Relevance of TSH evaluation in elderly in-patients with non-thyroidal illness.

BACKGROUND: Non-thyroidal illness (NTI) is frequent in hospitalized patients. Its recovery is characterized by a raise in TSH levels. However, the clinical significance of high TSH levels at admission in hospitalized elderly patients with NTI remains uncertain. AIM: To explore the relevance of baseline TSH evaluation in hospitalized elderly patients with NTI. METHODS: We examined the participants with NTI (n = 123) from our previous study (Sforza, 2017). NTI was defined as: low T3 (< 80 ng/dL) and normal or low total T4 in the presence of TSH values between 0.1 and 6.0 mU/L. Thyroid function tests were performed on day 1 and day 8 of the hospital stay. Positive TSH changes (+ ΔTSH) were considered when the day-8 TSH value increased more than the reference change value for TSH (+ 78%). Multiple logistic regression was used to evaluate the independent association of baseline TSH, sex, clinical comorbidities (by ACE-27) and medications with + ΔTSH. RESULTS: Out of 123 patients (77 ± 8 years, 52% female), 34 showed a + ΔTSH. These patients had a lower TSH at admission (p < 0.001) and intra-hospital mortality (p = 0.003) than the others. In multiple logistic regression, TSH > 2.11 mU/L at baseline was associated with reduced odds to show + ΔTSH [odds ratio (95 CI) 0.29 (0.11-0.75); p = 0.011] in a model adjusted by age, sex and ACE-27. DISCUSSION: Inappropriately higher TSH levels at admission in hospitalized elderly patients were associated with a reduced ability to raise their TSH levels later on. The present results confront the idea that TSH levels at admission are irrelevant in this clinical context.

Evaluation of dynamic testing for pituitary pars intermedia dysfunction diagnosis in donkeys.

BACKGROUND: Endocrine disorders are common in donkeys. Pituitary pars intermedia dysfunction (PPID) is thought to be a frequent disturbance in donkeys due to their longevity. However, information on PPID dynamic testing in donkeys is lacking. OBJECTIVES: The objective of this study was to evaluate the previously described guidelines for PPID diagnosis in horses in donkeys with suspicion of PPID. STUDY DESIGN: Prospective experimental study. METHODS: Eighty donkeys were evaluated for PPID suspicion based on clinical signs and baseline adrenocorticotropic hormone (ACTH) concentrations. Six mix-breed donkeys (one jack and five non-pregnant jennies) fulfilling inclusion criteria were subjected to dexamethasone suppression test (DST), thyrotropin-releasing hormone stimulation test (TRH) and combined DST-TRH challenge. Tests were interpreted according to guidelines for PPID diagnosis in horses. RESULTS: Donkeys fulfilling inclusion criteria were diagnosed with PPID by TRH stimulation test (six of six). Both DST (three of six) and DST-TRH (4/6) challenges failed to detect those animals and showed conflicting results. Similarly, cortisol basal concentrations were not consistent with PPID suspicion. MAIN LIMITATIONS: Characterisation of seasonal and geographical location effect on baseline ACTH concentrations and response to TRH is compelling in this species. Further studies with a larger number of donkeys are needed. CONCLUSIONS: This is the first study in donkeys to evaluate common dynamic tests used for PPID diagnosis in horses. Preliminary results agree with the guidelines for PPID diagnosis in horses and baseline ACTH measurement followed by TRH challenge are recommended tests for diagnosis of PPID in donkeys.

Intrauterine Zn Deficiency Favors Thyrotropin-Releasing Hormone-Increasing Effects on Thyrotropin Serum Levels and Induces Subclinical Hypothyroidism in Weaned Rats.

Individuals who consume a diet deficient in zinc (Zn-deficient) develop alterations in hypothalamic-pituitary-thyroid axis function, i.e., a low metabolic rate and cold insensitivity. Although those disturbances are related to primary hypothyroidism, intrauterine or postnatal Zn-deficient adults have an increased thyrotropin (TSH) concentration, but unchanged thyroid hormone (TH) levels and decreased body weight. This does not support the view that the hypothyroidism develops due to a low Zn intake. In addition, intrauterine or postnatal Zn-deficiency in weaned and adult rats reduces the activity of pyroglutamyl aminopeptidase II (PPII) in the medial-basal hypothalamus (MBH). PPII is an enzyme that degrades thyrotropin-releasing hormone (TRH). This hypothalamic peptide stimulates its receptor in adenohypophysis, thereby increasing TSH release. We analyzed whether earlier low TH is responsible for the high TSH levels reported in adults, or if TRH release is enhanced by Zn deficiency at weaning. Dams were fed a 2 ppm Zn-deficient diet in the period from one week prior to gestation and up to three weeks after delivery. We found a high release of hypothalamic TRH, which along with reduced MBH PPII activity, increased TSH levels in Zn-deficient pups independently of changes in TH concentration. We found that primary hypothyroidism did not develop in intrauterine Zn-deficient weaned rats and we confirmed that metal deficiency enhances TSH levels since early-life, favoring subclinical hypothyroidism development which remains into adulthood.

