Fatal fulminant cryptococcemia complicating sarcoidosis: Is it to be expected?

Cryptococcosis may be a life-threatening complication of sarcoidosis. We describe a case of cryptococcemia that rapidly progressed toward fatality without apparent other sites of infection. We discuss on the importance of serum cryptococcal polysaccharide antigen testing for identifying at-risk patients who might benefit from timely diagnosis and treatment of cryptococcosis.

[High prevalence of thyroid disfunction in primary hyperaldosteronism]. / Alta prevalenza di disfunzioni della tiroide nell'iperaldosteronismo primario.

Primary hyperaldosteronism is associated with other endocrinology pathologies, like pheochromocytoma, Cushing's syndrome, hyperprolactinemia, primary hyperparathyroidism and a type of multiple endocrine neoplasia. Furthermore, association between hyperaldosteronism and thyroid diseases were already pointed out. Aim of the study was to value the prevalence of some thyroid diseases in a series of patients with primary hyperaldosteronism. We studied 105 consecutive patients with primary hyperaldosteronism, 43 (40.95%) with adrenal adenoma, 62 (50.05%) with bilateral adrenal hyperplasia and a control group of 223 patients with essential arterial hypertension. In all patients we tested thyroid function (FT3, FT4, TSH), thyroid antibodies (AbTPO, AbTG) and, sometimes, thyroid morphology by ultrasonography (US scan). The results of the study show that thyroid disfunction occur in 28.6% of patients with primary hyperaldosteronism and in 16.6% of patients with essential hypertension, with a statistically significative difference (chi2 = 0.012). At present, the relationship between primary hyperaldosteronism and thyroid diseases is unclear, but it can be hypothesized that there are common pathogenetic mechanisms, like an imbalance between various growth factors. Further studies are necessary to confirm the results of our study.

[Bone mass, bone metabolism, and prevalence of spinal fractures in recipients of allogenic bone marrow transplantation for leukemia]. / Massa ossea, metabolismo scheletrico e prevalenza delle fratture vertebrali in pazienti precedentemente sottoposti a trapianto di midollo osseo allogenico per leucemia.

The aim of this study was to evaluate in 65 patients, who had previously undergone allogenic bone marrow transplantation (ABMT), the bone mineral density (BMD), the skeletal turnover and the prevalence of vertebral fractures. At the moment of recruiting, 10 of 65 transplanted subjects (15.3%) presented with signs of rejection of the transplanted tissue, thus they were excluded. The remaining 55 patients (21 males, 34 females, mean age 30.8 +/- 6.4 years), with a follow-up of 60 +/- 9 months after the transplant and without any treatment inducing osteopenia, underwent ABMT respectively for: chronic myeloid leukemia (n = 24); acute myeloid leukemia (n = 18); acute lymphatic leukemia (n = 13). One hundred and ten healthy control subjects (42 males and 68 females, mean age 31.0 +/- 3.7 years) matching with the patients for age, weight and height, were successively enrolled. All the participants were submitted to a densitometric evaluation (DEXA) of lumbar spine (L1-L4), of femoral neck and total femur; besides some skeletal metabolism parameters were dosed, such as: total alkaline phosphatase, bone alkaline phosphatase and urinary excretion of C-terminal telopeptide fragments normalized to creatinine. On the contrary, the morphometric evaluation, performed through a lateral dorsolumbar radiography, was actually carried out only in patients who had already undergone ABMT. The L1-L4 BMD study showed: 10/55 osteoporotic (18.1%), 19/55 osteopenic (34.5%) and 26/55 normal patients (47.4%). In transplanted patients BMD values, obtained at the three considered sites, resulted significantly reduced (p < 0.01) in comparison to controls. Moreover, in patients who underwent ABMT, a statistically significant increase was observed, in comparison to healthy subjects, in total alkaline phosphatase (p < 0.01), in bone alkaline phosphatase (p < 0.01) and in urinary excretion of C-terminal telopeptide fragments normalized to creatinine levels (p < 0.001). Seven of the 55 transplanted patients (12.7%) presented at the moment of Rx morphometric evaluation at least one vertebral fracture: 6 of whom were affected by osteoporosis and 1 by osteopenia. In conclusion, the subjects who had previously undergone ABMT maintain, even at a certain time after the transplant and without any rejection, an increased skeletal turnover and BMD values meanly lower than normal, leading to an increased risk for vertebral fracture.

[Turnover of bone metabolism and prevalence of vertebral fractures in adrenal incidentalomas]. / Valutazione del turnover osseo e delle fratture vertebrali in incidentalomi surrenalici.

