Patients with Central Hypothyroidism are Less Sufficiently Treated with Levothyroxine than Patients with Primary Hypothyroidism

2021 ◽  
Author(s):  
Barbara Samec ◽  
Gaja Setnikar ◽  
Simona Gaberscek ◽  
Tomaz Kocjan
Keyword(s):  
Primary Hypothyroidism ◽  
Free Thyroxine ◽  
Free Triiodothyronine ◽  
Central Hypothyroidism ◽  
Tsh Levels

Abstract Background Contrary to patients with hypothyroidism after radioiodine (HRI) or after thyroidectomy (HTh), patients with central hypothyroidism (CH) cannot rely on thyrotropin (TSH) level to guide their treatment with L-thyroxine (L-T4). Consequently, they are at constant risk of under- or overtreatment. We aimed to establish the adequacy of L-T4 treatment in patients with CH in our cohort. Methods Consecutive patients with CH on L-T4 treatment were compared with patients adequately treated for HRI or HTh. Levels of free thyroxine (fT4) and free triiodothyronine (fT3) were evaluated and the fT4/fT3 ratio was calculated. Results Forty patients with CH, 136 patients with HRI and 43 patients with HTh were included in this study. Patients with HRI were significantly younger than patients with HTh and CH (p<0.001 for both). Levels of fT4 were significantly lower in CH than in adequately treated patients with HRI and HTh (median (range), 15.6 (12.7–21.3), 18.4 (12.2–28.8), and 18.7 (13.8–25.5) pmol/L, respectively, p<0.001 for both comparisons). Levels of fT3 did not differ significantly (p=0.521) between CH, HRI and HTh (median (range), 4.5 (2.7–5.9), 4.3 (3.2–6.2), and 4.4 (2.9–5.5) pmol/L, respectively). Accordingly, the fT4/fT3 ratio was significantly lower in the CH group than in HRI and HTh groups (median (range), 3.7 (2.5–5.2), 4.2 (1.2–7.7), and 4.4 (2.5–6.1), respectively, p<0.001 for both comparisons). Conclusions Patients with CH have lower fT4 levels and lower fT4/fT3 ratios than patients adequately treated for HRI or HTh. The cause for this difference may be the unreliable TSH levels in patients with CH.

Serum free triiodothyronine (T3) to free thyroxine (T4) ratio in treated central hypothyroidism compared with primary hypothyroidism and euthyroidism

2011 ◽  
Vol 58 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Gemma Sesmilo ◽  
Olga Simó ◽  
Lucía Choque ◽  
Roser Casamitjana ◽  
Manel Puig-Domingo ◽  
...  
Keyword(s):  
Primary Hypothyroidism ◽  
Free Thyroxine ◽  
Free Triiodothyronine ◽  
Central Hypothyroidism ◽  
Serum Free

scholarly journals The diagnosis and management of central hypothyroidism in 2018

2019 ◽  
Vol 8 (2) ◽  
pp. R44-R54 ◽  
Author(s):  
Luca Persani ◽  
Biagio Cangiano ◽  
Marco Bonomi
Keyword(s):  
Therapy Monitoring ◽  
Hormone Replacement ◽  
General Assumption ◽  
Primary Hypothyroidism ◽  
Central Hypothyroidism ◽  
Diagnosis And Management ◽  
Expert Opinions ◽  
Critical Issues ◽  
Clinical Awareness ◽  
Tsh Levels

