Parathyroid Disorders.

Parathyroid disorders are most often identified incidentally by abnormalities in serum calcium levels when screening for renal or bone disease or other conditions. Parathyroid hormone, which is released by the parathyroid glands primarily in response to low calcium levels, stimulates osteoclastic bone resorption and serum calcium elevation, reduces renal calcium clearance, and stimulates intestinal calcium absorption through synthesis of 1,25-dihydroxyvitamin D. Primary hyperparathyroidism, in which calcium levels are elevated without appropriate suppression of parathyroid hormone levels, is the most common cause of hypercalcemia and is often managed surgically. Indications for parathyroidectomy in primary hyperparathyroidism include presence of symptoms, age 50 years or younger, serum calcium level more than 1 mg per dL above the upper limit of normal, osteoporosis, creatinine clearance less than 60 mL per minute per 1.73 m2, nephrolithiasis, nephrocalcinosis, and hypercalciuria. Secondary hyperparathyroidism is caused by alterations in calcium, phosphate, and vitamin D regulation that result in elevated parathyroid hormone levels. It most commonly occurs with chronic kidney disease and vitamin D deficiency, and less commonly with gastrointestinal conditions that impair calcium absorption. Secondary hyperparathyroidism can be managed with calcium and vitamin D replacement and reduction of high phosphate levels. There is limited evidence for the use of calcimimetics and vitamin D analogues for persistently elevated parathyroid hormone levels. Hypoparathyroidism, which is most commonly caused by iatrogenic surgical destruction of the parathyroid glands, is less common and results in hypocalcemia. Multiple endocrine neoplasia types 1 and 2A are rare familial syndromes that can result in primary hyperparathyroidism and warrant genetic testing of family members, whereas parathyroid cancer is a rare finding in patients with hyperparathyroidism.

The role of thyroid and parathyroid metabolism disorders in the etiology of sudden onset dizziness.

BACKGROUND: The aim of this study was to evaluate thyroid and parathyroid functions as a cause of sudden onset dizziness (SOD) in patients who were admitted to the Emergency Department (ED). MATERIAL AND METHODS: This study was conducted prospectively in 100 patients with sudden onset dizziness (SOD) admitted to the ED. Neurologic, ear-nose-throat, detailed neck examinations, serum calcium levels, thyroid function tests (TFT), and parathormone and thyroid ultrasounds were performed on all patients in our study. RESULTS: Thirty-seven (37%) females and 63 (63%) males were included in this study. Four patients (4%) had elevated serum TSH levels, 6 (6%) had decreased serum fT3 levels, 10 (10%) had decreased serum fT4 levels, 2 (2%) had elevated serum fT4 levels, and 2 (2%) had elevated serum parathormone levels. In 4 (4%) patients, the serum calcium levels were lower than normal, and 2 (50%) of these patients had symptomatic hypocalcemia. Thyroid ultrasound examinations showed multinodular goiter in 28 (28%) patients, 2 (2%) patients had thyroiditis, 12 (12%) had an isolated unilateral nodule, and 58 (58%) had normal thyroid tissues. CONCLUSIONS: We suggest that detailed neck examination, TFT, and thyroid ultrasound examination should be considered in the diagnostic algorithms of SOD to provide rapid diagnosis and proper treatment for a patient in the ED.

[A case of idiopathic neck bleeding from a parathyroid cyst].

Bleeding from parathyroid cysts is rare. The retropharyngeal space has a very soft structure and if bleeding spreads to this space, airway obstruction can easily occur. We report on a 50-year-old female case with idiopathic neck bleeding from a left parathyroid cyst without any episode of injury. The patient complained of neck swelling after exercise and went to a nearby hospital. At the hospital, the doctor thought this swelling was caused by retropharyngeal bleeding from a tumor behind the left thyroid gland. Embolization of the left thyroid artery was performed. However, the next day, airway obstruction.was occurred and she was brought to our hospital. An emergency operation was performed to open the left neck swelling region. The operation findings and pathological examination showed that the bleeding was caused by a parathyroid cyst and airway obstruction had occurred because of retropharyngeal edema. In this case, the bleeding may have been caused by torsion of the neck when the patient exercised. The retropharyngeal edema probably resulted from the delay of delivery of the lymphatic and venous return and the arterial embolization. 1 year after the operation, the patient is very well and there has been no recurrence.

