Do bone turnover markers reflect changes in bone microarchitecture during treatment of patients with thyroid dysfunction?

PURPOSE: This study aimed to compare changes in the bone turnover markers (BTMs)-C-terminal telopeptide of type I collagen (CTX-I) and procollagen I N-terminal peptide (PINP)-with changes in the bone microarchitecture, assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), during treatment of patients with thyroid dysfunction. METHODS: In women with newly diagnosed hypo- or hyperthyroidism, HR-pQCT variables, obtained from the tibia and the radius, were compared with BTMs. Data were collected at diagnosis and after at least 12 months of euthyroidism. RESULTS: 73 women completed the study (hypothyroidism, n = 27; hyperthyroidism, n = 46). Among hyperthyroid patients, correlations were found between changes in BTMs and HR-pQCT variables, primarily for cortical variables in the tibia, i.e. cortical thickness (CTX-I, p < 0.001; PINP, p < 0.001), and volumetric bone mass density (vBMD) (CTX-I, p < 0.001; PINP, p < 0.001). Moreover, correlations between BTMs and estimated bone strength were found. In the hypothyroid subgroup, no significant findings existed after adjustment. Following treatment, less decrease in tibial vBMD was seen among patients with increasing CTX-I compared to those with a decreasing CTX-I level (p = 0.009). Opposite findings applied to PINP, as patients with decreasing PINP showed an increase in tibial vBMD, in contrast to a decline in this parameter among patients with increasing PINP (p < 0.001). CONCLUSION: Changes in CTX-I and PINP correlated with HR-pQCT variables during the treatment of women with thyroid dysfunction. To some extent, these BTMs reflected the restoration of bone microarchitecture. CTX-I seems to be the most sensitive BTM in treatment-naïve thyroid diseases, while PINP is more useful for monitoring during treatment. TRIAL REGISTRATION NUMBER: NCT02005250. Date: December 9, 2013.

Evaluation of thyroid nodules by shear wave elastography: a review of current knowledge.

PURPOSE: Shear wave elastography (SWE), as a tool for diagnosing thyroid malignancy, has gathered considerable attention during the past decade. Diverging results exist regarding the diagnostic performance of thyroid SWE. METHODS: A comprehensive literature review of thyroid SWE was conducted using the terms "Thyroid" and "shear wave elastography" in PubMed. RESULTS: The majority of studies found SWE promising for differentiating malignant and benign thyroid nodules on a group level, whereas results are less convincing on the individual level due to huge overlap in elasticity indices. Further, there is lack of consensus on the optimum outcome reflecting nodule elasticity and the cut-off point predicting thyroid malignancy. While heterogeneity between studies hinders a clinically meaningful meta-analysis, the results are discussed in a clinical perspective with regard to applicability in clinical practice as well as methodological advantages and pitfalls of this technology. CONCLUSION: Technological as well as biological hindrances seem to exist for SWE to be clinically reliable in assessing benign and malignant thyroid nodules. Structural heterogeneity of thyroid nodules in combination with operator-dependent factors such as pre-compression and selection of scanning plane are likely explanations for these findings. Standardization and consensus on the SWE acquisition process applied in future studies are needed for SWE to be considered a clinically reliable diagnostic tool for detection of thyroid cancer.

Use of thyroid hormones in hypothyroid and euthyroid patients: A 2020 THESIS questionnaire survey of members of the Danish Endocrine Society.

