoporosis with the antiresorptive drug denosumab, vitamin D and its active metabolite, calcium preparations, and parathyroidectomy led to a significant increase in bone mineral density (BMD) and no repeated fractures 18 months after surgery.Conclusion. In patients with pre-dialysis CKD and high PTH levels, it is necessary to make a differential diagnosis between primary (PHPT) and secondary hyperparathyroidism (SHPT). Severe manifestations of primary hyperparathyroidism can be suspicious for parathyroid carcinoma.

Beyond Bipolar Disease: Primary Hyperparathyroidism in a Bipolar Patient

Primary hyperparathyroidism consists of a dysregulated production of parathyroid hormone that results in abnormal calcium homeostasis. It is mostly detected in the asymptomatic phase; however, presentation may include a broad spectrum of clinical manifestations. We describe the case of a 67-year-old female patient with a previous history of bipolar disorder and several vascular risk factors who presented with generalized muscular weakness, anorexia and weight loss, polydipsia, nausea, constipation and mental confusion with behavioural change. Mental and behaviour changes were previously considered a cognitive deficit. Blood tests revealed severe acute renal injury, severe hypercalcemia and frankly increased parathyroid hormone. During hypercalcaemia study, cervical ultrasound identified a nodule compatible with parathyroid adenoma, coincident with hypercaptant focus on the sestamibi scintigraphy. Patient underwent treatment with zolendronic acid and posterior parathyroidectomy with gradual symptomatic and analytical improvement. The authors report this case recalling that psychiatric pathologies can delay the diagnosis of physical conditions.

Brown Tumor with Multiple Lesions as a Manifestation of Tertiary Hyperparathyroidism: A Case Report and Literature Review

Brown tumor is an uncommon focal lytic bone lesion, which is considered as an end-stage lesion of abnormal bone metabolism, caused by long-standing increased parathyroid hormone levels. It is a rare manifestation of hyperparathyroidism that is classified into three types, of which tertiary is the rarest. It can be found in any part of the skeleton, and in some cases, occurs in multiple bones and can be easily misdiagnosed as a metastatic tumor. Therefore, although uncommon, it should be generally considered as a differential diagnosis with bone malignancy lesions, and particularly in patients with renal failure on long-term hemodialysis. In the present case report, a young patient with end stage renal disease presented with tertiary hyperparathyroidism revealed by multiple brown tumors of the pelvis and mandible. We recall through this observation the importance of clinical context, the complementary roles that different imaging modalities can play in different settings, and the relevance of measuring serum calcium and parathyroid hormone before the diagnosis of osteolytic bone lesions.

