Cause Of Primary Hyperparathyroidism Research Articles

1053 Parathyroid Phenomenon Causing Primary Hyperparathyroidism: A Case for Surgeons, Radiologists and Pathologists

Abstract Background Parathyroid lipoadenomas are a rare parathyroid phenomenon and an unusual cause of primary hyperparathyroidism. The histological composition of these neoplasms makes them a diagnostic challenge, as their high adipose content leads to difficulty localising them on imaging and can lead pathologists towards a wrong diagnosis. There are less than 100 cases in the literature since they were first described in 1958, and to our knowledge this is the largest parathyroid lipoadenoma to be reported. Method A minimally invasive parathyroidectomy with intraoperative parathyroid hormone monitoring was performed in the case of a male with a large neck mass and symptomatic primary hyperparathyroidism. Results A giant parathyroid lipoadenoma was excised, with an appropriate decrease in intraoperative parathyroid hormone level observed. The patient has been cured of his primary hyperparathyroidism, with no issues following his discharge from our institution. Conclusions We highlight the importance of having the parathyroid lipoadenoma as a differential diagnosis for patients who develop primary hyperparathyroidism.

Primary hyperparathyroidism: predictors of sporadic multi-gland disease.

In this review, we discuss the definition, prevalence, and etiology of sporadic multiglandular disease (MGD), with an emphasis on its preoperative and intraoperative predictors. Primary hyperparathyroidism (PHPT) is the third-most common endocrine disorder, and multiglandular parathyroid disease (MGD) is a cause of PHPT. Hereditary MGD can be definitively diagnosed with detailed family history and genetic testing, whereas sporadic MGD presents a greater challenge in clinical practice, and parathyroidectomy for MGD is associated with a higher risk of surgical failure than single gland disease (SGD). Therefore, it is crucial to be able to predict the presence of sporadic MGD in a timely manner, either preoperatively or intraoperatively. Various predictive methods cannot accurately identify all cases of sporadic MGD, but they can greatly optimize the management of MGD diagnosis and treatment and optimize the cure rate. Future research will urge us to investigate more integrative predictive models as well as increase our understanding of MGD pathogenesis.

Quality of life of patients with singleand multigland parathyroid disease in sporadic primary hyperparathyroidism before and after surgical treatment

Background. In 15–25 % of cases, the cause of primary hyperparathyroidism (PHPT) is multigland parathyroid disease. The complexity of clinical and laboratory prognosis, low efficiency of imaging methods, inaccurate assessment of the radicality of the surgery are the components of the problem of this variant of the disease. Quality of life (QOL) is an important criterion for the effectiveness of surgical treatment. A study of the QOL in patients with multigland parathyroid disease in PHPT has not been previously conducted in our country. The aim of the study. To assess the quality of life of patients with single- and multigland parathyroid disease in sporadic primary hyperparathyroidism before and after parathyroidectomy (PTE). Methods. As part of a prospective observational study, the quality of life of 64 patients with PHPT before and after PTE was assessed using SF-36 (Short Form 36) questionnaire: main group (n = 13) – patients with multigland parathyroid disease; comparison group (n = 51) – patients with single-gland parathyroid disease. The quality of life indicators of the patients were compared with those in a sample of the Irkutsk region population similar in gender and age. Results. Before performing PTE, the quality of life of patients with PHPT was lower than that of the Irkutsk region population. The greatest decrease in both health components was registered in the main group. In 90 % of patients, the quality of life improved after PTE, while in the main group changes were established 1 year after the surgery, in the comparison group – 6 months after the surgery. Transient complications (laryngeal paresis) and disease outcomes (hypocalcemia, hypoparathyroidism) did not interfere with the improvement of quality of life in both groups. When persistence was detected, no significant improvement in QOL was established. Conclusion. The quality of life of patients with PHPT is significantly reduced. PTE improves the QOL of these patients, and only persistence of the disease does not allow this to be achieved. Therefore, surgical tactics aimed at reducing the frequency of persistence will achieve a decent quality of life in the majority of patients with multigland parathyroid disease in PHPT.