PURPOSE: The standard treatment of hypothyroidism is levothyroxine (LT4), which is available as tablets or soft-gel capsules in Denmark. This study aimed to investigate Danish endocrinologists' use of thyroid hormones in hypothyroid and euthyroid patients. METHODS: An e-mail with an invitation to participate in an online survey investigating practices about substitution with thyroid hormones was sent to all members of the Danish Endocrine Society (DES). RESULTS: Out of 488 eligible DES members, a total of 152 (31.2%) respondents were included in the analysis. The majority (94.1%) of responding DES members use LT4 as the treatment of choice. Other treatment options for hypothyroidism are also used, as 58.6% prescribe combination therapy with liothyronine (LT3) + LT4 in their clinical practice. LT4 + LT3 combination is preferred in patients with persistent symptoms of hypothyroidism despite biochemical euthyroidism on LT4 treatment. Over half of the respondents answered that thyroid hormone therapy is never indicated for euthyroid patients, but 42.1% will consider it for euthyroid infertile women with high antibody levels. In various conditions that could interfere with the absorption of LT4, most responding Danish endocrinologists prefer tablets and do not expect a significant difference when switching from one type of tablet formulation to another. CONCLUSION: The treatment of choice for hypothyroidism is LT4. Combination therapy with LT4 + LT3 is considered for patients with persistent symptoms. Even in the presence of conditions affecting bioavailability, responding Danish endocrinologists prefer LT4 tablets rather than newer LT4 formulations, such as soft-gel capsules.

THE ROMANIAN VERSION OF THE THYROID-RELATED PATIENT-REPORTED OUTCOMES THYPRO AND THYPRO-39. TRANSLATION AND ASSESSMENT OF RELIABILITY AND CROSS-CULTURAL VALIDITY.

BACKGROUND: ThyPRO is a recently developed thyroid-specific quality of life (QoL) questionnaire applicable to patients with benign thyroid disorders(BTD). The aim of the present study was to translate ThyPRO and ThyPRO-39 into Romanian, and to evaluate reliability and cross-cultural validity. METHODS: Standard methodology for translation and linguistic validation of patient-reported outcomes (PRO) was applied. The questionnaire was completed by 130 patients with benign thyroid diseases seen at Department of Endocrinology in the Emergency County Hospital, Tîrgu Mures, Romania, between October 2015 and March 2016. Internal reliability of the Romanian version of the ThyPRO (ThyPROro) scales was assessed for multi-item scales using Cronbach's alpha coefficient. An efficient method for testing cross-cultural validity is analysis of differential item functioning (DIF). Uniform DIF between the Romanian and the original Danish sample was investigated using ordinal logistic regression. The translation process proceeded without difficulties, and any disagreements were revised by one of the developers and the language coordinator. RESULTS: Internal reliability for ThyPRO was satisfactory. Cronbach`s alpha coefficients for the 13 scales ranged from 0.78 to 0.93 for the ThyPROro and 0.78 to 0.87 for the ThyPROro-39. In the 85-item ThyPRO, nine instances of DIF were found. Most were minor, explaining <3% of the variation in scale score, but DIF in positively worded items were larger, with explained variance (R2's) around 10-15%. CONCLUSION: The ThyPROro questionnaire is ready for assessment of health-related quality of life in Romanian patients with benign thyroid diseases.

Serum thyroxine and age--rather than thyroid volume and serum TSH--are determinants of the thyroid radioiodine uptake in patients with nodular goiter.

BACKGROUND: Radioiodine (131I) therapy is widely used for treatment of non-toxic goiters. A limitation for this treatment is a low thyroid radioiodine uptake (RAIU), often encountered in these patients. AIM: To estimate the impact of various factors on the thyroid RAIU. METHODS: We examined prospectively 170 patients (146 females; age range: 22-87 yrs) with nodular goiter (median 64 ml, range: 20-464 ml) selected for 131I therapy. Serum TSH was sub-normal in 42.4%. None were treated with anti-thyroid drugs. The thyroid RAIU was determined at 24h and 96 h. The goiter volume was measured by ultrasound (no.=127), or by magnetic resonance imaging (no.=43). RESULTS: The 24h and the 96 h RAIU were 34.2 ± 9.8(SD)% (range: 11.4-66.0%) and 34.0 ± 10.0% (range: 10.5-60.9%), respectively. Sixty-one patients had a 24h RAIU <30% and these individuals were older than patients with a 24h RAIU ≥ 30% (median 58 vs 51 yrs, p=0.02). These two subgroups did not differ significantly in other variables. Overall, the 24h RAIU was positively correlated to the serum (s) free T4-index (r=0.20, p=0.01), and negatively to age (r=-0.18, p=0.02), but not significantly related to serum TSH or thyroid volume. Age correlated positively with thyroid volume (r=0.31, p < 0.001). In a regression analysis, s-free T4-index and age remained as the only determinants of the 24h and the 96 h RAIU. CONCLUSIONS: In patients with a symptomatic nodular goiter, serum T4 and age are the major determinants of the thyroid RAIU. A sub-normal serum TSH is not a marker of a compromised thyroid RAIU but reflects that the iodine is confined to a few 'hot spots'.

