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Health and Quality of Life Outcomes Apr 2024The quality of patient-reported outcome measures (PROMs) used to assess the outcomes of primary hyperparathyroidism (PHPT), a common endocrine disorder that can... (Review)
Review
BACKGROUND
The quality of patient-reported outcome measures (PROMs) used to assess the outcomes of primary hyperparathyroidism (PHPT), a common endocrine disorder that can negatively affect patients' health-related quality of life due to chronic symptoms, has not been rigorously examined. This systematic review aimed to summarize and evaluate evidence on the measurement properties of PROMs used in adult patients with PHPT, and to provide recommendations for appropriate measure selection.
METHODS
After PROSPERO registration (CRD42023438287), Medline, EMBASE, CINAHL Complete, Web of Science, PsycINFO, and Cochrane Trials were searched for full-text articles in English investigating PROM development, pilot studies, or evaluation of at least one PROM measurement property in adult patients with any clinical form of PHPT. Two reviewers independently identified studies for inclusion and conducted the review following the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) Methodology to assess risk of bias, evaluate the quality of measurement properties, and grade the certainty of evidence.
RESULTS
From 4989 records, nine PROM development or validation studies were identified for three PROMs: the SF-36, PAS, and PHPQoL. Though the PAS demonstrated sufficient test-retest reliability and convergent validity, and the PHPQoL sufficient test-retest reliability, convergent validity, and responsiveness, the certainty of evidence was low-to-very low due to risk of bias. All three PROMs lacked sufficient evidence for content validity in patients with PHPT.
CONCLUSIONS
Based upon the available evidence, the SF-36, PAS, and PHPQoL cannot currently be recommended for use in research or clinical care, raising important questions about the conclusions of studies using these PROMs. Further validation studies or the development of more relevant PROMs with strong measurement properties for this patient population are needed.
Topics: Adult; Humans; Quality of Life; Reproducibility of Results; Hyperparathyroidism, Primary; Patient Reported Outcome Measures; Consensus
PubMed: 38566079
DOI: 10.1186/s12955-024-02248-9 -
Cureus Sep 2023Hypercalcemia is a common biochemical abnormality caused by various etiologies, with primary hyperparathyroidism (PHPT) and malignancies being the most common culprits....
Hypercalcemia is a common biochemical abnormality caused by various etiologies, with primary hyperparathyroidism (PHPT) and malignancies being the most common culprits. Differentiating between PTH-dependent and PTH-independent hypercalcemia is crucial in clinical practice. However, in certain clinical contexts, it is important to consider the rare occurrence of two separate conditions causing hypercalcemia simultaneously. Herein, we have described the case of a patient who presented with high serum calcium, a normal PTH level, and histopathological evidence of active granulomatous disease, indicating the presence of both PHPT and sarcoidosis. The coexistence of these conditions poses diagnostic challenges due to their biochemical and clinical similarities. This case highlights the importance of individualized management for patients with concurrent conditions contributing to hypercalcemia. It also emphasizes the need for further research to unravel the underlying interactions between PHPT and sarcoidosis in the context of calcium metabolism. A better understanding of these interactions can guide optimal diagnostic and therapeutic strategies for patients with complex presentations of hypercalcemia.
PubMed: 37799241
DOI: 10.7759/cureus.44669 -
International Journal of Surgery... Nov 2023There are few data on outcomes after reintervention for persistent or recurrent primary hyperparathyroidism (PHPT). The authors hypothesized that the variation in...
BACKGROUND
There are few data on outcomes after reintervention for persistent or recurrent primary hyperparathyroidism (PHPT). The authors hypothesized that the variation in outcomes at the hospital level after reoperation would be significant. After accounting for this variability, some patient-level clinical criteria could be identified to help inform treatment decisions in this patient population. The aim of this study was to determine whether there is significant variation in outcomes after reoperation for PHPT between hospitals (hospital-level analysis) and identify clinical factors (patient-level analysis) that influence postoperative outcomes.
MATERIALS AND METHODS
This retrospective multicenter cohort study was performed using the Eurocrine registry. Data from 11 countries and 76 hospitals from January 2015 to October 2020 were extracted. A generalized linear mixed model was used to assess the variation in outcomes at the hospital level and to identify risk factors of postoperative outcomes at the patient level. The primary endpoint (textbook outcome) was achieved when all six of the following postoperative conditions were met: no hypocalcemia or persistent hypercalcemia, no laryngeal nerve injury, no negative exploration, no normal parathyroid gland only on histopathology, and no postoperative death.
