An easy diagnostic approach to primary aldosteronism.

The infusion of 40 mEq potassium (aspartate) in 250 ml isotonic 1-fructose at a rate of 20 mEq/h into 5 patients (34-56 years old) with aldosteronoma and 2 patients with bilateral primary aldosteronism consistently raised their mean arterial pressure by 15-20 mmHg. Their pressure values returned to the baseline levels 4-5 h after the infusion. In contrast, in controls (10 patients with idiopathic arterial hypertension, matched for age, sex, and magnitude of the untreated hypertension, and 7 patients with inactive adrenal nodules as incidental findings on upper abdomen ultrasound or computerized tomography) the same procedure caused negligible arterial pressure changes. The cause of the rise in blood pressure observed uniquely in patients with primary aldosteronism after infusion of potassium (aspartate) cannot be accounted for by an increase in plasma aldosterone, blood volume, or plasma angiotensin II. The cause of this response thus remains obscure; nonetheless, this simple procedure may prove useful in differentiating primary aldosteronism from idiopathic hypertension, in excluding the adrenal disorder, and in revealing even its mildest forms.

[Monoarthritis]. / Le monoartriti.

By definition, monoarticular arthritis means one-joint involvement, even though, in fact, such a condition is often an oligoarthritis because as many as two or three separate joints will be involved. Arthritis is often limited and may regress, so that it is frequently misdiagnosed. Sometimes, a monoarticular condition may be a polyarthritis onset (i.e., rheumatoid arthritis). Monoarticular arthritis can be caused by many factors, such as infections (septic arthritis), nonspecific inflammatory processes (reactive arthritis), crystals deposition (gout, CPPD crystal deposition disease), trauma, neoplasm (pigmented villonodular synovitis), immunologic conditions (amyloidosis) and hormonal changes (parathyroid disease). Its onset is usually acute and sometimes dramatic, with fever, pain and joint swelling, so that a decision must be made promptly to stop rapid illness evolution and to prevent the irreversible destruction of cartilage and bone (especially in septic arthritis). Diagnostic studies are performed with mono-bilateral radiographs of the joint. Radiographic findings (i.e., soft tissue swelling, joint effusion, widening and thinning of joint spaces, bone erosions and destruction of bone surface) are typical of the disease, but some findings (e.g., type of evolution and progression), laboratory tests, synovial biopsy and arthroscopy can differentiate infectious from inflammatory forms. Scintigraphy can depict isotopic joint uptake, before articular abnormalities are demonstrated with radiography, thanks to its high sensitivity; nevertheless, because of its low specificity, scintigraphy may miss some kinds of lesions (including osteoarthritis) and cannot easily differentiate osteomyelitis from septic arthritis. CT and MRI play a secondary, though not negligible, role, especially to study such deep infections as psoas abscesses, which may mimic arthritides.

Association between diffuse idiopathic skeletal hyperostosis and multiple myeloma.

OBJECTIVE: To determine whether an association exists between multiple myeloma and diffuse idiopathic skeletal hyperostosis (DISH). DESIGN AND PATIENTS: Radiologic studies were performed over a 26-month period in a series of 97 consecutive patients with multiple myeloma (56 male and 41 female, aged 42-91 years). RESULTS: Both myelomatous bone lesions and hyperostosis similar to DISH were found in these patients. The prevalence of DISH in association with multiple myeloma (21 male and 8 females patients) was higher (29.8%) than in our control group (973 patients, 449 male and 524 female) or in the general population (15-20%). The involved segments of the column were thoracic in 11 males and 7 females, cervical in 8 males and 2 females, and lumbar in 5 males and 4 females. Ossifying enthesopathy in the pelvis ("whiskering") was observed in 7 males and 1 female. CONCLUSIONS: The pathogenesis of hyperostosis remains unknown. It is possible that the coexistence of DISH and multiple myeloma is merely an association. For this reason, it is important for the real prevalence of DISH in the general population to be defined.

Platyspondyly in treated beta-thalassemia.

Flattening of the vertebral bodies with a platyspondyly appearance is described in 14 patients selected for evaluation of short stature from 106 patients affected by thalassemia major, who received an intensive transfusion regimen combined with continuous chelation therapy. The vertebral body height/width ratio was decreased at the level of all the investigated tracts, namely, cervical and/or dorsal and/or lumbar. The flattening of the vertebral bodies may be due to suppression of intramedullary hematopoiesis by a high transfusion regimen. The reduced intravertebral pressure due to disturbed hemopoiesis could cause weight-bearing and other biological stresses to provoke a reduction in vertebral body height.