Brown tumor due to primary hyperparathyroidism in a familial case: a case report

BackgroundPrimary hyperparathyroidism (PHPT) is an uncommon disorder characterised by hypercalcemia with an increased parathyroid hormone level. We reported a PHPT familial case with two subjects, a father and a daughter, and both of them had suffered from the brown tumor.Case presentationThe proband, a 43-year-old patient, developed parathyroid adenomas at the age of 15; a histologically confirmed right parathyroid adenoma was removed by parathyroidectomy; and after six months follow-up, the serum calcium level was normalised. At the age of thirty-three, a CT scan of his head and neck revealed a mass in the right maxilla, as well as PHPT (i.e., left inferior parathyroid adenoma). Then, he underwent a biopsy of an exophytic lesion in the right maxilla and was diagnosed by pathology as a brown tumor, with the serum calcium and PTH levels at 2.78 mmol/L and 221 pg/mL, respectively. Subsequently, the patient took a left inferior parathyroid microwave ablation with ultrasound guidance. After three months of follow-up, the serum calcium and PTH levels returned to normal, and the brown tumor was resolved. After three years, it mineralised as revealed in a CT scan. By the time he was 43 years old, during the 28-year follow-up period, the serum calcium and PTH levels were still within the normal range, and there was no discomfort reported. He has consistently taken calcium supplements throughout the 28 years. Since the initial diagnosis, his blood indicators of kidney function have been normal, and ultrasound showed renal calculus in the right kidney and a normal left kidney. The proband’s daughter, a 15-year-old girl, experienced left upper extremity pain for ten months. CT scan revealed a mass in the distal left radius, and a giant cell tumor was suspected. A surgical internal fixation was performed, and the pathology showed a brown tumor. Laboratory tests revealed a serum parathyroid hormone (PTH) level of 1554pg/mL, calcium level of 3.14 mmol/L, phosphorus level of 0.72 mmol/L, and alkaline phosphatase level of 1892 U/L. Given the osteitic changes and elevated levels of calcium and PTH, ultrasonography was performed, after which a mass was detected measuring 19 × 9 × 7 mm mixed with solid components and cystic fluid in the right thyroid gland. The results of 99mTc-MIBI scintigraphy confirmed the abnormal accumulation of 99mTc-MIBI in the right thyroid gland but not seen in the bilateral parathyroid glands. The patient underwent thyroidectomy, and the postoperative pathology report indicated an intra-thyroid ectopic parathyroid adenoma. The serum calcium and PTH levels became normal at 4 h after surgery. One to three months after operation, the serum calcium level was low, while the serum PTH level was high. Then, the patient was advised to take calcium supplements. Until the sixth month after the operation, the serum calcium level and serum PTH level returned to normal, and the bone pain was relieved. The patient’s blood tests for kidney function remained normal. There was no evidence of bilateral kidney disease (such as nephrolithiasis or nephrocalcinosis) detected by ultrasound scan. There were several similarities in the state of illness between these two subjects. Both the father and the daughter developed parathyroid adenomas at the age of 15, and there was no lesion in other endocrine glands. And genetic testing revealed mutations in the CDC73 genes in both father and daughter. On the other hand, there were also a few differences. The father’s first signs of brown tumor were in the right maxilla, while the daughter’s appeared in the distal left radius. The father presented pathological changes in the left and right parathyroid glands, whereas the daughter presented with an ectopic parathyroid adenoma in the right thyroid gland.ConclusionWe report a familial case in which father and daughter were diagnosed to have brown tumors due to parathyroid adenoma and ectopic parathyroid adenoma, and genetic testing revealed CDC73 gene mutations in both. Therefore, in the diagnostic and differential process of young patients having bone disease, clinicians should not only focus on the clinical manifestations of the skeleton, but also implement a comprehensive analysis of systemic symptoms, considering the possibility that the patient has familial PHPT.

Vitamin D Deficiency Increases Vulnerability to Canagliflozin-induced Adverse Effects on 1,25-Dihydroxyvitamin D and PTH.

Canagliflozin has been reported to increase the risk of bone fracture-possibly mediated by decreasing 1,25-dihydroxyvitamin D (1,25(OH)2D) and increasing parathyroid hormone (PTH). This work investigated whether baseline vitamin D (VitD) deficiency renders individuals vulnerable to this adverse effect and whether VitD3 supplementation is protective. This community-based, outpatient study had a paired design comparing individual participants before and after VitD3 supplementation. Eleven VitD-deficient (25-hydroxyvitamin D [25(OH)D] ≤ 20 ng/mL) individuals were recruited from the Amish population in Lancaster, Pennsylvania. Participants underwent 2 canagliflozin challenge protocols (300 mg daily for 5 days): the first before and the second after VitD3 supplementation. In the VitD3 supplementation protocol, participants received VitD3 supplementation (50 000 IU once or twice a week depending on body mass index for 4-6 weeks) to achieve 25(OH)D of 30 ng/mL or greater. Two coprimary end points were identified: effects of VitD3 supplementation on canagliflozin-induced changes in 1,25(OH)2D and PTH. Secondary end points included effects of VitD3 supplementation on baseline levels of VitD metabolites and PTH. VitD3 supplementation increased mean 25(OH)D from 16.5 ± 1.6 to 44.3 ± 5.5 ng/mL (P = .0006) and 24,25-dihydroxyvitamin D (24,25(OH)2D) from 1.0 ± 0.1 to 4.3 ± 0.6 ng/mL (P = .0002). Mean 1,25(OH)2D and PTH were unchanged. VitD3 supplementation decreased the magnitude of canagliflozin-induced changes in 1,25(OH)2D (from -31.3%±4.7% to -9.3%±8.3%; P = .04) and PTH (from +36.2%±6.2% to +9.7%±3.7%; P = .005). VitD deficiency rendered individuals more vulnerable to adverse effects of canagliflozin on biomarkers associated with bone health. VitD3 supplementation was protective against canagliflozin's short-term adverse effects on 1,25(OH)2D and PTH.