[Bilateral neck exploration with intraoperative iPTH assay in patients not eligible for minimally invasive parathyroidectomy]. / Obustronna eksploracja szyi ze sródoperacyjnym monitoringiem stezenia parathormonu u chorych niekwalifikujacych sie do maloinwazyjnej paratyreoidektomii.

BACKGROUND AND AIMS: Bilateral neck exploration (BNE) is the preferred surgical technique in patients with primary hyperparathyroidism (pHPT) not eligible for minimally invasive parathyroidectomy (MIP). The aim of this study was to assess indications for BNE in the era of MIP, including short-term outcomes of surgery with intraoperative intact parathyroid hormone (iPTH) monitoring added-value. METHODS: Data of 155 patients with pHPT qualified for BNE with intraoperative iPTH monitoring and treated in 2003-2012 were retrospectively analysed. All patients underwent biochemical and imaging testing in the preoperative work-up. The following endpoints were analysed in this study: indications for BNE, short-term outcomes of surgery, and intraoperative iPTH monitoring added-value. RESULTS: Indications for BNE were: negative preoperative imaging in 65 (41.9%) patients, concomitant goitre necessitating surgical removal in 51 (32.9%) patients, MEN 1 syndrome in 17 (11.0%) patients, lithium treatment in 12 (7.7%) patients, lacking consent for MIP in 5 (3.2%) patients, and MEN 2A syndrome in 5 (3.2%) patients. The extent of parathyroidectomy was a solitary parathyroid adenoma removal in 97 (62,6%) patients, subtotal parathyroidectomy in 41 (26.4%) patients, and double-parathyroid adenoma removal in 17 (11,0%) patients. Use of intraoperative iPTH monitoring influenced on the extent of parathyroid tissue resection in 16(10.3%) patients. Normalised total serum calcium values were observed in 154 (99.4%) patients during a 6-month follow-up. CONCLUSIONS: BNE in patients with pHPT is the preferred surgical technique in the following circumstances: a suspicion of multiglandular parathyroid disease (MEN 1 or 2A syndrome, familial hyperparathyroidism, lithium therapy), a negative preoperative imaging, in patients not consenting for MIP, and in cases with concomitant goitre necessitating surgical treatment. Use of intraoperative iPTH monitoring influences on the extent of parathyroid tissue resection in one often patients, hence assuring the highest quality of surgical treatment.

Approach to the Patient: Management of Parathyroid Diseases Across Pregnancy.

Taking care of patients with parathyroid disorders during pregnancy requires consideration of the physiological fundamental changes in bone and mineral metabolism occurring in these women. Diagnostic and therapeutic procedures regarding primary hyperparathyroidism (PHPT) and hypoparathyroidism significantly differ from the nonpregnant population. PHPT should preferably be cured by parathyroidectomy before pregnancy since in women with hypercalcemic PHPT, maternal and fetal pregnancy complications seem to increase according to the degree of hypercalcemia. Parathyroidectomy, if needed during pregnancy, is preferentially performed in the second trimester. Conservative treatment is recommended for milder cases and is mainly restricted to hydration, with only limited evidence regarding drug treatment. Women with hypoparathyroidism can be informed that there are no major concerns regarding disease-associated infertility and that the risk of pregnancy complications is low if the disease is properly managed. Regular active surveillance is recommended, as requirements for calcium and active vitamin D may change during the course of pregnancy in either direction, with an overall trend for rather reduced doses. Any woman suffering from parathyroid disorders during pregnancy requires further surveillance in the postpartum period and during lactation, as there is an increased risk of hypercalcemia after delivery. Newborns of mothers with parathyroid diseases should, depending on disease severity, be carefully monitored for calcium levels in the first days (to weeks) after delivery since intrauterine exposure to hyper- or hypocalcemia may impact their postnatal regulation of calcium metabolism.

[The role of calcium sensitive and vitamin D receptors in the pathogenesis of sporadic multiple parathyroid gland disease].

