Background/objective

Exogenous Cushing syndrome is usually diagnosed in the setting of known glucocorticoid exposure; however, occult glucocorticoid use is possible. We present 2 cases of patients who developed Cushing syndrome while taking Artri King (AK), an over-the-counter "herbal" supplement for joint pains reported to contain glucocorticoids.

Case report

Patient 1, a 49-year-old woman, reported rapid weight gain, large stretch marks, poor wound healing, and recent diagnoses of type 2 diabetes mellitus and hypertension over a course of 1 year. Her serum am cortisol level was <0.5 μg/dL (reference range, 4.0-22.0 μg/dL) and adrenocorticotropic hormone (ACTH) level was <5 pg/mL (reference range, 5-60 pg/mL). Synthetic glucocorticoid screening revealed a dexamethasone level of 210 ng/dL (reference value < 100 ng/dL) while she was taking AK; 5 days after stopping the supplement, the level was 24 ng/dL (reference value < 20 ng/dL). Patient 2, a 61-year-old woman, presented with weight gain, fatigue, swelling, and recent diagnoses of prediabetes and hypertension over a span of 6 months. Her serum am cortisol level was <1.0 μg/dL (reference range, 8.0-25.0 μg/dL) and ACTH level was <5 pg/mL (reference value < 46 pg/mL). She stopped AK, and 1 month later, her am cortisol level rose to 9.1 μg/dL (reference range, 8.0-25.0 μg/dL) and ACTH level rose to 68 pg/mL (reference value < 46 pg/mL).

Discussion

Supplements containing hidden glucocorticoids and causing Cushing syndrome have been reported in rare cases and can pose a diagnostic challenge for providers.

Conclusion

Exogenous glucocorticoid use because of unregulated herbal supplements should be considered when Cushing syndrome is suspected.

PURPOSE: Treatment guidelines for gender-affirming hormone therapy with estrogen (GAHT-E) recommend specific dosing regimens based on limited data. Well-controlled efficacy trials are essential to tailoring treatment to patient goals as the guidelines recommend. The goal of this study was to take a foundational step toward designing community-centered effectiveness trials for gender-diverse individuals seeking GAHT-E. METHODS: Our team developed a cross-sectional survey based on broad clinical experience and consultation with our community advisory board. The survey included 60 items covering demographics, transition history, goals and priorities for treatment, indicators of treatment success, sexual function goals, and future research priorities. The survey was distributed during the summer of 2021, primarily through social networks designed for gender-expansive individuals seeking treatment with estrogen. RESULTS: A total of 1270 individuals completed the survey. Overall treatment goals most frequently rated extremely important or very important were the following: (1) improved satisfaction with life (81%), (2) appearing more feminine (80%), (3) appearing less masculine (77%), (4) improved mental health (76%), and (5) being seen as your true gender by others (75%). The three body characteristics most frequently rated highest priority or high priority among changes were the following: (1) facial hair (85%), (2) breast shape or size (84%), and (3) body shape (80%). The highest-rated research priority was comparing feminization with different routes of estrogen administration. CONCLUSION: The goals and experiences of individuals seeking GAHT-E are diverse. Future clinical trials of GAHT-E should be grounded in the needs and priorities of community stakeholders.

The mechanism(s) by which fatty acids are sequestered and transported in muscle have not been fully elucidated. A potential key player in this process is the protein myoglobin (Mb). Indeed, there is a catalogue of empirical evidence supporting direct interaction of globins with fatty acid metabolites; however, the binding pocket and regulation of the interaction remains to be established. In this study, we employed a computational strategy to elucidate the structural determinants of fatty acids (palmitic & oleic acid) binding to Mb. Sequence analysis and docking simulations with a horse (Equus caballus) structural Mb reference reveals a fatty acid-binding site in the hydrophobic cleft near the heme region in Mb. Both palmitic acid and oleic acid attain a "U" shaped structure similar to their conformation in pockets of other fatty acid-binding proteins. Specifically, we found that the carboxyl head group of palmitic acid coordinates with the amino group of Lys45, whereas the carboxyl group of oleic acid coordinates with both the amino groups of Lys45 and Lys63. The alkyl tails of both fatty acids are supported by surrounding hydrophobic residues Leu29, Leu32, Phe33, Phe43, Phe46, Val67, Val68 and Ile107. In the saturated palmitic acid, the hydrophobic tail moves freely and occasionally penetrates deeper inside the hydrophobic cleft, making additional contacts with Val28, Leu69, Leu72 and Ile111. Our simulations reveal a dynamic and stable binding pocket in which the oxygen molecule and heme group in Mb are required for additional hydrophobic interactions. Taken together, these findings support a mechanism in which Mb acts as a muscle transporter for fatty acid when it is in the oxygenated state and releases fatty acid when Mb converts to deoxygenated state.