An Online Survey of Hypothyroid Patients Demonstrates Prominent Dissatisfaction.

BACKGROUND: Approximately 15% more patients taking levothyroxine (LT4) report impaired quality of life compared to controls. This could be explained by additional diagnoses independently affecting quality of life and complicating assignment of causation. This study sought to investigate the underpinnings of reduced quality of life in hypothyroid patients and to provide data for discussion at a symposium addressing hypothyroidism. METHODS: An online survey for hypothyroid patients was posted on the American Thyroid Association Web site and forwarded to multiple groups. Respondents were asked to rank satisfaction with their treatment for hypothyroidism and their treating physician. They also ranked their perception regarding physician knowledge about hypothyroidism treatments, need for new treatments, and life impact of hypothyroidism on a scale of 1-10. Respondents reported the therapy they were taking, categorized as LT4, LT4 and liothyronine (LT4 + LT3), or desiccated thyroid extract (DTE). They also reported sex, age, cause of hypothyroidism, duration of treatment, additional diagnoses, and prevalence of symptoms. RESULTS: A total of 12,146 individuals completed the survey. The overall degree of satisfaction was 5 (interquartile range [IQR] = 3-8). Among respondents without self-reported depression, stressors, or medical conditions (n = 3670), individuals taking DTE reported a higher median treatment satisfaction of 7 (IQR = 5-9) compared to other treatments. At the same time, the LT4 treatment group exhibited the lowest satisfaction of 5 (IQR = 3-7), and for the LT4 + LT3 treatment group, satisfaction was 6 (IQR = 3-8). Respondents taking DTE were also less likely to report problems with weight management, fatigue/energy levels, mood, and memory compared to those taking LT4 or LT4 + LT3. CONCLUSIONS: A subset of patients with hypothyroidism are not satisfied with their current therapy or their physicians. Higher satisfaction with both treatment and physicians is reported by those patients on DTE. While the study design does not provide a mechanistic explanation for this observation, future studies should investigate whether preference for DTE is related to triiodothyronine levels or other unidentified causes.

OPEN ACCESS TO DIABETES CENTER FROM THE EMERGENCY DEPARTMENT REDUCES HOSPITALIZATIONS IN THE SUSEQUENT YEAR.

OBJECTIVE: Patients who present to the emergency department (ED) for diabetes without hyperglycemic crisis are at risk of unnecessary hospitalizations and poor outcomes. To address this, the ED Diabetes Rapid-referral Program (EDRP) was designed to provide ED staff with direct booking into the diabetes center. The objective of this study was to determine the effects of the EDRP on hospitalization rate, ED utilization rate, glycemic control, and expenditures. METHODS: We conducted a single-center analysis of the EDRP cohort (n = 420) and compared 1-year outcomes to historic controls (n = 791). We also compared EDRP patients who arrived (ARR) to those who did not show (NS). The primary outcome was hospitalization rate over 1 year. Secondary outcomes included ED recidivism rate, hemoglobin A1c (HbA1c), and healthcare expenditures. RESULTS: Compared with controls, the EDRP cohort was less likely to be hospitalized (27.1% vs. 41.5%, P<.001) or return to the ED (52.2% vs. 62.3%, P = .001) at the end of 1 year. Total hospitalizations were also lower in the EDRP (157 ± 19 vs. 267 ± 18 per 1,000 persons per year, P<.001). The EDRP cohort had a greater reduction in HbA1c (-2.66 vs. -2.01%, P<.001), which was more pronounced when ARR patients were compared with NS (-2.71% vs. -1.37%, P<.05). The mean per patient institutional healthcare expenditures were lower by $5,461 compared with controls. CONCLUSION: Eliminating barriers to scheduling diabetes-focused ambulatory care for ED patients was associated with significant reductions in hospitalization rate, ED recidivism rate, HbA1c, and healthcare expenditures in the subsequent year. ABBREVIATIONS: ARR = arrived ED = emergency department EDRP = emergency department diabetes rapid-referral Program HbA1c = hemoglobin A1c NS = no show.

Euthyroid Sick Syndrome.