Propylthiouracil before 131I therapy of hyperthyroid diseases: effect on cure rate evaluated by a randomized clinical trial.

A randomized clinical trial was performed to clarify whether pretreatment with propylthiouracil (PTU) before radioiodine ((131)I) therapy influences the final outcome of this therapy, as has been indicated by retrospective studies. Untreated consecutive hyperthyroid patients with Graves' disease (n = 23) or a toxic nodular goiter (n = 57) were randomized to either PTU (+PTU; n = 39) or no pretreatment (-PTU; n = 41) before compensated (131)I therapy. The median PTU dose was 100 mg, which was discontinued 4 d before treatment. The median (131)I activity was 302 MBq (range, 87-600 MBq). After (131)I therapy, the serum free T(4) index increased in the +PTU group from 97.7 +/- 47.5(+/-sd) nmol/liter at the time of therapy to 152.3 +/- 77.6 nmol/liter at 3 wk (P < 0.001) and 140.4 +/- 75.9 nmol/liter at 6 wk (P < 0.001). In the -PTU group, the serum free T(4) index, which was initially 254.3 +/- 145.7 nmol/liter, decreased significantly to 212.0 +/- 113.0 nmol/liter at 3 wk (P < 0.05) and 165.8 +/- 110.0 nmol/liter at 6 wk (P < 0.005). After 1 yr of follow-up, the treatment failure rate in patients with a toxic nodular goiter was four times higher in the +PTU group than in the -PTU group (nine of 20 vs. three of 25 patients; P = 0.06), whereas the difference among patients with Graves' disease was less obvious (four of six vs. four of nine; P = 0.81). Patients in the +PTU group who were cured had higher serum TSH (s-TSH) levels at the time of (131)I therapy than those who were not cured. By adjusting for a possible interfactorial relationship through a regression analysis, including the s-TSH level and type of disease, only PTU pretreatment had a significant adverse effect on the cure rate (P = 0.03). In conclusion, this randomized trial demonstrates that PTU pretreatment reduces the cure rate of (131)I therapy in hyperthyroid diseases, although this adverse effect seems to be attenuated by the concomitant rise in s-TSH.

The feasibility of high dose iodine 131 treatment as an alternative to surgery in patients with a very large goiter: effect on thyroid function and size and pulmonary function.

Some patients with very large goiters (>150 mL) are not candidates for surgery. We evaluated the feasibility of high dose 131I in such patients. Twenty-three patients (2 men and 21 women; median age, 67 yr; range, 42-86 yr) with very large goiter (8 toxic) were treated with calculated high dose 131I [median, 2281 megabecquerels (61.6 mCi); range, 988-4620 megabecquerels (26.7-124.9 mCi)]. During the 12-month observation period, goiter reduction and tracheal anatomy were monitored by magnetic resonance imaging, and the respiratory capacity was monitored by pulmonary function tests. Five patients (22%) developed hypothyroidism. Thyroid volumes were at baseline, after 1 week, and after 1 yr [mean +/- SEM, 311 +/- 28, 314 +/- 26 (P = NS), and 215 +/- 26 (P < 0.01) mL]. The relative changes 1 week after therapy ranged from -14.1% to 15.3%. After 1 yr the mean size was reduced by 33.9% (range, 13.5-61.4%). Only the initial goiter size showed a significant negative correlation to the percent reduction. The smallest cross-sectional area of the trachea decreased 9.2% within 1 week after treatment, but eventually emerged with a 17.9% larger area [mean +/- SEM, 84.3 +/- 4.8, 75.5 +/- 5.1 (P < 0.01), and 98.2 +/- 6.0 (P < 0.01) mm2]. The inspiratory parameter, FIF50%, improved after an initial insignificant decline [baseline therapy, after 1 week, after 3 months, and after 1 yr (mean +/- SEM), 2.37 +/- 0.24, 2.20 +/- 0.21 (P = NS), 2.51 +/- 0.23 (P = NS), and 2.76 +/- 0.25 (P = 0.01) L/s]. FIF50% correlated significantly with the smallest cross-sectional tracheal area (baseline, 1 week, and 1 yr: r = 0.74; P < 0.001, r = 0.63; P < 0.005, and r = 0.46; P < 0.05). Changes in tracheal anatomy did not correlate with changes in either lung dynamics or goiter size. In conclusion, very large goiters can be reduced by a third, on the average, with high dose 131I therapy without any initial clinically significant tracheal compression. Tracheal cross-sectional area as well as pulmonary inspiratory capacity improve. No serious adverse effects are seen.

