Primary hyperparathyroidism due to parathyroid carcinoma

OBJECTIVES: Our aim was to determine whether tissue factor pathway inhibitor (TFPI), a physiologically important natural anticoagulant that acts by inhibiting the extrinsic pathway, concentrations decrease as liver disease progresses, and, second, whether TFPI has an etiologic role in portal vein thrombosis in cirrhotics. METHODS: After taking their informed consent, we determined TFPI concentrations in the plasma of healthy subjects (group I) (n = 15) (average age, 45.1 = 11.8 yr), cirrhotics (group II) (n = 16) (average age, 43.6 +/- 9.8 yr), and cirrhotics with portal vein thrombosis (group III) (n = 12) (average age, 42.6 +/- 10.7 yr). Mean and median TFPI values and interquartile ratios were determined for groups I, II, and III. Then group II and III were further divided according to the Child classes A, B, or C, and mean and median TFPI values and interquartile ratios were determined for these classes as well. Using the Man-Whitney U test, we compared the results. RESULTS: Statistically important differences were documented (p = 0.005) between the median TFPI levels of healthy adults and Child C cirrhotics (concentration lower in Child C) and between normal subjects and cirrhotics with portal vein thrombosis (p = 0.02) (TFPI concentration being lower in the latter group again). CONCLUSIONS: TFPI concentration decreases in advanced liver disease, and this may be a contributory factor for portal vein thrombosis in at least some cases of cirrhotics.     

Recurrent intracranial hemorrhage due to postpartum cerebral angiopathy: implications for management

BACKGROUND: Postpartum cerebral angiopathy as a cause of hemorrhagic stroke in young women is not well recognized. It is unknown whether this disorder represents a true inflammatory vasculitis or transient vasoconstriction related to the hormonal events of pregnancy and the postpartum period. CASE DESCRIPTION: A 39-year-old woman presented with postpartum intracranial hemorrhage and, 32 months later, with subarachnoid hemorrhage, following normal pregnancies. Cerebral angiography obtained after each stroke demonstrated diffuse irregularity of branches of the middle cerebral arteries consistent with a diffuse vasospastic process or classic vasculitis. Neurological deficits resolved and results of a transcranial Doppler study normalized after a short course of high-dose corticosteroids following the second stroke. CONCLUSIONS: Postpartum cerebral angiopathy should be considered in the differential diagnosis of recurrent intracranial hemorrhagic stroke in young women. Recognition of this condition may preclude treatment with potentially toxic therapies for vasculitis and will have important implications for counseling women on subsequent pregnancies.     

Primary hyperparathyroidism secondary to parathyroid carcinoma: report of a case

Distinguishing parathyroid carcinoma from benign hyperparathyroidism is often difficult. Clinical features most commonly associated with parathyroid carcinoma, such as palpable cervical mass, markedly higher serum calcium, high parathyroid hormone immunoassay, and evidence of bone disease may not be present. Therefore, intraoperative recognition is essential. We report a case in which the presenting symptoms, physical examination, and laboratory analysis were consistent with benign disease. During surgery, the finding of an enlarged firm gland with surrounding inflammatory reaction altered the approach to include the possibility of parathyroid carcinoma. The gland and surrounding tissue were removed, and pathologic examination led to the diagnosis of carcinoma. At 18-month follow-up, the patient was free from recurrence. Any parathyroid gland with a gray appearance, firm texture, and surrounding inflammatory reaction should be treated as carcinoma. Initial intraoperative recognition offers the best chance for cure, since local recurrences are rarely curable.     

Nephrolithiasis due to primary hyperparathyroidism and enteric hyperoxaluria: a case report

Enteric hyperoxaluria and primary hyperparathyroidism have been associated with the development of nephrolithiasis. We report a case involving a patient who had hyperparathyroidism due to a parathyroid adenoma and enteric hyperoxaluria resulting from a small bowel bypass and who had severe stone-related complications. This combination of stone-generating factors has heretofore not been reported. The pathophysiology of these entities is discussed.     

