Detection of Polyethylene Glycol Thyrotropin (TSH) Precipitable Percentage (Macro-TSH) in Patients with a History of Thyroid Cancer

BACKGROUND: Owing to its large molecular size, polyethylene glycol (PEG)-precipitable thyrotropin (TSH) can accumulate in the circulation, elevating TSH levels. PEG-precipitable TSH can be used to detect macro-TSH (mTSH) in serum. Our aim was to evaluate the prevalence of mTSH in patients who had undergone thyroidectomy for thyroid cancer. METHODS: Seventy-three thyroid cancer patients and 24 control subjects on levothyroxine (LT4) TSH-suppressive or replacement therapy were evaluated. Screening for mTSH was performed by adding PEG to serum in order to precipitate γ-globulin. A percentage of PEG-precipitable TSH ≥80% was considered suggestive of mTSH. RESULTS: No correlation between free-T4 (fT4) and TSH levels was found. PEG-precipitable TSH was 39.3%±1.9% in thyroid cancer patients and 44.1%±3.9% in controls. Macro-TSH was deemed to be present in one thyroid cancer patient and in two control subjects. Only in the thyroid cancer group was PEG-precipitable TSH found to be negatively correlated with fT4 concentration. No correlation was found between PEG-precipitable TSH and other clinical conditions in any patients. CONCLUSION: The presence of mTSH seems to be a rare phenomenon in thyroid cancer. In some patients with low PEG-precipitable TSH, a reduction in LT4 dosage could be suggested. LT4 dosage adjusted to body weight is the main factor in maintaining TSH in a semi-suppressed or normal range. Evaluation of mTSH could be necessary in patients in whom a balance is required between adequate TSH suppression and the avoidance of unnecessary exogenous hyperthyroxinemia.

Thyroxine binding globulin excess detected by neonatal screening

Inherited thyroxine binding globulin (TBG) disorder can be identified incidentally or through neonatal screening test. TBG excess is characterized by high levels of thyroxine (T4) but normal level of free T4 (fT4), while TBG deficiency presents with low T4 levels and normal fT4 levels. A 27-day-old newborn was brought to the hospital because of hyperthyroxinemia detected by neonatal screening. His T4 level was 18.83 µg/dL (normal range, 5.9-16.0 µg/dL). His mother had no history of any thyroid disease. His fT4 and thyroid stimulating hormone (TSH) levels were 1.99 ng/dL (normal range, 0.8-2.1 ng/dL) and 4.54 mIU/L (normal range, 0.5-6.5 mIU/L), respectively. His serum total triiodothyronine (T3) level was 322.5 ng/dL (normal range, 105.0-245.0 ng/dL). His TBG level was 68.27 mg/L (normal range, 16.0-36.0 mg/L) at the age of 3 months. At 6 months and 12 months of age, his TBG levels were 48.77 mg/L (normal range, 16.0-36.0 mg/L) and 50.20 mg/L (normal range, 14.0-28.0 mg/L), respectively, which were 2 to 3 times higher than normal values. Hormonal studies showed consistently elevated T3 and T4 levels and upper normal levels of fT4 and free T3 with normal TSH levels. His growth and development were normal. TBG excess should be considered as a potential differential diagnosis for hyperthyroxinemia and especially high T3 levels with normal TSH concentration.

