Long-term bone mineral density changes after surgical cure of patients with tumor-induced osteomalacia.

This paper reports our personal experience filling the gap regarding changes of bone mineral density after surgical treatment in patient suffering from tumor-induced osteomalacia. INTRODUCTION: No systematic data are available regarding long-term bone mineral density (BMD) changes after surgical cure of patients with tumor-induced osteomalacia. METHODS: From October 2001 through April 2018, we studied 10 consecutive patients (mean age ± SD, 45.5 ± 13.8 years; 5 males and 5 females) with tumor-induced osteomalacia. We evaluated BMD when initially presented at our Center and after surgical removal of the tumor. RESULTS: Basal BMD and corresponding Z-score values (mean values ± SD) measured by DXA were as follows: L1-L4 = 0.692 ± 0.15 g/cm2, Z-score = - 2.80 ± 1.60; femur neck 0.447 ± 0.10 g/cm2, Z-score = - 2.66 ± 0.93; total femur = 0.450 ± 0.08 g/cm2, Z-score = -3.04 ± 0.85). Furthermore, Trabecular Bone Score (TBS) was evaluated in three patients (basal values, 0.990 ± 0.32). Seven patients were intermittently followed after surgical excision of the tumor while supplemented with cholecalciferol and calcium salts; the remaining three were lost to follow-up. There was a striking increase of BMD values that peaked at 26.7 ± 6.50 months: L1-L4 = 1.289 ± 0.247 g/cm2, p < 0.001, Z-score + 1.75 ± 1.42; femur neck = 0.890 ± 0.235 g/cm2, p = 0.028, Z-score = + 0.50 ± 1.40; total femur = 0.834 ± 0.150 g/cm2, p = 0.005, Z-score = - 0.74 ± 1.14. In patients with the greatest bone involvement at lumbar site, there was a striking increase of an average 1.5% (p < 0.01) in respect to baseline Z-score value for each additional month of observation during the first 2-3 years post-surgery. An improvement of trabecular microarchitecture was also documented (TBS, 1.255 ± 0.16). CONCLUSION: This is the first case series documenting an impressive increase of BMD at both lumbar and femoral sites, together with an improvement of trabecular microarchitecture as documented by TBS. This is the consequence of huge mineralization of the large amount of osteoid tissue after resolution of the disease.

Zenker diverticulum in the right side of the neck resembling a thyroid mass at ultrasound.

Zenker’s diverticulum represents the most common form of pharyngo-oesophageal diverticula usually occurring on the left side of the neck. Due to its anatomical proximity to the thyroid, it can mimic a thyroid mass. Here we describe the case of an asymptomatic 49-year-old man referred to the Thyroid Clinic of the Policlinico Umberto I Hospital-“Sapienza” University of Rome for thyroid sonography due to a family history of autoimmune thyroid disease. The patient’s thyroid blood tests did not reveal any abnormalities. The sonographic examination showed a dishomogeneus and hypoechoic thyroid gland. In addition, in the third middle of the right lobe, a mass (with a diameter greater than 26 mm), with heterogeneous internal echogenicity, hypoechoic margins and internal hyperechoic spots was recorded, with no appreciable flow at the Doppler evaluation. The TI-RADS score was 4c. Hence, the patient underwent ultrasound-guided fine-needle aspiration cytology that revealed the presence of squamous cells without cytological atypia, erythrocytes, muscular and vegetable fibres, colonies of bacteria in the absence of inflammatory infiltrate. This was consistent with the diagnostic hypothesis of oesophagus diverticulum, which was confirmed by means of a barium-swallow oesophagography. This case report underlines the possibility that a suspicious thyroid mass may result from a Zenker’s diverticulum, even if located on the right side, especially if the lesion has a heterogeneous echo-texture, a hypoechoic rim and internal hyperechoic spots.

Skeletal turnover, bone mineral density, and fractures in male chronic abusers of alcohol.

