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European Thyroid Journal Dec 2023Evidence-based treatment guidelines for the management of postthyroidectomy hypocalcemia are absent. The aim of this study was to evaluate a newly developed...
OBJECTIVE
Evidence-based treatment guidelines for the management of postthyroidectomy hypocalcemia are absent. The aim of this study was to evaluate a newly developed symptom-based treatment algorithm including a protocolized attempt to phase out supplementation.
METHODS
In a prospective multicenter study, patients were treated according to the new algorithm and compared to a historical cohort of patients treated with a biochemically based approach. The primary outcome was the proportion of patients receiving calcium and/or alfacalcidol supplementation. Secondary outcomes were calcium-related complications and predictors for supplementation.
RESULTS
One hundred thirty-four patients were included prospectively, and compared to 392 historical patients. The new algorithm significantly reduced the proportion of patients treated with calcium and/or alfacalcidol during the first postoperative year (odds ratio (OR): 0.36 (95% CI: 0.23-0.54), P < 0.001), and persistently at 12 months follow-up (OR: 0.51 (95% CI: 0.28-0.90), P < 0.05). No severe calcium-related complications occurred, even though calcium-related visits to the emergency department and readmissions increased (OR: 11.5 (95% CI: 4.51-29.3), P <0.001) and (OR: 3.46 (95% CI: 1.58-7.57), P < 0.05), respectively. The proportional change in pre- to postoperative parathyroid hormone (PTH) was an independent predictor for supplementation (OR: 1.04 (95% CI: 1.02-1.07), P < 0.05).
CONCLUSIONS
Symptom-based management of postthyroidectomy hypocalcemia and a protocolized attempt to phase out supplementation safely reduced the proportion of patients receiving supplementation, although the number of calcium-related hospital visits increased. For the future, we envision a more individualized treatment approach for patients at risk for delayed symptomatic hypocalcemia, including the proportional change in pre- to post- operative PTH.
Topics: Humans; Calcium; Hypocalcemia; Thyroid Gland; Prospective Studies; Thyroidectomy; Parathyroid Hormone; Calcium, Dietary; Algorithms
PubMed: 37655701
DOI: 10.1530/ETJ-23-0044 -
Cureus Sep 2023Hypoparathyroidism requires management with both calcium supplementation and active vitamin D to avert a state of hypocalcemia. During late gestation and the postpartum... (Review)
Review
Hypoparathyroidism requires management with both calcium supplementation and active vitamin D to avert a state of hypocalcemia. During late gestation and the postpartum period (specifically lactation), there is an under-recognized, yet intriguing occurrence of apparent 'pseudohyperparathyroidism', whereby supplementation dosages may need to either be reduced or discontinued, to prevent hypercalcemia. The explanation for this apparent phenomenon of improved parathyroid status ('remission' or 'resolution') is incompletely understood; the purpose of this review is to analyze the case reports of this enigma within the medical (and grey) literature, providing an overall pathophysiological explanation and recommendation for the management of such patients. A literature search was conducted through PubMed/Medline, CINAHL, Cochrane Library Database, Scopus, UpToDate, Google Scholar, and the grey literature without a time-restricted period, analyzing all available articles within the literature describing an apparent improvement in parathyroid status in late-gestation and postpartum (lactating) females. Non-hypoparathyroid case reports were also included to further analyze and synthesize an overall likely pathophysiological explanation. Through the literature search, 24 papers were identified covering such a phenomenon in patients with hypoparathyroidism, alongside multiple additional reports of a similar occurrence in patients without underlying hypoparathyroidism. The pathophysiology is believed to occur due to the placental production of parathyroid hormone-related peptide (PTHrP) during gestation, with further production from the lactating mammary glands during the postpartum period. A typical pattern is observed, with increased PTHrP and suppressed PTH throughout both gestation and lactation (present in both normal and hypoparathyroid subjects). The concept of PTHrP-induced hypercalcemia is further demonstrated in patients without hypoparathyroidism, including subjects with placental hypersecretion and mammary gland enlargement. It is evident that patients with hypoparathyroidism may require a dosage reduction during late gestation and lactation, due to the risk for hypercalcemia. In addition to patients with hypoparathyroidism, this pathophysiological phenomenon occurs in unsuspecting patients, demonstrating the need for all clinicians in contact with pregnant females to be aware of this uncommon - yet perilous - occurrence.
PubMed: 37790033
DOI: 10.7759/cureus.46123 -
Frontiers in Endocrinology 2024Hypoparathyroidism following total thyroidectomy is globally the most common complication to thyroid surgery. The reported complication rates vary widely and might be...
BACKGROUND
Hypoparathyroidism following total thyroidectomy is globally the most common complication to thyroid surgery. The reported complication rates vary widely and might be highly dependent on the surgical experience. In this study we aimed to evaluate the rate of hypoparathyroidism following primary total thyroidectomy at a low-volume institution that only performs thyroid surgery and does not have any experience with parathyroid surgery.
