Chiefs’ Inquiry Corner – 11/3/2022

Polycystic ovarian syndrome (PCOS) affects 6-10% of women of reproductive age and is the most common endocrine disorder in young women. The Rotterdam criteria used to diagnose PCOS requires the presence of at least two of the following three findings: hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. However, non-classic adrenal hyperplasia (NC-CAH) – an autosomal recessive syndrome caused by deficiency of 21-hydroxylase – can also present with hirsutism and ovulatory and menstrual dysfunction. Both entities are associated with obesity, insulin resistance, and dyslipidemia as well, making distinguishing the two syndromes difficult on the basis of clinical presentation alone. While PCOS is 40-50 times more frequent than NC-CAH in reproductive aged women, it is recommended to send 17-hydroxyprogesterone (17-OHP) in all female patients with apparent PCOS to rule out NC-CAH. Elevated basal 17-OHP levels (measured around 8am during the follicular phase of the menstrual cycle) above 200 are diagnostic for NC-CAH. If 17-OHP levels are not diagnostic, ACTH stimulation testing can be used. Of note, classic CAH is usually identified at birth or in infancy due to atypical genitalia or adrenal crisis; routine newborn screening for 21-hydroxylase deficiency is now required in the US and many other countries. In contrast, non-classic CAH is a milder form that is not typically detected on the newborn screen and is usually diagnosed in adolescence or adulthood. Glucocorticoids are used to treat both types.

References: NC-CAH vs. PCOS

Tardive dyskinesia (TD) is a medication-induced hyperkinetic movement disorder associated with the use of dopamine receptor-blocking agents, such as first and second generation antipsychotic drugs, metoclopramide, and prochlorperazine. Prevention of TD can only be achieved by avoiding treatment with offending agents but symptoms may persist past the discontinuation of the drug. If continued treatment is needed, second generation antipsychotics are preferred over first generation, especially in older patients. For patients with persistent TD, the treatment of choice is Vesicular Monoamine Transporter Type 2 (VMAT2) inhibitors, such as valbenazine, deutetrabenazine, and tetrabenazine. If dystonia is focal, botulinum toxin injections can also be used to avoid systemic therapies. It is important to note that chronic use of prophylactic anticholinergic drugs – such as benztropine – is not recommended, as they do not prevent TD and may aggravate symptoms if they arise.

References: Tardive Dyskinesia

Incidentally discovered adrenal masses or “incidentalomas” are commonly revealed on abdominal imaging, but the prevalence varies considerably across studies. This is likely because studies typically involve cohorts undergoing imaging for a particular clinical indication, which could bias both prevalence and proportion of hormonally active or malignant lesions. To overcome this, researchers in China performed abdominal CT scans in 25,000 generally healthy, asymptomatic adults aged 18-78 who were presenting for routine “annual health checkups.” The overall prevalence of adrenal incidentalomas >10mm was 1.4% with prevalence increasing with age, up to 3.2% in people 65 years or older. Of the 351 incidentalomas, none were malignant. Two-thirds of these patients underwent laboratory evaluation; 20% had autonomous cortical secretion and 12% had primary aldosteronism. While this study likely provides the best estimate to date of adrenal incidentalomas in relatively healthy people, it is worth considering the external validity of the findings beyond China.

References: Adrenal Incidentalomas