Thyroxine binding globulin excess detected by neonatal screening

Inherited thyroxine binding globulin (TBG) disorder can be identified incidentally or through neonatal screening test. TBG excess is characterized by high levels of thyroxine (T4) but normal level of free T4 (fT4), while TBG deficiency presents with low T4 levels and normal fT4 levels. A 27-day-old newborn was brought to the hospital because of hyperthyroxinemia detected by neonatal screening. His T4 level was 18.83 µg/dL (normal range, 5.9-16.0 µg/dL). His mother had no history of any thyroid disease. His fT4 and thyroid stimulating hormone (TSH) levels were 1.99 ng/dL (normal range, 0.8-2.1 ng/dL) and 4.54 mIU/L (normal range, 0.5-6.5 mIU/L), respectively. His serum total triiodothyronine (T3) level was 322.5 ng/dL (normal range, 105.0-245.0 ng/dL). His TBG level was 68.27 mg/L (normal range, 16.0-36.0 mg/L) at the age of 3 months. At 6 months and 12 months of age, his TBG levels were 48.77 mg/L (normal range, 16.0-36.0 mg/L) and 50.20 mg/L (normal range, 14.0-28.0 mg/L), respectively, which were 2 to 3 times higher than normal values. Hormonal studies showed consistently elevated T3 and T4 levels and upper normal levels of fT4 and free T3 with normal TSH levels. His growth and development were normal. TBG excess should be considered as a potential differential diagnosis for hyperthyroxinemia and especially high T3 levels with normal TSH concentration.

A case of thyroid hormone resistance: a rare mutation / Caso de resistência aos hormônios tireóideos: mutação rara

Reduced sensitivity to thyroid hormones (RSTH) is a rare disease that affects about 3,000 individuals, belonging to about 1,000 families. It results from reduced intracellular action of thyroid hormones (TH) genetically determined and manifests as persistent hyperthyroxinemia with non-suppressed thyroid-stimulating hormone (TSH). We describe a 67-years old, Caucasian woman, with past history of subtotal thyroidectomy due to diffuse goiter, who presents with a recurrence of goiter. Although she is clinically euthyroid, laboratory evaluation shows persistent hyperthyroxinemia with non-suppressed TSH. Response to thyrotropin releasing hormone (TRH) test was normal and TSH concentrations were not suppressed during oral administration of suprafisiologic doses of levothyroxine (L-T4). Peripheral blood DNA was extracted from the patient and a mutation was found localized in cluster one, at codon 346 of the ligand binding domain of the THRB gene. The patient’s son underwent thyroid function testing (TFT) and genetic study, both negative, suggesting a sporadic mutation. RSTH should be considered in all hyperthyroxinemic patients who are clinically euthyroid. Mutations interfering with three major steps required for TH action on target tissues have been, so far, identified (TR-β, TR-α, MCT8, SPB2). Each mutation is associated with a distinctive syndrome. Goal of management is to maintain a normal serum TSH level and a eumetabolic state and offer appropriate genetic counselling and prenatal diagnosis. Inappropriate treatment of eumetabolic patients results in hypothyroidism and need for TH replacement.

A sensibilidade reduzida aos hormônios tiroidianos (RSTH) é uma doença rara que afeta cerca de 3.000 indivíduos em 1.000 famílias. Ela resulta de uma ação intracelular reduzida de hormônios tiroidianos (TH), é geneticamente determinada e se manifesta como hipertiroxinemia persistente com hormônio tireoestimulante (TSH) não suprimido. Descrevemos o caso de uma mulher caucasiana de 67 anos de idade com histórico de tiroidectomia subtotal por bócio difuso e que apresentou recorrência do bócio. Embora ela fosse clinicamente eutiroide, a avaliação laboratorial mostrou hipertiroxinemia persistente com TSH não suprimido. A resposta ao hormônio liberador da tireotrofina (TRH) foi normal e as concentrações de TSH não foram suprimidas durante a administração oral de doses suprafisiológicas de levotiroxina (L-T4). Foi extraído DNA de sangue periférico da paciente e encontrada uma mutação no cluster um do códon 346 do domínio de ligação do ligante do gene THRB. O filho da paciente foi submetido a um teste de função da tiroide e a um estudo genético, ambos negativos, o que sugeriu uma mutação esporádica. O RSTH deve ser considerado em todos os pacientes hipertiroxinêmicos que sejam clinicamente eutiroides. Foram identificadas, até hoje, mutações que interferem com os três passos principais necessários para a ação do TH sobre os tecidos-alvo (TR-b, TR-α, MCT8, SPB2). Cada mutação está associada com uma síndrome distinta. O objetivo do manejo é manter o nível sérico normal de TSH e um estado eumetabólico, além de se oferecer aconselhamento genético adequado e diagnóstico pré-natal. O tratamento inadequado de pacientes eumetabólicos leva ao hipotireoidismo e requer reposição de TH.