Treating intra-thyroid parathyroid adenoma by radiofrequency is a valuable alternative to hemithyroidectomy

Background Parathyroid adenoma (PA) is the most common cause of primary hyperparathyroidism (PHPT). One infrequent scenario (0.7%–6%) is represented by intra-thyroid PA (I-PA), an ectopic variant of the parathyroid gland included in the thyroid parenchyma. Radiofrequency (RF) of I-PA seems to be an excellent alternative to hemithyroidectomy for these patients. The present study aimed to report three cases of PHPT and I-PA treated with RF at two institutions. Materials and methods These two institutions share guidelines for thyroid RF. At both institutions, cases with surgical indication and difficult PA localization are discussed during thyroid multidisciplinary meetings involving all disciplines involved in managing these cases. RF was performed using a Viva RF System generator (STARMED). Ultrasound contrast evaluation was performed using a SonoVue (Bracco). All patients were followed-up by an expert endocrinologist. Results Three cases had indications for treating I-PA. All patients were proposed to undergo RF rather than hemithyroidectomy, and accepted this option. RF of I-PA was performed with a power of 30–50 W and delivering a total between 0.02 and 0.69 Kcal. The active treatment lasted just more than 1 min. Post-treatment follow-up revealed PTH and calcium normalization. Conclusion This study showed highly encouraging results in favor of treating I-PA with RF.

How often are intrathyroidal parathyroid glands a cause of primary hyperparathyroidism, and how should they be managed?

The purpose of our study was to determine the frequency and management of intrathyroidal parathyroid glands in patients with primary hyperparathyroidism and evaluate whether intrathyroidal parathyroid glands were more often superior or inferior glands. A retrospective review of the prospective parathyroid database was completed to determine the number of patients with primary hyperparathyroidism and an intrathyroidal parathyroid gland. Demographic data, laboratory and localization studies, operative management, pathology, and outcome were determined for patients with an intrathyroidal parathyroid gland and were compared with patients with an extrathyroidal parathyroid gland. From 1990-2023, 808 patients were operated on for primary hyperparathyroidism; 17 (2%) patients had an intrathyroidal parathyroid gland, an adenoma in 15 (88.2%), and a hyperplastic gland in 2(11.8%). The mean age was 53 years; 16 (94%) patients were female. Mean calcium and parathyroid hormone was 12 mg/dL and 150 pg/mL, and there were no differences from the extrathyroidal parathyroid group. Ultrasound and Sestamibi imaging were valuable in identifying an intrathyroidal parathyroid gland in 10 of 13 patients and 13 of 17 patients, respectively. Local excision was performed in 9(53%) patients and lobectomy in 8 (47%) patients. Intraoperative parathyroid hormone was measured and predictive of cure in 12 patients. The location of intrathyroidal parathyroid glands was determined in 15 patients and was inferior in 11 (73%). All patients were cured. No patient developed recurrent disease after a median 54-month follow-up. Intrathyroidal parathyroid glands are the cause of primary hyperparathyroidism in 2% of patients and are most often inferior glands. Local excision was accomplished in 53% of our patients.

SAT207 Parathyroid Carcinoma: A Case Report

Abstract Disclosure: K.T. Sy: None. Background: Parathyroid carcinoma is a rare malignancy, accounting for less than 1% of causes of primary hyperparathyroidism. Case reports have mentioned of parathyroid carcinoma arising in patients with prior neck irradiation, in secondary and tertiary hyperparathyroidism and in patients with history of thyroid cancer and parathyroid adenoma. However, none of these reported associations have been completely established. Clinical Case: The is a case of a 59-year old male presenting with hypercalcemia. He was diagnosed with primary hyperparathyroidism secondary to a parathyroid adenoma, underwent parathyroidectomy with resolution of the hypercalcemia. Six years later, patient had recurrence of hypercalcemia with elevated PTH levels. Parathyroid imaging revealed a mild sestamibi-avid focus in the left retrosternal region, suggestive of an ectopic parathyroid gland and radio-guided neck exploration was done with excision of lesion. Histopathological report revealed parathyroid carcinoma. Two years later, there was recurrence of parathyroid carcinoma but mediastinal exploration revealed no lesions consistent with parathyroid carcinoma. Hypercalcemia with hyperparathyroidism persisted, and cinacalet was started but the patient could not tolerate the nausea associated with the medication. Repeat parathyroid imaging revealed sestamibi-avid lesions in the right retroclavicular, left prevascular/retrosternal, and a left paratracheal areas. Surgical exploration was offered but the patient refused. The patient also developed hypertension and low bone density was noted on dual X-ray absorptiometry (DXA) scan. He was started on denosumab 60 mg subcutaneously every 6 months, which was increased to 60mg every month and then 120mg every month to maintain normal calcium levels. The patient also developed chronic kidney disease, eventually requiring hemodialysis for elevated creatinine levels and hypercalcemic crisis. Soon after hemodialysis was started, the patient had a myocardial infarction and eventually expired. Conclusion: Complete surgical resection is the primary mode of therapy in parathyroid carcinoma, although hypercalcemia is the main cause of morbidity and mortality, rather than the tumor burden. The adjuvant use of radiotherapy and chemotherapy are still controversial. Some studies have shown that long term survival is favorable, but recurrences are frequent and patients tend to live a life filled with long-term follow up, multiple laboratory exams and imaging, hospitalizations and frequent reoperations. Mortality is usually due to uncontrollable hypercalcemia, leading to renal failure and cardiac arrhythmias. Presentation: Saturday, June 17, 2023