Aim of the study was to evaluate, in a homogeneous group of patients with adrenal incidentalomas (AI), calcium-phosphorus metabolism alterations, bone mineral density (BMD) and the prevalence of vertebral fractures. We selected 46 patients with adrenal incidentalomas (26M, 20F; age: M = 61 +/- 14, F = 65 +/- 10 years, BMI: M = 26.2 +/- 4 Kg/m2, F = 28.8 +/- 4 Kg/m2) compared with 84 normal subjects (NS) (44M, 40F; age: M = 60 +/- 10, F = 62 +/- 8 years; BMI: M = 27 +/- 2 Kg/m2, F = 28.1 +/- 4.5 Kg/m2). In all subjects we estimated calcium-phosphorus parameters. Our results showed that in 46 patients with AI there were a significant reduction of BMD-LS (0.915 +/- 0.176 g/cm2; p = 0.01) and of BMD-FN (0.710 +/- 0.129; p = 0.034) respect to those of NS (respectively: 0.994 +/- 0.14 9 g/cm2; 0.758 +/- 0.117 g/cm2). BMD-LS of the 20 women with AI (0.864 +/- 0.157 g/cm2, p = 0.01) was significantly reduced compared with the 40 female normal subjects (0.904 +/- 0.148 g/cm2); BMD-LS of the 26 men with AI (0.967 +/- 0.187 g/cm2; p = 0.048) was significantly reduced compared with the male normal subjects (1.048 +/- 0.133 r/cm2; p = 0.048). The MXA showed vertebral fractures in 15 (75%) of 20 patients with AI (2 patients were osteoporotic, 9 osteopenic and 4 normal at the MXA scans). In 20 women with AI, compared with female NS, we found a significant reduction of serum 25 OH D3 (p = 0.024) levels and a significant increase of plasma i-PTH (P = 0.04) value; and we found a negative correlation between plasma i-PTH and 25 OH D3 values (r = -0.451; p > 0.045). In conclusion, we demonstrated that patients with non-functioning adrenal incidentalomas present calcium-phosphorus metabolism alterations, associated at a reduction of BMD and an increase of vertebral fractures.

[The use of parenteral clodronate in elderly women with postmenopausal osteoporosis: compliance, effects on bone mineral density and on bone turnover]. / L'uso del clodronato per via parenterale in donne anziane affette da osteoporosi postmenopausale: compliance, effetti sulla densità minerale ossea e sul turnover scheletrico.

The aim of the study was to evaluate parenteral clodronate (CLD) compliance in patients with postmenopausal osteoporosis and intolerance to aminobisphosphonates. Moreover, we have also assessed the effects of CLD on bone mineral density (BMD) and bone turnover. Eighty-four consecutive postmenopausal women with osteoporosis (range 62-74 years) were enrolled and randomly allocated to three groups: group A included 26 women who received CLD i.v., 300 mg/2 weeks and oral supplemental calcium carbonate (500 mg x 2/day) and vitamin D3 (400 IU x 2/day); group B included 28 women who received CLD i.m., 100 mg/week, and the same dose of calcium and vitamin D3 administered to group A; group C, the control group, included 30 women receiving only calcium and vitamin D3 at the same doses as the other two groups. The lumbar spine (L1-L4) and femoral neck (FN) BMD were measured by dual energy X-ray absorbiometry at time 0 (T0) and after 6 (T6), 12 (T12), 18 (T18) and 24 (T24) months. At the same time, the serum bone specific alkaline phosphatase and amino-terminal telopeptide of type I collagen normalized by creatinine (NTx/cr) were determined at T0, T6, T12, T18, and T24. Eighty (95.2%) women completed the study, 24 in group A, 27 in group B and 29 in group C. In groups A and B, after 6 months of treatment we found a significantly greater (p < 0.05) increase in the L1-L4 BMD with respect to group C. After 12 months of therapy, in group A the L1-L4 BMD (1.8 +/- 0.5%) was significantly higher (p < 0.05) than that in group B (0.9 +/- 0.3%). At the end of the study, in groups A (1.2 +/- 0.5%) and B (1.1 +/- 0.4%) the percentage increase in the FN BMD was significantly greater (p < 0.05) than in group C (0.6 +/- 0.5%). After 24 months of therapy, there was no difference in the FN BMD between groups A and B. Since the sixth month, both the bone specific alkaline phosphatase and NTx/cr were found to be more markedly and significantly decreased (p < 0.05) in groups A and B with respect to group C. After 18 months, in group A (NTx/cr -16.7 +/- 0.8%) we observed a significantly reduced (p < 0.05) bone resorption with respect to group B (NTx/cr -11.0 +/- 0.5%). In group B, only 3 patients (11.2%) referred pain at the site of drug administration. Our data demonstrate that compliance to parenteral CLD is satisfactory and that this drug reduces bone turnover, increases the L1-L4 BMD and decreases the FN BMD loss. Parenteral CLD administration can represent an effective alternative treatment for postmenopausal women with osteoporosis, especially those who do not tolerate oral aminobisphosphonates.

