Complication Of Primary Hyperparathyroidism Research Articles

Italian Guidelines for the Management of Sporadic Primary Hyperparathyroidism.

This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered. This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for the clinical practice recommendations. The present GL provides recommendations about the roles of pharmacological and surgical treatment for the clinical management of sporadic PHPT. Parathyroidectomy is recommended in comparison to surveillance or pharmacologic treatment in any adult (outside of pregnancy) or elderly subject diagnosed with sporadic PHPT who is symptomatic or meets any of the following criteria: • Serum calcium levels >1 mg/dL above the upper limit of normal range. • Urinary calcium levels >4 mg/kg/day. • Osteoporosis disclosed by DXA examination and/or any fragility fracture. • Renal function impairment (eGFR <60 mL/min). • Clinic or silent nephrolithiasis. • Age ≤50 years. Monitoring and treatment of any comorbidity or complication of PHPT at bone, kidney, or cardiovascular level are suggested for patients who do not meet the criteria for surgery or are not operated on for any reason. Sixteen indications for good clinical practice are provided in addition to the recommendations. The present GL is directed to endocrinologists and surgeons - working in hospitals, territorial services or private practice - and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.

Superficial phlebitis: mode of revelation or complication of primary hyperparathyroidism: about 2 cases

Superficial phlebitis: mode of revelation or complication of primary hyperparathyroidism: about 2 cases

Restless leg syndrome as a complication of primary hyperparathyroidism: insights from a retrospective study.

Restless leg syndrome (RLS) is an invalidating neurological disorder with a complex, largely unknown pathophysiology. While RLS is observed in Parkinson's disease and in renal failure, idiopathic cases are common. Limited reports associate RLS with parathyroid hormone (PTH). This study analyzes a cohort of patients with primary hyperparathyroidism (PHPT) and chronic post-surgical hypoparathyroidism (hypo PTH), to investigate RLS prevalence, and associated risk factors. Ninety-five patients (54 PHPT, 41 hypo PTH) were consecutively enrolled at the bone metabolism outpatient clinic. The revised IRLSSG diagnostic criteria were used to diagnose RLS, with assessments conducted through face-to-face interviews and neurological examination. When RLS was confirmed, the RLS severity scale was applied. Retrospective records included calcium-phosphate metabolism-related parameters, surgery details, renal lithiasis, fragility fractures, and densitometric features (T-score). RLS was diagnosed in 22.2% PHPT patients, compared to 4.9% of patients with hypo PTH (p = 0.02). Of RLS diagnosed patients, 91.7% had a history of parathyroidectomy, compared to 47.6% of patients without RLS (p = 0.01). Most of the operated patients reported that surgery determined an improvement of symptoms; however, mean score severity of RLS at our evaluation was 15/40, defined as moderate. PTH and calcium levels were not statistically associated to the presence of RLS. Our study suggests that PHPT may be one of the etiologies of RLS. Parathyroidectomy alleviates symptoms in the vast majority of the cases but does not remove them.

Association of patient-practitioner sex concordance with specialist referral in primary hyperparathyroidism

BackgroundPrior research has demonstrated barriers to the workup and management of primary hyperparathyroidism. As recent data have suggested that patient and practitioner sex concordance is associated with lower surgical complications, we sought to evaluate the effect of sex concordance on referral for primary hyperparathyroidism. MethodsWe queried an institutional database for patients with first-incident hypercalcemia and subsequent biochemical evidence of primary hyperparathyroidism between 2010 and 2018. Primary care practitioner and endocrinologist sex, laboratory values, and complications of primary hyperparathyroidism were collected. Sex concordance (male patient/male practitioner or female patient/female practitioner) was evaluated as a binary predictor of specialist evaluation using logistic regression and Cox proportional hazards modeling. ResultsAmong 1,100 patients, mean age was 62.5 (standard deviation 13.6), and 74% were female sex. Primary care practitioner sex was 52% female, and 63% of patients had sex concordance with their primary care practitioner. Endocrinologist sex was 59% female, and 45% of patients had sex concordance with their endocrinologist. Patients with sex concordance with their primary care practitioner (70 vs 80%, P = .001) and endocrinologist (71 vs 82%, P < .001) were less likely to be female sex compared to those with discordance. After adjusting for demographics and clinical covariates, those patients with primary care practitioner sex concordance had 32% higher odds of endocrinologist evaluation (odds ratio 1.32, 95% confidence interval 1.003–1.734, P = .047). Similarly, those patients with endocrinologist sex concordance had a 48% higher rate of surgeon evaluation (hazard ratio 1.48, confidence interval 1.1–2.0, P = .009). Stratified analysis revealed that sex discordance reduced the rate of surgeon referral for female patients (hazard ratio 0.63, confidence interval 0.44–0.89, P = .008) but not male patients (hazard ratio 1.06, CI 0.58–1.93, P = .861). ConclusionSex discordance between patients and their health care professionals may contribute to under-referral in primary hyperparathyroidism. Further evaluation of the effect of patient and practitioner identities on communication and decision-making in surgery are needed.

