Clinical Profile Of Primary Hyperparathyroidism Research Articles

Renal Manifestation in Patients with Primary Hyperparathyroidism: a Retrospective Analysis in a Tertiary Institute

<p><strong>Objectives:</strong> The classical renal manifestations of primary hyperparathyroidism (PHPT) are nephrolithiasis and nephrocalcinosis. The presence of renal stone categorizes PHPT as symptomatic variant. The clinical profile of PHPT has changed in past few decades with decreased prevalence of renal stone disease with the introduction of widespread routine biochemical screening in normal subjects. In developing countries, PHPT is still a late diagnosed disorder and most of the patients are symptomatic at presentation. Presence of renal stone in PHPT patients is an absolute indication of parathyroidectomy, hence it is important to identify renal involvement in PHPT. The objective of the study is to determine the rate of renal manifestations in patients of biochemically primary hyperparathyroidism and compared to control group. This retrospective review was performed to determine whether the rate of nephrolithiasis and nephrocalcinosis is still high in the patients who underwent dual phase 99mTc sestamibi scan for PHPT at National Institute of Nuclear Medicine and Allied Sciences (NINMAS) compared to those not affected by the disorder.</p><p><strong>Patients and Methods:</strong> A total 149 patients (male 72 and female 77) and mean age 41 ± 14.73 years with PHPT were included in this study. All patients underwent dual phase 99mTc sestamibi parathyroid scan. Result of 99mTc sestamibi scan were divided into two groups. Group I represented positive scan and group II indicated negative scan respectively.Relevant clinical history, biochemical values including serum calcium level, serum parathormone (PTH) level and data on renal manifestations were recorded. The control group comprised of 650 subjects who had abdominal ultrasonography for various clinical conditions without any history of PHPT. Renal manifestations were compared between PHPT patients and the control group.</p><p><strong>Results:</strong> Among 149 patients, scan was positive in 54(36.2%) cases (group I) and scan was negative in 95(63.8%) cases (group II). In group I, renal manifestations were present in 20 cases and absent in 34 cases. In group II, renal manifestations were present in 32 cases and were absent in 63 cases. Nephrolithiasis and nephrocalcinosis were present in 45(30.2%) and 7(4.7%) cases respectively in study population compared to 8(1.23%) persons of control group of 650 subjects. Pearson’s chi-square analysis showed that the difference in the rate of renal manifestations was significant (p < 0.001) between study population and control group. However, with in the study population the rate of renal manifestations between group I and group II was not significantly different (p = 0.137).</p><p><strong>Conclusion:</strong> This study showed eighteen fold increased renal manifestations in the patients with PHPT imaged for parathyroid gland compared to the subjects not affected by the disorder. Symptomatic variant of PHPT with renal manifestation was higher in this study compared to western countries. During parathyroid scanning in PHPT routine ultrasonographic evaluation of kidneys is necessary to exclude renal manifestation, even with negative parathyroid scan.</p><p>Bangladesh J. Nuclear Med. 20(1): 32-36, January 2017</p>

Multiple endocrine neoplasia type 1 syndrome: single centre experience from western India.

Multiple endocrine neoplasia type 1 syndrome (MEN1) is a rare autosomal dominant familial cancer syndrome affecting multiple endocrine glands. Published literature on MEN1 from Indian subcontinent is scarce. We report here a case series of MEN1 patients (n=18) from 14 unrelated families. Retrospective study describing the clinical profile of MEN1 patients from endocrine unit of a tertiary care hospital from western India. Additionally clinical profile of primary hyperparathyroidism (PHPT) in MEN1 patients was compared with that of apparently sporadic PHPT cohort from our centre. Eighteen patients (10 males, 8 females) diagnosed as MEN1 were included. Mean age at diagnosis was 31.5±10.6years (range 17-54). Incidence of primary hyperparathyroidism (PHPT), pituitary adenoma (PA), and gastro-entero-pancreatic neuroendocrine tumor (GEP-NET) was 94.4, 72.2, and 72.2%, respectively. GEP-NET was the commonest presenting lesion (33.3%), followed by PA (27.7%), PHPT (16.6%), thymic carcinoid (5.5%), while 16.6% cases were identified on family screening. PHPT manifestations (clinical and biochemical) in MEN1 were less severe as compared to those of sporadic PHPT. Contrast enhanced computed tomography (CECT) and (68)Ga-DOTANOC PET/CT were equally sensitive (64.7 vs. 63.5%) in identifying multiglandular parathyroid disease. Non functioning tumors (NFT) were the most common GEP-NET, followed by insulinoma (5/13, two were metastatic). (68)Ga-DOTANOC PET/CT had higher sensitivity in detecting GEP-NET lesions than CECT (100 vs. 62.5%). The most common pituitary lesion was prolactinoma, and all were cabergoline responsive. Genetic analysis was available in 13 patients and 11 patients showed mutation in MEN1 gene. The clinical profile of MEN1 in Asian Indian patients is largely comparable to that reported in other cohorts. Peculiar findings of our cohort are predominance of GEP-NET as a presenting manifestation and relatively higher prevalence of insulinoma with higher occurrence of metastatic insulinoma. Clinical and biochemical profile of MEN1 associated PHPT is less severe than that of our sporadic PHPT.