BACKGROUND: Sporadic multiple parathyroid gland disease is » cases of primary hyperparathyroidism (PHPT). However, a single tactic for diagnosing and operating volume in patients with this variant of PHPT has not yet been developed. One of the possible directions in the search for pathogenetically substantiated methods of diagnosis and treatment is the study of the molecular genetic features of the disease and associated clinical and laboratory factors. AIM: To study the features of the expression of calcium sensitive (CaSR) and vitamin D (VDR) receptors on the surface of parathyroid cells in primary hyperparathyroidism with solitary and multiple lesions of the parathyroid glands, as well as its changes under the influence of a decrease in the filtration function of the kidneys. MATERIALS AND METHODS: In a single center observational prospective study with retrospective data collection, there were patients who during 2019-2021. operated on for PHPT, secondary hyperparathyroidism (SHPT) and all cases of tertiary hyperparathyroidism (THPT) operated during 2014-2021. The expression of CaSR, VDR and its relationship with the main laboratory parameters, the clinical variant of hyperparathyroidism, and the morphological substrate were studied. RESULTS: The study included 69 patients: 19 with multiple and 25 with solitary PTG near PHPT, 15 with SHPT, 10 with THPT. A statistically significant decrease in the frequency of detection of normal expression of CaSR and VDR receptors occurs in any morphological variant of hyperparathyroidism and is observed in 93-60% of drugs. A decrease in the normal expression of CaSR in hyperplasia is detected statistically significantly less frequently than in adenoma (p≤0.01). The median expression intensity in adenoma was 2.5 (2:3), in hyperplasia 3.5 (3-4) (p≤0.01). The difference in the molecular mechanisms of the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma (PHPT with solitary adenoma) or hyperplasia (SHPT and PHPT with multiple PTG lesions) is realized in the frequency of maintaining normal CaSR expression in the PTG tissue. These mechanisms are implemented at the local level, their variability does not change under the influence of RRT. A common molecular genetic mechanism for the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma or hyperplasia has been found to reduce the frequency of maintaining normal VDR expression in PTG (up to 7-13%), p<0.01. This mechanism is implemented at the local level, its variability changes under the influence of RRT, reaching statistically significant differences in patients with THPT. CONCLUSION: The study demonstrates the features of changes in the expression of CaSR and VDR in PHPT with multiple lesions of the parathyroid glands. The relationship between the expression of these receptors and the clinical variant of hyperparathyroidism, the morphological substrate, the main laboratory parameters, and renal function was shown.

Auditory-perceptual voice characteristics in pre-operative patients undergoing thyroid or parathyroid surgery.

OBJECTIVES: To systematically evaluate auditory perceptual voice characteristics in people with thyroid disease prior to undergoing thyroid surgery. PATIENTS AND METHODS: This study examined the auditory perceptual voice characteristics of 96 individuals with thyroid disease. Participants were categorised by type of thyroid disease (i.e. multinodular goitre, thyroid cancer, thyroid nodule, toxicity or parathyroidism) and by status of compression (i.e. compression versus no compression). Auditory perceptual voice ratings were made on samples of connected speech by using the Perceptual Voice Profile. RESULTS: A high prevalence of participants had deviant auditory perceptual voice features; however, the majority of these abnormalities were slight to mild in severity and only 8% of participants had a clinically significant auditory perceptual abnormality. There was no significant difference in features between diagnostic categories, and only high pitch was rated as more significantly deviant in patients without compression versus those with compression. CONCLUSIONS: This study supports the need for auditory-perceptual ratings to be included as part of pre-operative multidimensional assessment of voice in patients with thyroid disease.

[Parathyroid dysfunction and rheumatic manifestations]. / Nebenschilddrüse und Rheumatologische Manifestationen.

