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Clinical Case Reports Dec 2023Parathyroid lipoadenoma is a rare type of parathyroid adenoma, described as a single parathyroid adenoma with more than 50% fat on histologic examination and an unknown...
Parathyroid lipoadenoma is a rare type of parathyroid adenoma, described as a single parathyroid adenoma with more than 50% fat on histologic examination and an unknown etiology, which is one of the rare causes of primary hyperparathyroidism. The difficulty of parathyroid lipoadenoma is mainly diagnosed by preoperative imaging localization. We hope to arouse attention to the parathyroid adenoma which is difficult to locate through our case report. The patient was a middle-aged male with a body mass index of 38.4 kg/m who admitted to our hospital with a 40-day history of an untreated thyroid nodule. We incidentally discovered parathyroid lipoadenoma in his thyroid surgery. His prognosis was good, and there were no signs of recurrence at his 12-month follow-up appointment. We believe that parathyroid lipoadenoma needs to rely on paraffin pathology to make a final diagnosis. This case report serves as a reminder that parathyroid lipoadenomas are also possible in patients who do not have primary hyperparathyroidism preoperatively and who have negative imaging. Clinicians must carefully examine the adipose tissue for the presence of parathyroid lipoadenomas during thyroid surgery to avoid postoperative hypoparathyroidism and persistent hypocalcaemia.
PubMed: 38033682
DOI: 10.1002/ccr3.8251 -
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 -
Endocrine Journal Jan 2024Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in several organs including endocrine glands. Among endocrine irAEs, thyroid and... (Review)
Review
Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in several organs including endocrine glands. Among endocrine irAEs, thyroid and pituitary irAEs are frequently observed, followed by primary adrenal insufficiency, insulin-dependent diabetes mellitus, and hypoparathyroidism. These conditions could lead to life-threatening consequences, such as adrenal crisis and diabetic ketoacidosis. On the other hand, several types of irAEs including thyroid and pituitary irAEs are reported to be associated with better overall survival. Therefore, it is important to understand and manage endocrine irAEs, which differ depending on the ICI regimen used. In this review, we describe the clinical features, potential biomarkers, management strategies, and possible mechanisms of thyroid and pituitary irAEs.
Topics: Humans; Thyroid Gland; Pituitary Gland; Pituitary Diseases; Biomarkers; Diabetes Mellitus, Type 1; Neoplasms
PubMed: 37940567
DOI: 10.1507/endocrj.EJ23-0524 -
European Journal of Human Genetics :... Jan 2024ATP2B1 encodes plasma membrane calcium-transporting-ATPase1 and plays an essential role in maintaining intracellular calcium homeostasis that regulates diverse signaling...
ATP2B1 encodes plasma membrane calcium-transporting-ATPase1 and plays an essential role in maintaining intracellular calcium homeostasis that regulates diverse signaling pathways. Heterozygous de novo missense and truncating ATP2B1 variants are associated with a neurodevelopmental phenotype of variable expressivity. We describe a proband with distinctive craniofacial gestalt, Pierre-Robin sequence, neurodevelopmental and growth deficit, periventricular heterotopia, brachymesophalangy, cutaneous syndactyly, and persistent hypocalcemia from primary hypoparathyroidism. Proband-parent trio exome sequencing identified compound heterozygous ATP2B1 variants: a maternally inherited splice-site (c.3060+2 T > G) and paternally inherited missense c.2938 G > T; p.(Val980Leu). Reverse-transcription-PCR on the proband's fibroblast-derived mRNA showed aberrantly spliced ATP2B1 transcripts targeted for nonsense-mediated decay. All correctly-spliced ATP2B1 mRNA encoding p.(Val980Leu) functionally causes decreased cellular Ca extrusion. Immunoblotting showed reduced fibroblast ATP2B1. We conclude that biallelic ATP2B1 variants are the likely cause of the proband's phenotype, strengthening the association of ATP2B1 as a neurodevelopmental gene and expanding the phenotypic characterization of a biallelic loss-of-function genotype.
Topics: Humans; Calcium; Phenotype; Genotype; RNA, Messenger; Hypoparathyroidism; Plasma Membrane Calcium-Transporting ATPases
PubMed: 37926713
DOI: 10.1038/s41431-023-01484-9 -
JCEM Case Reports Jul 2023Vitamin D hydroxylation-deficient rickets type 1A is an autosomal recessive disorder caused by pathogenic variants in gene, which encodes for 1α-hydroxylase, the...
