Medscape, April 28, 2026
The Medicalization of Normal Lab Variations: When ‘Abnormal’ Isn’t DiseaseUday S. Dadhwal, MS, MRCS“I think I have a thyroid problem.”
The patient sitting in front of me looked worried. She had come to my internal medicine clinic after a routine health check revealed a thyroid-stimulating hormone (TSH) level of 5.8 mIU/L — just above the laboratory reference range. She had already searched online, read about hypothyroidism, and wanted to know whether she needed medication.
But she felt completely well. Her free T4 was normal, and she had no fatigue, weight gain, or cold intolerance. If the test had never been done, neither of us would have suspected thyroid disease. We decided to repeat the test rather than start treatment. Three months later, her TSH was normal.
Cases like this are increasingly common and often fall under the category of
subclinical hypothyroidism— mildly elevated TSH with normal thyroid hormone levels. Yet the clinical significance of these mild abnormalities remains uncertain.
The Statistics Behind “Abnormal”Most laboratory reference ranges include the middle 95% of values from healthy individuals. By definition, 5% of healthy people will fall outside the range. That means an abnormal result does not necessarily indicate pathology — only that the value lies outside a statistical boundary. Yet in everyday practice, mild deviations frequently trigger further testing, specialist referrals, and sometimes treatment.
A randomized trial in older adults with subclinical hypothyroidism found that levothyroxine therapy did not improve symptoms or quality of life compared with placebo. A systematic review reached similar conclusions regarding symptom benefits. Despite this evidence, many patients with borderline TSH elevations are started on lifelong thyroid replacement therapy after a single abnormal result.
Prediabetes and the Expanding Disease BoundaryA different patient came to clinic distressed after a routine health screening showed an A1c of 5.8%. He had been told he had prediabetes. He assumed diabetes was inevitable. The American Diabetes Association emphasizes that prediabetes is not a disease in itself, but rather a risk factor for developing type 2 diabetes.
In his case, no medication was started. We focused on lifestyle measures — modest weight control, diet, and regular activity — and monitored his A1c. On follow-up about a year later, his levels had returned to the normal range, and he did not progress to type 2 diabetes.
In reality, progression from prediabetes to diabetes is far from certain. Depending on definitions and populations, 30%-60% of individuals with prediabetes revert to normal glucose regulation within 1-5 years, and pooled data from prospective cohorts suggest that reversion to normoglycemia can be more common than progression to overt diabetes.
Cortisol Testing and False AlarmsScreening for Cushing syndrome can also illustrate the limits of laboratory interpretation.
I recall a patient referred for evaluation after a slightly elevated late-night salivary cortisol test, which had been ordered as part of a broad endocrine workup for nonspecific symptoms such as fatigue and poor sleep. She had no classic physical features of Cushing syndrome but had recently been under intense psychological stress. Further testing showed normal cortisol regulation.
Conditions such as depression, obesity, alcoholism, and severe stress can produce false-positive cortisol tests, sometimes called pseudo-Cushing states. Pseudo‑Cushing syndrome mimics hypercortisolism but resolves once the underlying condition — such as depression, alcoholism, or severe stress — improves.
Endocrine guidelines emphasize that screening tests for Cushing syndrome must be interpreted in context and confirmed before diagnosing the condition.
Testosterone and the Medicalization of AgingAnother patient — a man in his late 50s — sought consultation after being told his testosterone level was “low.” He had mild fatigue but otherwise felt well. Repeat morning testing showed normal levels.
Testosterone varies widely depending on time of day, illness, sleep, and laboratory variability. It also declines gradually with age.
The testosterone measurement guidelines emphasize that a diagnosis of male hypogonadism should not be made on a single laboratory value. Morning testosterone should be confirmed on repeat testing and correlated with clinical symptoms before treatment is initiated.
Nevertheless, direct-to-consumer advertising and routine testing have contributed to an increase in testosterone prescriptions — sometimes for men whose levels fall within normal age-related variation.
How to Practice Medicine in the Gray ZoneAbnormal lab results should not be ignored, but they must be interpreted in clinical context. Physicians should focus on the patient’s symptoms and history rather than isolated numbers, repeat tests with borderline results before diagnosing disease, recognize normal statistical variation in laboratory values, and clearly communicate uncertainty so patients understand that reference ranges are statistical guides rather than absolute indicators of illness.
Modern medicine has powerful diagnostic tools. But when every deviation becomes disease, we risk pathologizing normal human physiology. The goal should not be fewer tests, but better interpretation of the tests we order. Sometimes the most appropriate response to an abnormal lab value is not treatment, imaging, or referral. Sometimes it is simply perspective.
This article was drafted with the assistance of an AI language model (ChatGPT) for language editing and organization. The author reviewed, revised, and approved the final content and takes full responsibility for the article. Δεν είναι ορατοί οι σύνδεσμοι (links).
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2 Ιουλίου 2012, 20:42:37