In this review, we discuss the characteristics, pathophysiology, and therapeutic implications of the euthyroid sick syndrome. Multiple mechanisms have been identified to contribute to the development of euthyroid sick syndrome, including alterations in the iodothyronine deiodinases, thyroid-stimulating hormone secretion, thyroid hormone binding to plasma protein, transport of thyroid hormone in peripheral tissues, and thyroid hormone receptor activity. The euthyroid sick syndrome appears to be a complex mix of physiologic adaptation and pathologic response to acute illness. The underlying cause for these alterations has not yet been elucidated. Treatment of the euthyroid sick syndrome with thyroid hormone to restore normal serum thyroid hormone levels in an effort to improve disease prognosis and outcomes continues to be a focus of many clinical studies, although currently available data do not provide evidence of a clear benefit of treatment.

Nonthyroidal illness syndrome.

PURPOSE OF REVIEW: The current state of the pathophysiology, diagnosis, and therapeutic implications of the nonthyroidal illness syndrome is reviewed. RECENT FINDINGS: Previous studies attributed the development of the nonthyroidal illness syndrome to alterations in three main areas of thyroid hormone metabolism: deiodinase activity, thyroid-stimulating hormone secretion, and hormone binding to serum proteins. New studies suggest that alterations in thyroid hormone transport into tissues and alterations of the nuclear thyroid hormone receptors may also play a role. Therapy of the nonthyroidal illness syndrome remains a controversial topic. SUMMARY: Multiple factors lead to the development of the nonthyroidal illness syndrome, including alterations in type 1 and 3 deiodinase activity, thyrotropin-releasing hormone and thyroid-stimulating hormone secretion, hormone binding to plasma proteins, thyroid hormone transporter expression and activity, and the thyroid hormone nuclear receptor complex. These data show that acute and chronic illness affect all aspects of thyroid hormone metabolism and action. Some of these changes are physiologic and some are pharmacologic. The mediators of these alterations are still largely unclear. There continues to be no indication for thyroid hormone therapy in the vast majority of patients with the nonthyroidal illness syndrome, although interesting data suggest a possible role for treating a small subset of patients.

Thyrotoxicosis with post-treatment hypothyroidism in a patient with acute suppurative thyroiditis due to porphyromonas.

BACKGROUND: Acute suppurative thyroiditis (AST) is a rare, life-threatening thyroid infection characterized by a tender neck mass and fever. As these features are shared with self-limited subacute thyroiditis (SAT), it is important to differentiate between the two disorders. PATIENT FINDINGS: We report a case of AST in a 21-year-old woman who presented with steadily worsening throat pain for 3 weeks, a tender left neck mass, and thyrotoxicosis. She was initially given prednisone for treatment of presumed SAT but then it acutely worsened. Fine needle aspiration yielded pus on gross examination, and she required intubation and emergent surgical drainage to maintain her airway. Culture of the abscess isolated Streptococcus F and Porphyromonas, a gram-negative intracellular anaerobe not previously reported to cause AST. She improved quickly after surgery, developed transient hypothyroidism that did not require treatment with thyroid hormone, and is currently euthyroid. An abnormal piriform sinus fistula was identified on the left using an esophagram. SUMMARY: AST may be difficult to clinically differentiate from SAT. Fine needle aspiration revealing pus, culture yielding bacteria or fungi, abscess on ultrasonography and computed tomography, and left-sided predominance are important in the diagnosis of AST. CONCLUSIONS: AST should be considered in any patient with SAT who does not rapidly improve following institution of steroids. Further, the presence of thyrotoxicosis does not eliminate AST as an initial diagnosis.

Effect of methyl iodide on deiodinase activity.

