Short-term Hypothyroidism Research Articles

Thyroid Function and Lipid Subparticle Sizes in Patients with Short-Term Hypothyroidism and a Population-Based Cohort

Relations between thyroid function and lipids remain incompletely understood. Our objective was to determine whether lipoprotein subparticle concentrations are associated with thyroid status. We conducted a prospective clinical study and cross-sectional cohort analysis at a university endocrine clinic and the Framingham Heart Study. Subjects included 28 thyroidectomized patients with short-term overt hypothyroidism and 2944 Framingham Offspring cohort participants. Fasting subclass concentrations of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) particles were measured by nuclear magnetic resonance spectroscopy. TSH values were also measured. Total cholesterol and LDL-C were increased during short-term overt hypothyroidism. Large LDL subparticle concentrations increased during hypothyroidism (917+/-294 vs. 491+/-183 nmol/liter; P<0.001), but more atherogenic small LDL was unchanged. Triglycerides marginally increased during hypothyroidism, small VLDL particles significantly increased (P<0.001), whereas more atherogenic large VLDL was unchanged. Total HDL-C increased during hypothyroidism (76+/-13 mg/dl vs. 58+/-15 mg/dl; P<0.001). There was no change in large HDL-C particle concentrations, whereas small (P<0.001) and medium (P=0.002) HDL-C particle concentrations decreased. Among Framingham women, adjusted total cholesterol and LDL-C were positively related to TSH categories (P<or=0.003). This was due to a positive correlation between adjusted large LDL subparticle concentrations and log-TSH (P<0.0001); log small LDL subparticle concentrations decreased slightly as log-TSH increased (P=0.045). Among Framingham men, the only significant association was a positive association between log-TSH and log large HDL subparticle concentrations (P=0.04). There is a shift toward less atherogenic large LDL, small VLDL, and large HDL subparticle sizes in hypothyroid women.

Recombinant human TSH acutely impairs endothelium-dependent vasodilation

We read with interest the review article by Duntas & Biondi dealing with clinical and quality of life consequences induced by short-term hypothyroidism (1). Withdrawal of levothyroxine therapy exacerbates neuropsychiatric symptoms and increases cardiovascular risk, although these effects are usually reversible restoring a condition of stable euthyroidism (1). Shortterm hypothyroidism is associated with cardiac abnormalities, increased peripheral vascular resistance, and endothelium dysfunction. In this setting, the recent use of recombinant human thyrotropin (rhTSH) in the clinical practice of thyroid carcinoma represents a valid alternative to levothyroxine withdrawal. The authors state that rhTSH administration is not accompanied by significant cardiac alterations and induces beneficial effects on the vascular system by increasing circulating nitric oxide (2). In this regard, we have recently assessed the acute effects of TSH on endothelial function in patients monitored for differentiated thyroid carcinoma (DTC) (3). Our data demonstrate that acutely raising serum TSH into the supraphysiological range leads to an acute impairment of endothelium-dependent vasodilation along with a significant increase in blood interleukin (IL)-6, tumour necrosis factor a (TNFa), and lipoperoxide levels. These observations are in keeping with the in vitro evidence of functional TSH receptors in several extra-thyroidal tissues, such as cardiomyocytes (4), aortic endothelium (5), and bone marrow cells (6), in which TSH is able to directly induce IL-6 and TNFa production (7) .T NFa is a pivotal NO-controlling cytokine and may promote the expression of inducible NO synthase, leading to increased oxidative stress (8). This mechanism may explain the increased NO metabolites previously described in patients receiving rhTSH for the follow-up of DTC (2). Therefore, while agreeing with the authors that rhTSH administration is generally safe and able to avoid most signs and symptoms of short-term hypothyroidism, we underline that rhTSH per se may acutely induce low-grade inflammation and endothelial function impairment.

