Plasma TSH Concentrations Research Articles

Neonatal plasma TSH – estimated upper reference intervals for diagnosis and follow up of congenital hypothyroidism

Age- and method-dependent plasma TSH reference intervals are essential for the diagnosis and management of congenital hypothyroidism. However, accurate reference intervals for plasma TSH have not been adequately defined due to the difficulties in obtaining samples from a healthy paediatric population. To overcome the difficulties in generating such intervals we estimated method-dependent plasma TSH upper-reference intervals by determining the blood spot TSH upper-reference interval from newborn blood spot TSH screening data (N = 10,697) and then derived method-dependent conversion factors for blood spot TSH to plasma TSH concentration from paired-blood spot and plasma TSH measurements. The upper reference interval for blood spot TSH of 3.04 mU/L was obtained from the 97.5th centile of the selected data. Using experimentally-derived conversion factors, estimates of plasma TSH upper reference intervals of 7.6, 6.3, 7.3, 8.3 and 6.5 mU/L were obtained for the Siemens Centaur, Abbott Architect, Roche Elecsys E170, Siemens Immulite 2000 and Beckman access HYPERsensitive TSH assays respectively. These estimated method-dependent plasma TSH upper reference intervals will be of great practical use to clinicians to diagnose and to follow up infants found to have increased blood spot TSH concentrations identified by Newborn Screening programmes.

Altered thyroid function in small for gestational age newborns: study based on screening test for congenital hypothyroidism

Background and Aims: Unequivocal data is not yet available on alterations in plasma concentrations of thyroid hormones that may characterize small-for-gestational-age (SGA) newborns. We used data from screening for congenital hypothyroidism in a large population to evaluate the relationship between growth restriction and thyroid function in the first week of life. Materials and Methods: Subjects: 14,092 newborns (13,333 appropriate-for-gestational-age (AGA) and 759 SGA) screened for congenital hypothyroidism on the third day of life. The screening test measured plasma concentrations of TSH and T4 by fluoroimmunoenzyme assay. Results: Comparison of SGA and AGA newborns revealed lower serum concentrations of T4 in preterm and term SGA infants (p=0.0001), whereas concentrations of TSH were significantly higher only in term SGA infants (p=0.0001). T4 concentrations were positively correlated with gestational age in SGA and AGA groups, whereas TSH concentrations were only correlated with gestational age in the AGA group. 1.84% of SGA babies were recalled for TSH and T4 anomalies against only 0.93% of AGA newborns (p=0.01). Conclusion: SGA babies had a higher incidence of transient hypothyroidism and required accurate follow-up and close monitoring of thyroid function.

Relationship of monocyte chemoattractant protein 1 (MCP-1) with insulin resistance and body mass index, but not with thermogenetic hormones in obesity

Monocyte chemoattractant protein 1 (MCP-1) has been implicated in the recruitment of monocytes to atheroma and of monocytes and macrophages to adipose tissue. The aim of the study was to examine whether MCP-1 levels are associated independently with the main thermogenetic hormones (serum TSH and thyroid hormones and 24-h urinary catecholamines) and insulin resistance in a population mainly represented by overweight and obese women. A cohort of 100 consecutive euthyroid women, aged 18–65 years, and with a wide range of BMI, was examined. Central fat accumulation (indirectly measured by waist circumference), fasting MCP-1 plasma levels, and TSH, FT3, FT4, insulin, glucose, and lipid (cholesterol, HDL-cholesterol and triglyceride) serum concentrations, and 24-h urinary catecholamines were measured. Insulin resistance was estimated by homeostasis model assessment (HOMAIR). MCP-1 levels were directly associated with BMI (p < 0.001), waist circumference (p < 0.001), insulin (p < 0.001), HOMAIR (p < 0.001), diastolic blood pressure (DBP) (p < 0.001), systolic blood pressure (SBP) (p < 0.001), triglycerides (TG) (p < 0.05), and 24-h urinary noradrenaline (p < 0.05), and negatively correlated with HDL-cholesterol (p < 0.01). When a multiple regression analysis was performed with MCP-1 as the dependent variable, and only parameters showing a significant univariate association with MCP-1 were considered as the independent variables, MCP-1 maintained an independent positive association with insulin (p < 0.01), and DBP (p < 0.05). When insulin was replaced by HOMAIR in the regression analysis, MCP-1 maintained an independent positive association with HOMAIR (p < 0.05), DBP (p < 0.05), and BMI (p < 0.05). In conclusion, this study suggests that insulin, BMI, and diastolic blood pressure cooperate independently in increasing MCP-1 levels, whereas thyroid hormones and catecholamines have no apparent influence on this chemokine.

