Biodistribution and image characteristics of 124 I-positron emission tomography in dogs with neuroendocrine neoplasia.

Radioactive iodine is frequently used for staging of human thyroid carcinomas. Iodine-124 scans performed using position emission tomography (PET) allow for more precise dosimetry of therapeutic radioiodine. The distribution of I-124 has not previously been described in veterinary medicine. The purpose of this prospective, exporatory, descriptive study is to evaluate the whole-body distribution of I-124 in dogs with suspected thyroid carcinoma. Ten dogs with either a cytologic diagnosis of a neuroendocrine neoplasm or biochemical hyperthyroidism were enrolled in a prospective clinical study. Whole-body I-124 PET/CT scans were performed and were evaluated for physiologic and pathologic uptake of I-124. The maximum and mean standardized uptake values (SUVmean) were recorded for several normal and abnormal tissues. Varying degrees of uptake were found in thyroid tumors (SUVmean = 66.37), ectopic thyroid masses (21.44), presumed metastatic lesions in lymph nodes (32.14), and the pulmonary parenchyma (4.50). In most dogs, physiologic uptake above background, measured in maximum SUV, was identified in parotid and mandibular salivary glands (14.00 and 1.57) the urinary tract (1.83), the gastrointestinal tract (19.90 stomach, 6.15 colon), the liver (1.41), and the heart (1.88). Occasionally, uptake was identified in the nasolacrimal duct (3.42), salivary duct (2.73), gallbladder (2.68), and anal gland (2.22). Physiologic uptake was also identified in normal thyroid glands and ectopic thyroid tissue. This study provides a baseline of pathologic and physiologic uptake of I-124 in dogs with thyroid carcinoma, to guide interpretation of future studies.

Permanent vs Transient Congenital Hypothyroidism: Assessment of Predictive Variables.

Objective: To assess clinical variables, including early thyroid scintigraphy, in predicting the outcome (permanent vs transient) in term infants with congenital hypothyroidism (CH). Methods: In a retrospective study, 142 full-term infants with CH diagnosed between 2000 and 2012 were categorized into three groups: agenesis/ectopic thyroid and permanent CH; eutopic thyroid and permanent CH; and eutopic thyroid and transient CH. All underwent early thyroid scintigraphy and were under regular follow-up in our tertiary Pediatric Endocrine Institute. Results: Thyroid scan showed agenesis/ectopic thyroid in 58 (41%) and eutopic thyroid in 84 (59%) infants. Imaging findings were similar in eutopic-permanent and eutopic-transient groups. At initial evaluation, TSH levels were higher in the agenesis/ectopic group than in the eutopic-permanent and eutopic-transient groups (71.5 ± 11.2 mIU/L vs 49.1 ± 27.9 mIU/L and 42.5 ± 29.1 mIU/L, respectively; P < 0.001). Higher l-T4 doses were required from the third month in the agenesis/ectopic than in the eutopic-permanent group (P < 0.001) and from the sixth month in the eutopic-permanent than in the eutopic-transient group (P < 0.01). Initial TSH >63.5 mU/L (P < 0.001) and l-T4 dose >4.6 µg/kg/d at age >6 months (P < 0.001) were found to be predictors for an agenesis/ectopic gland using receiver operating characteristic analysis, as was an l-T4 dose >2.2 µg/kg/d at age >6 months (P < 0.01) for permanent CH in patients with a eutopic gland. Conclusions: Although early thyroid scintigraphy is reliable in predicting permanent CH when detecting agenesis or ectopic gland, it cannot differentiate between permanent and transient CH in cases with a eutopic thyroid. Confirmatory TSH at diagnosis and the l-T4 dose through treatment may better distinguish between permanent and transient CH.

Decreased sensitivity of thyrotropin-thyroid hormone feedback control in hypothyroid and athyreotic patients treated with levothyroxine. Is serum triiodothyronine involved?

OBJECTIVES: The search for optimal therapy for hypothyroidism is challenging and complex and is still going on. We investigated TSH-thyroid hormone feedback control in hypothyroid and athyreotic patients properly treated with levothyroxine (LT4), based on normal TSH values. MATERIAL AND METHODS: We randomly selected 150 hypothyroid, 110 athyreotic and 210 euthyroid subjects, determined their serum T4, T3 and TSH values and calculated T4/TSH and T3/T4 ratios. RESULTS: The TSH distribution in hypothyroidism was significantly shifted to the higher and that in athyreosis to the lower values from the normal distribution in euthyroid controls. This TSH-thyroid hormone dissociation in hypothyroidism was characterized with higher T4 and higher matched TSH values. We found 5% hypothyroid and 10% athyreotic patients normalize TSH only with hyperthyroxinemia. Serum T3 was lower in both hypothyroid groups and unaffected by a higher LT4 dose and higher serum T4 in athyreosis. CONCLUSION: Our results suggest that the decreased serum T3 is a major cause of impaired TSH-thyroid hormone feedback control in hypothyroidism treated with LT4.