SAT186 Young Patient With Primary Hyperparathyroidism And Mutation Of CDKN1B Gene MEN 4 Variant

Abstract Disclosure: J.J. Faria Briceno: None. S.S. Jande: None. T. Lairmore: None. R.R. Yatavelli: None. Background: Parathyroid adenomas are the most common cause of primary hyperparathyroidism (PHPT)accounting for 80-85% of the cases. PHPT most commonly manifests between 50-60 years of age and when it presents at younger age, it can be associated with inherited genetic conditions like multiple endocrine neoplasia or Hyperparathyroid Jaw tumor syndrome. Clinical Case: A 34-year-old male without significant past medical history was noted to have elevated serum calcium on routine lab work and was advised to promptly go to the emergency room for further evaluation. In the ED, the patient’s corrected calcium was 13.8 mg/dL (normal range 8.7 - 10.5 mg/dL), ionized calcium elevated at 1.77 mmol/L (normal range 0.90 - 1.20 mmol/L), PTH was 786.2 pg/mL (normal range 9 - 77 pg/mL). The patient denied any history of fractures, kidney stones or bone pain. Patient was treated medically with IV fluids and calcium lowering agents. Given the elevated PTH, ultrasonography of the neck was done which revealed an oval, hypoechoic lesion measuring 1.2 x 2.25 cm with increased vascular flow posterior to the right thyroid lobe consistent with parathyroid adenoma. Parathyroidectomy was performed with excision of right inferior parathyroid adenoma measuring 2.7 x 1.2 x 0.6 cm (1.25 grams). The preoperative PTH level was 997.7 pg/mL, which rapidly improved 20 minutes post tumor excision to 75.9 pg/mL, a 90% fall in PTH level suggestive of successful tumor excision. The patient’s post-operative period was uneventful. Considering the very young age of presentation; hyperparathyroidism genetic panel was obtained to rule out any inherited conditions like MEN1 or Hyperparathyroid Jaw tumor syndrome. Genetic testing revealed a germline missense mutation in CKDN1B (variant c.287C &gt, heterozygous) and classified as Variant of Uncertain significance). Mutations in the cyclic dependence kinase inhibitor 1B (CDKN1B) have been identified as the culprit for tumor growth seen in multiple endocrine neoplasia 4. MEN4 is a rare autosomal dominant endocrine tumor syndrome characterized by hyperparathyroidism and pituitary adenomas. The variant described in our patient has classically not been associated with other tumors and the available evidence is currently insufficient to determine the role of this variant in disease and hence classified as Variant of Uncertain Significance. Conclusion: Genetic testing should be considered in patients with primary hyperparathyroidism who present at very young age or have multiglandular disease. Our patient does not have any other classic features of MEN 4 and as the genetic mutation is classified as Variant of Uncertain Significance, patient would be monitored clinically, and caution exercised before using this result to inform clinical management decisions. Presentation: Saturday, June 17, 2023

FRI692 Severe Hyperparathyroidism And Nephrolithiasis In An Adolescent Male Due To CDC73 Positive Parathyroid Carcinoma