Clinical significance of adanced glycation end products and inflammation products in the development of vascular calcification and cardiovascular complications in chronic kidney disease

Background. Vascular calcification underlies cardiovascular complications, which remain the leading cause of high mortality in chronic kidney disease (CKD). Uremic toxins, including the advanced glycation end products, play a significant role in the formation of this process.The Aim of the study is to clarify the role of the advanced glycation end products (AGEs) and inflammationproducts in the processes of vascular calcification at different stages of CKD.Patients and Methods. 105 patients aged 18 to 66 years at different stages of CKD C1-C5D were examined, 75 of which were caused by diabetic nephropathy (DN), 30 by other nosological forms. Serum concentrations of AGEs, IL6, TNF-α, troponin I, parathyroid hormone (PTH) were determined by enzyme immunoassay (ELISA). To study the AGEs concentration, the serum was separated by centrifugation (in Eppendorf tubes). The samples were stored at – 70 °C. The left ventricular myocardial mass index (LVMI) was determined. Left ventricular hypertrophy (LVH) was diagnosed with LVH&gt;115 g/m2 for men and &gt;95 g/m2 for women. The peak systolic velocity of blood flow in the aortic arch (Vps) was studied by duplex scanning using the Doppler effect.Results. A significant increase in serum phosphorus concentration (p &lt; 0.05) and PTH (p&lt; 0.01) was revealed as the glomerular filtration rate decreased. An increase in the concentration of AGEs, IL6 and TNF-α was found at all stages of CKD, most pronounced at the later stages – C4-C5D ((p&lt; 0.01, p&lt; 0.05, p&lt;0.05, respectively). Pronounced changes in LVMI and Vps were associated with high levels of AGEs, IL6 and TNF-α. CONCLUSION. An increase in the level of glycation end products and inflammatory factors directly and reliably correlated with the severity of uremia and the severity of morphofunctional changes in the heart and aorta, which confirms their significant role in the development of cardiovascular complications in CKD. Keywords: advanced glycation end products, inflammation, vascular calcification, chronic kidney disease&gt;˂0.05, respectively). Pronounced changes in LVMI and Vps were associated with high levels of AGEs, IL6 and TNF-α.Conclusion. An increase in the level of glycation end products and inflammatory factors directly and reliably correlated with the severity of uremia and the severity of morphofunctional changes in the heart and aorta, which confirms their significant role in the development of cardiovascular complications in CKD.

Interactions of vitamin D with parathyroid glands; an updated mini-review

Vitamin D is essential for regulating calcium and phosphate metabolism, and its deficiency or excess can significantly affect parathyroid function. The deficiency or insufficiency of vitamin D can lead to increased parathyroid hormone (PTH) production, resulting in secondary hyperparathyroidism. Conversely, adequate vitamin D levels suppress PTH synthesis and maintain normal calcium levels. Dysregulation of this delicate balance can contribute to various disorders such as osteoporosis, renal stones, and skeletal abnormalities. Hence, understanding the complex interactions between vitamin D and the parathyroid glands is important for diagnosing and managing disorders such as primary and secondary hyperparathyroidism.

High sodium promotes the secretion and synthesis of PTH through PiT-1-IKKβ pathway in parathyroid gland in vitro.

Parathyroid hormone (PTH) is secreted by the parathyroid glands (PTGs) and is an important hormone regulating mineral metabolism. Previous studies reported that high sodium diet will cause the increase in serum PTH, but the specific mechanism is unknown. Consequently, the present study aims to investigate the effects and mechanisms of high sodium on PTH synthesis and secretion from PTGs. We developed a tissue culture model using normal rat PTGs, discovered that sodium elicited and promoted concentration-dependent and time-dependent PTH secretion. Changes in sodium-associated transporters from PTGs incubated with high sodium were thoroughly examined. Increased expression of sodium-phosphate cotransporter Slc20a1 (also known as PiT-1) was observed. Further tests revealed that PiT-1 activated the NF-κB signaling pathway, resulting in increased IKKβ phosphorylation, IKBα degradation, and increased p65 phosphorylation followed by nuclear entry, which led to increased PTH transcription. Meanwhile, IKKβ phosphorylated SNAP23, promoting exocytosis and eventually led to increased PTH secretion. In conclusion, our findings indicate that PiT-1 plays an important role in the increased secretion and synthesis of PTH directly induced by high sodium under physiological conditions, and may provide a potential therapeutic target for secondary hyperparathyroidism (SHPT).

