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BMJ Case Reports Mar 2022Isolated hyperglycinuria is a rare disorder that is associated with osteoporosis and renal calculi. We report findings in a middle-aged, black woman who presented for...
Isolated hyperglycinuria is a rare disorder that is associated with osteoporosis and renal calculi. We report findings in a middle-aged, black woman who presented for renal function evaluation with a history of transient hypobicarbonataemia associated with topiramate therapy. She displayed the full triad of high urinary glycine, early-onset osteopenia despite normal reproductive hormones, and renal calculus with high urinary oxalate, phosphate and uric acid. Parathyroid hormone and fibroblast growth factor 23 were both normal. Formal genetic testing did not reveal mutations in SLC6A20, SLC6A18, SLC6A19, SLC36A2, the known genes associated with glycinuria; however, black individuals are poorly represented in the genetic databases. It may well be that otherwise unidentified mutations may be present or that topiramate may result in a lingering proximal tubule defect even after cessation of the drug.
Topics: Amino Acid Metabolism, Inborn Errors; Female; Humans; Kidney Calculi; Membrane Transport Proteins; Middle Aged; Parathyroid Hormone; Topiramate; Uric Acid
PubMed: 35236679
DOI: 10.1136/bcr-2021-246252 -
Endocrinology Jul 2022Rodent models are commonly used to evaluate parathyroid hormone (PTH) and PTH-related protein (PTHrP) ligands and analogues for their pharmacologic activities and...
Rodent models are commonly used to evaluate parathyroid hormone (PTH) and PTH-related protein (PTHrP) ligands and analogues for their pharmacologic activities and potential therapeutic utility toward diseases of bone and mineral ion metabolism. Divergence, however, in the amino acid sequences of rodent and human PTH receptors (rat and mouse PTH1Rs are 91% identical to the human PTH1R) can lead to differences in receptor-binding and signaling potencies for such ligands when assessed on rodent vs human PTH1Rs, as shown by cell-based assays in vitro. This introduces an element of uncertainty in the accuracy of rodent models for performing such preclinical evaluations. To overcome this potential uncertainty, we used a homologous recombination-based knockin (KI) approach to generate a mouse (in-host strain C57Bl/6N) in which complementary DNA encoding the human PTH1R replaces a segment (exon 4) of the murine PTH1R gene so that the human and not the mouse PTH1R protein is expressed. Expression is directed by the endogenous mouse promoter and hence occurs in all biologically relevant cells and tissues and at appropriate levels. The resulting homozygous hPTH1R-KI (humanized) mice were healthy over at least 10 generations and showed functional responses to injected PTH analog peptides that are consistent with a fully functional human PTH1R in target bone and kidney cells. The initial evaluation of these mice and their potential utility for predicting behavior of PTH analogues in humans is reported here.
Topics: Amino Acid Sequence; Animals; Ligands; Mice; Mice, Inbred C57BL; Mice, Transgenic; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Rats; Receptor, Parathyroid Hormone, Type 1; Receptors, Parathyroid Hormone; Signal Transduction
PubMed: 35460406
DOI: 10.1210/endocr/bqac054 -
F1000Research 2020Primary hyperparathyroidism is a hormonal disorder whose prevalence is approximately 1-2% in the United States of America. The disease has become more recognizable to... (Review)
Review
Primary hyperparathyroidism is a hormonal disorder whose prevalence is approximately 1-2% in the United States of America. The disease has become more recognizable to clinicians in an earlier phase and, at present, patients can be diagnosed with "classic", "normocalcemic", "normohormonal", or "mild, asymptomatic" primary hyperparathyroidism. Surgery, with a focused parathyroidectomy when possible, or a four-gland exploration, is the only way to cure the disease. Cure is determined by use of intra-operative parathyroid hormone monitoring with long-term cure rates ranging from 90-95%. Newer adjuncts to surgery include CT or PET imaging and near-infrared immunofluorescence. This article highlights updates in parathyroid disease and advances in parathyroid surgery; it does not provide a comprehensive summary of the disease process or a review of surgical indications, which can be found in the AAES guidelines or NIH Symposium on primary hyperparathyroidism.
Topics: Humans; Hyperparathyroidism, Primary; Monitoring, Intraoperative; Parathyroid Hormone; Parathyroidectomy
PubMed: 32148764
DOI: 10.12688/f1000research.21569.1 -
Endokrynologia Polska 2023Secondary hyperparathyroidism (SHPT) is one of the most common metabolic complications resulting from chronic kidney disease (CKD). The complexity of calcium and...
