According to a new guideline from the European Society of Endocrinology, patients with obesity should be routinely tested for thyroid function. However, testing for other endocrine-related conditions should be guided by the presence of symptoms.
The endocrine system and obesity can have a push-pull relationship.
Some endocrine disorders — such as hypothyroidism and Cushing’s syndrome — can cause weight gain and push patients toward the metabolic perturbations related to obesity. Obesity can pull patients toward endocrine dysfunction such as gonadal dysfunction, hypothalamic-pituitary-adrenal axis abnormalities, insulin resistance, and more.
This complexity can confuse the assignments of causes and effects and make it hard to ascertain the most effective testing strategies. The European Society of Endocrinology recently weighed in with help. “Endocrine Work-up in Obesity” is a new clinical practice guideline with evidence-based advice on testing in a host of conditions. It was published in the January issue of the European Journal of Endocrinology.
“An increased BMI leads to a number of hormonal changes,” the guideline notes. “Concomitant hormonal diseases can be present in obesity and have to be properly diagnosed — which in turn might be more difficult due to alterations caused by body fatness itself.”
But regardless of any testing strategies, the guideline underlines that “weight loss in obesity should be emphasized as key to restoration of hormonal [balances].” Weight loss is likely to be a more effective treatment for obesity-related conditions than attempting to treat the conditions separately and independently.
The guideline’s main sections are devoted to thyroid function, hypercortisolism, hypogonadism in males, gonadal dysfunction in females, and “other hormones.”
Thyroid Function’s Special Place
Given the high prevalence of hypothyroidism in obesity, the guideline recommends that all patients with obesity should be tested for thyroid function — the only condition for which it recommends testing without the need for signs and symptoms.
The guideline recommends thyroid screening because of the prevalence, but also because hypothyroidism “could potentiate weight gain and worsen comorbidities in obesity, and because assessment is simple, and treatment is inexpensive and safe.”
The guideline notes that it is worth testing for hypothyroidism because the “symptoms of hypothyroidism (such as fatigue, depression, cramps, menstrual disturbance or weight gain) are nonspecific and can be confused with those of obesity. If ‘true’ hypothyroidism is present, it potentiates the risk of obesity to develop cardiovascular risk factors and features of metabolic syndrome. Hypothyroidism contributes to an unfavorable lipid profile, and thus, potentially increases vascular risk. Finally, untreated hypothyroidism could blight the attempts at losing body weight.”
The testing should be based on thyroid-stimulating hormone, and if TSH is elevated, free T4 and antibodies should be measured.
“With the exception of screening for hypothyroidism, most endocrine testing is not recommended in the absence of clinical features of endocrine syndromes in obesity, and likewise hormone treatment is rarely needed,” writes John P.H. Wilding, MD, in a commentary that accompanied the guideline. Wilding is professor of medicine at the University of Liverpool in the U.K.
Testing for hypercortisolism should not be performed routinely, but only among people in whom there is clinical suspicion. The guideline specifies that patients using corticosteroids should not be tested for hypercortisolism but carves out an exception to this rule for patients planning on bariatric surgery — testing should be considered in these cases.
If hypercortisolism testing is in order, the guideline recommends an overnight dexamethasone suppression test as the first screening tool.
Although biochemical testing for hypogonadism is not routinely recommended in male patients with obesity, the guideline recommends investigating key clinical signs and symptoms, such as erectile dysfunction, reduced sexual desire, muscle weakness, changes in mood, fatigue, cognitive impairment, and more.
In the patients with clinical features of hypogonadism, the guideline suggests measuring total and free testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH).
Gonadal Dysfunction in Women
The guideline recommends against routine testing for gonadal dysfunction in female patients with obesity, and notes that symptoms that justify assessing gonadal function include menstrual irregularities, chronic anovulation, and infertility. The approach to testing depends on the suspected condition.
“The guidelines … not only identify when an endocrinological workup and referral is recommended, but also provide specific guidance on commonly encountered medical co-morbid conditions that are seen in the obesity population … They do not appear to conflict with recommendations and standards used in the U.S.” – Robert F. Kushner, MD, professor of medicine and medical education; director, Center for Lifestyle Medicine at Northwestern University Feinberg School of Medicine, Chicago, Ill.; member, Endocrine Society’s “The Science of Obesity Management: An Endocrine Society Scientific Statement” guideline committee
The guideline notes: “For evaluation of menstrual irregularity, we suggest to assess gonadal function by measuring LH, FSH, total testosterone, SHBG, Δ 4androstenedione, estradiol, 17-hydroxyprogesterone, and prolactin. If the menstrual cycle is irregular but somewhat predictable, we suggest that the assessment should take place during the early follicular phase. For evaluation of anovulation, we suggest gonadal function to be assessed by measuring LH, FSH, estradiol, progesterone, and prolactin.”
When clinical features suggest polycystic ovarian syndrome, the guideline recommends assessing androgen excess, and specifically, “we suggest to measure total testosterone, free testosterone, Δ 4androstenedione, and SHBG. We additionally recommend to assess ovarian morphology and blood glucose.”
The main points of the section on “other hormones” include:
- Recommending against routine testing for growth factor or insulin-like growth factor 1, with such testing reserved for patients with suspected hypopituitarism;
- Suggesting against performing routine tests for vitamin D deficiency;
- Suggesting not testing for hyperparathyroidism routinely in patients with obesity;
- Recommending not testing routinely for hormones such as leptin and ghrelin unless there is suspicion of a syndromic obesity; and
- Suggesting that secondary causes of hypertension be considered in the context of therapy-resistant hypertension in obesity.
“These guidelines should help reduce unnecessary endocrine testing in those referred for assessment of obesity,” Wilding notes in his commentary, “and encourage clinicians to support patients with their attempts at weight loss, which if successful has a good chance of correcting any endocrine dysfunction.”
These new guidelines “will be a welcome addition to the other existing obesity guidelines,” says Robert F. Kushner, MD, professor of medicine and medical education and director of the Center for Lifestyle Medicine at Northwestern University Feinberg School of Medicine. Kushner worked on the committee that wrote “The Science of Obesity Management: An Endocrine Society Scientific Statement.”
“The guidelines are structured as a logical set of practical and clinically useful recommendations that apply to patients who present with obesity. They not only identify when an endocrinological workup and referral is recommended, but also provide specific guidance on commonly encountered medical co-morbid conditions that are seen in the obesity population, such as hypothyroidism, erectile dysfunction, and menstrual irregularity. They do not appear to conflict with recommendations and standards used in the U.S.,” Kushner says.
— Seaborg is a freelance writer based in Charlottesville, Va., and a frequent contributor to Endocrine News. In the September issue, he wrote about real world evidence and the possibility of virtual clinical drug trials.