Abstract Disclosure: J.T. Nguyen: None. D.H. Geller: None. A. Ryabets-Lienhard: None. Introduction: Parathyroid carcinoma is a rare cause of primary hyperparathyroidism in the pediatric population, with only 20 previously reported cases. Variations in the CDC73 gene have been associated with sporadic parathyroid carcinoma, autosomal dominant hyperparathyroidism-jaw tumor syndrome (HPT-JT), and familial isolated hyperparathyroidism (FIHP). To our knowledge, only 3 cases of pediatric parathyroid carcinoma with confirmed variants of CDC73 have been reported. We present a case of severe hyperparathyroidism and nephrolithiasis due to parathyroid carcinoma caused by a pathogenic variant in CDC73 in a pediatric patient, highlighting the importance of early recognition and management. Clinical Case: An otherwise asymptomatic 14-year-old male presented with one year of recurrent nephrolithiasis. Initial tests demonstrated hypercalcemia (13.8 mg/dL, 8.4-10.2 mg/dL), normal phosphorous, elevated PTH (1,379 pg/mL, 7.5-53.5 pg/mL), and elevated alkaline phosphatase (514 U/L, 30-250 U/L). The hypercalcemia was treated with hyperhydration, furosemide, and pamidronate. Sestamibi scan revealed a focus of abnormal uptake suggestive of a left parathyroid mass, with ultrasonographic demonstration of a predominantly solid, hypoechoic, and vascular mass centered posterior to the inferior left thyroid lobe. Skeletal survey was notable for trabecular abnormalities and osteopenia. He underwent a left parathyroid mass excision. Final pathology confirmed the parathyroid carcinoma, with multiple foci of vascular invasion without evidence of capsular involvement. Immunohistochemistry demonstrated diffuse positivity for PTH and loss of parafibromin expression by the tumor cells. Genetic testing revealed a pathogenic germline heterozygous nonsense variant in CDC73 (c.376C>T(p.Arg126Ter)) resulting in protein truncation. Post-operative PTH was undetectable with normal calcium and phosphorous. Calcitriol, cholecalciferol, and calcium carbonate supplementation were implemented to prevent further hypocalcemia due to transient hypoparathyroidism and hungry bone syndrome. Calcium supplementation was discontinued within one year of his surgery. Serial thyroid ultrasounds and CT scans have been negative for recurrent or residual disease without evidence of metastasis. Mandibular x-ray showed no evidence of tumors or lesions involving the jaw. He has been noted to have small right renal cysts without other kidney abnormalities. Conclusion: Severe hyperparathyroidism due to parathyroid carcinoma can present as recurrent nephrolithiasis in an otherwise asymptomatic individual. Pediatric patients with a longstanding history of kidney stones should undergo screening for hypercalcemia and hyperparathyroidism even in the absence of other signs and symptoms of elevated calcium to ensure timely diagnosis and appropriate management. Presentation: Friday, June 16, 2023

SAT203 Parathyroid Adenoma Masquerading As Parathyroid Carcinoma

Abstract Disclosure: M. Fariduddin: None. A. Lupieri: None. H.L. Calero: None. A. Rubenfeld: None. Y. Eisenberg: None. Case: 22 y/o pregnant female (5 weeks gestation) presented to the endocrinology clinic after a hospital admission for nausea, vomiting, constipation, fatigue and joint pain with labs showing calcium (corrected) of 14 mg/dL and PTH of 1200 pg/ml. Labs in the clinic showed calcium at 16 mg/dL and PTH 1500 pg/ml. She was re-admitted for IV fluids, calcitonin and zoledronic acid. Severe hypercalcemia, young age, and extremely high PTH levels were highly suggestive of parathyroid cancer. CT of neck showed a 2 cm right inferior parathyroid mass abutting the esophagus with concern for esophageal invasion with no evident plane between the mass and the esophagus. No cervical adenopathy was noted. Patient in conjunction with her obstetrician made an informed decision to terminate the pregnancy as this was an undesired pregnancy. She underwent an urgent right inferior gland parathyroidectomy. The mass was not fixed to underlying structures and was resected in-toto. Pathology showed chief cells with clear cytoplasm, and homogeneously round nuclei. There were no atypical mitoses, lymphovascular invasion, perineural invasion, or other invasive features concluding the final pathology as parathyroid adenoma. Discussion: Primary hyperparathyroidism predominantly affects postmenopausal women. Most common cause is parathyroid adenoma (80-85%). Parathyroid carcinoma is a rare cause of primary hyperparathyroidism (1-2%).80% people with parathyroid adenoma and primary hyperparathyroidism are diagnosed incidentally with mildly elevated calcium. PTH elevation is around 1.5-2 times the upper limit of normal. Symptoms are mild sequelae of hypercalcemia. PTH levels 5-10 times upper limit of normal, severe hypercalcemia (Ca > 14 mg/dl) or a hypercalcemia crisis are highly suspicious for parathyroid cancer. Surgical resection is the mainstay of treatment. Clinical criteria play a key role in early identification of parathyroid carcinoma in order to get these patients to surgery before tumor spread and improve long term survival. Our patient with significantly elevated calcium and parathyroid hormone had an atypical presentation of a parathyroid adenoma thus uncovering the limitations of clinical criteria in identifying a parathyroid carcinoma. Most of the patients with a parathyroid adenoma will eventually require surgery, however the technique, extent and urgency of surgery is affected based on clinical situations like these. The timing of the surgery could be detrimental when coupled with a scenario like our patient’s pregnancy wherein you could delay the surgery until the second trimester had the patient wanted to continue the pregnancy. This case highlights the importance of awareness of atypical presentations of parathyroid adenomas and to have a cautious approach in patients with clinical concern for parathyroid carcinoma especially if there is a potential benefit to delay surgery. Presentation: Saturday, June 17, 2023