[The evolutionary effects of therapy on the skeletal lesions in beta-thalassemia]. / Effetti dell'evoluzione della terapia sulle lesioni scheletriche nella beta-talassemia.

Up to the mid-1960s, beta-thalassemia was treated with blood transfusions as frequent as needed to keep symptoms under control and to prevent transfusional hemosiderosis. In the following years, high transfusion regimens and iron chelation therapy with desferrioxamine were used. Because of these different treatment modalities, skeletal findings in thalassemia have markedly changed. In the past, thalassemic patients treated with a low transfusion regimen and without chelation therapy developed osteopenia--with widened medullary spaces, cortical thinning and trabecular atrophy--secondary to chronic expansion of red marrow, due to increased erythropoietin response to chronic anemic hypoxia. Typical radiographic patterns in the skull included widened diploic space, atrophic-especially outer--tables and, in some patients, the "hair-on-end" pattern. As for the face, obliteration of the paranasal sinuses and the typical "rodent facies" were observed. In the ribs, bulbous expansion of the posterior and anterior segments and the "rib within a rib" patterns were observed. As for the spine, coarse trabecular arrangement was seen. The "cobweb" pattern was seen in the pelvis and finally the lack of the normal concave outline was observed in the long bones. In the patients treated with high transfusion regimens and iron chelation therapy over the last 30 years, both skull anomalies and disfigurement are less frequent. The skull is almost normal, with the exception of osteopenia and thickened diploic space in the frontal bone only; the paranasal sinuses are usually not obliterated. The hands and rib are normal, just like long bones, pelvis, scapulae and vertebral bodies. Nevertheless, in some adequately treated patients new skeletal features have been recently observed in the long bones, which are similar to those occurring in rickets and/or scurvy, and in the vertebral bodies, resembling platyspondylia. These abnormal features might be caused by several factors--i.e., marrow expansion, transfusion regimens, direct/indirect effects of desferrioxamine, iron load, endocrine abnormalities, deficiency of some minerals and finally dysvitaminoses. Nevertheless, osteopenia remains the main negative factor of thalassemia.

[Osteoporosis and the thalassemia "trait"]. / Osteoporosi e "trait" talassemico.

The authors evaluated the prevalence of the thalassemia trait in a general population affected with femoral neck fractures. Our research was aimed at assessing whether hemoglobinopathy might affect osteoporosis, which is responsible for femoral fractures. Two hundred and thirty-eight patients admitted to St. Anna Hospital, Ferrara, for proximal femoral fractures, were retrospectively studied. The patients were 68 males and 170 females, aged 58 to 83 years (mean age: 70.4 years). The thalassemia trait was seen in 11.76% of cases, versus in 7-8% of the general population. The high prevalence of heterozygous beta-thalassemic subjects probably means that the beta-thalassemia condition is a further "variable" which is responsible for the more frequent occurrence of fractures of the proximal femur and is certainly related to an osteopenic condition much more severe than usual.

[Platyspondylisis+ in beta-thalassemia major]. / Platispondilia nella beta-talassemia maior.

Platyspondylia was observed in 14 patients affected with thalassemia major (7 males and 7 females, age range: 10-18 years) who received an intensive transfusion regimen combined with continuous chelation therapy (desferrioxamine: 50-80 mg/kg daily). Height/width ratio was decreased at all the investigated tracts--i.e., cervical and/or dorsal and/or lumbar spine. The range of height/width ratio values was 0.41-0.55 at the 5th cervical body, 0.33-0.53 at the 8th dorsal body, 0.43-0.56 at the 12th dorsal body and 0.47-0.62 at the 2nd lumbar body. The flattening of the vertebral bodies seems to be due to the depletion of hematopoetic tissue determined by the high transfusion regimen. The reduced intramedullary pressure is thought to counteract neither weight-bearing nor other biological stresses, which might ultimately provoke the thinning of vertebral bodies.

[The radiology of osteogenesis imperfecta]. / La radiologia dell'osteogenesi imperfetta.