Anesthetic experience in a clinically euthyroid patient with hyperthyroxinemia and suspected impairment of T4 to T3 conversion: a case report / 대한마취과학회지

We report an anesthetic experience in a clinically euthyroid patient with hyperthyroxinemia (elevated free thyroxine, fT4 and normal 3, 5, 3'-L-triiodothyronine, T3) and suspected impairment of conversion from T4 to T3. Despite marked hyperthyroxinemia, this patient's perioperative hemodynamic profile was suspected to be the result of hypothyroidism, in reference to the presence of T4 to T3 conversion disorder. We suspected that pretreatment with antithyroid medication before surgery, surgical stress and anesthesia may have contributed to the decreased T3 level after surgery. She was treated with liothyronine sodium (T3) after surgery which restored her hemodynamic profile to normal. Anesthesiologists may be aware of potential risk and caveats of inducing hypothyroidism in patients with euthyroid hyperthyroxinemia and T4 to T3 conversion impairment.

Resistencia a Hormonas Tiroideas (RHT): Descripción de una nueva mutación / Resistance to Thyroid Hormones (RTH): Description of a new mutation

Introducción: La resistencia a hormonas tiroideas (RHT) es un desorden genético de transmisión dominante poco frecuente, caracterizado por una respuesta reducida de los tejidos blanco a las hormonas tiroideas. RHT está ligada al gen del receptor beta de hormona tiroidea (TRβ). El síndrome se identifica por niveles persistentemente elevados de T4 y T3 totales y libres en presencia de TSH no suprimida. Materiales y Métodos: Paciente femenina de 62 años de edad con antecedente de hemitiroidectomía a los 22 años por bocio. Clínicamente, la mujer se encontraba eutiroidea y hemodinámicamente estable. En los exámenes complementarios se constató la presencia de nódulo tiroideo, con estudio citológico benigno y en el laboratorio hormonas tiroideas totales y libres elevadas con TSH no suprimida. La impresión diagnóstica fue RHT, siendo el principal diagnóstico diferencial el tirotropinoma. Se realizó perfil tiroideo completo en el caso índice y en dos familiares de primer grado. Se dosaron gonadotropinas y prolactina, y se realizó RMN de hipófisis en el caso índice. Se estudiaron mutaciones del gen TRβ en ADN genómico en la paciente y en uno de sus familiares. Resultados: Avalando la impresión diagnóstica, tanto el caso índice como los dos familiares mostraron un perfil tiroideo compatible con RHT. El estudio genético identificó una nueva mutación en el exón 10: c.1339C>A que resulta en una sustitución p.P447T. La misma fue observada tanto en el caso índice como en el familiar estudiado. Conclusión: La historia de esta paciente con RHT, al igual que otros casos descriptos en la bibliografía, remarcan la importancia de un diagnóstico adecuado y temprano de esta patología poco frecuente para evitar conductas terapéuticas iatrogénicas y con consecuencias relevantes en la vida de estos pacientes. Paralelamente, se describe una nueva mutación genética en esta familia.

