395 - Vitamin D Screening, Adrenal Incidentalomas, Gonorrhea Treatment

From the USPSTF

1) Screening for Vitamin D – Not Ready for Prime Time

It is known that vitamin D performs an important role in calcium homeostasis and bone metabolism and also affects many other cellular regulatory functions outside the skeletal system. Multiple association studies have hinted at a role of vitamin D deficiency in the pathogenesis of immune mediated inflammatory diseases (IMID), but no definitive relationship has been established.

No consensus exists regarding the precise serum levels of vitamin D that represent optimal health or sufficiency. The Institute of Medicine has defined vitamin D deficiency as 25(OH)D less than 12 ng/mL, with levels greater than 20 ng/mL being considered adequate for bone and overall health; whereas the Endocrine Society has classified 25(OH)D less than 20 ng/mL as deficient and greater than 30 ng/mL as optimal. 

The USPSTF recently updated and confirmed its 2014 recommendation regarding screening for vitamin D deficiency in community-dwelling, nonpregnant adults who have no signs or symptoms of vitamin D deficiency (such as bone pain or muscle weakness ) or conditions for which vitamin D treatment is recommended. The recommendation included the benefits and harms of screening and early treatment:

• The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for vitamin D deficiency in asymptomatic adults. (I statement)

Risk factors for vitamin D deficiency include low dietary vitamin D intake, little or no UV B exposure (eg, because of winter season, high latitude, or sun avoidance), older age, obesity (BMI > 30), increased skin pigmentation, malabsorption or altered GI anatomy, CKD, chronic liver disease, or those who have rickets, osteomalacia, or osteoporosis. Depending on the serum threshold used to define deficiency, the prevalence of vitamin D deficiency is 2 to 10 times higher in non-Hispanic Black persons than in non-Hispanic White persons, likely related to differences in skin pigmentation. A significant proportion of the variability in 25(OH)D serum levels among individuals is not explained by the risk factors noted above, which seem to account for only 20-30% of the variation in levels.

The recommendation statement was based on a 46-study systematic review that indicates treatment with vitamin D to have no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events. The authors also note that the harms of telling asymptomatic people that they are vitamin D deficient could include patient anxiety, costs of treatment for vitamin D repletion (minimal) and monitoring, the slight risk of toxicity from overtreatment.

The USPSTF did not review the emerging evidence on COVID-19 and vitamin D. The most updated NIH COVID-19 treatment guidelines indicate there are insufficient data to recommend either for or against the use of vitamin D for COVID treatment/prevention.

Mark’s Comments:

The varied and often strong opinions around this topic are intriguing to me. For full disclosure, I take a regular vitamin D3 supplement after having a level of 23 a few years ago. One accompanying editorial noted that "Approximately half of adults would be considered vitamin D deficient or insufficient using current definitions, with higher rates in racial/ethnic minorities … suggesting wide-spread vitamin D deficiency.” In that context, an additional editorial gave what I thought was a reasonable suggestion (but may give John hives): Individuals at increased risk for vitamin D deficiency (noted above) could be empirically prescribed a higher dose of vitamin D (eg, 2000 IU/d) that is still below the upper daily limit. The challenge of “insufficient evidence” continues.

References:

• USPSTF: Screening for Vitamin D Deficiency in Adults - Recommendation Statement. JAMA 13 April 2021;325(14):1436-1442. Link
• Burnett-Bowie SA and Cappola A. The USPSTF 2021 Recommendations on Screening for Asymptomatic Vitamin D Deficiency in Adults: The Challenge for Clinicians Continues. JAMA. 2021;325(14):1401-1402. Link
• NIH COVID-19 Treatment Guidelines. Updated 11 February 2021. Link

From the Literature

2) Dealing with Adrenal Incidentalomas

Adrenal “incidentalomas,” or nodules/masses discovered on imaging for other indications, are a common source of uncertainty in primary care. In 2002, the NIH put out a “Consensus and State of the Science” statement advising on the management of incidentally discovered adrenal masses. This statement decried the poor state of research into this problem, but recommended specific testing summarized as follows:

• For all adenomas, perform a dexamethasone (1 mg) suppression test and check plasma free metanephrine levels.
• For patients with hypertension or hypokalemia: measure serum potassium and plasma aldosterone/plasma renin activity ratio.
• Homogenous adenomas with low attenuation on CT (<10 Hounsfield units(HU)) are probably benign.
• Nodules > 6 cm are usually excised, but < 4 cm are usually monitored. Between those sizes, other factors (clinical effects, growth/time, etc.) should be considered.
• Any nodule that has clinically apparent effects (pheochromocytoma, hypercortisolism, etc.), appears cancerous, or grows on follow up imaging should be surgically removed.
• If an adenoma is stable in size for over at least 6 months and has no evidence of hyperfunction for 4 years, no follow up is necessary.