The clinical profile of primary hyperparathyroidism: a single centre experience

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

Changing clinical profile of primary hyperparathyroidism in Indian patients

Changing clinical profile of primary hyperparathyroidism in Indian patients

Asymptomatic Primary Hyperparathyroidism

The clinical profile of primary hyperparathyroidism (PHPT) as it is seen in the United States and most Western countries has evolved significantly over the past half century. The introduction of the multichannel serum autoanalyzer in the 1970s led to the recognition of a cohort of individuals with asymptomatic hypercalcemia, in whom evaluation led to the diagnosis of PHPT. The term “asymptomatic primary hyperparathyroidism” was introduced to describe patients who lack obvious signs and symptoms referable to either excess calcium or parathyroid hormone. Although it was expected that asymptomatic patients would eventually develop classical symptoms of PHPT, observational data suggest that most patients do not evolve over time to become overtly symptomatic. In most parts of the world, the asymptomatic phenotype of PHPT has replaced classical PHPT. This report is a selective review of data on asymptomatic PHPT: its demographic features, presentation and natural history, as well as biochemical, skeletal, neuromuscular, psychological, and cardiovascular manifestations. In addition, we will summarize available information on treatment indications and options for those with asymptomatic disease.

Successful Treatment of Osteitis Fibrosa Cystica from Primary Hyperparathyroidism

Osteitis Fibrosa Cystica (OFC) is defined as the classic skeletal manifestation of advanced primary hyperparathyroidism. With the increased detection by means of routine calcium screening, the clinical profile of primary hyperparathyroidism in Western countries has shifted from symptomatic disease to one with subtle or no specific symptoms (“asymptomatic” primary hyperparathyroidism). The authors describe a classical feature of advanced primary hyperparathyroidism due to a parathyroid adenoma and its successful treatment.

EPIDEMIOLOGIChESKIE ASPEKTY PERVIChNOGOGIPERPARATIREOZA V ROSSII

Primary hyperparathyroidism (PHPT) is the third most frequent endocrine disorder and has a variable clinical presentation. Asymptomatic PHPT became the predominant form of the disease with increase of its incidence after the introduction of automated serum calcium measurement in North America and Europe. Data from Russia is lacking. Aim: To present the clinical profile of PHPT in Russia. Materials and Methods: This retrospective study was conducted at endocrinology centers in 8 regions of Russia. We analyzed the clinical presentation, and treatment options in patients with confirmed PHPT (1995-2010). Results: 738 patients (F: M-8:1) with age ranging from 13 to 83,4 years (mean 54,3) were analyzed. 54% was from Moscow (n=397), 11% - from Moscow region (n=79) and 35% - from 53 regions of Russia (n=262). Symptomatic PHPT was the most common form (74%) and was revealed with osteoporosis in 56%, nephrolithiasis - in 45% and ulcer disease - in 18%. Our data showed an increase in the incidence of PHPT (especially mild PHPT) after 2005 compared with earlier period. 64,9% of patients were treated surgically, 17 patients undergone repeated parathyroid surgery. 28,3% received bisphosphonates, calcitonin and/or cinacalcet . 11,5% was observed without treatment. Conclusions: This data analyzes some causes of delayed diagnosis of PHPT in Russia, characterized age and gender distribution of patients with PHPT and demonstrates the changes in clinical profile of disease from 1995 to 2010. PHPT still remains symptomatic disorder in our country most frequently with skeletal and renal manifestations.

