Hyperthyroidism.

Thyrotoxicosis is a general term for excess circulating and tissue thyroid hormone levels, whereas hyperthyroidism specifically denotes disorders involving a hyperactive thyroid gland (Graves disease, toxic multinodular goiter, toxic adenoma). Diagnosis and determination of the cause rely on clinical evaluation, laboratory tests, and imaging studies. Hyperthyroidism is treated with antithyroid drugs, radioactive iodine ablation, or thyroidectomy. Other types of thyrotoxicosis are monitored and treated with ß-blockers to control symptoms given that most of these conditions resolve spontaneously.

Increased Risk of Radioiodine Treatment Failure Associated with Graves Disease Refractory to Methimazole.

OBJECTIVE: Iodine 131 (I-131) radioactive iodine (RAI) therapy has been the preferred treatment for Graves disease in the United States; however, trends show a shift toward antithyroid drug (ATD) therapy as first-line therapy. Consequently, this would favor RAI as second-line therapy, presumably for ATD refractory disease. Outcomes of RAI treatment after first-line ATD therapy are unclear. The purpose of this study was to investigate treatment failure rates and potential risk factors for treatment failure, including ATD use prior to RAI treatment. METHODS: A retrospective case control study of Graves disease patients (n = 200) after I-131 RAI therapy was conducted. Treatment failure was defined as recurrence or persistence of hyperthyroidism in the follow-up time after therapy (mean 2.3 years). Multivariable regression models were used to evaluate potential risk factors associated with treatment failure. RESULTS: RAI treatment failure rate was 16.5%. A majority of patients (70.5%) used ATD prior to RAI therapy, predominantly methimazole (MMI) (91.9%), and approximately two-thirds of patients used MMI for >3 months prior to RAI therapy. Use of ATD prior to RAI therapy (P = .003) and higher 6-hour I-123 thyroid uptake prior to I-131 RAI therapy (P<.001) were associated with treatment failure. MMI use >3 months was also associated with treatment failure (P = .002). CONCLUSION: More patients may be presenting for RAI therapy after failing first-line ATD therapy. MMI use >3 months was associated with RAI treatment failure. Further studies are needed to investigate the association between long-term first-line ATD use and RAI treatment failure.

5-alpha-dihydrotestosterone elevations associated with phentermine use.

BACKGROUND: A case of 5-alpha-dihydrotestosterone (DHT) elevation associated with phentermine initiation is reported, and possible mechanisms are discussed. There are no published reports of this association in the literature. METHODS: Clinical and laboratory information is described. RESULTS: A 72-year-old male with metastatic prostate cancer taking dutasteride to lower his DHT levels initiated phentermine 15 mg daily for weight loss. His DHT level drawn within 1 week prior to starting phentermine was 9.9 pg/ml. When reporting for follow up 2 weeks later, his DHT level had increased to 114 pg/ml. The DHT level was checked again 2 weeks after that visit, and had increased to 174 pg/ml. At that time, phentermine was discontinued, and 1 week later, the DHT level had decreased to 20.1 pg/ml. Over the next 4 months, the patient's DHT levels were maintained at less than 20 pg/ml. Phentermine 15 mg daily was then reinitiated while his DHT level was 7.5 pg/ml. Two weeks after resuming phentermine, his DHT level had again increased to 196 pg/ml. The patient's phentermine was then discontinued, and around 1 week later, his DHT level had fallen to 5.1 pg/ml. CONCLUSION: A 72-year-old male with metastatic prostate cancer experienced profound increases in DHT upon initiation of phentermine despite continuation of his baseline dutasteride therapy. The etiology of these increases is still unclear.

In the clinic. Hypothyroidism.

The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including PIER (Physicians' Information and Education Resource) and MKSAP (Medical Knowledge and Self Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing division and with assistance of science writers and physician writers. Editorial consultants from PIER and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult www.acponline.org, http://pier.acponline.org, and other resources referenced within each issue of In the Clinic.

The relationship between adipokines, body composition, and bone density in men with chronic obstructive pulmonary disease.

