A makro-TSH diagnosztikus és terápiás jelentősége Hashimoto-thyreoiditises betegekben | Diagnostic and therapeutical significance of macro-TSH in patients with Hashimoto’s thyroiditis

Absztrakt: Bevezetés: A makro-TSH szerkezete, incidenciája és klinikai szerepe pajzsmirigybetegekben nem tisztázott. Célkitűzés: A makro-TSH előfordulási gyakoriságának, tulajdonságainak meghatározása Hashimoto-thyreoiditises betegek savójában. Módszer: A Hashimoto-thyreoiditises betegek vérmintáiban a makro-TSH-t meghatározták polietilén-glikol precipitációs módszerrel és protein G agaróz abszorpciós, illetve gélfiltrációs kromatográfiával. A makro-TSH biológiai aktivitását TSH-receptorral transzfektált CHO bioassay módszerével mérték. A betegek L-tiroxin-kezelésben részesültek (átlagosan 66,5 µg/nap), a betegek fele pedig szelént is kapott (átlagosan 60 µg/nap). Eredmények: 880 Hashimoto-thyreoiditises beteget (728 nő, átlagéletkor 44,8 év) vontak be a vizsgálatba. A makro-TSH-t 41 betegben (4,6%) mutatták ki, az átlagos TSH-szint a PEG-precipitáció előtt 185,4 ± 35 IU/l volt, a precipitáció után pedig 5,55 ± 1,8 IU/l. Az anti-TPO-szint 445 ± 51 IU/l volt és fokozatosan csökkent 212 ± 51 IU/l-re egyéves tiroxin- és szelénkezelés után. Mind a PEG-precipitációs, mind a protein G abszorpciós módszerrel, illetve gélkromatográfiás eljárással a TSH elleni antitest jelenlétét mutatták ki a makro-TSH-immunkomplexben. A makro-TSH biológialag inaktívnak bizonyult, mivel a CHO-sejteket nem stimulálta. A makro-TSH a szelénnel nem kezelt csoportban 18 ± 3,2 hónapig, a szelénnel kezeltben 12 ± 1,9 hónapig volt kimutatható. Következtetés: A TSH elleni antitestek fő komponensei a makro-TSH-nak és diagnosztikus, illetve terápiás nehézségeket okozhatnak. A PEG-precipitációs eljárás alkalmas szűrőmódszer a makro-TSH bizonyítására. A szelén képes nemcsak az anti-TPO-, hanem a makro-TSH-szint csökkentésére egyaránt. Amikor a TSH-szint 40,0 IU/l feletti a hypothyreosis jelei nélkül, gondolnunk kell a makro-TSH jelenlétére. Orv Hetil. 2017; 158(34): 1346–1350. | Abstract: Introduction: Structure, importance and incidence and clinical role of macro-TSH not clarified in thyroid diseases. Aim: This study was undertaken to determine the incidence and biological role of macro-TSH in patients with Hashimoto’s thyroiditis. Method: Blood samples taken from patients with Hashimoto’s thyroiditis were screened for the presence of macro-TSH with the polyethylene glycol method and confirmed with protein G agarose absorption test and gel filtration chromatography. Stimulatory capacity of macro-TSH was measured by CHO cells bio-assay. Patients were treated with L-thyroxine (mean 66.5 µg/day) and half of them with selenium (mean 60 µg/day), respectively. Results: 880 patients (728 female, aged 44.8 yr) with Hashimoto’s thyroiditis was involved in the study. Macro-TSH was found in the serum of 41 patients (4.6%), the mean TSH 185.4 ± 35 IU/l was before PEG precipitations and after 5.55 ± 1.8 IU/l. Titre of anti-TPO proved to be 445 ± 51 IU/l and gradulally decreased to 212 ± 51 IU/l after one year therapy. Both the precipitation, protein G absorption and gel chromatography supported the presence of anti-TSH antibody in the macro-TSH complex. Stimulatory capacity of macro-TSH on CHO bio-assay was not proved. The macro-TSH was detected in the selenium not treated group for 18 ± 3.2 months, selenium-treated for 12 ± 1.9 months. Conclusion: It is concluded that anti-human TSH autoantibodies are a major components of macro-TSH and may cause diagnostic and therapeutical difficulties. The PEG precipitation is a suitable screening method for detection of macro-TSH. Selenium is able to decrease of anti-TPO antibodies and macro-TSH, respectively. When the TSH level is greater than 40.0 IU/l, without the signs of hypothyroidism, the presence of macro-TSH is to be considered. Orv Hetil. 2017; 158(34): 1346–1350

Clinical Characteristics of the Study Population.