Thyroid function in altered nutritional state.

We studied plasma concentrations of TSH (basal and after TRH), thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3; rT3), free T4 and free T3 in thirty obese subjects, twenty patients with anorexia nervosa, fifteen malnourished subjects and twenty normal weight subjects. Total serum T4 values were similar for the four groups of subjects while serum free T4 values were slightly increased in anorexia nervosa and normal in the other groups. Serum total and free T3 levels were both significantly decreased in anorexia nervosa and malnutrition, and within normal limits in obesity. The mean serum rT3 level was increased in anorexia nervosa and malnutrition while was reduced in obesity. A delay in peak response of TSH to TRH stimulation (30' rather than 20') was noted in anorexia and malnourished patients. The results suggest that these alterations of serum iodothyronines are due to a different peripheral conversion of T4 to T3 according to nutritional status.

Retinol Binding Protein-4 Elevation Is Associated with Serum Thyroid-Stimulating Hormone Level Independently of Obesity in Elderly Subjects with Normal Glucose Tolerance

Elevated levels of retinol binding protein-4 (RBP4) are positively correlated with insulin resistance, obesity, diabetes mellitus, and cardiovascular disease (CVD). Subclinical hypothyroidism (SCH) has also been associated with CVD; however, the factors linking SCH to CVD are not clear. The objective of the study was to evaluate risk factors for CVD in elderly patients grouped according to thyroid function. 217 subjects (> or =65 yr old) were randomly selected from a population and allocated to a euthyroid group (n = 177) and an SCH group (n = 40) on the basis of plasma concentrations of TSH and free T(4). We included subjects with normal glucose tolerance by a 75-g oral glucose tolerance test and subjects with impaired fasting glucose. We measured anthropometric parameters, levels of fasting glucose and insulin, hemoglobin A(1c), adiponectin, RBP4, lipid profiles, total body fat content, and the area of sc and visceral fat. The SCH group had higher RBP4 levels than the euthyroid group, irrespective of body mass index and fat content. Subcutaneous and visceral fat areas and total body fat percentage did not differ between groups and were not correlated with RBP4 level. Other CVD risk factors did not differ between groups. RBP4 level was positively correlated with TSH level (r = 0.241, P = 0.001) after adjustment for age, sex, and body mass index. Plasma RBP4 levels were associated with SCH independent of obesity in elderly subjects with normal glucose tolerance, indicating that RBP4 level could be used as an index of CVD risk in SCH.

Functional and morphological changes in the adenohypophysis of dogs with induced primary hypothyroidism: Loss of TSH hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with transdifferentiation

From case studies in humans it is known that primary hypothyroidism (PH) may be associated with morphological and functional changes of the pituitary. There is no insight into the time scale of these changes. In this study, seven beagle dogs were followed up for 3 years after the induction of primary hypothyroidism. Three of these dogs were followed up for another 1.5 years while receiving l-thyroxine. Adenohypophyseal function was investigated at 2-month intervals with the combined intravenous injection of CRH, GHRH, GnRH, and TRH, and measurement of the plasma concentrations of ACTH, GH, LH, PRL, and TSH. In addition, after 2 years of hypothyroidism a single TRH-stimulation test and a somatostatin test were performed, with measurements of the same pituitary hormones. Every 6 months the pituitary gland was visualized by computed tomography (CT). Induction of PH led to high plasma TSH concentrations for a few months, where after concentrations gradually declined to values no longer significantly different from pre-PH values. A blunted response to stimulation of TSH release preceded this decline. Basal plasma GH concentrations increased during PH and there was a paradoxical hyperresponsiveness to TRH stimulation. Basal GH concentrations remained elevated and returned only to low values during l-thyroxine treatment. Basal PRL concentrations decreased significantly during PH and normalized after several months of l-thyroxine treatment. The pituitary gland became enlarged in all dogs. Histomorphology and immunohistochemical studies in 4 dogs, after 3 years of PH, revealed thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and decreased numbers of mammotrophs. Several cells stained for both GH and TSH. In conclusion, with time PH led to a loss of the TSH response to low T 4 concentrations, hypersecretion of GH, and hyposecretion of PRL. The enlarged pituitaries were characterized by thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and double-staining cells, which are indicative of transdifferentiation.

