Search

Primary hyperparathyroidism is a common endocrine disorder. It is characterised by elevated parathyroid hormone (PTH) level causing hypercalcemia. 90-95% of cases have a spontaneous cause, with the remaining 5-10% having a genetic basis. On routine examination, a 47-year-old patient was found to have hypercalcemia, vitamin D deficiency, normal PTH levels and no hypercalciuria. Despite vitamin supplementation, calcemia remained unchanged. Single photon emission computed tomography (SPECT) examination detected possible adenomas in the lower parathyroids regions, and ultrasound revealed an adenoma of the lower left parathyroid gland and hypertrophy of the lower right parathyroid gland. The atypical clinical presentation - young age, inadequate normal PTH levels and the location of the lesions within the two parathyroid glands suggested genetic testing, which confirmed the presence of a genetic mutation - the GCM2 variant. Treatment included exploration of the parathyroid area using fluorescence. Both lower parathyroid glands were dissected. PTH monitoring showed a decrease in baseline levels of more than 50% after surgery. One month after surgery, PTH and calcium levels remained normal. Primary hyperparathyroidism is usually asymptomatic, detected when laboratory tests are performed for another cause. Symptoms include nephrolithiasis, bone and joint pain, osteoporosis, arrhythmias and fatigue. The typical patient has high PTH levels and hypercalcemia, but not every case will be schematic. High serum calcium levels do not always result in increased PTH levels and an in-depth diagnosis is required. The GCM2 mutation, detected in the patient presented here, may occur in familial isolated hyperparathyroidism. Correct diagnosis and treatment is crucial not only for the patient, as it significantly improves their quality of life, but also for their family members, who may also have a genetic mutation and be unaware of the disorder developing in their body. [ABSTRACT FROM AUTHOR]

We describe a case of severe symptomatic tumoral calcinosis in a young man with end stage kidney disease secondary to antineutrophil cytoplasmic antibodies‐associated vasculitis with longstanding hyperphosphatemia and secondary hyperparathyroidism while on several years of peritoneal dialysis. The use of intravenous sodium thiosulfate, optimization of clearance with five times weekly hemodialysis, and intradialytic nutrition were used to treat his inoperable tumoral calcinosis. Over 3 months, he had a remarkable reduction in the size of his calcified masses and associated improvement in pain. He subsequently received a living donor kidney transplant. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions 4D‐CT has garnered attention as complementary imaging for patients with primary hyperparathyroidism (pHPT). Herein we evaluated a diagnostic strategy using [18F]Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT), followed by 4D‐CT integrated into PET/4D‐CT after negative/inconclusive PET/CT results in a single‐center retrospective cohort of 166 pHPT patients who underwent parathyroidectomy after [18F]Fluorocholine PET/4D‐CT.PET/CT and 4D‐CT images were interpreted by three nuclear medicine physicians and one expert radiologist. Pathological findings were documented, and concordance rates were assessed. PET/CT results were categorized as positive/negative, with positive cases rated on a 3‐level certitude scale: low, moderate, high. Inconclusive cases included low/moderate positivity. The added value of PET/4D‐CT was assessed for negative/inconclusive cases through joint reading.PET/CT lesion‐based analysis showed almost perfect interobserver concordance (Cohen's kappa >.8). Across the cohort, PET/CT had a sensitivity of 83%, specificity of 97%, PPV of 90% and NPV of 94%. For 4D‐CT, these values were sensitivity: 53%, specificity: 84%, PPV: 56% and NPV: 82%. PET/CT was significantly more accurate than 4D‐CT. Among 44 patients with negative/inconclusive results, PET/CT had sensitivity: 60%, specificity: 91%, PPV: 71% and NPV: 86%. In the same patients, sensitivity and specificity of the sequential diagnostic algorithm increased to 80% and 97%, showing significantly better global accuracy (92% vs. 83%) than standard PET/CT.We support a personalized imaging algorithm for pHPT, placing [18F]Fluorocholine PET/CT at the forefront, followed by 4D‐CT integrated into PET/4D‐CT in the same imaging session for negative/inconclusive results. When PET/CT results are clearly positive, the additional sensitivity benefit of 4D‐CT is minimal. [ABSTRACT FROM AUTHOR]

