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PubMed2006

Differential RNA expression profile by cDNA microarray in sporadic primary hyperparathyroidism (pHPT): primary parathyroid hyperplasia versus adenoma.

BACKGROUND: Differential diagnosis between adenoma and hyperplasia in primary hyperparathyroidism (pHPT) remains a dilemma. The aim of this study was to assess differences in transcriptional genomic expression profiles between sporadic (nonfamilial) parathyroid hyperplasia (SPH), adenoma, and normal tissue. METHODS: Parathyroid tissue from 12 patients with parathyroid adenoma, 3 with SPH, and 2 with normal glands was selected for analysis. Histopathology was reviewed in all cases, and all patients with adenomas presented normocalcemia for a minimum of 6 months after one gland resection. Hybridizations were performed in a microarray containing 19,968 human cDNA clones including contiguous replicates. Direct comparisons were performed with reverse labeling for every different pooled sample entity. Expression levels were analyzed using the SAM, SMA, LIMMA, Cluster, and PAM packages in the R environment for statistical computing. RESULTS: There were significant statistical differences between SPH and adenomas. In the direct comparison, a total of 200 genes showed differential expression (P < 0.03): 61 genes were upregulated (> 1.65-fold increase) and 139 were downregulated (> 1.58-fold decrease) with a B value > 4.68 (99.08% probability of real differential expression). When SPH was compared to normal parathyroid tissue, 50 genes were differentially expressed: 42 were upregulated (> 1.89) and 8 were downregulated (> 1.7) with a B > 4.26 (98.6% probability of real differential expression). At least 17 genes were differentially expressed and able to discriminate SPH from adenoma or normal tissue. Upregulated genes were related to apoptosis inhibition, cell proliferation, transcriptional activity and cell adhesion, among other activities. Downregulated genes were mainly related to ion channel activity, lipopolysaccharides, prostaglandin-d synthase, and integral membrane proteins. CONCLUSIONS: Our data suggest that SPH and adenoma have a singular molecular signature that, theoretically, could be used for the differential diagnosis of these entities and normal parathyroid tissue.

Adenoma↗
PubMed1998

Hypercalcemic cardiomyopathy associated with primary hyperparathyroidism mimicking primary obstructive hypertrophic cardiomyopathy.

A 72-year-old woman presented to hospital with rapidly progressive dyspnea and chest pain on exertion. Physical findings included a grade 3/6 systolic murmur increased by the Valsalva manoeuvre. Transthoracic echocardiography revealed concentric left ventricular hypertrophy, systolic anterior motion of the mitral valve and critical dynamic outflow tract obstruction. The myocardium was strikingly heterogeneous with hyperdynamic left ventricular systolic function. Laboratory findings included severe hypercalcemia secondary to primary hyperparathyroidism. The patient's outcome was unfavourable with nephrogenic diabetes insipidus, pancreatitis, shock, severe acidosis and death. Postmortem examination confirmed the presence of severe concentric left ventricular hypertrophy, a narrowed left ventricular outflow tract and localized endocardial fibrosis of the left interventricular septum. Microscopic findings showed diffuse calcium deposits of the myocardium, coronary arteries, kidneys and lungs. This appears to be the first report of two-dimensional and Doppler echocardiographic findings in hypercalcemic cardiomyopathy mimicking obstructive hypertrophic cardiomyopathy.

Acute Disease↗
PubMed1983

Primary hyperparathyroidism associated with primary hyperaldosteronism.

Two patients with both primary hyperparathyroidism and primary hyperaldosteronism are described. Each presented with high blood pressure and a history of renal calculi. Mild hypercalcaemia was associated with raised plasma parathyroid hormone concentrations and a parathyroid adenoma was excised from each. Both patients also had hypokalaemia, hyperaldosteronism and low plasma renin concentrations. Quadric analysis, adrenal vein plasma aldosterone concentrations, adrenal venography and CT scanning all suggested an adrenal adenoma in each patient. This suspicion was confirmed at operation in one patient; the other patient is unfit for adrenal surgery but her blood pressure and plasma potassium concentration have remained within the normal range during prolonged treatment with either spironolactone or amiloride. Because of this unusual association a search was made for parathyroid hormone excess in patients with primary hyperaldosteronism and for aldosterone excess in primary hyperparathyroidism. None was found.