Secondary hyperparathyroidism: pathophysiology, histopathology, and medical and surgical management

It is generally accepted that morphological changes of the parathyroid glands appear early in renal failure. When diffuse hyperplasia develops into a nodular type, the cells grow monoclonally and proliferate aggressively, with abnormal suppression of parathyroid hormone (PTH) secretion under high extracellular calcium. Based on histopathological and pathophysiological findings, patients with nodular hyperplasia in renal hyperparathyroidism might be refractory to medical treatment, including calcitriol pulse therapy. Thus, parathyroid surgery is indicated for individuals developing hypercalcemia, elevated PTH levels, and/or bone disease, who cannot be effectively treated medically. The detection of enlarged parathyroid glands by image diagnosis is another criterion for surgery. In our experience, parathyroidectomy is an effective treatment; however, the timing of the operation is important, because skeletal deformity and vessel calcification cannot be expected to diminish even after successful surgery. Technically, it is important to identify all parathyroid glands and, in autotransplantation, to use an adequate amount of suitable tissue, namely, a diffuse type of hyperplastic tissue, to guarantee satisfactory postoperative function.     

Spinal tumour due to primary hyperparathyroidism causing sciatica: case report

We report a unilateral intraspinal cyst-like lesion adjacent to the lamina and facet joint at the L4-L5 level producing sciatica. Histological examination revealed multinucleate giant cells suggesting a brown tumour. Further studies disclosed primary hyperparathyroidism, whose first manifestation was the lumbar nerve root compression. Previous cases of compression of neural structures by spinal brown tumours are reviewed and a radiological differential diagnosis is presented.     

Vitamin D receptor polymorphisms correlate to parathyroid cell function in primary hyperparathyroidism

Calcitriol acts via its receptor (VDR) and inhibits PTH secretion and parathyroid cell proliferation. Increased prevalence of the polymorphic VDR alleles b, a, and T has been demonstrated in sporadic primary hyperparathyroidism. Sixty-two patients with primary hyperparathyroidism due to parathyroid adenoma (mean age, 69.5 +/- 1.4 yr) were genotyped for these VDR polymorphisms. Dispersed cells of the adenomas were exposed to increasing concentrations of extracellular Ca2+ and analyzed for PTH release and cytoplasmic Ca2+ concentrations. Ca2+-mediated PTH inhibition exhibited higher ED50 and less suppression in the cells of patients who were homozygous for the b, a, and T alleles (P < 0.05-0.10). When analyzing haplotypes, the patients with baT demonstrated a ED50 of 1.81 +/- 0.15 vs. 1.29 +/- 0.10 for BAt (P < 0.05). As VDR alleles were unrelated to parathyroid intracellular Ca2+, influences of polymorphic VDR alleles on PTH secretion seem to involve mechanisms other than the Ca2+-sensing protein of the parathyroid cell surface.     

Recurrent goiter, hyperthyroidism, galactorrhea and amenorrhea due to a thyrotropin and prolactin-producing pituitary tumor

A 22-year-old woman with recurrent goiter, hyperthyroidism, galactorrhea, and amenorrhea due to a pituitary tumor is described. She had been treated surgically twice for recurrent goiter with tracheal compression. Despite clinical signs of hyperthyroidism and slightly elevated plasma thyroid hormone levels (T4: 11 mug/dl; T3: 189 ng/dl), without thyroid hormone replacement therapy the basal TSH level was elevated up to 23 muU/ml and could not be suppressed by exogenous thyroid hormones: even when the serum thyroid hormone levels were raised into the thyrotoxic range (T4: 16.2 mug/dl T3: 392 ng/dl), the basal TSH fluctuated between 12 and 29 muU/ml. The basal PRL level was elevated up to 6000 muU/ml. The administration of TRH (200 mug iv) led only to small increments of TSH and PRL levels. Bromocriptin (5 mg p.o.) or l-dopa (0.5 g p.o.) suppressed TSH and PRL values significantly. After transsphenoidal hypophysectomy, TSH and PRL were below normal and the patient development panhypopituitarism. The adenoma showed two cell types which could be identified as lactotrophs and thyrotrophs by electronmicroscopy and immunofluorescence. From these data we conclude that the patient had a pituitary tumor with an overproduction of thyrotropin and prolactin.     

