K. K. Pun

Loss of bone mass in patients with Klinefelter's syndrome despite sufficient testosterone replacement

To determine whether testosterone replacement therapy reverses the detrimental effects of hypogonadism on bone density, we measured the total body, lumbar spine and proximal femur bone mineral density (BMD) by dual-energy X-ray absorptiometry in 14 patients with Klinefelters syndrome on long-term testosterone replacement therapy and compared the results with 14 age- and sex-matched normal controls. Seven of the patients were receiving oral testosterone undecanoate thrice daily (240 mg/day) and the others were having intramuscular testosterone enanthate injections once every 3 weeks (250 mg/injection). Their serum testosterone levels were maintained within the normal limits (10–40 nmol/l). We showed that patients on testosterone replacement had decreased amount of bone density in the left femoral neck when compared with the controls (p<0.01). Similar decreases were also observed in the left Wards triangle (p<0.01) and in the left trochanter (p<0.05). There were no significant differences in the total body and the lumbar spine measurements in these two groups of subjects. No correlation was found between the BMD values of femur and the duration of testosterone treatment in the patients with Klinefelters syndrome. The type of testosterone treatment was also not associated with significant differences in BMD. In conclusion, sufficient testosterone replacement with currently available methods does not reverse the decrease in bone mass associated with hypogonadism in patients with Klinefelters syndrome.

Addisonian crisis as presenting feature in malignancies

Metastases to the adrenal glands are common in patients with malignancy but malignant disease presenting as Addisonian crisis is rare. The authors presented two patients with acute Addisonian crises due to metastatic infiltration of the adrenal glands. They were otherwise asymptomatic from the primary tumor. Computed tomographic scan showed bilateral adrenal enlargement and transcutaneous biopsy confirmed metastatic adenocarcinoma in the adrenals. Adequate glucocorticoid replacement improves quality of life and prolongs survival.

Vitamin D status among patients with fractured neck of femur in Hong Kong

Vitamin D deficiency leads to secondary hyperparathyroidism initially and then to mild osteomalacia, both of which conditions may be aymptomatic and may predispose to bone fracture. To assess the importance of vitamin D deficiency in predisposing to fractured neck of femur, we studied the vitamin D status, dietary intake and socio-economic characteristics in 69 patients with fractured neck of femur (group A), 28 normal subjects with age above 60 (group B), and 101 normal volunteers (group C). Patients with fractured neck of femor had significantly lower levels of serum 25-hydroxy-cholecalciferol compared with subjects of groups B and C. There is no statistically significant difference in other biochemical parameters, including calcium, phosphate, and alkaline phosphatase. Patients with fractured neck of femur and with 25-hydroxycholecalciferol below 20 ng/mL were characterized by a home-bound and/or institutionalized life-style, smaller living place, and limited access to open space. To conclude, hypovitaminosis D is a common problem among elderly patients with fractured neck of femur in Hong Kong. The fact that such vitamin D deficiency is associated with muscle weakness may contribute to falls, and thus indirectly account for an increased rate of hip fractures over the normal control.

Hypokalemic Periodic Paralysis due to the Sjögren Syndrome in Chinese Patients

Excerpt The Sjogren syndrome is complicated by distal renal tubular acidosis in about 40% of the patients (1). Three patients presented with hypokalemic paralysis as a result of renal tubular acido...

25-HYDROXYCHOLECALCIFEROL AND INSULIN-LIKE GROWTH FACTOR I ARE DETERMINANTS OF SERUM CONCENTRATION OF OSTEOCALCIN IN ELDERLY SUBJECTS WITH AND WITHOUT SPINAL FRACTURES

Osteocalcin is one of the major proteins in the osseous matrix. To evaluate the determinants and thus the physiological control of osteocalcin production in normal and osteoporotic subjects, the serum levels of osteocalcin, 25-hydroxycholecalciferol (25-OH-D3), and insulin-like growth factor I (IGFI) were measured by radioimmunoassay in 44 subjects over 60 years old. Circulating osteocalcin, 25-OH-D3, and IGFI were 0.28 +/- 0.10 nmol/L (1.65 +/- 0.96 ng/mL), 70.5 +/- 25.1 nmol/L (28.3 +/- 10.1 ng/mL), and 23.8 +/- 12.0 nmol/L in 27 healthy controls respectively, as compared with 0.09 +/- 0.09 nmol/L (0.52 +/- 0.52 ng/mL), 48.2 +/- 19.9 nmol/L (19.35 +/- 7.91 ng/mL), and 16.56 +/- 6.96 nmol/L in 17 patients with spinal fractures. Significant correlation was found between osteocalcin and 25-OH-D3 level, as well as between osteocalcin and IGFI. The results show that IGFI and 25-OH-D3 are important determinants for serum concentration of osteocalcin in elderly subjects with and without spinal fractures.