Adult↗
PubMed2006

The diagnosis and management of asymptomatic primary hyperparathyroidism.

Classical primary hyperparathyroidism--a disease of 'bones, stones, and psychic groans'--is a rarity in the US, although it is still seen in some parts of the world. Today, most patients with primary hyperparathyroidism are asymptomatic. This change in clinical profile is not merely because of improved detection techniques, and patients with primary hyperparathyroidism who lack symptoms, if left untreated, rarely develop the 'classical' features that were common previously. Indeed, currently available data suggest that there is, today, a disorder with different, yet characteristic, effects on the end-organs of the hyperparathyroid process. In this review, the features of the skeletal, renal, neuropsychologic, cardiovascular, and gastrointestinal manifestations of 'asymptomatic' primary hyperparathyroidism will be discussed. The considerable body of data that has emerged since the recognition of the new clinical profile of primary hyperparathyroidism has allowed a reconsideration of standards of care for this disease. These data were reviewed and incorporated into new clinical guidelines at the 2002 NIH workshop on asymptomatic primary hyperparathyroidism. These recommendations highlight both what is known about the disease, and important areas that need investigation. Continued interest in the skeletal, cardiovascular, and neuropsychiatric manifestations of the disease, and therapeutic trials of medical approaches for its management, will further refine our current understanding, and could lead to additional modifications in the approach to patients with this common endocrine disorder.

Bone Diseases↗
PubMed2005

Arterial stiffness in mild primary hyperparathyroidism.

When primary hyperparathyroidism was a more symptomatic disease, it was often associated with increased cardiovascular risk. As the clinical manifestations of the disease have changed to a milder, more asymptomatic disorder, investigation is shifting to more subtle cardiovascular abnormalities. We measured arterial stiffness in 39 patients with mild primary hyperparathyroidism [serum calcium, 2.66 +/- 0.2 mmol/liter (10.7 +/- 0.6 mg/dl); PTH, 21.7 +/- 9.5 pmol/liter (89 +/- 39 pg/ml)] and in 134 controls. Arterial stiffness was measured mathematically at the radial artery with a noninvasive device as the "augmentation index" (AIx). The AIx measures the difference between the second and first systolic peaks in the pressure waveform and correlates with increased cardiovascular risk. When physiological variables affecting augmentation index and potentially confounding cardiovascular risk factors (age, gender, heart rate, height, blood pressure, diabetes mellitus, smoking, and hyperlipidemia) were adjusted for, primary hyperparathyroidism was an independent predictor of increased augmentation index (B = 3.37; P < 0.03). A matched-pair analysis showed that 15% of the variance in AIx was uniquely accounted for by the presence of primary hyperparathyroidism. The presence of primary hyperparathyroidism was a stronger predictor of elevated AIx than age, gender, smoking, hypertension, hyperlipidemia, or diabetes mellitus. AIx was also directly correlated with evidence of more active parathyroid disease, including higher PTH levels (r = +0.42; P < 0.05) and lower bone mineral density at the distal one-third radius (r = -0.33; P < 0.05). The diagnosis of primary hyperparathyroidism was therefore an independent predictor of increased AIx, an early measure of arterial stiffness, and the increase was associated with evidence of more active parathyroid disease.

Aged↗
PubMed1987

Acute primary hyperparathyroidism.

Acute primary hyperparathyroidism is an unusual form of primary hyperparathyroidism characterized by life-threatening hypercalcemia. Forty-three cases reported in the literature since 1974 are reviewed, along with five new cases. The average age of the patients was 55 (27 to 82), with an even distribution between men and women. Marked hypercalcemia (17.5 +/- 2.1 mg/dl) was accompanied by parathyroid hormone levels 20 times normal. Virtually all patients had symptoms. Hyperparathyroid bone disease occurred in 53 percent of patients; even more (69 percent) had nephrolithiasis or nephrocalcinosis. Combined renal and skeletal involvement was seen in 50 percent. Only three deaths were recorded. The pathophysiology of the acute hyperparathyroid state is unknown but appears to consist of uncontrolled parathyroid hormone secretion followed by cycles of hypercalcemia, polyuria, dehydration, reduced renal function, and worsening hypercalcemia. These features of acute primary hyperparathyroidism are compared with the features reported in the literature antedating multichannel screening, and with the features of the common form of primary hyperparathyroidism. Clinical guidelines by which the diagnosis may be suspected are also reviewed.