Mediastinal parathyroid carcinoma: a case report and review of the literature

BackgroundParathyroid carcinoma (PC) is an uncommon cause of primary hyperparathyroidism (PHPT) and particularly rare in the mediastinum. Herein, we present a case of mediastinal PC and conduct a related literature review.Case presentationWe described a case of a 50-year-old female patient with PHPT due to mediastinal PC. She was initially admitted to a local hospital in her hometown with hypercalcemia and high blood concentrations of PTH (parathyroid hormone). The patient underwent neck parathyroidectomy and pathological examination suggested parathyroid adenoma. Although the overproduction of serum calcium and PTH declined after the surgery, calcium and PTH increased again one month later, so the patient was transferred to our hospital. A 99mTc-sestamibi scan revealed an ectopic finding in the mediastinum, which was also indicated on the CT image. After removing the mediastinal mass, the metabolism of calcium and PTH quickly reverted to normal and the pathologic features of the mass were consistent with PC. By reviewing the related literature, we noticed that only scattered reports were published before 1982, and those were not included in the present review due to their differences with current radiological examination and treatment methods. After excluding outdated studies, we summarized and analyzed 20 reports of isolated mediastinal PC and concluded that. Parathyroidectomy remains the only curative treatment for the disease. Furthermore, the success of treatment directly depends on accurate preoperative localization.ConclusionWith this study, we emphasize the importance of accurate preoperative diagnosis of mediastinal PC and improve clinicians’ understanding of the disease.

Abstract #1373163: A Rare Case of Ectopic Parathyroid Adenoma in the Left Axillary Region

A parathyroid adenoma is a benign neoplasm that arises from parathyroid parenchymal cells. Parathyroid adenomas are the most common cause of primary hyperparathyroidism (PHPT). Ectopic parathyroid adenomas arise within the parathyroid glands located at the four poles of the thyroid [2]. Ectopic parathyroid adenomas result from aberrant migration of the gland during the early stages of development and can be identified in up to 16% of cases of PHPT [3]. They are commonly found in the mediastinum, within the thyroid, and along the path of the vagus or recurrent laryngeal nerves [4]. 45% of ectopic parathyroid adenomas are found in the paraesophageal region, 25% in the cervical thymus, 20% in the cervical mediastinum, 5% in the anterior portion of the mediastinum, and 5% at the level of the thymus [5]. A 64-year-old man with a past medical history of over 20-year history of recurrent nephrolithiasis, type II diabetes mellitus, dyslipidemia, hypertension, and pancreatic cancer presented to our outpatient endocrine clinic for evaluation of hyperparathyroidism. Further investigation of his history revealed that he had struggled with several bouts of urinary calculi throughout his life. These episodes required multiple surgical interventions to treat, including left nephrectomy and ureteral stenting. He had been evaluated for high serum calcium in the past and was diagnosed with PHPT by his urologist, who referred him to our clinic. Also complicating his health was a recent diagnosis of prostate cancer for which, he was undergoing radiation treatment. He had a family history of thyroid disorder in his mother but no family history of parathyroid disorders. Physical examination was unremarkable. Laboratory investigations revealed high serum calcium and high serum parathyroid hormone. Parathyroid scintigraphy with 99mTc-sestamibi revealed a subtle persistent focal region of increased uptake in the left axilla with no other areas of increased uptake, raising the suspicion for parathyroid adenoma in the left axilla. As discussed earlier, ectopic parathyroid adenomas result from aberrant migration of parathyroid tissue during embryological development. Additionally, ectopic parathyroid adenomas are a cause of failed surgery for hyperparathyroidism as well as persistent and recurrent hyperparathyroidism [3, 7-9]. Ectopic parathyroid tissue has a prevalence of 2-43% in anatomic series and has been detected in up to 16% of patients undergoing evaluation for hyperparathyroidism [3, 7, 10]. Ectopic parathyroid adenomas arising within the axilla may present with hypercalcemia and associated skeletal and renal involvement [11, 12]. The case that has been reported had a presentation of PHPT with recurrent nephrolithiasis. As mentioned earlier, 45% of ectopic parathyroid lesions are found in the paraesophageal region with 38% arising within the thymus [7, 10]. However, in this case, the patient presented with a possible ectopic parathyroid adenoma localized to the left axilla and no other areas of increased uptake on tc99m-sestamibi parathyroid scintigraphy.