Treatment of Hypothyroidism in Elderly Patients and in Patients with Cardiac Disease

Hypothyroidism is often associated with adverse cardiovascular risk factors such as high cholesterol together with hypertension, endothelial dysfunction, and other atherosclerotic cardiovascular risk factors. The changed hemodynamic characteristics result in reduced cardiac index, and the renal perfusion is impaired with hyponatremia, and low renin and aldosterone production. The ischemic abnormalities are probably related to long-term consequences of a slow development of hypothyroidism, while the hemodynamic changes can develop in very short-term hypothyroidism. Replacement of hypothyroidism with levothyroxine is associated with a normalization of basal metabolic rate. Most patients with preexisting angina experience a gradual amelioration of symptoms, but in some cases the initial therapy may precipitate an unrecognized ischemic state, worsen a preexisting angina, or even result in myocardial infarction. It is therefore advisable to start replacement slowly and if needed perform a stress test and/or coronary angiography before. It may also in some cases be necessary to monitor the patients closely in a hospital setting during initiation of levothyroxine. Elderly hypothyroid patients with unstable angina pose a particular challenging problem, especially if coronary vascular surgery is indicated. No increased risk of peri- or postoperative death has been noted in small studies, although more complications have been described. It may be relevant to treat the cardiac vascular occlusion before starting replacement with levothyroxine in some cases, after careful weighting of pros and cons in each individual case.

Pain Perception, Blood Pressure Levels, and Peripheral Benzodiazepine Receptors in Patients Followed for Differentiated Thyroid Carcinoma: A Longitudinal Study in Hypothyroidism and During Hormone Treatment

Elevated blood pressure levels that are associated with hypalgesia and hypothyroidism have major influences on the cardiovascular system. The potential modulation of pain sensitivity by thyroid hormones is largely undetermined. Moreover, a few experimental studies show that peripheral benzodiazepine receptors (PBRs), which may be altered in hypothyroidism, seem to be related with pain perception. Dental pain threshold and tolerance were evaluated in 19 patients followed for differentiated thyroid carcinoma (1) in severe short-term hypothyroidism (phase 1) and (2) during thyroid stimulating hormone-suppressive LT4 treatment (phase 2). PBR expression (cytofluorimetric evaluation) on peripheral blood mononuclear cells was also investigated in the 2 phases. Pain perception differed throughout the study, the dental pain threshold was higher in phase 1 (P<0.05) whereas pain tolerance was higher but not significantly (P=0.07). Although the systolic blood pressure was higher during hypothyroidism (P<0.01), no relationship was found between blood pressure changes and pain sensitivity variations. Moreover, the multiple regression analysis showed an independent association of the clinical phase with pain sensitivity (r=-2.61, P=0.029), while accounting for systolic blood pressure. The intensity of PBRs was significantly higher in the first phase of the study (P=0.047) whereas the ratio did not significantly differ. However, no relationship was observed between pain sensitivity and PBRs. In conclusion, in athyreotic patients, the pain sensitivity is related to the thyroid status and is independent of the increase in blood pressure induced by thyroid hormone deprivation. The PBRs do not seem to have major influence on pain sensitivity changes in hypothyroidism.

Effect of short-term hypothyroidism on reproduction in the bitch

Hypothyroidism in bitches has been reported to cause a variable interestrus interval, infertility, abortion, and stillbirth. The objective of this study was to evaluate the effect of experimentally induced hypothyroidism in bitches on fertility, pregnancy, parturition, and neonatal health. Eighteen healthy multiparous bitches were used; hypothyroidism was induced (by radioiodine administration) in nine bitches and the remaining nine served as untreated controls. After breeding, bitches were evaluated for pregnancy, fetal resorption, gestation length, litter size, duration and strength of uterine contractions (during parturition), interval between delivery of pups, viability of pups at birth, periparturient survival, and weight of pups at birth through 4 weeks of age. Bitches were bred a median of 19 weeks after induction of hypothyroidism. All bitches became pregnant and delivered term litters. There was no difference in the interestrus interval, litter size, or gestation length between hypothyroid and control bitches. Duration of uterine contractions was longer, but contraction strength was weaker in hypothyroid than control bitches; however, the interval between delivery of pups was not affected. Periparturient puppy mortality was significantly higher in litters from hypothyroid bitches. Viability scores and weight at birth were significantly lower in pups from hypothyroid bitches than controls. There was no difference between groups in pup weight gain during the first 4 weeks, in the interval from birth to the eyes opened, or to the onset of walking. Although hypothyroidism of relatively short duration did not affect fertility, it prolonged parturition and reduced pup survival in the periparturient period.

