Daily Endocrinology Research Analysis
Three impactful endocrinology studies stood out: a population-based age–period–cohort analysis showing that the long-rise and recent plateau in U.S. thyroid cancer incidence are driven by period effects consistent with diagnostic pressure; integrative multi-omics in rats revealing previously unrecognized roles of ChREBP in coenzyme A, purine, and NAD metabolism; and a large human follicular-fluid study indicating that age-related fertility decline is unlikely due to diminished granulosa/theca/oo
Summary
Three impactful endocrinology studies stood out: a population-based age–period–cohort analysis showing that the long-rise and recent plateau in U.S. thyroid cancer incidence are driven by period effects consistent with diagnostic pressure; integrative multi-omics in rats revealing previously unrecognized roles of ChREBP in coenzyme A, purine, and NAD metabolism; and a large human follicular-fluid study indicating that age-related fertility decline is unlikely due to diminished granulosa/theca/oocyte secretory outputs in small antral follicles.
Research Themes
- Endocrine oncology overdiagnosis and epidemiologic dynamics
- Transcriptional control of metabolic pathways (ChREBP) and energy homeostasis
- Ovarian follicle biology and reproductive endocrinology
Selected Articles
1. Trends in incidence, metastasis, and mortality from thyroid cancer in the USA from 1975 to 2019: a population-based study of age, period, and cohort effects.
Using SEER and national mortality data (1975–2019), thyroid cancer incidence in the USA rose until 2009 and then plateaued, with age–period–cohort modeling attributing changes primarily to period effects consistent with diagnostic pressure. The findings indicate persistent overdiagnosis, especially among middle-to-older adults, and underscore the need for strategies to curb diagnostic drivers without compromising necessary care.
Impact: Clarifies that the long-observed incidence surge and recent plateau are driven by period effects, reframing rising thyroid cancer rates as an overdiagnosis problem. This has direct implications for screening, imaging, and biopsy practices.
Clinical Implications: Prioritize risk-based imaging and biopsy thresholds to minimize overdiagnosis and overtreatment, refine follow-up algorithms for low-risk nodules, and monitor population-level diagnostic intensity as a quality metric.
Key Findings
- Thyroid cancer incidence increased from 5.0 per 100,000 (1975) to 14.6 (2009) and then plateaued through 2019.
- Age–period–cohort modeling attributes incidence dynamics primarily to period effects consistent with changing diagnostic pressure.
- Incidence increases were most prominent in women 40–69 and men 50–79; cohort-wise increases persisted across generations.
Methodological Strengths
- Large, population-based datasets (SEER, NCHS) spanning 45 years
- Joinpoint regression and age–period–cohort modeling to disentangle temporal drivers
Limitations
- Observational design susceptible to coding changes and diagnostic practice shifts
- APC models infer but cannot prove causal mechanisms (e.g., imaging adoption)
Future Directions: Evaluate policy and practice interventions (e.g., ultrasound/biopsy thresholds, reporting standards) to reduce overdiagnosis and assess effects on outcomes and resource use.
2. Integration of metabolomic and transcriptomic analyses reveals regulatory functions of the ChREBP transcription factor in energy metabolism.
In vivo hepatic ChREBP knockdown followed by integrated metabolomics and transcriptomics uncovered non-canonical roles of ChREBP: regulation of CoA biosynthesis, substrate transport (maintaining pyruvate), anaplerosis/TCA intermediates, and late steps of purine and NAD synthesis. These findings expand ChREBP’s scope from carbohydrate/lipid gene regulation to broader energy metabolism control.
Impact: Reveals new regulatory axes controlled by ChREBP that link carbohydrate sensing to CoA, purine, and NAD metabolism, offering mechanistic targets for metabolic diseases.
Clinical Implications: Identifies candidate pathways (CoA biosynthesis, substrate transporters, purine/NAD synthesis) that could be modulated to treat metabolic disorders such as diabetes, NAFLD, or cardiometabolic disease.
Key Findings
- Hepatic ChREBP suppression decreases expression of CoA biosynthesis genes and lowers CoA and short-chain acyl-CoA levels.
- Despite reduced pyruvate kinase, pyruvate levels are maintained, likely via increased pyruvate/amino acid transporter expression.
- Anaplerotic enzyme expression and late steps of purine and NAD synthesis are downregulated, altering TCA intermediates and nucleotide redox metabolism.
Methodological Strengths
- Integrated multi-omics (transcriptomics and metabolomics) in vivo
- Targeted hepatic knockdown via GalNAc-siRNA enabling pathway-level causality
Limitations
- Preclinical rat model may not fully translate to humans
- Focus on liver may not capture systemic or tissue-specific compensations
Future Directions: Validate findings in human tissues and disease models, test whether modulating CoA, purine, or NAD pathways ameliorates metabolic disease phenotypes.
3. Impact of female age on concentrations of reproductive hormones and oocyte-specific growth factors in follicular fluid from human small antral follicles.
Analysis of 381 human small antral follicular-fluid samples (diameter 3–13 mm) showed that concentrations of AMH, inhibins, sex steroids, and oocyte factors (GDF9, BMP15, cumulin) do not decline with maternal age. Age explained little of the variance in progesterone, supporting that fertility decline with age relates more to oocyte quality/quantity than diminished follicular-cell secretory capacity.
Impact: Provides human evidence that secretory outputs of granulosa/theca cells and oocytes in small antral follicles remain stable with age, refining mechanistic understanding of age-related infertility.
Clinical Implications: Clinical strategies should prioritize preserving and selecting high-quality oocytes (e.g., earlier cryopreservation, optimizing stimulation) rather than expecting to restore follicular fluid hormone milieu in small follicles.
Key Findings
- Across ages 5–43 years, follicular-fluid concentrations of AMH, inhibin A/B, estradiol, androstenedione, testosterone, GDF9, BMP15, and cumulin showed no decline with age after adjusting for follicle volume.
- Age explained at most 5% of the variance in progesterone concentrations, indicating minimal age effect.
- Data support the hypothesis that age-related fertility decline is driven primarily by oocyte quality/quantity rather than reduced secretory capacity of follicular cells in small antral follicles.
Methodological Strengths
- Large human sample size (n=381) spanning a wide age range
- Comprehensive panel including granulosa/theca hormones and oocyte-derived TGF-β factors
Limitations
- Health status (atresia) of individual follicles was not characterized
- Few follicles >10 mm and no women >43 years, limiting generalizability to older ages and larger follicles
Future Directions: Characterize follicular health status and extend analyses to larger follicles and older women; link follicular-fluid profiles to embryo competence and live birth outcomes.