Abstract #1398160: A Rare Case of Water Clear Cell Parathyroid Adenoma Escaping Sestamibi Scan and Neck Ultrasound – A Diagnostic Conundrum of a Rare Pathological Intity with a Rare Presentation

Parathyroid water-clear cell hyperplasia (WCCH) and water-clear cell adenoma (WCCA) are extremely rare causes of primary hyperparathyroidism (PHPT). WCCH contributes to < 1% of all PHPT however WCCA is exceptionally rare and has been reported only in less than 30 case reports. We are presenting a very rare indolent pathological entity with a very rare presentation escaping common diagnostic measures of Sestamibi scan and neck ultrasound. A 63-year-old female presented for evaluation of severe osteoporosis with a T-score of -3.6. Laboratory workup revealed elevated parathyroid hormone (PTH) of 122 pg/ml (reference range 12-88 pg/ml), Normal calcium 9.8 mg/dl, Normal vitamin D 50 ng/ml, and normal magnesium 2.2 mg/dl. 24-hour urine calcium was 421 mg/24H. Diagnosis was consistent with normocalcemic PHPT and meeting surgical criteria with osteoporosis and high urine calcium. Sestamibi scan did not identify any focal activity. CT H&N revealed an 8 mm mass inferior and posterior to right thyroid lobe with partial washout and slightly different enhancement compared to thyroid gland. Neck ultrasound (US) reported that previously noted tissue activity on the CT H&N is not visualized and most likely represents normal thyroid tissue. Patient was referred to otolaryngology surgery and underwent four gland explorations, including right inferior and left superior parathyroidectomy. Pathology of superior parathyroid gland revealed parathyroid water clear cell adenoma. 3-month Postoperative PTH 29.4 pg/ml and calcium level of 9.3 mg/dl. Solitary parathyroid adenoma (SPA) attributes to 80-85% of PHPT. Majority of cases is due to Chief cell adenomas, less frequent pathologies include oxyphil cell adenoma, lipoadenoma, WCCA or mixed type. Scientific literature regarding WCCA presentation and diagnosis is blurred due to its rarity. Clinical presentation of WCCA resembles other etiologies of PHPT, though some data suggest that is frequently indolent and manifests with mild PHPT. Literature suggests that WCCA has low biochemical activity and most cases had normal to mildly elevated calcium-our patient support this hypothesis-. Hypercalcemia does not manifest until significant growth of the adenoma, though few reported cases manifested with hypercalcemia. Unlike other SPA where Sestamibi scan sensitivity is 91%, literature suggests possibility of false-negative results with WCCA which is hypothesized to be attributed to its different histology of glycogen-rich vacuolized cytoplasm that leads to fast Sestamibi wash-out, for the same reason data suggest that US is more decisive given high water content of cells -Our patient didn’t follow this rule and escaped Sistamibi and US though seen on CT- which still makes the diagnosis of WCCA a conundrum. Some cases underwent surgical excision based on clinical diagnosis which led to revision of PHPT and/or hypercalcemia. There is no available data suggesting different long-term follow-up regimens for WCCA compared to other SPA. Further literature with longer follow-up is needed for this extremely rare entity for a comprehensive understanding of its natural course.

Endocrinological cause behind recurrent miscarriages: primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a common endocrinological pathology; nonetheless, it is rarely diagnosed in pregnancy. Primary hyperparathyroidism can present with clinically expressed hypercalcemia. High Ca levels in the blood may lead to a miscarriage. We present the case of a 39-year-old woman who visited our Endocrinology clinic in search of a cause of infertility. Blood work showed elevated Ca and parathyroid hormone (PTH) levels. Upper left parathyroid gland adenoma was found during a neck ultrasound. Parathyroid gland adenoma was likely the cause of PHPT and was treated with parathyroidectomy. Surgery was carried out, and the upper left parathyroid lobe adenoma was removed. High levels of Ca were found in all performed blood works since the first visit to the clinic, but following the surgery, Ca levels of the patient were in the normal range and the woman got pregnant for the third time, later delivering a healthy baby. In conclusion, we would like to put forward the idea that an evaluation of Ca level in the blood should be included in the protocol for treating patients with recurrent miscarriages. Early detection of hypercalcemia can improve the outcomes of disease that primary hyperparathyroidism can cause. Swift and accurate decrease of serum Ca correspondingly safeguards the woman from a possible pregnancy loss along with complications that arise from it. Primary hyperparathyroidism (PHPT) is a common endocrinological pathology, nonetheless, it is rarely diagnosed in pregnancy. Primary hyperparathyroidism can present with clinically expressed hypercalcemia, and high Ca levels in the blood may lead to a miscarriage. Early detection of hypercalcemia can improve the outcomes of disease that primary hyperparathyroidism can cause. Swift and accurate decrease of serum Ca correspondingly safeguards the woman from a possible pregnancy loss along with complications that arise from it. All pregnant patients with hypercalcemia should be assessed for the presence of primary hyperparathyroidism as it is likely the cause.