Short-term hypothyroidism after Levothyroxine-withdrawal in patients with differentiated thyroid cancer: clinical and quality of life consequences

Acute hypothyroidism induced by thyroid hormone withdrawal in patients with differentiated thyroid cancer during monitoring for remnant or metastatic disease, seriously affects multiple organs and systems, and especially in severe cases can impair quality of life. Indeed, it may induce untoward cardiovascular effects and can be hazardous in patients with underlying cardiovascular disease, particularly in the elderly. Moreover, acute hypothyroidism deranges the lipid profile and exacerbates neuropsychiatric illness. The introduction of recombinant human TSH (rhTSH) as a diagnostic and therapeutic tool in the care of patients with thyroid cancer has widened the scope of disease management. The use of rhTSH prevents derangement of various systems at approximately equivalent societal costs to that of withdrawal and promotes compliance while preserving the patient's normal daily functioning and productivity. Its reliability allied with its safety render this compound a valid alternative in the monitoring of patients with differentiated thyroid carcinoma as well as providing an alternative therapeutic procedure whenever LT4-withdrawal may be hazardous or in cases of patient non-compliance.

Changes in Autonomic Modulation to the Heart and Intracellular Catecholamines

Background: The effects of thyroid deprivation on the autonomic modulation to the heart remain controversial. Methods: In this study in patients followed for thyroid carcinoma, we investigated (1) heart rate variability parameters and the baroreflex gain and (2) intracellular catecholamine levels in circulating lymphocytes during short-term hypothyroidism (phase 1) and after reinstitution of TSH-suppressive thyroid hormone replacement (phase 2). Results: The RR interval value (p < 0.01) and systolic blood pressure (p < 0.05) were higher in phase 1 than in phase 2. The low-frequency/high-frequency (LF/HF) ratio was significantly lower in the hypothyroid state (p < 0.05), with a higher HF component (p < 0.05). After adjusting for mean RR interval in the regression model, the difference between the power of RR interval oscillations calculated in the two states was greater for the LF band (p = 0.005) and it was borderline significant for the HF band (p = 0.052). The baroreflex gain α_LF index was similar in the two phases. The stimulus-induced cellular production of norepinephrine and epinephrine in peripheral blood mononuclear cells was significantly higher in phase 2. Conclusion: The neurally-mediated influences on the sinus node and the study of intracellular catecholamine production suggest a reduced sympathoexcitation in hypothyroidism compared with the treatment phase. The early increase in blood pressure observed after thyroid hormone withdrawal is not due to impaired sensitivity of the baroreflex arc.

Influence of L-Thyroxine Administration on Poor-platelet Plasma VEGF Concentrations in Patients with Induced Short-term Hypothyroidism, Monitored for Thyroid Carcinoma

Angiogenesis is a process of new blood vessel development from pre-existing vasculature. It is a crucial process in normal physiology, as well as in several pathological conditions. The vascular endothelial growth factor (VEGF) represents a family of specific endothelial cell mitogens, involved in normal angiogenesis and in tumour development. The aim of the present study was to estimate the influence of L-thyroxine (L-T4) administration on poor-platelet plasma (P-PP) VEGF concentrations in patients with induced short-term hypothyroidism, monitored for differentiated thyroid carcinoma. In the present study, P-PP concentrations of VEGF, thyroglobulin, thyrotropin and free thyroid hormones were investigated in a population of 24 hypothyroid patients, who were withdrawn from L-T4 treatment for 5 weeks and studied before and after 2 months of L-T4 therapy. Only healthy female patients with no evidence of metastasis in whole body scintigraphy were included in the study. They were then compared with 20 healthy control subjects, matched for age, sex and body mass index (BMI). The patients had significantly lower plasma VEGF concentrations before treatment with L-T4 than after administration of that hormone. There was no significant difference in plasma VEGF levels, either between the patients treated with L-T4, and the controls, or between the patients untreated with L-T4, and the controls. Even short-time changes in thyrometabolic profile exert an important influence on P-PP VEGF concentrations, even if there is no thyroid tissue.

