Thyroid gland and pulmonary hypertension. What's the link?

Both hyperthyroidism and hypothyroidism produce changes in cardiac contractility, myocardial oxygen consumption, cardiac output, blood pressure, and systemic or pulmonary vascular resistance. In almost all cases these cardiovascular changes are reversible when the underlying thyroid disorder is recognized and treated. Pulmonary hypertension (PAH) has been associated with thyroid dysfunction, but primarily with hyperthyroidism. The vast majority of patients with this form of PAH are usually older with toxic multinodular goitre. Data currently available suggest a direct influence of TH on pulmonary vasculature. Possible mechanisms include: 1) enhanced catecholamine sensitivity, causing pulmonary vasoconstriction, a reduction in pulmonary vascular compliance and an increase in vascular resistance; 2) increased metabolism of intrinsic pulmonary vasodilating substances (prostacyclin, nitric oxide); 3) decreased or impaired metabolism of vascontrictors (serotonin, endothelin 1 and tromboxane). In some cases (Graves's and Hashimoto's disease) and an autoimmune process inducing endothelial damage may play a key role. Future studies should focus on discovering the immunogenetic overlap between autoimmune thyroid diseases and PAH: common human leukocyte antigen alleles, susceptibility loci and so on. Such an understanding of the genetic and immune factors may ultimately lead to novel effective approaches in the treatment of PAH. At present, thyroid function tests should be considered in the investigation of all patients with PAH.

A new type of Hypersensitivity Pneumonitis: salami brusher's disease.

We observed five consecutive cases of Hypersensitivity Pneumonitis in subjects working in a salami factory. The workers had to clean the white mould growing on salami surface using a manual wire brush. The five patients (four female) had a mean age of 39 +/- 15 years; two were smokers. Three patients had an acute clinical presentation with fever, dyspnoea, dry cough, oxygen desaturation, and presented at the emergency department with suspected diagnosis of community acquired pneumonia. The mean latency for developing respiratory symptoms was 11.6 days. Pulmonary function test demonstrated a reduction in diffusing capacity (DLCO) in all 5 patients (60 +/- 15% of predicted value). Skin prick test was positive for Penicillium spp in 3 cases and for Cladosporium and Aspergillus spp in 2 others. Specific IgG antibodies against Penicillium spp were positive in 3 subjects; 2 were positive for Aspergillus Fumigatus. The prevailing radiological pattern was a ground glass appearance in the three patients with acute clinical onset and a centrilobular one in patients with subacute onset. All patients were advised to avoid exposure to the antigens. Follow-up visits including pulmonary function testing, and DLCO measurement were conducted at one, three and six months. HRCT was performed at six month. Four subjects had a complete radiological and clinical resolution after changing work. Only one patient was treated with oral steroids for severe dyspnoea and progressive reduction of DLCO, gaining a complete radiological and clinical stability at six months.

DLCO correlates with intestinal inflammation in ulcerative colitis, but albuminuria does not.

AIM: The aim of this study was to evaluate the frequency of carbon monoxide diffusing capacity (DLCO) impairment and microalbuminuria in patients with active ulcerative colitis (UC) and to assess whether these nonexpensive and noninvasive tests correlate with intestinal inflammation. METHODS: A prospective observational study was set up at the Fiorenzuola Hospital and performed during a 4-year period. We enrolled 30 consecutive subjects with clinical and histological diagnosis of active UC and 20 healthy subjects matched for age and sex. After full colonscopic assessment with multiple mucosal biopsies, the clinical disease activity of each patient was quantified. A global spirometry and 24-h urine collection at rest to measure microalbuminuria were performed. Each biopsy specimen was assessed blindly by a histopathologist, who assigned a score according to the severity of enterocyte damage, cryptitis and acute and chronic inflammation of the lamina propria. RESULTS: A latent pulmonary involvement with a reduction in DLCO was present in 20 patients (67%). A subclinical renal involvement with microalbuminuria was detected in 19 subjects (63%). The mean DLCO was 78.2+/-15.2 in Group 1 vs 94.7+/-13.1 in Group 2 (P<0.001). Microalbuminuria was 103.6+/-90.8 in Group 1 vs 57+/-31.7 in the control group (P=0.062). DLCO reduction correlated significantly with intestinal histopathological grading in Group 1 (r = -0.742, P< 0.001), although there was no correlation between microalbuminuria and histological grading (r = -0.273, P= 0.143). CONCLUSION: Our data confirm that latent pulmonary involvement (DLCO impairment) and microalbuminuria are frequent in UC. The DLCO may provide a useful noninvasive indicator of colonic inflammation in subjects with UC and concomitant subclinical lung involvement.