Recurrent anaphylaxis: diagnostic approach and management

The purpose of this study was to examine the effect of cycle rate (CR) variations on the metabolic cost and upper body forces during roller skiing with the V2-alternate technique on flat terrain. Nine highly skilled cross-country skiers roller skied at a paced speed of 18.0+/-0.1 km x h(-1) using their chosen CR, and CRs that were 10% slower and 20% faster. Oxygen uptake (VO2) was determined through collection of expired gases into a meterological balloon and poling forces were measured with piezoelectric transducers during the last 30 s of each four minute trial of roller skiing. One-way repeated measures ANOVA revealed that VO2 varied significantly with CR (p=0.02) with the chosen CR being significantly lower than the higher CR (p < 0.05). Poling forces and poling time were not significantly different among the CR conditions. The present results demonstrate that 1) an alteration in cycle rate affects metabolic cost of roller ski skating, 2) skiers tend to naturally select the most economical cycle rate, and 3) moderate variations in cycle rate do not appear to affect propulsive force generation through the poles in roller skiing.     

Trabecular bone mineral density in primary hyperparathyroidism: relationship to clinical presentation and biomarkers of skeletal turnover

This study was carried out in order to investigate the entity of trabecular bone involvement in 62 patients with primary hyperparathyroidism (PHPT). Bone mineral density (BMD) was measured in all patients at the ultradistal radius (UDR) of the non-dominant arm by a dual photon densitometer and also at the lumbar spine (L) in 40 of the patients by means of quantitative dual energy radiography. Mean Z score values of UDR-BMD (-2.4 +/- 0.4) and L-BMD (-3.5 +/- 0.2) in patients with the skeletal variety of the disease (n = 6) were significantly reduced in respect to values of both asymptomatic (n = 31) and kidney stone patients (n = 25). As far as the comparison between the two sites of trabecular bone mass measurement in each hyperparathyroid subgroup of patients was concerned, a significant difference (P < 0.05) was found in patients with skeletal manifestations of the disease. Either serum total alkaline phosphatase activity, or osteocalcin and the 24-h hydroxyproline/creatinine ratio were significantly inversely related to the entity of bone mass evaluated at these two sites. Z score changes following surgery in 14 patients showed a positive trend in 13 of them at L compared to 7 out of 14 at UDR (P < 0.036 by chi square analysis). There was a very good inverse correlation between basal Z score values and the changes following surgery at the L (r = -0.851; P < 0.001) but not at the UDR. Our results demonstrate firstly that, in PHPT skeletal sites with almost similar composition of trabecular bone are differently involved in patients with more severe skeletal damage and that different skeletal sites may be divergently affected by the cessation of parathyroid gland hyperfunction.     

Myocardial infarct and diabetes mellitus: incidence, management and prognosis

The authors analyse the data of the Myocardial and Diabetes Register, where 2436 diabetic patients (pts) and 1448 pts with acute myocardial infarction (AMI) were registered between 1st of January, 1992 and 31st of December 1994. In the history of diabetic patients previous AMI was present in 14.4% of the cases. The 21.6% of the AMI pts had diabetes mellitus as well. According to the type of diabetes (IDDM and NIDDM) the prevalence of AMI in the history of the registered persons was significantly different: among pts with NIDDM the previous AMI was found 14.8% of the pts and only 2% of pts with IDDM (p = 0.012). The clinical picture of AMI was also different of AMI pts with and without diabetes: chest pain suggesting AMI was present 10.9% of pts with proved AMI and diabetes mellitus, and 86.2% of pts with AMI without diabetes (p < 0.0001). The Streptokinase treatment was more common among AMI pts without diabetes (18.2% versus 12.5% p = 0.022). The hospital lethality was significantly higher among AMI pts with diabetes (42.8% versus 29.4% (p < 0.0001). The poorer prognosis was independent of age.     

Secondary membranoproliferative glomerulonephritis due to hemolytic uremic syndrome: an unusual presentation

In vitro selection can be used to generate nucleic acid ligands (aptamers) to target molecules ranging in size and structure from cations to cells. However, the selection process is repetitive and time-consuming. We have automated a protocol for in vitro selection using an augmented Beckman Biomek 2000 pipetting robot. The automated selection procedure requires the integration of four devices and the optimization of four molecular biology methods, and is one of the most complex automated protocols attempted to date. Initial attempts at selection yielded robust replication parasites, but optimization of the automated selection procedure suppressed the emergence of these parasites and led to the selection of true nucleic acid ligands. Automated selection can now be used to generate nucleic acid aptamers in days rather than weeks or months.     