Controversies in radioiodine therapy: relation to ophthalmopathy, the possible radioprotective effect of antithyroid drugs, and use in large goitres.

In routine use for more than 50 years, radioiodine ((131)I) is generally considered safe and devoid of major side effects. Therefore, it is surprising that relatively many aspects of radioiodine therapy are controversial, as illustrated by recent international questionnaire studies. Our review aims at highlighting three of these areas - namely, the influence of (131)I on the course of Graves' ophthalmopathy, the possible radioprotective effects of antithyroid drugs, and the use of (131)I in large goitres. (131)I therapy carries a small (but definite) risk of causing progression of Graves' ophthalmopathy. Identification of risk factors (thyroid dysfunction, high level of thyroid-stimulating hormone (TSH) receptor antibodies, cigarette smoking) allows the identification of patients at risk and the institution of concomitant glucocorticoid treatment, thereby hindering progression of eye disease. On the basis, largely, of retrospective data, it appears that carbimazole (or methimazole), if stopped 3-5 days before treatment, does not influence the outcome of (131)I therapy. Simultaneous thyrostatic medication most probably reduces the efficacy of (131)I, as does restarting it within 7 days. Propylthiouracil seems to have a more prolonged radioprotective effect than carbimazole. Surgery is the treatment of first choice in patients with a large goitre. However, in the case of patient ineligibility or preference, (131)I therapy may be an option. The treatment has a favourable effect on tracheal compression and inspiratory capacity, but the reduction in thyroid volume is only 30-40%. Inpatient treatment, necessitated by the large doses, makes the treatment cumbersome. Controversy related to radioiodine therapy is mainly based on the lack of adequate prospective randomised studies comparing efficacy, side effects, cost and patient satisfaction.

[The combination of ACE inhibitor and thiazide may cause severe hyponatremia]. / Kombinationen ACE-inhibitor/tiazid kan give svaer hyponatriaemi.

A case of a woman aged 79 years presenting severe hyponatraemia is described. The patient was not dehydrated and the urine was hypertonic. There was no history of renal, hepatic or cardiac disorders. Some weeks previously she had been treated with lisinopril and bendroflumethiazide on account of arterial hypertension. After withdrawal of the drugs and intensive therapy the patient recovered rapidly. The combination of an ACE-inhibitor and a thiazide drug may lead to serious disturbances in body fluid compartments and serum electrolytes. The need for frequent control of serum electrolytes is emphasized.

[Guillain-Barre syndrome. Cytomegalovirus infections and pregnancy]. / Guillain-Barré-syndromet. Cytomegalovirusinfektion og graviditet.

A case of Guillain-Barré syndrome during pregnancy is presented. The patient was 11 weeks' pregnant and developed tetraparesis over a few weeks. She did not require mechanical ventilation. Elevated liver enzymes and virocytosis in the peripheral blood were noted. Based on a positive IgM-antibody titre, a primary cytomegalovirus infection was diagnosed. The patient recovered completely and gave birth to a child of 43 weeks' gestation. Cytomegalovirus IgM-antibody was demonstrated in umbilical cord blood. The child appeared healthy without abnormalities at nine weeks of age.