Parathyroid dysfunction, leading to severe clinical symptoms and radiographic changes, has decreased over the last years due to routine laboratory checks including serum calcium levels. Thus, abnormal calcium levels are detected early in the course of the disease and the underlying cause treated accordingly. Hyperparathyroidism often leads to osteoporosis and low-trauma fractures. When evaluating secondary osteoporosis analysis of calcium, phosphate and intact parathyroid hormone levels are mandatory. Osteitis fibrosa cystica and brown tumors are less frequent findings of hyperparathyroidism. However, in patients with arthritis or bone symptoms, hyperparathyroidism has to be evaluated as a possible reason. Other manifestations of hyperparathyroidism include myopathy, tendon ruptures and unspecific symptoms of the muscles and skeleton. Gout as well as pseudogout may be associated with hyperparathyroidism. Hypoparathyroidism may cause musculoskeletal diseases mimicking ankylosing spondylitis or diffuse idiopathic skeletal hyperostosis. Myopathies are sometimes induced by hypoparathyroidism. An association between systemic lupus erythematosus and hypoparathyroidism seems to exist.

Cardiovascular consequences of parathyroid disorders in adults.

PTH is a metabolic active hormone primarily regulating calcium and phosphate homeostasis in a very tight and short term-manner. Parathyroid disorders in adult patients reflect a variety of different conditions related either to the parathyroid glands itself or to the effects of the secreted hormone. The clinical spectrum varies from the common disease primary hyperparathyroidism (PHPT) to the orphan conditions pseudohypoparathyroidism (Ps-HypoPT) and chronic hypoparathyroidism (HypoPT). The purpose of this review is to describe the consequences of disturbances in levels or action of PTH for cardiac function and cardiovascular risk in adult patients with these disorders. Most patients with PHPT achieve the diagnose by chance and have minor or no specific symptoms. Still, these patients with mild PHPT do possess cardiovascular (CV) morbidity, however so far not proven ameliorated by surgery in controlled trials. In severe cases, the CV risk is increased and with a potential reversibility by treatment. Patients with Ps-HypoPT have resistance to PTH action, but not necessarily total resistance in all tissues. So far, no clear CV morbidity or risk has been demonstrated, but there are several aspects of interest for further studies. Most patients with HypoPT do get their hormonal deficiency syndrome following neck surgery. These patients do experience multiple symptoms and do have an increased CV-risk before the primary surgery. Based on existing data, their CV mortality do not deviate from the expected when adjusting for the preexisting increased risk. Patients with nonsurgical (NS-) HypoPT do demonstrate increased CV-risk also associated with exposure time. Endocrine disorders with alterations in PTH function have major impact on the cardiovascular system of importance for morbidity and mortality, wherefore management of these specific diseases should be optimized currently, as new data become available, however also avoiding over-treating asymptomatic patients.

Is extensive surgery really necessary in patients with parathyroid carcinoma? Single-centre experience and a brief review of the literature.

AIM: Parathyroid carcinoma (PC) represents a rare cause of primary hyperparathyroidism (PHPT). In this paper, among patients who underwent surgery for PHPT, we compared those with benign parathyroid disease with those affected by PC in terms of demographic and preoperative biochemical features. Moreover, we singularly described all 10 cases of PC treated at our Institution (including a case that occurred in a patient with tertiary hyperparathyroidism) and a brief review of the literature. MATERIAL AND METHODS: Patients undergoing surgery for PHPT in our Unit between 2003 and 2018 were retrospectively analysed. They were divided into two groups: Group A (benign parathyroid disease), Group B (PC). The case of PC that occurred in the patient with tertiary hyperparathyroidism was not included into the two groups. RESULTS: Three hundred and eight patients were included: 299 in Group A and 9 in Group B. The mean preoperative serum PTH value and mean preoperative serum calcium level were significantly higher in Group B than in Group A (P = 0.018, P = 0.027; respectively). Including the case of PC that occurred in the patient with tertiary hyperparathyroidism, 10 patients with PC were treated at our Institution. Among these, 3 underwent a re-exploration. Disease recurrence occurred in 1 (10%) patient, who developed a local recurrence and distant metastases. CONCLUSIONS: In the presence of PHPT characterized by particularly high preoperative levels of serum PTH and calcium this malignancy should be suspected. On the basis of our experience, we believe that extensive surgery is not always necessary. KEY WORDS: Hyperparathyroidism, Parathyroid carcinoma, Parathyroid surgery.