Clinical profile of primary hyperparathyroidism from western India

Primary hyperparathyroidism (PHPT) has a variable clinical presentation and symptomatic PHPT is still the predominant form of the disease in India. Data from western India is lacking. To present the clinical profile of PHPT from western India. This retrospective study was conducted at a tertiary care referral center. We analyzed the clinical presentation, biochemical, radiological features, and operative findings in adult patients with PHPT (1986-2008) and compared with our published data of children and adolescent patients with PHPT. was done with SPSS 16 software. Seventy-nine patients (F: M-2:1) with age ranging from 21 to 55 years (mean 33.5+/-8.82) were analyzed. Skeletal manifestations (75.5%), renal calculi (40.5%) and proximal muscle weakness (45.5%) were the most common symptoms of presentation with mean duration of symptoms being 33.70 (median: 24, range 1-120) months. Biochemical features included hypercalcemia (total corrected calcium 12.55+/-1.77 mg/dl), low inorganic phosphorus (1.81+/-0.682 mg/dl), elevated total alkaline phosphatase (mean: 762.2; median: 559; range: 50-4930IU/L) and high parathyroid hormone (PTH) (mean+/-SD: 866.61+/-799.15; median: 639.5; range: 52-3820 pg/ml). Preoperative localization was achieved in 74 patients and single adenoma was found during surgery in 72 patients. Hungry bone disease was seen in 30.3% and transient hypoparathyroidism developed in 62% patients. In comparison to PHPT in children there were no significant differences with regard to clinical, laboratory and radiological features. PHPT in western India is symptomatic disorder with skeletal and renal manifestations at a much younger age. Clinical profile of PHPT in children is similar to that of adults.

Manifestaciones clínicas y formas asintomáticas del hiperparatiroidismo primario

El perfil clínico del hiperparatiroidismo primario (HP) ha variado mucho, especialmente desde que se introdujeron los autoanalizadores en el laboratorio, con lo que el calcio se determina con más frecuencia y, además, se detecta un gran número de hipercalcemias, de cuyas causas las más frecuentes son el HP y las relacionadas con los cánceres. Todo esto ha modificado la prevalencia de las manifestaciones clínicas y hoy día la presencia de litiasis renal recidivante se observa en el 20% de los casos y las lesiones óseas, incluso las más sutiles, son poco frecuentes; de todos modos, es difícil diferenciar y establecer los límites entre el HP sintomático y asintomático, y en muchos de los casos asintomáticos la enfermedad, como hipercalcemia grave, enfermedad ósea, hipercalciuria y/o nefrolitiasis, nunca progresará. Una de las cuestiones importantes que se plantea es si los casos que no presentan manifestaciones clásicas de HP se beneficiarían de la intervención quirúrgica, ya que, además de los no tratados quirúrgicamente, muchos interrumpen el seguimiento entre los 5 y los 10 años, y hay que tener en cuenta que el coste económico del seguimiento es superior al de la intervención quirúrgica. Los no intervencionistas se basan en la falta de progresión de muchos casos y en la posibilidad de tratamientos alternativos. The clinical profile of primary hyperparathyroidism (PHPT) has changed considerably, especially since the introduction of autoanalyzers in the laboratory, allowing calcium to be determined more frequently and a large number of cases of hypercalcemia to be detected. The most frequent causes are PHPT and cancer-related hypercalcemia. All of these factors have modified the prevalence of the clinical manifestations and currently the presence of recurrent kidney stones is observed in 20% of patients, while bone lesions, even the most subtle, are infrequent. Differentiating and establishing the limits between symptomatic and asymptomatic PHPT is difficult and many asymptomatic cases will never show disease progression, such as severe hypercalcemia, bone disease, hypercalciuria and/or kidney stones. An important question is whether patients not showing the classical manifestations of PHPT will benefit from surgery. This question is all the more important since, among patients not surgically treated, many are lost to follow-up after 5 to 10 years and the cost of follow-up exceeds that of surgery. Those against intervention base their arguments on the lack of progression in many patients and the possibility of alternative treatments.

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.

