Different FT3/TSH Correlation in Acquired and Congenital Hypothyroid Patients Reveals a Different Hypothalamic Set-Point

Marco Russo; Damiano Gullo; Dario Tumino; Daniela Leonardi; Pasqualino Malandrino; Francesco Frasca


Clin Endocrinol. 2023;98(1):117-122. 

In This Article

Abstract and Introduction


Objective: To understand differences in thyroid hormone replacement therapy with levo-thyroxine (L-T4) between acquired and congenital hypothyroid (CH) patients.

Design: We compared biochemical thyroid parameters between euthyroid subjects (EU) and both CH adult patients and thyroidectomized patients (TP) under replacement therapy.

Patients and Measurements: A retrospective analysis was performed on a series of 98 consecutive adult CH patients (27 males and 71 females) with a median age of 24 years (range 18–58). Serum TSH, FT3, FT4, L-T4 dose and body weight were assessed. For comparison purposes, large series of 461 TP for thyroid cancer and 1852 EU followed at our Thyroid Clinic were used as control groups.

Results: The daily weight-based L-T4 dose was significantly higher in CH than TP group (1.9 vs. 1.7 mcg/kg, p = .03). FT3/FT4 ratio was significantly higher in the EU group, intermediate in CH and lower in TP groups (0.32, 0.28 and 0.24, respectively). Linear regression analysis displayed an inverse correlation between FT4 and TSH in all the groups. An inverse correlation between FT3 and TSH was observed in the TP group, but not in the EU and CH group suggesting that CH patients, under replacement therapy, display biochemical thyroid parameters similar to EU subjects.

Conclusions: Adult CH patients require a higher daily L-T4 dose than adult TP. However, the different correlation of TSH and FT3 values between CH and TP patients suggests an adaptive and different hypothalamic–pituitary–thyroid axis regulation that may depend on the early timing of the onset of hypothyroidism in CH.


Congenital hypothyroidism (CH) is the most frequent endocrine disease present at birth (1/2000 newborn).[1] CH is due to a defect in the developmental process of the thyroid gland during foetal life in 80%–85% of cases, resulting in either absence of any thyroid tissue (athyreosis) or a hypoplasic/ectopic gland. Less frequently (15%–20% of cases), genetic defects in thyroid hormones synthesis may result in a properly developed but nonfunctioning thyroid gland.[2]

Oral administration of levo-thyroxine (L-T4) is the therapy of choice in both congenital and acquired hypothyroidism and theL-T4 dose is based on the tissue requirement of thyroid hormone in hypothyroid patients.[3–5] Several studies reported that adult CH patients require a higher weight-basedL-T4 dose than adult-acquired hypothyroid patients. Moreover, compared to adult hypothyroid subjects, many CH patients exhibit higher serum TSH levels despite normal serum FT4 and FT3 levels.[6–8] This apparent 'resistance' toL-T4 has been attributed to an altered hypothalamus–pituitary feedback set-point to T4 levels.[9,10]

The purpose of this study is to evaluate theL-T4 requirement dose and biochemical thyroid parameters in adult CH patients, in comparison with adult thyroidectomized subjects underL-T4 replacement therapy and euthyroid subjects (EU).