Gayet Wernicke's encephalopathy: An exceptional complication of primary hyperparathyroidism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Bone disorders in type 1 multiple endocrine neoplasia syndrome: A review of clinical data

Primary hyperparathyroidism (PHPT) is a result of the parathyroid tumors, usually manifesting by elevated serum parathyroid hormone and hypercalcemia. One of the most common complications of PHPT are bone disorders. It mainly occurs as sporadic disease, while the remaining 5–10% is the component of hereditary syndromes, more often – type 1 multiple endocrine neoplasia syndrome (MEN1). MEN1 is caused by the germinal mutation of the oncosuppressor menin gene, founded in all cells of the human body, including the osteogenic cells. Data on the bone state in MEN1 is limited and contradictory. At the same time, some studies indicate that MEN1-related PHPT differs from sporadic form in bone manifestation, which can be presumably associated with the inadequate functioning of mutant menin. The results of experimental works suggest that menin plays an important role in the metabolism and differentiation of bone cells. This article is a literature review on this problem and contains information on the current clinical data on the bone state in patients with MEN1.

Anemia in primary hyperparathyroidism

Introduction. Anaemia is a complication of primary hyperparathyroidism (PHPT). Pathogenesis of PHPT-induced anaemia involves inhibited erythroid cell proliferation associated with the underlying disease and non-specific factors (blood loss, chronic kidney disease). However, its specific mechanisms remain unclear.Aim. Clinical description of a PHPT case with multifactorial complicating anaemia.Main findings. With putative evidence existing on relationships between PHPT and anaemia, no large clinical trials substantiated suitable algorithms for such patients’ management. The genesis of anaemia reported in this case was multifactorial and not decisively excluding PHPT from putative causes.

Preeclampsia: A Possible Complication of Primary Hyperparathyroidism.

Background. Primary hyperparathyroidism is rare in pregnancy. An association between primary hyperparathyroidism and preeclampsia has been reported in few cases worldwide. Case. A 28-year-old woman (gravida 2, para 0, and abortus 1) in her 27th week of gestation was hospitalized due to a high reading of blood pressure (194/115 mmHg) that was not accompanied by any symptoms or signs of preeclampsia. Incidentally, she was found to have a high adjusted calcium and serum parathyroid hormone (PTH) level during admission. Ultrasonographic examination of the neck revealed the presence of parathyroid adenoma. She was scheduled for surgical excision after receiving an intravenous hydration. Fetal ultrasonography revealed a growth restricted fetus with normal biophysical profile. On the sixth day of hospitalization, the patient complained of headache and epigastric pain, with elevated BP and proteinuria. The fetal nonstress test was “nonreassuring.” Subsequently, she had an emergency cesarean delivery and surgical removal of the adenoma. The mother and her newborn were then transferred to intensive care, where their clinical course was unremarkable. The mother was discharged after 3 days, while the neonate stayed for close observation for 60 days. Conclusion. Early recognition of primary hyperparathyroidism among women with preeclampsia is important to prevent maternal and fetal morbidity and mortality.

Anemia and Thrombocytopenia Improves after Curative Parathyroidectomy in a Patient of Primary Hyperparathyroidism (PHPT)

Hematological manifestations are less known in primary hyperparathyroidism (PHPT). Anemia has been recognized as a complication of PHPT in 5-30% of the individuals in various series. Our objective was to identify hematological improvement after the curative parathyroidectomy in a PHPT patient with anemia and thrombocytopenia. A 30-yr-old female presented with recurrent renal stone disease, anemia, and thrombocytopenia diagnosed as PHPT. Bone marrow examination revealed megakaryocytic thrombocytopenia. Two months after the curative parathyroidectomy, her symptoms and hematological parameters were improved. Our finding showed a causal association of both anemia and thrombocytopenia with marrow fibrosis in a symptomatic PHPT patient because both anemia and thrombocytopenia improved after the curative parathyroidectomy.