Hypercalcemia can result from either hyperparathyroidism or non-parathyroid conditions. When hypercalcemia is accompanied by undetectable parathyroid hormone (PTH) levels, hyperparathyroidism is rarely considered the diagnosis. Herein, we report the case of a 65-year-old Caucasian woman referred to our hospital for further evaluation of hypercalcemia. Her symptoms included fatigue and brain fog, with undetectable PTH levels. A comprehensive workup, including a series of laboratory and imaging tests, excluded common non-parathyroid causes such as malignancy and familial hypocalciuric hypercalcemia. Ultrasound identified a likely enlarged parathyroid gland, which was further confirmed by a sestamibi scan. After 2 weeks of cinacalcet treatment, the patient's calcium levels decreased, indicating the parathyroid gland as the likely source of hypercalcemia. Parathyroidectomy was subsequently performed, revealing a 1927 mg adenoma. Postoperatively, the patient's calcium levels normalized, PTH levels became detectable within the normal range, and her symptoms resolved, with a marked improvement in energy. This case demonstrates that primary hyperparathyroidism can present with hypercalcemia and undetectable PTH. A genetic mutation in the PTH gene within the adenoma may explain the undetectable PTH levels preoperatively. Plain Language Summary: This case report discusses a 65-year-old woman who was found to have high calcium levels in her blood, a condition known as hypercalcemia. Typically, hypercalcemia can result from either a condition where the parathyroid glands produce too much parathyroid hormone (PTH) or from other non-parathyroid-related issues like cancer. However, when hypercalcemia occurs with undetectable levels of PTH, it is unusual for hyperparathyroidism to be the cause. In this patient's case, she experienced symptoms like fatigue and brain fog, but her initial tests showed undetectable PTH levels. Further tests ruled out other common causes of high calcium, such as cancer or a genetic condition called familial hypocalciuric hypercalcemia. An ultrasound and a special scan called a sestamibi scan revealed an enlarged parathyroid gland, suggesting the presence of a parathyroid adenoma, a non-cancerous tumor. To confirm this, the doctors gave the patient a medication called cinacalcet, which is known to lower calcium levels if the parathyroid glands are involved. After two weeks of treatment, her calcium levels dropped, indicating that the parathyroid gland was indeed the source of the problem. The patient underwent surgery to remove the adenoma, which weighed nearly two grams. Following the surgery, her calcium levels returned to normal, and her PTH levels became detectable again within the normal range. Her symptoms, including fatigue, improved significantly, and she reported feeling more energetic. This case is unusual because it demonstrates that primary hyperparathyroidism can still be the cause of hypercalcemia even when PTH levels are initially undetectable. The doctors suspect that a genetic mutation in the adenoma might explain why PTH levels were undetectable before surgery. This case emphasizes the importance of thorough clinical evaluation, even when initial test results are not typical. [ABSTRACT FROM AUTHOR]

Background and hypothesis: Parathyroid carcinoma (PTTC) is a rare malignant endocrine tumor seen in up to 1–2% of all cases of primary hyperparathyroidism. However, incidence of parathyroid carcinoma in renal hyperparathyroidism is a rare phenomenon. We aimed to evaluate the outcomes of PTTC in renal hyperparathyroidism published in the literature. Methods: Cohort review of parathyroid cancer cases reported in Medline (via PubMed), COCHRANE and EMBASE between the period 1985 – 2023 in patients with renal hyperparathyroidism. Results: A total of 48 patients (20 M: 28F), with a mean age of 49.8 (± 11.7 SD: range 20–75) years. Dialysis vintage was for a period of 8.9 (± 7.2; range 6 months to 40 years). The mean preoperative values were as follows: serum corrected calcium—2.87 IQR 2.56–3.01), PTH – 221.8 (IQR 86.6 -257.2 pmol/L) and serum phosphate – 2.07 (IQR 1.72–2.28) mmol/L. Preoperative imaging was in the form of ultrasound of the neck in 21 of 48 (44%), MIBI scan in 27/48 (56%), contrast enhanced computerized tomography in 14/48 (29%) and MRI neck in 1/48 (2%). The mean size of the cancer was 2.7 (± 1.35) cm and weight of the gland ranged between 0.9 to 4.98 g. 18/48 (37%) patients underwent a total parathyroidectomy and 30/48 (63%) had subtotal parathyroidectomy. En bloc excision of the tumour along with the thyroid along and central compartment lymph nodes was only performed in 12/48 (25%), of whom 9 (19%) had it performed at index surgery, whereas in the rest was done for persistent or recurrent disease. After a mean follow up of 34 months, 14 (29%) had local recurrence, 1 (2%) had distant metastasis to the skeletal system, and 12 (25%) to the lungs. Cohort mortality was 6 (13%) due to refractory hypercalcemia. Conclusions: Parathyroid carcinoma in renal hyperparathyroidism is rare but when encountered, en bloc excision with parathyroidectomy provides the best chance of cure. Recurrences can be difficult to treat but may be needed to treat intractable hypercalcaemia. [ABSTRACT FROM AUTHOR]

