Alan P. Farwell

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.

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.

Nongenomic actions of thyroid hormone during fetal brain development

Purpose of reviewThyroid hormone has long been identified as an essential regulatory factor in the brain developmental program. Although transcriptional regulation is the traditional mechanism of thyroid hormone action, and multiple genes have been identified that are altered in response to thyroid hormone, the demonstration of developmentally important T3-regulated genes has been elusive. In fact, the lack of abnormal brain development in mice lacking all known thyroid hormone receptors suggests a role for actions independent of thyroid hormone-thyroid hormone receptor binding. This review examines the role of nongenomic actions of thyroid hormone on brain development. Recent findingsA possible role for unliganded thyroid hormone receptors in brain development has been proposed as a result of the absence of a significant abnormal phenotype in thyroid hormone receptor knockout mice. Also, actions of thyroid hormone on the organization of the actin cytoskeleton, leading to thyroid hormone-dependent regulation of neuronal migration, neuronal process formation, and deposition of the neuronal guidance molecule laminin on the astrocyte surface, has recently been reported. These two topics are discussed in detail. SummaryAlthough regulated gene expression, either due to thyroid hormone-thyroid hormone receptor binding or via the unliganded thyroid hormone receptor, plays a role in thyroid hormone-dependent brain development, it is clear that other nongenomic actions also participate in the brain developmental program. The regulation of cytoskeletal organization leading to altered interactions between astrocytes, laminin, and neurons during development likely plays a major role in neuronal migration, neuronal process outgrowth, and the establishment of the complex wiring system of the brain.

Schmidt'S syndrome and severe hyponatremia: report of an unusual case and review of the related literature.

OBJECTIVE To describe a rare case of profound hyponatremia in a male patient with autoimmune polyglandular syndrome type 2 (Schmidts syndrome). METHODS We present the clinical and laboratory data in our patient and review the related published reports from the English language literature on the association of hyponatremia with Schmidts syndrome. RESULTS A 31-year-old man presented to the emergency department because of nausea, anorexia, and weakness for 6 days. He was found to have severe hyponatremia (serum sodium concentration, 101 mEq/L) and mild hyperkalemia. Endocrine testing revealed the presence of Addisons disease and severe primary hypothyroidism, consistent with Schmidts syndrome. The patient responded to treatment with volume and hormone replacement. An extensive literature search disclosed only one previously reported case (of a female patient) in which Schmidts syndrome led to the development of a degree of hyponatremia as severe as that in our patient. CONCLUSION Concomitant occurrence of primary adrenal insufficiency and primary hypothyroidism can result in a greater degree of hyponatremia than would be expected from either disease alone. Likely explanations include the additive effects of primary hypothyroidism and adrenal failure in the development of hyponatremia and, possibly, in some patients exquisite renal sensitivity to hemodynamic changes and altered hormonal status.

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.

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.

Sick Euthyroid Syndrome

Critical illness causes multiple alterations in thyroid hormone concentrations in patients who have no intrinsic thyroid disease. These effects are nonspecific, and they relate to the severity of illness. Because a wide variety of illnesses tend to result in the same changes in serum thyroid hormone levels, such alterations in thyroid hormone indexes has been termed the sick euthyroid syndrome. These changes are rarely isolated, and they are often associated with alterations in other endocrine systems. Similar changes in endocrine function has been shown experimentally by administration of cytokines from the interleukin and interferon families, as well as tumor necrosis factor-α. Thus, the sick euthyroid syndrome should not be viewed as an isolated pathological event, but as part of a coordinated systemic reaction to illness that involves both the immune and the endocrine systems. Recovery from the illness usually results in resolution of the alterations in thyroid hormone parameters. Supplemental thyroid hormone therapy in patients with the sick euthyroid syndrome is of no benefit and is not indicated.

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

Thyroid Function Testing in Ambulatory Practice

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.

Effect of methyl iodide on deiodinase activity

Thyroid function tests are commonly obtained by both primary care physicians and various specialists in ambulatory practice for both the evaluation of symptomatic and screening assessment of asymptomatic thyroid disease. Abnormalities of thyroid function testing, including those which may not be clinically apparent, are common in the general population. Epidemiological studies have identified hypothyroidism (subclinical and overt) in 4.6–9.5% and hyperthyroidism (subclinical and overt) in 1.3–2.2% of individuals [1], while the incidence of mild/subclinical dysfunction in certain populations is much more common [2–4].