Thyroid ectopy - diagnostic and therapeutic challenges before and in the era of TSH neonatal screening.

Despite TSH screening in newborns is currently conducted in most developed countries, patients with thyroid ectopy born before the procedure was introduced or those in whom the screening failed to establish diagnosis, might still appear. In the paper we revise the current state of knowledge regarding the clinical presentation, diagnosis and treatment of patients with thyroid ectopy. As an example, we report diagnostic and therapeutic difficulties in our three patients with thyroid ectopy remaining undiagnosed and untreated during early childhood. Introduction of neonatal screening for congenital hypothyroidism does not guarantee that all patients with thyroid ectopy will be correctly diagnosed and properly treated due to the possibility of falsely negative result of TSH screening or lack of compliance from parents. Visualization of an ectopic thyroid on ultrasound examination may be challenging for unexperienced sonographists; muscles in the thyroid bed may be misdiagnosed as heterogeneous and hypoechogenic thyroid gland with features suggesting autoimmune thyroid disease. Thyroid scintiscan is crucial for confirmation of the diagnosis of thyroid ectopy. In conclusion, hypothyroidism due to thyroid developmental anomaly should be taken into consideration in case of hypothyroidism and normal thyroid autoantibodies in a patient at any age.

Thyroid Hemiagenesis: Incidence, Clinical Significance, and Genetic Background.

Context: Thyroid hemiagenesis (THA) constitutes a rare, congenital disorder that is characterized by an absence of one thyroid lobe. Because the pathogenesis and clinical significance of this malformation remain undefined, specific clinical recommendations are lacking, especially for asymptomatic cases. Evidence Acquisition: The PubMed database was searched (years 1970 to 2017), and the following terms were used to retrieve the results: "thyroid hemiagenesis," "thyroid hemiaplasia," "one thyroid lobe agenesis," and "one thyroid lobe aplasia." Subsequently, reference sections of the retrieved articles were searched. Evidence Synthesis: There is a noticeable susceptibility of subjects with THA to develop additional thyroid and nonthyroidal pathologies. In pathogenesis of concomitant thyroid pathologies, a chronic elevation in thyroid-stimulating hormone values may play an important role. Thus far, genetic studies failed to find a common genetic background of the anomaly, and the potential underlying cause was identified in a minority of the cases. Conclusions: Patients with THA are prone to develop additional thyroid pathologies and theoretically might benefit from l-thyroxine treatment to lower the thyrotropin levels to those observed in the normal population. However, further research should be done to ascertain whether such intervention early in life would prevent development of associated thyroid conditions. At least, increased vigilance should be maintained to reveal all of the concomitant disorders as soon as possible during follow-up examinations. Application of high-throughput technologies enabling a genome-wide search for novel factors involved in thyroid embryogenesis might be the next step to expand the knowledge on THA pathogenesis.

Seasonal variations in TSH serum levels in athyreotic patients under L-thyroxine replacement monotherapy.

BACKGROUND: Whether serum TSH undergoes seasonal fluctuations in euthyroid and hypothyroid residents of temperate climates is controversial. METHODS: Monthly TSH and thyroid hormone levels were cross-sectionally analysed in a large cohort of euthyroid subjects (n=11 806) and L-thyroxine (L-T4)-treated athyreotic patients (n=3 934). Moreover, in a small group (n=119) of athyreotic patients treated with an unchanged dosage of L-T4 monotherapy, hormones were measured both in the coldest and in the hottest seasons of the same year (longitudinal study). RESULTS: No seasonal hormone change was observed in the euthyroid subjects except for a small FT3 increase in winter (+2.9%, P<.001). In contrast, the L-T4-treated athyreotic patients had significantly higher serum TSH values in the cold season when the FT4 values were significantly lower. The differences were more notable in the longitudinal series (TSH, 0.80 vs. 0.20 mU/L and FT4, 16.3 vs. 17.8 pmol/L in December-March vs. June-September, respectively). In these patients also serum FT3 values significantly decreased in winter (in the longitudinal series, 3.80 in winter vs 4.07 pmol/L in summer). Regression analysis showed that in athyreotic subjects, a greater FT4 change is required to obtain a TSH change similar to that of euthyroid controls and that this effect is more pronounced in the summer. CONCLUSION: Athyreotic patients undergoing L-T4 monotherapy have abnormal seasonal variations in TSH. These changes are secondary to the FT4 and FT3 serum decreases in winter, which occur in spite of the constant treatment. The underlying mechanisms are unclear, but in some cases, these changes may be clinically relevant.