RESULTS
Among 13 593 patients who underwent parathyroidectomy for PHPT, 617 (4.5%) underwent reoperative parathyroidectomy. At follow-up, 231 patients (37.4%) were hypocalcemic, 346 (56.1%) were normocalcemic without treatment, and 40 (6.5%) had persistent hypercalcemia. Textbook outcomes were achieved in 321 (52.0%) patients. The hospital-level variation in textbook outcome rates was significant ( P <0.001), and this variation could explain 29.1% of the observed outcomes. The criterion that remained significant after controlling for inter-hospital variation was 'a single lesion on sestamibi scan or positron emission tomography (PET) imaging' (odds ratio 2.08, 95% confidence interval 1.24-3.48; P =0.005).
CONCLUSION
Outcomes after reoperation are significantly associated with hospital-related factors. A 'single lesion observed on preoperative sestamibi scan or PET' appears relevant to select patients before reoperation.
Topics: Humans; Hyperparathyroidism, Primary; Hypercalcemia; Reoperation; Cohort Studies; Parathyroid Glands; Parathyroidectomy; Retrospective Studies; Technetium Tc 99m Sestamibi; Parathyroid Hormone
PubMed: 37578454
DOI: 10.1097/JS9.0000000000000613 -
CEN Case Reports Feb 2024Hypercalcemia is a vital laboratory marker because it can show underlying severe diseases like cancer and infections. Of all the causes of hypercalcemia, primary...
Hypercalcemia is a vital laboratory marker because it can show underlying severe diseases like cancer and infections. Of all the causes of hypercalcemia, primary hyperparathyroidism, and malignancies are the most common, but granulomatous diseases, such as certain fungal infections, can also be the cause. Here we describe the case of a 29-year-old woman, an insulin-dependent diabetic, found unconscious and tachypneic at home. In the emergency room, the medical team diagnosed diabetic ketoacidosis (DKA) and acute kidney injury (AKI). During hospitalization, despite resolving acidemia, persistent hypercalcemia attracted attention. Laboratory tests showed decreased parathyroid hormone (PTH) levels, confirming non-PTH-dependent hypercalcemia. Computed tomography (CT) of the chest and abdomen demonstrated no alterations, but an upper digestive endoscopy revealed an ulcerated and infiltrative lesion in the stomach. A biopsy showed a granulomatous infiltrate due to mucormycosis infection. The patient received liposomal amphotericin B for 30 days and isavuconazonium for two months. Serum calcium levels improved during treatment. Inquiry of the etiology of hypercalcemia should begin with the PTH assay; high levels are consistent with hyperparathyroidism; low levels, with calcium or vitamin D intoxication, malignancies, prolonged immobilization, and granulomatous diseases. In the latter cases, the overproduction of 1-alpha-hydroxylase by the granulomatous tissue increases the conversion of 25(OH)vitamin D into 1-25(OH)vitamin D, which causes the intestinal absorption of calcium. We have described the first hypercalcemia related to mucormycosis infection in a young diabetic patient, although case presentations associate other fungal infections with elevated serum calcium.
Topics: Female; Humans; Adult; Hypercalcemia; Calcium; Mucormycosis; Vitamin D; Parathyroid Hormone; Neoplasms; Diabetes Mellitus
PubMed: 37289341
DOI: 10.1007/s13730-023-00800-y -
European Journal of Nuclear Medicine... Mar 2024Accurate preoperative localization is imperative to guide surgery in primary hyperparathyroidism (pHPT). It remains unclear which second-line imaging technique is most...
Head-to-head comparison of [C]methionine PET, [C]choline PET, and 4-dimensional CT as second-line scans for detection of parathyroid adenomas in primary hyperparathyroidism.
PURPOSE
Accurate preoperative localization is imperative to guide surgery in primary hyperparathyroidism (pHPT). It remains unclear which second-line imaging technique is most effective after negative first-line imaging. In this study, we compare the diagnostic effectiveness of [C]methionine PET/CT, [C]choline PET/CT, and four dimensional (4D)-CT head-to-head in patients with pHPT, to explore which of these imaging techniques to use as a second-line scan.
METHODS
We conducted a powered, prospective, blinded cohort study in patients with biochemically proven pHPT and prior negative or discordant first-line imaging consisting of ultrasonography and Tc-sestamibi. All patients underwent [C]methionine PET/CT, [C]choline PET/CT, and 4D-CT. At first, all scans were interpreted by a nuclear medicine physician, and a radiologist who were blinded from patient data and all imaging results. Next, a non-blinded scan reading was performed. The scan results were correlated with surgical and histopathological findings. Serum calcium values at least 6 months after surgery were used as gold standard for curation of HPT.