[Juvenile renovascular hypertension of unusual origin]. / Juvenil renovaskulaer hypertension af sjaelden genese.

The case history of a girl aged 10 years with renovascular hypertension is presented. The symptoms were atypical. The diagnosis was made on basis of positive captopril renography. Angiography showed delayed filling of the right main renal artery by a long collateral vessel. The right renal artery was found to be occluded proximally by intimal hyperplasia. Renal angioplasty was performed and resulted in normalized blood pressure and normalized right kidney function.

[ST elevation in a patient with a healthy heart and acute appendicitis]. / ST-elevation hos en hjerterask patient med appendicitis acuta.

A male aged 57 years with acute appendicitis was found to have ST elevations in the EGG (precordial V1-V3 leads) suggesting acute myocardial infarction. The ECG returned to normal postoperatively. The patient showed no signs of ischaemic heart disease and the exercise test and myocardial scintigraphy were found to be normal.

[Transesophageal atrial stimulation is useful in supraventricular arrhythmias]. / Transøsofageal atrial stimulation er brugbar ved supraventrikulaere arytmier.

The results of transoesophageal atrial stimulation (TAS) were retrospectively evaluated in 22 patients (13 women, nine men, mean age forty-five years), in whom the method was used in the process of diagnosing or specifying supraventricular arrhythmias. The patients were tested for corrected sinus node recovery time, the response to incremental stimulation and burst pacing. TAS resulted in a pathological outcome in 11 patients (50%). Among 14 patients suffering from unprovoked palpitations suspicious of tachyarrhythmias TAS was able to induce a pathological response in 10 patients (71%). In five of eight patients (63%) with inducible SVT, this arrhythmia had not previously been observed. TAS was able to induce atrial fibrillation in four of eight patients with an accessory pathway. Typical symptoms rather than a prior pathological electrocardiography (12-lead ECG, Holter-monitoring, exercise-ECG) was able to predict the outcome of TAS (p < 0.05). We conclude that TAS is a safe and suitable supplement in the evaluation of supraventricular arrhythmias; primarily among patients with characteristic symptoms.

[Carpal tunnel syndrome and hand edema in temporal arteritis]. / Karpaltunnelsyndrom og håndødem ved arteritis temporalis.

An 89 year-old male was admitted to hospital presenting oedema, reduced sensibility, paraesthesia and reduced mobility of both hands. EMG was in accordance with bilateral carpal tunnel syndrome. An elevated sedimentation rate was found and biopsy from the temporal artery showed arteritis. During glucocorticoid treatment the symptoms disappeared and the EMG and sedimentation rate returned to normal.

[Danish endocrinologists' examination and treatment of non-toxic multinodular goiter. A questionnaire study]. / Danske endokrinologers udredning og behandling af atoksisk, multinodøs struma. En spørgeskemaundersøgelse.

AIM: To assess the attitudes towards the management of the non-toxic multinodular goitre by means of a questionnaire concerning on case history, which was circulated to all Danish endocrinologists ("A 42-year-old woman with an irregular, non-tender, bilaterally enlarged thyroid of 50-80 g and no clinical suspicion of malignancy"). DESIGN: Eleven variations of the (basic) case report were proposed in order to evaluate the impact on the management of each alteration. In the index case, serum TSH was the routine choice of 100%, serum T4/free T4-index and T3/free T3-index were measured by 83% and 79%, serum TPOab and serum calcitonin by 49% and 4%, respectively. RESULTS: The median number of blood tests was three (range 1-7). Thyroid scintigraphy was used by 96% and ultrasound by 94%, both methods were employed by 90% with scintigraphy most often having the first priority. Fine-needle aspiration biopsy was not routinely used, unless a scintigraphically dominant "cold" area was present; 70% used ultrasound guidance. Radioiodine was the preferred treatment of 51%, surgery 7%, L-T4 4%, and no treatment 38%. DISCUSSION: In the case of young patients or factors predisposing to thyroid cancer, treatment preferences changed to surgery. The prevailing use of radioiodine in Denmark contrasts with the situation in most other European countries, but Danish endocrinologists also disagree about the optimum management of multinodular non-toxic goitre.