The different requirement of L-T4 therapy in congenital athyreosis compared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic-pituitary level.

BACKGROUND: Levothyroxine (l-T4) is commonly employed to correct hormone deficiency in children with congenital hypothyroidism (CH) and in adult patients with iatrogenic hypothyroidism. OBJECTIVE: To compare the daily weight-based dosage of the replacement therapy with l-T4 in athyreotic adult patients affected by CH and adult patients with thyroid nodular or cancer diseases treated by total thyroidectomy. DESIGN AND METHODS: A total of 36 adult patients (27 females and nine males) aged 18-29 years were studied; 13 patients (age: 21.5±2.1, group CH) had athyreotic CH treated with l-T4 since the first days of life. The remaining 23 patients (age: 24±2.7, group AH) had hypothyroidism after total thyroidectomy (14 patients previously affected by nodular disease and nine by thyroid carcinoma with clinical and biochemical remission). Patient weight, serum free thyroid hormones, TSH, thyroglobulin (Tg), anti-Tg, and anti-thyroperoxidase antibodies were measured. Required l-T4 dosage was evaluated. At the time of the observations, all patients presented free thyroid hormones within the normal range and TSH between 0.8 and 2 µIU/ml. RESULTS: Patients had undetectable Tg and anti-thyroid antibodies. The daily weight-based dosage of the replacement therapy with l-T4 to reach euthyroidism in patients of group CH was significantly higher than that in those of group AH (2.16±0.36 vs 1.73±0.24 µg/kg, P<0.005). Patients of group CH treated with l-T4 had significantly higher serum TSH levels than patients of group AH (P=0.05) as well as higher FT4 concentrations. CONCLUSIONS: To correct hypothyroidism, patients of group CH required a daily l-T4 dose/kg higher than group AH patients, despite higher levels of TSH. The different requirement of replacement therapy between adult patients with congenital and those with surgical athyroidism could be explained by a lack of thyroid hormones since fetal life in CH, which could determine a different set point of the hypothalamus-pituitary-thyroid axis.

Unexpected conversion from hypothyroidism to an euthyroid state due to Graves' disease in a patient with an ectopic thyroid.

A 15-year-old woman was diagnosed with hypothyroidism and unilateral ectopic thyroid. Levothyroxine treatment was introduced; however, the patient was non-compliant and took the medication irregularly. When she presented to an endocrinologist at the age of 30, she had not been using levothyroxine for at least 6 months. Surprisingly, she was clinically and biochemically euthyroid. Due to decreased echogenicity on ultrasound examination, enhanced vascularization on Color Doppler examination and increased concentration of anti-TSH receptor autoantibodies, she was diagnosed with Graves' disease. Eventually, she underwent total thyroidectomy due to diagnosis of follicular neoplasm in fine-needle aspiration biopsy of the focal lesion found in the thyroid gland. To our knowledge, our patient is the first described with ectopic thyroid, presenting a nodular variant of Graves' disease and no signs of orbitopathy, who was initially hypothyroid and became euthyroid in the course of autoimmune thyroid disease.

Medical management of thyroid ectopia:report of three cases.

Thyroid ectopia (TE) is an embryological aberration of the thyroid gland migration most commonly observed in the lingual region followed by the sublingual, hyoid, and mediastinal regions. TE is often complicated by local compressive symptoms resulting in dysphagia, dysphonia, and dyspnea. Surgical removal of TE is frequently complicated by difficulties in intubation, increased perioperative bleeding, and severe primary hypothyroidism; on the other hand, I131 ablation is limited by high doses needed and the concern for long-term effects especially in children. We report three children with TE who all presented with compressive symptoms and were managed conservatively with levothyroxine resulting in resolution of compressive symptoms and favorable outcomes. Levothyroxine supplementation is effective and has an important role in managing TE, not only in correcting the associated hypothyroidism but also in resolving the associated compressive symptoms by reducing the size of the ectopic thyroid tissue.

[Congenital hypothyroidism secondary to thyroid hypoplasia detected in adulthood]. / Hipotiroidismo congénito secundario a hipoplasia tiroidea detectado en edad adulta.