Central hypothyrodism (CeH) is a hypothyroid state caused by an insufficient stimulation by thyrotropin (TSH) of an otherwise normal thyroid gland. Several advancements, including the recent publication of expert guidelines for CeH diagnosis and management, have been made in recent years thus increasing the clinical awareness on this condition. Here, we reviewed the recent advancements and give expert opinions on critical issues. Indeed, CeH can be the consequence of various disorders affecting either the pituitary gland or the hypothalamus. Recent data enlarged the list of candidate genes for heritable CeH and a genetic origin may be the underlying cause for CeH discovered in pediatric or even adult patients without apparent pituitary lesions. This raises the doubt that the frequency of CeH may be underestimated. CeH is most frequently diagnosed as a consequence of the biochemical assessments in patients with hypothalamic/pituitary lesions. In contrast with primary hypothyroidism, low FT4 with low/normal TSH levels are the biochemical hallmark of CeH, and adequate thyroid hormone replacement leads to the suppression of residual TSH secretion. Thus, CeH often represents a clinical challenge because physicians cannot rely on the use of the ‘reflex TSH strategy’ for screening or therapy monitoring. Nevertheless, in contrast with general assumption, the finding of normal TSH levels may indicate thyroxine under-replacement in CeH patients. The clinical management of CeH is further complicated by the combination with multiple pituitary deficiencies, as the introduction of sex steroids or GH replacements may uncover latent forms of CeH or increase the thyroxine requirements.

scholarly journals L-T4 Therapy in the Presence of Pharmacological Interferents

2020 ◽  
Vol 11 ◽  
Author(s):  
Salvatore Benvenga
Keyword(s):  
Thyroid Function ◽  
Cardiovascular Complications ◽  
Primary Hypothyroidism ◽  
Free Thyroxine ◽  
Thyroid Function Tests ◽  
Central Hypothyroidism ◽  
Serum Free ◽  
Function Tests ◽  
Frequent Monitoring ◽  
Serum Free Thyroxine

Pharmacological interference on L-thyroxine (L-T4) therapy can be exerted at several levels, namely from the hypothalamus/pituitary through the intestine, where the absorption of exogenous L-T4 takes place. A number of medications interfere with L-T4 therapy, some of them also being the cause of hypothyroidism. The clinician should be aware that some medications simply affect thyroid function tests with no need of modifying the dose of L-T4 that the patient was taking prior to their prescription. Usually, the topic of pharmacological interference on L-T4 therapy addresses the patient with primary hypothyroidism, in whom periodic measurement of serum thyrotropin (TSH) is the biochemical target. However, this minireview also addresses the patient with central hypothyroidism, in whom the biochemical target is serum free thyroxine (FT4). This minireview also addresses two additional topics. One is the costs associated with frequent monitoring of the biochemical target when L-T4 is taken simultaneously with the interfering drug. The second topic is the issue of metabolic/cardiovascular complications associated with undertreated hypothyroidism.

scholarly journals Routine free thyroxine reference intervals are suboptimal for monitoring children on thyroxine replacement therapy and target intervals need to be assay-specific

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Elizabeth Wheeler ◽  
Kay Weng Choy ◽  
Lit Kim Chin ◽  
Nilika Wijeratne ◽  
Alan McNeil ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Reference Intervals ◽  
Clinical Diagnostics ◽  
Free Thyroxine ◽  
Thyroid Function Tests ◽  
Free Triiodothyronine ◽  
Central Hypothyroidism ◽  
Thyroxine Replacement ◽  
Ortho Clinical Diagnostics ◽  
Serum Tsh

AbstractCentral hypothyroidism is a condition where there is (qualitatively or quantitatively) TSH deficiency, leading to reduced thyroid hormone production. In such patients, serum TSH does not accurately reflect the adequacy of thyroxine replacement, as the log-linear relationship between thyrotropin (TSH) and free thyroxine (FT4) is lost. We aimed to prospectively determine the optimal physiological FT4 treatment range for children treated for primary hypothyroidism, based on their serum TSH concentrations. This information could be used to guide optimal therapy for all children on thyroxine replacement, including those with central hypothyroidism. In total, sixty children (median age: 11 years, range: 11 months to 18 years) were recruited over 21 months. They were prescribed a stable dose of thyroxine for at least 6–8 weeks prior to a thyroid function test that consisted of serum TSH, FT4 and free triiodothyronine (FT3) measurements. The serum sample for the thyroid function tests was collected before ingestion of the daily dose, i.e. the trough concentration, and measured using Beckman Coulter UniCel DxI 800 instrument, Siemens Advia Centaur, Roche Cobas, Abbott Architect, Ortho Clinical Diagnostics Vitros 5600 (Ortho-Clinical Diagnostics, Raritan, NJ) platforms. The FT4 and FT3 reference intervals showed significant inter-method difference. The lower limit of the FT4 reference intervals were generally shifted mildly higher when the TSH concentration of the children were restricted from 0.5–5.0 mIU/L to 0.5–2.5 mIU/L. By contrast, the upper limit of the FT3 and FT4 reference intervals were relatively stable for the different TSH concentrations. Assay-specific target ranges for optimal thyroxine therapy are required until FT4 assay standardisation is realised.