[Dopaminergic and somatostatinergic pathways decrease serum thyrotropin in rats bearing the 256-Walker mammary carcinoma]. / Vias dopaminérgicas e somatostatinérgicas diminuem o TSH sérico em ratos portadores de carcinoma mamário Walker-256.

The hypothalamus-pituitary-thyroid axis was studied in rats with the "low T(3) syndrome" caused by the implantation of the Walker-256 mammary carcinoma. Male adult rats were injected s.c. with 1 x 106 viable tumoral cells and killed 10 days later. The tumor development was associated with decreased thyroid activity characterized by a approximately 15% reduction in the nuclear area of the thyrocytes and 131I-thyroid uptake (down by approximately 50%), as well as about 70% lower serum levels of T4 and rTg. The functional thyroidal response to exogenous TSH was decreased in the tumor-bearing rats, as well as the rTSH secretion in response to TRH (50 microg/kg). To investigate the role of other hypothalamic neuromediators in this process, tumor-bearing rats received an i.v. injection of metoclopramide (5 mg/kg) and/or physostigmine (12.5 microg/kg), with or without concomitant stimulus with TRH. Each drug improved the rTSH response to TRH, which in the case of physostigmine, almost normalized. When both drugs were injected simultaneously the rTSH response to TRH returned to normal. Thus, in addition to the well known alterations in the extrathyroidal metabolism of thyroid hormones, TSH secretion is decreased in rats with the Walker-256 tumor, indicating a generalized reduction in the thyroid function.

Vias dopaminérgicas e somatostatinérgicas diminuem o TSH sérico em ratos portadores de carcinoma mamário walker-256 / Dopaminergic and somatostatinergic pathways decrease serum thyrotropin in rats bearing the 256-walker mammary carcinoma

A funcão do eixo hipotálamo-hipófise-tireóide em animais portadores da "síndrome do T3 baixo", foi estudada em ratos implantados com o tumor de Walker-256. Ratos machos adultos foram injetados com 1 x 106 células tumorais viáveis, por via SC, e sacrificados após 10 dias. A intensidade da síndrome guardou relacão positiva com o tamanho do tumor desenvolvido. Houve diminuicão da atividade tireoideana documentada pela diminuicão da área nuclear das células foliculares, das concentracões plasmáticas do T4, da rTg e da captacão do 131I. Mesmo o implante SC de um pellet de TSH de liberacão lenta causou menor estimulacão tireoideana, avaliada após 2 e 24h nos ratos com tumor. A secrecão do rTSH avaliada através da administracão IV de TRH mostrou-se significativamente diminuída nestas condicões, indicando aumento do tônus inibidor hipotalâmico sobre a secrecão deste hormônio. A participacão de outros neuro-mediadores hipotalâmicos foi verificada através da administracão prévia de metoclopramida e/ou fisostigmina, com ou sem estímulo subseqüente pelo TRH. Nos animais tratados com metoclopramida, os valores do rTSH aumentaram significativamente, assim como a resposta ao estímulo de secrecão pelo TRH. A fisostigmina mostrou-se mais eficiente na mediacão da resposta de secrecão do rTSH, bem como na resposta ao estímulo de secrecão pelo TRH. A administracão concomitante dos dois fármacos, seguida do estímulo pelo TRH, normalizou a secrecão do rTSH. Conclui-se que, além das alteracões conhecidas do metabolismo das iodotironinas, a secrecão de TSH encontra-se diminuída nos animais portadores de tumor de Walker-256, sugerindo diminuicão global do tônus tireoideano.

[Thyroid function tests in viral chronic hepatitis]. / Teste da função tiroidiana na hepatite crônica viral.