Vitamin D hydroxylation-deficient rickets type 1A is an autosomal recessive disorder caused by pathogenic variants in gene, which encodes for 1α-hydroxylase, the enzyme responsible for the conversion of 25-OH vitamin D into its active form 1,25(OH)2 vitamin D. We report the case of a 3-year-old female Mexican patient with growth retardation and progressive bone deformity, whose laboratory studies showed 25-OH vitamin D deficiency, a normal serum calcium and an elevated intact parathyroid hormone level that remained high despite calcitriol, cholecalciferol, and calcium supplementation. Tc sestamibi gammagram showed findings suggestive of parathyroid hyperplasia. Bone histomorphometry showed an image consistent with hyperparathyroidism without findings of osteomalacia, so normocalcemic primary hyperparathyroidism was suspected and a subtotal parathyroidectomy was performed, with the patient developing postoperative hypoparathyroidism. When she arrived at our clinic at age 18 years, she showed calcium- and calcitriol-dependent hypocalcemia, with secondary hyperparathyroidism and low levels of 1,25(OH)2 vitamin D in the absence of a 25-OH vitamin D deficiency, reflecting a defect in 1α-hydroxylation. Molecular testing revealed compound heterozygous variants in gene. This is the first reported case of an inherited disorder of vitamin D metabolism that was diagnosed and surgically treated as primary hyperparathyroidism.
PubMed: 37908980
DOI: 10.1210/jcemcr/luad084 -
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 -
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 -
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 Neurology 2023Fahr's disease, or primary familial brain calcification (PFBC), is a rare genetic neurologic disease characterized by abnormal calcification of the basal ganglia,...
Fahr's disease, or primary familial brain calcification (PFBC), is a rare genetic neurologic disease characterized by abnormal calcification of the basal ganglia, subcortical white matter and cerebellum. Common clinical features include parkinsonism, neuropsychiatric symptoms, and cognitive decline. Genes implicated in Fahr's disease include , , , , , and . We present the case of a 51-year-old woman who developed subacute cognitive and behavioral changes primarily affecting frontal-subcortical pathways and parkinsonism in association with extensive bilateral calcifications within the basal ganglia, subcortical white matter, and cerebellum on neuroimaging. Relevant family history included a paternal aunt with parkinsonism at age 50. Normal parathyroid hormone and calcium levels in the patient's serum ruled out hypoparathyroidism or pseudohypoparathyroidism as causes for the intracranial calcifications. Genetic panel sequencing revealed a variant of unknown significance in the gene resulting in a p.Arg919Gln substitution in the tyrosine kinase domain of PDGFRB protein. To our knowledge this is the first report of a p.Arg919Gln variant in the gene associated with PFBC. Although co-segregation studies were not possible in this family, the location of the variant is within the tyrosine kinase domain of PDGFRB and pathogenicity calculators predict it is likely to be pathogenic. This report adds to the list of genetic variants that warrant functional analysis and could underlie the development of PFBC, which may help to further our understanding of its pathogenesis and the development of targeted therapies for this disorder.
PubMed: 37780723
DOI: 10.3389/fneur.2023.1235909 -
The British Journal of Surgery Nov 2023Techniques for autofluorescence have been introduced to visualize the parathyroid glands during surgery and to reduce hypoparathyroidism after thyroidectomy. (Randomized Controlled Trial)
Randomized Controlled Trial
Impact of autofluorescence for detection of parathyroid glands during thyroidectomy on postoperative parathyroid hormone levels: parallel multicentre randomized clinical trial.
BACKGROUND
Techniques for autofluorescence have been introduced to visualize the parathyroid glands during surgery and to reduce hypoparathyroidism after thyroidectomy.
METHODS
This parallel multicentre RCT investigated the use of Fluobeam® LX to visualize the parathyroid glands by autofluorescence during total thyroidectomy compared with no use. There was no restriction on the indication for surgery. Patients were randomized 1 : 1 and were blinded to the group allocation. The hypothesis was that autofluorescence enables identification and protection of the parathyroid glands during thyroidectomy. The primary endpoint was the rate of low parathyroid hormone (PTH) levels the day after surgery.
RESULTS
Some 535 patients were randomized, and 486 patients received an intervention according to the study protocol, 246 in the Fluobeam® LX group and 240 in the control group. Some 64 patients (26.0 per cent) in the Fluobeam® LX group and 77 (32.1 per cent) in the control group had low levels of PTH after thyroidectomy (P = 0.141; relative risk (RR) 0.81, 95 per cent c.i. 0.61 to 1.07). Subanalysis of 174 patients undergoing central lymph node clearance showed that 15 of 82 (18 per cent) in the Fluobeam® LX group and 31 of 92 (33 per cent) in the control group had low levels of PTH on postoperative day 1 (P = 0.021; RR 0.54, 0.31 to 0.93). More parathyroid glands were identified during operation in patients who had surgery with Fluobeam® LX, and fewer parathyroid glands in the surgical specimen on definitive histopathology. No specific harm related to the use of Fluobeam® LX was reported.
CONCLUSION
The use of autofluorescence during thyroidectomy did not reduce the rate of low PTH levels on postoperative day 1 in the whole group of patients. It did, however, reduce the rate in a subgroup of patients. Registration number: NCT04509011 (http://www.clinicaltrials.gov).
Topics: Humans; Parathyroid Glands; Thyroidectomy; Parathyroid Hormone; Hypoparathyroidism; Lymph Nodes; Postoperative Complications; Hypocalcemia
PubMed: 37758507
DOI: 10.1093/bjs/znad278