The direct and indirect economic burden of hypothyroidism in the United States: a retrospective claims database study.

OBJECTIVE: To examine direct and indirect economic burden associated with hypothyroidism in the United States. METHODS: Medical costs attributable to hypothyroidism were estimated for patients with hypothyroidism. Non-hypothyroid (euthyroid) controls were matched to patients with hypothyroidism based upon patient characteristics and availability of productivity data. Multivariable analyses examined resource utilization, annual medical costs, comorbidities, and productivity costs. RESULTS: Estimates of hypothyroidism-related total medical costs ranged from $460 to $2,555 per patient per year. Compared to euthyroid controls, patients with hypothyroidism had significantly higher all-cause medical costs and medical resource utilization. For the subset of patients with available productivity data, hypothyroidism was associated with significantly higher absenteeism and long- and short-term disability costs but significantly lower worker's compensation costs. CONCLUSIONS: Hypothyroidism is associated with significant direct and indirect economic burden among employed, commercially insured patients in the US. Clinical Significance: Despite the availability of relatively inexpensive generic therapies for hypothyroidism, this study found significant direct and indirect costs associated with the condition. The large number of patients diagnosed with hypothyroidism combined with increased costs associated with hypothyroidism result in a significant burden for patients, payers, and employers.

Effect of Levothyroxine on Kidney Function in Chronic Kidney Disease with Subclinical Hypothyroidism in US Veterans: A Retrospective Observational Cohort Study.

INTRODUCTION: Chronic kidney disease (CKD) may be associated with overt or subclinical hypothyroidism [SCH; defined as elevated serum thyroid-stimulating hormone (TSH) despite normal free thyroxine levels). Although some studies have demonstrated that thyroid replacement therapy may improve renal function in overt hypothyroidism, there is no consensus on its benefits in SCH. Clinical and limited economic outcomes were evaluated in levothyroxine-treated US veterans with CKD + SCH. METHODS: Veterans Health Administration claims data from April 2013 to March 2018 for levothyroxine-treated versus nontreated CKD + SCH patients were compared. Eligible patients with CKD + SCH (≥ 2 elevated TSH values recorded; ≥ 2 normal thyroxine values recorded) had ≥ 1 TSH values recorded during 24-month follow-up, and ≥ 1 estimated glomerular filtration rate (eGFR) measurement during baseline and follow-up. Continuous levothyroxine use (treatment cohort) was required during follow-up. The primary endpoint was eGFR at 6, 12, 18, and 24 months; secondary endpoints included eGFR change from baseline, CKD progression, and length of hospital stay (LOS). Propensity score matching (PSM) was performed. RESULTS: Of 453 eligible patients, 157 remained in each cohort after PSM. Most were male (96%) and white (88%); mean age was 75 years. No significant differences were observed between cohorts at any time point for eGFR, eGFR change from baseline, or CKD progression. Treated patients had numerically higher mean eGFR at 6 and 12 months, lower proportions of progression to higher CKD stages at 12, 18, and 24 months, and shorter mean all-cause LOS versus nontreated patients (1.92 vs. 3.30 days; P = 0.3483) within the 24-month follow-up period. A significantly shorter mean CKD-related LOS was observed versus nontreated patients (0.11 vs. 1.38 days; P < 0.0001) during the 24-month follow-up. CONCLUSION: Levothyroxine use was associated with economic and clinical benefit in some patients with CKD + SCH, despite an absence of overall benefit on eGFR; confirmatory research is needed.

The association between adherence to levothyroxine and economic and clinical outcomes in patients with hypothyroidism in the US.