METHODS
Retrospective cohort study. All patients undergoing primary total thyroidectomy at the ENT-Department, Goedstrup Hospital, Denmark, over a 5-year period (2016-2020) were identified through the procedure codes for total thyroidectomy. Medical records, pathology reports, biochemical and medical histories were fully assessed for each patient. The primary endpoint was the rate of hypoparathyroidism- both immediate and permanent. Secondary outcomes were parathyroid gland identification rates, rates of parathyroid gland autotransplantation, and rates of inadvertent parathyroid gland excision.
RESULTS
A total of 89 patients were included in the final analysis. A total of 33 patients (37.1%) experienced immediate hypoparathyroidism following surgery, while 30 patients (33.7%) still were on active vitamin D two months postoperatively. One year following surgery, 28 patients (31.5%) were still on active vitamin D and were considered as having permanent hypoparathyroidism. Sixty-one percent of the parathyroid glands were identified intraoperatively, and 19% of the patients experienced parathyroid autotransplantation. Inadvertent parathyroid gland excision occurred for 21% of the patients and was associated with a significantly increased risk of permanent hypoparathyroidism (RR = 2.99; 95% CI: 1.36 - 6.62, p = 0.005).
CONCLUSION
Both transient and permanent hypoparathyroidism following total thyroidectomy at a low-volume, non-parathyroid institution occurred with much higher frequencies than previously reported. The elevated rates were most likely due to the low-volume, non-parathyroid nature of the surgeons which in part was mirrored in low parathyroid gland identifications rates, and high rates of autotransplantation and inadvertent parathyroid gland excision.
Topics: Humans; Parathyroid Glands; Thyroidectomy; Retrospective Studies; Postoperative Complications; Hypoparathyroidism; Vitamin D
PubMed: 38304463
DOI: 10.3389/fendo.2024.1330524 -
Frontiers in Endocrinology 2023The serum calcium (Ca)-to-phosphorus (P) ratio has been proposed to identify patients with primary hyperparathyroidism and chronic hypoparathyroidism (HPT), but it has... (Observational Study)
Observational Study
OBJECTIVE
The serum calcium (Ca)-to-phosphorus (P) ratio has been proposed to identify patients with primary hyperparathyroidism and chronic hypoparathyroidism (HPT), but it has never been tested in pseudohypoparathyroidism (PHP). The aim of this study was to test the performance of Ca/P ratio in PHP diagnosis compared with that in healthy subjects and patients with HPT for differential diagnosis.
DESIGN
A retrospective, cross-sectional, and observational study was carried out.
METHODS
Serum Ca, P, creatinine, parathyroid hormone (PTH), and albumin were collected. Ca and P were expressed in mmol/L. Ca/P diagnostic performance was evaluated by receiver operating characteristic curve, sensitivity, specificity, and accuracy.
RESULTS
A total of 60 patients with PHP, 60 patients with HPT, and 120 controls were enrolled. The Ca/P ratio was lower in patients with PHP and HPT than that in controls (p < 0.0001). The cutoff of 1.78 (2.32 if Ca and P measured in mg/dL) for Ca/P ratio could identify patients with PHP and HPT among the entire cohort (sensitivity and specificity of 76%). No valid cutoff of Ca/P was found to distinguish patients with PHP from patients with HPT; in this case, PTH above 53.0 ng/dL identified patients with PHP (sensitivity and specificity of 100%). The index (Ca/P × PTH) above 116 ng/L recognized patients with PHP from controls (sensitivity of 84.7% and specificity of 87.4%), whereas (Ca/P × PTH) below 34 ng/L recognized patients with HPT from controls (sensitivity of 88.9% and specificity of 90.8%).
CONCLUSIONS
The Ca/P ratio below 1.78 (2.32 CU) is highly accurate to identify patients with PHP and HPT, although it is not reliable to differentiate these two conditions. The index (Ca/P × PTH) is excellent to specifically recognize PHP or HPT from healthy subjects.
Topics: Humans; Calcium; Retrospective Studies; Cross-Sectional Studies; Pseudohypoparathyroidism; Parathyroid Hormone; Hypoparathyroidism; Phosphorus
PubMed: 37854194
DOI: 10.3389/fendo.2023.1268704 -
The Journal of International Medical... Aug 2023Idiopathic hypoparathyroidism is a rare endocrine disorder characterized by hypocalcemia secondary to inadequate parathyroid hormone secretion. Hypocalcemia-related...