The effect of calcium supplementation on calcium and bone metabolism during load carriage in women: protocol for a randomised controlled crossover trial

BackgroundMilitary field exercises are characterised by high volumes of exercise and prolonged periods of load carriage. Exercise can decrease circulating serum calcium and increase parathyroid hormone and bone resorption. These disturbances to calcium and bone metabolism can be attenuated with calcium supplementation immediately before exercise. This randomised crossover trial will investigate the effect of calcium supplementation on calcium and bone metabolism, and bone mineral balance, during load carriage exercise in women.MethodsThirty women (eumenorrheic or using the combined oral contraceptive pill, intrauterine system, or intrauterine device) will complete two experimental testing sessions either with, or without, a calcium supplement (1000 mg). Each experimental testing session will involve one 120 min session of load carriage exercise carrying 20 kg. Venous blood samples will be taken and analysed for biochemical markers of bone resorption and formation, calcium metabolism, and endocrine function. Urine will be collected pre- and post-load carriage to measure calcium isotopes for the calculation of bone calcium balance.DiscussionThe results from this study will help identify whether supplementing women with calcium during load carriage is protective of bone and calcium homeostasis.Trial registrationNCT04823156 (clinicaltrials.gov).

Big data-based parathyroid hormone (PTH) values emphasize need for age correction

PurposeWe aimed to study the relationship between aging and increased parathyroid hormone (PTH) values.MethodsWe performed a retrospective cross-sectional study with data from patients who underwent outpatient PTH measurements performed by a second-generation electrochemiluminescence immunoassay. We included patients over 18 years of age with simultaneous PTH, calcium, and creatinine measurements and 25-OHD measured within 30 days. Patients with glomerular filtration rate < 60 mL/min/1.73 m2, altered calcemia, 25-OHD level < 20 ng/mL, PTH values > 100 pg/mL or using lithium, furosemide or antiresorptive therapy were excluded. Statistical analyses were performed using the RefineR method.ResultsOur sample comprised 263,242 patients for the group with 25-OHD ≥ 20 ng/mL, that included 160,660 with 25-OHD ≥ 30 ng/mL. The difference in PTH values among age groups divided by decades was statistically significant (p < 0.0001), regardless of 25-OHD values, ≥ 20 or ≥ 30 ng/mL. In the group with 25-OHD ≥ 20 ng/mL and more than 60 years, the PTH values were 22.1–84.0 pg/mL, a different upper reference limit from the reference value recommended by the kit manufacturer.ConclusionWe observed a correlation between aging and PTH increase, when measured by a second-generation immunoassay, regardless of vitamin D levels, if greater than 20 ng/mL, in normocalcemic individuals without renal dysfunction.

2 Effects of extra-label bisphosphonate use on growth parameters and endocrine biomarkers of bone health in juvenile horses

Extra-label bisphosphonate use in juvenile horses is widespread despite limited scientific understanding of biological and welfare impacts on skeletally immature, exercising horses. The objective of this study was to determine the effects of bisphosphonate (clodronate disodium; CD) on endocrine regulation of bone growth, hypothesizing there would be no effect. To test this, 32 Quarter Horses were stratified by age (500 ± 13 d of age), BW (336 ± 26 kg), sex (n = 16 males, n = 16 females), and initial bone optical density by aluminum equivalence into 4 treatment groups for a 168-d trial. The experimental period was divided into 2 phases mimicking sales preparation (Phase I: d 0–83) and early performance training (Phase II: d 84–168). Horses were housed in individual stalls (3.6 m × 7.3 m) and fed diets formulated to meet nutrient requirements. Investigators were blinded, and all horses received iso-volumetric intramuscular injections of either 1.8 mg/kg BW CD (OSPHOS®) or saline (placebo) on d 0, 42, 84, and 126. Treatments consisted of control (CON; n = 8), single-dose CD (1X; n = 8; d 84), 2-dose CD (2X; n = 8; d 0, 84), and 4-dose CD groups (4X;n = 8; d 0, 42, 84, 126). Physical measurements including BW, wither height (WH), hip height (HH), body length (BL), and heart girth (HG) circumference were recorded every 42 d from d 0. Likewise, serum samples were collected every 42 d before treatment administration to quantify growth hormone (GH), calcitonin (CT), parathyroid hormone (PTH), and ionized calcium. Data were analyzed using PROC MIXED of SAS. All physical growth measurements increased over time (P ≤ 0.01) but were not affected by treatment (P ≥ 0.62). Similarly, there was no effect of treatment (P = 0.44) for GH, but concentrations tended to decrease over time as growth rate slowed (P = 0.09). A treatment ´ time interaction was observed for PTH (P = 0.05) where concentrations increased following 2 clodronate doses. Specifically, concentrations increased on d 84 in 4X and on d 126 in 2X following the second administration of clodronate while 1X and CON remained unchanged. There was no effect of treatment (P = 0.98), time (P = 0.33), nor treatment × time interaction (P = 0.61) for CT despite the increase in PTH. Ionized calcium concentrations decreased over time (P < 0.01) with no effect of treatment (P = 0.26) or treatment × time interaction (P = 0.32). These results suggest that while administration of bisphosphonate has no effect on growth morphometrics, its repetitive use alters PTH concentrations after 2 doses.