Acute Disease↗
PubMed2002

Outcome study of psychological distress and nonspecific symptoms in patients with mild primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism is a common endocrinopathy. The appropriate management of its mild form, however, remains controversial. HYPOTHESIS: Mild primary hyperparathyroidism is associated with psychological distress and other nonspecific symptoms that improve following parathyroidectomy. DESIGN: Two-year prospective before-after study. SETTING: University hospital. PATIENTS: Twenty-six consecutive patients with mild hypercalcemia (<12 mg/dL [<3 mmol/L]) due to primary hyperparathyroidism, without osteitis fibrosa cystica or urolithiasis were enrolled from January 11, 1997, through April 21, 1998. INTERVENTION: Parathyroidectomy. MAIN OUTCOME MEASURES: Primary outcome was psychological distress as measured by the 28-item version of the General Health Questionnaire. Secondary outcomes included body weight, joint pain, and occurrences of bowel movements and urination. RESULTS: Before surgery, 15 patients (58%; 95% confidence interval, 37%-77%) showed psychological distress (case group) while 11 patients did not (noncase group). A clinically and statistically significant reduction in the General Health Questionnaire score was detected at 3 months in the case group (-6.1; 95% confidence interval, -11.0 to -1.2), but the reduction was smaller (-1.9; 95% confidence interval, -6.9 to 3.0) at 24 months after surgery. No significant change in the General Health Questionnaire score was observed in the noncase group during the follow-up. No significant change was noted in any of the secondary outcomes. CONCLUSIONS: Psychological distress was associated with mild primary hyperparathyroidism and was ameliorated after surgery. The improvement, however, was limited in extent and duration.

Aged↗
PubMed1998

Germline mutation of the multiple endocrine neoplasia type 1 (MEN1) gene in a family with primary hyperparathyroidism.

Familial primary hyperparathyroidism (FHP) is a rare hereditary disorder characterized by isolated parathyroid tumors without any other lesions related to multiple endocrine neoplasia (MEN). Primary hyperparathyroidism is usually expressed at an early age and is highly penetrated in MEN type 1 (MEN1), suggesting that some FHP may be a variant type or early stage of MEN1. The MEN1 gene has recently been cloned and its germline mutations have been considered to play an important role in the tumorigenesis of MEN1. We studied a Japanese family with primary hyperparathyroidism which included 4 patients. To investigate the possible relationship between primary hyperparathyroidism in this family and the MEN1 gene, we analyzed a proband for a germline mutation of the MEN1 gene in this study. We identified a novel heterozygous mutation (1350del3) at codon 414 in exon 9. Restriction digestion analysis revealed the same mutation pattern in his brother with hyperparathyroidism. These findings suggest that our patients may belong to a variant type of MEN1.

Adult↗
PubMed2002

[Changes in calcium metabolism after parathyroidectomy in primary hyperparathyroidism].

INTRODUCTION: Primary hyperparathyroidism causes elevated serum calcium level and osteopenia in most patients. AIMS: The authors measured the changes of calcium and bone mineral metabolism after parathyroidectomy in patients with primary hyperparathyroidism. PATIENTS: From 1995 to 2000, osteopenia was detected in 34 patients with primary hyperparathyroidism before surgery. There were 26 females (16 women were post-menopausal) and 8 males. The mean age of the patients was 54 years (range 19 to 64). The serum levels of calcium, phosphorus, alkaline phosphatase and the parathyroid hormone were measured before the operation and every year thereafter. Bone densitometry was performed at the lumbar spine (L II-IV) during the same period. RESULTS: The mean levels of calcium and parathyroid hormone rapidly decreased and varied in the normal range after the operation. The mean alkaline phosphatase concentrations also decreased after surgery, but in most cases the difference was not statistically significant. Bone densitometry showed increased bone mineral density at the lumbar spine (L II-IV) after the parathyroidectomy. One, 2, 3, 4 and 5 years after surgery the bone mineral density increased with 8.5%, 12.5%, 14.1%, 13.5% and 11.3% compared to the preoperative value respectively. The changes in bone mineral density values were not statistically significant 1 year after parathyroidectomy. The increase in the bone mineral density was significant two years after the operation. Nine patients had T-scores less than -2.5 before parathyroidectomy. CONCLUSION: The authors conclude, that the serum levels of calcium and parathyroid hormone significantly decreased after the parathyroidectomy in primary hyperparathyroidism. After successful surgical treatment the bone mineral density significantly increases and the osteopenia decreases or resolves.