OBJECTIVE: To evaluate outcomes associated with adherence to levothyroxine (LT4) in the US adult hypothyroidism population. METHODS: We used data from Truven's MarketScan databases from 1 July 2011 through 31 December 2015. Patients aged 18 or older were diagnosed with hypothyroidism (confirmed at least twice) and prescribed LT4. Patients were excluded if they did not have continuous insurance coverage or if they received a diagnosis of thyroid cancer or pregnancy during the study period. Multivariable analyses on a matched cohort of adherent and nonadherent patients examined the relationships among patient outcomes and adherence, defined as the proportion of days covered ≥80%. Outcomes included all-cause and hypothyroidism-related medical costs and resource utilization and comorbid diagnoses measured over the 1 year post-period following the first prescription for LT4. The analyses controlled for patient age, sex, region of residence, type of insurance coverage, diagnosing physician and pre-period general health status as proxied by the Charlson Comorbidity Index. RESULTS: Prior to matching, there were 168,457 patients identified as adherent and 198,443 patients identified as nonadherent. The matched cohort consisted of 318,628 individuals, with equal numbers of adherent and nonadherent patients (n = 159,314). Patients who were adherent used significantly fewer resources and had significantly lower all-cause ($14,136 vs. $14,926; p < .0001) and hypothyroidism-related ($1672 vs. $1709; p < .0001) total costs, although the costs of drugs were higher in the adherent group. Furthermore, adherent patients, compared to nonadherent patients, were significantly less likely to be diagnosed with comorbid Addison's disease, bipolar disorder, chronic kidney disease, depression, migraine, obesity, type 1 diabetes or type 2 diabetes during the follow-up period. CONCLUSIONS: Compared to nonadherence, adherence to LT4 among patients with hypothyroidism was associated with a significant reduction in all-cause and hypothyroidism-related costs and resource utilization as well as significantly lower rates of many comorbid diagnoses.

Cushing's syndrome with no clinical stigmata - a variant of glucocorticoid resistance syndrome.

BACKGROUND: Cortisol resistance syndrome is a very rare condition characterized by high cortisol levels, but without any clinical features of Cushing's syndrome. Our objective is to present such a case. CASE PRESENTATION: A 41 year old female presented with mild hirsutism and elevated urinary cortisol levels. Plasma cortisol levels were elevated and were not suppressed by conventional doses of dexamethasone on multiple occasions, but decreased following administration of higher doses of dexamethasone. Adrenocorticotropic hormone (ACTH) levels were inappropriately elevated. Despite significantly elevated cortisol levels, she did not develop any clinical signs or symptoms of Cushing's syndrome. Pituitary and adrenal imaging did not reveal any abnormalities. Genetic testing for human glucocorticoid receptor did not reveal any mutations. CONCLUSIONS: Although we were not able to identify any new mutations, we believe that our patient has a variant of cortisol resistance syndrome. This syndrome should be considered in the differential diagnosis of patients who present with high levels of cortisol but have no clinical features of Cushing's syndrome.

Update on diabetes diagnosis: a historical review of the dilemma of the diagnostic utility of glycohemoglobin A1c and a proposal for a combined glucose-A1c diagnostic method.

The role of glycohemoglobin A1c (A1c) for the diagnosis of diabetes has been debated for over three decades. Recently, the American Diabetes Association (ADA) has recommended adding A1c as an additional criterion for diabetes diagnosis. In view of the continued debate about the diagnostic utility of A1c, and in view of the unabated burden of undiagnosed diabetes, the search for alternative diagnostic methods is discussed. A historical literature review is provided, in view of the new ADA diagnostic guidelines, and a proposal is provided for combining A1c and a glucose measurement as a diagnostic alternative/adjunct to the use of a single criterion. This proposal is based on the non-overlapping of the advantages and disadvantages of these individual tests. The cost-effectiveness of this method remains to be tested.

Peripheral microvascular response to muscle contraction is unaltered by early diabetes but decreases with age.

Long-term or untreated diabetes leads to micro- and macrovascular complications. However, there are few tests to evaluate microvascular function. A postcontraction blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) technique was exploited to measure peripheral microvascular function in diabetics and healthy controls matched with respect to age, body mass index, and physical activity. Postcontraction BOLD microvascular response was measured following 1-s maximal isometric ankle dorsiflexion in individuals with diabetes mellitus type I [DMI, n = 15, age 33 ± 3 yr (means ± SE), median diabetes duration = 5.5 yr] and type II (DMII, n = 16, age 45 ± 2 yr, median duration = 2.4 yr); responses were compared with controls (CONI and CONII). Peripheral macrovascular function of the popliteal and tibial arteries was assessed during exercise hyperemia with phase contrast magnetic resonance angiography following repetitive exercise. There were no group differences as a result of diabetes in peripheral microvascular function (peak BOLD response: DMI = 2.04 ± 0.38% vs. CONI = 2.08 ± 0.48%; DMII = 0.93 ± 0.24% vs. CONII = 1.13 ± 0.24%; mean ± SE), but the BOLD response was significantly influenced by age (partial r = -0.384, P = 0.003), supporting its sensitivity as a measure of microvascular function. Eleven individuals had no microvascular BOLD response, including three diabetics with neuropathy and four controls with a family history of diabetes. There were no differences in peripheral macrovascular function between groups when assessing exercise hyperemia or the pulsitility and resistive indexes. Although the BOLD microvascular response was not impaired in early diabetes, these results encourage further investigation of muscle BOLD as it relates to peripheral microvascular health.