The anatomical location of the thyroid gland and its hormone byosinthesis are regulated by the expression of certain genes, whose disruption leads to the so-called thyroid dysgenesis: agenesis, ectopia and hypoplasia, and to dyshormonogenesis. We present the case of a patient with mental retardation and hypothyroidism whose diagnosis was made in adulthood. Biochemical determinations confirmed the diagnosis without evidence of thyroid autoimmunity. This patient represents the extended evolution of a thyroid hypofunction, which lasted in an unsuspected way for 53 years, with important consequences of this deficiency at diagnosis. Exogenous therapy achieved great improvement in clinical symptoms, but did not reverse the neurological damage attributable to the lack of thyroid hormone necessary for fetal development. The necropsy revealed little thyroid tissue in the neck corresponding to eutopic thyroid hypoplasia. The discovery of a remaining thyroid of less than 1 cm justified the patient survival up to old age.

Hipotiroidismo congénito secundario a hipoplasia tiroidea detectado en edad adulta / Congenital hypothyroidism secondary to thyroid hypoplasia detected in adulthood

La ubicación anatómica de la glándula tiroidea y su biosíntesis hormonal están reguladas por la expresión de ciertos genes, cuya alteración puede conducir a las denominadas disgenesias tiroideas: agenesia, ectopía e hipoplasia, así como a las variantes dishormonogenéticas. Se presenta el caso de una paciente con retraso mental y diagnóstico de hipotiroidismo realizado en la edad adulta. Las determinaciones bioquímicas confirmaron el diagnóstico de hipotiroidismo no autoinmune. Este caso representa la evolución prolongada de una hipofunción tiroidea, que cursó en forma solapada y no diagnosticada durante 53 años de vida, con secuelas relevantes de esta deficiencia al momento del diagnóstico. La terapia exógena logró mejorías evidentes en la signo sintomatología, pero no revirtió el presunto daño neurológico atribuible a la falta de hormona tiroidea necesaria durante el desarrollo fetal. En la necropsia realizada se encontró escaso tejido tiroideo cervical correspondiente a hipoplasia tiroidea eutópica. El hallazgo de un remanente tiroideo menor a 1 cm permite explicar la supervivencia de la paciente hasta una edad avanzada.

The anatomical location of the thyroid gland and its hormone byosinthesis are regulated by the expression of certain genes, whose disruption leads to the so-called thyroid dysgenesis: agenesis, ectopia and hypoplasia, and to dyshormonogenesis. We present the case of a patient with mental retardation and hypothyroidism whose diagnosis was made in adulthood. Biochemical determinations confirmed the diagnosis without evidence of thyroid autoimmunity. This patient represents the extended evolution of a thyroid hypofunction, which lasted in an unsuspected way for 53 years, with important consequences of this deficiency at diagnosis. Exogenous therapy achieved great improvement in clinical symptoms, but did not reverse the neurological damage attributable to the lack of thyroid hormone necessary for fetal development. The necropsy revealed little thyroid tissue in the neck corresponding to eutopic thyroid hypoplasia. The discovery of a remaining thyroid of less than 1 cm justified the patient survival up to old age.

Infant's bilobar thyroid agenesis and mother's I-131 accidental administration.

Bilobar thyroid agenesis is one of rare diseases. Genetic and environmental factors may associate with bilobar thyroid agenesis. But the mechanism is still not completely understood. It had been showed that I-131 administration during pregnancy may induce thyroid dysfunction in newborn. Here we reported a case of female hospital staff who received I-131 accidently during (10-12th gestational weeks) and after her pregnancy. The absorbed dose to fetus was higher than 30mGy. At birth, the infant was found to have no thyroid. It was speculated that the fetal thyroid agenesis may be related with mother' I-131 administration during pregnancy. In addition, this case report also indicated that the radiation dose should be minimized to any developing embryo.

Congenital hypothyroidism.