Methyl iodide (MeI) has been proposed as an alternative for methyl bromide in pre-plant soil fumigation applications that does not affect stratospheric ozone. Preliminary studies in rabbits noted fetal resorptions if the pregnant does were exposed to MeI during a critical period during gestation. In addition, abnormalities in thyroid hormone parameters were also observed in animals exposed to MeI. Since monodeiodination is the major metabolic pathway of the thyroid hormones, we examined the effect of MeI on deiodinase activity as a possible etiology for the alteration in thyroid hormone parameters and ultimate fetal demise. In vitro studies using tissue microsomes and cell culture showed that MeI has no effect on type I 5'-deiodinase (D1) or type II 5'-deiodinase (D2) at physiologically relevant concentrations. At high concentrations (>10 mM,>10,000 ppm), MeI caused a nonspecific inactivation of D1 and D2. Analysis of D1 and D2 activity in rats exposed by inhalation to increasing concentrations of MeI showed a significant decrease in enzyme activity at 100 ppm, while brain type III 5'-deiodinase (D3) was unaffected by MeI at the exposures studied. While the drop in D1 can be explained by the induction of a hypothyroid state in the exposed rats, there is no clear explanation for the fall in D2 levels. In the rabbit studies, there was a significant decrease in kidney D1 in the adult rabbits exposed to 20 ppm MeI. However, there was no effect on liver D1, brain D2, or placental D3 in the MeI-exposed rabbits. Similarly, there was no effect of MeI on fetal D1 or D2 activity. The lack of a significant direct effect of MeI on deiodinase activity and the absence of a change in placental or fetal deiodinase activity make it unlikely that alterations in deiodinase activity plays a role in the fetal resorptions in the MeI-exposed rabbits.

Dynamic nongenomic actions of thyroid hormone in the developing rat brain.

Two well-characterized nongenomic actions of thyroid hormone in cultured brain tissues are: 1) regulation of type 2 iodothyronine 5'deiodinase (D2) activity and 2) regulation of actin polymerization. In particular, the latter is likely to have profound effects on neuronal migration in the developing brain. In this study, we determined whether these nongenomic actions also occurred in vivo during brain development. Neonatal hypothyroidism was induced by propylthiouracil given to pregnant dams beginning on d17 of gestation and continued throughout the neonatal period. On postnatal d 14, rats were injected with either cold or [(125)I]-labeled iodothyronines and killed sequentially after injection. In contrast to reports in the adult rat, all three iodothyronines readily and equally entered developing brain tissues. As expected, cerebrocortical D2 activity was markedly elevated in the hypothyroid brain and both reverse T(3) (rT(3)) and T(4) rapidly decreased D2 to euthyroid levels within 3 h. Furthermore, cerebellar G-actin content in the hypothyroid rat was approximately 5-fold higher than in the euthyroid rat. Again, both rT(3) and T(4) rapidly decreased the G-actin content by approximately 50%, with a reciprocal increase in F-actin content to euthyroid levels without altering total actin. Neither T(3) nor vehicle had any effect on D2 activity in the cortex or G- or F-actin content in the cerebellum. The thyroid hormone-dependent regulation of actin polymerization in the rat brain provides a mechanism by which this morphogenic hormone can influence neuronal migration independent of the need for altered gene transcription. Furthermore, these data suggest a prominent role for rT(3) during brain development.

Regulation of cerebellar neuronal migration and neurite outgrowth by thyroxine and 3,3',5'-triiodothyronine.

The timing of granule cell migration in the developing cerebellum is regulated by thyroid hormone. Granule cell migration depends on the recognition of extracellular neuronal guidance molecule(s), such as laminin, and this, in turn, requires cell surface adhesion molecules (integrins) that are anchored on the cell membrane by the actin cytoskeleton. While many of the actions of thyroid hormone, specifically 3,5,3'-triiodothyronine (T3), are mediated by regulated gene expression, both thyroxine (T4) and 3,3',5'-triiodothyronine (rT3) also exert direct, positive control of the quantity of polymerized actin in cultured astrocytes without affecting gene expression. T4-dependent actin polymerization has been shown to (i) participate in the immobilization of laminin to the cell surface, (ii) help deposit laminin in the molecular layer of the developing cerebellum, and (iii) anchor integrin(s) that recognize laminin present in the extracellular matrix. In this study, we show that both T4 and rT3, but not T3, directly regulate the F-actin content of elongating neurites of cerebellar neurons. T4 and rT3 also promoted extensive granule cell migration from cerebellar explants, as well as, dense cell clustering and extensive neuronal process formation when granule cells were grown on a laminin-coated surface. Both granule cell migration and neuronal process outgrowth were markedly attenuated by the addition of integrin-blocking antibodies or binding peptides, by the absence of thyroid hormone or the presence of T3. These data suggest that the T4-dependent actin polymerization in developing neurons is necessary for these migrating cells to recognize the laminin guidance molecule, thereby providing a novel molecular mechanism for the profound influence of thyroid hormone on brain development that is independent of regulated gene expression.