Severe hypercalcemia and acute renal failure: an unusual presentation of sarcoidosis.

Although hypercalcemia is a known metabolic complication of sarcoidosis, it is rarely a presenting manifestation. Long-standing hypercalcemia and hypercalciuria can cause nephrocalcinosis and chronic renal failure. Acute renal failure, although described, is also a rare presentation of patients with sarcoidosis. We describe two patients with sarcoidosis, who presented with severe hypercalcemia and worsening renal function. Parathyroid hormone levels were appropriately suppressed. This led to an extensive search for the cause of hypercalcemia. Finally, after a lymph node biopsy in both cases, a diagnosis of sarcoidosis was established, hypercalcemia resolved, and renal function improved in both cases after administration of prednisone.

Evaluation of control of diabetes mellitus in a subspecialty clinic.

OBJECTIVE: To determine whether patients with diabetes under follow-up surveillance in a subspecialty clinic are receiving care that meets the guidelines recommended by the American Diabetes Association and American Association of Clinical Endocrinologists. METHODS: We abstracted 2 years of medical records of patients sampled from 2 academic diabetes clinics, managed by board-certified endocrinologists. Information regarding the testing for and results of hemoglobin A1c (A1C), lipids, blood pressure, and microalbuminuria was recorded and analyzed. RESULTS: The data on 499 patients were analyzed. More than 90% of patients had the recommended A1C, lipid, and blood pressure testing. Approximately 25% of patients had A1C levels >7%, and about 14% had A1C levels >6.5%. Total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were at target in approximately 82%, 65%, and 68% of patients, respectively. Approximately 55% of male and 50% of female patients had high-density lipoprotein cholesterol levels at target. Blood pressure was controlled in approximately a third of the patients. Approximately 30% of patients tested had microalbuminuria. Only 6.8% of patients in year 1 and 3.5% of patients in year 2 had all these risk factors (A1C, lipids, and blood pressure) at target levels. CONCLUSION: The results indicate that in our subspecialty clinics, although testing for "risk factors" is being done at a high frequency, the targets for these risk factors are being met by only a limited number of patients. We believe that this result may be due to patient- or system-related factors but not due to physician knowledge. Therefore, emphasis should be placed on patient and system factors to improve the outcomes of the care of patients with diabetes.

Hypertension in Asian/Pacific Island Americans.

Asian/Pacific Islander Americans (APIAs) are the fastest growing population in the United States by percentage. Hypertension is common and increases cardiovascular risk to a great extent in this population. The medical problems of this group are being increasingly encountered by US physicians. Many gene mutations associated with hypertension are more common in Asians. The significance of these polymorphisms in the pathogenesis of hypertension in APIAs is unclear. The percentage of APIAs who are aware, treated, and controlled is small. There may be some differences in the responses to antihypertensive medications between APIAs and whites. The results of human studies on the effect of drinking of tea on blood pressure in different groups are conflicting. Cough associated with angiotensin-converting enzyme inhibitor therapy may be more common in APIAs than in whites. There is a need for more education of APIAs regarding hypertension and for more effective treatment of hypertension by the physicians caring for this population.

Hemoglobin A1c: past, present and future.

Hemoglobin A1c (HbA1c) has been used for decades to monitor the control of glycemia in diabetes. Although HbA1cis currently undergoing a reassessment, and major developments have been underway in recent years, HbA1c is not recommended at present for diabetes screening or diagnosis. The objective of this review is to summarize the recent developments and to review a potential diagnostic role for HbA1c. Implementation of changes in HbA1c results and units of measurements have been suggested for the purpose of test standardization. These include lower reference ranges (by about 1.5-2 points) and measurement units expressed in percentage (%), as mg/dL (mmol/L) or mmol/mol (or a combination of these units). In diabetes screening and diagnosis, the current diagnostic guidelines use measurement of plasma glucose either fasting or after glucose load. These diagnostic methods have shortcomings warranting a potential diagnostic role for HbA1c. While recent developments in HbA1c methodologies are acknowledged, it is not yet known which changes will be implemented, and how soon. Given the recent literature supporting HbA1c diagnostic abilities, and given the shortcomings of the current guidelines, it is possible that a diagnostic role for HbA1c may be considered in future practice guidelines, globally. Very recently, the first of such recommendations has been proposed by an expert panel, as announced by the US Endocrine Society.