Adult↗
PubMed2006

[Surgery of primary hyperparathyroidism].

Surgery of primary hyperparathyroidism. Primary hyperparathyroidism is usually caused by a single parathyroid adenoma, rarely by multiple adenomas or hyperplasia and in 1-2% of cases by carcinoma. The definitive cure of the disease can be achieved only by surgical means. Unfortunately, only 10% of expected cases based on the number of population are diagnosed in Hungary. The main reason is that the disease has no specific symptoms and it causes only a few cases present with clinical entities such as nephrolithiasis, osteoporosis-osteopenia, pancreatitis, hypertension, peptic ulcer disease, depression, etc. The clue to the diagnosis of primary hyperparathyroidism is usually the laboratory result of hypercalcemia and in order to this aim the measurement of serum Ca would be an obligatory part of routine laboratory investigation in Hungary. The diagnosis of primary hyperparathyroidism rests on the laboratory confirmation of increased serum calcium and inappropriately elevated intact parathyroid hormone concentrations. If surgical intervention is planned, cervical ultrasonography and parathyroid-scintigraphy are indicated for the exact localization of hyperfunctioning parathyroid gland(s). CT and/or MRI are usually not necessary, except in cases of previous neck operation. The operation must be performed by surgeon skilled in parathyroid surgery. The surgical success can be assessed intraoperatively by the use of a gamma probe or by intraoperative measurement of parathyroid hormone concentrations in the serum or in the removed tissue(s). Support of these procedures is recommended. Although many recent publications deal with the minimal invasive methods of parathyroidectomy, the cost-effectiveness of these newer techniques are controversial.

Adenoma↗
PubMed1992

Results of a multidisciplinary strategy for management of mediastinal parathyroid adenoma as a cause of persistent primary hyperparathyroidism.

Persistent primary hyperparathyroidism due to mediastinal parathyroid adenoma was effectively treated by either angiographic ablation or median sternotomy in this study of 49 patients managed at the National Institutes of Health since 1977. Each patient presented here with symptomatic persistent primary hyperparathyroidism after failed initial surgical procedures done at other institutions. Each patient underwent extensive parathyroid localization procedures, including selective angiography, and most had a parathyroid adenoma localized to the mediastinum. Angiographic ablation, the deliberate injection of large doses of contrast material into the artery that selectively perfuses the adenoma, was initially successful in 22 of 30 procedures (73%) in 27 patients. Long-term control of persistent primary hyperparathyroidism was achieved in 17 of 27 patients (63%) by angiographic ablation. Each unsuccessful ablation could be easily salvaged by surgical resection. Surgical resection of the parathyroid adenoma by median sternotomy achieved immediate success in 24 of 24 procedures (p2 less than 0.02 versus ablation), and long-term cure in 23 of 23 evaluable patients (p2 less than 0.001 versus ablation). However, ablation did have benefits for the patients in whom it was successfully performed. It was associated with a significantly shorter hospital stay (median, 6 days versus 9 days for sternotomy, p2 less than 0.003), much less pain, and easier recuperation. Complications of each procedure were transient and similar in both groups. Operative resection is the most effective single means to eradicate mediastinal parathyroid adenoma; however, angiographic ablation can provide similar long-term control of hyperparathyroidism in 63% of patients with less pain and shorter convalescence than that seen in patients after median sternotomy. Our results suggest that angiographic ablation should be attempted as the initial procedure for patients with persistent primary hyperparathyroidism caused by an angiographically identified mediastinal parathyroid adenoma. Operation can be reserved for those who fail ablation.