Free thyroxine, free triiodothyronine, and thyrotropin concentrations in hypothyroid and thyroid carcinoma patients receiving thyroxine therapy

1987 ◽  
Vol 116 (3) ◽  
pp. 418-424 ◽  
Author(s):  
K. Liewendahl ◽  
T. Helenius ◽  
B.-A. Lamberg ◽  
H. Mähönen ◽  
G. Wägar
Keyword(s):  
Thyroid Carcinoma ◽  
Equilibrium Dialysis ◽  
Primary Hypothyroidism ◽  
Free Thyroxine ◽  
Suppressive Therapy ◽  
Free Triiodothyronine ◽  
Thyroxine Therapy ◽  
Thyroxine Replacement ◽  
Hypothyroid Patients ◽  
Serum Tsh

Abstract. Free thyroxine (FT4) and free triiodothyronine (FT3) concentrations in serum were measured by direct equilibrium dialysis methods in patients receiving thyroxine replacement or suppression therapy. Four of 50 hypothyroid patients euthyroid on replacement therapy (mean thyroxine dose 120 μg/day) had supra-normal FT4 concentrations, whereas the FT3 concentrations were normal in all. Forty-one of 56 operated thyroid carcinoma patients on suppressive therapy (mean thyroxine dose 214 μg/day) had raised FT4 concentrations, whereas the FT3 concentration was elevated in only one patient. There was a large difference in mean FT4 values for hypothyroid and thyroid carcinoma patients (17.2 vs 29.5 pmol/l), whereas the difference in mean FT3 values was small (5.0 vs 6.1 pmol/l), suggesting a decreased peripheral conversion of T4 to T3 with increasing concentrations of FT4. Serum TSH concentrations, as determined by an immunoradiometric assay, varied from < 0.02 to 11.9 mU/l in treated hypothyroid patients; 21 patients (42%) had values outside the reference limits. As a single test, serum TSH is therefore not very useful for the assessment of adequate thyroxine dosage in patients with primary hypothyroidism. In thyroid carcinoma patients, the TSH concentrations were < 0.18 mU/l; 45 patients had values < 0.02 mU/l indicating sufficient suppression of TSH secretion in the majority of cases. On the basis of these results we recommend the combination of FT3 and TSH tests for monitoring thyroxine replacement and suppression therapy. FT4 appears less useful than FT3 for this purpose even if special reference values values were adopted for each patient group.

Thyroid autoimmunity in hyperprolactinaemic disorders

1983 ◽  
Vol 104 (1) ◽  
pp. 35-41 ◽  
Author(s):  
C. Ferrari ◽  
M. Boghen ◽  
A. Paracchi ◽  
P. Rampini ◽  
F. Raiteri ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Thyroid Autoimmunity ◽  
Empty Sella ◽  
Primary Hypothyroidism ◽  
Graves Disease ◽  
Toxic Adenoma ◽  
Central Hypothyroidism ◽  
Nodular Goitre ◽  
The One ◽  
Tsh Levels