Rhabdomyolysis associated with cranial diabetes insipidus.

Rhabdomyolysis has been reported to be associated with hyperosmolality in diabetic ketoacidosis and non-ketotic hyperosmolal state. Whether the rhabdomyolysis was due to hyperosmolality per se or whether hyperglycaemia also played a role is not clear. We hereby report a case of cranial diabetes insipidus with hypernatraemia and hyperosmolality complicated by rhabdomyolysis. None of the known risk factors, such as coma, hypokalaemia, hypophosphataemia, diabetic ketoacidosis or non-ketotic hyperosmolality, were present in this patient. We believe that severe hyperosmolality per se is an important predisposing factor for non-traumatic rhabdomyolysis, and serum muscle enzymes should be closely monitored in the management of patients with diabetes insipidus.

Hypocalcemic Heart Failure in End-Stage Renal Disease

A 37-year-old woman presented with hypocalcemic heart failure complicating end-stage renal disease. Heart failure persisted despite conventional therapy but improved after correction of hypocalcemia. Continuous monitoring of left ventricular function by radionuclide study during calcium replacement showed dramatic improvement. Our case showed that hypocalcemia could be a rare but reversible cause of frank heart failure in uremic patients.

Eight-Month Longitudinal Study of Urinary Excretion of Albumin and Tubular Proteins in Diabetic Subjects

To evaluate the importance of tubular proteinuria in diabetic nephropathy, we studied the serial changes of micro-albuminuria, microproteinuria and protein patterns by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) in 38 diabetic patients over 8 months. There was a significant correlation between the amount of micro-albuminuria measured by radio-immunoassay and the amount of microproteinuria quantitated by the Coomassie brilliant blue dye binding method (r = 0.976; p less than 0.0001). Micro-albuminuria of 50 mg/day was equivalent to microproteinuria of 190 mg/day. Among the 38 diabetic patients, 26 had micro-albuminuria above 50 mg/day, while 12 had micro-albuminuria below this level. There was a significant correlation between the amount of microproteinuria and haemoglobin A1, showing that the quantity of microproteinuria was affected by metabolic control. Diabetic patients with micro-albuminuria of above 50 mg/day have a significantly higher diastolic blood pressure than those below this level. Among the diabetic patients with micro-albuminuria of less than 50 mg/day, the amount of micro-albuminuria and microproteinuria remained constant, whereas progressive increases in micro-albuminuria and microproteinuria were observed among the 12 diabetic subjects with micro-albuminuria above 50 mg/day. These support the prognostic importance of this quantity of micro-albuminuria. The protein patterns as revealed by SDS-PAGE with Coomassie blue staining show a significant loss of low-molecular-weight proteins in 7 patients, which may therefore suggest tubular damage. The loss of tubular proteins persisted over a period of 8 months in all 7 subjects, and the amount gradually increased over this period.(ABSTRACT TRUNCATED AT 250 WORDS)

C-peptide in non-alcoholic cirrhosis and hepatocellular carcinoma

Fourteen normal controls, eleven patients with non-alcoholic cirrhosis, twenty-nine with hepatocellular carcinoma (HCC) and six with HCC and hypoglycemia were studied. The tests performed include iv glucose tolerance test (25 g) and glucagon challenge test (2 mg). In cirrhosis, glucose intolerance and insulin resistance were demonstrated. The fasting hyperinsulinemia in cirrhosis is the result of decreased degradation as shown by the normal fasting C-peptide. The increased insulin responses to glucose, despite a normal C-peptide response, further supports the importance of impaired degradation in the pathogenesis of hyperinsulinemia after challenge. Despite a strong etiological association between cirrhosis and HCC, patients with HCC do not have significant hyperinsulinemia or glucose intolerance. This provides metabolic evidence to support the clinico-pathological observation that HCC occurred when cirrhosis was not advanced or in a precirrhotic stage. In HCC patients with clinically overt hypoglycemia, the fasting glucose, insulin and C-peptide were very low. The C-peptide responses to glucose and glucagon challenges were suppressed despite pharmacologic stimulation. This can be explained by the suppression of insulin secretion by a circulating substance secreted by hepatoma. The results support the pathogenetic importance of insulin-like activities recently detected in HCC patients with hypoglycemia.

Absorption of intranasal salmon calcitonin in normal subjects and hypogonadic men

SummaryThe absorption kinetics of intranasal salmon calcitonin were assessed in 4 normal subjects and 9 patients with Klinefelters syndrome. After administration, absorption occurred within 5 minutes. There was a highly significant correlation between the amount administered and the amount absorbed (r=−0.83,P<0.0005).