RESULTS
A total of 32 patients were included in the study. With blinded evaluation, [C]choline PET/CT was positive in 28 patients (88%), [C]methionine PET/CT in 23 (72%), and 4D-CT in 15 patients (47%), respectively. In total, 30 patients have undergone surgery and 32 parathyroid lesions were histologically confirmed as parathyroid adenomas. Based on the blinded evaluation, lesion-based sensitivity of [C]choline PET/CT, [C]methionine PET/CT, and 4D-CT was respectively 85%, 67%, and 39%. The sensitivity of [C]choline PET/CT differed significantly from that of [C]methionine PET/CT and 4D-CT (p = 0.031 and p < 0.0005, respectively).
CONCLUSION
In the setting of pHPT with negative first-line imaging, [C]choline PET/CT is superior to [C]methionine PET/CT and 4D-CT in localizing parathyroid adenomas, allowing correct localization in 85% of adenomas. Further studies are needed to determine cost-benefit and efficacy of these scans, including the timing of these scans as first- or second-line imaging techniques.
Topics: Humans; Parathyroid Neoplasms; Positron Emission Tomography Computed Tomography; Hyperparathyroidism, Primary; Methionine; Choline; Cohort Studies; Prospective Studies; Parathyroid Glands; Technetium Tc 99m Sestamibi; Racemethionine
PubMed: 37975887
DOI: 10.1007/s00259-023-06488-7 -
JCEM Case Reports Jul 2023Pathogenic variants of CYP24A1 are associated with hypercalcemia due to disruptions in the ability of 24-hydroxylase to break down 1,25-dihydroxyvitamin D (1,25-DHVD). A...
Pathogenic variants of CYP24A1 are associated with hypercalcemia due to disruptions in the ability of 24-hydroxylase to break down 1,25-dihydroxyvitamin D (1,25-DHVD). A case involving a heterozygous pathogenic variant of CYP24A1 and primary hyperparathyroidism leading to severe hypercalcemia has not been previously reported. A 23-year-old woman presented with fatigue and was found to be hypercalcemic at 13.8 mg/dL [reference range, 8.4-10.2 pg/mL]. Her parathyroid hormone (PTH) was 62 pg/mL [reference range, 19-88 pg/mL] and 1,25-DHVD was elevated to 242.7 pg/mL [reference range, 18-72 pg/mL]. Other laboratory workup was unrevealing. She had a bone scan, whole body CT scan, and thyroid ultrasound that were normal. Her 25-hydroxy-vitamin D to 24,25-dihydroxy-vitamin D ratio was elevated at 25.18 (normal, < 25). Because of concern for primary hyperparathyroidism, she was referred to an endocrine surgeon and underwent a parathyroidectomy with the removal of a 3.5-gram adenoma. Pathology showed a parafibromin-deficient parathyroid neoplasm. Genetic testing demonstrated a heterozygous pathogenic variant in CYP24A1. Three weeks after surgery, PTH was 14 pg/mL (1.48 pmol/L), calcium and 1,25-DHVD normalized. In summary, we report a case where a patient with severe symptomatic hypercalcemia was found to have primary hyperparathyroidism exacerbated by an underlying heterozygous pathogenic variant in CYP24A1.
PubMed: 37909006
DOI: 10.1210/jcemcr/luad071 -
Cureus Oct 2023Background Parathyroid hormone (PTH) and Dickkopf-related protein 1 (DKK-1) have been mentioned together at the intersection of autoimmune rheumatologic diseases (ARDs)...