BACKGROUND: Chronic alcohol abuse is a risk factor for osteoporosis and fractures, whose pathogenesis is still unclear. We investigated the influence of alcoholism and other risk factors on calcium and skeletal metabolism, bone mineral density (BMD), and fractures. MATERIALS AND METHODS: In 51 chronic male alcoholics without liver failure and 31 healthy controls, serum total and ionised calcium, phosphate, creatinine, 25-hydroxy vitamin D (25OHD), PTH, total (ALP) and bone-specific (BALP) alkaline phosphatase, osteocalcin (BGP), carboxy-terminal telopeptide of type I collagen (beta-CTx), osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) were assessed. In patients only, we also measured serum testosterone, 17-beta estradiol, LH, and IGF-I. BMD was measured by dual energy x-ray absorptiometry at lumbar spine (LS-) and femur [neck (FN-) and total hip (TF-)]. Vertebral fractures were identified by a semiquantitative method on thoraco-lumbar spine x-ray, non-vertebral fractures (as life-style factors) by history. RESULTS: Alcoholics were leaner, had significantly higher ALP and BALP, and lower BGP and 25OHD levels than controls. No significant difference in other calcium and bone metabolism parameters was found. OPG/RANKL ratio was significantly higher in alcoholics. Beta-CTx negatively correlated with abuse duration. OPG positively correlated with daily alcohol assumption and with indexes of liver cytolysis. Though LS-, FN- and TF-BMD of alcoholics and controls did not significantly differ, patients had a much higher prevalence of vertebral fractures. The same was found considering both vertebral and non-vertebral fractures. CONCLUSIONS: Ethanol-induced skeletal damage seems mainly dependent on negative effects on bone formation. Lifestyle factors and traumas likely contribute to the high fracture incidence of alcohol abusers, independently of BMD.

Adrenomedullin concentrations are elevated in plasma of patients with primary hyperparathyroidism.

The aim of the study was to evaluate plasma adrenomedullin (AM) concentration in primary hyperparathyroidism (PHP) and its effect on the regulation of blood pressure. Forty-one patients with PHP (25 normotensive and 16 hypertensive), and 31 healthy subjects (HS) were included in the study. As expected the total and ionized calcium and i-PTH serum levels were significantly higher in patients with PHP than in HS (P <.001). No significant difference was found in calcium-phosphorus metabolism parameters between normotensive and hypertensive PHP patients. Serum i-PTH levels correlated positively with systolic blood pressure (SBP) (r = 0.510; P <.02), diastolic blood pressure (DBP) (r = 0.586; P <.01) and heart rate (HR) (r = 0.486; P <.043) only in hypertensive PHP patients. Overall, mean plasma AM concentrations were significantly higher in PHP patients (16.1 +/- 7.9 pg/mL) than in HS (11.3 +/- 4.8 pg/mL) (P <.003) and correlated with i-PTH (r = 0.430; P <.005). However, in hypertensive PHP patients plasma AM levels (22.5 +/- 4.7 pg/mL) were higher than in normotensive PHP patients (11.6 +/- 1.8 pg/mL) (P <.001) and correlated with DBP (r = 0.902, P <.0029). In HS no correlation was found between plasma AM values and biohumoral, hormonal, or hemodynamic parameters. In conclusion, we demonstrated that in patients with PHP, plasma AM concentrations are increased and correlate with i-PTH and blood pressure values. We suggest that increased AM levels could be a compensatory factor in the defence mechanism against further blood pressure elevation.

Plasma adrenomedullin concentrations in patients with adrenal pheochromocytoma.

