Treating hypothyroidism is not always easy: when to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy

Ross, Douglas S.

doi:10.1111/joim.13410

Cited by 42Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryThyroid Cancer Diagnosis and Treatment

Treating hypothyroidism is not always easy: when to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy

Ross, Douglas S.·2022·Journal of Internal Medicine

DOI 10.1111/joim.13410

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Abstract

The majority of patients with hypothyroidism feel better when levothyroxine treatment restores thyroid-stimulating hormone (TSH) concentrations to normal. Increasingly, a significant minority of patients remain symptomatic and are dissatisfied with their treatment. Overzealous treatment of symptomatic patients with subclinical hypothyroidism may contribute to dissatisfaction among hypothyroidism patients, as potential hypothyroid symptoms in patients with minimal hypothyroidism rarely respond to treatment. Thyroid hormone prescriptions have increased by 30% in the United States in the last decade. The diagnosis of subclinical hypothyroidism should be confirmed by repeat thyroid function tests ideally obtained at least 2 months later, as 62% of elevated TSH levels may revert to normal spontaneously. Generally, treatment is not necessary unless the TSH exceeds 7.0-10 mIU/L. In double-blinded randomized controlled trials, treatment does not improve symptoms or cognitive function if the TSH is less than 10 mIU/L. While cardiovascular events may be reduced in patients under age 65 with subclinical hypothyroidism who are treated with levothyroxine, treatment may be harmful in elderly patients with subclinical hypothyroidism. TSH goals are age dependent, with a 97.5 percentile (upper limit of normal) of 3.6 mIU/L for patients under age 40, and 7.5 mIU/L for patients over age 80. In some hypothyroid patients who are dissatisfied with treatment, especially those with a polymorphism in type 2 deiodinase, combined treatment with levothyroxine and liothyronine may be preferred.

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Most cases of primary hypothyroidism are initially mild or subclinical and there is no consensus on when to start treatment.
“This issue is further complicated by the evidence that most cases of primary hypothyroidism are initially mild or subclinical and there is no consensus on when to start treatment (3, 9).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [9]
There is robust evidence that serum TSH levels increase slightly with age, particularly after age 65-70 years.
“There is robust evidence that serum TSH levels increase slightly with age, particularly after the age of 65–70 years (9, 74).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [9]
Treatment of elderly patients is usually suggested only for patients showing persistent TSH levels >10 mU/L, while the decision is patient-tailored for TSH levels between 7 and 10 mU/L.
“Therefore, the treatment of elderly patients is usually suggested only for patients showing persistent TSH levels >10 mU/L, while the decision is patient-tailored for TSH levels between 7 and 10 mU/L (9).”
From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [9]
Recent expert advice provides similar recommendations, which encompasses the physiological ratio of T4:T3 in the circulation.
“Recent expert advice provides similar recommendations 65 , which encompasses the physiological ratio of T4:T3 in the circulation 66,67 .”
From A review of the safety of triiodothyronine in combination with levothyroxine for the management of hypothyroidism (2024) · cites this paper as [66]

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Authors: Ross, D. S.
Affiliations: Harvard University (US)
Corresponding author: Ross, Douglas S.
ORCID: Ross, Douglas S.
Venue: Journal of Internal Medicine
Publisher: Wiley
Published: 2021-11-11
Volume: 291
Issue: 2
Pages: 128-140
ISSN: 0954-6820 (ISSN-L)
1365-2796
DOI: 10.1111/joim.13410
OpenAlex: W3212871472
Cited by: 42
References: 86
Citations by year: 2026: 8 · 2025: 12 · 2024: 8 · 2023: 12 · 2022: 2
FWCI: 0.84
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Internal Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords: subclinical hypothyroidism, hypothyroidism treatment, levothyroxine, elderly patients, liothyronine, treatment thresholds, cardiovascular events, treatment dissatisfaction
MeSH terms: Aged, Aged, 80 and over, Humans, Hypothyroidism, Thyroid Hormones, Thyrotropin, Thyroxine

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Treating hypothyroidism is not always easy: when to treat subclinical hypothyroidism, TSH goals in the elderly, and alternatives to levothyroxine monotherapy

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