Background Parathyroid hormone (PTH) and Dickkopf-related protein 1 (DKK-1) have been mentioned together at the intersection of autoimmune rheumatologic diseases (ARDs) and osteoimmunology. However, few studies have evaluated the association between primary hyperparathyroidism (PHPT) and ARDs. Methodology This retrospective study included 225 PHPT patients and 386 patients with thyroid nodules as a control group. The electronic hospital records of all patients were screened going back nine years for the presence of ARDs. Patients who were diagnosed at least three months ago, had complete serologic tests, and were continuing with rheumatologic follow-up were included. Results The prevalence of ARDs in the PHPT group was 9.77% (22/225), while the prevalence of ARDs in the CG was 1.04% (4/386, p < 0.001). The prevalence of rheumatoid arthritis in the PHPT group was 4.4% (10/225), ankylosing spondylitis 3.1% (7/225), systemic lupus erythematosus 0.88% (2/225), Behçet's disease 0.88% (2/225), and mixed connective tissue disease 0.44% (1/225). Of the 22 patients with ARDs, 21 (95.45%) were diagnosed before they were diagnosed with PHPT, and the median time from diagnosis with ARD to the onset of PHPT was 36 months (interquartile range = 61.5). Logistic regression analysis showed a positive correlation between the duration of PHPT and ARDs (odds ratio (OR) = 1.06; 95% confidence interval (CI) = 1.02-1.09, p < 0.001) and a negative correlation between ARDs and calcium levels (OR = 0.26; 95% CI = 0.09-0.79, p = 0.018). Conclusions The prevalence of ARDs increased in PHPT patients and PHPT accompanying ARDs developed after rheumatologic disease. ARDs with PHPT are cases with a prolonged duration of PHPT and mildly elevated calcium, probably preceded by parathyroid hyperplasia. Therefore, the factors that cause ARDs may trigger a process that leads to mild PHPT.
PubMed: 37841984
DOI: 10.7759/cureus.46906 -
AME Case Reports 2024Familial hypocalciuric hypercalcemia (FHH) is a hypercalcemic syndrome that is usually characterized by uncomplicated hypercalcemia and normal longevity. The inheritance...
BACKGROUND
Familial hypocalciuric hypercalcemia (FHH) is a hypercalcemic syndrome that is usually characterized by uncomplicated hypercalcemia and normal longevity. The inheritance pattern is autosomal dominant with high penetrance, and it affects both men and women equally. FHH is caused by mutations that disturb the normal functioning of the calcium-sensing receptor () gene. This causes a general lack of sensitivity to calcium, eventually leading to hypercalcemia and low calcium levels in the urine.
CASE DESCRIPTION
We report a case of a healthy 24-year-old female with longstanding hypercalcemia and a family history indicating asymptomatic hypercalcemia. The patient was also asymptomatic and had no significant past medical or surgical history. Laboratory investigations and the genetic study revealed findings suggestive of FHH subtype 1.
CONCLUSIONS
The phenotype of FHH is normal, and symptoms of hypercalcemia are usually not present. Patients with FHH and hypoparathyroidism have lower calcium clearance than controls with hypoparathyroidism. This shows that relative hypocalciuria in FHH is not caused by hyperparathyroidism. Since calcium does not appropriately suppress or affect the parathyroid glands in FHH, this means that FHH is a disorder of abnormal transport of extracellular calcium and/or response to it in at least two organs, the parathyroid gland and the kidney. It is quite similar to primary hyperparathyroidism (pHPT) biochemically hence it is important to differentiate this condition from pHPT and hypercalcemia caused by other diseases to avoid any unnecessary surgical or medical intervention.
PubMed: 38711891
DOI: 10.21037/acr-23-132 -
Cureus Oct 2023Primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH) are the main differential diagnoses in a patient presenting with parathyroid hormone...
Primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH) are the main differential diagnoses in a patient presenting with parathyroid hormone (PTH)-mediated hypercalcemia. PHPT is most often caused by a single-gland parathyroid adenoma and FHH is the result of an inactivating mutation of the calcium-sensing receptor (CaSR) gene. In this paper, we present a unique case of the co-existence of an inactivating CaSR gene mutation and PHPT due to a single-gland parathyroid adenoma. The patient is a 67-year-old female with a history of recurrent nephrolithiasis who presented with hypercalcemia, elevated PTH level, and hypocalciuria. As a result of the patient's hypocalciuria, familial hypocalciuric hypercalcemia was suspected, and genetic testing was pursued. CaSR gene analysis revealed a heterogeneous inactivating mutation of the CaSR gene. Additionally, nuclear imaging with technetium sestamibi revealed a large focus of activity on the right side of the neck suspicious of a parathyroid adenoma. This was resected and confirmed to be a hypercellular parathyroid adenoma. Two years after her surgery, the patient continues to have normal calcium levels with no further episodes of nephrolithiasis. She is currently undergoing treatment for osteoporosis and is being periodically monitored for recurrence of hypercalcemia due to the presence of the inactivating CaSR gene mutation. This case highlights an exceedingly rare case of a patient with both an inactivating CaSR gene mutation and PHPT due to a single parathyroid adenoma, and it underscores the importance of further research to determine any potential relationship between the two.
PubMed: 38021951
DOI: 10.7759/cureus.46980