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Daily Thyroxine Dose Up to 1.4 mcg/kg Not Adequate in Hypopituitary Patients: Presented at ECE

By Chris Berrie

BERLIN -- May 5, 2008 -- Thyroxine replacement therapy at daily doses up to 1.4 mcg/kg results in inadequate treatment for patients with central hypothyroidism (CH), according to a study presented here at the 10th European Congress of Endocrinology (ECE).

This finding is important because "even minor thyroid dysfunction may have detrimental metabolic effects," said Helena Filipsson, MD, Principal Investigator and Consultant in Internal Medicine and Endocrinology, Department of Endocrinology, Sahlgrenska Academy, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden.

Dr. Filipsson presented an analysis of collected data from the KIMS (Pfizer International Metabolic Database) database in a presentation on May 4.

In particular, hypopituitary patients with untreated growth hormone deficiency (GHD) show increases in fat mass, dyslipidaemia, and insulin resistance. Thus, patients with CH who are taking inappropriately low doses of thyroxine may also have such clinical features.

In their study, Dr. Filipsson and colleagues aimed to assess the outcome of thyroxine replacement therapy before and after growth hormone replacement in a large cohort of hypopituitary patients.

By June 2006, the KIMS database comprised 11,591 patients with GHD living in 31 countries. A total of 1,595 GHD patients were identified; of these, 1,080 had CH and 515 were thyroid-stimulating hormone (TSH) sufficient. Clinical profile data were available from baseline and after 2 years of growth hormone treatment. Patients had severe GHD (<3 mcg/L) and were growth hormone-treatment naive.

Patients with CH also were on stable thyroxine replacement therapy. For the comparative assessments, these patients were divided into quartiles according to their daily dose per kilogram of body weight (CHQ1, <= 1.08 mcg/kg/day; CHQ2, 1.09-1.36 mcg/kg/day; CHQ3, 1.37-1.70 mcg/kg/day; CHQ4, >= 1.71 mcg/kg/day).

Patient variables retrieved were also standardised for gender, age, peak growth hormone level, onset of pituitary disease, and number of additional pituitary insufficiencies and other aetiologies.

At baseline, all CH quartiles differed significantly (P < .001) from the TSH-sufficient group, with higher scores for weight, body mass index (BMI), waist circumference (WC), waist/hip ratio (W/H), and high-density lipoprotein cholesterol and total cholesterol levels. In contrast, these patients showed lower scores for glucose levels, IGF-I standard deviation, and quality-of-life assessment of growth hormone deficiency in adults (QoL AGHDA).

When compared across quartiles within the CH group, CHQ1 and CHQ2 patients showed significantly higher weight, blood pressure, and serum IGF-I standard deviation (P < .05 to < .001), and significantly lower QoL AGHDA (P < .05) than the CHQ4 patients. Similarly, CHQ2 patients had higher WC and W/H as compared with the CHQ3 and CHQ4 patients, while W/H also was greater for the CHQ1 versus CHQ3 patients.

After 2 years of growth hormone treatment, these metabolic aberrations in the CH patients were sustained. Further, compared with the TSH-sufficient patient group, the CH patients showed significantly greater growth hormone sensitivity (delta IGF-I/growth hormone dose x10) (P < .001), with more hyperlipidaemia and less cancer.

Therefore, hypothyroid patients with thyroxine levels of up to 1.4 mcg/kg daily presented an unfavourable metabolic profile, indicating inadequate replacement, with the 2 highest thyroxine dose quartiles resembling the TSH-sufficient patients most closely; these differences remained after growth hormone replacement.

Database access approval and statistical support were supplied by Pfizer Inc., and some of the study's co-authors are employees of Pfizer Inc.

Dr. Filipsson thus concluded by stating, "This implies that a patient with a body weight of 50 kg would receive 90 mcg thyroxine per day, and if 70 kg, he will receive 130 mcg per day, and a 90-kg patient [will receive] 165 mcg per day, on average."


[Presentation title: The Adequacy of Thyroxine Replacement in Hypopituitary Patients. Abstract OC1.2]

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