Torquil Watt

Background: Considering the high prevalence of benign thyroid disorders, the availability of an instrument measuring health-related quality of life (HRQoL) in this population is very important. Objectives: The current study aims to translate and validate the Persian version of the ThyPRO-39. Methods: In accordance with standard methodology, a double forward, reconciliation, and backward translation of the questionnaire was conducted. A field consultant identified discrepancies between the original questionnaire and the back translation. Discrepancies were addressed, revised, and retested before submitting it for developer review. Finally, five cognitive interviews were conducted among patients with benign thyroid problems to ensure alignment between their understanding of the Persian items and their original English counterparts. Results: Translation and linguistic validations of the Persian version of the ThyPRO-39 Questionnaire were developed according to the established rules. Two translators did the forward translation with no significant disagreement. Considering backward translation, the field consultant changed eight items, and the developer provided seven additional comments. After interviewing five patients, nine revisions were performed by the field consultant. Finally, an external consultant reviewed all changes and approved the questionnaire. Conclusions: We translated and linguistically validated the Persian version of the ThyPRO-39. Now, the ThyPRO-IR is ready for assessment of thyroid-specific QoL in Iranian patients with benign thyroid disorders.

Purpose: Autonomic nervous system dysfunction (ANSD), for which presently no treatment exists, has a negative impact on prognosis in people with type 2 diabetes (T2D). Periosteal pressure sensitivity (PPS) on sternum may be a measure of autonomic nervous system dysfunction (ANSD). We tested if a non-pharmacological PPS-feedback-guided treatment program based on non-noxious sensory nerve stimulation, known to reduce PPS, changed empowerment, treatment satisfaction, and quality of life in people with T2D, compared to usual treatment. Patients and Methods: Analysis of secondary endpoints in a single center, two-armed, parallel-group, observer-blinded, randomized controlled trial of individuals with T2D. Participants were randomized to non-pharmacological intervention as an add-on to treatment as usual. Endpoints were evaluated by five validated questionnaires: Diabetes specific Empowerment (DES-SF), Diabetes Treatment Satisfaction (DTSQ), quality of life (QOL) (WHO-5), clinical stress signs (CSS), and self-reported health (SF-36). Sample size calculation was based on the primary endpoint HbA1c. Results: We included 144 participants, 71 allocated to active intervention and 73 to the control group. Active intervention compared to control revealed improved diabetes-specific empowerment (p = 0.004), DTSQ (p = 0.001), and SF-36 self-reported health (p=0.003) and tended to improve quality of life (WHO-5) (p = 0.056). The findings were clinically relevant with a Cohen’s effect size of 0.5 to 0.7. Conclusion: This non-pharmacological intervention, aiming to reduce PPS, and thus ANSD, improved diabetes-specific empowerment, treatment satisfaction, and self-reported health when compared to usual treatment. The proposed intervention may be a supplement to conventional treatment for T2D.

Purpose: Studies have suggested improved metabolic profiles in patients with adrenal insufficiency treated with dual-release hydrocortisone (DR-HC) compared with conventional hydrocortisone (C-HC). This study investigates the effect of DR-HC compared with C-HC treatment on five health variables: diurnal salivary cortisol/cortisone, body composition, bone health, glucose metabolism, lipids, and blood pressure. Methods: Prospective study of 27 participants (24 men) with secondary adrenal insufficiency with measurements during stable C-HC and 16 weeks after treatment switch to DR-HC. Outcomes: Diurnal salivary-cortisol/cortisone, body composition assessed by Dual-Energy X-ray absorptiometry scan, bone status indices (serum type I N-terminal procollagen [PINP], collagen type I cross-linked C-telopeptide [CTX], osteocalcin, receptor activator kappa-B [RANK] ligand, osteoprotegerin, and sclerostin), lipids, haemoglobin A_1c (HbA_1c), and 24-hour blood pressure. Results: After the switch to DR-HC, the diurnal salivary-cortisol area under the curve (AUC) decreased non-significantly (mean difference: −55.9 nmol/L/day, P = 0.06). The salivary-cortisone-AUC was unchanged. Late-evening salivary-cortisol and cortisone were lower (−1.6 and −1.7 nmol/L, P = 0.002 and 0.004). Total and abdominal fat mass (−1.5 and −0.5 kg, P = 0.003 and 0.02), HbA_1c (−1.2 mmol/mol, P = 0.02), and osteocalcin decreased (−7.0 µg/L, P = 0.03) whereas sclerostin increased (+41.1 pg/mL, P = 0.0001). The remaining bone status indices, lipids, and blood pressure were unchanged. Conclusion: This study suggests that switching to DR-HC leads to lower late-evening cortisol/cortisone exposure and a more favourable metabolic profile and body composition. In contrast, decreased osteocalcin with increasing sclerostin might indicate a negative impact on bones. Clinical trial registration: EudraCT201400203932