Thyrotropin-releasing hormone-induced growth hormone secretion in dogs with primary hypothyroidism

Primary hypothyroidism in dogs is associated with increased release of growth hormone (GH). In search for an explanation we investigated the effect of intravenous administration of thyrotropin-releasing hormone (TRH, 10 μg/kg body weight) on GH release in 10 dogs with primary hypothyroidism and 6 healthy control dogs. The hypothyroid dogs had a medical history and physical changes compatible with hypothyroidism and were included in the study on the basis of the following criteria: plasma thyroxine concentration <2 nmol/l and plasma thyrotropin (TSH) concentration >1 μg/l. In addition, 99mTcO 4 − uptake during thyroid scintigraphy was low or absent. TRH administration caused plasma TSH concentrations to rise significantly in the control dogs, but not in the hypothyroid dogs. In the dogs with primary hypothyroidism, the mean basal plasma GH concentration was relatively high (2.3 ± 0.5 μg/l) and increased significantly ( P = 0.001) 10 and 20 min after injection of TRH (to 11.9 ± 3.5 and 9.8 ± 2.7 μg/l, respectively). In the control dogs, the mean basal plasma GH concentration was 1.3 ± 0.1 μg/l and did not increase significantly after TRH administration. We conclude that, in contrast to healthy control dogs, primary hypothyroid dogs respond to TRH administration with a significant increase in the plasma GH concentration, possibly as a result of transdifferentiation of somatotropic pituitary cells to thyrosomatotropes.

Seasonal and pulsatile dynamics of thyrotropin and leptin in mares maintained under a constant energy balance

The objective of this study was to determine if seasonal and/or pulsatile variations occur in plasma concentrations of thyrotropin (TSH) and leptin in mares while maintaining a constant energy balance. Blood samples were collected every 20 min during a 24 h period in winter and again in summer from six Quarter Horse type mares. Plasma concentrations of TSH, leptin, and T 4 were determined by radioimmunoassay. No differences were observed in body weight between winter (388.1 ± 12.5 kg) and summer (406.2 ± 12.5 kg; P = 0.11). Plasma concentrations of TSH were greater in the summer (2.80 ± 0.07 ng/ml) when compared to winter (0.97 ± 0.07 ng/ml; P < 0.001). Pulse frequency of TSH was not different between winter (6.17 ± 0.78 pulses/24 h) and summer (5.33 ± 0.78 pulses/24 h; P = 0.49). Mean TSH pulse amplitude, pulse area, and area under the curve were all greater in summer compared to winter (3.11 ± 0.10 ng/ml versus 1.20 ± 0.10 ng/ml, 24.86 ± 0.10 ng/ml min versus 13.46 ± 1.90 ng/ml min, 3936 ± 72.93 ng/ml versus 1284 ± 72.93 ng/ml, respectively; P < 0.01). Mean concentrations of leptin were greater in summer (2.48 ± 0.17 ng/ml) compared to winter (0.65 ± 0.17 ng/ml; P < 0.001). Pulsatile secretion patterns of leptin were not observed in any horses during experimentation. Mean concentrations of T 4 were greater in winter (20.3 ± 0.4 ng/ml) compared to summer (18.2 ± 0.4 ng/ml; P < 0.001). These seasonal differences between winter and summer provide evidence of possible seasonal regulation of TSH and leptin.