Abstract. Circulating thyroglobulin antibodies (TgAb) and microsomal antibodies (MsAb) and thyroid function (total and free T4 and T3, TSH basal and after TRH) have been evaluated in 92 hyperprolactinaemic patients (82 females and 10 males; 9 with macroprolactinoma, 22 with microprolactinoma, 4 with acromegaly, 5 with organic lesions of the hypothalamus, 2 with empty sella, 2 with idiopathic hypopituitarism, 2 with primary hypothyroidism, and 46 with idiopathic hyperprolactinaemia). Thyroid function was normal in all cases except 3 with hypothalamic disease and central hypothyroidism, the 2 patients with primary hypothyroidism and 2 with thyrotoxicosis (one due to Graves' disease and one to autonomous thyroid adenoma). High titres of TgAb (≥1/1250) and/or MsAb (≥ 1/1600) were found in the subject with Graves' disease, in one acromegalic, in the 2 primary hypothyroids, and in 12 women with either adenomatous or idiopathic hyperprolactinaemia; low titres of one or both antibodies were found in 9 other euthyroid women and in the one with toxic adenoma. In a control population of 185 subjects studied with the same methods, the prevalence of TgAb and/or MsAb positive (low titres) was 3.3% in females and 2.5% in males. Diffuse thyroid hyperplasia was clinically detectable in 12 euthyroid women and in the one with Graves' disease; 3 others had been previously operated for nodular goitre with histological evidence of Hashimoto's thyroiditis (2 cases) or for a cold nodule; a single thyroid nodule was present in the woman with toxic adenoma and in one euthyroid woman. Most of these subjects also had circulating TgAb and/or MsAb, and a few had increased TSH secretion. No significant differences were found in mean thyroid hormone and TSH levels between euthyroid hyperprolactinaemic subjects and healthy controls, but TRH-stimulated TSH levels were significantly higher in thyroid antibodies positive than negative subjects. These data, in agreement with a few previous reports, suggest that autoimmune thyroid disorders (especially asymptomatic autoimmune thyroiditis) occur in hyperprolactinaemic women with a prevalence far exceeding that observed in many surveys in the general population.

Thyroid Function in Greek Patients with Thalassemia Major

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5176-5176
Author(s):  
Polyxeni Delaporta ◽  
Maria Karantza ◽  
Sorina Boiu ◽  
Konstantinos Stokidis ◽  
Theoni Petropoulou ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Thalassemia Major ◽  
Primary Hypothyroidism ◽  
Central Hypothyroidism ◽  
Secondary Hypothyroidism ◽  
Group A ◽  
Low Levels ◽  
Group B ◽  
Tsh Levels