Introduction: Resistance to thyroid hormones (RTH) is an unusual autosomal dominant inherited disorder characterized by a reduced target organ responsiveness to thyroid hormones. RTH is linked to the gene encoding the thyroid receptor β (TR β). This syndrome is characterized by persistent high levels of total and free T4 and T3 while TSH is not inhibited. Materials and Methods: 62 years old female who underwent a partial thyroidectomy because of goiter forty years ago. Clinically, she seemed to be an euthyroid patient and her hemodynamic status was normal. The exams revealed the existence of a benign thyroid nodule, high levels of total and free thyroid hormones and normal values of TSH. Our diagnostic impression was RTH, though differential diagnosis with thyrotropin secreting pituitary adenoma was mandatory. Complete assays of thyroid hormones were performed in the patient and in two first degree relatives. Basal LH, FSH and prolactin were assayed in the patient; and a magnetic resonance imaging of her pituitary gland was obtained. Finally we performed genetic testing in patient's DNA and a relative's DNA to demonstrate gene defect. Results: According to our diagnostic impression, not only the patient's laboratory was compatible with RTH, but so was the laboratory of the two relatives. DNA mutation analisys demonstrated a new mutation in exon 10: c.1339C>A responsible for the substitution p.P447T. This mutation was found in DNA of the patient and DNA of her relative. Conclusion: This patient with RTH, as well as other reported cases, reminds us about the importance of a certain and early diagnosis of this rare disorder in order to avoid iatrogenic treatments. A new mutation is described in this family.

antithyroid drugs must be started in patients with hyperemesis gravidarum?

To find out rote of anti-thyroid drugs in patients with Hyperemesis gravidarum and thyroid dysfunction. One hundred thirty five patients with hyperemesis gravidarurn who were admitted to obstetric and gynecology hospital were enrolled in this study. Thirty two patients were excluded because of diabetes mellitus and thyroid diseases. Hence, one hundred three patients underwent investigations including thyroid function test and beta-hCG [Human chorionic gonadotropin] Thirty five women were found with abnormal thyroid function test with FT[4]I [Free Thyroxin index] 4.74 +/- 0.54 and in another group [68 women] was 2.9 +/- 0.39 [P<0.0001]. B[4]- hCG in first group was 59406 +/- 14899 miu/ml and in second group was 6750 +/- 3476 miu/ml [P<0.0001]. In five patients PTU [propylthiouracil] was started due to severe sign and symptoms of hyperthyroidism. Thyroid function test was rechecked for all of 35 patients after four weeks routine therapy for hyperemesis gravidarum. Thyroid function test was normalized in 11 patients with hyperemesis graridarum but remained abnormal in 22 patients. In our study thyroid dysfunction in hyperemesis gravidarum was 35% and, 20% of patients needed anti-thyroid therapy. Routine assessment of thyroid function is necessary for women with hyperemesis gravidarurn especially in patients with clinical features of hyperthyroidism. We must consider PTU [propyithouracil] in hyperemesis gravidarum with severe weight loss, vomiting and biochemical hyperthyroidism

A case of familial euthyroid hyperthyroxinemia--thyroid hormone resistance syndrome?

We describe a case of euthyroid hyperthyroxinemia in whom clinical and laboratory investigations strongly supported the diagnosis of generalised thyroid hormone resistance.

Hipertiroxinemia con eutiroidismo clínico: análisis a propósito de un caso / Hyperthyroxinemia and clinical euthyroidism: report of one case

The association of hyperthyroxinemia and euthyroidism is frequent and characterized by high plasma thyroxin concentrations, normal TSH values and absence of clinical signs of hyperthyroidism. We report an asymptomatic 28 years old male presenting with a serum total plasma thyroxin of 18.5 µg/dl (N 6.1-12.5), a free thyroxin of 2.9 ng/dl (N 0.8-1.4), a TSH of 3.4 µIU/ml (N 0.5-5), and a triiodothyronine of 128 ng/dl (N 80-180). Laboratory assessment did not find high thyroxin binding globulin, albumin or prealbumin concentrations or antithyroxin antibodies. The thyroxin binding capacity of albumin was elevated to 58.2 µg/dl (N 11.5-34.1). TSH responded normally to TRH stimulus and was suppressed with exogenous triiodothyronine, which caused an hyperthyroid syndrome. We concluded that this patient had a familial dysalbuminemia