Objective Treatment options in Graves’ disease are limited, do not target the underlying autoimmunity, and relapse rates following a course of anti-thyroid drug reach 50%. Previous research has shown promising results for a role for vitamin D in Graves’ disease. We aimed to investigate whether vitamin D reduces failure to enter and sustain remission in patients with Graves’ disease treated with anti-thyroid drug. Design A multicenter, double-blinded, randomized, placebo-controlled trial comparing Vitamin D 70 mcg once daily (2800 IU) or placebo. The intervention was given first as add-on to anti-thyroid drug treatment, maximally 24 months, and then for 12 months after anti-thyroid drug cessation. Inclusion 2015 to 2017 and study completion December 2020. Patients included were adults with a first-time diagnosis of Graves’ disease treated with anti-thyroid drug. Exclusion criteria included pregnancy and glucocorticoid treatment. The primary endpoint was failure to enter and sustain remission defined as relapse of hyperthyroidism within 12 months after anti-thyroid drug cessation, inability to stop anti-thyroid drug within 24 months, or radioiodine treatment or thyroidectomy. Two-hundred-seventy-eight patients were included, four withdrew consent. No adverse effects. Results Participants were 44±14 years at enrollment and 79% were female. The risk of failure to enter and sustain remission was 42% (95% confidence interval [CI], 33% to 50%) in the vitamin D group and 32% (24% to 40%) in the placebo group corresponding to a relative risk (RR) of 1.30 (95% CI, 0.95 to 1.78). Conclusions Vitamin D supplementation did not improve the treatment of Graves’ disease in patients with a normal or insufficient vitamin D status. Thus, supplementation with high-dose vitamin D cannot be recommended for Graves’ disease.

Background: Subjects receiving levothyroxine (LT4) treatment have increased prevalence of depression, anxiety, and antidepressant use, but whether the underlying mechanism relates to thyroid autoimmunity is still unclarified. Methods: This is a population-based longitudinal study. Baseline biochemical and questionnaire data from the Danish General Suburban Population Study (GESUS) in 2010-2013 were linked with individual-level longitudinal data in national health registries. The aim was to investigate the associations between thyroid peroxidase antibodies (TPOAbs) and LT4 treatment, separately and through interaction, and at least one redeemed prescription for antidepressants. Logistic and Cox regression were used to evaluate initiation of antidepressant use before and after the baseline examination in GESUS, respectively. All exposures and covariates were fixed at the date of baseline examination. Thyroid autoimmunity was defined as serum TPOAbs >60 U/mL. Adjustments included sex, age, education, income, Charlson comorbidity index, smoking, and alcohol. Sensitivity analyses were performed for missing variables, exclusion of lithium use, exclusion of thyroid surgery, and conservative definitions for LT4 treatment and antidepressant use requiring at least two prescriptions. Results: We included 12,894 individuals, of whom 2353 (18%) had “past or current” antidepressant use at baseline, leaving 10,541 individuals at risk for incident antidepressant use after baseline. The median follow-up was 7.8 years during which 783 individuals (7.4% of 10,541 individuals) had incident antidepressant use. TPOAb positivity was not associated with “past or current” (odds ratio [OR] 0.90 [confidence interval, CI 0.78–1.03], p = 0.13) nor incident antidepressant use (hazard ratio [HR] 1.02 [CI 0.83–1.25], p = 0.88). LT4 treatment was associated with increased “past or current” antidepressant use (OR 1.33 [CI 1.10–1.62], p = 0.004) and increased incident antidepressant use (HR 1.38 [CI 1.03–1.85], p = 0.03). There were no interactions between the effects of TPOAb positivity and LT4 treatment on the use of antidepressants in logistic ( p = 0.87) or Cox regression models ( p = 0.82). Sensitivity analyses were robust, except that incident use of at least two redeemed antidepressant prescriptions was not statistically significant. Conclusions: LT4 treatment, but not TPOAb positivity, was associated with increased prevalent or incident antidepressant use with at least one prescription. Our findings do not support that thyroid autoimmunity is an important factor for antidepressant use in patients receiving LT4 treatment.

Patient-reported outcomes (PROs) are increasingly used in clinical practice to improve clinical care. Multiple studies show that systematic use of PROs can enhance communication with patients and improve patient satisfaction, symptom management and quality of life. Further, such data can be aggregated to examine health levels for patient groups, improve quality of care, and compare patient outcomes at the institutional, regional or national level. However, there are barriers and challenges that should be handled appropriately to achieve successful implementation of PROs in routine clinical practice. This paper briefly overviews thyroid-related PROs, describes unsolved quality of life issues in benign thyroid diseases, provides examples of routine collection of PROs, and summarizes key points facilitating successful implementation of thyroid-related PROs in routine clinical practice. Finally, the paper touches upon future directions of PRO research.