Health-related Quality of Life, Depression and Anxiety in Thyroid Cancer Patients

We examined the relationships among physical complaints, health-related quality of life (HRQL), anxiety and depression in differentiated thyroid cancer (DTC) patients under short-term hypothyroidism. We conducted a cross-sectional study in 136 patients hypothyroid on thyroid hormone withdrawal (THW) hospitalized for radioiodine administration. Patients were assessed using Short Form SF-36 (SF-36), Hospital Anxiety and Depression Scale (HADS), Profile of Mood States (POMS), Beck Depression Inventory (BDI), and physical complaints. Compared to the German general population, hypothyroid patients had significantly impaired HRQL. Surprisingly, the prevalence of anxiety (62.5%), but not depression (17.9%) was much higher in hypothyroid DTC patients than in the general population. In multivariate analysis, depression and age were independently associated with the physical health score (R(2) = 0.21), but only psychological variables (depression, mood disturbance, and anxiety) were associated with the mental health score (R(2) = 0.43), on the SF-36 HRQL instrument. HRQL is severely impaired in DTC patients under short-term hypothyroidism. As potential predictors of generic HRQL impairment, depression, anxiety, and mood disturbance could be used to preselect the patients most needing psychiatric care. The high frequency of anxiety should be considered in the aftercare of thyroid cancer patients.

Impact of Short-Term Hypothyroidism on Systemic Anticoagulation in Patients with Thyroid Cancer and Coumarin Therapy

Unlike hyperthyroidism, few data exist regarding the impact of hypothyroidism on systemic anticoagulation with coumarin derivates. Therefore, we evaluated a potential impact of short-term hypothyroid conditions on systemic anticoagulation with coumarin derivates in patients after complete thyroidectomy for treatment of thyroid cancer. Fifteen patients with differentiated thyroid cancers and continued international normalized ratio (INR)-adjusted therapy with coumarin derivates were included in this retrospective analysis. A total of 88 laboratory tests was analyzed. INR values were compared between thyroid-stimulating hormone (TSH) values greater than 10 and 10 mU/L or less. An INR value of less than 2.0 was defined as being out of the therapeutic range. Analysis of significant differences between categorized TSH and INR values were performed by using X(2) analysis, correlation of continuous TSH and INR values by using the Pearson's analysis. When TSH was greater than 10 mU/L (n = 50) the INR value was less than 2.0 in 76.0% (n = 38) cases. In contrast, the INR value was less than 2.0 in only 21.1% (n = 8; p < 0.0001) of patients with TSH of 10 mU/L or less (n = 38). Correlation between continuous TSH and INR values was r = -0.589 (p < 0.0001). Based on the results of the present study, it seems to be necessary to monitor the anticoagulation parameters more often in patients with hypothyroidism and either to correct the hypothyroid state, or in cases of desired hypothyroid conditions, to adjust the therapy with coumarin derivates in order to ensure a sufficient anticoagulation.