BACKGROUND: The hypotensive peptide adrenomedullin was first isolated in extracts of human pheochromocytoma. There is, however, no information available on the behaviour of circulating adrenomedullin or on the correlation with catecholamines in patients with pheochromocytoma. OBJECTIVES: 1) to investigate whether plasma adrenomedullin levels were changed in 10 patients with pheochromocytoma when compared to 21 healthy subjects and 16 patients with essential hypertension; 2) to determine whether or not adrenomedullin has a counter-regulatory role in catecholamine excess in pheochromocytoma or is responsible for hemodynamic modifications before and after tumour resection; 3) to determine tissue distribution of iradrenomedullin in the pheochromocytoma. METHODS: Plasma adrenomedullin and catecholamine levels were measured in all patients with pheochromocytoma before and four weeks after tumour removal. In the four patients undergoing resection of tumours, plasma levels of adrenomedullin were measured at different time-points during surgery. RESULTS: The mean plasma adrenomedullin concentrations ( SD) in patients with pheochromocytoma (37.9 +/- 6pg/ml) were significantly higher (p<0.0001) than those in normal subjects (13.7 +/- 6.1 pg/mI) and patients with essential hypertension (22.5 +/- 9.lpg/ml). Adrenomedullin levels correlated with plasma noradrenaline (r = 0.516, p = 0.0124). In all patients with pheochromocytoma, plasma adrenomedullin concentrations decreased after removal of tumours (from 37.9 +/- 6 to 10.9 +/- 4.6 pg/ml; p < 0.0001). In the four patients studied during surgery, baseline plasma adrenomedullin and noradrenaline levels were markedly elevated, and increased significantly with tumour manipulation, decreasing 24 hours after operation. Adrenal medulla cells surrounding the pheochromocytoma site stained for ir-adrenomedullin, whereas only isolated cells of pheochromocytoma stained for the peptide. CONCLUSIONS: This study demonstrates that circulating adrenomedullin is increased in pheochromocytoma, and is also correlated with plasma noradrenaline levels. Adrenomedullin may represent an additional biochemical parameter for clinical monitoring of patients with pheochromocytoma.

Annual skeletal balance and metabolic bone marker changes in healthy early postmenopausal women: results of a prospective study.

The aim of this study was to establish the duration and annual rate of menopause-related bone loss and to investigate the relationship between bone turnover and bone loss in early healthy postmenopausal women. The rate of change in bone mineral density (BMD) at the lumbar spine and in bone turnover was measured twice at the exact interval of 12 months by dual-energy X-ray absorptiometry (DXA) and by the determination of plasma alkaline phosphatase levels (ALP) and fasting urinary hydroxyproline/creatinine ratio (OHPr/Cr), respectively, in 123 healthy premenopausal and postmenopausal women 45-60 years of age. The subjects were divided into nine groups according to their menstrual status and years since menopause (YSM). Annual bone loss at the lumbar spine of women who were menopausal for 1, 2, 3, 4, and 5 years was -2.62 +/- 0.37 (95% confidence interval -3.66, -1.58), -3.87 +/- 0.96 (-6.02, -1.73), -2.50 +/- 0. 37 (-3.29, -1.70), -2.86 +/- 0.73 (-4.44, -1.27), and -1.54 +/- 0.41 (-2.42, -0.66), respectively, and was significantly less than zero. But, the annual bone loss of women who were premenopausal or menopausal for 6, 7, and 8 years was -0.76 +/- 0.60 (-2.04, +0.53), -1.16 +/- 0.68 (-2.61, +0.29), 0.24 +/- 0.48 (-0.78, +1.26), and 0. 16 +/- 0.63 (-1.18, -1.49), respectively, and was not significantly different from zero. These results demonstrate that the early hormone-dependent bone loss commences in the first year after menopause and is arrested within 6 years after the onset of menopause. The overall bone loss for this phase is estimated to be approximately 15%. Annual change in ALP and OHPr/Cr seems to indicate that bone resorption prevails on bone formation in the first 2 YSM, whereas osteoblastic activity relatively prevails from YSM 3 to YSM 5, which explains the progressive repairing of the imbalance between bone resorption and formation.

Doppler sonography of the superior mesenteric artery in Crohn's disease.