Molecular and Clinical Spectrum of Primary Hyperparathyroidism.

Recent data suggest an increase in the overall incidence of parathyroid disorders with primary hyperparathyroidism (PHPT) being the most prevalent parathyroid disorder. PHPT is associated with morbidities (fractures, kidney stones, chronic kidney disease) and increased risk of death. The symptoms of PHPT can be non-specific, potentially delaying the diagnosis. Approximately 15% of patients with PHPT have an underlying heritable form of PHPT which may be associated with extra-parathyroidal manifestations, requiring active surveillance for these manifestations as seen in multiple endocrine neoplasia type 1 and 2A. Genetic testing for heritable forms should be offered to patients with multi-glandular disease, recurrent PHPT, young onset PHPT (age ≤ 40 years) and those with a family history of parathyroid tumors. However, the underlying genetic cause of majority of patients with heritable forms of PHPT remains unknown. Distinction between sporadic and heritable forms of PHPT is useful in surgical planning for parathyroidectomy and has implications for family. The genes currently known to be associated with heritable forms of PHPT account for approximately half of the sporadic parathyroid tumors. But the genetic cause in approximately half of the sporadic parathyroid tumors remains unknown. Furthermore, there is no systemic therapy for parathyroid carcinoma, a rare but potentially fatal cause of PHPT. Improved understanding of the molecular characteristics of parathyroid tumors will allow us to identify biomarkers for diagnosis and novel targets for therapy.

Parathyroid Carcinoma: Case Report and Literature Review

Parathyroid carcinoma is a malignant tumor derived from the parenchymal cells of the parathyroid glands. It represents one of the less frequent causes of primary hyperparathyroidism, with an incidence of 0.36 per 10 million people. Knowledge about the history of the disease and prognostic factors is currently limited. It should be suspected in a patient with marked hypercalcemia and very high parathyroid hormone (PTH), with a large tumor, and with bone and kidney repercussions that should be evaluated initially.

A rare case of intrathyroidal cystic parathyroid adenoma

Cystic parathyroid adenomas are rare causes of primary hyperparathyroidism, representing about 1–2% of cases.1 Even rarer are cystic ectopic intrathyroidal parathyroid adenomas, with only eight cases in reported literature.1 Due to its rarity, it is rarely considered as a differential diagnosis on imaging, fine needle aspiration and macroscopic examination of the thyroid. We report a case for a 79-year-old female patient who presented with primary hyperparathyroidism and left thyroid nodule. The patient initially underwent fine needle aspiration for the nodule which was designated a Bethesda Category 3 result.

Main parathyroid tumors

Primary hyperparathyroidism is the third most common disease of the endocrine system. It is characterized by an increase in parathyroid hormone, hypercalcemia, hypercalciuria, hypophosphatemia. Symptoms include polyuria, bone pain, weakness, and constipation. In most cases, primary hyperparathyroidism is caused by solitary parathyroid adenoma — 85%. Other causes include hyperplasia (5%), multiple adenomas (&lt;5%), and cancer (&lt;1%). However, particular attention in this article is paid to two causes of primary hyperparathyroidism: parathyroid adenoma and cancer, as they are of high interest both from a molecular point of view and from the clinical features of these tumors. In addition, these tumors overlap in their symptoms and signs and the diagnosis is often made only after histological examination. In total, we identified 2700 articles, of which 66 met the inclusion criteria. The 66 included studies were topical for tumor lesions of the parathyroid gland. They were held between 1997 and 2022. This review emphasizes the importance of further research of the molecular features of these diseases and, possibly, targeted treatment options, since, for example, in cancer, even with R0 resection, the risk of recurrence is high. The article also focuses on the issues of the new World Health Organization 2022 classification of tumor lesions of the parathyroid gland, which is also important for a unified study of these tumors.

