Menachem S. Shapiro

Autoimmune thyroid disease and antiphospholipid antibodies

Autoimmune thyroid disease (ATD) is associated with circulating autoantibodies reactive with epitopes on thyroid tissue and that are thought to be pathogenic in the development of these diseases. Antiphospholipid antibodies (APLA) are a family of immunoglobulins that recognize a variety of plasma proteins in association with anionic phospholipids. These antibodies may lead to a number of clinical syndromes including venous and arterial thromboses, thrombocytopaenia, and recurrent fetal loss. We have studied the prevalence of APLA in patients with ATD and have determined the prevalence of the APLA syndrome among APLA‐positive patients.

Prevalence and Evaluation of B12 Deficiency in Patients with Autoimmune Thyroid Disease

Background:Patients with autoimmune thyroid disease (AITD) have a higher prevalence of pernicious anemia compared with the general population. Clinical signs of B12 deficiency may be subtle and missed, particularly in patients with known autoimmune disease. We assessed the prevalence of vitamin B12 deficiency in patients with AITD and whether their evaluation may be simplified by measuring fasting gastrin levels. Methods:Serum B12 levels was measured in 115 patients with AITD (7 men and 108 women), with a mean age of 47 ± 15 years. In patients with low serum B12 levels (≤133 pmol/L), fasting serum gastrin and parietal cell antibodies (PCA) were measured. Results:Thirty-two patients (28%) with AITD had low B12 levels. Fasting serum gastrin was measured in 26 and was higher than normal in 8 patients. PCA were also measured in 27 patients with B12 deficiency and were positive in 8 patients. Five patients with high gastrin levels underwent gastroscopy with biopsy, and atrophic gastritis was diagnosed in all. The prevalence of pernicious anemia as assessed by high serum gastrin levels in patients with low B12 was 31%. Conclusions:Patients with AITD have a high prevalence of B12 deficiency and particularly of pernicious anemia. The evaluation of B12 deficiency can be simplified by measuring fasting serum gastrin and, if elevated, referring the patient for gastroscopy.

Clinical relevance of non-palpable thyroid nodules as assessed by ultrasound-guided fine needle aspiration biopsy

It is known from autopsy data that thyroid nodules are far more common than can be detected by palpation alone. With the wide use of modern non-invasive imaging many nonpalpable thyroid nodules are discovered but the proper approach to these nodules is still debatable. In a retrospective study, we reviewed the data from 186 US-guided FNA biopsies (US-FNAB) performed between May 1995 and March 1997 at the Sapir Medical Center, Israel, a iodine-sufficient urban area. Sixty-one of the 186 US-FNAB of the thyroid were performed in non-palpable nodules. The mean size of these nodules was 2.4±1.0 cm (mean±SD) ranging from 1.1–5.5 cm. Description of the nodule consistency was available in 53 cases; 42/53 were solid and 11/53 were solid-cystic. FNAB was diagnostic in 46 patients and non-diagnostic in 15. Forty-three of the diagnostic cytology reports were benign, one revealed papillary carcinoma, one had suspicious findings and the third was suspicious for a follicular neoplasm. The last two patients were referred to surgery and a follicular adenoma was found in both. Among the 61 non-palpable thyroid nodules, only one was papillary carcinoma, a prevalence of 1.6%. The other two patients referred to surgery had benign lesions. We found a low prevalence of malignancy in relatively large nonpalpable thyroid nodules.

Identification and preliminary characterization of two human digitalis-like substances that are structurally related to digoxin and ouabain.

In order to characterize the structure of endogenous digitalis-like immunoreactive factor (DLIF), we utilized peritoneal dialysis fluid from patients with chronic renal failure as a source of endogenous digitalis-like immunoreactive factor (DLIF), and subjected it to one-step ion exchange chromatography, followed by one step reverse HPLC. Crude dialysis fluid contained 0.09 ng/ml of DLIF, and using Amberlite XAD-2 chromatography we extracted 110 ng of DLIF from 800 ml of dialysis fluid. By applying this partially purified DLIF to our HPLC system, we discerned three peaks of DLIF activity, with retention times of 34, 58 and 63 minutes. The first peak overlapped the elution profile of ouabain, and the third peak co-eluted precisely with digoxin. The second DLIF peak was not in proximity to any of the digitalis-like markers employed. Thus, our results indicate that DLIF isolated from peritoneal dialysis fluid exists in three distinct forms, one of which resembles ouabain, and one which is identical to digoxin.

The polyglandular deficiency syndrome: a new variant in Persian Jews

Five Persian Jews were detected with the polyglandular deficiency syndrome (PDS). Primary hypoparathyroidism and hypogonadism were present in each, adrenal insufficiency in two, and insulin-dependent diabetes mellitus and latent hypothyroidism in single subjects. The percentage of T and B cells, and the mononuclear cell response to phytohemagglutinin and Concanavalin A were normal in all five. IgG and IgA levels and the OKT4+/OKT8+ cell ratio were low in one subject. Antinuclear and antithyroid antibodies were present in one subject. HLA-DR5 was present in 4/4, HLA-24 and B5 (B51) in 3/4 subjects. A single case of isolated hypoparathyroidism (IHP) was detected among 12 first degree relatives. HLA antigens B8, DR3, were absent in all of these subjects. Seven non-Iranian Jews with IHP were also examined. HLA A26 or A25 were present in all seven. Persian Jews appear to have a unique variant of PDS.