OBJECTIVE: The aim of this study was to evaluate blood flow in the superior mesenteric artery (SMA) in patients with active and inactive Crohn's disease (CD) using Doppler sonography to dynamically assess the changes of resistance in both fasting and postprandial states. SUBJECTS AND METHODS: Doppler sonography of the SMA was performed on 15 patients (mean age, 38 +/- 4 years) with active CD and on 15 patients (mean age, 41 +/- 5 years) with inactive CD. Imaging was performed at both fasting and 15 min after an 1890-kJ meal. A preliminary examination of 10 healthy volunteers with no signs of intestinal disease (mean age, 28 +/- 2 years) was necessary to define the parameters of normality. Because we wanted to express the postprandial resistive change in the SMA, we introduced a parameter called resistive difference (RD), defined as the mathematic difference between the resistive index measured at fasting (highest value) and measured at 15 min after the meal (lowest value). RESULTS: By evaluating the relationship between the RD and extension of disease, we found a direct correlation between progressive extension of disease and reduction of the RD in patients with active CD (correlation coefficient, .98) whereas we found no such correlation in patients with inactive CD (correlation coefficient, .05). CONCLUSION: We believe that Doppler sonography of the SMA is a promising noninvasive method to detect inflammatory disease of the small bowel, to evaluate its extension, and to document resolution of disease after therapy.

Computed tomography of bowel wall in patients with Crohn's disease: relationship of inflammatory activity to biological indices.

Bowel wall thickening in Crohn's disease can be demonstrated by Computed Tomography. The aim of this investigation was to correlate different patterns of bowel wall thickening, detected with Computed Tomography, with serological parameters of activity of Crohn's disease. Thirty-eight patients (24 males, 14 females, aged 21 to 62 years) were studied. Patients were divided into 3 groups according to Computed Tomography appearance of bowel wall: 1) homogeneous symmetrical thickening of wall; 2) bowel showing a layer of submucosal low attenuation; 3) scarred narrowing of wall producing stenosis. A patient was considered to have biochemically active disease if at least 2 of the following parameters were abnormal: ESR, C-reactive protein, seromucoids, serum albumin, serum alpha-2 globulin. The first group comprised 20 patients (16 active disease, 4 inactive) and the second group 13 (all inactive); the 2 groups showed a significant difference (Fisher exact test: p < 0.0005) in biological activity. Since only 5 patients belonged to the third group (3 active, 2 inactive disease), no definite conclusion can be drawn on the possible correlation between this Computed Tomography pattern and activity of disease. Results shows a correlation between Computed Tomography patterns of bowel wall disease and biochemical activity of Crohn's disease.

Role of ageing, chronic renal failure and dialysis in the calcification of mitral annulus.

Mitral annulus calcification, a common lesion of the elderly (over age 60 years), has been detected with increased frequency and at younger ages in patients with uraemia. To date a pathogenic role for dialysis and secondary hyperparathyroidism has been suggested only on the basis of older dialytic age and increased serum iPTH observed in the affected individuals. Because this is a potentially dangerous lesion we deemed it useful to evaluate more completely the respective roles of possible pathogenetic factors in uraemic individuals. Evaluation included echocardiography, ECG, limb radiography, and serum assays. A total of 225 dialysis (HD) patients, 67 chronic renal failure (CRF) patients on conservative treatment and 67 normal subjects were studied. Mitral annulus calcification was detected in 87 of 225 (38.6%) HD patients, 11 of 67 (16.4%) CRF and six of 67 (8.9%) normals. In HD, patients with calcification were older and on longer-term renal replacement therapy compared to those without calcification. They also had greater values of iPTH, BGP, AP, and Rx score of secondary hyperparathyroidism. Mitral annulus calcification was associated more frequently (chi 2 = 14.8; P < 0.0001) with rhythm and cardiac conduction defects, but not with ectopic calcifications. Multiple stepwise regression analysis, with mitral annulus calcification score as dependent variable, selected dialysis duration, age, and iPTH (rm = 0.368) as the most predictive parameters, with the first two carrying most of the information. The stratification of patients according with these two parameters showed a progressive increase in the frequency of calcification both with HD duration and age.(ABSTRACT TRUNCATED AT 250 WORDS)

[Efficacy of L-thyroxine (L-T4) therapy on the volume of the thyroid gland and nodules in patients with euthyroid nodular goiter (ENG)]. / Efficacia della terapia con L-tiroxina (L-T4) sul volume della tiroide e dei noduli in pazienti con gozzo nodulare eutiroideo (GNE).

