Thyroid diseases during pregnancy: a number of important issues.

The most common thyroid diseases during pregnancy are hyper- and hypothyroidism and their variants including isolated hypothyroxinemia (hypo-T4), autoimmune thyroid disease (AITD) and different types of goiter. AITD represents the main cause of hypothyroidism during pregnancy ranging in prevalence between 5 and 20% with an average of 7.8%. The incidence of isolated hypo-T4 is about 150 times higher compared to congenital hypothyroidism. Prevalence of Graves' disease (GD) ranges between 0.1% and 1% and the Transient Gestational Hyperthyroidism Syndrome between 1 and 3%. Thyroid stimulating hormone (TSH) is a sensitive marker of thyroid dysfunction during pregnancy. Normal values have been modified recently with a downward shift. Thus, the upper normal range is now considered to be 2.5 mUI/mL in the first trimester and 3.0 mUI/mL for the remainder of pregnancy. Most studies have shown that children born to women with hypothyroidism during gestation had significantly lower scores in neuropsychological tests related to intelligence, attention, language, reading ability, school performance and visual motor performance. However, some studies have not confirmed these findings. On the other hand, multiple retrospective studies have shown that the risks of maternal and fetal/neonatal complications are directly related to the duration and inadequate control of maternal thyrotoxicosis. The latter is associated with a risk of spontaneous abortion, congestive heart failure, thyrotoxic storm, preeclampsia, preterm delivery, low birth weight and stillbirth. Despite the lack of consensus among professional organizations, recent studies, which are based on sophisticated analyses, support universal screening in all pregnant women in the first trimester for thyroid diseases.

A rare case of a parathyroid adenoma inside a parathyroid cyst.

Parathyroid cysts (PCs) are rare lesions, located in the neck and anterior mediastinal region. The vast majority are non-functioning, presented as nodular cervical lesions. Large, non-functioning PCs can manifest with compressive symptoms of the surrounding tissues. Rarely, PCs produce excessive amounts of parathyroid hormone (PTH), resulting in primary hyperparathyroidism. We report a case of functional PC, describing its diagnostic and therapeutic approach.

A rare case of a parathyroid adenoma inside a parathyroid cyst / Um caso raro de adenoma de paratireoide em um cisto de paratireoide

Parathyroid cysts (PCs) are rare lesions, located in the neck and anterior mediastinal region. The vast majority are non-functioning, presented as nodular cervical lesions. Large, non-functioning PCs can manifest with compressive symptoms of the surrounding tissues. Rarely, PCs produce excessive amounts of parathyroid hormone (PTH), resulting in primary hyperparathyroidism. We report a case of functional PC, describing its diagnostic and therapeutic approach.

Os cistos de paratireoide (PCs) são lesões raras, localizadas no pescoço e na região do mediastino anterior. A grande maioria é não funcionante, apresentando-se como lesões cervicais nodulares. PCs não funcionantes de grandes dimensões podem se manifestar com sintomas compressivos. Raramente, PCs produzem quantidades excessivas de hormônio da paratireoide (PTH), o que resulta em hiperparatiroidismo primário. Relatamos um caso de PC funcional, descrevendo sua abordagem diagnóstica e terapêutica.

Genetic basis of familial isolated hyperparathyroidism: a case series and a narrative review of the literature.

Primary hyperparathyroidism is a heterogeneous clinical entity. In the clinical setting, the diagnosis and management of familial isolated hyperparathyroidism (FIHP) and other familial hyperparathyroidism (FHPT) forms continue to rely on clinical, laboratory, and histological findings, with careful examination of the family. In this article, we report a case series of FIHP in a four-generation Greek family, with no identifiable gene mutations. Clinical approach and long-term follow-up are discussed and a narrative review of the genetic basis of this entity has been performed.

Selenium status in patients with autoimmune and non-autoimmune thyroid diseases from four European countries.