BACKGROUND: One hundred and twenty five patients with virus B or C chronic active hepatitis and postnecrotic cirrhosis and different degrees of liver dysfunction were studied. AIM: 1) To determine a thyroid hormonal profile; 2) to evaluate the prognostic value of these tests in relation to the progression of the disease and mortality; 3) compare these findings with Child-Pugh classification. PATIENTS AND METHODS: The patients were divided in four groups: a) 31 with chronic active hepatitis; b) 41 with postnecrotic cirrhosis Child A; c) 35 with postnecrotic cirrhosis Child B and d) 18 with postnecrotic cirrhosis Child C. The protocol comprised serum measurements of albumin and bilirrubin, estimates of prothrombin time and clinical evaluation of ascites and encephalopathy, measurement of total serum triiodothyronine, thyroxine, thyroid-stimulating hormone, free thyroxine, reverse triiosothyronine, calculated rT3/T3 index (IrT3) and thyrotropin-releasing hormone test. RESULTS: Total serum triiodothyromnine showed the most significant difference among the groups, gradually lower as the disease became more advanced (CAH: 149.2 +/- 42.3 ng/dL; PNC-A: 137.4 +/- 37.2 ng/dL; PNC-B: 88.0 +/- 28.4 ng/dL and PNC-C: 41.8 +/- 21.9 ng/dL). Low levels of T4 (4.5 +/- 2.0 micrograms/dL) and FT4 (0.7 +/- 0.4 ng/dL) and elevated levels of thyroid-stimulating hormone (7.2 +/- 11.5 microIU/mL), reverse triiosothyronine (60.8 +/- 52.1 ng/dL) and calculated rT3/T3 index (2.2 +/- 2.6) were more frequent in patients with postnecrotic cirrhosis Child C. Thyrotropin-releasing hormone test was normal in the majority of the patients. CONCLUSION: The present study shows a positive relationship between the low serum levels of T3 and elevated serum levels of rT3 and IrT3/T3 with the degree of hepatic dysfunction according to the Child-Pugh classification.

Pituitary apoplexy. Clinical course, endocrine evaluations and treatment analysis.

BACKGROUND: The purpose was to analyze clinical manifestations, hormonal changes, diagnosis difficulties and treatment of pituitary apoplexy (PA). EXPERIMENTAL DESIGN: A retrospective study of clinical records from patients with pituitary adenomas admitted from January 1980 to June 1996; the purpose was to identify the patients with clinical evidence compatible with PA. SETTING: Neurosurgery unit of an institutional hospital. PATIENTS: Sixteen (12.8%) of 125 patients with pituitary adenomas were analyzed because they had pituitary apoplexy. INTERVENTIONS: Surgical treatment by the trans-sphenoidal or transcranial route or both routes; dexamethasone (DXM) treatment with 16 mg/day i.v. MEASURES: Hormone assays were performed either by radioimmunoassay or by chemical luminescence. RESULTS: Tumors were nonfunctioning in nine patients and functioning in seven. TSH and prolactin basal serum levels were impaired in 55.5% and 10%, respectively; after exogenous TRH 80% of the patients did not show stimulation of TSH and prolactin secretions. LH and FSH levels were low in 63.6% and 54.6% of the patients, respectively; gonadotrophin-releasing hormone (GnRH) testing was abnormal in 75% of the patients evaluated. Cortisol levels were low in 50% of the patients. After insulin-induced hypoglycemia, cortisol and GH failed to rise in 25% and 40% of cases, respectively. Ten patients were submitted to surgical treatment, but none during PA. The average time from the onset of apoplectic symptoms and surgery was 70+/-50 days. Only one patient died two months after surgery. Five patients were treated with dexamethasone (DXM) during the apoplectic symptoms: three patients died; one patient had good quality of life; the other patient was treated initially with DXM with improvement of vision, but after surgery he developed panhypopituirarism. Two other patients did not receive specific treatment for PA. CONCLUSIONS: PA is not a rare pituitary adenoma complication and its prognosis may be poor; baseline hormone levels showed a wide range of abnormalities of pituitary function; surgical treatment was required in the majority of patients and the prognosis was relatively good; on the contrary, the treatment with DXM only had high levels of mortality.

Early activation of thyrotropin-releasing-hormone and prolactin plays a critical role during a T cell-dependent immune response.