Purpose: We conducted a cost-effectiveness analysis in which we compared a preoperative [18F]Fluorocholine PET/CT-based one-stop-shop imaging strategy with current best practice in which [18F]Fluorocholine PET/CT is only recommended after negative or inconclusive [99mTc]Tc-methoxy isobutyl isonitrile SPECT/CT for patients suffering from primary hyperparathyroidism. We investigated whether the one-stop-shop strategy performs as well as current best practice but at lower costs. Methods: We developed a cohort-level state transition model to evaluate both imaging strategies respecting an intraoperative parathyroid hormone monitored treatment setting as well as a traditional treatment setting. The model reflects patients' hospital journeys after biochemically diagnosed primary hyperparathyroidism. A cycle length of twelve months and a lifetime horizon were used. We conducted probabilistic analyses simulating 50,000 cohorts to assess joint parameter uncertainty. The incremental net monetary benefit and cost for each quality-adjusted life year were estimated. Furthermore, threshold analyses regarding the tariff of [18F]Fluorocholine PET/CT and the sensitivity of [99mTc]Tc-methoxy isobutyl isonitrile SPECT/CT were performed. Results: The simulated long-term health effects and costs were similar for both imaging strategies. Accordingly, there was no incremental net monetary benefit and the one-stop-shop strategy did not result in lower costs. These results applied to both treatment settings. The threshold analysis indicated that a tariff of €885 for [18F]Fluorocholine PET/CT was required to be cost-effective compared to current best practice. Conclusion: Both preoperative imaging strategies can be used interchangeably. Daily clinical practice grounds such as available local resources and patient preferences should inform policy-making on whether a hospital should implement the one-stop-shop imaging strategy. [ABSTRACT FROM AUTHOR]

A recent article in the European Journal of Nuclear Medicine & Molecular Imaging discusses the use of [18F]Fluorocholine PET/CT as a first-line imaging method for localizing parathyroid adenomas in primary hyperparathyroidism. The article emphasizes the importance of considering multiple domains, including technical capacity, diagnostic performance, clinical impact, influence on patient outcome, and cost-effectiveness, when evaluating diagnostic tests. The authors present the results of a cost-effectiveness analysis comparing a one-stop-shop imaging strategy with current standard imaging methods and conclude that first-line [18F]Fluorocholine PET/CT can be cost-effective in Europe and should be integrated into routine clinical practice. The findings suggest that [99mTc]Tc-MIBI scan may become obsolete in primary hyperparathyroidism if [18F]Fluorocholine PET/CT is available. [Extracted from the article]

Objectives: We aimed to review and summarise the existing human literature on the association between lithium and hyperparathyroidism. Methods: A systematic literature search was carried out according to PRISMA guidelines (last search 27 February 2024), using MEDLINE, Web of Science, Embase and the Cochrane Library. A meta-analysis was performed to determine the prevalence of lithium-associated hypercalcemia (LAHca) in lithium-treated patients. Results: The pooled prevalence of LAHca based on total calcium and ionised calcium was comparable, at 3.17% and 4.23%, respectively. Calcium, and PTH if the patient is hypercalcaemic, is insufficiently measured in lithium-treated patients in clinical practice. Lithium use is associated with higher calcium and PTH levels, as well as a higher incidence of hyperparathyroidism. There is a high prevalence of multiglandular disease in lithium-associated hyperparathyroidism (LAH), with a pooled prevalence of 51.28%. Parathyroid surgery and cinacalcet are effective treatments for LAH. Regarding lithium discontinuation, there is anecdotal but conflicting evidence suggesting that it can result in the resolution of LAH in selected cases. Conclusions: Lithium treatment increases the risk of hyperparathyroidism, a treatable complication with a pooled prevalence of around 4%, compared to 0.5% in the healthy population. [ABSTRACT FROM AUTHOR]