Changes in Bone Turnover Markers after Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy: a Systematic Review and Meta-Analysis.

This systematic review and meta-analysis was performed to compare the alterations in bone turnover markers between SG and RYGB. A literature search was conducted in PubMed, Medline, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases to find the studies. There was significant less increment in osteocalcin [WMD = - 5.98, 95% CI (- 9.30, - 2.47) P < 0.01] and parathyroid hormone (PTH) [WMD = - 9.59, 95% CI (- 15.02, - 4.16) P < 0.01] in the SG group compared to the RYGB group. No significant differences were seen in change of C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type I collagen (PINP), Ca, and 25(OH)-D between SG and RYGB groups. According to our meta-analysis, bone formation markers appear to have more increment following RYGB than SG. This observation is accompanied by a larger increase in PTH after RYGB patients compared to SG patients. PROSPERO: CRD42022308985.

Successful removal of a functional parathyroid adenoma using a radio‐guided parathyroidectomy technique with a hand‐held gamma detector and technetium Tc 99m sestamibi scintigraphy in a horse

SummaryThis clinical case report details the use of a radio‐guided parathyroidectomy technique using a hand‐held gamma detector and technetium Tc 99m sestamibi scintigraphy for detection and removal of a functional parathyroid adenoma in a horse. An 18‐year‐old Arabian gelding was diagnosed with primary hyperparathyroidism based on persistent hypercalcaemia and increased parathyroid hormone concentration. Single gland disease was suspected after technetium Tc 99m sestamibi scintigraphy showed focal increased radiopharmaceutical uptake (IRU) at the thoracic inlet. Ultrasonography failed to identify a discrete mass in the region of IRU. Surgical excision was recommended; however, due to unreliable preoperative localisation, a radio‐guided parathyroidectomy technique was elected. A radio‐guided parathyroidectomy technique was performed under general anaesthesia using a hand‐held gamma detector and technetium Tc 99m sestamibi scintigraphy to identify the parathyroid adenoma, which was subsequently excised. The horse recovered from the procedure without complication. Successful removal of the parathyroid adenoma was confirmed based on histopathological and serum bioch findings. Following the procedure, the horse showed no evidence of hyperparathyroidism and returned to light pleasure riding. Three years postoperatively, the gelding died of unrelated natural causes; a post‐mortem examination was not performed. This radio‐guided parathyroidectomy technique was effective in facilitating the removal of a parathyroid adenoma in this gelding and might be useful in other equids that have primary hyperparathyroidism IRU on technetium Tc 99m sestamibi scintigraphy, particularly if a discrete mass cannot be identified ultrasonographically.

Kidney Failure Alters Parathyroid Pin1 Phosphorylation and Parathyroid Hormone mRNA-Binding Proteins, Leading to Secondary Hyperparathyroidism.

Secondary hyperparathyroidism (SHP) is a common complication of CKD that increases morbidity and mortality. In experimental SHP, increased parathyroid hormone (PTH) expression is due to enhanced PTH mRNA stability, mediated by changes in its interaction with stabilizing AUF1 and destabilizing KSRP. The isomerase Pin1 leads to KSRP dephosphorylation, but in SHP parathyroid Pin1 activity is decreased and hence phosphorylated KSRP fails to bind PTH mRNA, resulting in high PTH mRNA stability and levels. The up- and downstream mechanisms by which CKD stimulates the parathyroid glands remain elusive. Adenine-rich high-phosphate diets induced CKD in rats and mice. Parathyroid organ cultures and transfected cells were incubated with Pin1 inhibitors for their effect on PTH expression. Mass spectrometry was performed on both parathyroid and PTH mRNA pulled-down proteins. CKD led to changes in rat parathyroid proteome and phosphoproteome profiles, including KSRP phosphorylation at Pin1 target sites. Furthermore, both acute and chronic kidney failure led to parathyroid-specific Pin1 Ser16 and Ser71 phosphorylation, which disrupts Pin1 activity. Pharmacologic Pin1 inhibition, which mimics the decreased Pin1 activity in SHP, increased PTH expression ex vivo in parathyroid glands in culture and in transfected cells through the PTH mRNA-protein interaction element and KSRP phosphorylation. Kidney failure leads to loss of parathyroid Pin1 activity by inducing Pin1 phosphorylation. This predisposes parathyroids to increase PTH production through impaired PTH mRNA decay that is dependent on KSRP phosphorylation at Pin1-target motifs. Pin1 and KSRP phosphorylation and the Pin1-KSRP-PTH mRNA axis thus drive SHP.