Osteoporosis is common in patients with chronic obstructive pulmonary disease (COPD). Data regarding the relationship between adipokines and bone mineral density (BMD) in this population is lacking. The purpose of this pilot study was to determine associations between the adipokines tumor necrosis factor-alpha (TNF-alpha), leptin, adiponectin and resistin, body composition, and BMD in men with severe COPD. This was a cross-sectional study of men with severe COPD who visited the University of Colorado Hospital COPD Center. Bone density and parameters of body composition were measured by dual-energy X-ray absorptiometry. Twenty-three men were included (mean age = 66 years, mean percent predicted forced expiratory volume in one second = 32%). On bivariate analysis, there was no association between TNF-alpha and BMD. Parameters of body composition and serum concentrations of leptin and adiponectin were significantly associated with total hip and spine bone density. However, with partial correlation analysis, total body mass was the only independent predictor of total hip BMD, explaining approximately 50% of the variability. Overall, 18 out of 23 men enrolled (78%) had low bone density by T-score, and nine (39%) were classified as having osteoporosis. The men with osteoporosis had lower parameters of body composition, lower mean serum leptin concentrations, and a greater impairment in measures of lung function compared to the men without osteoporosis. We conclude that the effect of adipokines on BMD does not appear to be independent of body mass. However, larger studies are needed to further evaluate the relationship between adipokines, body weight, and BMD in patients with COPD.

Osteoporosis risk in premenopausal women.

Although clinically significant bone loss and fractures in healthy premenopausal women are rare, more women are seeking evaluation for osteoporosis from their health care providers. As pharmacists are in an ideal position to influence the management of premenopausal women with osteoporosis, it is important that pharmacists understand the available data on bone loss, fractures, and risk factors and secondary causes for osteoporosis, as well as when to recommend testing and treatment in premenopausal women. Limited data are available; therefore, we conducted a MEDLINE search of the literature from January 1993-August 2008. Studies evaluating bone loss, fractures, and fracture risk in healthy premenopausal women were targeted and summarized; most recommendations are based on expert opinion. A small but statistically significant loss in bone mineral density of 0.25-1%/year by dual-energy x-ray absorptiometry is seen healthy premenopausal women; the clinical significance of this is unknown. Whereas absolute fracture risk is low, premenopausal fractures appear to increase postmenopausal fracture risk by 1.5-3-fold. Risk factors for low bone density appear to be similar between pre- and postmenopausal women. Bone density screening in healthy premenopausal women is not recommended, but bone mineral density testing is advisable for those who have conditions or who receive drug therapy that may cause secondary bone loss. Lifestyle modification emphasizing bone-healthy habits such as adequate calcium and vitamin D nutrition, regular exercise, limitation of caffeine and alcohol consumption, and avoidance of tobacco are essential to the management of osteoporosis risk. The efficacy and safety of osteoporosis drugs have not been adequately demonstrated in premenopausal women. Therefore, pharmacologic interventions cannot be recommended in young women with low bone mass but may be considered in those having a more significant fracture risk, such as those with a previous low-trauma fracture or an identified secondary cause for bone loss.

Palpable pediatric thyroid abnormalities - diagnostic pitfalls necessitate a high index of clinical suspicion: a case report.

A 12-year-old girl presented with a 4 year history of an enlarged, firm thyroid gland. On exam, her thyroid was firm and fixed and an enlarged cervical lymph node was palpable as well. Though a thyroid ultrasound prior to referral was read as thyroiditis, clinical suspicion for thyroid carcinoma mandated continued investigation. The diagnosis of papillary thyroid cancer was established and her workup revealed lymph node metastases as well as a tremendous burden of pulmonary metastases. Pediatric thyroid cancer is extremely rare, but often presents with aggressive disease. Palpable thyroid abnormalities in an individual under 20-years-old should be viewed with suspicion and should be thoroughly investigated to rule out malignancy even in the face of negative diagnostic procedures. Though pediatric papillary thyroid cancer often presents with loco-regional and even distant metastatic disease, mortality rates in follow-up for as long as 20 years are very favorable.

The management of subclinical hyperthyroidism by thyroid specialists.

Subclinical hyperthyroidism is a relatively common condition for which prospectively derived evidenced-based management guidelines do not exist. We have conducted a case-based mail survey to solicit opinions from members of the American Thyroid Association (ATA) about various issues that arise in the management of patients with this disorder. The survey was completed and returned by 185 of 300 (62%) of the original survey recipients. Four hypothetical cases varying in age, thyrotropin (TSH) level and underlying etiology were presented. The majority of respondents recommended further evaluation of all cases, most commonly choosing a radioactive iodine uptake (42%-71%), thyroid scan (39%-68%) and antithyroid (TPO/Tg) antibodies (49%-55%) as the additional tests to be ordered. The large majority (84%) recommended observation rather than active treatment for a young patient with a low but detectable serum TSH level. A small majority also recommended observation alone for a young woman with an undetectable serum TSH level (58%) and for an older woman with a low but detectable serum TSH value (63%). However, the majority (66%) favored treating an older woman with an undetectable serum TSH. When treatment was advised in the patients with subclinical hyperthyroidism, the respondents strongly favored anti-thyroid drugs when the etiology was Graves' disease and radioactive iodine when the etiology was toxic nodular thyroid disease. In the absence of adequate evidence-based guidelines, it is hoped that this survey of expert opinions may provide useful guidance for physicians providing care for patients with subclinical hyperthyroidism.

