News from the latest research

The Endocrine Society’s Guidelines for DIAGNOSIS AND TREATMENT OF PCOS

The Endocrine Society, along with a Society-appointed task force, a methodologist, and a medical writer, has developed new practice guidelines for the diagnosis and treatment of polycystic ovary syndrome (PCOS).

The evidence-based guidelines, published in this month’s Journal of Clinical Endocrinology and Metabolism, aim for a consensus among medical providers for managing PCOS, a disorder that affects more than 5 million in the U.S. alone, and can occur in girls as young as 11. Symptoms include infertility, irregular or even absent menstrual periods, acne, hirsutism, obesity, anxiety, and depression, among others.

The Society task force, led by Richard S. Legro, MD, of Penn State University College of Medicine, recommends using the Rotterdam criteria for diagnosing PCOS — presence of at least two of the following: androgen excess, ovulatory dysfunction, or polycystic ovaries. Caution should be used when diagnosing adolescents and menopausal women with PCOS, as “hyperandrogenism is central to the presentation in adolescents, whereas there is no consistent phenotype in postmenopausal women,” according to the authors.

The guidelines lay out suggestions for associated morbidity and evaluation of the disorder, as well as each of the symptoms and complications associated with PCOS:
• For pregnancy complications, the Society recommends preconceptual assessment of BMI, blood pressure, and oral glucose tolerance.
• Women with PCOS are at a higher risk for endometrial cancer, but the Society warns against routine ultrasound screening for endometrial thickness in women with PCOS.
• Women and adolescents with PCOS should be screened for depression and anxiety by history and treated appropriately.
• Hormonal contraceptives should be the first-line management for menstrual abnormalities and hirsutism/acne in PCOS. The Society recommends against the use of metformin as a first-line treatment for cutaneous manifestations, prevention of pregnancy complications, or obesity.
• Lifestyle therapy should be used for overweight and obese women with PCOS, as it improves weight loss and lowers cardiovascular and diabetes risk.

Combination Therapy for Treating ADVANCED PANCREATIC CANCER

The drug nab-paclitaxel, when used in combination with gemcitabine, showed promise in significantly improving overall survival in patients with advanced pancreatic cancer, according to a study recently published in the New England Journal of Medicine.

The Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT), led by Daniel D. Von Hoff , MD, of the Translational Genomics Research Institute, treated 861 patients randomized to receive either a combination of nab-paclitaxel and gemcitabine or gemcitabine alone. Overall, patients who were treated with the nab-paclitaxel/gemcitabine combination had a median survival of 8.5 versus 6.7 months, with doubling of the two-year survival rate compared with patients treated with gemcitabine only (9% vs. 4%).

More patients treated with nab-paclitaxel plus gemcitabine showed a significant reduction in a key tumor marker called carbohydrate antigen 19-9 (CA19-9), which led to longer survival. Patients who had a decrease of at least 90% in CA19-9 and who received the combination therapy had a median survival of 13.5 months, while patients on gemcitabine alone had a median survival of 8.2 months.

PET scans were performed on 257 patients to measure their metabolic response rate, the percentage of patients whose tumor signals decreased (von Hoff et al., ASCO 2013). The results of that particular study showed that 63% of patients who took nab-paclitaxel plus gemcitabine had a reduction in tumor signal, while just 38% of patients who took gemcitabine alone had the same outcome.

A Novel Approach to Treating BENIGN PROSTATIC HYPERPLASIA

Researchers may have discovered a new avenue for treating benign prostatic hyperplasia (BPH), a potentially debilitating disorder that affects many older men.

A team of scientists, led by Chawnshang Chang, PhD, at the University of Rochester, established the first stromal fibromuscular androgen receptor knockout (ARKO) in a probasin promoter–,driven prolactin transgenic (Pb-PRL tg) mouse to study the stromal AR functions in the benign prostatic hyperplasia development.

BPH is a slow, progressive disease that commonly affects men age 50 and older. Symptoms include urinary hesitancy, frequent urination, urinary retention, and increased risk of urinary tract infections, among others, which severely diminish quality of life in these men.

The study, published in Molecular Endocrinology, demonstrated that the stromal fibromuscular AR was able to modulate the epithelial-stromal interaction through epithelial prolactin/ prolactin receptor (PRL/ PRLR)-granulocyte macrophage-colony stimulating factor (GMCSF)–stromal signal transducer and activator of transcription 3 (STAT3) axes to facilitate the stromal cell growth. Phenotypic characterization showed that loss of stromal fibromuscular AR displayed reduced prostate size, diminished epithelial/stromal cell proliferation, and alleviated microenvironmental changes including extracellular matrix remodeling and immune cells infiltration.

The researchers concluded that targeting stromal fibromuscular AR with the AR degradation enhancer, ASC-J9®, led to the reduction of prostate size.