Functional interaction between the immune and neuroendocrine systems is mediated by humoral mediators, neurotransmitters, and cytokines, including TRH and PRL. We examined the role of neuroendocrine changes, particularly TRH and PRL, during the T cell-dependent immune response. After immunization of rats with sheep red blood cells (SRBC, a T cell-dependent antigen), an increase of hypothalamic TRH messenger RNA (mRNA) was observed at 4-24 h post immunization, in contrast to the decrease observed after treatment with lipopolysaccharide (LPS). During the above period, with SRBC, there was an increase in pituitary TRH receptor mRNA and plasma PRL levels but no changes in TSH and GH. Also, in contrast to the early corticosterone peak induced by LPS, the activation of the hypothalamic-pituitary-adrenocortical suppressive response appears in a late phase, 5-7 days after SRBC. Intracerebroventricular injection of antisense oligonucleotide complementary to rat TRH mRNA in conscious freely-moving rats immunized with SRBC resulted in a significant inhibition of specific antibody production and a concomitant inability to produce the peak in plasma PRL levels. These studies demonstrate, for the first time, that the T cell-dependent immune response is critically dependent on the early activation of TRH and PRL and that the neuroendocrine changes occurring during it are profoundly different from those occurring during the T cell-independent and inflammatory responses (LPS model).

[Critical involvement of the specific neuroendocrine profile for an adequate T-dependent immune response]. / El perfil neuroendocrino específico es crítico para una correcta respuesta inmune T-dependiente.

A functional relationship between the neuroendocrine and immune systems has been clearly established. We examined the role of neuroendocrine changes, particularly thyrotropin-releasing hormone (TRH) and prolactin (PRL), during the T cell-dependent immune response. After immunization of rats with sheep red blood cells (SRBC, a T cell-dependent antigen) we observed: a) an increase of hypothalamic TRH mRNA at 4 to 24 h post-immunization (i.e.: SRBC vs saline: 4 h, 2.8x), in contrast to the decrease of TRH mRNA observed following treatment with LPS, a T-independent antigen (LPS vs saline: 4 h, 1.6x); b) an increase in pituitary TRH receptor mRNA and plasma PRL levels but no changes in thyroid-stimulating hormone and growth hormone plasma levels. Intracerebroventricular (icv) injection in conscious freely-moving rats of antisense oligonucleotide complementary to rat TRH mRNA resulted in: a) a significant inhibition of specific antibody production [ELISA 7 days: Ig(M/G): TRH sense vs TRH-antisense: 384 +/- 27 (n = 11) vs 193 +/- 22 (n = 11); p < 0.001]b) an inability to produce the peak in plasma PRL levels in rats immunized with SRBC [(12h post-immunization, TRH-sense vs TRH-antisense: 8.3 +/- 1.4 (n = 6) vs 2.2 +/- 0.5 (n = 6); p < 0.01]; c) a decrease in hypothalamic TRH mRNA (TRH-sense vs TRH-antisense: 12h, 1.7x). These studies demonstrate that the T-cell antigen needs an early activation of TRH and PRL for an adequate immune response, in contrast to the inhibition induced by a T-cell independent antigen.

El perfil neuroendocrino especifico es critico para una correcta respuesta inmune T-dependiente / The specific neuroendocrine profile is critically involved in an adequate T-dependent immune response

Existe una relación funcional entre los sistemas neuroendocrino e inmune. Examinamos el rol de los cambios neuroendocrinos, particularmente hormona liberadora de tirotrofina (TRH) y prolactina (PRL), durante el curso de la respuesta inmune T-dependiente. En ratas inmunizadas ip con eritrocitos de carnero (SRBC, antígeno T-dependiente), se observó: a) un incremento del ARNm de TRH hipotalámica entre las 4 y 24 h post-inmunización (ej: SRBC vs salina: 4 h, 2,8x), en contraste a una disminución del ARNm de TRH observado por tratamiento con antígenos T-independientes (ej: LPS vs salina: 4 h, 1,6x); b) un incremento del ARNm del receptor de TRH y de los niveles de PRL plasmática sin observarse cambios, en los niveles plasmáticos de hormona de crecimiento y tirotrofina. La inyección intracerebroventricular (icv) en ratas conscientes y en movimiento de oligonucleótidos antisentido al mRNA de TRH produjo: a) una inhibición en la producción de anticuerpos anti-SRBC [ELISA 7 días: Ig(M+G): TRH sentido vs TRH-antisentido: 384 + 27 vs 193 + 22 (n = 11); p < 0.001, ANOVA con test de Scheffé's]; b) una incapacidad en producir el pico de liberación de PRL luego de la inmunización (12 h post-inmunización, TRH-sentido vs TRH-antisentido: 8.3 + 1.4 vs 2.2 + 0.5 (n = 6), p < 0.01, ANOVA con test de Scheffé's); c) una dismunución del ARNm de TRH hipotalámica (TRH-sentido vs TRH-antisentido: 12 h, 1.7x). Estos estudios demuenstran que un antígeno T-dependiente requiere de una activación temprana de TRH y PRL, instrumental para montar una respuesta adecuada, en contraste a la inhibición inducida por antígenos T-independientes.