CONTEXT: Selenium supplementation has been suggested for Hashimoto thyroiditis and Graves' ophthalmopathy. Objective, Design: Our aim is to measure selenium status (p-Se, p-SePP), urine iodine (UI) levels and urine iodine/creatinine ratio (UI/C) in different thyroid diseases (n = 416) from four European countries and to compare the results between patients with and without thyroid autoimmunity. RESULTS: p-Se and p-SePP showed positive correlation and did not correlate with UI/C. Also, these measurements were higher in patients from Italy in comparison with the other countries. Austria had the lowest UI/C ratios. Selenium deficiency exists in these four European countries. Selenium status was lower in patients with Hashimoto thyroiditis and Graves' disease in comparison with non-autoimmune thyroid disease patients and did not differ between autoimmune patients with or without thyroid peroxidase antibodies. The latter correlated positively with age. CONCLUSIONS: Our findings suggest that Se supplementation might have a beneficial effect in autoimmune thyroid patients.

Thyroid papillary carcinoma arising in ectopic thyroid tissue within a branchial cleft cyst.

Ectopic thyroid tissue comprises a rare clinical entity which can clinically manifest with the whole spectrum of thyroid disorders, including thyroid malignancy. Thyroid carcinoma arising in ectopic thyroid tissue is extremely rare, with only a few cases described in the literature so far. We present a very unusual case of a primary papillary thyroid carcinoma arising in a left lateral branchial cyst, describing our diagnostic and therapeutic approach for this uncommon clinical entity. This is the first case where recombinant thyrotropin was used along with radioiodine treatment in primary ectopic thyroid cancer.

Pharmacokinetic evaluation of cabozantinib for the treatment of thyroid cancer.

INTRODUCTION: Conventional treatment modalities for thyroid cancer lead to complete remission in only one-third of patients with distant metastases. On the other hand, medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC), although rare, are responsible for a significant percentage of thyroid cancer-related deaths. New treatments are needed to treat such patients. AREAS COVERED: The aim of this review is to provide the latest information on cabozantinib (CBZ), a new tyrosine kinase inhibitor (TKI) that is currently used mainly as a treatment of MTC. The authors collated data that were retrieved from a PubMed literature search. EXPERT OPINION: CBZ targets multiple cell-signaling pathways involved in the molecular pathogenesis of thyroid cancer. These are namely VEGF receptor-2, hepatocyte growth factor receptor and rearranged during transfection receptor. Furthermore, it is a drug which may be used in cases where conventional therapies (mainly for MTC) are proved ineffective or have shown poor results with a good outcome. CBZ may also be administered alone or in combination with other drugs of the same family.

Diagnostic and therapeutic review of cystic parathyroid lesions.

BACKGROUND: Parathyroid cysts (PC) are uncommon entities in routine clinical practice. The vast majority are nonfunctioning and are commonly present as asymptomatic nodular cervical lesions. PC should be considered in the differential diagnosis of an asymptomatic neck mass. Large PC can manifest with compressive symptoms of the surrounding tissues. OBJECTIVE: The aim of this study is to describe nine new cases of PC and review the current literature regarding the clinical presentation, the aetiopathology, the diagnostic procedures, as well as the therapeutic approaches for this relatively rare clinical entity. METHODS-PATIENTS: We present nine new patients (7 females and 2 males) diagnosed with PC, which in three were ectopic. The diagnosis of PC was based on the elevated levels of PTH in the cysts fluid. Six of the patients had nonfunctioning parathyroid lesions, while the other three had functioning ones. Patients with functioning PC had elevated serum calcium and PTH levels. Five out of nine of the cases had no symptoms, while two patients had compressive symptoms and the other two had signs and symptoms of hypercalcaemia. Needle aspiration (NA) was performed in five out of six patients with nonfunctioning PC. Surgery was the treatment in all three patients with functioning PC. RESULTS: Remission after NA was achieved in four out of five patients with non-functioning PC (follow-up time: 17.7±2.3 months). In two of them, two and three aspirations were needed. One patient with nonfunctioning PC submitted to surgery with no previous NA. Patients with functioning PC maintained remission after surgery (mean follow-up time: 22.1±2.9 months). In one of them, a second surgery was performed due to the co-existence of an ectopic parathyroid adenoma. CONCLUSIONS: The diagnosis of a PC can be established by finding high levels of PTH in the fluid collected by the aspiration of the cyst. PTH and Ca levels in the serum can differentiate functioning from nonfunctioning PC. The treatment of choice in nonfunctioning cysts is aspiration. Surgical removal of the cyst is indicated in hyperfunctioning cysts in cases of relapse after NA in nonfunctioning cysts and when compressive symptoms are present. Based on our series, which appears to be one of the largest reported, we propose a diagnostic algorithm to guide the diagnostic and therapeutic approach to PC.