Factors in the occurrence and restoration of hypoparathyroidism after total thyroidectomy for thyroid cancer patients with intraoperative parathyroid autotransplantation.

IntroductionPostoperative hypoparathyroidism (POH) is the most common and important complication for thyroid cancer patients who undergo total thyroidectomy. Intraoperative parathyroid autotransplantation has been demonstrated to be essential in maintaining functional parathyroid tissue, and it has clinical significance in identifying essential factors of serum parathyroid hormone (PTH) levels for patients with parathyroid autotransplantation. This retrospective cohort study aimed to comprehensively investigate influential factors in the occurrence and restoration of POH for patients who underwent total thyroidectomy with intraoperative parathyroid autotransplantation (TTIPA).MethodThis study was conducted in a tertiary referral hospital, with a total of 525 patients who underwent TTIPA. The postoperative serum PTH levels were collected after six months, and demographic characteristics, clinical features and associated operative information were analyzed.ResultsA total of 66.48% (349/525) of patients who underwent TTIPA were diagnosed with POH. Multivariate logistic regression indicated that Hashimoto’s thyroiditis (OR=1.93, 95% CI: 1.09-3.42), P=0.024), the number of transplanted parathyroid glands (OR=2.70, 95% CI: 1.91-3.83, P<0.001) and postoperative blood glucose levels (OR=1.36, 95% CI: 1.06-1.74, P=0.016) were risk factors for POH, and endoscopic surgery (OR=0.39, 95% CI: 0.22-0.68, P=0.001) was a protective factor for POH. Multivariate Cox regression indicated that PTG autotransplantation patients with same-side central lymph node dissection (CLND) (HR=0.50; 95% CI: 0.34-0.73, P<0.001) demonstrated a longer time for increases PTH, and female patients (HR=1.35, 95% CI: 1.00-1.81, P=0.047) were more prone to PTH increases. Additionally, PTG autotransplantation with same-side CLND (HR=0.56, 95% CI: 0.38-0.82, P=0.003) patients had a longer time to PTH restoration, and patients with endoscopic surgery (HR=1.54, 95% CI: 1.04-2.28, P=0.029) were more likely to recover within six months.ConclusionHigh postoperative fasting blood glucose levels, a large number of transplanted PTGs, open surgery and Hashimoto’s thyroiditis are risk factors for postoperative POH in TTIPA patients. Elevated PTH levels occur earlier in female patients and patients without CLND on the transplant side. PTH returns to normal earlier in patients without CLND and endoscopic surgery on the transplant side.

PARATHYROID ADENOMA: A RARE TUMOUR CASE REPORT

Parathyroid adenoma is a rare tumour and are generally small size (&lt; 2 cm) and &lt;1gm weight. Giant adenomas are infrequent, are mostly elucidated as &gt; 3.5 gm weight, along with few reports weights up to 110 gm. Parathyroid adenoma are usually found with primary hyperparathyroidism syndrome which is common, seen as third most common endocrine disorder. In this study a case of 52-year-old lady was refereed with complain of neck swelling, lethargy and generalized drowsiness. The results obtained from laboratory revealed increased serum calcium and increased parathyroid hormone. There is no significant history of renal stone, renal dysfunction or any family history of endocrinal tumours. Ultrasonography revealed a composite nodule with cystic and solid elements. Focused surgical neck exploration was performed with removal of 4 gm adenoma . Microscopic examination showed, encapsulated lesion formed of chief cells of parathyroid organized within network of capillaries. The most exact mechanism for localizing a Parathyroid Adenoma is altogether MIBI scan along with neck ultrasonography. Surgical excision with monitoring of parathyroid hormone screening during operation is the recommended conductance. Need for the intraoperative Parathyroid hormone monitoring is debatable in Parathyroid adenoma due to accuracy of preoperative imaging.