El perfil neuroendocrino especifico es critico para una correcta respuesta inmune T-dependiente / The specific neuroendocrine profile is critically involved in an adequate T-dependent immune response

Existe una relación funcional entre los sistemas neuroendocrino e inmune. Examinamos el rol de los cambios neuroendocrinos, particularmente hormona liberadora de tirotrofina (TRH) y prolactina (PRL), durante el curso de la respuesta inmune T-dependiente. En ratas inmunizadas ip con eritrocitos de carnero (SRBC, antígeno T-dependiente), se observó: a) un incremento del ARNm de TRH hipotalámica entre las 4 y 24 h post-inmunización (ej: SRBC vs salina: 4 h, 2,8x), en contraste a una disminución del ARNm de TRH observado por tratamiento con antígenos T-independientes (ej: LPS vs salina: 4 h, 1,6x); b) un incremento del ARNm del receptor de TRH y de los niveles de PRL plasmática sin observarse cambios, en los niveles plasmáticos de hormona de crecimiento y tirotrofina. La inyección intracerebroventricular (icv) en ratas conscientes y en movimiento de oligonucleótidos antisentido al mRNA de TRH produjo: a) una inhibición en la producción de anticuerpos anti-SRBC [ELISA 7 días: Ig(M+G): TRH sentido vs TRH-antisentido: 384 + 27 vs 193 + 22 (n = 11); p < 0.001, ANOVA con test de Scheffés]; b) una incapacidad en producir el pico de liberación de PRL luego de la inmunización (12 h post-inmunización, TRH-sentido vs TRH-antisentido: 8.3 + 1.4 vs 2.2 + 0.5 (n = 6), p < 0.01, ANOVA con test de Scheffés); c) una dismunución del ARNm de TRH hipotalámica (TRH-sentido vs TRH-antisentido: 12 h, 1.7x). Estos estudios demuenstran que un antígeno T-dependiente requiere de una activación temprana de TRH y PRL, instrumental para montar una respuesta adecuada, en contraste a la inhibición inducida por antígenos T-independientes. (AU)

Facilitatory role of serotonin (5-HT) in the control of thyrotropin releasing hormone/thyrotropin (TRH/TSH) secretion in rats.

In order to investigate the role of serotonin in the regulation of thyrotropin (TSH) secretion, control and propylthiouracil (PTU)-treated male Wistar rats weighing approximately 250 g were subjected to ip injections of methysergide (MET, 10 micrograms/100 g body weight), a serotonergic receptor blocker, and killed 60 min later by decapitation. Serum and pituitary concentrations of TSH were measured by radioimmunoassay. An addition, the pituitary release of TSH was estimated in an in vitro system in which pituitary glands were incubated with hypothalamic extracts. MET treatment led to a decrease in pituitary (94.12 +/- 18.55 vs 199.30 +/- 31.47 micrograms/mg, N = 20), and serum (1.95 +/- 0.92 vs 4.26 +/- 1.40 ng/ml, N = 20) TSH concentration (P < 0.001) and also to a decreased in vitro pituitary response to control hypothalamic extracts (55 +/- 8 vs 78 +/- 7%, N = 5, P < 0.005). In addition, hypothalamic extracts of MET-treated rats significantly facilitated in vitro pituitary TSH secretion, suggesting an enhanced hypothalamic thyrotropin releasing hormone (TRH) activity (347 +/- 62 vs 78 +/- 7%, N = 5, P < 0.001). These results suggest that serotonin participates in the physiological control of TRH/TSH secretion, probably by increasing TRH production/secretion, and/or by facilitating the pituitary TSH response to TRH.