Hypothyroidism has an adverse effect on human spermatogenesis: a prospective, controlled study.

BACKGROUND: Abnormalities of spermatogenesis are associated with numerous diseases and aging. The objective of this study was to investigate the impact of hypothyroidism on human spermatogenesis and different sperm function tests. METHODS: Twenty-five hypothyroid men and 15 normal individuals were investigated. Semen analysis, fructose and acid phosphatase measurements, teratozoospermia index (TZI), and acridine orange test were determined before and 6-9 months after the initiation of treatment with levothyroxine. RESULTS: Morphology is the only sperm parameter that differs significantly between hypothyroid patients and controls (p < 0.0001). After treatment, morphology improved significantly (p < 0.001). Motility was also decreased before treatment in comparison with controls, and improved after treatment. However, the difference was not significant. TZI correlated with free thyroxine. CONCLUSIONS: Hypothyroidism has an adverse effect on human spermatogenesis. Morphology is the only sperm parameter that is significantly affected. Motility may also be affected, but further studies regarding this are needed. Screening for thyroid dysfunction in males who present with a defect in spermatogenesis is strongly recommended, and if hypothyroidism is noted, the response to thyroid hormone should be evaluated before initiating other treatments.

Erectile dysfunction in patients with hyper- and hypothyroidism: how common and should we treat?

CONTEXT: Erectile dysfunction (ED) is associated with numerous diseases and aging. OBJECTIVE: The objective of the study was to investigate the impact of hyper- and hypothyroidism on male sexual health by using the Sexual Health Inventory for Males (SHIM). DESIGN: Seventy-one men, 27 hyper- and 44 hypothyroid and a similar number of controls were included in the study. A validated SHIM 5-item questionnaire was administered to all participants. Patients were asked to respond before and a year after initiation of treatment for thyroid dysfunction. A score between 25 and 22 is considered normal, between 21 and 11 diagnostic of mild to moderately severe ED, and 10 or less diagnostic of severe ED. RESULTS: Fifty-six men with thyroid dysfunction (78.9%; 19 hyperthyroid and 37 hypothyroid) had a SHIM score of 21 or less, compared with 24 controls (33.8%) (P < 0.0001). Twenty-one patients with ED (37.5%) had SHIM scores 10 or less, indicative of severe ED, compared with six controls (25%) (P < 0.01). ED was more prevalent in patients with hyperthyroidism and hypothyroidism, compared with controls (P < 0.001 and P < 0.0001, respectively). Positive correlation was found between SHIM scores and serum free T(4) (r = 0.413, P = 0.005) and negative for TSH (r = -0.669, P < 0.001). After treatment a significant increase of SHIM scores was noted in both hyperthyroid (P < 0.0001) and hypothyroid (P < 0.0001) patients. CONCLUSIONS: ED is extremely common in males with dysthyroidism. Treatment of the latter restores erectile function. Screening for thyroid dysfunction in men presenting with ED is recommended, whereas specific treatment for ED should be postponed in such patients for at least 6 months after achieving euthyroidism because the latter might be responsible for ED.

Basic endocrine products of adipose tissue in states of thyroid dysfunction.

Over the past decade it has been established that adipose tissue is capable of secreting a variety of hormones, cytokines, growth factors, and other peptides that are capable of changing adipocyte biology as well as different organ systems, like the central nervous system, liver, pancreas, and skeletal muscles. Also, it is well known that changes of thyroid function are associated with marked changes in both body weight and energy expenditure. In recent years an extensive research is under way to explore the mutual roles of different adipokines and thyroid hormones. The aim of this review is to summarize our current knowledge on the role of basic peptides of adipose tissue, such as adiponectin, interleukin-6, tumor necrosis factor-alpha, and resistin, in states of altered thyroid function.

Seasonality of month of birth of patients with Graves' and Hashimoto's diseases differ from that in the general population.