Parathyroid Carcinoma Mimicking Multiple Myeloma: A Tale of Refractory Hypercalcemia

Primary hyperparathyroidism yields various symptoms, including hypercalcemia, pathological fracture, and renal impairment. Parathyroid carcinoma is the rarest cause of primary hyperparathyroidism, accounting for <1% of the cases. We reported a case of a 46-year-old male with closed fractures at the humerus and femur. Further findings revealed severe refractory hypercalcemia, renal impairment, anemia, and bone lytic lesion (CRAB). No palpable cervical mass was identified. Surprisingly, the serum protein electrophoresis was normal, and urinary Bence-Jones protein was negative along with normal bone marrow aspiration. Hence, multiple myeloma was unlikely. The intact parathyroid hormone level was very high, along with a suspicious nodule on the left thyroid lobe (TIRADS 4). Total thyroidectomy and total parathyroidectomy were performed. The post-surgical pathological examination confirmed the diagnosis of parathyroid carcinoma. After the surgery, the patient was in stable condition with normal intact parathyroid hormone and serum calcium levels. In this case, primary hyperparathyroidism was caused by parathyroid carcinoma with “CRAB” symptoms, mimicking multiple myeloma. Primary hyperparathyroidism should be considered in the patient with refractory hypercalcemia.

Brown tumor of the mandible - a possible clinical manifestation of primary hyperparathyreoidism

Introduction. One of the possible manifestations of primary hyperparathyroidism (PHPT) is the appearance of a benign bone tumor. We hereby present a case of a young woman whose first clinical manifestation of PHPT was a brown tumor of the mandible. Case report. A 27-year-old female patient was hospitalized at the Clinic for Endocrinology, Diabetes, and Metabolic Diseases due to problems occurring in the form of nausea, exhaustion, the feeling of suffocation, dysphagia, pain in the right ear and the right half of the cheeks, with suspected PHPT. Initial laboratory findings pointed out the high levels of parathyroid (PT) hormone (PTH) and calcium (Ca2+) ions, low levels of vitamin D, and increased parameters of bone metabolism with signs of osteopenia. Cone beam computed tomography revealed the presence of bilateral radiolucent lesions of the mandible. Scintigraphy verified a retrosternal hot focus consistent with PT adenoma. After parathyroidectomy was performed, there was a normalization of PTH values, bone metabolism parameters, and the Ca2+ values. Four months after parathyroidectomy, a significant regression of the mandibular tumefaction was confirmed, clinically and radiologically. Conclusion. Brown tumors are rare first clinical manifestations of PHPT. Owing to their histological similarities with other giant-cell lesions (GCLs), definitive diagnosis is sometimes difficult and is based on a correlation of pathohistological, radiological, and laboratory findings. Due to the spontaneous regression of bone lesions after treatment of the basic cause of PHPT, brown tumors should be considered in the differential diagnosis of any GCLs in order to avoid unnecessary surgical procedures.

The Role of 4D-CT for Pre-Operative Localization in Patients with Primary Hyperparathyroidism with Negative Ultrasonography and/or Sestamibi SPECT/CT.

The major cause of primary hyperparathyroidism (pHPT) is parathyroid adenoma. Today, minimally invasive parathyroidectomy (MIP) has become the standard treatment for patients in whom the pathological gland can be localized with pre-operative imaging methods. In this study, we aimed to evaluate the role of 4D-CT in pre-operative localization in patients with pHPT who are negative for ultrasonography (USG) and/or sestamibi single-photon emission computed tomography/CT (SPECT/CT) and will undergo primary surgery. Patients whom were operated between 2018 and 2023 were included to this study. 4D-CT results of patients with one- or two-negative USG and SPECT/CT results were evaluated retrospectively. In this study, 19 patients (5 men and 14 women) with a mean age of 57.1±8.5 years were evaluated. Pathology results were consistent with parathyroid adenoma in 18 patients (94.7%) and parathyroid hyperplasia in 1 patient (5.3%). USG was negative in six patients, SPECT/CT was negative in 14 patients, and both were negative in four patients. In 4D-CT, positive images were detected in 15 patients and these results were finalized as true positive in 14 patients and false positive in 1 patient. The sensitivity of 4D-CT was 82.4% (95% CI: 60.4-95.3%), positive predictive value was 93.3% (95% CI: 73.8-99.6%), accuracy was 78.9%, and localization rate was 73.7%. In 14 (73.7%) patients, the pathological glands were removed by MIP. In approximately 75% of patients with negative USG and/or SPECT/CT, the pathological gland can be localized with 4D-CT and MIP can be applied in these patients.