Thyroid cancer in patients with hyperthyroidism.

OBJECTIVE: The coexistence of hyperthyroidism and thyroid cancer is considered a rare event. With the aim of assessing the clinical relevance of this association, we have retrospectively analyzed the incidence of thyroid cancer in 425 hyperthyroid patients seen and treated by surgery in our institutions. METHODS: Among these hyperthyroid patients, we observed 241 (56.7%) cases of multinodular toxic goiter, 120 (28.3%) of uninodular toxic goiter and 64 (15%) cases of Graves' disease. RESULTS: Thyroid cancer was diagnosed in 7 (1.65%) hyperthyroid patients. Histological examination revealed the presence of papillary carcinoma in 5 cases and follicular carcinoma in 2 cases. Neoplasia was detected in 4 patients with nodular toxic goiter and in 3 with uninodular toxic goiter. None of the patients with Graves' disease had thyroid cancer. During the follow-up of 74 months (range 4-154), there were no deaths or any recurrences. CONCLUSION: Although the occurrence of thyroid cancer in hyperthyroid patients is a rare event, the presence of a 'cold' nodule in a hyperfunctioning thyroid should be carefully evaluated to exclude the presence of concurrent malignancy.

[Clinical aspects of osteoporosis]. / Gli aspetti clinici dell'osteoporosi.

The main clinical presentation of osteoporosis is fracture and its consequences. However a number of diseases and factors can induce bone loss and increase the risk of fracture. Therefore the clinical approach should be initially directed to exclude secondary osteoporosis. Vertebral fractures are the most common osteoporotic fractures; they are characterized by back pain, typical physical changes such as kyphosis and height loss, functional impairment and social decline. On the other hand, hip fracture is the most severe consequence of osteoporosis, because of its higher morbility and mortality. The main pathogenetic determinants of hip fracture are represented by both bone loss and several factors contributing to fall in the elderly. Moreover, a number of conditions are responsible for the high mortality rate following hip fracture. Colles' fracture is rarely hospitalized; however, most patients complain a complex algodystrophic syndrome which impairs the quality of life.

High plasma adrenomedullin concentrations in patients with high-renin essential hypertension.

Adrenomedullin (AM) is a novel peptide, first isolated from human phaeochromocytoma, which elicits a long-lasting vasorelaxant activity. Recently, it has been reported that endothelial cells produce AM and that immunoreactive AM plasma levels may be elevated in human arterial hypertension, although the exact pathophysiological role of AM remains to be established. The aim of our study was to determine the relationship between the components of the enin-angiotensin-aldosterone system (RAAS) and plasma AM levels in patients with low-, medium- or high- renin essential hypertension. The study groups included 10 patients with low-renin essential hypertension (average age 42+15 years), nine patients with medium-renin essential hypertension (46+13 years), 11 patients with high-renin essential hypertension (42+14 years) and 12 healthy subjects (43+11 years). Our results demonstrated that the mean AM values of all patients with essential hypertension were 10.85+3.14 pg/ml; there was a statistical correlation (r=0.705; p<0.001) between plasma renin activity (PRA) and AM levels in hypertensives. In patients with high-renin essential hypertension, plasma AM levels (14.2+2.2 pg/ml) were significantly higher (p<0.001) than those of healthy subjects (8.7+2.1 pg/ml), patients with medium-renin essential hypertension (8.5+1.4 pg/ml), and patients with low-renin essential hypertension (9.1+1.5 pg/ml). There was no statistical difference in AM concentrations between medium- and low-renin hypertensive patients. In conclusion, we have found that, in hypertensive patients, plasma AM levels were increased only in high-renin individuals, suggesting a role of AM in this particular form of human essential hypertension.

[Hyponatremia in clinical practice]. / L'iposodiemia nella practica clinica.

Hyponatremia is defined as serum sodium level below 135 mEq/l; this electrolyte disorder can be associated with low, normal or high plasma tonicity. Hyponatremia with normal plasma osmolality, pseudohyponatremia, has little clinical value. Hyponatremia with increased plasma osmolality results from hyperglycemia or mannitol infusion. Patients with hyposmotic hyponatremia may be normovolemic, hypovolemic or hypervolemic; it is most important to know clinical history, physical examination that focuses on volume assessment and laboratory evaluation that includes urine osmolality and urine sodium concentration. Severe hyponatremia is associated with neurological complications and occasionally with mortality; for mild hyponatremia water restriction is usually sufficient, but in serious cases hypertonic saline infusion should be administered. Rapid correction of severe hyponatremia can cause brain demyelination; to prevent brain damage the rate of correction should be no more than 0.5 mEq/l/h (10-15 mEq/l/24 h).