The role of urinary fractionated metanephrines in the diagnosis of phaeochromocytoma.

Background & objectives: Plasma and urinary metanephrines are used as screening tests for the diagnosis of phaeochromocytoma. The recommended cut-off levels are not standardized. This study was conducted to identify a cut-off level for 24 h urinary fractionated metanephrines viz. metanephrine (uMN) and normetanephrine (uNMN) using enzyme immunoassay for the diagnosis of phaeochromocytoma. Methods: Consecutive patients suspected to have phaeochromocytoma were included in the study. uMN and uNMN in 24 h urinary sample were measured using a commercial ELISA kit. Results: Overall, 72 patients were included over a period of 18 months. Twenty patients had histopathologically confirmed phaeochromocytoma and in 52 patients phaeochromocytoma was ruled out. Using the upper limit of normal stated by the assay manufacturer as the cut-off, uMN >350 μg/day had a low sensitivity and uNMN >600 μg/day had a poor specificity. By increasing the cut-off value of uNMN to twice the upper limit, specificity increased significantly without much loss in sensitivity. Combining uMN and uNMN using a cut-off twice the upper limit improved the diagnostic performance - sensitivity (95%); specificity (92.3%); positive predictive value (PPV - 82.6%); negative predictive value (NPV - 98%). In subsets of patients with a variable pretest probability for phaeochromocytoma, the PPV correlates well with the occurred of these tumors decreased, while the NPV remained at 100 per cent. Interpretation & conclusions: ELISA is a simple and reliable method for measuring uMN and uNMN. The test has a good NPV and can be used as an initial screening test for ruling out phaeochromocytoma. Each hospital will have to define the cut-off value for the assay being used, choosing a proper control population.

Hypertensive crisis in a patient with thyroid cancer.

Phaeochromocytomas may be discovered incidentally when patients present with hypertensive crisis during general anaesthesia. A 49-year-old man underwent thyroidectomy 25 years ago and was diagnosed to have spindle cell carcinoma of the thyroid. He presented with recent onset of hoarseness of voice and was found to have a vocal cord nodule. He developed a hypertensive crisis during surgery. He was subsequently evaluated and found to have bilateral phaeochromocytoma. Further evaluation revealed a RET proto-oncogene mutation at codon 634 consistent with multiple endocrine neoplasia (MEN)-2A.

Aetiological, clinical and metabolic profile of hypokalaemic periodic paralysis in adults: a single-centre experience.

BACKGROUND: Hypokalaemic periodic paralysis constitutes a heterogeneous group of disorders that present with acute muscular weakness. In this analysis, we discuss the aetiological factors that appear to be more common in the Indian population. METHODS: From 1995 to 2001, 31 patients presented with periodic paralysis (mean age 34.5 years, range 11-68 years). Of the 31 patients, 19 were men. The clinical and laboratory data of these patients were analysed. Patients were investigated for possible secondary causes of hypokalaemla. RESULTS: There were 13 patients (42%) with renal tubular acidosis, 13 with primary hyperaldosteronism (42%), 2 each with thyrotoxic periodic paralysis and sporadic periodic paralysis, and I with Gitelman syndrome. Of the 13 patients with renal tubular acidosis, 10 had proximal and 3 distal renal tubular acidosis. Three of these patients with renal tubular acidosis had Sjogren syndrome. The patients diagnosed to have renal tubular acidosis had significantly lower serum bicarbonate (18.7 [14.6] v. 29.6 [5.0] mEq/L; p < 0.05) and higher levels of chloride (107.5 [6.0] v. 99.5 [3.4] mEq/L; p < 0.05) compared with those who had primary hyperaldosteronism, although the potassium values were similar (2.4 [0.65] v. 2.26 [0.48] mEq/L; p = 0.43). All patients with primary hyperaldosteronism had hypertension at presentation and were proven to have adrenal adenomas. CONCLUSION: A significant number of patients in this study had secondary and potentially reversible causes of hypokalaemic periodic paralysis. The common causes were renal tubular acidosis and primary hyperaldosteronism. A detailed work-up for secondary causes should be undertaken in Indian patients with hypokalaemic periodic paralysis.

Paget's disease of bone: experience from a centre in southern India.

BACKGROUND: Paget's disease is a localized disorder of the skeleton characterized by increased osteoclastic activity. While the prevalence in the Western Population is 1-2%, the prevalence in India is not known. We studied the clinical profile, biochemical parameters, bone scans, therapeutic details and follow up data of patients with Paget's disease, attending the Endocrinology outpatient clinic in our institution. METHODS: A retrospective review was done of the medical records of 51 patients seen in a tertiary referral centre in Southern India from 1995 to 2003.The data was analyzed using SPSS 9.0 software package. RESULTS: There were a total of 51 patients (41 male and 10 female). The mean age at presentation was 56 years and the mean duration of symptoms was 43 months. At least 6 months of follow-up was available in 31 patients and longer term (>2 years) follow-up in 22 patients. The symptoms at presentation were bone pain in 65%, low backache in 37%, skeletal deformities in 33%, pathological fractures in 20%, neurogenic claudication in 4%, deafness and head enlargement in 7% and renal stones in 4% of subjects. Five patients (9.8%) were asymptomatic and were incidentally diagnosed during evaluation of an elevated alkaline phosphatase. The mean serum alkaline phosphatase (range and SD) at the time of presentation was 690 IU/L (91-3873 U/L, 698 U/L). There was no statistically significant difference in the serum alkaline phosphatase values between female and male patients (576 U/L versus 718 U/L). Polyostotic involvement was seen in 90.2% of the patients. The pattern of skeletal involvement was very similar to that described in the Western literature. Twenty patients were started on Calcitonin and of these, 13 patients were later changed over to bisphosphonates to induce remission. In all, thirty six subjects received Alendronate and of them, 31 received lower doses (10-20mg/day). All the treated patients showed a good clinical and biochemical improvement. Two patients with severe Pagetic involvement of the bone who also had neurologic symptoms (root pains in one and cauda equina lesion in the other) needed intravenous Pamidronate to obtain a rapid response in the initial phase of treatment. CONCLUSIONS: In our series, Paget's disease had a male predominance. The clinical presentation and the pattern of skeletal involvement was similar to the Western series. Serum alkaline phosphatase declined by 40% at 6 months of therapy and by 64% by one year of treatment in patients who were on lower doses of Alendronate (10-20 mg/day) in our series, which is similar to what has been described with conventional doses (40 mg per day) in the Western series.