Surgical indications of primary hyperparathyroidism

Clinical profile of primary hyperparathyroidism (PHPT) had shifted from symptomatic disorder, with hypercalcemic symptoms, kidney stones, overt bone disease, or a specific neuromuscular dysfunction toward a more asymptomatic state. Patients with symptomatic PHPT absolutely require parathyroidectomy (PTX). Surgical treatment is the well established and definitive treatment for PHPT. Consensus Conference at National Institute of Health (NIH) proposed the guidelines for PTX in asymptomatic PHPT. They included (1) serum calcium level was 1.0 mg/dL above upper limit of normal, (2) 24-h urinary calcium was over 400 mg, (3) creatinine clearance is reduced by 30%, (4) bone mineral density (T-score) reduced 2.5 SD below the peak bone mass at any site, and (5) patients under 50 years of age, and (6) patients for whom medical surveillance was either not desirable or not possible. Because in about 25% of patients asymptomatic PHPT will show progression, because it is important to monitor patients who are not undergoing PTX. Normocalcemic PHPT has been frequently found in patients whose bone mineral density is reduced. This diagnostic consideration requires that all potential causes of secondary HPT. The surgical procedure has been progressive induced by the developments of preoperative image diagnosis and intraoperative PTH assay. Minimally invasive PTX could expand surgical indications in patients with mild asymptomatic PHPT.

Utilidad de la densitometría ósea en la evaluación del hiperparatiroidismo primario

In recent years, the clinical profile of primary hyperparathyroidism (PH) is predominantly characterized by mild or asymptomatic forms. In this context, the effects of the PH on bone metabolism reach a growing importance in the adoption of therapeutic decisions. 116 patients with PH were studied, 95 women (25 premenopausal, 70 postmenopausal) and 21 males. In all cases parathyroidectomy criteria were evaluated. Bone mineral density (BMD) was determined in 71 patients in lumbar spine (LS) and femoral neck by dual-X-Ray absorptiometry (DXA) and the influence of this measurement in the decision of surgical treatment was analyzed. The patients with PH showed a significant reduction of BMD at all sites (p < 0.001) and 71.8% met osteoporosis densitometric criteria. The most frequent parathyroidectomy criteria was the presence of specific clinical manifestations (51.7%) followed by decrease of the BMD in LS (49.3%). The probability of meeting criteria for surgical treatment was significantly higher in patients in which BMD was measured (odds ratio: 3.09 [1.03-9.22]; p = 0.036). In its current presentation, PH presents a significant decrease of bone mass. The systematic performance of bone densitometry has a decisive influence in its appropriate management.

Clinical profile of primary hyperparathyroidism in adolescents and young adults.

Primary hyperparathyroidism (PHPT) is an uncommonly diagnosed condition among adolescents and young adults. We review the clinical characteristics of these patients based on our institutional experience. Patients aged 12-28 years treated for PHPT at our institution from 1990 to 1996 were evaluated by a review of medical records and current follow-up data. This consisted of 22 patients (8M:14F), constituting approximately 3% of all patients operated for PHPT during this period. Serum and urinary calcium concentrations, renal function, and serum intact parathyroid hormone (IPTH) levels were measured in all patients. After biochemical confirmation of diagnosis, the patients completed a questionnaire to evaluate the presence of symptoms and/or conditions associated with PHPT. All the patients underwent parathyroidectomy and their tumour characteristics were evaluated. Surgical outcome was determined by measurements of serum calcium and IPTH levels postoperatively and during long-term follow-up. A third of the patients were diagnosed by routine serum chemistry whereas two-thirds presented with symptoms or conditions associated with hypercalcaemia. Non-specific complaints such as fatigue or exhaustion, and weakness or lethargy constitute the most common findings on questionnaire review. A family history of PHPT was present in only 2 patients. The preoperative peak serum calcium levels ranged from 2.67 to 4.19 mmol/l (norm: 2.10-2.54 mmol/l), with a median of 3.07 mmol/l. Surgical pathologies revealed 59% solitary adenoma, 27% hyperplasia, 9% multiple adenomas and 5% carcinoma. Comparison between the adolescents (aged 12-18 years) and young adults (aged 19-28 years) revealed no differences in the clinical, pathological or laboratory profiles, except for a male predominance in adolescent patients. Fifteen patients had resection of one or more adenomas while 7 underwent subtotal parathyroidectomy. Six patients (27%) were reoperated cases, all received primary treatment elsewhere. All patients with benign PHPT were cured surgically, with a median follow-up of 47 months (range 3-77 months). One reoperated patient developed permanent hypocalcaemia. One patient with carcinoma underwent several operations for recurrence; he is now eucalcaemic despite persistent disease at 80 months from diagnosis. We found a high incidence of multiglandular disease and relatively non-specific symptomatology in our adolescent and young adult patients with primary hyperparathyroidism. In view of the heterogeneous clinical expression noted in young patients, one should consider primary hyperparathyroidism in the differential diagnosis of unexplained non-specific complaints, and perform serum calcium estimations more readily in these subjects. Our experience suggests that primary hyperparathyroidism can be a serious disease with significant morbidity if left untreated, whereas parathyroidectomy provides successful results.