Adenohypophyseal function in bitches treated with medroxyprogesterone acetate

The aim of this study was to investigate the effects of treatment with medroxyprogesterone acetate (MPA) on canine adenohypophyseal function. Five Beagle bitches were treated with MPA (10 mg/kg, every 4 weeks) and their adenohypophyseal function was assessed in a combined adenohypophyseal function test. Four hypophysiotropic hormones (CRH, GHRH, GnRH, and TRH) were administered before and 2, 5, 8, and 11 months after the start of MPA treatment, and blood samples for determination of the plasma concentrations of ACTH, cortisol, GH, IGF-1, LH, FSH, prolactin, α-MSH, and TSH were collected at −15, 0, 5, 10, 20, 30, and 45 min after suprapituitary stimulation. MPA successfully prevented the occurrence of estrus, ovulation, and a subsequent luteal phase. MPA treatment did not affect basal and GnRH-induced plasma LH concentrations. The basal plasma FSH concentration was significantly higher at 2 months after the start of MPA treatment than before or at 5, 8, and 11 months after the start of treatment. The maximal FSH increment and the AUC for FSH after suprapituitary stimulation were significantly higher before treatment than at 5, 8, and 11 months of MPA treatment. Differences in mean basal plasma GH concentrations before and during treatment were not significant, but MPA treatment resulted in significantly elevated basal plasma IGF-1 concentrations at 8 and 11 months. MPA treatment did not affect basal and stimulated plasma ACTH concentrations, with the exception of a decreased AUC for ACTH at 11 months. In contrast, the maximal cortisol increment and the AUC for cortisol after suprapituitary stimulation were significantly lower during MPA treatment than prior to treatment. MPA treatment did not affect basal plasma concentrations of prolactin, TSH, and α-MSH, with the exception of slightly increased basal plasma TSH concentrations at 8 months of treatment. MPA treatment did not affect TRH-induced plasma concentrations of prolactin and TSH. In conclusion, the effects of chronic MPA treatment on adenohypophyseal function included increased FSH secretion, unaffected LH secretion, activation of the mammary GH-induced IGF-I secretion, slightly activated TSH secretion, suppression of the hypothalamic–pituitary–adrenocortical axis, and unaffected secretion of prolactin and α-MSH.

High Circulating Thyrotropin Levels in Obese Women Are Reduced after Body Weight Loss Induced by Caloric Restriction

Previous clinical studies concerning the impact of body weight loss on single plasma TSH concentration measurements or the TSH response to TRH in obese humans have shown variable results. The objective of this study was to investigate the effect of weight loss induced by caloric restriction on diurnal TSH concentrations and secretion in obese humans. This was a clinical, prospective, crossover study. The study was conducted at the Clinical Research Center of Leiden University Medical Center. Eleven obese premenopausal women (body mass index, 33.3 +/- 0.7 kg/m2) were studied. The study intervention was weight loss (50% reduction overweight by caloric restriction). Twenty-four-hour plasma TSH concentrations (10-min intervals) and the 24-h TSH secretion rate, calculated by a waveform-independent deconvolution technique (Pulse), were determined. The 24-h TSH secretion rate was significantly higher in obese women than in normal weight controls, and weight loss was accompanied by diminished TSH release (before weight loss, 43.4 +/- 6.4 mU/liter.24 h; after weight loss, 34.4 +/- 5.9 mU/liter.24 h; P = 0.02). Circulating free T3 levels decreased after weight loss from 4.3 +/- 0.19 to 3.8 +/- 0.14 pmol/liter (P = 0.04). Differences in 24-h TSH release correlated positively with the decline of circulating leptin (r2 = 0.62; P < 0.01). Elevated TSH secretion in obese women is significantly reduced by diet-induced weight loss. Among various physiological cues, leptin may be involved in this phenomenon. The decreases in TSH and free T3 may blunt energy expenditure in response to long-term calorie restriction, thereby frustrating weight loss attempts of obese individuals.