Cardiac troponin T is not increased in patients with hypothyroidism

Patients with hypothyroidism often have increased creatine kinase (CK) levels. It is possible that there is increased production of CK, but other mechanisms, such as an increased cell membrane permeability or decreased enzyme clearance were also proposed. Recently, troponins T and I have been extensively studied because of their cardiac specificity. Cardiac troponins are sensitive and specific markers of cardiac injury. The objective of the study was to measure cardiac troponin T (cTnT) levels in patients with hypothyroidism. Twenty‐five patients with primary hypothyroidism were evaluated (thyroid‐stimulating hormone (TSH) >30 mU/L and low FT4). In all patients thyrotropin (TSH), free thyroxine (FT4), CK, CK‐MB and cTnT were measured.There were 3 men and 22 women with a mean age of 47.5 ± 12.4 years. TSH levels ranged from 31 to 75 mIU/L and mean FT4 levels were 4.5 ± 1.9 pmol/L. CK was normal in 11 patients and increased in 14. CK levels ranged between 86 and 1221 U/L (normal levels <170 in women, <195 in men) with a mean of 322 U/L ± 279. CK‐MB was increased in 4 patients (16%) and normal in 21. All 25 patients had normal cTnT levels, < 0.01 ng/mL (normal levels 0–0.1 μg/L). Increase in CK and its MB fraction are common in patients with hypothyroidism but cTnT levels are not, even in patients with increased CK‐MB. Therefore, cTnT is a reliable marker of cardiac injury even in the hypothyroid patient.

Gonadotropin, prolactin and TSH secretion in patients with myasthenia gravis

Hypothalamic pituitary function was studied in 13 patients with myasthenia gravis. Gonadotropin, TSH, and prolactin dynamics were investigated using conventional provocative stimuli. No consistent abnormality was found in either gonadotropin or prolactin release. Abnormal TSH responses to TRH administration was present in six of the 13 patients in association with normal free thy roxine indices and the absence of antithyroid antibodies. This latter observation is relevant when the association of myasthenia gravis with hyperthyroidism, thyroiditis and hypothyroidism is considered.

Digoxinlike Immunoreactive Factor Isolated From Human Pleural Fluids is Structurally Similar to Digoxin

To further define the chemical structure of human endogenous digoxinlike immunoreactive factors (DLIF) we used human pleural effusions as a source of the substance. Digoxinlike immunoreactive factor activity was detected by radioimmunoassay in the pleural fluid of each of four patients; average concentration was 0.35 ng/mL. The chemical profile of DLIF was determined by initial extraction and concentration of DLIF by ion exchange chromatography followed by reverse phase-high-pressure liquid chromatography (RP-HPLC) separation and purification. Using high-pressure liquid chromatography cochromatography of DLIF, together with several radioactively marked glycosides, we observed a single peak of DLIF activity that was chromatographically identical to digoxin. The present study further supports the recent finding that DLIF is related structurally to the cardiac glycosides, and for the first time it has been proven that DLIF is present in pleural fluids.

Anti-thyroid antibodies, parietal cell antibodies and tissue transglutaminase antibodies in patients with autoimmune thyroid disease

Introduction The co-existence of tissue-specific autoantibodies in autoimmune thyroid disease (ATD) is well established. The published prevalence of anti-parietal cell antibodies (PC-Ab) is 20–25%, and that of celiac antibodies is 2–5%. The goal of this study was to determine the prevalence of PC-Ab and anti-tissue transglutaminase antibodies (tTG-Ab) in patients with ATD and to evaluate the correlation between anti-thyroid antibodies and the other antibodies. Material and methods The files of 120 Israeli Jews and Arabs with ATD were evaluated for anti-thyroglobulin antibodies (Tg-Ab), anti-thyroid peroxidase antibodies (TPO-Ab), PC-Ab and tTG-Ab. For patients with positive PC-Ab and/or tTG-Ab, upper gastrointestinal (GI) endoscopy results were recorded. Gastrin levels were collected in patients with positive PC-Ab. Results Twelve (10%) males and 108 (90%) females were evaluated, of whom 93.33% had Hashimoto’s thyroiditis. Thirty-four (28.3%) subjects had positive PC-Ab. This rate was not affected by gender, ethnicity or thyroid disease. Abnormal gastroscopy findings were documented in 95.2% of the upper GI endoscopies. The mean gastrin level in this subgroup was 660.4 pg/ml. Five of 114 tTG-Ab tests were positive (4.4%). All were females with Hashimoto’s thyroiditis. Rates were equal among Jews and Arabs. Higher TPO-Ab levels were associated with higher risk for PC-Ab positivity (p = 0.027), but not tTG-positivity. Higher Tg-Ab levels were not associated with higher levels of other antibodies. Conclusions Considering the frequency of PC-Ab and tTG-Ab positivity in ATD, checking for the presence of these two entities should be an integral part of the workup of this disease.