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ORIGINAL ARTICLE
Year : 2010  |  Volume : 56  |  Issue : 2  |  Page : 79-84

Clinical profile of primary hyperparathyroidism from western India: A single center experience


1 Department of Endocrinology, KEM Hospital, Parel, Mumbai, India
2 Department of General Surgery, KEM Hospital, Parel, Mumbai, India

Date of Submission30-Aug-2009
Date of Decision22-Oct-2009
Date of Acceptance30-Dec-2009
Date of Web Publication8-Jul-2010

Correspondence Address:
R A Gopal
Department of Endocrinology, KEM Hospital, Parel, Mumbai
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0022-3859.65279

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 :: Abstract 

Background: 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. Aim : To present the clinical profile of PHPT from western India. Settings and Design : This retrospective study was conducted at a tertiary care referral center. Materials and Methods : 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. Statistical Analysis : was done with SPSS 16 software. Results : 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. Conclusions : PHPT in western India is symptomatic disorder with skeletal and renal mani-festations at a much younger age. Clinical profile of PHPT in children is similar to that of adults.


Keywords: Hypercalcemia, parathyroid adenoma, primary hyperparathyroidism


How to cite this article:
Gopal R A, Acharya S V, Bandgar T, Menon P S, Dalvi A N, Shah N S. Clinical profile of primary hyperparathyroidism from western India: A single center experience. J Postgrad Med 2010;56:79-84

How to cite this URL:
Gopal R A, Acharya S V, Bandgar T, Menon P S, Dalvi A N, Shah N S. Clinical profile of primary hyperparathyroidism from western India: A single center experience. J Postgrad Med [serial online] 2010 [cited 2018 Apr 21];56:79-84. Available from: http://www.jpgmonline.com/text.asp?2010/56/2/79/65279


The clinical spectrum in primary hyperparathyroidism (PHPT) though varied, has undergone a striking change in developed countries, with the predominant form being asymptomatic PHPT, detected on routine biochemical screening for other causes. [1],[2],[3],[4],[5] Recent data from India showed that PHPT still presents with classic florid skeletal and renal manifestations. [6],[7],[8],[9],[10],[11] Earlier studies from India have attributed the severity of PHPT to delayed diagnosis and widely prevalent vitamin D deficiency or recurrent nephrolithiasis. [6],[7],[9] Published data from India is mostly from north and south India. Clinical profile of PHPT from western India is lacking. In this study, we analyzed clinical presentation, investigations, management, operative findings and immediate postoperative course of patients with histologically proven PHPT at our center. We also compared the clinical profile of these patients with children with PHPT from our center.


 :: Materials and Methods Top


A retrospective, consecutive review of medical records of all patients above age of 20 years who underwent parathyroid resection for PHPT at our institute between January 1987 and March 2009 was done. This resulted in 79 histologically proven cases, which were analyzed. Clinical data such as age at presentation, symptoms, duration, presence of complications and family history were analyzed. In addition, preoperative biochemical and hormonal findings, localization techniques, operative findings, postoperative course, histopathology and long-term disease status were also assessed. Follow-up was obtained by review of medical records and direct contact with the patient. The institutional review at our institution approved this study protocol. Statistical comparison was done according to sex for clinical features. The data was compared with the published data of 18 pediatric and adolescent patients (age <20 years) with PHPT from our department earlier.

Statistical analysis was done using SPSS 16 software. All results are expressed as mean±SD and median. A value of P<0.05 was considered significant.


 :: Results Top


Seventy-nine patients who were analyzed included 53 females and 26 males (ratio: 2:1) ranging in age from 21 to 55 (mean 33.5±8.82) years, (median age: 32 years). Mean duration of symptoms before presentation was 33.70 (median: 24, range 1-120) months.