OBJECTIVE: We aimed to test the viral hypothesis in the pathogenesis of autoimmune thyroid disease (AITD). DESIGN: We determined the pattern of month of birth (MOB) distribution in patients with AITD and in the general population and searched for differences between them. METHODS: A total of 1023 patients were included in this study; 359 patients had Graves' hyperthyroidism (GrH) and 664 had Hashimoto's hypothyroidism (HH). We divided the patients with HH into three subgroups according to their thyroid peroxidase (TPO) antibody titers at diagnosis: low levels (<500 IU/ml), high levels (500-1000 IU/ml), and extremely high levels (>1000 IU/ml). We used cosinor analysis to analyze the data. RESULTS: Overall, patients with GrH and HH had a different pattern of MOB distribution when compared with the general population and between groups. Furthermore, among both patients with GrH and HH, both genders had a different pattern of MOB distribution when compared with the general population and this pattern was also different between genders. Finally, only women with extremely high titers of TPO antibodies at diagnosis and men with low or extremely high TPO antibody levels showed rhythmicity in MOB, with a pattern of MOB distribution different from that in controls. CONCLUSIONS: The different MOB seasonality in both GrH and HH points towards a similar maybe even common etiology with type 1 diabetes mellitus and multiple sclerosis, namely a seasonal viral infection as the initial trigger in the perinatal period, the clinical disease resulting from further specific damage over time.

Resistin levels in hyperthyroid patients before and after restoration of thyroid function: relationship with body weight and body composition.

BACKGROUND: Resistin is a recently discovered peptide hormone that belongs to a family of tissue-specific resistin-like molecules. To date, very few studies have reported on resistin concentrations in hyperthyroid patients, and they present controversial results. OBJECTIVES: To undertake a controlled, prospective study to investigate resistin concentrations in hyperthyroidism before and after restoration of euthyroidism and to correlate the results with body weight, body fat, waist circumference and body mass index (BMI). PATIENTS AND METHODS: A total of 43 hyperthyroid patients (12 men and 31 women) were investigated, in addition to 23 controls. Anthropometric parameters and resistin concentrations were measured. All the patients commenced taking antithyroid drugs and 3-4 months later the same investigations were performed in 36 of the 43 individuals. RESULTS: Hyperthyroid patients exhibited increased resistin concentrations in comparison with controls. Normalization of thyroid hormones was accompanied by a significant decrease in resistin concentration. A sex difference was also found, men showing a significant decrease in resistin concentrations, whereas in women no such difference was found. Resistin concentrations did not correlate with different anthropometric parameters, age and thyroid hormones, either before or after treatment. CONCLUSIONS: This study demonstrates for the first time that, although resistin concentrations are increased in hyperthyroidism, they are not associated with body weight, body fat, waist circumference or BMI, which makes it unlikely that resistin plays a crucial part in thermogenesis and energy homeostasis in thyrotoxic patients.

Male reproductive function in relation with thyroid alterations.

Despite the high prevalence of thyroid diseases in the general population, the impact of the latter on male reproductive function has been the subject of only a few well-controlled clinical studies. Hyperthyroidism appears to cause alterations in the sex steroid hormone metabolism as well as in spermatogenesis and fertility. Sperm motility is mainly affected. These abnormalities reverse after restoration of euthyroidism. The effects of hypothyroidism on male reproduction appear to be more subtle than those of hyperthyroidism and reversible. Severe juvenile hypothyroidism may be associated with precocious puberty. Hypothyroidism in adults is associated with disturbances in the sex steroid hormone metabolism as well as infertility, although available data concerning the latter are scarce. Radioiodine ((131)I) treatment for dfferentiated thyroid cancer may cause transient impairment of testicular function Gonadal damage may be cumulative in those requiring multiple administrations and sperm banking should be considered in such patients.

Consequences of an intracranial germ cell-tumor in a young adolescent.

Germ cell tumors (GCTs) are relatively rare tumors, which arise in patients of all ages. They are most common in the first and second decades of life with a male predominance. The most frequent tumors arise in the pineal and suprasellar region. The long-term consequences of these tumors have not been very well characterized, as few series with a limited number of patients have reported on the neuro-endocrine development and quality of life of these young people. In this communication we present a male patient who was diagnosed clinically in 1998 at the age of 17 years to have a GCT and subsequently treated with radiotherapy. Today, 6 years after the initial diagnosis his neuro-endocrine and neuro-cognitive outcomes are quite good, while his quality of life is poor mainly due to many psychological problems that he experiences in his every day life. However, it has to be noted that 6 years is insufficient follow-up to assess late post radiation effects.