Adenoma↗
PubMed2003

Clinical spectrum of primary hyperparathyroidism.

OBJECTIVE: Primary hyperparathyroidism (1HPT) is now being diagnosed with increasing frequency. Simultaneously there has been an apparent change in the presentation of the disease and indications for surgery. The aim of this study was to examine the clinical presentation, indications for surgery, and outcomes of neck explorations for primary hyperparathyroidism. METHODS: This study was carried out over a 12 year period, January 1990 to April 2002 at Jordan University Hospital, Amman, Jordan. Information on the indications, procedure performed, pathology and complications of all neck explorations for 1HPT was obtained from a retrospective thyroid/parathyroid surgical database. A minimum of 12 months follow-up was required in order to determine outcome of surgery. RESULTS: Out of 40 patients diagnosed with primary hyperparathyroidism at Jordan University Hospital, Amman, over 12 years, 14 patients (35%) diagnosed 4 years after the onset of their disease. Severe bone disease was the main indication for surgery in 28 patients; 5 patients with fractured bones, 2 patients with bone cysts, 3 patients with brown tumors and severe osteoporosis and backache in 22 patients; renal calculi in 10 patients; muscle ache and weakness in 14 patients; acute pancreatitis in one patient and asymptomatic HPT following biochemical screening in one patient. Two patients continued to have persistent hypercalcemia after the first operation; one of them has been cured by reoperation for an ectopic parathyroid in the anterior mediastinum resulting in an overall cure rate of 97.5%. CONCLUSION: This study showed that severe bone disease with fractures, bone cysts and brown tumors are still the most common presentation of primary hyperparathyroidism in Jordan; this is most likely due to delay in diagnosis and initiation of treatment. It is important to screen for hyperparathyroidism in high risk patients and to refer these patients to specialized centers for proper management.

Acute Disease↗
PubMed1998

Surgery for primary hyperparathyroidism 1962-1996: indications and outcomes.

OBJECTIVE: To examine changes over the past three decades in the indications for, and outcomes of, surgery for primary hyperparathyroidism. DESIGN: Survey of a prospective hospital database. SETTING: Royal North Shore Hospital (a tertiary referral and university teaching hospital), Sydney, New South Wales, January 1962 to December 1996. PATIENTS: All 733 patients who underwent neck exploration for primary hyperparathyroidism. RESULTS: The annual number of parathyroidectomies increased virtually exponentially, from a mean of two in 1962-1969 to 73 in 1996. In the 1960s and 1970s, the most common indication for surgery was the presence of renal calculi (58% and 43%, respectively), but in the 1980s there was a marked increase in presentation of asymptomatic disease after biochemical screening (19%). In the 1990s, low bone mineral density detected by osteodensitometry has become the most common indication for surgery (31%). After initial operation, 11 patients (2%) had persistent hypercalcaemia, with five of these cured by reoperation--an overall failure rate of 1%. CONCLUSIONS: Surgery for primary hyperparathyroidism has become increasingly common, with low bone mineral density replacing renal calculi as the most common indication for surgery. Neck exploration in experienced hands results in an overall cure rate of 99%.

Adolescent↗
PubMed2002

[Personal experience with a bilateral approach in the surgical treatment of primary hyperparathyroidism. (A group of 222 patients with surgery for primary hyperparathyroidism from 1994 to 2000)].

Surgical treatment offers a definite cure of patients with primary hyperparathyroidism. When making the diagnosis of primary hyperparathyroidism the success of a surgical solution depends on the experience and judgment of the surgeon. Our experience with 222 operations and re-operations convinced us on the preference of a bilateral approach, i.e. exploration of both sides of the neck. The ectopic localization of the parathyroid glands, the limited possibilities of an unequivocal interpretation of the histological examinations but also the frequent incidence of thyropathies leads the surgeon, in our opinion, to the complete exploration of both sides of the neck within the framework of the primary operation for primary hyperparathyroidism. This approach leads most probably to the best results. We use an aimed unilateral approach only in old patients who are in a very bad condition where we anticipate a benefit from a short operation.

Adolescent↗