Cinacalcet in the management of primary hyperparathyroidism

Parathyroidectomy is currently the only curative treatment for primary hyperparathyroidism (PHPT). There are few alternative treatment options in patients who are ineligible for, or unwilling to undergo, surgery and those in whom parathyroidectomy has failed. Current options include the recently approved drug cinacalcet. Cinacalcet is an allosteric modulator of the calcium-sensing receptor, acting to sensitize this receptor to extracellular calcium. Cinacalcet has been found to be effective in reducing or normalizing serum calcium levels in several groups of PHPT patients, including those with mild-to-moderate PHPT, intractable disease, parathyroid carcinoma and multiple endocrine neoplasia Type 1. Cinacalcet slightly reduces parathyroid hormone levels and has no effect on bone mineral density. Cinacalcet is well tolerated when used at low doses, but side effects are not uncommon when relatively high doses are needed to control hypercalcemia. The current evidence indicates that cinacalcet may be of benefit in a wide spectrum of PHPT severities, offering a novel therapeutic option for the control of hypercalcemia in PHPT patients who are not able to undergo parathyroidectomy. It is presently unknown how much of the biochemical benefit of cinacalcet treatment translates into a clinical benefit, particularly in patients with mild-to-moderate hypercalcemia. Moreover, there are no data as to whether long-term treatment with cinacalcet can prevent the complications of PHPT.

Update on the use of cinacalcet in the management of primary hyperparathyroidism.

Cinacalcet is an allosteric modulator of the calcium sensing receptor acting to sensitize this receptor to the extracellular calcium. Cinacalcet has been shown to be effective in reducing or normalizing serum calcium levels in several groups of patients with primary hyperparathyroidism (PHPT), including patients with mild to moderate PHPT, intractable PHPT, and parathyroid carcinoma, and in PHPT as a part of multiple endocrine neoplasia type 1. Cinacalcet slightly reduces PTH levels and has no effects on bone mineral density. Cinacalcet at low doses is well tolerated, but side effects are more frequent and severe when relatively high doses are needed to control hypercalcemia. Cinacalcet may be of benefit in a wide spectrum of PHPT severity, offering a novel therapeutic option for the control of hypercalcemia in PHPT patients who are not able to undergo parathyroidectomy. To what extent the reduction of serum calcium particularly in patients with mild to moderate hypercalcemia, translates into a clinical benefit is currently unknown. Moreover, there are no data as to whether long-term treatment with cinacalcet can prevent the complications of PHPT. Finally, more data are needed on the long-term safety of cinacalcet, particularly at the renal level.

Management and surgical treatment of parathyroid crisis secondary to parathyroid tumors: report of four cases

Parathyroid crisis, also known as a parathyroid storm, is a rare and serious complication of primary hyperparathyroidism. Four cases are reported here in which patients presented to hospital with general complaints due to hypercalcemia secondary to hyperparathyroidism. Blood test results upon admission showed high levels of serum calcium and parathyroid hormone, and medical treatment initiated to lower the calcium level was ineffective. After relevant investigations, each patient underwent surgical exploration of the parathyroid glands, followed by excision of a pathological parathyroid tumor. There was a prompt decrease in parathyroid hormone level immediately after surgery. Histology reports revealed that patients had parathyroid adenoma. All patients recovered after surgery, with serum calcium levels restored back to normal and with resolution of all symptoms of hypercalcemia. This report illustrates how often this disease is initially misdiagnosed, and how prompt appropriate surgical treatment provides the best outcome for the patient.

Cinacalcet for the Treatment of Primary Hyperparathyroidism

The objective of this article is to review the literature regarding the treatment of primary hyperparathyroidism (PHPT) with a focus on cinacalcet. A MEDLINE (1965-June 2009) and bibliographic search of the English-language literature was conducted using the search terms cinacalcet, calcimimetics, primary hyperparathyroidism, and treatment. All articles identified in the search were included. Parathyroidectomy is curative for patients with PHPT; however, there are few options for patients who are not surgical candidates, who refuse surgery, or those with refractory PHPT after parathyroidectomy. Possible treatment options include estrogens, raloxifene, bisphosphonates, calcitonin, and cinacalcet. Cinacalcet has been shown to decrease serum calcium and parathyroid hormone serum levels in patients with PHPT. These trials, however, have not studied the effect of cinacalcet on patient-oriented outcomes such as bone mineral density, nephrolithiasis, or other complications of PHPT. Cinacalcet may be considered to reduce serum calcium and parathyroid hormone serum levels in patients with PHPT who cannot or will not undergo surgery and those with refractory PHPT after parathyroidectomy. Because the effects of cinacalcet on bone mineral density are uncertain, more frequent monitoring of bone mineral density may be required along with a medication proven to improve bone mineral density. Future studies should evaluate the effect of cinacalcet on complications of PHPT.