The effect of cervical X-irradiation on activity index of thyrocytes and plasma TSH: A pre-clinical model for radiation-induced thyroid damage

Because radiotherapy in the head and neck region is necessary in the treatment of childhood cancer, possibilities to prevent damage to the thyroid gland must be explored. We developed a model in which radiation-induced effects can be investigated in a way that these effects can be quantified, using thyroid dysmorphology and plasma TSH. Thirty-five Wistar rats, 5 weeks old, were X-irradiated on the cervical region, with a single dose varying from 0 to 20 Gy. After 6 weeks, TSH, T4 and T3 were determined, and thyroid glands were processed for histological examination by two independent pathologists. A histological classification scale was developed, using follicular size, colloid density and cell height of thyrocytes to measure hyperplasia and hypertrophy. By the sum of these scores, a cell-activity index was calculated, which was related to plasma TSH concentration. Numbers of PAS-positive droplets and epithelial desquamation were also counted. Inter-observer reliability was assessed. Good to very good reliability was found for scores of follicular size, colloid density and cell height. Significant increase of cell-activity index was found after 10, 15 and 20 Gy. The plasma TSH concentration was positively correlated to the cell-activity index, increasing with radiation-doses up to 15 Gy. The number of desquamated cells was significantly increased after radiation doses >10 Gy, with moderate reliability. In conclusion, this model using cell-activity index of thyrocytes together with plasma thyrotropin concentrations and desquamation of cells can be used for interpretation and future (pre-clinical) studies of prevention of radiation-induced thyroid damage.

Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men

Narcolepsy is a sleep disorder caused by disruption of hypocretin (orexin) neurotransmission. Injection of hypocretin-1 acutely suppresses TRH and TSH release in rats. In contrast, subchronic administration does not appear to affect the hypothalamo-pituitary-thyroid ensemble in animals. We explored (in 7 patients and 7 controls) whether hypocretin deficiency impacts circulating TSH levels and circadian timing of TSH release in narcoleptic humans. Plasma TSH concentration profiles (blood samples taken at 10-min intervals during 24 h) and TSH levels in response to TRH injection were analyzed by Cluster, robust regression, approximate entropy (ApEn), and deconvolution. Circulating TSH levels were lower in patients, which was primarily attributable to lower pulse amplitude and nadir concentrations. TSH secretion correlated positively with mean 24-h leptin levels (R2 = 0.46, P = 0.02) and negatively with amount of sleep (R2 = 0.29, P = 0.048). Pattern-synchrony between 24-h leptin and TSH concentrations was demonstrated by significant cross-correlation and cross-ApEn analyses with no differences between controls and patients. Sleep onset was closely associated with a fall in circulating TSH. Features of diurnal rhythmicity of circulating TSH fluctuations were similar in patients and controls, with the acrophase occurring shortly after midnight. Thyroxine and triiodothyronine concentrations were similar in patients and controls and did not display a diurnal rhythm. The response of plasma TSH levels to TRH was also similar in both groups. Sleep patterns in narcoleptics were significantly disorderly compared with controls, as measured by ApEn (P = 0.006). In summary, circulating TSH concentrations are low in hypocretin-deficient narcoleptic men, which could be attributable to their low plasma leptin levels and/or their abnormal sleep-wake cycle.

Aspectos da função tireóidea em lactentes submetidos à cirurgia cardíaca com circulação extracorpórea