The Importance of Clinician-Performed ULTRASOUND FOR THYROID CANCER

Researchers at the Endocrinology & Metabolism Institute at Cleveland Clinic recently presented findings that stress the importance of clinician-performed ultrasounds (C-US) for the proper initial surgical management of differentiated thyroid cancer (DTC).

The study results, presented at the American Thyroid Association’s 84th Annual Meeting in Coronado, Calif., make the case for endocrine surgeons performing the initial ultrasounds on their patients, since radiology-performed US (R-US) do not typically evaluate the lateral neck for pathologic lymph nodes (LN). According to lead author Jamie Mitchell, MD, “As many pathologic lymph nodes are not palpable, reliance on radiology reports alone can lead to an inadequate operation being performed.”

The scientists analyzed 137 patients who underwent modifi ed radical neck dissection (MRND) for DTC. Ninety-four (69%) had prereferral imaging of their necks, which included US, CT, and MRI. The remaining patients had C-US done as their initial imaging test. “Of those patients with pre-referral imaging,” the authors wrote, “C-US detected non-palpable cytologically confirmed, pathologic lateral LN previously not identified in 29 (31%).” Furthermore, 55 (59%) patients had R-US done as part of their initial pre-referral imaging, and 39 (41%) had other imaging procedures done. “Of the 55 patients with R-US, 19 (35%) had non-palpable ultrasound-detected pathologic lateral LN detected on C-US, significantly altering the surgical plan.”

Based on these results, Mitchell and his team concluded that without C-US, one-third of the patients in their study population would have had an “inadequate initial operation” to manage their DTC. Healthcare providers should be aware of the limitations of R-US when evaluating patients with DTC, “and C-US is critical in ensuring patients with DTC get the correct initial operation.”

Higher Glucose Levels and COGNITIVE IMPAIRMENT

A team of German researchers has discovered that higher glycosylated hemoglobin (HbA1c) and glucose levels — even those still within the normal range — can impair memory function and performance.

The study, published in the journal Neurology, examined a “cohort of healthy, older, nondiabetic individuals without dementia” — 141 individuals (72 women, mean age 63.1 years ± 6.9 SD). Agnes Floel, MD, of Charite-University Medicine in Berlin, and her team tested memory function of the participants using the Rey Auditory Verbal Learning Test. They also determined peripheral levels of fasting HbA1c, glucose, and insulin through blood samples, and used 3-tesla MRI scans to measure hippocampal volume and microstructure.

The scientists observed that higher levels of HbA1c were significantly associated with lower scores on delayed recall, learning ability, and memory consolidation. They also noted the relationship of higher HbA1c levels and reductions in hippocampal volume, which could explain some of the cognitive impairment. The authors wrote that “mediation analyses indicated that beneficial effects of lower HbA1c on memory are in part mediated by hippocampal volume and microstructure,” and concluded that chronically elevated levels of HbA1c and glucose in the older population could lead to an overall decline in cognitive function, although further research is needed.

PTH and CARDIOVASCULAR PROBLEMS

Elderly people who have elevated serum parathyroid hormone (PTH) levels could be at a higher risk for cardiovascular disease (CVD), according to a study recently published in the Journal of Clinical Endocrinology and Metabolism.

Researchers at the VU University Medical Center in The Netherlands wrote that “PTH is known to be one of the key regulatory hormones of mineral homeostasis and bone metabolism. Furthermore, hyperparathyroidism has been reported to be associated with cardiovascular mortality and cardiovascular morbidity.”

The scientists, led by Elisabeth M. W. Eekhoff, analyzed data of the Longitudinal Aging Study Amsterdam (LASA), including 558 men and 537 women, aged 65–88 years. Participants for this particular study were chosen from a larger cohort of 3,107 people who “took part in a baseline examination” in 1992– 1993 and were subsequently seen for a follow-up in 1995–1996, as well as being born in 1930 or earlier. Blood samples were taken from this group in 1995 and 1996 after an overnight fast and stored at -20 degrees Celsius. Serum PTH levels and serum 25-hydroxyvitamin D (25(OH)D) levels were then determined in 1997 and 1998 and measured against the extent of abdominal aortic calcification (AAC) and self-reported chronic CVD in each patient.

The authors found that those in the highest quintile of serum PTH levels had a “significantly higher” risk for CVD than those in the lowest quintile, “independently of serum 25(OH)D, BP, or other known confounders.” They found no association between serum 25(OH)D and CVD. They also observed that only the men in the study showed a relationship between PTH and AAC, writing, “this association may partly be explained by a direct relation of PTH to calcifications of the abdominal aorta.” They concluded that “because CVD poses an important health risk, further elucidation of the role of serum PTH in CVD and arteriosclerosis is relevant.”

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