Secondary hyperparathyroidism (SHPT) is one of the most common metabolic complications resulting from chronic kidney disease (CKD). The complexity of calcium and phosphate disorders associated with CKD is defined by the Kidney Disease Improvement Global Outcomes (KDIGO) working group as CKD-related mineral and bone disorders (CKD-MBD). The last update of the KDIGO guidelines on the conduct in CKD-MBD was published in 2017. The treatment of SHPT is based on 2 strategies: counteracting hyperphosphataemia and suppressing parathyroid hormone (PTH) secretion. Therapy should be based on optimally selected drugs, taking into account additional effects to reduce the risk of chronic complications and side effects. The creation of new drugs with a better safety profile, significant reduction of side effects, and greater efficiency in achieving target serum phosphorus and PTH values forces the gradual replacement of existing treatment with new pharmacotherapies. The aim of this study is to discuss the latest issues (in connection with the latest KDIGO guidelines) regarding the pathomechanism of secondary hyperparathyroidism and the current directions of the therapy in these disorders.
Topics: Humans; Chronic Kidney Disease-Mineral and Bone Disorder; Parathyroid Hormone; Hyperparathyroidism, Secondary; Renal Insufficiency, Chronic; Calcium
PubMed: 37902013
DOI: 10.5603/ep.95820 -
Orthopaedic Surgery Sep 2022To investigate the effect of intermittent parathyroid hormone (PTH) on gut microbiota (GM) in ovariectomized (OVX) osteoporotic rats.
OBJECTIVE
To investigate the effect of intermittent parathyroid hormone (PTH) on gut microbiota (GM) in ovariectomized (OVX) osteoporotic rats.
METHODS
Thirty female Sprague-Dawley rats were divided into three groups: sham-operation (SHAM) group, OVX group and PTH treatment group. After 3 months of treatment, the femurs, serum and feces were acquired for micro-CT, biochemical analysis and 16S rRNA sequencing, respectively. For 16S rRNA sequencing, after raw reads filtrated and chimera sequences removed, the clean reads were obtained. According to these clean reads, the operational taxonomic units (OTUs) were clustered. Venn diagram analysis was conducted to explore common and unique GM among the three groups. The α-diversity analysis including Shannon and Simpson indexes were used to evaluate the richness and diversity of the GM. The β-diversity analysis was performed to estimate the structure of GM. The metabolic function was predicted by Tax4Fun analysis.
RESULTS
With micro-CT and biochemical analysis, significant improvements were found in the PTH group compared with the OVX group. In Venn diagram analysis, more unique OTUs were found in the SHAM and PTH groups than the OVX group. According to the rank abundance curve, the SHAM and PTH groups had similar richness and evenness, which were higher than the OVX group. Simpson and Shannon indexes were higher in the SHAM and PTH groups compared with the OVX group, indicating that the SHAM and PTH groups had higher microbiota complexity than the OVX group. In β-diversity analysis, apparent separation was found in the OVX group from the PTH and SHAM groups, which suggested that osteoporosis is the critical factor influencing the GM composition and PTH treatment and can restore the structure of GM. Compared with the OVX group, treatment with PTH increased the abundances of GM which were reported to increase bone mass, such as Lactobacillus_reuteri, Muribaculaceae, Ruminococcaceae, and Clostridia, and inhibited the relative abundance of Rikenellaceae, which was reported to be potentially related to osteoporosis. GM function analysis showed that PTH could promote butyrate synthesis. In Tax4Fun analysis, the function of butanoate metabolism is more vital in the PTH group than the OVX and SHAM groups, suggesting PTH treatment could regulate microbial metabolic function, including butanoate metabolism.
CONCLUSION
Intermittent PTH can interact with GM through increasing the abundance of probiotics and reducing the abundance of the pathogenic bacteria to enhance the bone mass.
Topics: Animals; Female; Rats; Bone Density; Butyrates; Gastrointestinal Microbiome; Osteoporosis; Ovariectomy; Parathyroid Hormone; Rats, Sprague-Dawley; RNA, Ribosomal, 16S
PubMed: 35946436
DOI: 10.1111/os.13419 -
World Journal of Surgical Oncology Jan 2021Primary hyperparathyroidism is an endocrine pathology that affects calcium metabolism. Patients with primary hyperparathyroidism have high concentrations of serum...