<p>AST≥40 IU/L or ALT≥40 IU/L were defined as Transaminase elevation;Serum PA levels≤170 mg/L were defined as PA decreased.</p>*<p><i>P<</i>0.05, compared to both TB and healthy individuals groups.</p>***<p><i>P<</i>0.001, compared to both lung cancer patients and health individuals groups.</p>**<p><i>P<</i>0.01, compared to both lung cancer patients and health individuals groups.</p

Influencing factors of PA decrease in patients with TB.

<p>Serum PA levels≤170 mg/L were defined as PA decreased;</p><p>Patients were divided into two types:lung TB(pulmonary tuberculosis patients without pleuritis) and with pleuritis(incluing both pulmonary tuberculosis patients with pleuritis and simple pleuritis patients).</p>**<p><i>P<</i>0.01.a: age≥60 compared to other subgroups; b: smoking status≥20 compared to other subgroups.</p

The serum PA levels in different subgroups of TB patients.

<p>There were significant differences in the serum PA levels between following subgroups: pleuritis and lung tuberculosis, TB patients with higher ESR (≥20 mm/h) and normal ESR (<i><</i>20 mm/h), TB patients with higher smoking status (≥20 year×pack) (<i>P<</i>0.01).</p

The change of serum PA levels in different group of patients.

<p>Serum PA levels slowly elevated after the TB patients accepted anti-TB drugs. Nine months after use of anti-TB drugs, the average of serum PA levels (194.1±29.2 mg/L) among these TB patients significantly rised to normal range. However, the serum PA levels of drug-resistant TB patients remained at a low level state. The serum PA levels in lung cancer patients were slowly reduced after chemotherapy.</p

Relationship between Apparent Diffusion Coefficient and Tumour Cellularity in Lung Cancer

<div><p>Background and objective</p><p>To prospectively investigate the relationship between the apparent diffusion coefficient (ADC) and cellularity in lung cancer.</p><p>Methods</p><p>Sixty patients histopathologically confirmed with lung cancer (41 men, 19 women) underwent diffusion-weighted magnetic resonance imaging of the chest (with <i>b values</i> of 50 and 1000 s/mm²). The median mean ADC (ADCmean) value and median minimum ADC (ADCmin) value within each primary tumour were calculated and compared with the median nucleo-cytoplasmic ratio (NCR), which was selected to represent the cellularity. The correlation between the NCR and ADCmean/ADCmin was calculated with SPSS 18.0 software.</p><p>Results</p><p>The mean ADCmean values, ADCmin values and median NCR were (1.07±0.12)×10⁻³ mm²/s, (0.86±0.14)×10⁻³ mm²/s, and (14.9±2.6) %, respectively, in adenocarcinoma; (0.88±0.10)×10⁻³ mm²/s, (0.73±0.12)×10⁻³ mm²/s, and (20.6±4.4) %, respectively, in squamous cell carcinoma; and (0.89±0.13)×10⁻³ mm²/s, (0.67±0.13)×10⁻³ mm²/s, and (18.3±3.5) %, respectively in small cell lung cancer. The NCR of squamous cell carcinoma and small cell lung cancer is greater than that of adenocarcinoma (P<0.01 and P = 0.002, respectively). There was an inverse relationship between ADCmean/NCR and ADCmin/NCR (r = −0.60, P = 0.001 and r = −0.47, P<0.001, respectively).</p><p>Conclusion</p><p>There is a significant inverse relationship between tumour cellularity and ADC in lung cancer. However, tumour cellularity most likely is not the sole determinant of the ADC.</p></div

Histopathologic correlation of MR imaging data with biopsy specimens in a 48-year-old woman with small cell lung cancer.

<p>A, CT-guided biopsy; B, T2WI-TIRM; C, ADC map and ROI where ADCs have been measured are illustrated, 1 = ROI; D, corresponding histopathologic results for the tumour sample (original magnification, HE×400).</p

Scatter matrix of the PET/CT and DCE-MRI metrics in SCC of the lung.

<p>Scatter matrix of the PET/CT and DCE-MRI metrics in SCC of the lung.</p

Clinical characteristics of included NSCLC patients.

<p>Data are reported as mean ± SD with minimum and maximum in parentheses.</p

ADCs and Cellularity among Histologic Types of Lung Cancer (Data is expressed as mean ± standard deviation).

<p>ADCs and Cellularity among Histologic Types of Lung Cancer (Data is expressed as mean ± standard deviation).</p