Diagnosis and Management of Central Congenital Hypothyroidism

Abstract

Central congenital hypothyroidism (CH) is defined as thyroid hormone (TH) deficiency at birth due to insufficient stimulation by the pituitary of the thyroid gland. The incidence of central CH is currently estimated at around 1:13,000. Central CH may occur in isolation, but in the majority of cases (60%) it is part of combined pituitary hormone deficiencies (CPHD). In recent years several novel genetic causes of isolated central CH have been discovered (IGSF1, TBL1X, IRS4), and up to 90% of isolated central CH cases can be genetically explained. For CPHD the etiology usually remains unknown, although pituitary stalk interruption syndrome does seem to be the most common anatomic pituitary malformation associated with CPHD. Recent studies have shown that central CH is a more severe condition than previously thought, and that early detection and treatment leads to good neurodevelopmental outcome. However, in the neonatal period the clinical diagnosis is often missed despite hospital admission because of feeding problems, hypoglycemia and prolonged jaundice. This review provides an update on the etiology and prognosis of central CH, and a practical approach to diagnosis and management of this intriguing condition.

Congenital Hypothyroidism in Preterm Newborns – The Challenges of Diagnostics and Treatment: A Review

“…Consequently, there is an increasing incidence of congenital hypothyroidism (60,61). Despite its estimated prevalence between 1:2000 and 1:4000 in infants, there is evidence about epidemiological differences dependent on the geographic location (62).…”

An Overview on Different L-Thyroxine (l-T4) Formulations and Factors Potentially Influencing the Treatment of Congenital Hypothyroidism During the First 3 Years of Life

“…Many data and recently updated CH consensus guidelines support the treatment of cCH with a once daily administration of l-T 4 ( 13 ). In severe cCH (serum FT 4 levels before treatment below 5 pmol/L), the minimum l-T 4 starting dose should be no less than 10 μg/kg/day, in order to promptly bring FT 4 within the normal age-adjusted range ( 49 ). A lower starting dose of l-T 4 (from 5 to 10 μg/kg per day) should be used in milder forms to avoid overtreatment.…”

“…A lower starting dose of l-T 4 (from 5 to 10 μg/kg per day) should be used in milder forms to avoid overtreatment. For primary CH, the long-term biochemical aim must be to bring and maintain serum FT 4 within the upper half of the reference interval for the patient’s age ( 49 ). Although it remains essential to conduct randomized clinical trials in children to obtain specific results for the paediatric population, data from adult studies support this approach ( 50 , 51 ).…”

“…Instead, serum FT 4 is the most reliable indicator of efficacy of treatment. If TSH levels prior to treatment are low, it is not necessary to take subsequent TSH measurements ( 13 , 49 ).…”

Hypothyroidism and Diabetes-Related Dementia: Focused on Neuronal Dysfunction, Insulin Resistance, and Dyslipidemia

“…Thyroid dysfunctions are classified based on the serum levels of TH and TSH. Overt hypothyroidism manifests as decreased T3 and T4 levels and increased TSH; overt hyperthyroidism manifests as increased T3 and T4 levels and decreased TSH; subclinical hypothyroidism shows normal T3 and T4 levels with increased TSH and subclinical hyperthyroidism shows normal T3 and T4 levels and decreased TSH levels [ 57 , 58 , 59 ].…”