The efficacy of treatment with TSH suppressive doses of L-thyroxine was evaluated by echography in 35 patients with euthyroid nodular goiter. Patients have been subdivided in two groups comparable for sex age and size of the goiter. Sixteen patients were treated for nine months with suppressive doses of thyroxine and nineteen were followed without therapy as control. Patients in treatment were then followed up for additional 9 months without therapy. The mean decrease of thyroid volume at nine months was 25% (27 +/- 10 ml vs 20 +/- 8 ml; p < 0.01). After discontinuation of treatment thyroid volume increased and had returned to base line values after nine months of follow up. In the control group mean thyroid volume had increased by 17.7% at nine months (28 +/- 17 vs 33 +/- 19 ml; p < 0.001). Thyroid nodules in response to thyroid hormone treatment showed a variable behaviour: 30.7% (4/13) of the nodules responded to the therapy with a reduction > to 25% at the ninth month; the remaining nodules were insensitive to the therapy. In conclusion suppressive thyroxine treatment is effective in reducing the goiter, nodules instead are only in part sensitive to the treatment. Thyroxine therapy of euthyroid nodular goiter must be followed for long term since upon thyroxine discontinuation there is a prompt reappearance of the goiter.

Effects of salmon calcitonin on the bone loss induced by ovariectomy.

We present the results of a 12-month clinical study assessing the effects of synthetic salmon calcitonin (sCT) on a group of fertile white women who had undergone ovariectomy for uterine fibromatosis. The study was performed to verify whether CT can prevent the loss of bone mass and the changes in calcium-phosphorus metabolism associated with acute estrogen deficiency. The study consisted of an initial double-blind phase of 6 months, followed by a 6-month open period. Treated patients were given 100 MRC U of synthetic salmon CT injected i.m. in the morning, every other day, starting on the 7th day after the operation and continued for 12 months. Control patients received a placebo injection for the first 6 months; subsequently, they too were treated with sCT i.m. every other day for 6 months at the same dose as the 12 month-treated group. All patients received 500 mg of elementary calcium p.o., b.i.d. Bone mineral content (BMC) was measured at the extreme distal radius of the nondominant arm by a dual photon bone densitometer which utilizes two radio nuclides, 241 Am and 125 I, with energies of about 60 and 30 KeV. Biochemical parameters of the calcium-phosphorus metabolism were also measured. After 12 months of study, no significant changes of BMC were observed in the 12 months sCT treated group, while control patients, treated 6 months after the ovariectomy, showed a significant decrease in BMC values.(ABSTRACT TRUNCATED AT 250 WORDS)

[Tubercular Addison's disease with high titers of microsomal thyroid antibodies and reduced thyroid function reserve]. / Morbo di Addison tubercolare con elevato titolo di anticorpi antimicrosomiali tiroidei e ridotta riserva funzionale della tiroide.

This case reports deals with a male patient, white, aged 51, bricklayer, tobacco smoker. At 43 years old a tubercular epididimite was surgically treated with orchiectomy. Recently, the reports marked weakness, weight loss, headache, vertigo, hypotension. On admittance to the hospital, hyperpigmentation was also present. Previous therapy (cortisone acetate 40 mg/die), was suspended, clinical investigations showed impaired adrenal and thyroidal functions; antimicrosomal antibodies were also present. Therefore therapy with cortisone acetate (25 mg x 2/die, 9-alpha-fluorohydrocortisone 0.1 mg/die and L-thyroxine 100 mcg/die) was instituted with marked improvement of the patient's conditions. This case reports highlights the importance of proceeding with complete investigations on the system, even when dealing with a tubercular Addison's disease.