Calcium deposition with or without bone formation in the lung.

Pulmonary calcification and ossification occurs with a number of systemic and pulmonary conditions. Specific symptoms are often lacking, but calcification may be a marker of disease severity and its chronicity. Pathophysiologic states predisposing to pulmonary calcification and ossification include hypercalcemia, a local alkaline environment, and previous lung injury. Factors such as enhanced alkaline phosphatase activity, active angiogenesis, and mitogenic effects of growth factors may also contribute. The clinical classification of pulmonary calcification includes both metastatic calcification, in which calcium deposits in previously normal lung or dystrophic calcification, which occurs in previously injured lung. Pulmonary ossification can be idiopathic or can result from a variety of underlying pulmonary, cardiac, or extracardiopulmonary disorders. The diagnosis of pulmonary calcification and ossification requires various imaging techniques, including chest radiography, computed tomographic scanning, and bone scintigraphy. Interpretation of the presence of and the specific pattern of calcification or ossification may obviate the need for invasive biopsy. In this review, specific conditions causing pulmonary calcification or ossification that may impact diagnostic and treatment decisions are highlighted. These include metastatic calcification caused by chronic renal failure and orthotopic liver transplantation, dystrophic calcification caused by granulomatous disorders, DNA viruses, parasitic infections, pulmonary amyloidosis, vascular calcification, the idiopathic disorder pulmonary alveolar microlithiasis, and various forms of pulmonary ossification.

Clinical comparison of whole-body radioiodine scan and serum thyroglobulin after stimulation with recombinant human thyrotropin.

Sensitive monitoring for thyroid cancer recurrence or persistence includes whole-body radioiodine scanning (WBS) and measurement of serum thyroglobulin (Tg) after endogenous or exogenous thyrotropin (TSH) stimulation. We reviewed our experience using recombinant human thyrotropin (rhTSH) in 83 patients to compare the clinical relevance of a positive WBS and/or Tg. Ten patients had a positive WBS; eight of these patients had activity limited to the thyroid bed. rhTSH-stimulated Tg was 2 ng/mL or more in 25 and 5 ng/mL or more in 13 patients. Of the patients with a negative WBS, 11 of 20 patients with a Tg 2 ng/mL or more and 7 of 9 patients with a Tg 5 ng/mL or more received therapy or further evaluation based on the Tg alone. Conversely, only 1 of 5 patients with a serum Tg less than 2 ng/mL received therapy or further evaluation based on a positive WBS alone. Three of the patients who did not receive therapy or further evaluation, had subsequent negative WBS 10-12 months later, suggesting lack of clinically significant disease. Twenty patients had a negative WBS and serum Tg 2 ng/mL or more. Eleven of 20 patients had a Tg less than 5 ng/mL and 4 of these patients had further evaluation with a neck ultrasound. One patient had a biopsy-proven recurrence (rhTSH-stimulated Tg 4 ng/mL). Subsequent evaluations (> or = 6 months later) have been negative for 8 patients. Of the nine patients with a Tg 5 ng/mL or more and a negative WBS, 7 had further evaluation and 6 of 7 had identified disease. In summary, rhTSH-stimulated WBS and Tg are complementary, but Tg is a more sensitive indicator of disease recurrence or persistence. In our practice, an rhTSH-stimulated Tg greater than 4-5 ng/mL often resulted in further evaluation, while a Tg less than 4 ng/mL rarely resulted in further immediate evaluation.

Congenital isolated central hypothyroidism caused by a "hot spot" mutation in the thyrotropin-beta gene.

Two adult siblings presented to our practice with a known history of congenital central isolated hypothyroidism. Their growth, development, and general health had been normal. Although the disorder was known to result from thyrotropin (TSH) deficiency, providers in the past had made multiple adjustments in their levothyroxine replacement doses in attempts to normalize serum TSH levels. This suggests a need for better education of providers who care for patients with central hypothyroidism. We performed DNA sequencing of the TSHbeta gene and identified a homozygous single base deletion in codon 105, on exon 3, resulting in a frameshift and a premature termination signal at codon 114. This same mutation (C105FS114X) has been previously reported in South America and Europe and appears to be the most common genetic mutation associated with congenital isolated TSH deficiency. The identification of this mutation for the first time in the United States suggests that this disorder, now described in patients from countries on multiple continents, is more common than previously appreciated and may be a mutational "hot spot."