A Comparison of Short-Term Changes in Health-Related Quality of Life in Thyroid Carcinoma Patients Undergoing Diagnostic Evaluation with Recombinant Human Thyrotropin Compared with Thyroid Hormone Withdrawal

Thyroid carcinoma requires lifelong monitoring with serum thyroglobulin, radioactive iodine whole body scanning, and other imaging modalities. Levothyroxine (L-T4) withdrawal for thyroglobulin measurement and whole body scanning increases these tests' sensitivities but causes hypothyroidism. Recombinant human TSH (rhTSH) enables testing without L-T4 withdrawal. Our objective was to examine the impact of short-term hypothyroidism on the health-related quality of life (HRQOL) of patients after rhTSH vs. L-T4 withdrawal. In this multicenter study, the SF-36 Health Survey was administered to 228 patients at three time points: on L-T4, after rhTSH, and after L-T4 withdrawal. INTERVENTIONS included administration of rhTSH on L-T4 and withdrawal from thyroid hormone. Mean SF-36 scores were compared during the two interventions and with the U.S. general population and patients with heart failure, depression, and migraine headache. Patients had SF-36 scores at or above the norm for the general U.S. population in six of eight domains at baseline on L-T4 and in seven of eight domains after rhTSH. Patients' scores declined significantly in all eight domains after L-T4 withdrawal when compared with the other two periods (P < 0.0001). Patients' HRQOL scores while on L-T4 and after rhTSH were at or above those for patients with heart failure, depression, and migraine in all eight domains. After L-T4 withdrawal, patients' HRQOL scores were significantly below congestive heart failure, depression, and migraine headache norms in six, three, and six of the eight domains, respectively. Short-term hypothyroidism after L-T4 withdrawal is associated with a significant decline in quality of life that is abrogated by rhTSH use.

Health-related quality of life, anxiety and depression in thyroid cancer patients under short-term hypothyroidism and TSH-suppressive levothyroxine treatment

Very few previous studies have compared the degree of health-related quality of life (HRQL), depression and anxiety of differentiated thyroid cancer patients (DTC) under short-term hypothyroid-ism and levothyroxine treatment. Using patient-completed instruments, we examined the frequency of physical complaints, HRQL, anxiety and depression in 130 DTC patients hospitalized for radioiodine therapy or whole-body diagnostics (age 52 years, female 71%) under short-term hypothyroidism (4 weeks of levothyroxine withdrawal; DTC-H) and in 100 DTC out-patients under TSH-suppressive doses of levothyroxine subsequent to radioiodine therapy (DTC-L; age 49 years, female 81%). Compared with the German general population, DTC-H as well as DTC-L patients had significantly impaired HRQL. Notably, the decrease in HRQL was significantly higher in DTC-H than in DTC-L patients. Surprisingly, the prevalence of anxiety (44.6%) but not depression (17.7%) was much higher in the DTC-H patients than in the general population. In contrast to expectations, similar results for anxiety (44.0%) and depression (17.6%) were observed in the DTC-L patients. This mounting evidence suggests that a consistent pattern of HRQL impairment is experienced by patients with DTC. The high frequency of anxiety and the significantly reduced HRQL should be considered in the aftercare of DTC patients.

Thyroid function differently affects serum cystatin Cand creatinine concentrations

Cystatin C (Cys C) is a cysteine protease inhibitor produced at a constant rate by nucleated cells, filtered through the glomerular membrane and reabsorbed by kidney tubular cells. Aim of this cross-sectional and longitudinal study was to assess serum Cys C and creatinine (Crea) concentrations in thyroid dysfunction. One hundred and eighty-one patients, 26 with untreated non-toxic nodular goiter, 58 with hyperthyroidism, 31 on L-T4 suppressive therapy for non-toxic nodular goiter, 35 with short-term hypothyroidism after L-T4 withdrawal to perform whole body scan for thyroid cancer, 11 with long-term hypothyroidism due to chronic autoimmune thyroiditis and 20 patients with mild hypothyroidism were enrolled in the study. Fifty-seven age- and sex-matched normal subjects served as controls. Serum Cys C, Crea, free T4 (FT4), FT3 and TSH were assessed. Thirty hyperthyroid patients and 35 short-term hypothyroid patients were followed prospectively until euthyroidism was reached by methimazole or L-T4 therapy. The cross-sectional study showed that mean serum Crea concentrations were significantly reduced in overt hyperthyroid or subclinical hyperthyroid patients, while it was increased in overt hypothyroid patients, but not in mild hypothyroidism. Conversely, serum Cys C levels were significantly increased in overt hyperthyroid patients compared to controls (p<0.05), and significantly decreased in short-term, long-term and mild hypothyroids (p<0.05, p<0.05, p<0.01, respectively). However, 36 (62%) hyperthyroid patients and 50 (76%) hypothyroid patients had normal serum Cys C values. In the prospective study, restoration of euthyroidism by either methimazole or L-T4 therapy was associated with normalization of mean serum Cys C concentrations. In conclusion, thyroid dysfunction affects serum Cys C concentration, possibly influencing the production rate of the protein. However, the observation that hyper- or hypothyroid patients have normal serum Cys C levels limits its use as a marker of peripheral thyroid hormone effect.