Autonomic neuropathy and secondary hyperparathyroidism in uraemia.

To evaluate the relationship between autonomic neuropathy, and biochemical and X-ray parameters of secondary hyperparathyroidism, we examined 19 predialysis and 24 haemodialysis non-diabetic uraemic patients. Autonomic neuropathy was assessed using four tests: deep breathing, Valsalva manoeuvre, lying to standing, and postural hypotension. Serum Ca, Ca2+, P, Mg, alkaline phosphatase, iPTH, and osteocalcin were assayed. Hand X-ray was obtained to evaluate acro-osteolysis (score A) and subperiosteal resorption (score B). Ten predialysis patients (52%) and 15 haemodialysis patients (62%) showed one or more abnormal autonomic tests. Age, dialysis duration, and biochemical parameters of secondary hyperparathyroidism did not differ significantly in uraemic patients with and without abnormal autonomic tests. Furthermore, there was no significant relation between autonomic tests and iPTH or osteocalcin. Score A and score B was significantly greater in patients with abnormal tests than in patients without (P less than 0.009 and P less than 0.025). When predialysis and haemodialysis patients were considered separately the correlation between score A, score B, and autonomic neuropathy was confirmed only in haemodialysis patients. In conclusion, autonomic neuropathy does not seem to be related to the biochemical parameters of secondary hyperparathyroidism, while it appears significantly associated with the radiological signs of osteodystrophy, suggesting a possible pathogenetic linkage between autonomic neuropathy and secondary hyperparathyroidism.

[Hypothyroidism in adults: a magnetic resonance study of cerebral and hypophyseal changes]. / Ipotiroidismo dell'adulto: studio con la risonanza magnetica delle alterazioni cerebrali e ipofisarie.

The case of a 55-year-old woman with postpartum (at age of 22) hypopituitarism is reported. The patient, with signs of myxedema, was admitted to a psychiatric hospital for hallucinations. In addition to routine tests and measurements of thyroid hormones level, magnetic resonance imaging (MRI) of the brain and pituitary region was performed. The results of MRI showed cerebral atrophy and a large "empty sella". On the basis of clinical, laboratory and instrumental data, a diagnosis of panhypopituitarism with prevalent hypothyroidism was achieved. Many hypotheses could be made regarding its pathogenesis. Initially we considered the diagnosis of Sheehan's syndrome in which the sella turcica usually presents normal or reduced dimensions. However the presence of a large "empty sella" with thin walls, excludes this diagnosis. The delay of menarche and the short stature suggest the hypothesis of a preexistent pathological condition. It is possible that the patient had liquefied pituitary adenoma as a consequence of the postpartum shock or that she was hypothyroid, a condition in which the "empty sella" is very common.

[Radiological study of the duodenum in celiac disease in adults]. / L'esame radiologico del duodeno nel morbo celiaco dell'adulto.

Celiac disease (CD) is the most common form of malabsorption in childhood when it presents with diarrhea and growth failure, a jejunal biopsy is considered the first diagnostic investigation by some authors. In adulthood, clinical symptoms of CD may mimic several different disease, such as peptic ulcer and IBS, and the first diagnostic investigation is an upper GI series. Radiological features of duodenum and small bowel were evaluated in twenty patients with adult onset celiac disease. Sign of duodenitis such as thickened folds, mucosal nodules, dilatation of duodenum and erosions were observed in 19 out of our 20 patients (95%); particularly, thickened folds in 17 (85%), nodularity in 16 (80%), duodenal dilatation in 12 (60%) and erosions in 4 (20%). In celiac disease the lesions are more severe in the upper part of small bowel, and duodenitis may be the unique sign of CD. Duodenitis may be part of a disease involving the entire small bowel; so, a duodenitis observed in the upper gastrointestinal tract requires the study of the entire small bowel--which seems to be very important in the case of celiac disease.