Glycohemoglobin A1c: A promising screening tool in gestational diabetes mellitus.

CONTEXT: Current screening tests for gestational diabetes mellitus (GDM) are inconvenient. Therefore, alternative screening tests for GDM are desirable. The use of glycohemoglobin A1c (HbA1c) in screening for GDM remains controversial. AIM: We undertook this study to evaluate the utility of HbA1c in screening for GDM. SETTINGS AND DESIGN: Retrospective study in a tertiary teaching hospital. MATERIALS AND METHODS: Laboratory records were reviewed to identify pregnant women who underwent both oral glucose tolerance test (OGTT) and HbA1c measurements over a 16-months period. The association of OGTT with HbA1c was evaluated. STATISTICAL ANALYSIS USED: Data were collected using SPSS software. Comparisons of the means and calculations of sensitivities were performed. RESULTS: Of 145 eligible patients, 124 had GDM and 21 patients did not, per OGTT. The percentages of patients with HbA1c values (reference range of 4.8%-6.0%) equal to or above sequential cut-point values of 5.0%, 5.5%, 6.0%, 6.5% and 7.0% (i.e., sensitivity values) were 100%, 98.4%, 87.1%, 62.9% and 39.5%, respectively. The mean HbA1c of the patients with GDM was 6.9 + 0.8% compared to 6.4 + 0.6% for those without GDM (P< 0.006). At an arbitrary cut-off value of 6.0% (the upper limit of normal), HbA1c would have picked up 87.1% of patients with GDM. CONCLUSIONS: This study suggests that HbA1c is a reasonably sensitive screening measure of GDM in this high-risk population. Acknowledging limitations resulting from the study design, further prospective studies are warranted to verify this conclusion, and to evaluate the specificity of HbA1c as a screening test for GDM.

Hypothyroidism: mimicker of common complaints.

Hypothyroidism is a common condition presenting a challenge to emergency physicians in diagnosing the underlying etiology of vague complaints. Making the diagnosis of a critically ill patient in myxedema coma allows early treatment with appropriate thyroid hormone replacement and avoids higher patient mortality. To do this, the emergency physician must maintain a high degree of clinical suspicion for thyroid disease.

Hyperthyroidism.

The clinical spectrum of hyperthyroidism varies from asymptomatic,subclinical hyperthyroidism to the life-threatening "thyroid storm". Hyperthyroidism is a common form of thyroid disease that mimics many of the common complaints in the emergency department. The diagnosis of hyperthyroidism is often challenging due to the multitude of physical and even psychiatric complaints. Recognition and treatment by emergency physicians of severe hyperthyroidism is critical and can be life saving.

Spontaneous long-term remission in a patient with premature ovarian failure.

OBJECTIVE: To describe a patient with premature ovarian failure who after a pregnancy achieved a prolonged remission, which has lasted for more than 10 years. METHODS: Clinical and laboratory data of a patient who had premature ovarian failure with a spontaneous pregnancy and a prolonged remission are described. The pertinent literature is reviewed and summarized. RESULTS: A 26-year-old woman presented with secondary amenorrhea of 6 months' duration in 1984. Her serum total estrogen level was low, and gonadotropins were in the postmenopausal range. She also had a history of primary hypothyroidism, diagnosed in 1979. The physical examination showed normal findings, except for an enlarged thyroid gland and a few areas of vitiligo on her back, arms, and legs. Antithyroid antibodies were present. Adrenal insufficiency was excluded on the basis of results of the cosyntropin stimulation test. She had a normal 46,XX karyotype. A diagnosis of premature ovarian failure was made, and therapy with cyclic estrogen and progesterone was initiated. In 1991, she spontaneously conceived and gave birth to a healthy baby. After delivery, the patient began to have normal menstrual cycles and continues to do so without hormone replacement therapy. Subsequently, serum estrogen and gonadotropins were in the normal range. Her thyroid antibodies also became negative. When last contacted by her primary-care physician in November 2002, she was still having normal menstrual periods, and the patches of vitiligo were no longer present. CONCLUSION: It is well known that many autoimmune diseases subside during pregnancy; however, most of them relapse in the postpartum period. The mechanism of the prolonged remission in our patient is unknown, but hormonal as well as autoimmune changes related to pregnancy and the post partum period might have had a role.