High prevalence of thyroid dysfunction in pregnant women.

BACKGROUND/AIM: Maternal thyroid dysfunction during pregnancy has been associated with adverse obstetric and neonatal outcomes. This prospective study evaluates the prevalence of these disorders in pregnant women. SUBJECTS AND METHODS: Serum levels of TSH, free T4 (fT4), and thyroperoxidase antibodies (TPO-Ab) were measured in 951 women at different gestational ages of pregnancy. Trimester-specific reference ranges for TSH were used to classify pregnant women into five groups: 1) Overt hypothyroidism (OH); 2) Subclinical hypothyroidism (SCH); 3) Isolated hypothyroxinemia (IH); 4) Low TSH (isolated or associated with high fT4); and 5) Normal. A classification was made also according to the lower and upper ranges provided by the manufacturer for thyroid hormones. Pregnant women who were at a high risk of developing thyroid disease were identified. RESULTS: Altogether, 117 women (12.3%) had hypothyroidism and 25 (2.6%) had low TSH. The prevalence of both OH and SCH was higher in the high-risk group than in the low-risk group, but 17.9% of women with hypothyroidism were classified at low-risk. A family history of thyroid disorders and TPO-Ab positivity increased the risk of SCH. Using non-pregnant reference range for TSH, 10.6% of women were misclassificated. CONCLUSIONS: The high prevalence of hypothyroidism observed in this study suggests that accurate thyroid screening with trimester specific reference ranges should be warranted, particularly in areas with mild to moderate iodine deficiencies.

Original evaluation of endothelial dysfunction in men with erectile dysfunction and metabolic syndrome.

We have recently demonstrated the diagnostic value of a new immunophenotype of blood endothelial progenitor cells (EPCs=CD45neg/CD34pos/CD144pos) and endothelial microparticles (EMPs=CD45neg/CD144pos/AnnexinVpos) in patients with arterial erectile dysfunction (ED) according to severity of cavernous arterial insufficiency evaluated through penile Doppler. The aim of this study was to evaluate both EPCs and EMPs in patients with arterial ED and metabolic syndrome (MetS), comparing these patients with another group of patients without MetS and ED and a third group with MetS but without ED. For this study 50 patients with arterial ED and MetS were selected (age: 55.0±3.0 years; range: 47-60). A group of age-matched (age: 54.0±2.0 years; range: 44-60) patients without arterial ED and MetS (n=30), and another group of age-matched (age: 57.0±4.0 years; range: 40-62) patients with MetS but without ED (n=20) represented the control groups. EPCs and EMPs were significantly higher in patients compared with other groups (P<0.01). Both EPCs and EMPs correlated positively with the age, body mass index, and score of international index of ED (version five items) and with the following cavernous artery indices: peak systolic velocity, acceleration time and intima-media thickness. Among control groups patients with MetS but without ED showed serum concentrations of EPCs and EMPs significantly higher (P<0.05) compared with patients without MetS and ED. Patients with arterial ED and MetS have higher EPCs and EMPs compared with patients with MetS but without ED and patients without MetS and ED.

L-thyroxin treatment and post-menopausal osteoporosis: relevance of the risk profile present in clinical history.

AIM: Nodular thyroid disease and osteoporosis share some common factors such as: 1) elevated frequency in the general population; 2) major prevalence in the female sex; 2) incidence proportional to the age. There is a wide debate in literature regarding the real impact of chronic treatment with L-thyroxin (LT4) on the bone mineral density (BMD), especially in post-menopausal women. The aim of this study was to undertake to evaluate the effects of LT4 administration for the treatment of normo-functioning nodular thyroid disease on the BMD in post-menopausal women after one year of continuative treatment. Particular attention was paid in examining the role of some anamnestic risk factors for osteoporosis on the clinical response. METHODS: Ninety nine postmenopausal women of age comprised between 50 and 56 years were examined before and after 1 year of therapy with a fixed dose of LT4 for the treatment of nodular thyroid disease by monitoring the following laboratory parameters: thyroid stimulating hormone (TSH), FT4, FT3, antithyroglobulin antibodies [AbTG], hyroid peroxidase antibodies [AbTPO], serum calcium and alkaline phosphatase levels and 24-urinary excretion of calcium and hydroxyproline. Bone mineral density (BMD) was measured by dual X-ray absorptiometry of the lumbar vertebrae. RESULTS: The results of this study showed that the patients on treatment with LT4 have a slight, but significant reduction of the BMD after 1 year of treatment, associated with increased serum levels of alkaline phosphatase and urinary excretion of hydroxyproline. Comparison between patients with unsuppressed (group A) or suppressed (group B) TSH following LT4 treatment showed that group B patients had significantly lower BMD. The following risk factors influenced, in a statistically significant manner, the BMD: 1) Body Mass Index <19 kg/m(2); 2) the onset of menarche after the age of 15 years; 3) history positive for period of amenorrhoea; 4) nulliparity; 5) surgical menopause; 6) lack of hormonal replacement therapy; and 7) presence of auto-antibodies against thyroid antigens. CONCLUSION: LT4 treatment in postmenopausal women reduced significantly the BMD. This treatment should be therefore prescribed with caution in this condition and particularly when the following risk factors are present: surgically driven menopause, constitutional thinness, history of nulliparity, absence of hormonal treatment, positive history of secondary amenorrhoea during the reproductive age, autoimmune thyroid disease and delayed menarche.