BACKGROUND
Primary hyperparathyroidism is an endocrine pathology that affects calcium metabolism. Patients with primary hyperparathyroidism have high concentrations of serum calcium or high concentrations of parathyroid hormone, or incorrect parathyroid hormone levels for serum calcium values. Primary hyperparathyroidism is due to the presence of an adenoma/single-gland disease in 80-85%. Multiple gland disease or hyperplasia accounts for 10-15% of cases of primary hyperparathyroidism. Atypical parathyroid adenoma and parathyroid carcinoma are both responsible for about 1.2-1.3% and 1% or less of primary hyperparathyroidism, respectively.
METHODS
We performed a retrospective cohort study and enrolled 117 patients with primary hyperparathyroidism undergoing minimally invasive parathyroidectomy. Histological and immunohistochemical examination showed that 107 patients (91.5%) were diagnosed with typical adenoma (group A), while 10 patients (8.5%) were diagnosed with atypical parathyroid adenoma (group B). None of the patients were affected by parathyroid carcinoma.
RESULTS
Significant statistical differences were found in histological and immunohistochemical parameters as pseudocapsular invasion (p < 0.001), bands of fibrosis (p < 0.001), pronounced trabecular growth (p < 0.001), mitotic rates of > 1/10 high-power fields (HPFs) (p < 0.001), nuclear pleomorphism (p = 0.036), thick capsule (p < 0.001), Ki-67+ > 4% (p < 0.001), galectin-3 + (p = 0.002), and protein gene product (PGP) 9.5 + (p = 0.038).
CONCLUSIONS
Atypical parathyroid adenoma is a tumor that has characteristics both of typical adenoma and parathyroid carcinoma. The diagnosis is reached by excluding with strict methods the presence of malignancy criteria. Atypical parathyroid adenoma compared to typical adenoma showed significant clinical, hematochemical, histological, and immunohistochemical differences. We did not find any disease relapse in the 10 patients with atypical parathyroid adenoma during 60 months of follow-up time.
Topics: Adenoma; Humans; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Parathyroidectomy; Prognosis; Retrospective Studies
PubMed: 33472651
DOI: 10.1186/s12957-021-02123-7 -
Revista Medica de Chile Mar 2021Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic...
Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic syndromes. It occurs with equal frequency in both sexes, unlike PHP caused by parathyroid adenoma that is more common in women. It should be suspected in cases of severe hypercalcemia, with high parathyroid hormone levels and a palpable cervical mass. Given the difficulty in distinguishing between parathyroid carcinoma and adenoma prior to the surgery, the diagnosis is often made after parathyroidectomy. The only curative treatment is complete surgical resection with oncologic block resection of the primary tumor to ensure free margins. Adjuvant therapies with chemotherapy or radiation therapy do not modify overall or disease-free survival. Recurrences are common and re-operation of resectable recurrent disease is recommended. The palliative treatment of symptomatic hypercalcemia is crucial in persistent or recurrent disease after surgery since morbidity and mortality are more associated with hypercalcemia than with tumor burden.
Topics: Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Male; Neoplasm Recurrence, Local; Parathyroid Hormone; Parathyroid Neoplasms; Parathyroidectomy
PubMed: 34479319
DOI: 10.4067/s0034-98872021000300399 -
Archives of Razi Institute Oct 2022Breast cancer represents one of the most popular kinds of cancer worldwide. During the early stages of the disease, the level of Osteoprotegerin remained within normal...