Hyperthyroidism and pulmonary hypertension.

In recent years, many authors have described several cases revealing an association between hyperthyroidism and pulmonary hypertension (PH). This observational study was designed to evaluate the incidence of PH in hyperthyroidism and was set in a department of internal medicine and pulmonary diseases with an out-patients department of endocrinology. Thirty-four patients, 25 women and nine men, with a mean age of 38 +/- 15 SD years participated. Twenty had Graves' disease and 14 had a nodular goitre. The patients were divided into two equally matched groups: those with a recently diagnosed hyperthyroidism, taking no drugs (group 1; n = 17) and those in a euthyroid state taking methimazole (group 2; n= 17). Transthoracic Doppler echocardiography was performed and systolic pulmonary artery pressurements of (PAPs) was determined by the tricuspid regurgitation method using the Bernoulli equation. Measurements of triiodothyronine, tetraiodothyronine, free thyroxine (Ft4), thyroid-stimulating hormone (TSH) and antithyroglobulin and antimicrosomal antibodies were also taken. We found a mild PH in seven patients of group 1 and in none of group 2. The mean +/- SD systolic pulmonaryartery pressurewas 28.88 +/- 6.41 in group 1 and 22.53 +/- 1.84 ingroup 2 (P<0.0001). A correlation was found between the TSH value and PAPs (r = -082;P < 0.001) and Ft4 and PAPs (r = 0 85; P < 0.001) in group 1. These findings indicate the presence of a frequent association between PH and hyperthyroidism. We suggest that hyperthyroidism be included in the differential diagnosis of PH.

Pulmonary function in non-insulin-dependent diabetes mellitus.

BACKGROUND: In type I diabetes mellitus, lung function has been investigated in several clinical studies, but there are few data concerning pulmonary function abnormalities in patients with non-insulin-dependent diabetes mellitus (NIDDM). OBJECTIVES: The aim of this study was to assess the presence of pulmonary function abnormalities in patients with NIDDM and to verify the possible associations between diabetic renal microangiopathy, retinopathy and diabetes control. METHOD AND PATIENTS: Thirty patients with NIDDM were collected and divided into two similar groups: subjects with retinopathy and/or diabetic glomerulopathy (group 1, n = 15) and patients without any complications (group 2, n = 15). 17 were males and 13 females, aged from 45 to 81 years. They had had diabetes for 3-23 years and were studied at the Division of Internal Medicine, with an outpatient service for diabetic patients. All patients were non-smokers. The presence of diabetic glomerulopathy was determined by measuring the 24-hour protein excretion rate using the nephelometric method. The presence of retinopathy was determined by using ophthalmoscopy. Glycosylated hemoglobin was measured as an indicator of glycemic control. We performed a global spirometry and measured pulmonary diffusion capacity by the single-breath method corrected by alveolar volume. RESULTS: We found a significant reduction in lung diffusion capacity for carbon monoxide (DL(CO)) in the group of patients with other signs of diabetic microangiopathy (p < 0.005) and a significative correlation between DL(CO )and the grade of albuminuria (r = -0.83, p < 0.001). CONCLUSIONS: Pulmonary function abnormalities, in particular a reduction in diffusion capacity, are common in patients with NIDDM and signs of diabetic microangiopathy. A possible explanation is related to an impaired pulmonary microvasculature and alveolar epithelial basal lamina.

[Is the lung a target organ in inflammatory bowel disease?]. / Il polmone è un organo bersaglio nella malattia infiammatoria intestinale?

Inflammatory bowel disease is a systemic illness that may involve the lung. The most common manifestation of pulmonary involvement is an asymptomatic reduction in lung transfer factor for carbon monoxide (Dlco) and a small airway disorders easy to find in subjects with active disease. Some patients show a bronchial inflammation and suppuration with or without bronchiectasis poorly responsive to antibiotics but responding dramatically to inhaled steroids. Others present a severe tracheal inflammation and obstruction with an inflammatory mass bulging into the tracheal lumen, these subjects usually respond to methylprednisolone, in rare cases an emergency laser ablation may be necessary. Interstitial lung disease and pulmonary infiltrate with eosinophilia are the most difficult patterns to address because in some cases drugs such as sulfasalazina and 5-aminosalicylate may play a contributing role.