The term "osteogenesis imperfecta" refers to a heterogeneous group of hereditary diseases characterized by osteopenia, increased bone fragility, blue sclerae and dentinogenesis imperfecta. The abnormal synthesis of type-I collagen is responsible for the pathologic changes occurring not only in bone, but also in skin, tendons and ligaments, sclerae and teeth. The clinical and radiographic features of 5 cases (2 males and 3 females; age range: 1 month to 29 years) were analyzed. The patients were unrelated with each other. The diagnosis of the different types of osteogenesis imperfecta is as difficult as the identification of the various genotypes which are responsible for the different clinical pictures. The most characteristic radiographic pattern--which is observed in any type of the disease--consists in osteopenia associated, in most cases, with multiple fractures and deformities--e.g., micromelia, large metaphysis, archon long bones. Typically, "pop corn" calcifications are observed in both epiphysis and metaphysis of long bones. Dentinogenesis imperfecta is one of the most significant clinical patterns, and it can be the only bone abnormality. The prognosis of osteogenesis imperfecta is as varied as its genetics--i.e., the fractures discovered at birth are not necessarily a negative prognostic sign.

Growth plate injury of the long bones in treated beta-thalassemia.

In 12 patients affected by thalassemia major who received an intensive transfusion regimen combined with continuous iron chelation therapy (desferrioxamine 50-80 mg/kg daily), radiologic abnormalities of the long bones were observed similar to those observed in rickets and scurvy. These abnormalities were associated with a growth retardation. The pathogenesis of these lesions is uncertain, but probably the toxic effect of desferrioxamine plays an important role in their development. A relative deficiency of vitamins D and/or C cannot be entirely excluded.

[Rickets- and/or scurvy-like bone lesions in beta-thalassemia major]. / Lesioni scheletriche simil-rachitiche e/o scorbutiche nella beta-talassemia major.

Recently, a new type of skeletal lesions has been described in Cooley's anemia as a possible complication secondary to therapy. In 12 children affected with thalassemia major, who received an intensive transfusional regimen combined with continuous iron chelation therapy (desferoxamine-B: 50-80 mg/kg/day), some radiological abnormalities of the long bones were observed similar to those described in rickets and scurvy. These rickets and/or scurvy-like lesions had never been reported before the introduction of high-dose desferoxamine therapy. The pathogenesis of these lesions is uncertain, but the toxic effect of desferoxamine probably plays an important role in their development. The association of growth retardation and rickets and/or scurvy-like skeletal lesions in Cooley's anemia patients may be used as a valuable clinical criterion in long-term chelation management.

[Erythrocyte carbonic anhydrase in subjects on periodic hemodialysis]. / Anidrasi carbonica eritrocitaria in soggetti sottoposti ad emodialisi periodica.

Red cell carbonic anhydrase isoenzymes I and II have been measured by means of cellulose acetate membrane electrophoresis in patients with chronic renal failure and dependent on periodic hemodialysis; these patients showed a chronic anemia due to many factors. Carbonic anhydrase isoenzymes were higher in uremic and anemic patients than in the controls. Since hemoglobin can act as a protons acceptor from the active site of carbonic anhydrase during the hydratation of CO2 (and vice-versa), the increase of carbonic anhydrase can facilitate, via the Bohr effect, the transfer of the oxygen to the peripheral tissues. Therefore an increase of red cell carbonic anhydrase can constitute a compensating mechanism of anemic hypoxia in uremic patients.

[The "lamellar cranium": a particular radiologic feature of Cooley's disease]. / Il "cranio lamellare": un particolare aspetto radiologico del morbo di Cooley.

The skull in homozygous beta-thalassemia (Cooley's anemia) may present with several abnormalities, such as osteopenia, widening of the diploic space, and a "hair on end" appearance. In some cases it presents also a particular stratified aspect owing to a variable number of osseous lamellae, arranged so as to be parallel to the inner table. This "lamellated skull" was observed in 16 patients, selected from 150 patients with Cooley's anemia (10.6%). The possible mechanisms are discussed. The pluristratified lamellar osseous production could be brought about by repeated periosteal osteoblastic reaction to the sinusoidal neovascularization associated with marrow hyperplasia in poorly or not at all transfused patients.

The "lamellated" skull in beta-thalassaemia.

