Familial hyperaldosteronism type III.

Primary aldosteronism is the most common form of endocrine hypertension. This disorder comprises both sporadic and familial forms. Four familial forms of primary aldosteronism (FH-I to FH-IV) have been described. FH-III is caused by germline mutations in KCNJ5, encoding the potassium channel Kir3.4 (also called GIRK4). These mutations alter the selectivity filter of the channel and lead to abnormal ion currents with loss of potassium selectivity, sodium influx and consequent increased intracellular calcium that causes excessive aldosterone biosynthesis. To date, eleven families have been reported, carrying six different mutations. Although the clinical features are variable, FH-III patients often display severe hyperaldosteronism with an early onset, associated with hypokalemia and diabetes insipidus-like symptoms. In most cases FH-III patients are resistant to pharmacological therapy and require bilateral adrenalectomy to control symptoms. In the present manuscript, we review the genetics and pathological basis of FH-III, the diagnostic work-up, clinical features and therapeutic management. Finally, we will describe a new case of FH-III of an Italian patient carrying a Gly151Arg mutation.

Subtype Diagnosis of Primary Aldosteronism: Approach to Different Clinical Scenarios.

Identification and management of patients with primary aldosteronism are of utmost importance because it is a frequent cause of endocrine hypertension, and affected patients display an increase of cardio- and cerebro-vascular events, compared to essential hypertensives. Distinction of primary aldosteronism subtypes is of particular relevance to allocate the patients to the appropriate treatment, represented by mineralocorticoid receptor antagonists for bilateral forms and unilateral adrenalectomy for patients with unilateral aldosterone secretion. Subtype differentiation of confirmed hyperaldosteronism comprises adrenal CT scanning and adrenal venous sampling. In this review, we will discuss different clinical scenarios where execution, interpretation of adrenal vein sampling and subsequent patient management might be challenging, providing the clinician with useful information to help the interpretation of controversial procedures.

Taurine deficiency in thalassemia major-induced osteoporosis treated with neridronate.

The aetiology of thalassemia major-induced osteoporosis is multifactorial. Up to now, bisphosphonates seem to be a promising therapy. Taurine is found in a high concentration in bone cells enhancing bone tissue formation and inhibiting bone loss. Recently we found a decrease taurine plasma level in children affected by osteogenesis imperfecta during neridronate (amino-bisphosphonate) therapy suggesting a possible interaction between pharmacological effect of this drug and taurine availability. On the basis of these results, we performed plasma and urine amino acid (AA) analysis in thalassemia major-induced osteoporosis before and after 12 months of neridronate treatment. Twelve patients, five males and seven females, aged from 20 to 29 years following a hypertransfusion treatment protocol were enrolled in the study. Patients were treated with neridronate infusion every one month (30 mg in 100ml of saline). Plasma and urine specimens for AA analysis, bone mineral density, bone mineral content and vertebral project area were examined at baseline (T0) and after 12 months of treatment (T12). A significant decrease was observed for plasma level and urinary excretion of taurine (T0 vs. T12=p<0.01) whereas bone mineral content and vertebral projection area showed a statistical significant increase (T0 vs. T12=p<0.05). These results and other experimental researches warrant further studies examining the long-term effect of taurine supplementation in association with neridronate treatment.

Absence of severe recurrent infections in glycogen storage disease type Ib with neutropenia and neutrophil dysfunction.

We describe a 10-year-old boy with glycogen storage disease type Ib (GSD Ib) with neutropenia and neutrophil dysfunction who never suffered from severe recurrent infections. Lymphocyte subpopulations and assay of intracellular cytokines (IL-2, IL-4 and IFN-gamma) showed a pattern of lymphocyte activation suggesting a shift of T(H)1/T(H)2 balance towards a T(H)1 response. This is the first report of GSD Ib without severe recurrent infections in spite of neutropenia and neutrophil dysfunction.

Breast cancer cellular proliferation indexes and 99mTc-sesta Mibi capture: what correlation?

Aim of this study was to verify existing correlations between breast cancer 99mTc-sestaMIBI cells uptake and their cytological characteristics. Forty-five patients with clinically and/or mammographically suspect breast cancer were enrolled. In all patients 99mTc-sestaMIBI scintimammography was performed and malignant lesions were detected in 44 cases and benign in one case. In positive uptake (PU) lesions with diameter <1.5cm, 85.7% showed a high tumor grade (II-III degrees) while in negative uptake (NU) lesions with diameter <1.5cm, 100% showed a low tumor grade (I degrees). In PU lesions, 70% had expressed a high value of Ki 67, while 100% of the NU lesions showed normal values. In this series, tumor diameter does not play a basic role, while the correlations between uptake and the histological grade (G) and/or cellular kinetics (Ki67) seem to be more important. Further studies are needed to confirm our present results.

[Breast carcinoma and the axillary lymph node status: the use of 99mTc-sestamibi scintimammography for the diagnosis and preoperative staging. Preliminary results]. / Il carcinoma mammario e lo status linfonodale ascellare: uso della 99mTc sestaMIBI scintimammografia a scopo diagnostico e stadiativo prechirurgico. Risultati preliminari.

BACKGROUND: The purpose of this study is the sensitivity and specificity evaluation of the 99mTc-sestaMIBI scintimammography (SMM) in the diagnosis and pre-surgical staging of patients with clinical and/or radiological suspicion of breast cancer. MATERIALS AND METHODS: Forty-five patients with clinical and/or mammographic breast cancer suspicion were enrolled. Prone lateral views of both mammalian glands and anterior of chest, to evaluate the axillary lymph node infiltration, were acquired 60 min after i.v. injection of 20-25 mCi of 99mTc-sestaMIBI. RESULTS: Breast cancer was diagnosed by histological findings in 44 patients; benign disease in 1 case. The tumors diameter ranged from 0.3 to 4 cm. The SMM sensitivity in the detection of breast cancer was 90% and the VPP was 100%. The smallest diameter in these detected lesions was 0.5 cm. The pathologic examination showed metastatic axillary involvement in 15 patients. The SMM sensitivity in the detection of axillary lymph node metastases was 75%, specificity was 90%. For each lesion grading, mitosis number, 67Ki expression, diameter, were considered and correlated to 99mTC-sestaMIBI uptake. The 5 breast cancer non-uptake cases had low cytoproliferative indexes. According to our data it is possible to observe that there is a correlation between uptake and cellular proliferation. CONCLUSIONS: The 99mTc-sestaMIBI SMM is a highly accuracy test in the breast cancer detection. The sensitivity in the axillary lymph node metastatic detection is just little below average according to the literature; it is possible that the results can improve with higher accrual of patients, operator experience and equipment improvement and the using of SPECT.

[Use of orgotein in the treatment of reactive damage to the use of high-energy radiation]. / Utilizzazione dell'orgoteina per la cura dei danni reattivi all'impiego di radiazioni ad alta energia.

A study has been carried out on 62 patients submitted to pre- and postoperative X-ray treatment, evaluating tolerance and effectiveness of orgotein administered i.m. The therapeutic results obtained may be considered very satisfactory.