Testosterone therapy improves the clinical response to conventional treatment for male patients with metabolic syndrome associated to late onset hypogonadism.

AIM: Recently, the clinic characterization of the gonadic male function has been put in tight correlation on the pathogenetic level with the main variables forming the condition of metabolic syndrome (MS); probably the serum testosterone (T) concentration in males is to be considered as an additional parameter completely related to the traditional clinical-metabolic findings. Currently the matter of the substitutive hormonal therapy with androgens is apparently influenced by some important unresolved aspects: 1) who really benefits from the T therapy? 2) are the actual dosage methods of T reliable? 3) which vascular and metabolic targets are to be monitored during the T therapy? METHODS: In an analytical longitudinal study, carried out 12 months long on 60 men (average age 58 years, range 54-63 years) affected by metabolic syndrome (MS) and combined hypogonadism late onset (LOH), authors have evaluated the clinical response (androgenic asset, non-invasive hospital monitoring of the arterial pressure, lipidic asset study, body composition and the biologic resistance to the insulinic action) after conventional medical therapy (insulin-sensibilizing and anti-hypertensive) and after substitutive hormonal therapy with testosterone (T) by transdermic way. A group of five patients with MS and LOH, not treated, was used as group of control. RESULTS: The group of patients treated with T showed a profile of clinical response better than the group of controls. CONCLUSIONS: In conclusion, the seric determination of T is useful to better characterize the dismetabolic patient at the moment of the first level active medical therapy planning on the controls of the main risk factors constituting MS, expressing a potential role of conditioning.

Bilateral adrenal non-Hodgkin lymphoma type B.

The adrenal localization of a primary non-Hodgkin lymphoma (NHL) is rare. We report a case of a 66-yr-old woman who had severe asthenia, diffuse skin hitching and abdominal pain. The physical examination revealed poor general conditions, irritability, pallor, dehydration and diffuse skin scratching lesions. The abdomen was painful at left hypochondrium and the Giordano's maneuvre was positive on both sides. A peripheral blood smear showed the presence of big rare lymphocytes with dyshomogeneous chromatin and granulated and hyperbasophil cytoplasm. She underwent abdominal ultrasonography which showed the presence of a hypoechogenic ovoidal mass (major diameter 8.4 cm) within the splenorenal left region. The presence of the suprarenal mass was confirmed by computed tomography (CT) scan which showed an enlarged left adrenal gland (8.1 x 6.2 cm) of solid structure. The right adrenal gland was also enlarged and of round shape (4.5 cm). CT scan-guided fine needle aspiration biopsy was then carried out on the left adrenal mass. It revealed the presence of NHL type B with large cells and modest T-lymphocyte reactive component. The patient was treated with three cycles of cyclophosphamide, adriamycin, vincristine and prednisolone. At the end of the third cycle, there was a transient clinical improvement and the hitching disappeared, but the patient worsened rapidly and she died few weeks later.

Similarities and differences in the phenotype of members of an Italian family with hereditary non-autoimmune hyperthyroidism associated with an activating TSH receptor germline mutation.

Constitutively activating germline mutations of the TSH receptor (TSH-R) are considered the cause of hereditary non-autoimmune hyperthyroidism. In this study, 10 members (8 affected and 2 unaffected) of an Italian family with hereditary non-autoimmune hyperthyroidism were investigated for the presence of mutations in the TSH-R gene. The clinical features of the disease were also analyzed. PCR-amplified fragments of the TSH-R gene were obtained from genomic DNA extracted from peripheral blood leukocytes of each family member and analyzed by direct nucleotide sequencing and restriction analysis. An identical germline TSH-R mutation was detected in all the patients with hyperthyroidism but in none of the unaffected family members. The mutation was heterozygotic and determined the substitution of valine for methionine (codon 463; ATG-->GTG) in the second transmembrane domain of the TSH-R. When expressed in chinese hamster ovary (CHO) cells, the Val463 mutant TSH-R induced constitutive activation of the TSH receptor. Analysis of the clinical features of our family and those of other families with hereditary non-autoimmune hyperthyroidism, including one with the same Val463 mutation, revealed wide variability in the phenotypical expression of the disease. Our findings indicate that an activating germline mutation in the TSH-R gene plays a key role in hereditary non-autoimmune hyperthyroidism although the onset of clinical manifestations and the evolution of the disease seem to depend heavily on other factors, thus far unidentified. The absence of a clear correlation between mutant genotypes and phenotypic expression of the disease currently limits the prognostic value of genetic testing in families with hereditary non-autoimmune hyperthyroidism.

Spontaneous regression over time of the germinal epithelium in a Y chromosome-microdeleted patient: Case report.