Sarcoid granulomas in the parathyroid gland - a case of dual pathology: hypercalcaemia due to a parathyroid adenoma and coexistent sarcoidosis with granulomas located within the parathyroid adenoma and thyroid gland.

We present a highly unusual and interesting case of coexistent hyperparathyroidism and sarcoidosis leading to hypercalcaemia. A 70 year old female presented with weight loss, constipation and dehydration. Investigations revealed marked hypercalcaemia with a non-suppressed PTH. In view of the degree of hypercalcaemia as well as the unintentional weight loss, investigations for malignancy were conducted -these were negative. Parathyroid imaging was then requested and an adenoma was identified. Surprisingly, surgery revealed the coexistence of a parathyroid adenoma with the unexpected finding of sarcoid granulomas within the parathyroid and thyroid glands. To our knowledge, this is the first such case reported. Further imaging confirmed pulmonary sarcoidosis and a serum ACE was elevated. Serum calcium levels did not respond to parathyroidectomy but eventually fell with steroid therapy.

Orbital involvement in craniofacial brown tumors.

PURPOSE: To describe the clinical and radiologic features of orbital involvement in craniofacial brown tumors and to compare the rate of brown tumors in primary and secondary hyperparathyroidism. METHODS: A retrospective hospital-based study of 115 patients with chronic kidney disease and secondary hyperparathyroidism and 34 with primary hyperparathyroidism was conducted. Laboratory results such as serum levels of alkaline phosphatase, calcium, phosphorus, and parathyroid hormone were recorded. Demographic data (age, sex, duration of disease) and image findings (bone scan scintigraphy, skull and long bone x-rays, CT) were also obtained. The main outcome measures were analysis of clinical, biochemical, and radiologic findings of all patients. RESULTS: Of the 115 patients with chronic kidney disease, 10 (8.7%) had brown tumors in different bones of the skeleton. Five patients had lesions in the craniofacial bones. The maxilla, mandible, maxillary sinus, and nasal cavity were the most affected sites. The orbit was involved in 2 patients with lesions arising in the maxillary and ethmoid sinuses. One patient had facial leontiasis. All patients with brown tumors had extremely high levels of parathyroid hormone (>1,000 pg/ml, normal values 10-69 pg/ml) and alkaline phosphatase (>400 U/l, normal values 65-300 U/l). The mean serum levels of phosphorus and calcium were not abnormal among the patients with brown tumors. Age and time of renal failure were similar for patients with and without brown tumors. Among the patients with primary hyperparathyroidism, only 2 (5.8%) had brown tumors, and in just 1, the lesion was localized in the craniofacial skeleton. A 2-tailed Z test applied to compare the proportion of occurrence of brown tumors in the 2 groups revealed that the difference at the 90% of confidence level was not significant. CONCLUSIONS: Brown tumors are equally found in secondary and primary hyperparathyroidism. Craniofacial brown tumors involve the orbit, usually because of the osteodystrophy process that involves the maxilla and paranasal sinuses. The lesions do not necessarily need to be excised and may regress spontaneously after the control of hyperparathyroidism.

[Association between thyroid and parathyroid diseases]. / Associazione tra patologia tiroidea e paratiroidea.

The association between thyroid and parathyroid diseases is well known in the context of MEN, but we find also in nonsyndromic scenarios. In our study, were considered the latter. Between 2003 and 2008 in our Division of General Surgery 61 patients underwent operation for hyperparathyroidism, 13 for primary, 41 secondary and 7 tertiary. Twenty-six of these patients underwent also total thyroidectomy. 31% of our patients with primary hyperparathyroidism had concomitant thyroid disease. In the literature, in this regard, there is a correspondence between the data of various authors (Keus, Masatsugu). The association between IPT and primary thyroid carcinoma is discussed. Of our 41 patients with secondary IPT, 32% had associated thyroid disease (77% for goitre). The literature shows considerable variability in this direction, depending on geographical areas and methods of diagnosis. The thyroid disease associated with tertiary IPT was in all of our cases benign. The association of thyroid and parathyroid disease is therefore relatively common. It follows therefore the importance of careful preoperative evaluation in patients with hyperparathyroidism, in order to avoid a reoperation on the neck, because of higher complication rate.