Major presenting symptom was skeletal involvement [bone pain, fracture and palpable osteitis fibrosa cystica (OFC)] in 60 (75.5%) patients. Bone pain was a symptom in 59 patients (74.8%) while this was one of the presenting symptoms in 37 (46.8%) patients. Fracture was observed in 41 patients (51.8%) and it was the presenting complaint in 14 patients (17.7%) [Table 1].OFC was palpable in 14 (17.7%) patients. Renal calculi including nephrocalcinosis was present in 32 (40.5%) patients and was a presenting complaint in 12 (15.1%) patients. Eleven patients (13.9%) had renal failure. Pancreatitis was observed in nine patients and two patients had pancreatic calculi with no evidence of pancreatitis [Table 2].Thirty-six (45.5%) patients had proximal muscle weakness while 15 (18.9%) patients presented with this symptom. Parathyroid adenoma was palpable on careful examination in nine patients. History of hypertension was noticed in 15 (18.9%) patients [Table 1]. None of the patients had psychiatric symptoms or obvious neurological deficit. Gastrointestinal symptoms of nausea, vomiting and constipation were not seen except in a few who volunteered on direct questioning. There was no statistically significant difference in the frequency of clinical manifestations between males and females. Two patients had multiple endocrine neoplasia Type 1 (MEN Type 1); one female patient was diagnosed with PHPT, gastrinoma and prolactinoma and a male patient had acromegaly and PHPT.

Serum biochemistry showed elevated total corrected calcium (mean±SD:12.55±1.77 mg/dl) with a low inorganic phosphorus (mean±SD:1.81±0.682 mg/dl) and an elevated total alkaline phosphatase (mean:762.2; median:559; range 50-4930 IU/L). Levels parathyroid hormone (PTH) were elevated (mean±SD: 866.61±799.15; median 639.5, range: 52-3820 pg/ml) in all (initially done with IRMA till 2004 and later by chemilumiscence assay [Table 3]. Twelve patients had low calcium (<10.5 mg %) at presentation with classical symptoms of PHPT with mean calcium level of 9.5 mg/dl. These patients were challenged with 6 lakh units of cholecalciferol and repeat calcium values were done after three weeks. In seven patients calcium was raised to more than 10.5 mg/dl and the remaining five patients had corrected calcium less than 10.5 mg/dl; 25 OH Vitamin D was available in about 15 patients (only one patient had >30 ng/ml).

Eleven patients had elevated levels of serum creatinine. Skeletal involvement studied using radiography revealed subperiosteal resorption (SPR) in 48 (60.7%), osteopenia in 66 (83.5%), OFC in 40 (50.6%) and pseudo fracture in 28 (35%) [Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5].

Preoperative localization was done using ultrasonography (USG) [n=44 (55.6%), sensitivity: 77%], computed tomography (CT) [n=46 (58.2%), sensitivity: 93.5%] and thallium-technetium subtrac≠tion study/ technetium - 99 m (Tc - 99 m) sestamibi, [n=47, (59.4%), sensitivity: 86.9%]. Thallium-technetium subtrac≠tion study was done in initial 35 patients. There was no false localization. First five patients underwent surgery without any preoperative localization and adenoma was found intraoperatively. The sensitivity of all these modalities has improved over the years with improvement in equipment and expertise and stands at 95% for nuclear scan and 80% for USG and CT since the year 2000.

After localization, all the patients were subjected to inpatient parathyroidectomy under short general anesthesia. Ten patients (12.6%) required treatment with IV pamidronate at a dose 60-90 mg as calcium level was more than 14 mg/dl prior to surgery. A single experienced surgeon performed all surgeries. Operative procedure consisted of unilateral neck exploration directed by the preoperative localization, with removal of the abnormal looking gland and biopsy of the other gland of the same side, if visualized. In earlier eight patients in the series, all the four glands were explored and later all the glands were explored if preoperative localization was not available. Single adenoma was removed in 72 patients. Adenoma was not localized preoperatively in five patients. Five patients had multiple adenomas (two-gland involvement in three, three-gland involvement in two patients).

All the four glands were removed in three patients in whom no adenoma was visualized. Sixty-five per cent of the tumors were from inferior glands with almost equal distribution between right and left side. The data on tumor weight was available in 25 patients and mean weight was 3.31 (range: 0.23-15) g. Only one patient in our series had ectopic parathyroid which was localized to retrosternal area and removed through a cervical incision.