JUSTIFICATIVA E OBJETIVOS: A cirurgia cardíaca com circulação extracorpórea (CEC) relaciona-se à doença eutireóidea ou à depressão do eixo hipotálamo-hipofisário-tireóideo. O estado hemodinâmico incomum imposto pela CEC é responsável por diversas alterações endócrino-metabólicas, acarretando complexa resposta inflamatória sistêmica. Esta investigação teve como objetivo analisar o comportamento da triiodotironina (T3), tetraiodotironina (T4) e tireotrofina (TSH) em lactentes submetidos à cirurgia cardíaca com CEC. MÉTODO: Foram estudados 15 lactentes. As amostras de sangue para pesquisa de T3, T4 e TSH foram obtidas em 4 momentos designados: M1 - após a indução da anestesia; M2 - após o final da cirurgia; M3 - 6 horas após o final da cirurgia e M4 - 24 horas após o M1. Para complementar esta investigação, foram estudadas as variações dos seguintes parâmetros: pressão arterial média (PAM), temperatura sangüínea central (ºC), atributos da oxigenação tecidual e do equilíbrio ácido-base (M1, CEC, M2, M3 e M4). RESULTADOS: As médias de idade, peso, altura e superfície corpórea dos pacientes foram 3,9 meses; 4,708 kg; 0,65 m e 0,3 m², respectivamente. As concentrações plasmáticas de T3 (p < 0,0001), T4 (p < 0,0001) e TSH (p = 0,0021) variaram significativamente durante o período estudado, sendo que as de T3 declinaram progressivamente. As menores taxas de T3 e T4 coincidiram com as maiores de Ht e Hb, descartando os efeitos da hemodiluição. As maiores concentrações séricas de TSH demonstraram a provável reação do eixo hipotálamo-hipofisário-tireóideo aos efeitos da hipotermia e da absorção maciça pelo iodo (uso tópico de soluções anti-sépticas). Foram identificados aspectos da "Síndrome do T3 baixo" em todos os momentos estudados. CONCLUSÕES: Foram observadas alterações nas concentrações séricas de T3, T4 e TSH em lactentes submetidos à cirurgia cardíaca com circulação extracorpórea.

Pituitary-Thyroid State Correlates with Central Dopaminergic and Serotonergic Activity in Healthy Humans

Data from lower animals suggest anatomic and physiological interactions between brain dopamine and serotonin (5-hydroxytryptamine, 5-HT) systems and the hypothalamic-pituitary-thyroid axis. However, in humans, investigations of interactions between these central neurochemical systems (especially the dopaminergic system) and thyroid function are rare; in healthy humans they are practically nonexistent. Using cerebrospinal fluid (CSF) and blood samples simultaneously obtained from indwelling subarachnoid and venous catheters in healthy humans, we determined the CSF concentrations of homovanillic acid (HVA) and 5-hydroxyindolacetic acid, the major metabolites of dopamine and 5-HT, and plasma concentrations of TSH, total triiodothyronine (T₃), free T₃, total thyroxine (T₄) and free T₄. CSF HVA concentrations were significantly and negatively correlated with plasma TSH and T₃ (free and total), but not with T₄ (free or total). CSF 5-HIAA concentrations were significantly and negatively correlated with plasma TSH and total T₃ but not with free T₃ or T₄ (free or total). These results indicate that CNS monoamine-thyroid interactions are of physiological significance in the normal, euthyroid human.

Changes in diurnal sympathoadrenal balance and pituitary hormone secretion in subjects with Leu7Pro polymorphism in the prepro-neuropeptide Y.

Neuropeptide Y (NPY) is an important neurotransmitter in the central and peripheral nervous systems. It has a regulatory role in cardiovascular and metabolic functions and control of hormone release. The leucine 7 to proline 7 (Leu7Pro) polymorphism in the signal peptide of prepro-NPY is associated with increased blood lipid levels, accelerated atherosclerosis, and diabetic retinopathy. This study elucidated the role of this polymorphism in diurnal cardiovascular, metabolic, and hormonal functions of healthy subjects during rest. The two study groups comprised individuals with different genotype, but they were matched for age and body mass index. Subjects with the Leu7Pro polymorphism had significantly lower plasma NPY and norepinephrine concentrations, lower insulin concentrations, higher glucose concentrations, and lower insulin-glucose ratio in plasma than the controls. Heart rate was significantly higher during daytime in the subjects with Leu7Pro polymorphism. Furthermore, these subjects had significantly lower prolactin concentrations in plasma. Systolic and diastolic blood pressure, serum free fatty acid and plasma leptin, ACTH, cortisol, LH, FSH, TSH, free thyroxin, and melatonin concentrations were similar during the 24-h period, compared with controls. These results show that genetically determined changes in NPY levels lead to widespread consequences in the control of sympathoadrenal, metabolic, and hormonal balance in healthy subjects.

Dynamics of the plasma concentrations of TSH, FT4 and T3 following thyroxine supplementation in congenital hypothyroidism.