Idiopathic hypoparathyroidism is a rare endocrine disorder characterized by hypocalcemia secondary to inadequate parathyroid hormone secretion. Hypocalcemia-related cataract is most often observed in patients with postoperative hypoparathyroidism, whereas primary hypoparathyroidism-related cataract is rare and displays slow progression. Cataract usually occurs in people aged 18 to 50 years. Here, we describe a 17-year-old boy with bilateral cataract and a history of hypocalcemic tetany who was diagnosed with idiopathic hypoparathyroidism. Phacoemulsification with implantation of a monofocal aspherical intraocular lens was performed in the right eye; 6 months later, it was performed in the left eye. Elevated phosphorus and diminished calcium were observed in blood and aqueous humor. A deep anterior chamber, relatively thin central corneal thickness, large white-to-white distance, and thin lens were also observed. During follow-up, neither eye displayed intraocular lens decentration; best-corrected visual acuity was 20/20 in both eyes. These findings suggest that ophthalmologists should be vigilant when hypocalcemic tetany and cataract are present, especially in adolescents and young adults.
Topics: Male; Young Adult; Humans; Adolescent; Tetany; Hypocalcemia; Cataract; Hypoparathyroidism; Eye
PubMed: 37622441
DOI: 10.1177/03000605231193820 -
JBMR Plus Mar 2024Hypoparathyroidism (HypoPT) is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing... (Clinical Trial)
Clinical Trial
UNLABELLED
Hypoparathyroidism (HypoPT) is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing pharmacokinetics and pharmacodynamics of different dosing regimens of recombinant human parathyroid hormone 1-84 (rhPTH[1-84]) for treating HypoPT. The present study (NCT03364738) was a phase 4, 1-yr open-label extension of PARALLAX. Patients received only 2 doses of rhPTH(1-84) in PARALLAX and were considered treatment-naive at the start of the current study. rhPTH(1-84) was initiated at 50 μg once daily, with doses adjusted based on albumin-corrected serum calcium levels. Albumin-corrected serum calcium (primary outcome measure), health-related quality of life (HRQoL), adverse events, and healthcare resource utilization (HCRU) were assessed. The mean age of the 22 patients included was 50.0 yr; 81.8% were women, and 90.9% were White. By the end of treatment (EOT), 95.5% of patients had albumin-corrected serum calcium values in the protocol-defined range of 1.88 mmol/L to the upper limit of normal. Serum phosphorus was within the healthy range, and albumin-corrected serum calcium-phosphorus product was below the upper healthy limit throughout, while mean 24-h urine calcium excretion decreased from baseline to EOT. Mean supplemental doses of calcium and active vitamin D were reduced from baseline to EOT (2402-855 mg/d and 0.8-0.2 μg/d, respectively). Mean serum bone turnover markers, bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide, and type I collagen C-telopeptide increased 2-5 fold from baseline to EOT. The HCRU, disease-related symptoms and impact on HRQoL improved numerically between baseline and EOT. Nine patients (40.9%) experienced treatment-related adverse events; no deaths were reported. Treatment with rhPTH(1-84) once daily for 1 yr improved HRQoL, maintained eucalcemia in 95% of patients, normalized serum phosphorus, and decreased urine calcium excretion. The effects observed on urine calcium and the safety profile are consistent with previous findings.
CLINICAL TRIAL IDENTIFIER
NCT03364738.
PubMed: 38741607
DOI: 10.1093/jbmrpl/ziad010 -
Cureus Oct 2023Multiple endocrine neoplasia (MEN) is an inherited, autosomal dominant condition characterized by primary parathyroid hyperplasia, medullary thyroid neoplasm, and...
Multiple endocrine neoplasia (MEN) is an inherited, autosomal dominant condition characterized by primary parathyroid hyperplasia, medullary thyroid neoplasm, and pheochromocytoma. It most commonly presents with medullary thyroid cancer and less frequently with other complaints. Pheochromocytoma can also manifest through gastrointestinal complaints such as abdominal pain, nausea, and constipation. We present a normotensive case of pheochromocytoma, initially featuring abdominal pain and vomiting, which was later found to be associated with neck swelling and medullary thyroid cancer. The patient underwent an adrenalectomy and has continued to visit our endocrinology clinic for ongoing monitoring and treatment of iatrogenic hypoparathyroidism and hypothyroidism. A brief review is also provided.
PubMed: 38022135
DOI: 10.7759/cureus.47063 -
OTO Open 2024This systematic review and meta-analysis aimed to assess whether preoperative administration of calcium and vitamin D prevents postoperative hypocalcemia. (Review)
Review
OBJECTIVE
This systematic review and meta-analysis aimed to assess whether preoperative administration of calcium and vitamin D prevents postoperative hypocalcemia.
DATA SOURCES
A computerized search in Medline, Embase, and CENTRAL databases was performed.