Abstract Abstract 5176 Background: Disturbances of thyroid function is known to frequently occur in Thalassemia Major (TM); its types prevalence and severity vary in different cohorts. Primary hypothyroidism is caused by failure of thyroid function, while central (secondary) hypothyroidism by inefficient secretion of thyroid-stimulating hormone (TSH) due to pituitary gland dysfunction or reduced thyrotropin-releasing hormone (TRH) secretion from the hypothalamus. TSH levels in primary hypothyroidism are increased, while levels of free T4 (FT4) are decreased or within normal range. In secondary hypothyroidism FT4 levels are low and TSH levels normal or low. The main objective of this retrospective study was to assess the prevalence of central and primary hypothyroidism in a cohort of 364 Greek patients with TM (mean age 33. 0±9. 9 years, range: 1–56 years). Patients and Methods: Data from sequential laboratory evaluation on thyroid function in 364 patients with TM were retrospectively collected and analyzed. Assessment of thyroid function included measurements of TSH, T4, T3, FT4, FT3, anti-TPO, anti-TG by classical methods. Diagnostic criteria for primary hypothyroidism consisted of two consecutive measurements of low T4 or FT4 with increased TSH levels or two consecutive abnormally high levels of TSH despite normal levels of FT4, FT3, T4 and T3. The criteria for diagnosis of central hypothyroidism consisted of two consecutive measurements of low levels of T4 or FT4 with normal or low levels of TSH. In addition the age and ferritin levels at diagnosis of the hypothyroidism, as well as the type of thyroid treatment and chelation were recorded. To study the longitudinal prevalence of thyroid dysfunction, patients were stratified into 3 groups, according to the year of birth (Group A=1960–1970, 49 patients; Group B =1971–1980, 195 patients; Group C=1981–1990, 75 patients). As thyroid dysfunction increases with age, the incidence of thyroid disorders was compared between all three groups for patients ≤30years old, and for patients ≤40 years old between the groups A and B. Statistical analysis as well as BoxPlot values and regression lines presentation were performed using the STATGRAPHICS Centurion XVI. Statistical significance was set at p<0. 05. Results: A total of 364 patients (mean age 33. 0±9. 9 years, 180 females, 184 males) with TM were evaluated. Relevant data on the type and prevalence of thyroid dysfunction in all three groups of patients are summarized in table 1. Figure 1 illustrates the correlation between the age and the year of diagnosis of hypothyroidism. Comparing the data of the three age groups no significant differences in the overall prevalence of hypothryroidism was found. A significantly higher incidence of central hypothyroidism was found in group C compared to groups B and A (p=0. 00087, p=0. 0097 respectively) and higher prevalence of primary hypothyroidism in group A (for patients aged <40 years) in comparison with group B (p=0. 012). Ferritin levels at the time of diagnosis were significantly lower in group A compared to B and C and in group B compared to C (A/B p=0. 0014; B/C p=0. 0342; A/C p<0. 0001). A significant correlation (R2 =0. 47) was found between the age at diagnosis of hypothyroidism and the year of diagnosis (figure 1). Conclusions: The study demonstrated that thyroid disorders remain a frequent problem in Greek patients with TM with a trend of increasing prevalence with age and modification of the ratio of primary to secondary hypothyroidism. The increased incidence of central hypothyroidism in recent years could be attributed to an increased awareness and a more precise evaluation of this condition. The fact that ferritin levels at diagnosis were significantly higher in the younger age cohort may be suggestive that novel iron chelation modalities are more protective against iron-induced thyroid toxicity. Nevertheless, as toxicity may occur in early stages, the impact of these modalities in the incidence and severity of thyroid dysfunction may take years to be apparent. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Median-lower normal levels of serum thyroxine are associated with low triiodothyronine levels and body temperature in patients with central hypothyroidism

2015 ◽  
Vol 173 (2) ◽  
pp. 247-256 ◽  
Author(s):  
Yu Hirata ◽  
Hidenori Fukuoka ◽  
Genzo Iguchi ◽  
Yasuyuki Iwahashi ◽  
Yasunori Fujita ◽  
...  
Keyword(s):  
Body Temperature ◽  
Replacement Therapy ◽  
Primary Hypothyroidism ◽  
University Hospital ◽  
Free Triiodothyronine ◽  
Central Hypothyroidism ◽  
Serum Free ◽  
Gh Replacement ◽  
Single Center Study ◽  
And Control

ObjectiveAlthough it has been recommended that serum free thyroxine (FT4) levels should be targeted to middle-upper normal levels during levothyroxine (l-T4) replacement therapy in patients with central hypothyroidism (CeH), the rationale has not been clarified.MethodsA retrospective single-center study enrolled 116 patients with hypothyroidism (CeH,n=32; total thyroidectomy (Tx),n=22; primary hypothyroidism (PH),n=33; and control benign thyroid nodule (C),n=29). The patients had receivedl-T4therapy at the Kobe University Hospital between 2003 and 2013. They were stratified according to serum FT4level (≥1.10 or <1.10 ng/dl), and body temperature (BT), serum free triiodothyronine (FT3) levels, FT3/FT4ratio, and lipid profiles were compared. The effect of GH replacement therapy on thyroid function was also analyzed.ResultsFT3levels and FT3/FT4ratios were significantly lower in patients with CeH than in patients with PH (P<0.05) or C (P<0.05). In patients with FT4<1.10 ng/dl, BT was significantly lower in patients with CeH (P=0.002) and Tx (P=0.005) than in patients with PH, whereas no differences were found in patients with FT4≥1.10 ng/dl. In patients with CeH, FT3levels were higher in those with GH replacement therapy (P=0.018).ConclusionIn CeH, patients with median-lower normal levels of serum FT4exhibited lower serum FT3levels and lower BT. These results support the target levels of serum FT4as middle-upper normal levels duringl-T4replacement therapy in patients with CeH.

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