Changes in the carbon monoxide diffusing capacity of the lung in ulcerative colitis.

The aim of this study was to investigate lung function in patients with ulcerative colitis and to assess the incidence of latent pulmonary involvement in subjects with active and inactive disease. After full colonscopic assessment with multiple mucosal biopsy, the clinical disease activity of each patient was quantified, using the simple index of Harvey and Bradshaw. The patients were divided into 2 equal groups: subjects with active disease (group 1; n=16); and those with inactive disease (group 2; n=16). Global spirometry was then performed. A latent pulmonary involvement was found in 17 of 32 patients (53%), the incidence was higher in the group 1 patients (81%). The majority of patients presented a reduction in the carbon monoxide diffusing capacity of the lungs (DL,CO). The mean DL,CO value was 73.87+/-14.87 in group 1 and 87.31+/-11.23 in group 2. The DL,CO and KCO reduction correlated significantly with intestinal histopathological grading in the group of patients with active disease (r=0.87, p<0.001; r=0.603, p=0.015). To conclude, a high incidence of pulmonary function abnormalities were identified, despite the lack of radiological alterations (High Resolution Computed Tomography) and pulmonary symptoms, in ulcerative colitis patients. These alterations were more common in patients with active disease. The strong correlation between DL,CO values and histopathological grading suggests that this test may reflect bowel disease activity.

[Osteoarticular sarcoidosis]. / La sarcoidosi osteoarticolare.

Sarcoidosis (S) is a systemic disease affecting above all lymph nodes and lung tissue. Skeletal involvement is reported to occur in 14% of patients, the most common manifestations is cystoid osteitis, an asymptomatic lesion localized to the small bones of hand and feet. Lytic lesions are rare and usually accompanied by visceral involvement, the lesions may be detected in vertebral bodies and in long bones, pelvis and scapulae. MRI may be a good diagnostic tool, but open biopsy is often necessary. Joints are involved in about 89% of patients with acute sarcoidosis. Arthritis is localized more frequently to knees and ankles, is polyarticular, a little painful, migratory and transient, often accompanied by erythema nodosum. Clinical manifestations disappear in a few weeks, chronic and erosive disease is rare and always associated with systemic involvement. In these patients it may be useful to perform gallium citrate 67 scintigram and evaluation of serum ACE. Synovial biopsy lacks of specificity and sensibility, and in some cases it is necessary to perform open biopsy. S is a disease that may spontaneously regress and therapy may be unnecessary. In some cases, methotrexate may be useful in addition to prednisone. Chloroquine and hydroxychloroquine are effective in cases of skeletal involvement.

[Pulmonary complications in diabetes mellitus]. / Complicanze polmonari in corso di diabete mellito.

The lung is not considered a target organ in diabetes mellitus. In English language literature there are many papers showing the opposite. Many studies demonstrated a thickened alveolar epithelial and pulmonary capillary basal lamina and a reduced lung elasticity, others showed that these histopathological alterations developed into functional abnormalities: reduced lung volumes, reduced pulmonary diffusion capacity and elastic recoil. The pathogenesis is currently thought to involve the nonenzymatic glycosylation (NEG) of tissue proteins inducing an alteration in connective tissue. In patients with diabetic autonomic neuropathy there is an abnormal basal airway tone due to an alteration in vagal pathways: these patients have a reduced bronchial reactivity and bronchodilatation. Diabetic patients have an increased propensity to acquire infections, in particular tuberculosis and pulmonary fungal diseases (coccidioidomycosis, aspergillosis and mucormycosis). The frequency of occurrence of tuberculosis is reported to be four times than in non diabetics, there is a predilection for the lower lobes and the disease is more aggressive in poorly controlled diabetes mellitus. Pulmonary mucormycosis is an infection caused by Phycomycetes, the fungus has the propensity to invade vascular structures giving hemoptysis and leading to a high mortality unless diagnosed promptly. The mechanism for the increased susceptibility to infection is due to an alteration in chemotactic, phagocytic and bactericidal activity of polymorphonuclear leukocytes.