Parathyroid crisis as first manifestation of primary hyperparathyroidism

We report the case of a 61-year-old woman who suffered a parathyroid crisis due to a parathyroid adenoma. The patient presented with the typical clinical symptoms of hypercalcemia. Ca + 2 and PTH were markedly increased. Initially, she was treated conservatively until Ca + 2 returned to normal levels. Then, she underwent surgical excision of a newly diagnosed parathyroid adenoma. Parathyroid crisis (PC), also known as parathyroid storm or acute primary hyperparathyroidism, is a rare and serious complication of primary hyperparathyroidism (PH). Fewer than 200 cases have been described in the literature. Prognosis is poor: mortality is 100% in non-operable cases and 20% in cases in which parathyroidectomy is performed. We emphasize the importance of early diagnosis and aggressive treatment.

Mechanism of nephrocalcinosis in primary hyperparathyroidism.

Although nephrocalcinosis is a well-known complication of primary hyperparathyroidism, the mechanism by which calcium is deposited in the kidney is not understood. It is not known, for example, whether nephrocalcinosis is caused by hypercalcemia, hypophosphatemia or the product of calcium x phosphorus in plasma. In man it is not possible to regulate the independent variables that may be involved in the induction of nephrocalcinosis, and chronic animal models simulating primary hyperparathyroidism have not been developed. The present study was performed to examine the individual roles of Ca, P and the Ca x P product as causative factors in the induction of nephrocalcinosis, using an animal model of primary hyperparathyroidism in which each variable could be regulated by experimental design (1).

A Lack of Unique Pathophysiologic Background for Nephrolithiasis of Primary Hyperparathyroidism

The metabolic picture of 32 patients with surgically proven primary hyperparathyroidism presenting with renal stones was compared with that of 37 patients without stones. Between stone-forming and nonstone-forming groups, there was no significant difference in serum 1,25-dihydroxyvitamin D [6.82 ± 2.62 vs. 6.22 ± 2.33 ng/dl (mean ± SD); P > 0.05], fractional (intestinal) calcium absorption (0.726 ± 0.141 vs. 0.690 ± 0.120), urinary clacium (299 ± 139 vs. 284 ± 144 mg/day), serum calcium, phosphorus, and parathyroid hormone, or bone density. Similarly, no differences were found between 29 patients presenting with stones alone and 9 presenting with bone disease alone with respect to the above measures. Moreover, urinary environment was typically supersaturated with respect to stoneforming salts regardless of the presence of stones. The results indicate that there is no unique pathophysiological background for the nephrolithiasis of primary hyperparathyroidism. (J Clin Endocrinol Metab 53: 536,1981) C nephrolithiasis is a frequent complication of primary hyperparathyroidism (1, 2). It is generally recognized that the formation of renal stones is pathogenetically related to the hyperparathyroid state and is not a coincidental occurrence. The most convincing evidence for the existence of this etiological relationship is provided by the favorable response to parathyroid surgery. After successful parathyroidectomy, the new stone formation often ceases, unless there has been a complication by a chronic urinary tract infection. The exact cause of the formation of renal stones in primary hyperparathyroidism has not been elucidated. It has been suggested that the biochemical and clinical picture of patients with primary hyperparathyroidism presenting with nephrolithiasis may be unique from that of patients without stones. Patients with stones were believed to have a longer duration of the disease process, a less severe hypercalcemia, and a smaller size of abnormal parathyroid tissue than patients who present with reduced bone density (3, 4). Hypercalciuria is frequently encountered in stone-forming patients with primary hyperparathyroidism (4,5). This disturbance has often been implicated as one of the causes of renal stone formation, since it is a frequent metabolic derangement associated Received February 9, 1981. Address requests for reprints to: Dr. Charles Y. C. Pak, Department of Internal Medicine, University of Texas Health Science Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235. * This work was supported by USPHS Grants P50-AM20543, R01AM16061, and M01-RR-00633. with calcium nephrolithiasis (6). The hypercalciuria could have resulted from an excessive parathyroid hormone (PTH)-dependent bone resorption and/or an enhanced intestinal absorption of calcium ensuing from the PTH-dependent synthesis of 1,25-dihydroxyvitamin D [1,25-(OH)2D] (7, 8). There is some evidence that the hypercalciuria of intestinal origin may be more critical in the formation of renal stones (9). Thus, an apparent predilection for nephrolithiasis has been reported in the group of patients with primary hyperparathyroidism who possess a high circulating concentration of 1,25-(OH^D (9) and an increased intestinal absorption of calcium (9, 10). The current study was undertaken to determine if the stone-forming patients with primary hyperparathyroidism could be distinguished from their nonstone-forming counterpart on the basis of metabolic and biochemical presentations. It will be shown that the two groups of patients cannot be readily separated from the above criteria. Materials and Methods Sixty-nine patients with primary hyperparathyroidism participated in the study after informed written consent was obtained. These patients represented all of the patients with surgically proven primary hyperparathyroidism who were evaluated by us during the past 7 yr. Before surgery, they underwent an in-patient diagnostic evaluation according to the protocol previously described (5,8). The evaluation permitted an assessment not only of parathyroid function and vitamin D status,