Breast cancer represents one of the most popular kinds of cancer worldwide. During the early stages of the disease, the level of Osteoprotegerin remained within normal limits, showing that the bone was not being damaged to get calcium due to an increase in parathyroid hormone. The current study aimed to assess a number of biochemical variables in a group of women with malignant breast cancer who had reached menopause (less than 45 years old). One hundred thirty women were randomly divided into three groups as follows. The first group (G1) is made up of women who have never had breast cancer or any other disease, and their number (40) corresponds to the same age range (below menopause) as the control group. The second group (G2) comprises women diagnosed with breast cancer at an early stage whose numbers were relatively low (45). The third group (G3) included women of the same age who received one or two doses of chemotherapy and whose total number was (45) over the same period. The variables studied include Vitamin D, Parathyroid Hormone, Osteoprotegerin, blood calcium, and urine calcium, all of that are thought to play a role in the progress of the disease. Vitamin D levels were extremely low in the second group (G2), while they were slightly higher in the third group (G3) but remained extremely low. The first group (G1) maintained parameters within acceptable limits. There was a significant difference between the two breast cancer groups (9.38 1.43) and (4.98 1.67) when compared to the control group (20.04 2.80). (G1). The two breast cancer groups (G2) and (G3) had higher parathyroid hormone levels than the control group (G1), and there was a significant difference between the two breast cancer groups (136.52 58.56) (G3) and (G2) (167.79 35.21) compared to the control group (68.52 20.44) (G1). There was no significant difference in Osteoprotegerin levels between the two breast cancer groups (313.38 109.02) (G3) and (315.0 123.98) (G2) compared to the control group (G1) (324.11 104.73). The three groups' blood calcium levels were all within normal ranges, and there was no statistically significant difference between them (9.21 0.45), (9.23 0.38), and (9.23 0.38) (G3) (9.28 0.43). (G1), but urine-calcium levels were lower in both groups of breast cancer patients compared to the control group, and there was a significant difference between the two breast cancer groups (63.96 15.66) (G3) and (68.42 14.05) (G2) compared to the control group (213.77 63.94) (G1). In breast cancer patients, vitamin D deficiency and high parathyroid hormone levels were discovered, suggesting that vitamin D may play a role in cancer prevention. Osteoprotegerin levels were within normal ranges early in the illness, although this may alter as the patient matures and the disease advances.
Topics: Female; Humans; Breast Neoplasms; Calcium; Osteoprotegerin; Parathyroid Hormone; Vitamin D
PubMed: 37123149
DOI: 10.22092/ARI.2022.358485.2226 -
Endocrinology and Metabolism (Seoul,... Jun 2024Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder.... (Review)
Review
Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder. Levels of both hormones increase progressively in advanced CKD and can lead to damage in multiple organs. Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia with increased PTH secretion, is associated with fractures and mortality. Emerging evidence suggests that these associations may be partially explained by PTH-induced browning of adipose tissue and increased energy expenditure. Observational studies suggest a survival benefit of PTHlowering therapy, and a recent study comparing parathyroidectomy and calcimimetics further suggests the importance of intensive PTH control. The mechanisms underlying the regulation of FGF23 secretion by osteocytes in response to phosphate load have been unclear, but recent experimental studies have identified glycerol-3-phosphate, a byproduct of glycolysis released by the kidney, as a key regulator of FGF23 production. Elevated FGF23 levels have been shown to be associated with mortality, and experimental data suggest off-target adverse effects of FGF23. However, the causal role of FGF23 in adverse outcomes in CKD patients remains to be established. Further studies are needed to determine whether intensive SHPT control improves clinical outcomes and whether treatment targeting FGF23 can improve patient outcomes.
Topics: Humans; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Parathyroid Hormone; Renal Insufficiency, Chronic; Hyperparathyroidism, Secondary; Animals
PubMed: 38752265
DOI: 10.3803/EnM.2024.1978 -
Endocrinology and Metabolism (Seoul,... Apr 2024The conventional treatment of hypoparathyroidism (HypoPT) includes active vitamin D and calcium. Despite normalization of calcium levels, the conventional treatment is... (Review)
Review
The conventional treatment of hypoparathyroidism (HypoPT) includes active vitamin D and calcium. Despite normalization of calcium levels, the conventional treatment is associated with fluctuations in calcium levels, hypercalciuria, renal impairment, and decreased quality of life (QoL). Replacement therapy with parathyroid hormone (PTH)(1-84) is an option in some countries. However, convincing beneficial effects have not been demonstrated, which may be due to the short duration of action of this treatment. Recently, palopegteriparatide (also known as TransCon PTH) has been marketed in Europe and is expected also to be approved in other countries. Palopegteriparatide is a prodrug with sustained release of PTH(1-34) designed to provide stable physiological PTH levels for 24 hours/day. A phase 3 study demonstrated maintenance of normocalcemia in patients with chronic HypoPT, with no need for conventional therapy. Furthermore, this treatment lowers urinary calcium and improves QoL. Another long-acting PTH analog with effects on the parathyroid hormone receptor (eneboparatide) is currently being tested in a phase 3 trial. Furthermore, the treatment of autosomal dominant hypocalcemia type 1 with a calcilytic (encaleret) is also being tested. All in all, improved treatment options are on the way that will likely take the treatment of HypoPT to the next level.
Topics: Humans; Hypoparathyroidism; Parathyroid Hormone; Hormone Replacement Therapy; Quality of Life; Calcium
PubMed: 38572533
DOI: 10.3803/EnM.2024.1916