Autoimmune thyroid disease and brain

Changes of the affective and cognitive function are usually associated with thyroid gland dysfunction. In autoimmune thyroid disease, these changes can be caused by thyroid dysfunction (hypo- or hyperthyroidism) or associated with the presence of antithyroid antibodies. Even a small change in thyroid hormone concentration is associated with change of cognitive function. In euthyroid older males, variation of total and free thyroxin accounts for about 10% of Wechsler adult intelligence test variance. In euthyroid females, lower cognitive function, measured by Mini Mental test, also correlates with blood thyroxin. Short-term (4 weeks) hypothyroidism induces clinically significant cognitivedysfunction, which is reversible by thyroid hormone substitution. Mild hypothyroidism (TSH less than 10) also induces reversible cognitive dysfunction. In hypothyroidism, PET scanning shows global reduction of brain blood flow and glucose metabolism. Hashimoto's encephalopathy is characterized by corticosteroid reversible encephalopathy associated with the presence of antithyroid antibodies. Encephalopathy can be manifested as multiple stroke-like episodes (vasculitis like), or as diffuse, progressive type characterized by dementia and psychiatric symptoms. In euthyroid patients with Hashimoto's thyroiditis and no evidence of neurological disease, SPECT showed brain perfusion abnormalities. Post mortem and brain biopsy findings can be normal or show perivascular lymphocytic infiltration. Recently, presence of antineuronal antibodies has been found in patients with Hashimoto's thyroiditis. Specific high reactivity against human alpha-enolase was high in patients with Hashimoto's encephalopathy, but absent in patients with other neurological disorders and healthy subjects. Specific antineural antibodies were found in another group of Hashimoto's encephalopathy patients. Furthermore, Ferracci et al, found antithyroid antibodies in the CSF of patients with Hashimoto's encephalopathy.

Cognitive changes in short-term hypothyroidism assessed with event-related brain potentials

Hypothyroidism is a common clinical problem during 131Iodine-therapy of thyroid cancer. In the present investigation, possible cognitive dysfunction during hypothyroid state was assessed by means of neuropsychological tests and the recording of event-related brain potentials (ERPs). Fifteen patients undergoing therapy for thyroid cancer were examined twice: (1) substituted with thyroid hormones, (2) during hypothyroid state immediately prior to treatment. Standard neuropsychological tests were applied during both sessions and subjects showed a mild-to-moderate impairment in their hypothyroid state. In addition, ERPs were recorded from 19 scalp sites while subjects performed two visual search tasks. The serial task required the effortful one-by-one scanning of several items within a visual array, while the parallel task allowed processing of all stimulus items in parallel and automatically. ERPs showed a marked amplitude decrement and delay of the P3 component known to index the speed of stimulus evaluation and the amount of available processing resources. This effect was present only for the serial search task, while no changes were seen in the parallel search task. These data show that hypothyroidism during 131Iodine-therapy is associated with clinically relevant cognitive dysfunctions, especially with effortful attention demanding tasks.