Objective: Active vitamin D analogs and calcimimetic agents are primary drugs for patients with secondary hyperparathyroidism. Due to the different pharmacological mechanisms, they have different effects on the level of parathyroid hormone, serum calcium, phosphorus, and bone turnover biomarkers. This study aimed to evaluate the active vitamin D analogs and calcimimetic agents in hemodialysis patients with secondary hyperparathyroidism. Methods: We included randomized clinical trials of hemodialysis patients with secondary hyperparathyroidism, comparing active vitamin D analogs to calcimimetic agents or placebo/control. The primary outcome was the change of PTH level from baseline to end-up. The secondary outcome was the change in serum calcium, phosphorus, calcium-phosphorus product, and bone turnover biomarkers. A network meta-analysis method was applied to complete this study. The forest plots reflected statistical differences in the outcomes between active vitamin D analogs and calcimimetic agents. The SUCRA result presented the ranking of impact on the outcomes. Results: Twenty-one randomized clinical trials with 4653 patients were included in this network meta-analysis. Global and splitting-node inconsistencies provided no evidence of inconsistency in this study. There was no statistical difference between two active vitamin D analogs and three calcimimetic agents in the PTH, and phosphorus levels changed. Considering serum calcium level, compared with placebo, calcitriol (9.73, 3.09 to 16.38) and paricalcitol (9.74, 3.87 to 15.60) increase serum calcium. However, cinacalcet (− 1.94, − 3.72 to − 0.15) and etelcalcetide (− 7.80, − 11.80 to − 3.80) reduced the serum calcium, even a joint use of cinacalcet with active vitamin D analogs (− 5.83, − 9.73 to − 1.93). Three calcimimetic agents decreased calcium levels much more than calcitriol and paricalcitol. The same type of drugs was not distinct, with each one affecting the change in calcium level. Cinacalcet reduced calcium-phosphorus product much more than paricalcitol (− 3.66, − 6.72 to − 0.60). Evocalcet decreased calcium-phosphorus product more than cinacalcet (− 5.64, − 8.91 to − 2.37), calcitriol (− 9.36, − 14.81 to − 3.92), and paricalcitol (− 9.30, − 13.78 to − 4.82). Compared with paricalcitol, cinacalcet significantly increases the level of ALP (24.50, 23.05 to 25.95) and bALP (0.67, 0.03 to 1.31). The incidence of gastrointestinal disorders in cinacacet (29.35, 1.71 to 504.98) and etelcalcetide (20.92, 1.20 to 365.68) was notably higher than in paricalcitol. Etelcalcetide (0.71, 0.53 to 0.96) and evocalcet (0.46, 0.33 to 0.64) presented a lower rate of gastrointestinal disorders than cinacalcet. Cinacalcet ranked first in adverse gastrointestinal, nervous, and respiratory reactions. Conclusion: The same kinds of agents perform similar efficacy on the level of PTH, serum calcium, phosphorus, and calcium-phosphorus product. Paricalcitol did not lead to more hypercalcemia than calcitriol. The calcium decrease induced by cinacalcet was not settled even by associating it with active vitamin D analogs. Cinacalcet and evocalcet were superior to calcitriol and paricacitol in reducing calcium-phosphorus product. Calcimimetics induced more gastrointestinal disorders than active vitamin D analogs, especially cinacalcet. [ABSTRACT FROM AUTHOR]