Background: Evidence of the efficacy of laser thermal ablation (LTA) in benign thyroid nodules is abundant. However, little is known about the effect on quality of life (QoL) of this treatment. Methods: Prospective cohort study investigating the effect of LTA before, three, and six months after LTA on QoL using the thyroid-specific patient-reported outcome (ThyPRO) measure. Patients receiving LTA (laser group [LG]) was compared with a well-characterized control group (CG) from the Danish civil registry. Results: The LG comprised 54 patients, with no age or sex differences compared with the CG ( n = 739). Sixty-nine percent of the patients had a recurrent cystic thyroid nodule, 6% had a solid nodule, while the remaining 25% were of mixed character. The median nodule volume was 6.8 mL (interquartile range [IQR]: 4.0–11.1) before LTA, and 1.8 mL (IQR: 0.6–4.1) at 6 months post-LTA ( p < 0.001), corresponding to a median reduction of 78%. All cystic fluid (median: 6 mL; IQR: 2.0–9.0) was aspirated before LTA. Median treatment time was 400 seconds (IQR: 300–600), applying a median energy of 823 J (IQR: 600–1200). At baseline and according to the ThyPRO scales, the LG differed significantly from the CG by having more goiter symptoms, hyperthyroid symptoms, tiredness, and cognitive complaints ( p < 0.05 for all variables), but only the difference in the goiter symptom scale was of a clinically important magnitude. At three months, the LG experienced a large improvement in goiter symptoms (effect size [ES] = 1.05), a moderate improvement in cosmetic complaints (ES = 0.50), and a moderate improvement in the overall QoL (ES = 0.64). Only the improvements in the goiter symptom and the cosmetic complaint scales were clinically important. Six months after LTA, the anxiety scale showed further improvement of moderate size (ES = 0.52). At 6 months, the results above were maintained, and 79% of patients experienced a large and clinically important improvement in the goiter symptom scale and no clinically important differences were found between the LG and the CG. Conclusions: In this unblinded, prospective observational study, measures of disease-specific QoL were significantly improved compared with preprocedure levels, in patients with solid-cystic nodules.

Objective: The aim of the present study was to investigate the differences in quality of life (QOL) following complete or partial thyroidectomy and with regard to thyroid hormone replacement (LT4) therapy.Study Design: Patients who underwent thyroidectomy were asked to complete the validated thyroid‐specific ThyPRO QOL questionnaire at least 6 months following surgery.Setting: Tertiary medical center.Methods: Thyroid specific QOL questionnaire analysis.Results: A total of 190 patients completed the ThyPRO questionnaire. Of them 89 patients had complete thyroidectomy and 101 patients had unilateral thyroid lobectomy. The total thyroidectomy group had significantly worse overall QOL self‐assessment score than the lobectomy patients (p < 0.0001). Patients receiving LT4 therapy regardless of the extent of surgery, reported worse QOL compared to patients not receiving LT4.Conclusions: Quality of life following thyroid surgery is significantly related to hypothyroidism and the requirement for LT4 therapy, rather to the extent of surgery. The best QOL was reported in patients treated with lobectomy who did not require LT4 therapy.

Glucocorticoid-induced adrenal insufficiency is caused by exogenous glucocorticoid suppression of the hypothalamic-pituitary-adrenal axis and is the most prevalent form of adrenal insufficiency. The condition is important to diagnose given the risk of life-threatening adrenal crisis and impact on patients’ quality of life. The diagnosis is made with a stimulation test such as the ACTH test. Until now, testing for glucocorticoid-induced adrenal insufficiency has often been based on clinical suspicion rather than routinely but accumulating evidence indicates that a significant number of cases will remain unrecognized. During ongoing oral glucocorticoid treatment or initially after withdrawal, ~50% of patients have adrenal insufficiency, but, outside clinical studies, ≤ 1% of patients have adrenal testing recorded. More than 70% of cases are identified during acute hospital admission, where the diagnosis can easily be missed because symptoms of adrenal insufficiency are nonspecific and overlap those of the underlying and intercurrent conditions. Treatment of severe glucocorticoid-induced adrenal insufficiency should follow the principles for treatment of central adrenal insufficiency. The clinical implications and thus indication to treat mild-moderate adrenal deficiency after glucocorticoid withdrawal has not been established. Also, the indication of adding stress dosages of glucocorticoid during ongoing glucocorticoid treatment remains unclear. In patients with established glucocorticoid-induced adrenal insufficiency, high rates of poor confidence in self-management and delayed glucocorticoid administration in the acute setting with an imminent adrenal crisis call for improved awareness and education of clinicians and patients. This article reviews different facets of glucocorticoid-induced adrenal insufficiency and discusses approaches to the condition in common clinical situations.