Predictors of outcomes following pediatric thyroid and parathyroid surgery.

PURPOSE OF REVIEW: Recent studies have demonstrated racial/ethnic and socioeconomic disparities in adults undergoing thyroidectomy and parathyroidectomy. To date, few studies have examined outcomes in children undergoing cervical endocrine surgery. RECENT FINDINGS: Children undergoing thyroidectomy and parathyroidectomy have higher complication rates than adults undergoing similar procedures. Complication rates appear to be lower when procedures are performed by high-volume surgeons. Access to high-volume surgeons continues to be limited for children of racial/ethnic minorities and in families of a lower socioeconomic status. SUMMARY: Complications following thyroidectomy and parathyroidectomy in children can have profound, life-long effects on development and quality of life. Outcomes are optimized when surgery is performed by high-volume surgeons. Obtaining access to high-volume surgeons requires a multidisciplinary approach by parents, pediatricians, pediatric endocrinologists, and third-party payers.

Advantages of a video-assisted approach to parathyroidectomy.

In recent years the advances in preoperative localization studies, the availability of intraoperative parathyroid hormone (PTH) assay and the introduction of cervicoscopy revolutionized the surgical treatment of primary hyperparathyroidism (PHPT). Several endoscopic and video-assisted techniques for parathyroidectomy have been described. In spite of the enthusiasm manifested by some authors, the role of these techniques with respect to the time-honored conventional surgery have been largely debated. Among them, video-assisted parathyroidectomy (VAP) has emerged as one of the leading and more diffuse techniques. To date many large and comparative studies have shown that VAP is an efficacious and feasible procedure with the same complication rate as conventional surgery. Moreover, VAP seems to have significant advantages in terms of cosmetic results, postoperative pain, recovery, and patient satisfaction. When compared with other minimally invasive techniques, it offers the significant advantages of being more similar to conventional surgery and reproducible in different surgical settings. Moreover, it permits bilateral neck exploration, associated thyroid resections and can be performed under locoregional anesthesia. All these characteristics and the excellent results obtained render VAP a valid and well-validated, and even preferable, alternative to conventional surgery for the surgical treatment of sporadic PHPT, especially in case of suspected single adenoma.

Metachronous thyroglossal duct cyst and inferior parathyroid cyst: a case report.

Thyroglossal duct cysts (TDC) are the most common cervical cysts and are usually considered to be a benign embryonic malformation where the thyroglossal duct fails to obliterate. Parathyroid cysts (PTC) are a rare disease and may also result from malformation of the remnants of the third pharyngeal pouch. Although several sporadic cases of concurrent TDC with other head and neck malformations have been reported in the literature, a combination of TDC and PTC has never been reported. Here, we report the first case of a 35-year-old woman with a metachronous TDC and PTC. The embryologic origins of TDCs and inferior PTCs are revealed from the experience of this case.

Metabolic Syndrome in Parathyroid Diseases.

Parathyroid glands are the main regulator of body mineral metabolism through parathormone (PTH) actions on bone and kidney. Experimental evidence suggests that PTH may have non-classical target organs such as adipose tissue, arterial vascular wall, cardiac muscle cells, and adrenal cortex cells, where it may play a role in controlling body energy, blood pressure, and metabolism. Cardiometabolic features have been investigated in the wide spectrum of clinical parathyroid disorders, from hyperparathyroidism to pseudohypoparathyroidism and hypoparathyroidism. Indeed, in parathyroid disorders, besides altered PTH secretion, impaired serum calcium levels and vitamin D status occur. Both calcium and vitamin D have been shown to regulate metabolism and to be associated with cardiovascular diseases. However, despite the complexity of parathyroid disorders, features of metabolic syndrome, such as obesity, insulin resistance, and glucose intolerance, arterial blood hypertension, and dyslipidemia, are frequently diagnosed in primary and secondary hyperparathyroidism as well as in pseudohyperparathyroidism. Here, we reviewed the most consistent data highlighting challenges and providing clinical remarks.