Facilitatory role of serotonin (5-HT) in the control of thyrotropin releasing hormone/thyrotropin (TRH/TSH) secretion in rats

In order to investigate the role of serotonin in the regulation of thyrotropin (TSH) secretion, control and propylthiouracil (PTU)treated male Wistar rats weighing approximately 250 g were subjected to ip injections of methysergide (MET, 10 mug/l00 g body weight), a serotonergic receptor blocker, and killed 60 min later by decapitation. Serum and pituitary concentrations of TSH were measured by radioimmunoassay. In addition, the pituitary release of TSH was estimated in an in vitro system in which pituitary glands were incubated with hypothalamic extracts. MET treatment led to a decrease in pituitary (94.12 ñ 18.55 vs 199.30 ñ 31.47 mug/mg, N = 20), and serum (l.95 ñ 0.92 vs 4.26 ñ 1.40 ng/ml, N = 20) TSH concentration (P

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

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.

Informe preliminar sobre el programa para la detección precoz de hipotiroidismo congénito / Preliminary report on the Programme for the Early Detection of congenital hypothyroidism

Se desarrolla un método sandwich de ultramicro ELISA para la determinación de la hormona liberadora de tirotropina (TSH). La técnica es sensible, simple, económica con un alto grado de automatización usando un sistema ultramicroanalítico (SUMA, patente cubana). En el Programa Piloto de Pesquisaje de Hipotiroidismo Congénito en la Ciudad de La Habana, realizado desde mayo de 1986 hasta diciembre de 1987, se estudiaron 44 596 recién nacidos utilizando sangre del cordón umblical para la determinación de TSH. Se detectaron 10 hipotiroideos para una frecuencia de 1 en 4 460. Se reevaluaron 416 (0,93%) por presentar TSH superiores que 25 mU/L. No se han conocido falsos negativos en el programa. Se analiza la relación costo/beneficio del programa con este método y ser recomienda como proceder de elección en los programas masivos de pesquisaje de hipotiroidismo congénito

Variaciones de la función tiroidea expresadas por el cálculo del área bajo la curva de TRn-TSH / Variations of thyroid function expressed by the calculation of the area under the TRH-TSH curve

En este trabajo, tomando un método descripto por Ridgway y col. se analizaron pruebas de TRH-TSH con el objeto de: a) expresar este examen funcional mediante un valor numérico; b) establecer sus valores en sujetos normales; c) comparar la capacidad discriminativa de esta prueba en relación con otros parámetros de función y diagnóstico clínico, y d) estudiar la validez de una prueba corta estableciendo los tiempos más adecuados para la misma. El área bajo la curva de TRS-TSH discriminó perfectamente al grupo testigo (877 ñ 57 micronUI/ml1/min) de los tirotóxicos (145 ñ 25) y de los hipotiroideos (8846 ñ 1092). El análisis de las tiroideopatías eutiroideas mostró la presencia de dos grupos que se ubicaron funcionalmente uno entre los tirotóxicos y los testigos (266 ñ 17 micronUI/ml1/min) y otro entre los hipotiroideos y los testigos (2610 ñ 195). Estos eran dos grupos estadísticamente diferentes a los clásicamente conocidos, que no se podían diferenciar por los niveles séricos de T3 y T4, ya que estaban dentro de parámetros normales y a los que definimos como hipertiroideos subclínicos e hipotiroideos subclínicos, respectivamente. El análisis global de todas las curvas estudiadas mostró que de los cuatro parámetros de función analizados, T4, T3, TSH basal y área de TRH-TSH, el que mostró mayor poder discriminativo fue el último, pudiéndose establecer nueve estadios funcionales diferentes que abarcan toda una gama que va desde la tirotoxicosis franca hasta el hipotiroidismo manifiesto. Se buscó la correlación entre el área total y una área corta de 20 y 30min, siendo la misma altamente significaticva (r + 0,975; p <0,000001). El delta de TSH se produjo en el 77% de los casos entre los 20 y 30min en el 12,8% a los 40min. Se puede concluir que el cálculo del área bajo la curva de TRH-TSH es el método más válido para valorar función tiroidea

Variaciones de la función tiroidea expresadas por el cálculo del área bajo la curva de TRn-TSH / Variations of thyroid function expressed by the calculation of the area under the TRH-TSH curve