The dynamics of the plasma concentrations of various diagnostic determinants of thyroid function were analysed in children with congenital hypothyroidism (CH) after the start of T4 supplementation. The description of the biochemical dynamics of TSH and free T4 (FT4) during the first period of thyroxine treatment is important to depict the practical outlines of the initial dosage of T4 and dosage adjustments for newborns with variable forms of CH. A retrospective analysis was performed of frequent plasma TSH, total T4 (T4), FT4 and total T3 (T3) measurements in 30 CH neonates during the first weeks of treatment, treated with initial daily T4 dosages ranging from 4.8 to 11.1 microg/kg. A 50% reduction in the initial plasma TSH concentration was achieved after 3-4 days of treatment, independent of CH severity. At a median of 32 days after the start of T4 supplementation, plasma TSH ranged between 0.4 and 4.0 mU/l. The mean interval needed for FT4 to reach the age-related normal values (12-29 pmol/l) was 3 days. The increase in plasma T3 concentrations levelled off within a few days, when T4 reached concentrations of around 100 nmol/l. Plasma T3 and FT4 concentrations reach the normal range a few days after thyroxine treatment is started. By contrast, normalization of plasma TSH concentration takes several weeks. At the time that plasma TSH is normalized, CH neonates show a higher range of plasma FT4 concentrations than the normal range. When TSH normalization is the goal of treatment in CH, the target range for plasma FT4 during treatment in the first months needs to be adapted. During the first month of treatment the plasma TSH concentration is not helpful in assessing the proper T4 supplementation dosage. Once plasma TSH has reached normal values, it becomes a reliable determinant in addition to plasma FT4.

Rat thyroid gland expresses the long form of leptin receptors, and leptin stimulates the function of the gland in euthyroid non-fasted animals

Leptin is an adipose tissue-secreted hormone, which decreases caloric intake and increases energy expenditure. Some effects of leptin on energy balance seem to be mediated by the hypothalamo-pituitary-thyroid axis. The present study was designed to ascertain whether i) rat thyroid gland expresses the long form of leptin receptor (ObRb) and ii) the prolonged leptin administration (daily subcutaneous injections of 24 nmol/kg leptin for 6 consecutive days) affects thyroid-gland function in this species. Coupled RT-PCR, Western blotting and immunocytochemical findings demonstrated the expression of Ob-Rb as mRNA and protein in the thyroid gland of normal rats. Prolonged leptin treatment raised thyroid-gland weight, and morphometry showed that in the enlarged glands the volume of the follicle epithelium was increased, while that of colloid remained unchanged, so that epithelium/colloid ratio was markedly lowered. In leptin-administered rats, the plasma concentration of TSH was decreased, while those of thyroid hormones (free T3 and total T4) were notably raised. Collectively, these findings suggest that systemically administered leptin stimulates growth and secretion of thyroid gland in the rat, through a direct mechanism involving Ob-Rb.

Responses of seasonally anovulatory mares to daily administration of thyrotropin-releasing hormone and(or) gonadotropin-releasing hormone analog.

Seventeen seasonally anovulatory light horse mares were treated daily, starting January 5 (d 1), for 28 d with GnRH analog (GnRH-A; 50 ng/kg BW) and(or) thyrotropin-releasing hormone (TRH; 5 microg/kg BW) in a 2 x 2 factorial arrangement of treatments to test the hypothesis that combined treatment may stimulate follicular growth and development. Ovaries were examined via ultrasonography and jugular blood samples were collected every 3 d. Frequent blood samples were collected after treatment injections on d 1, 2, 4, 7, 11, 16, and 22; on d 29, all mares received an i.v. mixture of GnRH, TRH, sulpiride, and EP51389 (a growth hormone secretagogue) to assess pituitary responsiveness. No consistent effects (P > 0.1) of treatment were observed for plasma LH, FSH, prolactin, or thyroxine concentrations in samples collected every 3 d. The only effect on ovarian follicle numbers was a reduction in number of follicles 11 to 19 mm in diameter due to TRH treatment (P = 0.029). No mare ovulated during treatment. On the days of frequent sampling, mean LH (P = 0.0001) and FSH (P = 0.001) concentrations were higher in mares receiving GnRH-A and tended to increase from d 1 through 7. In contrast, mean prolactin (P = 0.001) and thyroid-stimulating hormone (P = 0.0001) concentrations were high in mares receiving TRH on d 1 but rapidly decreased thereafter. When mares were administered the secretagogue mixture on d 29, the LH response was greater (P = 0.0002) in mares that had previously received GnRH-A but the FSH response was not affected (P > 0.1); the prolactin response was greater (P = 0.014) and the TSH response was smaller (P = 0.0005) in mares that had previously received TRH. Surprisingly, an immediate growth hormone response to EP51389 was absent in all mares. In conclusion, daily GnRH-A treatment stimulated plasma LH and FSH concentrations immediately after injection; although no long-term elevation in preinjection concentrations was achieved, the responses gradually increased over time, indicating a stimulation of gonadotropin production and storage. Daily treatment with TRH stimulated plasma TSH and prolactin concentrations, but the response diminished rapidly and was minimal within a few days, indicating a depletion of pituitary stores and little or no stimulation of production. There was no beneficial effect of adding TRH treatment to the daily GnRH-A regimen.