Formas atípicas de hipertiroidismo e outras de difícil diagnóstico / Atypical appearence of hyperthyroidism and other with difficult diagnosis

Ao longo de vários anos, em ambulatório de Endocrinologia, encontramos casos clínicos que sao devidos exclusivamente ao hipertireoidismo, mas que, por sua apresentaçao atípica, confundem o diagnóstico ou, outras vezes, o retardam. Pela importância deste tema os autores descrevem casos de hipertireoidismo diferentes dos padroes tradicionais da doença, fazem uma revisao e descrevem alguns casos - tanto de sua casuística pessoal quanto da literatura -, com a finalidade de mostrar que o hipertireoidismo, fora - ou mesmo dentro - da investigaçao do especialista pode se tornar um diagnóstico difícil ou demorado e ensejar condutas que podem agravar o estado metabólico do paciente.

Etiology and outcome of non-estrogen associated hyperthyroxinemia in euthyroid patients at the San Juan City Hospital

INTRODUCTION: Hyperthyroxinemia does not always equate to hyperthyroidism. Laboratory tests should always be correlated with the clinical picture. A mismatch should make one doubt true hyperthyroidism. The purpose of our study was to assess the etiology of euthyroid hyperthyroxinemia not associated with estrogen use or pregnancy and to review the outcome of those erroneously treated. METHODS: The medical records of thirteen euthyroid patients with non estrogen associated hyperthyroxinemia were reviewed. They had a complete set of thyroid function tests including free T3 and free T4 by membrane dialysis, TRH stimulation test and thyroid hormone binding panel. RESULTS: Two diagnostic groups were identified: Hyperthyroxinemia secondary to binding abnormalities (7/13), better known as familial dysalbuminemic hyperthyroxinemia (FDH) and hyperthyroxinemia secondary to Thyroid Hormone Resistance (THR) (6/13). The FDH group had an elevated T4 and FTI, with normal T3RU, TSH, TRH stimulation test but an abnormal thyroid hormone binding panel which was used to confirm the diagnosis. The THR group had two laboratory presentations: Four patients presented with all the thyroid hormone tests elevated (T4, T3, T3RU, FTI) including a free T3 and free T4 by membrane dialysis with a normal TSH and TRH stimulation test and a normal T4 binding panel. This presentation is typical for a TRH patient with a nuclear receptor defect where all the precursos to the defect accumulate. Two patients with THR presented elevated T4 and free T4 but normal T3 and free T3, localizing the defect at the level of the active T4 transport mechanism across the cellular membrane. These two patients had a normal TSH, TRH stimulation test and T4 binding panel. Two patients were treated erroneously with radioactive iodine and became extremely hypothyroid in spite of normal TFTs. Very high dose of thyroid hormone replacement were required to restore euthyroidism. CONCLUSION: One must suspect these two entities in patients clinically euthyroid who have elevated T4 but non-suppressed TSH. A normal TSH and TRH test confirm euthyroidism. A thyroid hormone binding panel differentiates FDH from THR. Neither group require treatment. If treated erroneously and T4 drops to normal values, one must again induce hyperthyroxinemia to restore euthyroidism in these patients

Doença do pânico: experiência de um ambulatório de psiquiatria com protocolo de estudo / Panic disease: the experience of psychiatric outpatient with protocol and study

