Antigen-Specific Immunotherapy with Thyrotropin Receptor Peptides in Graves' Hyperthyroidism: A Phase I Study.

Background: Graves' disease is one of the most common autoimmune conditions, but treatment remains imperfect. This study explores the first-in-human use of antigen-specific immunotherapy with a combination of two thyrotropin receptor (TSHR) peptides (termed ATX-GD-59) in Graves' hyperthyroidism. Methods: Twelve participants (11 female) with previously untreated mild to moderate Graves' hyperthyroidism were enrolled in a Phase I open label trial to receive 10 doses of ATX-GD-59 administered intradermally over an 18-week period. Adverse events, tolerability, changes in serum free thyroid hormones, and TSHR autoantibodies were measured. Results: Ten subjects received all 10 doses of ATX-GD-59, five (50%) of whom had free triiodothyronine within the reference interval by the 18-week visit. Two further subjects had improved free thyroid hormones by the end of the study (7/10 responders), whereas three subjects showed worsening thyrotoxicosis during the study. Serum TSHR autoantibody concentrations reduced during the study and correlated with changes in free thyroid hormones (r = 0.85, p = 0.002 for TSHR autoantibody vs. free triiodothyronine). Mild injection-site swelling and pain were the most common adverse events. Conclusions: These preliminary data suggest that ATX-GD-59 is a safe and well-tolerated treatment. The improvement in free thyroid hormones in 70% of subjects receiving the medication suggests potential efficacy as a novel treatment for Graves' hyperthyroidism.

Long-term effects of testim(r) 1% testosterone gel in hypogonadal men.

A new transdermal preparation, Testim(R) 1% testosterone gel, has recently become available for normalization of serum testosterone in hypogonadal men. In short-term studies, it has been shown to reverse the clinical signs and symptoms of low testosterone and to be well tolerated with less applicationsite irritation than with testosterone patches. In 2 long-term studies with Testim, the predose early morning serum testosterone (T), dihydrotestosterone (DHT), and free testosterone (FT) levels were assessed. Serum T, DHT, and FT were all maintained in the normal range for up to 12 months. In these studies, involving a total of 371 hypogonadal men, evaluation by means of dual-energy x-ray absorptiometry revealed a significant increase from baseline in bone mineral density. A significant improvement was also observed in body composition (increased lean body mass, decreased fat mass, and decreased percentage fat). In addition, significant improvements in mood and sexual function were maintained for up to 12 months of treatment. The parameters measured included sexual performance, sexual motivation, sexual desire, and occurrence of spontaneous erections. These data from the 2 long-term studies support the results of the 90-day studies with Testim showing that the gel significantly improves the signs and symptoms associated with low testosterone compared with placebo. The data also support the conclusion that these improvements are maintained for up to 1 year of additional treatment.

Long-term effects of testim(r) 1% testosterone gel in hypogonadal men.

A new transdermal preparation, Testim(R) 1% testosterone gel, has recently become available for normalization of serum testosterone in hypogonadal men. In short-term studies, it has been shown to reverse the clinical signs and symptoms of low testosterone and to be well tolerated with less application-site irritation than with testosterone patches. In 2 long-term studies with Testim, the predose early morning serum testosterone (T), dihydrotestosterone (DHT), and free testosterone (FT) levels were assessed. Serum T, DHT, and FT were all maintained in the normal range for up to 12 months. In these studies, involving a total of 371 hypogonadal men, evaluation by means of dual-energy x-ray absorptiometry revealed a significant increase from baseline in bone mineral density. A significant improvement was also observed in body composition (increased lean body mass, decreased fat mass, and decreased percent fat). In addition, significant improvements in mood and sexual function were maintained for up to 12 months of treatment. The parameters measured included sexual performance, sexual motivation, sexual desire, and occurrence of spontaneous erections. These data from the 2 long-term studies support the results of the 90-day studies with Testim showing that the gel significantly improves the signs and symptoms associated with low testosterone compared with placebo. The data also support the conclusion that these improvements are maintained for up to 1 year of additional treatment.

Diagnosis of hypogonadism: clinical assessments and laboratory tests.

Hypogonadism can be of hypothalamic-pituitary origin or of testicular origin, or a combination of both, which is increasingly common in the aging male population. In the postpubertal male, testosterone replacement therapy can be used to treat the signs and symptoms of low testosterone, which include loss of libido, erectile dysfunction, diminished intellectual capacity, depression, lethargy, osteoporosis, loss of muscle mass and strength, and some regression of secondary sexual characteristics. Before initiation of testosterone replacement therapy, an examination of the prostate and assessment of prostate symptoms should be performed, and both the hematocrit and lipid profile should be measured. Absolute contraindications to testosterone replacement therapy are prostate or breast cancer, a hematocrit of 55% or greater, or sensitivity to the testosterone formulation.