Maya Beth Lodish

Context: Hyperandrogenism is a hallmark of polycystic ovary syndrome (PCOS), yet the androgen(s) responsible remain ambiguous. Recent studies have suggested that 11‐oxygenated C₁₉ steroids (11‐oxyandrogens), specifically 11‐ketotestosterone, may be a good marker for hyperandrogenism in PCOS.Objective: To investigate the utility of 11‐oxyandrogens to differentiate women with and without PCOS relative to classical androgens.Design Setting: Case–control study performed at a PCOS clinic and research center in an academic setting.Patients: 114 women with PCOS and 78 healthy controls.Interventions: Using the PCOS Tissue Bank, serum samples and data from 114 women registered from 2013 to 2017 between the ages of 18–40 years, were obtained and classified using Rotterdam PCOS criteria. Data were compared to 78 healthy women of similar age, with serum samples obtained between 2017 and 2020. 11‐oxyandrogens and sex steroids were measured using mass spectrometry, and their associations to Rotterdam PCOS, age, and BMI were assessed.Main Outcome Measures: 11‐oxyandrogens and sex steroids.Results: Total testosterone, androstenedione, and four 11‐oxyandrogens were significantly elevated in women with PCOS compared to age matched controls, controlling for age and BMI (p < 0.01 for all). When considered together, the four 11‐oxyandrogens were more predictive of PCOS compared to testosterone and androstenedione. When all androgens were considered individually, 11‐ketoandrostenedione was the most predictive of PCOS. Of the six androgens studied, 11‐ketotestosterone was the only androgen that demonstrated a weak association with hirsutism score (r = 0.17; p = 0.07) within the PCOS group.Conclusion: 11‐oxyandrogens were statistically higher in women with PCOS and may serve as better predictors of PCOS than testosterone and androstenedione.

Overgrowth due to growth hormone (GH) excess affects approximately 10% of patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). Our aim is to describe the clinical, biochemical, pathological, and genetic features of GH excess in a retrospective case series of 10 children and adults with NF1 referred to a tertiary care clinical research center. Six children (median age = 4 years, range of 3–5 years), one 14-year-old adolescent, and three adults (median age = 42 years, range of 29–52 years) were diagnosed with NF1 and GH excess. GH excess was confirmed by the failure to suppress GH (n = 9) and frequent overnight sampling of GH levels (n = 6). Genetic testing was ascertained through targeted or whole-exome sequencing (n = 9). Five patients (all children) had an OPG without any pituitary abnormality, three patients (one adolescent and two adults) had a pituitary lesion (two tumors, one suggestive hyperplasia) without an OPG, and two patients (one child and one adult) had a pituitary lesion (a pituitary tumor and suggestive hyperplasia, respectively) with a concomitant OPG. The serial overnight sampling of GH levels in six patients revealed abnormal overnight GH profiling. Two adult patients had a voluminous pituitary gland on pituitary imaging. One pituitary tumor from an adolescent patient who harbored a germline heterozygous p.Gln514Pro NF1 variant stained positive for GH and prolactin. One child who harbored a heterozygous truncating variant in exon 46 of NF1 had an OPG that, when compared to normal optic nerves, stained strongly for GPR101, an orphan G protein-coupled receptor causing GH excess in X-linked acrogigantism. We describe a series of patients with GH excess and NF1. Our findings show the variability in patterns of serial overnight GH secretion, somatotroph tumor or hyperplasia in some cases of NF1 and GH excess. Further studies are required to ascertain the link between NF1, GH excess and GPR101, which may aid in the characterization of the molecular underpinning of GH excess in NF1.

Purpose of review: Great progress has been made in understanding the genetic and molecular basis of pheochromocytoma and paragangliomas (PPGLs). This review highlights the new standards in the diagnosis and management of pediatric PPGLs. Recent findings: The vast majority of pediatric PPGLs have an associated germline mutation, making genetic studies imperative in the work up of these tumors. Somatostatin receptor-based imaging modalities such as ⁶⁸Ga-DOTATATE and ⁶⁴Cu-DOTATATE are shown to have the greatest sensitivity in pediatric PPGLs. Peptide receptor radionuclide therapies (PRRTs) such as ¹⁷⁷Lu-DOTATATE are shown to have efficacy for treating PPGLs. Summary: Genetics play an important role in pediatric PPGLs. Advances in somatostatin receptor-based technology have led to use of ⁶⁸Ga-DOTATATE and ⁶⁴Cu-DOTATATE as preferred imaging modalities. While surgery remains the mainstay for management of PPGLs, PRRT is emerging as a treatment option for PPGLs

Summary: Objective: To investigate early signs of cardiovascular arterial remodelling in paediatric patients with Cushing syndrome (CS) in comparison with normative values from healthy children.Study Design: The metrics used to assess cardiac health were from thoracic aorta and carotid MRI. Scans were performed on 18 children with CS (mean: 12.5 ± 3.1 years, range: 6.0‐16.8 years, 10 female). Pulse wave velocity (PWV), aortic distensibility (AD) and carotid intima‐media thickness (cIMT), well‐validated measurements of cardiac compromise, were measured from the images and compared to normative age‐matched values where available.Results: Patients with CS had significantly higher PWV compared to age‐adjusted normal median control values (4.0 ± 0.7 m/s vs. 3.4 ± 0.2 m/s, respectively, P = 0.0115). PWV was positively correlated with midnight plasma cortisol (r = 0.56, P = 0.02). Internal and common cIMT were negatively correlated with ascending AD (r = −0.75, P = 0.0022, r = −0.69, P = 0.0068, respectively).Conclusion: Pulse wave velocity data indicate that paediatric patients with CS have early evidence of cardiovascular remodelling. The results suggest the opportunity for monitoring as these changes begin in childhood.

The diagnosis of endogenous Cushing syndrome is often challenging and requires multiple repeated blood, urine, and saliva tests to detect elevated cortisol levels. Hair cortisol concentration has been described as a marker of long-term exposure to systemic cortisol in patients with Cushing syndrome. Like hemoglobin A1c is used to detect serum glucose exposure over months, segmental hair cortisol can help identify patients with milder forms of and/or periodic or cyclical Cushing syndrome, which may reduce time and costs associated with collection of urine, salivary, and serum cortisol. Success of hair cortisol in detection of Cushing syndrome will be discussed in context of current literature, including differences between total or segmental hair cortisol in accurately determining timeline of cortisol exposure. Optimal methods of hair collection, storage, processing, and analysis and efforts toward standardization will be a major focus. Recent evidence suggests increased sensitivity and specificity of hair cortisol in detecting Cushing syndrome. Future guidelines should consider this test as a routine part of the repertoire of screening tests for Cushing syndrome. Possible confounders to explain discrepant results in the literature will be discussed.