O presente trabalho visa mostrar o resultado do estudo e da identificaçao da doença do pânico através de um Protocolo implantado em um ambulatório de psiquiatria, aprovado pelo hospital do qual faz parte e do órgao governamental responsável pelo controle das contas médicas. A freqüência dos quadros compatíveis com doença do pânico em 28 pacientes foi de 68 por cento entre as mulheres (32 por cento para os homens) sendo a idade mais freqüente de primeira consulta aquela entre 30-40 anos. No diagnóstico diferencial encontramos 14,28 por cento de casos de prolapso de válvula mitral (PVM) e 7,14 por cento de hipertiroxinemia (HT) entre estes pacientes. Aqueles com PVM e HT nao preenchiam claramente os critérios do DSM-III-R usado no Protocolo, como conclusao, vimos que nossos resultados nao sao superponíveis aos da literatura e dos pesquisadores em nosso meio, os quais obtiveram resultados maiores nos casos de PVM sob ataque de pânico; com relaçao à HT, nao encontramos dados para comparaçao. O estudo mostra a importância do estabelecimento de critérios semelhantes para o atendimento de pacientes com queixas de pânico.

Detección precoz de hipotiroidismo congénito en Chile: resultados en 24 meses / Neonatal early screening of congenital hypothyroidism in Chile: results in 24 months

Se informa el resultado de 2 años de aplicación en las regiones Metropolitana y VI de Chile, de un plan de rastreo masivo de hipotiroidismo congénito en recién nacidos, financiado por el Ministerio de Salud. Se midió TSH por ensayo radioinmunométrico en sangre obtenida de punción del talón y recolectada en papel filtro, de 130 383 recién nacidos entre los 2 y 5 días de vida, con coberturas de 58,9 en el primero y 98,8 por ciento en el segundo año de aplicación del programa. Se rellamaron los 66 niños cuya concentración sérica de TSH fue igual o mayor a 20 mUI/I para realizar examen de confirmación en suero con TSH por IRMA y T4 por radioinmunoensayo y simultáneamente cintigrafía tiroidea con Tc99. Ocho niños rellamados no respondieron, 21 (0,016 por ciento) resultaron falsos positivos y 37 (0,028 por ciento) tenían TSH > 10 mUI/I en el examen de comprobación. De estos últimos, 23 tenían hipotiroidismo congénito y 14 hipertirotropinemia. En el segumiento de los casos de hipertirotropinemia se pesquisaron otros 8 de hipotiroidismo congénito compensado, 3 de hipertirotropinemia transitoria y 3 continuaron siendo sospechosos de hipotiroidismo congénito. En total se pesquisaron 31 casos de hipotiroidismo congénito, incidencia de 1/4 206 RN vivos, proporción de 25:6 entre mujeres y varones. La cintigrafía tiroidea mostró agenesia en 3 pacientes (10,34 por ciento), ectopia en 16 (55,17 por ciento), bocio en 7 (24,14 por ciento), en uno había sólo disminución de concentración de Tc99 (3,4 por ciento) y en dos no existían alteraciones cintilográficas (6,9 por ciento). El tratamiento con levotiroxina 10 a 15 µgúkg se inició a la edad de 19,74 días, promedio. Sólo un caso se trató después de un mes, a los 73 días de edad. La psicometría (prueba de Bayley y Stanford Binet) y el examen neurológico fueron normales en todos los casos, excepto en el caso que se trató tardíamente

Hyperthyroxinemia of acute psychiatric illness

The present study was undertaken to determine the frequency of abnormal thyroid function tests in patients admitted with acute psychiatric illness. Elevated thyroxine [T4] levels were noted in ten [11.4%] of 88 psychiatric patients during short-term admissions and these levels retuned to normal by three weeks after admission [P< 0.0001]. None of the patients had schizophrenia. There were no patients with hypertriiodothyroninemia. Hypothyroidism was not observed in any of the patients studied. High normal T4 levels were noted on admission in 32 patients [mean T4, 117.46 +/- 19.18I/L], and decreased to a mean of 93.52 +/- 15.2 mmol/L three weeks later [P< 0.0001]. Fiver of the patients who showed hyperthyoxinemia on the previous admission were readmitted to the psychiatry unit during the study period because of relapse of their psychiatric illness, but none showed hyperthoxinemia on the second admission. Hyperthyroxinemia of acute psychiatric illness is a graded phenomenon. Its incidence is unpredicatable and may not be reproducible