Anemia and Secondary Hyperparathyroidism

Anemia has been recognized recently as a possible complication of primary hyperparathyroidism. If the hyperparathyroid state can induce anemia in patients with normal kidney function, the extremely high levels of circulating parathyroid hormone usually observed in hyperparathyroidism secondary to chronic renal failure may have an unfavorable influence on the anemia of uremic patients. We investigated the influence of subtotal parathyroidectomy on the severity of the anemia of 18 uremic subjects undergoing long-term hemodialysis therapy. Subtotal parathyroidectomy resulted in a significant increase of mean hematocrit value. RBC count, and hemoglobin level. Serial bone biopsies suggested a relationship between the amount of marrow fibrosis and the improvement of anemia after surgery, but the precise mechanism of this phenomenon is still unknown.

Anemia in primary hyperparathyroidism

Although anemia has not been widely appreciated as a complication of primary hyperparathyroidism, 5.1% of the individuals with this disorder seen at the Massachusetts General Hospital since 1962 had a normochromic, normocytic anemia that could not be related to blood loss, a deficiency state, or uremia. The anemic group had more advanced bone disease and higher levels of serum calcium, alkaline phosphatase, and parathyroid hormone than the nonanemic group. Results of bone marrow biopsies performed in five patients showed variable degrees of myelofibrosis. However, none of the patients had hepatosplenomegaly, a myelophthisic peripheral blood smear, leukopenia, or thrombocytopenia. Removal of the abnormal parathyroid glands led to improvement or correction of the anemia. (<i>Arch Intern Med</i>137:588-590, 1977)

Anemia in Primary Hyperparathyroidism

Although anemia has not been widely appreciated as a complication of primary hyperparathyroidism, 5.1% of the individuals with this disorder seen at the Massachusetts General Hospital since 1962 had a normochromic, normocytic anemia that could not be related to blood loss,a deficiency state, or uremia. The anemic group had more advanced bone disease and higher levels of serum calcium, alkaline phosphatase, and parathyroid hormone than the nonanemic group. Results of bone marrow biopsies performed in five patients showed variable degrees of myelofibrosis. However, none of the patients had hepatosplenomegaly, a myelophthisic peripheral blood smear, leukopenia, or thrombocytopenia. Removal of the abnormal parathyroid glands led to improvement or correction of the anemia.

Anemia in Hypercalcemic Hyperparathyroidism

Clinicians have long been amazed by the myriad of symptoms and complications that can be produced by hypercalcemic (primary) hyperparathyroidism. Osteitis fibrosa cystica, renal stone, nephrocalcinosis, pancreatitis, and peptic ulcer disease are the most widely recognized. Other complications or associations have received emphasis more recently, including spinal osteoporosis with pain and compression fractures, 1 gout, 2 pseudogout, 3 hypertension, 4 neuromuscular disease, 5 and mental changes such as depression and psychosis. 6,7 Also proposed as associations, but less well established, are cholelithiasis, 8 ankylosing spondylitis, 9 and an increased incidence of concomitant papillary thyroid carcinoma 10 or other malignancy. 11 The article by Boxer et al in this issue (see p 588) supplements other recent reports indicating that we must now add anemia to the list of complications of hyperparathyroidism. 12,13 Anemia is actually not a newly recognized complication of primary hyperparathyroidism, since it was mentioned in earlier reviews by Albright