Primary Hyperparathyroidism: Another Important Metabolic Bone Disease of Women

The clinical profile of primary hyperparathyroidism has changed markedly with the advent of the multichannel screening test. It has become a common disease, characterized best by asymptomatic hypercalcemia. It is seen most commonly in postmenopausal women. The potential complications of primary hyperparathyroidism are seen much less frequently now but still loom as potential features of the disease. The ability to measure bone mass in primary hyperparathyroidism with great sensitivity and accuracy has helped to detect aspects of this disorder that lie beneath the clinical surface of the disease. With knowledge of current clinical and biochemical features of hyperparathyroidism, combined with evaluation of the skeleton by bone mineral densitometry, it is possible to develop a rational approach to the patient, vis à vis surgical or medical approaches. These guidelines are useful until we learn more about the natural history of the modern profile of primary hyperparathyroidism.

Bone Disease in Primary Hyperparathyroidism

The classic bone disease of primary hyperparathyroidism, osteitis fibrosa cystica, was characterized by subperiosteal bone resorption, osteopenia, and "brown tumors." Since the description of this skeletal disorder, the clinical profile of primary hyperparathyroidism has evolved markedly. The disease today is often characterized by no more than asymptomatic hypercalcemia, and severe bone disease is a distinct rarity. However, as we have endeavored to show in this article, newer and more sensitive techniques show significant evidence of the effect of excess parathyroid hormone on the skeleton. Bone density as measured by photon absorptiometry and bone histomorphometry show a deficit of cortical bone and a preservation or increase in cancellous bone elements in mild primary hyperparathyroidism with no clinical evidence of skeletal disease. Important questions exist as to the therapeutic implications of these data. Does the presence of parathyroid hormone effect on sophisticated testing portend the development of clinical bone disease? Should these data be used as a rationale for surgical intervention in patients who might otherwise be followed conservatively with mild primary hyperparathyroidism? The answers to these questions must await further data collection and study.

Neuromuscular involvement in mild, asymptomatic primary hyperparathyroidism

The classic neuromuscular abnormalities of primary hyperparathyroidism are based on observations from an earlier time when the disease presented commonly with signs and symptoms. The purpose of the present study was to test for neuromuscular abnormalities among patients currently seen with primary hyperparathyroidism, in whom the vast majority are asymptomatic. Forty-two patients (30 women, 12 men) were studied. Serum calcium level was 11.1 +/- 0.1 mg/dL (normal, 8.7 to 10.7 mg/dL); phosphorus level was 2.8 +/- 0.1 mg/dL (normal, 2.5 to 4.5 mg/dL). Parathyroid hormone levels by radioimmunoassay for N-terminal and for mid-molecule regions were 32.6 +/- 2.4 pg/mL (normal, 8 to 24 pg/mL) and 831 +/- 127 pg/mL (normal, 50 to 330 pg/mL), respectively. Although generalized weakness and easy fatigability were common complaints, they were not seen on neurologic examination. No patient showed typical neuromuscular findings such as muscle weakness or atrophy, hyperreflexia, abnormal gait, tongue fasciculations, or objective changes in mental status. On the other hand, paresthesias and muscle cramps were reported by 22 patients (52%). Neurologic examination in 12 patients (29%) demonstrated findings consisting of either stocking-glove loss of pain sensation or loss of vibratory sensation with diminished reflexes. Creatine phosphokinase levels were normal in all patients. Electromyography and nerve conduction studies were performed in nine patients. None showed myopathy or signs of motor unit denervation. Isolated nerve abnormalities (n = 6) and nonspecific sensory neuropathy (n = 2) were observed. We conclude that the classic neuromuscular syndrome of primary hyperparathyroidism is rarely seen among a typical modern-day group of patients with primary hyperparathyroidism. The results suggest that the neurologic component of primary hyperparathyroidism should be included among those features of the disease that have changed along with other aspects of the clinical profile of primary hyperparathyroidism.