Isotopic Renal Function Studies in Severe Hypothyroidism and after Thyroid Hormone Replacement Therapy

Aim: To investigate the possible changes in the renal tubular function in severe short-term hypothyroidism using ^99mTc-MAG₃ renography. Methods: 27 consecutive thyroidectomized patients (7 males and 20 females) aged 19–79 (mean 53) years were included in the present study. ^99mTc-MAG₃ renography was performed in all patients before and after thyroid hormone replacement therapy. In addition, ⁵¹Cr-EDTA clearance and serum creatinine concentrations were determined. Results: The serum creatinine concentrations were significantly increased in hypothyroidism as compared with the concentrations after thyroxine substitution (1.30 ± 0.44 vs. 1.04 ± 0.32 mg/dl, p < 0.05). According to the ⁵¹Cr-EDTA clearance, the glomerular filtration rate was significantly lower in hypothyroidism than after treatment (61 ± 18 vs. 75 ± 23 ml/min). In contrast, we did not find any significant change in the renographic parameters for ^99mTc-MAG₃ before and after treatment (total excreted activity 20 min after administration 51 ± 12 vs. 54 ± 14%; T_max left:right 4.2 ± 1.77 : 3.91 ± 1.06 min vs. 4.1 ± 1.66 : 4.4 ± 1.96 min). Conclusions: We did not find any influence of thyroid hormones on the outcome of ^99mTc-MAG₃ renography. As ^99mTc-MAG₃ reflects the tubular function, it seems that the renal hemodynamic changes in severe hypothyroidism mainly affect the glomerular function. In general, the glomerular filtration rate reduction seems to be reversible after hormone substitution therapy; however, care has to be taken in patients with renal insufficiency.

The prevalence of elevated serum C-reactive protein levels in inflammatory and noninflammatory thyroid disease.

C-reactive protein (CRP) levels have not been routinely used to diagnose thyroid disease, although many thyroid conditions involve inflammation. This study was intended to determine whether CRP levels could differentiate between inflammatory and noninflammatory thyroid conditions, especially between type II inflammatory amiodarone-induced thyrotoxicosis (AIT) and type I iodine-induced AIT. Serum high-sensitivity CRP levels were measured in 100 euthyroid controls (7 taking amiodarone) and 353 patients with one of the following thyroid conditions: AIT, subacute thyroiditis, toxic diffuse goiter, nodular goiter, Hashimoto's thyroiditis, shortterm hypothyroidism, or postpartum thyroiditis. No patients with nontoxic multinodular goiter (n = 34), toxic nodular goiter (n = 23), or toxic diffuse goiter, either untreated (n = 49) or euthyroid while taking methimazole (n = 33), had positive CRP levels (>10 mg/L). The occurrence of positive CRP levels among patients with Hashimoto's thyroiditis (n = 35), short-term hypothyroidism (n = 38), and postpartum thyroiditis (n = 70) did not differ significantly from controls. The occurrence of positive CRP values did not differ significantly between patients with type I and type II AIT and controls. Six of 7 patients (86%) with untreated subacute thyroiditis had positive CRP levels (p < 0.00001). These results indicate that there is only a limited role for measurement of CRP levels in the diagnosis of thyroid diseases other than subacute thyroiditis.

Low cholesteryl ester transfer protein (CETP) concentration but normal CETP activity in serum from patients with short-term hypothyroidism Lack of relationship to lipoprotein abnormalities.