Background: In patients with X-linked hypophosphatemia (XLH), conventional therapy with oral phosphate salts and active vitamin D has been associated with nephrocalcinosis. However, the nature of the relationships among XLH, its treatment, nephrocalcinosis, and kidney function remain poorly understood. Methods: Renal ultrasounds were performed and glomerular filtration rates were estimated (eGFR) at baseline in burosumab-naïve patients with XLH who participated in burosumab clinical trials (NCT02181764, NCT02526160, NCT02537431, NCT02163577, NCT02750618, NCT02915705) or enrolled in the XLH Disease Monitoring Program (XLH-DMP; NCT03651505). In this cross-sectional analysis, patient, disease, and treatment characteristics were described among patients with and without nephrocalcinosis. Results: The analysis included 196 children (mean [SD] age 7.6 [4.0] yr) and 318 adults (40.3 [13.1] yr). Mean (SD) height z-score was −1.9 (1.2) for children and −2.3 (1.7) for adults. Nearly all children (97%) and adults (94%) had previously received conventional therapy. Nephrocalcinosis was detected in 22% of children and 38% of adults. In children, reduced eGFR <90 mL/min/1.73 m2 was more prevalent in those with nephrocalcinosis (25%) than in those without (11%), a finding that was not observed in adults. Children with nephrocalcinosis had lower mean values of TmP/GFR (p<.05), serum 1,25(OH)2D (p<.05), and eGFR (p<.001) and higher mean serum calcium concentrations (p<.05) than did those without nephrocalcinosis. Adults with nephrocalcinosis had lower mean serum phosphorus (p<.01) and 1,25(OH)2D (p<.05) concentrations than those without. Exploratory logistic regression analyses revealed no significant associations between the presence of nephrocalcinosis and other described patient or disease characteristics. Conclusions: Nephrocalcinosis was observed in nearly one-quarter of children and more than one-third of adults with XLH. Further study is needed to better understand the predictors and long-term consequences of nephrocalcinosis, with surveillance for nephrocalcinosis remaining important in the management of XLH. Lay Summary: Conventionally, patients with X-linked hypophosphatemia (XLH) were treated with phosphate and vitamin D taken by mouth. However, this therapy might lead to a buildup of calcium in the kidney, called nephrocalcinosis. Here, we tried to better understand how XLH, conventional therapy, nephrocalcinosis, and kidney function are related. Nephrocalcinosis was detected with kidney ultrasounds. Kidney function, called the estimated glomerular filtration rate (eGFR), was determined using blood levels of creatinine. Patients had been part of burosumab clinical trials or part of the XLH Disease Monitoring Program. Data were collected from patients before they received burosumab. The study included 196 children and 318 adults. Almost all children and adults had received conventional therapy. 22% of children and 38% of adults had nephrocalcinosis. Some lab values were different among patients with vs without nephrocalcinosis. Children with nephrocalcinosis had significantly greater loss of phosphate by the kidneys, lower blood levels of the active form of vitamin D (1,25(OH)2D), lower eGFR, and higher blood levels of calcium than those without nephrocalcinosis. Adults with nephrocalcinosis had significantly lower blood levels of phosphorus and 1,25(OH)2D concentrations than those without. It remains important to monitor patients with XLH for nephrocalcinosis. Further study is needed to better understand nephrocalcinosis. [ABSTRACT FROM AUTHOR]