The skull in homozygous beta-thalassaemia may present several abnormalities, such as osteopenia, widening of the diploic space, and a "hair-on-end" appearance. In some cases it presents also a particular stratified appearance caused by a variable number of osseous lamellae, parallel with the inner table. This "lamellated skull" was observed in 16 out of 150 patients affected by the disease (10.6%). Possible mechanisms are discussed. The lamellar osseous changes could be due to repeated periosteal osteoblastic reactions to the sinusoidal neovascularization associated with marrow hyperplasia in poorly transfused patients.

[Ochronotic arthropathy in alkaptonuria. Radiological manifestations and physiopathological signs]. / L'artropatia ocronotica dell'alcaptonuria. Manifestazioni radiologiche e cenni di fisiopatologia.

Alkaptonuria is a rare autosomal recessive metabolic disease, due to the lack of homogentisic acid oxidase. The following accumulation of homogentisic acid brings about a black discoloration of both the urine (alkaptonuria) and connective tissue (ochronosis). The ochronotic alterations into joint cartilages cause degenerative arthropathy and osteopenia. The radiological features of three unrelated cases of alkaptonuria are reported. Radiographic abnormalities of ochronotic arthropathy are found in both the spine and the extraspinal joints. In the spine, the progressive calcification and "vacuum" phenomenon of disc spaces are the most characteristic findings. Disc space narrowing is associated with calcification and marginal sclerosis of vertebral bodies and is accentuated by osteopenia. Osteophytes are usually absent or of small size; nevertheless progressive formation of marginal intervertebral bridges and obliteration of disc spaces at multiple levels ("pseudoblock vertebrae") may occur. In extraspinal sites, space narrowing, bone sclerosis and fragmentation may also be observed. Diagnosis of ochronotic arthropathy is often suggested by radiographs of the spine, and it is confirmed afterwards by clinical and laboratory findings. The characteristic radiological findings of ochronotic spondylitis, in the final stage, include narrowing of at least four lumbar disc spaces, associated with their calcification and "vacuum" phenomenon, "pseudoblock vertebrae", marginal sclerosis and osteopenia of vertebral bodies.

Circumscribed lytic lesions of the thalassaemic skull.

Solitary or multiple circumscribed osteolytic areas are described in seven patients, selected from 250 patients with homozygous beta-thalassaemia (Cooley's anaemia). On X-ray examinations, these areas appear as purely osteolytic lesions with well-defined margins not associated with sclerosis. The possible mechanisms are discussed.

[Clinico-radiologic aspects of calcium pyrophosphate dihydrate deposition disease]. / Aspetti clinico-radiologici della malattia da depositi di pirofosfato di calcio diidrato.

Calcium pyrophosphate dihydrate crystal deposition disease is a clinical condition characterised by Gout-like synovitis (pseudogout), calcification on and around the joints and an arthropathy that is radiologically similar to osteoarthritis (chronic pyrophosphate arthropathy). Though all these radiological clinical aspects may coexist in the same patient this is often not the case. An examination of the X-ray data on the 68 cases studied which were diagnosed on the basis of the criteria proposed by McCarty, shows that the disease is relatively common especially in the over-fifties. When chronic pyrophosphate arthropathy is the only clinical manifestation of the disease differential diagnosis from the osteoarthrosis so common in the elderly is difficult and depends on the greater severity and progression of the joint damage that may often affect joints not subjected to weight such as the shoulder, unlike what happens in osteoarthritis.

[Aseptic necrosis of the head of the femur in Cooley's disease]. / La necrosi asettica della testa del femore nel morbo di Cooley.

The incidence of aseptic necrosis of femoral head in homozygous beta-thalassaemia (Cooley's anaemia)--which is indeed significantly high--is not satisfactorily referred in late literature regarding haemolytic syndromes. Therefore, 4 cases of osteonecrosis of femoral head, recently recognized in a series of 280 patients affected by Cooley's anaemia (14.5 0/00) are presented, and a review of hypotheses about the pathogenesis of the lesions is considered. In Cooley's anaemia, the skeletal lesion (osteoporosis) must be believed as a propitious state, in which some other pathogenetic events (i.e. local ischemia, bony age, etc.) and microtraumas overlap. In any case, characteristic blood circulation of the femoral head is the "conditio sine qua non" in developing osteonecrosis.

Aseptic necrosis of femoral head complicating thalassemia.

Aseptic necrosis of the femoral head is described in 4 patients, selected from 280 patients with homozygous beta-thalassemia (Cooley anemia). The incidence of the complication appears to be very high (14.5%) in thalassemia, compared to the general population. The possible mechanism are discussed.