Combined pituitary hormone deficiency in German shepherd dogs with dwarfism

In German shepherd dogs pituitary dwarfism is known as an autosomal recessive inherited abnormality. To investigate whether the function of cells other than the somatotropes may also be impaired in this disease, the secretory capacity of the pituitary anterior lobe (AL) cells was studied by a combined pituitary AL stimulation test with four releasing hormones (4RH test) in four male and four female German shepherd dwarfs. In addition, the morphology of the pituitary was investigated by computed tomography. The physical features of the eight German shepherd dwarfs were primarily characterized by growth retardation and stagnant development of the hair coat. The results of the 4RH test confirmed the presence of hyposomatotropism. The basal plasma TSH and prolactin concentrations were also low and did not change upon stimulation. Basal plasma concentrations of LH were relatively low and responded only slightly to suprapituitary stimulation. With respect to the plasma FSH levels there was a clear gender difference. In the males plasma FSH concentrations remained below the detection limit throughout the 4RH test, whereas in the females the basal plasma FSH levels were slightly lower and there was only a small increase following suprapituitary stimulation, compared with the values in age-matched controls. In contrast, basal and stimulated plasma ACTH concentrations did not differ between the dwarfs and the controls. Computed tomography of the pituitary fossa revealed a normal sized pituitary with cysts in five dogs, an enlarged pituitary with cysts in two dogs, and a small pituitary gland without cysts in the remaining dog. The results of this study demonstrate that German shepherd dwarfs have a combined deficiency of GH, TSH, and prolactin together with impaired release of gonadotropins, whereas ACTH secretion is preserved. The combined pituitary hormone deficiency is associated with cyst formation and pituitary hypoplasia.

Secretion pattern of thyroid-stimulating hormone in dogs during euthyroidism and hypothyroidism

In as many as one third of dogs with primary hypothyroidism a plasma thyrotropin (TSH) concentration within the reference range for euthyroid dogs is found. To determine whether this is due to fluctuations in the release of TSH, the plasma profiles of TSH were analyzed in 7 beagle bitches by collecting blood samples every 10 min for 6 hr, both before and after induction of primary hypothyroidism. After induction of primary hypothyroidism, a 37-fold increase in mean basal plasma TSH concentration and a 34-fold increase in mean area under the curve for TSH were found. Analysis by the Pulsar program demonstrated pulsatile secretion of TSH in the hypothyroid state, characterized by relatively low amplitude pulses (mean [±SEM]) amplitude 41 ± 3% of basal plasma TSH level) and a mean pulse frequency of 2.0 ± 0.5 pulses/6 hr. In the euthyroid state, significant TSH pulses were identified in only 2 dogs. The mean basal plasma TSH level correlated positively (r = 0.84) with the mean amplitude of the TSH pulses, and correlated negatively (r = −0.88) with the TSH pulse frequency. The results of this study demonstrate pulsatile secretion of TSH in dogs during hypothyroidism and only small fluctuations in plasma TSH concentrations during euthyroidism. The findings also suggest that the low TSH values occasionally found in dogs with spontaneous primary hypothyroidism may in some cases in part be the result of ultradian fluctuations.