The effect of long-term somatostatin analogue treatment on free and total insulin-like growth factor (IGF) -I, -II and IGF binding protein -1, -2 and -3 serum levels in euthyroid patients with active thyroid eye disease.

The aim of this study was to investigate the effect of long-term somatostatin analogue (SM-a) treatment on serum levels of free (F) and total (T) insulin-like growth factor (IGF)-I, -II and IGF binding protein (IGFBP) - 1, -2 and -3 in euthyroid patients with active thyroid ophthalmopathy. For this purpose, we measured the above-mentioned parameters in 21 patients (11M, 10F), aged 50.8+/-11.8 years (range 35-70) and 19 healthy individuals matched for age, gender and body mass index (BMI). A total of 4 SM-a (sandostatin LAR((R))-30) injections, each monthly, were administered in each patient and measurements were performed prior to treatment and 20-30 days after the last injection, while in control individuals the same determinations were performed only once. All patients had active thyroid eye disease (TED), with clinical activity scores (CAS) >/= 4 (5.3+/-1.1) and positive orbital octreoscan in both eyes. Serum F and T IGF-I and IGF-II were determined using non-competitive, time-resolved monoclonal immunofluorometric assays. IGFBP-1 and IGFBP-2 were determined by an in-house radioimmunoassay, while IGFBP-3 by commercially available IRMA. Our results showed that F and T IGF-I, -II and IGFBP-1, -2 and -3 levels in patients before and after administration of SM-a were comparable and the levels did not differ significantly from those of controls. Furthermore, no statistically significant differences emerged in the ratio between molar weights of TIGF-I/IGFBP-3 and TIGF-II/IGFBP-3, as well as in the ratio of F/TIGF-I and F/TIGF-II in patients before and after SM-a therapy. Fourteen patients (66%) experienced a decline in CAS of at least >1 point in each eye after SM-a administration, whereas in the remaining the CAS did not change. Finally, no relationship was found between the levels of the above-mentioned parameters (post therapy) and CAS, octreoscan scores and thyroid hormones levels. In conclusion, we showed that although SM-a administration in euthyroid patients with active TED had a beneficial effect in a significant percentage of patients, this effect was not associated with a decline in the circulating IGF-I, -II and IGFBP-1, -2 and -3 levels, at least under the conditions of the present study. It can be postulated that if the mechanism of action of SM-a is through reduction of IGF-I levels, this effect is possibly exerted in the retrobulbar tissues by local paracrine/autocrine action.

Extramedullary hemopoiesis in a thyroid nodule with extensive bone metaplasia and mature bone formation.

Thyroid nodules may undergo a wide range of degenerative change such as infarction, hemorrhage, or fibrosis, which may be localized or extensive and associated with calcification or even ossification. However, the detection of true bone formation in a thyroid nodule is a very rare occurrence. Extramedullary hemopoiesis (EMH) has been described in almost every organ of the body, mainly in tissues active in hemopoiesis in embryonic life. It is extremely rare for EMH to occur in the thyroid gland especially in patients without known chronic anemia. We describe a case of a cold thyroid nodule with histologically proven extensive bone metaplasia and formation of mature bone with foci of hemopoietic tissue in a young woman without chronic anemia, which, to the best of our knowledge, is the first to be reported in the English language literature.

Influence of cigarette smoking on thyroid function, goiter formation and autoimmune thyroid disorders.

Both smoking and thyroid dysfunction are frequent in the general population. Many studies have shown that cigarette smoking interferes with thyroid function and with the evolution of thyroid pathology (e.g. goiter formation and thyroid cancer development). Some studies have also suggested a significant correlation of Graves' hyperthyroidism and Graves' ophthalmopathy with the severity of smoking. In addition, cigarette smoking may reduce the effectiveness of some therapeutic modalities, such as orbital radiotherapy or high-dose systemic glucocorticoid administration for severe thyroid eye disease. Tobacco smoking seems to induce similar changes in thyroid function in the adult and the fetus. This review article discusses the effect of cigarette smoking on thyroid function and morphology as well as on thyroid autoimmunity.