Congenital hypothyroidism (CH) occurs in approximately 1:2,000 to 1:4,000 newborns. The clinical manifestations are often subtle or not present at birth. This likely is due to trans-placental passage of some maternal thyroid hormone, while many infants have some thyroid production of their own. Common symptoms include decreased activity and increased sleep, feeding difficulty, constipation, and prolonged jaundice. On examination, common signs include myxedematous facies, large fontanels, macroglossia, a distended abdomen with umbilical hernia, and hypotonia. CH is classified into permanent and transient forms, which in turn can be divided into primary, secondary, or peripheral etiologies. Thyroid dysgenesis accounts for 85% of permanent, primary CH, while inborn errors of thyroid hormone biosynthesis (dyshormonogeneses) account for 10-15% of cases. Secondary or central CH may occur with isolated TSH deficiency, but more commonly it is associated with congenital hypopitiutarism. Transient CH most commonly occurs in preterm infants born in areas of endemic iodine deficiency. In countries with newborn screening programs in place, infants with CH are diagnosed after detection by screening tests. The diagnosis should be confirmed by finding an elevated serum TSH and low T4 or free T4 level. Other diagnostic tests, such as thyroid radionuclide uptake and scan, thyroid sonography, or serum thyroglobulin determination may help pinpoint the underlying etiology, although treatment may be started without these tests. Levothyroxine is the treatment of choice; the recommended starting dose is 10 to 15 mcg/kg/day. The immediate goals of treatment are to rapidly raise the serum T4 above 130 nmol/L (10 ug/dL) and normalize serum TSH levels. Frequent laboratory monitoring in infancy is essential to ensure optimal neurocognitive outcome. Serum TSH and free T4 should be measured every 1-2 months in the first 6 months of life and every 3-4 months thereafter. In general, the prognosis of infants detected by screening and started on treatment early is excellent, with IQs similar to sibling or classmate controls. Studies show that a lower neurocognitive outcome may occur in those infants started at a later age (> 30 days of age), on lower l-thyroxine doses than currently recommended, and in those infants with more severe hypothyroidism.

Children with congenital hypothyroidism: long-term intellectual outcome after early high-dose treatment.

We aim to determine long-term intellectual outcome of adolescents with early high-dose treated congenital hypothyroidism (CH). Sixty-three prospectively followed children with CH were assessed at age of 14 y with the Wechsler Intelligence Scale for Children-Revised and compared with 175 healthy controls. Median age at onset of treatment was 9 d (range 5-18 d) and median starting dose of levothyroxine (L-T4) was 14.7 microg/kg/d (range 9.9-23.6 microg/kg/d). Full-scale intelligence quotient (IQ) was significantly lower than in controls after adjustment for socioeconomic status (SES) and gender (101.7 versus 111.4; p < 0.0001). Children with athyreosis had a lower performance IQ than those with dysgenesis (adjusted difference 7.6 IQ scores, p < 0.05). Lower initial thyroxine (T4) levels correlated with poorer IQ (r = 0.27, p = 0.04). Lower SES was associated with poorer IQ, in particular in children with CH (interaction, p = 0.03). Treatment during childhood was not related to IQ at age 14 y. Adolescents with CH manifest IQ deficits when compared with their peers despite early high-dose treatment and optimal substitution therapy throughout childhood. Those adolescents with athyreosis and lower SES are at particular risk for adverse outcome. Therefore, early detection of intellectual deficits is mandatory in children with CH.

Analysis of physical and mental development of children with aplasia, hypoplasia and ectopy of the thyroid gland.

OBJECTIVE: Evaluation of clinical and biochemical differences between various forms of thyroid dysgenesia in children. METHODS: The study involved 102 children at the age between 4.8 and 14.2 years who were born with congenital hypothyroidism (CH), as diagnosed by neonatal screening examinations. In all the children diagnosis was settled and the levothyroxine (L-T4) administration was started by the 19th day of life. Out of the examined children, 79 were selected with following three forms of developmental thyroid disorders: Group I--athyroidism (thyroid aplasia or agenesis), Group II--thyroid hypoplasia, Group III--thyroid ectopy. On the basis of neonatal TSH (nTSH) levels obtained by screening and serum TSH, FT4 and Tg concentrations, the severity of hypothyroidism was determined at the time of diagnosis. Physical and mental development of the children was evaluated on the basis of growth and bone age indices and Wechsler's scale, respectively. RESULTS: Developmental disorders were diagnosed in 79 cases (77.4% CH) which included 45 cases (44.1%) of athyroidism, 31 cases (30.4%) of thyroid hypoplasia and 3 cases (2.9%) of thyroid ectopy. The physical and mental development in the studied groups was evaluated as normal. CONCLUSIONS: In the group of children with athyroidism, significantly lower growth indices and IQ values were found in comparison with respective values observed in the other study groups. However, the indices of physical and mental development in all the studied groups were within the normal values for children population. An early diagnosis and early administration of hormonal replacement therapy by L-T4 ensure normal development of children with CH, regardless of underlying causes and associated with them severity of congenital hypothyroidism.