REVIEW METHODS
Trials comparing preoperative calcium and vitamin D administration with either placebo or nothing were eligible for inclusion. The primary outcomes were the occurrence of laboratory hypocalcemia, mean postoperative calcium level, and symptomatic hypocalcemia. The secondary outcomes were the development of permanent hypoparathyroidism and length of hospitalization. Continuous outcomes were represented as standardized mean difference (SMD), and dichotomous outcomes were represented as risk ratio (RR).
RESULTS
Nine trials that enrolled 1079 patients were found eligible. Postoperative laboratory hypocalcemia occurred less in patients who received preoperative calcium and vitamin D, but it was not statistically significant (RR = 0.77, 95% CI: 0.60-1.00; = .05). Mean postoperative calcium level was significantly higher in the intervention group (SMD = 0.10, 95% CI: 0.07-0.12; < .00001). The number of patients with symptomatic hypocalcemia was significantly lower in the intervention group (RR = 0.54, 95% CI: 0.38-0.76; = .0005). There was no significant difference between the 2 groups in cases of permanent hypoparathyroidism and length of hospitalization.
CONCLUSION
Administration of calcium and vitamin D preoperatively achieves lower rates of postthyroidectomy symptomatic hypocalcemia in comparison with no intervention.
PubMed: 38371915
DOI: 10.1002/oto2.116 -
Journal of Clinical Medicine Jun 2024Transient hypoparathyroidism (TH) is the main post-thyroidectomy complication, significantly impacting surgical outcomes, hospitalization length, and perceived...
Transient hypoparathyroidism (TH) is the main post-thyroidectomy complication, significantly impacting surgical outcomes, hospitalization length, and perceived perceived quality of life understood as mental and physical well-being. This study aims to identify possible associated risk factors. We analyzed 238 thyroidectomies (2020-2022), excluding instances of partial surgery, primary hyperparathyroidism, neck irradiation history, and renal failure. The variables considered were as follows: demographics, histology, autoimmunity, thyroid function, pre- and postoperative Vitamin D levels (where available), type of surgery, number of incidentally removed parathyroid glands (IRP), and surgeons' experience (>1000 thyroidectomies, <500, in training). Univariate analysis applied: χ, Fisher's exact test for categorical variables, and Student's -test for continuous variables. Subsequently, logistic multivariate analysis with stepwise selection was performed. Univariate analysis did not yield statistically significant results for the considered variables. The 'No Complications' group displayed a mean age of 55 years, whereas the TH group showed a mean age of 51 (-value = 0.055). We considered this result to be marginally significant. Subsequently, we constructed a multivariate logistic model. This model (AIC = 245.02) indicated that the absence of incidental parathyroidectomy was associated with the age class >55 years, presenting an odds ratio (OR) of 9.015 (-value < 0.05). Simultaneously, the age class >55 years exhibited protective effects against TH, demonstrating an OR of 0.085 (-value < 0.01). Similarly, the absence of incidental parathyroidectomy was found to be protective against TH, with an OR of 0.208 (-value < 0.01). Multivariate analysis highlighted that having "No IRP" was protective against TH, while younger age was a risk factor. Surgeon experience does not seem to correlate with IRP or outcomes, assuming there is adequate tutoring and a case volume close to 500 to ensure good results. The effect of reimplantation has not been evident in transient hypoparathyroidism.
PubMed: 38893037
DOI: 10.3390/jcm13113326 -
Journal of the Endocrine Society Oct 2023The glial cells missing 2 () gene functions as a transcription factor that is essential for parathyroid gland development, and variants in this gene have been associated...
CONTEXT
The glial cells missing 2 () gene functions as a transcription factor that is essential for parathyroid gland development, and variants in this gene have been associated with 2 parathyroid diseases: isolated hypoparathyroidism in patients with homozygous germline inactivating variants and primary hyperparathyroidism in patients with heterozygous germline activating variants. A recurrent germline activating missense variant of , p.Y394S, has been reported in patients with familial primary hyperparathyroidism.
OBJECTIVE
To determine whether the p.Y394S missense variant causes overactive and enlarged parathyroid glands in a mouse model.
METHODS
CRISPR/Cas9 gene editing technology was used to generate a mouse model with the germline heterozygous variant p.Y392S that corresponds to the human p.Y394S variant. Wild-type () and germline heterozygous () mice were evaluated for serum biochemistry and parathyroid gland morphology.
RESULTS
mice did not show any change compared to mice in serum calcium and parathyroid hormone levels, parathyroid gland histology, cell proliferation, or parathyroid gland size.
CONCLUSION
The mouse model of the p.Y392S variant of shows that this variant is tolerated in mice, as it does not increase parathyroid gland cell proliferation and circulating calcium or PTH levels. Further investigation of mice to study the effect of this variant of on early events in parathyroid gland development will be of interest.
PubMed: 37885910
DOI: 10.1210/jendso/bvad126