Indications, technique, and efficacy of alcohol injection of enlarged parathyroid glands in patients with primary hyperparathyroidism

BACKGROUND: Percutaneous alcohol ablation of the parathyroid gland (PAAP) has been proposed as an alternative treatment for primary hyperparathyroidism in patients unsuitable for surgery. The current study aimed to determine the (1) selection criteria, (2) associated morbidity, and (3) efficacy of PAAP. METHODS: From 1987 to 1998, 36 patients with primary hyperparathyroidism (mean age 65 years) underwent PAAP. The indications for PAAP were (1) medical comorbidity, (2) technically unsafe reoperative surgery, (3) partial ablation of a single remaining gland, and (4) patient choice. RESULTS: There were no long-term complications. Two patients had temporary recurrent laryngeal nerve injury and 4 had temporary hypocalcemia. Over a median follow-up of 16 months, 12 (33%) of the patients remained eucalcemic. For analysis purposes patients were separated into 2 separate groups: 29 with attempted complete ablation and 7 with partial ablation of a single remaining gland only. Ten of the complete ablation group (34%) remained eucalcemic. In the partial ablation group only 2 remained eucalcemic, but all had adequately controlled serum calcium levels. CONCLUSION: PAAP should be considered for hyperparathyroid patients with excessive reoperative morbidity or prohibitive medical comorbidity or those in whom the intent is to partially ablate a single remaining enlarged gland. In these patients close follow-up of serum calcium is required, and repeat treatments may be necessary because recurrence of hypercalcemia is likely.     

Major histocompatibility complex class II expression and parathyroid autoantibodies in primary hyperparathyroidism

We evaluated whether kinins exert a protective action against the development of two-kidney, one clip (2K1C) hypertension, a model characterized by an activated renin-angiotensin system in the ischemic kidney and increased expression of the bradykinin (BK) B2 receptor in the contralateral kidney. BK B2-receptor knockout (B2-/-), wild-type (B2+/+), and heterozygous (B2+/-) mice underwent clipping of the left renal artery, with the other kidney remaining untouched. Basal systolic blood pressure (SBP, via tail-cuff plethysmography) was higher in B2-/- mice than in B2+/- or B2+/+ mice (121+/-2 versus 113+/-2 and 109+/-1 mm Hg; P<0.05 for both comparisons). SBP did not change from basal values after sham operation, but it increased in mice that underwent clipping. The increase in SBP was greater in 2K1C B2-/- mice than in B2+/- or B2+/+ mice (28+/-2 versus 14+/-2 and 14+/-2 mm Hg, respectively, at 2 weeks; P<0.05 for both comparisons). Blockade of the BK B2 receptor by Icatibant enhanced the pressure response to clipping in B2+/+ mice (29+/-2 mm Hg at 2 weeks). Intra-arterial mean blood pressure (MBP) was higher in 2K1C than in respective sham-operated mice, with the MBP difference being higher in B2-/- mice (32 and 38 mm Hg, at 2 and 4 weeks, respectively), and higher in B2+/+ mice given Icatibant (30 and 32 mm Hg) than in B2+/+ mice without Icatibant (17 and 18 mm Hg). At 4 weeks, acute injection of an angiotensin type 1 receptor antagonist normalized the MBP of 2K1C hypertensive mice. A tachycardic response was observed 1 week after clipping in B2-/- and B2+/- mice, but this effect was delayed in B2+/+ mice. However, the HR response to clipping in B2+/+ mice was enhanced by Icatibant. Within each strain, heart weight to body weight ratio was greater in 2K1C hypertensive mice than in sham-operated control animals (B2-/-: 5.7+/-0.1 versus 5.2+/-0.1; B2+/+: 5.1+/-0.1 versus 4.5+/-0.1; P<0.01 for both comparisons). The clipped kidney weight to nonclipped kidney weight ratio was consistently reduced in mice with 2K1C hypertension. Our results indicate that kinins acting on the BK B2 receptor exert a protective action against excessive blood pressure elevation during early phases of 2K1C hypertension.