All patients were put on oral calcium carbonate with first oral feed. Six lakh units of cholecalciferol were also given to all a day prior to surgery. Serum calcium and phosphorous were estimated on the second day or earlier if the patient developed symptoms of hypocalcemia. Hungry bone syndrome characterized by severe hypocalcemia, hypophosphatemia, tetany, peri-oral tingling and numbness occurred in 24 (30.3%) patients. Transient hypoparathyroidism developed in 49 (62%) patients (35 asymptomatic and 14 symptomatic) and permanent hypoparathyroidism was seen in two patients excluding patients who underwent excision of all four glands. There were no other surgical complications including vocal cord palsy. Histopathology showed adenoma in 69 cases, hyperplasia in eight patients and two patients had parathyroid carcinoma. Parathyroid carcinoma was diagnosed on histopathology; both these patients were younger (21 and 32-year-old), had high calcium levels (11.8 and 14mg%), and high PTH levels (540 and 1688 ng/ml). Both of them didn't have metastasis at presentation and were lost to follow-up. Postoperative follow-up was available in 52 patients for mean duration of 16.2 (range: 12 to 36) months.

The published data of PHPT in children and adolescents from our center (n=18) was compared with adult PHPT [Table 4]. Duration of symptoms prior to diagnosis was shorter in the pediatric population (12 months) as compared to adults (32 months). Apart from this, the major manifestations of the disease including complications were comparable between the two groups except for absence of renal failure in the pediatric population (13.9% in adults). Another difference noticed between the groups was the occurrence of cases of hyperplasia (10.1%) and carcinoma (2.5%) in adult patients. But none of these differences were statistically significant.


 :: Discussion Top


Patients from various regions of western India are referred to our center rightly qualifying our cohort as a representative sample of western India. Our patients with PHPT presented at a younger age, later in the course of disease and had symptomatic presentation. This is contrast to the Western data and in agreement with earlier published data from India. [6],[7],[8],[9],[10],[11]

Female: male ratio in our cohort was 2:1 which is concurrent with other Indian and Western data. Age of presentation was far younger than that described in the Western literature though we excluded patients below the age of 20 years. This mean age is comparable to that of presentation in other Indian studies. [6],[7],[8],[9],[10],[11]

Skeletal involvement was the most common presenting symptom and was higher compared to recent literature from the West. The frequency of specific radiological manifestations of PHPT has fallen from 23% in the Cope Series to less than 2% in the series of Silverberg et al. [3],[12] Calcium and vitamin D nutrition usually determine the severity of skeletal disease in PHPT, but additional pathogenetic factors may also contribute. [13],[14] Fractures secondary to PHPT were present in 41 patients (51.8%) and OFC was seen in 40 (50.6%) patients. The incidence of OFC and fractures is comparable to other Indian data.

The incidence of renal disease in our cohort (40.5%) was less compared with other Indian data (which ranges from 54-70%). [9],[11] Reasons for a lesser incidence in our series are not clear. In the Western literature, prevalence of renal stones has fallen from 57% to less than 5% in recent years. [15] This may probably be due to the introduction of routine calcium estimations by autoanalyser with detection of more asymptomatic cases of PHPT.

Pancreatitis was observed in nine (11.3%) patients and two patients had evidence of pancreatic calculi without any symptoms. The previous data from India also reports that 12-13% of patients have pancreatitis. [11],[16] This incidence is higher compared to the Western literature and proposed causes for a higher incidence are increased number of patients with symptomatic hyperparathyroidism and probably by precipitation of unusual pancreatic diseases like tropical chronic pancreatitis (TCP). [16] The higher incidence in males is in agreement with previously published literature. [16],[17]

The mechanism of hypercalcemia as a cause of pancreatitis is controversial and poorly understood. Four possible mechanisms are postulated; calcium-phosphate deposition in the pancreatic ducts; calcium dependent conversion of trypsinogen to trypsin; increased permeability of pancreatic duct due to hypercalcemia; and an apparent direct toxic effect of PTH on pancreas. [16] Higher incidence of pancreatitis in Indian series may be due to the higher proportion of patients with symptomatic PHPT. Interestingly, none of our patients had behavioral manifestations .