A recent review in the Journal of Urology lamented that despite the NIH statement’s foundation, current guidelines differed on some key management decisions for these adenomas. They examined guidelines from 5 organizations. Unfortunately, they only compared the actual recommendations from the guidelines, and not the process by which the guidelines were developed. The guidelines agreed on most of the recommendations: hormone testing on diagnosis, CT can diagnose benign masses as < 4 cm, and <10 HU attenuation, surgery is not recommended for benign masses but is recommended for pheochromocytoma, adenomas that are growing, or which look cancerous. However, the guidelines differed in the more nuanced questions: reimaging for either benign or indeterminate initial imaging, repeat hormonal testing frequency, etc.

John’s Comments:

Having an idea of the basic workup of these incidental findings can prepare us for the questions we may get from patients, particularly when they see the results before us.

There are two learning points from this sort of article. First, understanding the process of how a guideline is developed can help us choose which guideline to follow. The authors missed an opportunity to help us decide which guidelines were most trustworthy. In this case, however, it seems that for most of the recommendations for adrenal incidentalomas, and certainly for the decisions that we can make in primary care, the recommendations are very similar to the NIH’s 2002 conference.

Second, in primary care, we can do the initial evaluation of adrenal incidentalomas using imaging and some simple blood tests. If our patients have benign-appearing and non-hormonally active adenomas, we can monitor them with re-imaging once and hormonal evaluation for 4 years and stop if that workup is unrevealing. If the patient falls out of these parameters, we can always ask for specialty opinion.

References:

• Maas M, et al. Discrepancies in the Recommended Management of Adrenal Incidentalomas by Various Guidelines. J Urol. 2021 Jan;205(1):52–9. Link
• Grumbach MM. Management of the Clinically Inapparent Adrenal Mass (“Incidentaloma”). Ann Intern Med. 2003 Mar 4;138(5):424. Link

From the CDC and Question from a Colleague

3) Management of Uncomplicated Gonococcal (GC) Infections

Question:

Recently I worked in a college student health center and was surprised to see how prevalent gonorrhea is currently in the college community. Would you please highlight the recently updated CDC guidelines regarding GC management?

Answer:

Sexually transmitted infections (STIs) caused by Neisseria gonorrhoeae (GC infections) have increased 63% since 2014 and are a cause of sequelae including PID, ectopic pregnancy, and infertility and can facilitate transmission of HIV. According to the CDC, in 2018 rates of reported gonorrhea cases continued to be highest among adolescents and young adults, with the highest rates for both females and males aged 20-24.

Due to increasing antibiotic resistance, the CDC recently updated their guideline for the treatment of GC infections. Recommendations include:

For uncomplicated GC infections of the cervix, urethra, rectum, or pharynx:

• Ceftriaxone 500 mg IM x 1 weight <300 lb (150 kg)
• Ceftriaxone 1 gm IM x 1 weight ≥300 lb (150 kg) (300 lb)
• If chlamydial infection has not been excluded, treat with doxycycline 100 mg orally twice daily for 7 days. Don’t treat empirically – test and if negative, don’t’ treat.
• During pregnancy, azithromycin 1 gm x 1 recommended to treat chlamydia.

 NOTE:

• If ceftriaxone not available, gentamicin 240 mg IM as a single dose plus azithromycin 2 g orally as a single dose OR cefixime 800 mg orally as a single dose.
• If treating with cefixime, and chlamydial infection has not been excluded, treat for chlamydia with doxycycline 100 mg orally twice daily for 7 days.

• No reliable alternative treatments are available for pharyngeal gonorrhea. For persons with a history of a beta-lactam allergy, a thorough assessment of the reaction is recommended.*

A test-of-cure is unnecessary for persons with uncomplicated urogenital or rectal gonorrhea who are treated with any of the recommended or alternative regimens; however, for persons with pharyngeal gonorrhea, a test-of-cure is recommended.

In cases where gonococcal expedited partner therapy (provision of prescriptions or medications for the patient to take to a sex partner without the health care provider first examining the partner) is permissible by state law and the partner is unable or unlikely to seek timely treatment, the partner may be treated with a single 800 mg oral dose of cefixime, provided that concurrent chlamydial infection in the patient has been excluded. Otherwise, the partner may be treated with a single oral 800 mg cefixime dose plus oral doxycycline 100 mg twice daily for 7 days. Counsel patients to abstain from sexual activity during treatment and for days after they AND all of their partners are treated. Inform patients they can anonymously notify partners about the need to be evaluated using websites such as TellYourPartner.org.

Mark’s Comments:

I reached out to Tom Knisely, DO, a FM colleague who is the Regional Medical Director for our Carilion Student Health Services involving multiple universities, for his perspective. He responded: “Remember, women are far more likely to have an asymptomatic gonorrhea infection than men – men very rarely have gonorrhea without symptoms. Men and women will routinely have asymptomatic chlamydia infections and I recommend STI testing be done routinely during well women and well men exams 26 years and younger. First void urine collections are nearly as sensitive as cervical or urethral swabs and two urine collections (first void and mid-stream) are ideal to improve the sensitivity/specificity for patients who have clinical symptoms that at first assessment could be a STI or UTI. Also, oral and anal swabs should be considered in the proper clinical setting.” 

Reference:

Cyr S et al. Update to CDC's Treatment Guidelines for Gonococcal Infection, 2020.

MMWR Morbid Mortal Wkly Rep. December 18, 2020:69(50);1911–1916. Link.

______________

Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org