Hypothyroidism is associated with a number of abnormalities in lipoprotein metabolism. Although alterations in neutral lipid exchanges among plasma lipoproteins might be one characteristic feature of hypothyroidism, a few human studies of cholesteryl ester transfer protein (CETP) activity have led to heterogeneous and fragmentary observations. The aim of the present study was to analyse the influence of short-term hypothyroidism on CETP activity, as well as on the structure and composition of lipoproteins. PATIENTS, DESIGN AND MEASUREMENTS: Sixty-six thyroidectomized patients were withdrawn from L-thyroxine (L-T4) treatment for 5 weeks. Subsequently, L-T4 therapy was reinstated for 2 months and patients were compared to 61 matched normolipidaemic controls. Serum CETP activity and mass concentration, serum lipids, apolipoproteins and lipoprotein size distribution were determined in the three groups. Serum CETP mass concentration was significantly decreased in short-term hypothyroid patients, as compared to control subjects (3.22 +/- 0.98 vs. 3.79 +/- 1.2 mg/l, respectively; P < 0.001), and the values were normalized during L-T4 therapy. The ability of endogenous serum lipoproteins to interact with CETP was normal in short-term hypothyroid patients. Concordant observations were made regardless of whether neutral lipid transfers were measured from high-density lipoproteins (HDL) toward apo B-containing lipoproteins or from liposomes toward HDL. The size distribution of HDL was significantly different in short-term hypothyroid patients, compared to either the control or treated subgroups, with significant higher proportions of large-sized HDL2b and HDL2a (HDL2b: 13.6 +/- 6.5% before vs. 8.5 +/- 4.2% during L-T4 therapy, P < 0.05; HDL2a, 33.0 +/- 7.0% before vs. 29.3 +/- 6.9% during L-T4 therapy, P < 0.05). Although serum CETP mass concentration correlated negatively with the HDL2 to HDL3 ratio in control subjects (r = -0.588; P < 0.0001), no significant correlations were observed in hypothyroid patients, regardless of whether they were treated or not. Similarly, whereas the previously recognized positive correlation of CETP mass concentration with serum LDL cholesterol levels was found in control subjects (r = 0.264; P < 0.05), no significant correlations appeared in treated and untreated patients. Short-term hypothyroidism may constitute an unique situation in which concomitant alterations in serum cholesteryl ester transfer protein concentration and lipoprotein parameters are disconnected.

The role of thyroid hormone in blood pressure homeostasis: evidence from short-term hypothyroidism in humans.

Arterial hypertension is known to be frequently associated with thyroid dysfunction, with a particularly high prevalence in chronic hypothyroidism. However, to our knowledge no comprehensive study addressed causal mechanisms possibly involved in this association. We here report the physiological relationships between blood pressure and neuro-humoral modifications induced by acute hypothyroidism in normotensive subjects. Twelve normotensive patients with previous total thyroidectomy were studied. Ambulatory 24-h blood pressure monitoring was performed, and free T(3), free T(4), TSH, PRA, aldosterone, cortisol, adrenaline, and noradrenaline were assayed 6 wk after oral L-T(4) withdrawal (phase 1) and 2 months after resumption of treatment (phase 2). During the hypothyroid state (TSH, 68.1 +/- 27.7 microIU/ml; mean +/- SD), daytime arterial systolic levels slightly, but significantly, increased (125.5 +/- 9.7 vs. 120.4 +/- 10.8 mm Hg; P < 0.05), and daytime diastolic levels (84.6 +/- 7.9 vs. 76.4 +/- 6.8 mm Hg; P < 0.001), noradrenaline (2954 +/- 1578 vs. 1574 +/- 962 pmol/liter; P < 0.001), and adrenaline (228.4 +/- 160 vs. 111.3 +/- 46.1 pmol/liter; P < 0.05) also increased. PRA remained unchanged (0.49 +/- 0.37 vs. 0.35 +/- 0.21 ng/ml.h; P = NS), whereas both aldosterone (310.3 +/- 151 vs. 156.9 +/- 67.5 pmol/liter; P < 0.005) and cortisol (409.2 +/- 239 vs. 250.9 +/- 113 pmol/liter; P < 0.02) significantly increased. By using univariate logistic regression daytime arterial diastolic values, noradrenaline and aldosterone were found to be significantly related to the hypothyroid state (P < 0.02, P < 0.036, and P < 0.024, respectively). In conclusion, our data show that thyroid hormones participate in the control of systemic arterial blood pressure homeostasis in normotensive subjects. The observed sympathetic and adrenal activation in hypothyroidism, which is reversible with thyroid hormone treatment, may also contribute to the development of arterial hypertension in human hypothyroidism.

The Role of Thyroid Hormone in Blood Pressure Homeostasis: Evidence from Short-Term Hypothyroidism in Humans

The Role of Thyroid Hormone in Blood Pressure Homeostasis: Evidence from Short-Term Hypothyroidism in Humans