En este trabajo, tomando un método descripto por Ridgway y col. se analizaron pruebas de TRH-TSH con el objeto de: a) expresar este examen funcional mediante un valor numérico; b) establecer sus valores en sujetos normales; c) comparar la capacidad discriminativa de esta prueba en relación con otros parámetros de función y diagnóstico clínico, y d) estudiar la validez de una prueba corta estableciendo los tiempos más adecuados para la misma. El área bajo la curva de TRS-TSH discriminó perfectamente al grupo testigo (877 ñ 57 micronUI/ml1/min) de los tirotóxicos (145 ñ 25) y de los hipotiroideos (8846 ñ 1092). El análisis de las tiroideopatías eutiroideas mostró la presencia de dos grupos que se ubicaron funcionalmente uno entre los tirotóxicos y los testigos (266 ñ 17 micronUI/ml1/min) y otro entre los hipotiroideos y los testigos (2610 ñ 195). Estos eran dos grupos estadísticamente diferentes a los clásicamente conocidos, que no se podían diferenciar por los niveles séricos de T3 y T4, ya que estaban dentro de parámetros normales y a los que definimos como hipertiroideos subclínicos e hipotiroideos subclínicos, respectivamente. El análisis global de todas las curvas estudiadas mostró que de los cuatro parámetros de función analizados, T4, T3, TSH basal y área de TRH-TSH, el que mostró mayor poder discriminativo fue el último, pudiéndose establecer nueve estadios funcionales diferentes que abarcan toda una gama que va desde la tirotoxicosis franca hasta el hipotiroidismo manifiesto. Se buscó la correlación entre el área total y una área corta de 20 y 30min, siendo la misma altamente significaticva (r + 0,975; p <0,000001). El delta de TSH se produjo en el 77% de los casos entre los 20 y 30min en el 12,8% a los 40min. Se puede concluir que el cálculo del área bajo la curva de TRH-TSH es el método más válido para valorar función tiroidea (AU)

Padronizaçäo da resposta do TSH ao teste com o TRH no sexo feminino / Standardization of TSH response to the TRH test in female

Com o objetivo de estabelecer um padräo de resposta normal do TSH ao TRH em nosso meio, em pacientes do sexo feminino, avaliamos 69 indivíduos normais, distribuídos segundo a faixa etária (menor que 20 anos, de 20 a 40 anos, maior que 40 anos), submetidos `a infusäo EV de 200 mec de TRH (Escola Paulista de Medicina) e colhidas amostras com 0,30, 60 e 90 minutos. O valor máximo obtido sempre foi aos 30 minutos, devendo se desprezar as demais colheitas. O menor valor obtido no pico foi 4,2 mU/1, correspondendo a uma variaçäo de 2,8 mU/1 e o valor máximo foi de 25 mU/1 correspondendo a uma variaçäo de 23 mU/1. Os intervalos de confiança das variáveis Basal, Máximo e Delta no grupo total foram respectivamente 1,95 ñ 0,21 mU/1, 12,81 ñ 1,28 mU/1 e 10,85 ñ 1,22 mU/1. Para fixaçäo dos limites da normalidade, os intervalos de tolerância (X ñ 2DP), säo os seguintes: Basal: 0,22 a 3,69 mu/L, Máximo: 2,14 a 23,49 mu/L, Delta: (delta) 0,68 a 21,03

Increased risk of primary hypothyroidism in preterm infants.

Serum levels of thyroid stimulating hormone, thyroxine, triiodothyronine, free T4, thyroxine-binding globulin, reverse T3, and the TSH secretory areas and peak T3 after intravenous injection of 40 micrograms thyrotropin-releasing hormone were determined weekly from day 5 to 6 to 11 weeks of age in 42 unselected full-term and 61 preterm Belgian infants. The results on day 5 indicated a progressive deficit of thyroid function related to the degree of prematurity. In 92 infants this deficit progressively decreased with age and disappeared at 5 to 7 weeks. However, 11 infants developed biochemical evidence of overt but transient hypothyroidism. Belgian neonates are relatively iodine deficient, and this factor affects the constitution of iodine stores within the thyroid gland: (1) the urinary concentrations of iodine in the 103 infants studied in Belgium were markedly lower than in 30 infants from California; and (2) The iodine concentration of the thyroid gland in preterm infants who died during the 10 first days of life was almost three times lower in Brussels than in Toronto. The results indicate that, in Belgium, the effects of relative iodine deficiency on thyroid function are superimposed on and mask the physiologic state of tertiary hypothyroidism in prematurity.