Azoospermia factor (AZF) region microdeletions, which account for about 10-15% of patients with oligoazoospermia, seem to lack a close genotype-testicular phenotype correlation. Although many genetic and non-genetic factors may contribute to this outcome, it was thought that a spontaneous regression of testicular germ cells might also play a relevant role. The opportunity for carrying out two different testicular biopsies one year apart in an AZFc-microdeleted patient enabled corroboration of this possibility. Indeed, the first biopsy showed a spermatocyte maturation arrest with mean Johnsen scores of 4 and 3.9 in the right and left testes respectively. One year later, the right testicular biopsy showed a picture of Sertoli cell-only syndrome in 90% of the tubules examined, and of spermatogonial maturation arrest in the remaining tubules, with a mean Johnsen score of 2.1. The almost complete absence of germinal cells was confirmed by four left testicular sperm aspirations (TESA), conducted at the same time as the biopsy during an intracytoplasmic sperm injection cycle, which showed the almost exclusive presence of Sertoli cells (85% of the whole cell population). No spermatozoa could be retrieved by TESA or testicular biopsy. To our knowledge, this is the first case of a spontaneous regression of the germinal cell epithelium over time in a patient with a Yq microdeletion without the apparent intervention of any cause known to affect the germinal epithelium.

Appearance of antithyroglobulin antibodies as the sole sign of metastatic lymph nodes in a patient operated on for papillary thyroid cancer: a case report.

We report a case in which the appearance of a progressively rising titer of thyroglobulin (Tg) antibodies was the most sensitive marker of papillary thyroid cancer relapse at loco-regional lymph nodes. The patient, a 60-year-old man, had been treated with total thyroidectomy plus lymphadenectomy and radioiodine ablation for a 1-cm papillary thyroid cancer. Twelve years after surgery, while undergoing levothyroxine (LT4) therapy, Tg antibodies were first detected and progressively rose from 99 to 1,697 U/mL in 18 months, while serum Tg remained undetectable. Both neck ultrasonography and 131I whole-body scan (WBS) were unremarkable. Enlarged lymph nodes became palpable at the left laterocervical region only 2 years after the first appearance of Tg antibodies and were surgically removed after cancer relapse was confirmed by fine-needle aspiration cytology. This case emphasizes the possibility that in thyroid cancer patients who have undergone total thyroidectomy, the appearance of Tg antibodies may indicate metastatic lymph nodes even when serum Tg is undetectable and WBS negative.

Detection of an activating mutation of the thyrotropin receptor in a case of an autonomously hyperfunctioning thyroid insular carcinoma.

Thyroid carcinomas, even when well differentiated, usually appear as hypofunctioning at scintigraphy. We report a case of an aggressive insular thyroid carcinoma presenting as an autonomously functioning thyroid nodule and causing severe thyrotoxicosis. The tumor was metastatic to a cervical lymph node and both lungs. An activating mutation of the TSH receptor gene in both the primary tumor and the lymph node metastasis was found, due to a base substitution at codon 633 (normal guanine at position 1896 replaced by cytosine CAC for GAC causing aspartic acid substitution by histidine). Other known oncogenes (gsp, ras, PTC/ret, trk, met, and p53) were not involved. This is the first description of an activating TSH receptor mutation in a thyroid hyperfunctioning carcinoma in which an aggressive malignant phenotype coexisted with activation of the cAMP cascade and differentiated thyroid functions.

Transition from cold to hot thyroid nodules.

We report three cases of autonomously functioning thyroid nodules (AFTNs) that appeared hypofunctioning at radioactive iodine (131I) thyroid scan carried out at initial observation. Since at that time thyroid hormones and thyrotropin (TSH) were also normal, they were initially classified as "cold" nodules and treated with levothyroxine (LT4). The correct diagnosis of AFTN was made years later when a thyroid scintigraphy was repeated. In two of these patients, re-evaluation of the nodule was done because of the development of LT4 intolerance. A possible explanation is that these AFTNs had undergone hemorrhagic/cystic degeneration when they were first studied, but in subsequent years, proliferation of residual AFTN tissue caused the recurrence of a typical functioning nodule.

[Physiopathology of the autonomous thyroid nodule]. / Fisiopatologia del nodulo "autonomo" della tiroide.

"Autonomous" thyroid nodule is a localized nodular lesion of the thyroid gland characterized by growth, iodine uptake and function, all independent from TSH control. These nodules represent a heterogeneous anatomic and clinical entity. The clinical diagnosis is based upon a negative suppression of nodule iodine uptake and scan imaging by T3 administration. The nodule function is determined by high serum thyroid hormone levels and/or low TSH (measured by ultrasensitive assay). Etiology and pathogenesis of these nodules is not yet completely clarified. Both genetic and environmental factors determine nodule growth and function: thyroid cells, in fact, are genetically heterogeneous and may have intrinsic (congenital) characteristics that may promote the growth of cellular clones having mitotic and functional activity that is partially independent of TSH. In these particular cell clones, environmental factors like iodine deficiency or other goitrogens may favour the growth of autonomous nodules and also, by activating their function, may induce toxicity. The autonomous thyroid nodules need to be treated only when they become toxic: in this case both surgical excision or radioiodine may be used.