Context Primary hyperparathyroidism (PHPT) is commonly diagnosed in the setting of hypercalcemia, whereas normocalcemic primary hyperparathyroidism (NHPT) may be misdiagnosed. Objective Our objective was to compare patients with hypercalcemic hyperparathyroidism (HPHPT) vs patients with NHPT hypercalciuric renal stones. Methods We took advantage of a routine calcium load test performed in patients with hypercalciuric renal stones to assess retrospectively among patients with PHPT the prevalence and characteristics of NHPT and HPHPT under a calcium-restricted diet Results Among 1671 patients with hypercalciuria, 91 patients had a final diagnosis of PHPT (postload ionized calcium [iCa] > 1.31 mmol/L and parathyroid hormone [PTH] > 30 pg/mL). Prevalence of NHPT is 40% of all PHPT; however, according to total serum calcium, 4/35 NHPT and 7/56 HPHPT cases would have been misclassified in the other group. Eighteen of 35 NHPT and 40/56 HPHPT cases underwent parathyroidectomy. No significant characteristics relating to parathyroid weight, stone composition, or bone remodeling biomarkers were detected between groups. Although iCa is higher in HPHPT in the fasting state and after calcium load, we found no difference for calcium diet, 24-hour calciuria, or calcitriol. Renal calcium excretion postload increased by 303% in NHPT but only 176% in HPHPT (P =.01) likely explained by a lesser PTH decrease (P =.02). However, a strong negative association (P <.0001) detected between pooled preload and postload iCa and PTH only in the NHPT group suggests a persistent efficient PTH-CaSR control within the parathyroid glands in this group. Conclusion Our data show the relevance of dynamic tests to unmask NHPT in patients with hypercalciuric renal stones. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we analyse the possibility to omit pre-incision PTH measurement since we routinely measure it at the time of pre-surgery ambulatory admission. Methods: A total of 435 patients were enrolled. All patients with pHPT included underwent pre-surgical PTH level assessment as part of the pre-admission preparation to surgery. Intraoperative PTH was routinely assessed after induction of the anaesthesia (pre-incision PTH) and 15 min after resection of the enlarged gland(s) (post-excision PTH). Moreover, calcium and PTH levels were routinely assessed on the first postoperative day. Cure was defined as an intraoperative drop of > 50% or into normal range on first post-operative day. Results: The median value of the preoperative and pre-incision PTH were both 127 pg/ml (p = ns). Thirty-two patients (7.3%) exhibited a not appropriate drop of post-excision PTH level. Nevertheless, nineteen of them (59.3%) showed a satisfying PTH drop on 1st POD. Ten patients (2.3%) experienced a persistent disease with six achieving cure through reoperation. Additionally, three patients (0.6%) showed normalization of calcium and PTH values during the follow-up. Three patients, apparently deemed cured after an adequate PTH-drop on the day of surgery, showed persistence. Cure rate at primary surgery was 98.4%. Accuracy of our simplified protocol is 99.3%. Conclusion: Pre-incision PTH is not superior to preoperative PTH blood test and can be omitted without compromising the sensitivity of cure prediction. One blood sample 15 min after resection, along with the postoperative PTH value on the day after surgery, is sufficient to predict the surgical outcome bearing the cost of a very low reoperation rate. [ABSTRACT FROM AUTHOR]

Background: Although the skeleton remains a common target of primary hyperparathyroidism, the classic bone disease "osteitis fibrosa cystica" is currently rare due to early diagnosis. This case represents severe classic bone manifestations of primary hyperparathyroidism due to delayed diagnosis and delayed medical attention. Case presentation: A 19-year-old young female was symptomatically managed for chronic back pain and nonspecific bone pain in the small joints of both hands over 2 months by a general practitioner. The patient had delayed seeking for treatment for 3 months. Later, she was evaluated for tuberculosis, hematological malignancies and rheumatic disorders following a fractured T12 vertebra and underwent pedicle screw fixation. However, clinical examination and investigations, including biochemistry, imaging and histology, ruled out the above conditions. Unfortunately, serum calcium level was not performed at the initial presentation. Later, primary hyperparathyroidism was diagnosed on the basis of moderate hypercalcaemia and elevated intact PTH levels (2064 pg/ml). She had sufficient vitamin D levels and normal kidney function. Her DXA scan revealed severe secondary osteoporosis with the lowest Z score of -8 at the total lumbar spine. Ultrasonography of the thyroid revealed a hypo echoic mass in the left lower neck, and localization studies with technetium-99 m sestamibi and 4D-CT revealed a left inferior parathyroid adenoma (1.6 × 1.5 × 1.6 cm). CT scan also revealed brown tumors in the mandible and vertebrae and diffuse bony changes in the skull, sternum, humerus and vertebrae. Her radiographs revealed subperiosteal bone resorption on the radial aspects of the middle and distal phalanges and brown tumors in both the ulna and fibula. We excluded MEN and other hereditary syndromes in our patient with a personal and family history and with a normal pituitary hormone profile because of poor resources for genetic testing. She underwent parathyroid adenoma excision, and the postoperative period was complicated with hungry bone syndrome, requiring high doses of calcium and active vitamin D supplements. These supplements were gradually weaned off over 6 months, and she recovered with normal biochemical investigations. Histology revealed parathyroid adenoma without malignant features. Conclusion: In developing countries where routine calcium screening is not available, clinicians should be aware of various manifestations of primary hyperparathyroidism to allow diagnosis as soon as possible without delay to prevent further progression, as it is a treatable condition. [ABSTRACT FROM AUTHOR]