Corrected mean serum calcium was 12.55 mg/dl and 12 patients had normocalcemia at presentation (calcium levels less than 10.5 mg/dl.). However, seven patients who had concurrent vitamin D deficiency responded with increase in calcium levels to more than 10.5 mg/dl. This is in agreement with the recent data from India but contradicts an earlier report by Harinarayan et al., from India who observed normocalcemia in 50% of patients. [6],[9],[11] Mean inorganic phosphorus was 1.81 mg/dl and is in concurrence both Western and Indian data. Elevated ALP (mean: 762.2: median: 559IU/L) and PTH (mean: 866.61; median: 639.5 pg/ml) are higher than reported for developed countries, but similar to that reported previously from India; [5],[6],[7],[8],[9],[10],[11] 25 OH vitamin D levels were available in only 15 patients, which made it difficult to analyze the relation of PHPT with vitamin D in our cohort. However, only one patient had normal 25 OH vitamin D level (>30 ng/ml).

The parathyroid glands are well-known to vary in anatomic location and the typical ectopic sites are intrathyroidal, ret≠roesophageal, lateral neck and mediastinum. Tests to confirm the diagnosis and localize abnormal gland have undergone a sea change for the better in last decade. Noninvasive imaging of parathyroids includes use of USG, CT, magnetic resonance imaging (MRI), technetium-99 m (Tc-99 m) sestamibi, and thallium-technetium subtrac≠tion study. Although each of these approaches has advantages and disadvantages, Tc-99 m sestamibi has the advantage that the entire mediastinal and cervical regions can be visualized. Preoperative localization was not achieved in the first five patients in the series and adenoma was found intraoperatively.

We used USG, CT, Tc-99 m sestamibi scan, and thallium-technetium subtrac≠tion study. In recent years we have used the Tc-99 m ses≠tamibi scan, USG or CT for localization. In our series USG had a sensitivity of about 77%, which was comparable to the data from other series from India. [6],[7],[8],[9],[10],[11] The sensitivity of CT scan and thallium-technetium subtrac≠tion study/ Tc-99 m sestamibi in our series was 93.5% and 86.9% respectively which are comparable to the data from literature. [6],[7],[8],[9],[10],[11]

Surgery is the curative treatment for PHPT. Our earlier patients underwent bilateral neck exploration with resection of enlarged parathyroid glands. With improved preoperative localization available, later patients underwent unilateral neck exploration as directed by preoperative localization, with removal of abnormal looking gland and biopsy of other gland of the same side if visualized. Postoperative follow-up of at least one year was available in 52 patients. Repeat surgery was done in five patients due to recurrence of symptoms. In three patients out of five who underwent repeat surgery, the initial surgery was done outside the institution. In five patients, multiple adenomas have been noted intraoperatively and all were excised and showed adenomatous changes. As described in a previous report from India, adenomas were predominantly arising from inferior glands. [9]

Hungry bone syndrome was observed in about 30% of our patients. Transient hypoparathyroidism developed in 49 patients and two patients had permanent hypoparathyroidism. Children and adolescent patients with PHPT in our series had a clinical and laboratory profile almost similar to the adult patients. [18] One reason for this could be the clustering of disease in early adulthood with more than one-third of cases (35.29%) occurring between 15 and 25 years of age. The disease occurred with median age at onset of 33 years with more than three quarter patients below the age of 40 years. Western literature suggests the symptoms in children with PHPT to be more severe and more common than their adult counterparts. [19] The high incidence of patients who were symptomatic at diagnosis in our series (100%) is similar to earlier reports of 79-91% patients being symptomatic. [20],[21] But these differences in symptomatic PHPT are not seen in Indian patients as adult patients also have symptomatic PHPT. We also did not observe any difference in skeletal manifestations among the two groups. But early and severe skeletal manifestations may be inferred from the fact that severe and comparable skeletal involvement was present in our pediatric population at diagnosis despite the shorter duration of symptoms (12 months) compared to adults (32 months). The absence of renal failure in the pediatric population (13.9% in adults) may also be due to skeletal involvement leading to earlier diagnosis before onset of renal failure. This assumption is corroborated by the fact that asymptomatic renal disease in our pediatric cohort (renal calculus disease: 40% vs. 40.5%) was similar to that of adults.

In conclusion, presentation of PHPT in western India occurs at a younger age and is symptomatic with regard to skeletal, renal and pancreatic manifestations, with classical biochemical abnormalities (hypercalcemia, hypophoshatemia and inappropriately elevated PTH). Preoperative localization techniques have improved over years which help in more localized surgery with high cure rates and lesser complications. There is no significant change in the clinical, laboratory and radiological features between adults and children with PHPT.

 
 :: References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]

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