[Thyrotoxic periodic paralysis]. / Tyreotoksisk periodisk paralyse.

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism mainly seen in patients of Oriental origin and is rarely encountered in Western countries. TPP clinically resembles familial periodic paralysis with recurrent episodes of weakness or flaccid paralysis of especially the legs. Transient hypokalaemia is regularly observed during attacks and remission can be achieved by administration of potassium salts. The definitive treatment of TPP is to restore euthyroidism. This case describes a thyrotoxic patient who initially presented with periodic paralysis.

Increased risk of long-term sickness absence, lower rate of return to work, and higher risk of unemployment and disability pensioning for thyroid patients: a Danish register-based cohort study.

CONTEXT: Little is known about how thyroid diseases affect work ability. OBJECTIVE: The objective of this study was to evaluate the risk of work disability for patients with thyroid disease compared with the general population. DESIGN, SETTING, AND PARTICIPANTS: In a longitudinal register study, outpatients (n = 862) with nontoxic goiter, hyperthyroidism, Graves' orbitopathy (GO), autoimmune hypothyroidism, or other thyroid diseases and their matched controls (n = 7043) were observed in the years 1994-2011 in Danish national registers of social benefits, health, and work characteristics. Cox regression analyses estimated adjusted hazard ratios (HRs) for the first year after diagnosis and subsequent years. MAIN OUTCOME MEASURES: Transitions between work, long-term sickness absence, unemployment, and disability pension were measured. RESULTS: Patients differed significantly from the general population with regard to sickness absence, disability pension, return from sickness absence, and unemployment. In the first year after diagnosis, higher risks of sickness absence was seen for GO (HR 6.94) and other hyperthyroid patients (HR 2.08), who also had lower probability of returning from sickness absence (HR 0.62) and higher risk of disability pension (HR 4.15). Patients with autoimmune hypothyroidism showed a lower probability of returning from sickness absence (HR 0.62). In subsequent years, GO patients had significantly higher risk of sickness absence (HR 2.08), lower probability of return from sickness absence (HR 0.51), and unemployment (HR 0.52) and a higher risk of disability pension (HR 4.40). Hyperthyroid patients also had difficulties returning from sickness absence (HR 0.71). CONCLUSIONS: Thyroid patients' risk of work disability is most pronounced in the first year after diagnosis and attenuates in subsequent years. GO patients have the highest risk of work disability.

Radioiodine therapy of benign non-toxic goitre. Potential role of recombinant human TSH.

This review provides an update on recombinant human TSH (rh-TSH) augmented radioiodine (¹³¹I) therapy and outlines its potential role in the treatment of symptomatic benign multinodular non-toxic goitre. In some countries, ¹³¹I has been used for three decades to reduce the size of nodular goitres. The feasibility of ¹³¹I therapy depends on an adequate thyroid ¹³¹I uptake. Based on a two-fold increase in thyroid ¹³¹I uptake, superiority studies have convincingly demonstrated that the absorbed thyroid ¹³¹I dose can be increased without increasing the administered ¹³¹I activity, resulting in a 35-56% amplification of goitre reduction at one-year post radioiodine compared to conventional (without rh-TSH) ¹³¹I therapy. Although patient satisfaction is not improved at one-year, this approach facilitates tracheal decompression and is particularly promising in large goitres. The majority of multinodular non-toxic goitre patients may not require amplified goitre reduction. But as an alternative strategy, rh-TSH allows up to 80% reduction of the therapeutic ¹³¹I activity while still achieving goitre reduction comparable to that of conventional ¹³¹I therapy and maintaining high patient satisfaction. The dose-reduction (equality) strategy is attractive in terms of minimizing post-therapeutic restrictions and in reducing the potential risk of radiation-induced malignancy. Adverse effects like temporary thyroid swelling and thyroid hormone excess are to a large extent dose-dependent and generally 0.1mg rh-TSH or less is well tolerated. Based on these results we conclude that rh-TSH augmented ¹³¹I therapy is a promising new therapeutic principle allowing the tailoring of an optimal ¹³¹I therapy on the individual level.