Objective: The aim of this study was to report on two women in early menopause with alopecia and high mercury (Hg) levels which reversed with a decrease in toxic levels. Methods: Retrospective chart review and case studies in a reproductive endocrinology practice. Results: A 43-year-old woman initially evaluated for early menopause later experienced sudden circumscribed hair loss on the scalp. Blood tests indicated elevated Hg levels and further investigation revealed a diet high in tuna. Levels fell with elimination of dietary tuna. Another woman, 39 years old was complaining of severe hot flashes, night sweats, and menstrual irregularity also developed alopecia. Treated unsuccessfully for low testosterone, blood tests indicated high Hg levels and simultaneous hair loss was observed; recommendation to alter diet, including fish intake, was followed by a reversal of alopecia, along with a decrease in blood Hg levels. Literature searches were conducted with a focus on Hg toxicity or poisoning with symptom of alopecia. Conclusions: Women of reproductive age frequently seek treatment for what is thought to be hormone-related hair loss especially at menopause. Two women demonstrated a strong temporal correlation to high Hg levels associated with early menopause, which was reversible. The development of alopecia in the setting of mild Hg intoxication has not been reported in the medical literature despite its appearance in the popular press. Measurement of Hg levels should be considered in women with alopecia and its relationship to early menopause is unclear but bears further research.

Aims Treatment of prolactinomas with ergoline dopamine agonists can be complicated by intolerance and resistance. This study investigated the pharmacokinetics and pharmacodynamics of the nonergot dopamine agonist ropinirole, to assess its therapeutic potential as a novel therapy for prolactinomas. Methods Five female subjects with prolactinomas participated in this dose–response study. Subjects received up to three doses of ropinirole (0.5, 1.0 and 2.0 mg), each on separate occasions. Frequent blood samples for prolactin and ropinirole were collected for 24 h following drug administration. Data were analysed using noncompartmental and compartmental pharmacokinetic–pharmacodynamic (PKPD) techniques. Results Seven 24‐h curves revealed increased systemic drug exposure with increasing ropinirole doses. Ropinirole concentrations peaked at 4.4 ± 2.7 h and exhibited a half‐life of 5.8 ± 1.7 h. A dose‐dependent prolactin nadir occurred 4.4 ± 1.2 h after drug intake and prolactin concentrations transiently normalized in two of five subjects. PKPD modelling revealed that single‐dose PK of ropinirole is dose‐independent and can be described with a one‐compartment model with linear absorption and elimination. An indirect response model successfully captures the inhibitory effect of ropinirole on prolactin secretion and incorporates time‐dependent receptor desensitization for three of five subjects whose prolactin concentrations nadired before ropinirole reached Cmax. Conclusions This data‐rich study has informed our understanding of the clinical pharmacokinetics and pharmacodynamics of ropinirole, which are successfully captured by the proposed semi‐mechanistic PKPD model. This model can be used to further investigate the PKPD of ropinirole and may facilitate the identification of optimal dose regimens for the treatment of prolactinomas and the establishment of a new therapeutic option for patients impacted by this rare disease.

Context Glucocorticoids regulate energy balance, in part by stimulating the orexigenic neuropeptide agouti-related protein (AgRP). AgRP neurons express glucocorticoid receptors, and glucocorticoids have been shown to stimulate AgRP gene expression in rodents. Objective We sought to determine whether there is a relationship between plasma AgRP and hypothalamic AgRP in rats and to evaluate the relationship between cortisol and plasma AgRP in humans. Methods We retrospectively evaluated plasma AgRP levels prior to transsphenoidal surgery in 31 patients with Cushing disease (CD) vs 31 sex- and body mass index–matched controls from a separate study. We then prospectively measured plasma AgRP, before and 6 to 12 months after surgery, in a subgroup of 13 patients with CD. Plasma and hypothalamic AgRP were measured in adrenalectomized rats with and without corticosterone replacement. Results Plasma AgRP was stimulated by corticosterone in rats and correlated with hypothalamic AgRP expression. Plasma AgRP levels were higher in patients with CD than in controls (139 ± 12.3 vs 54.2 ± 3.1 pg/mL; P < 0.0001). Among patients with CD, mean 24-hour urine free cortisol (UFC) levels were 257 ± 39 μg/24 hours. Strong positive correlations were observed between plasma AgRP and UFC (r = 0.76; P < 0.0001). In 11 of 13 patients demonstrating surgical cure, AgRP decreased from 126 ± 20.6 to 62.5 ± 8.0 pg/mL (P < 0.05) postoperatively, in parallel with a decline in UFC. Conclusions Plasma AgRP levels are elevated in CD, are tightly correlated with cortisol concentrations, and decline with surgical cure. These data support the regulation of AgRP by glucocorticoids in humans. AgRP’s role as a potential biomarker and as a mediator of the adverse metabolic consequences of CD deserves further study.