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      Anastrozole Improves Final Adult Height in Severe Hypothyroidism With Rapid Pubertal Progression

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          Abstract

          Severe prolonged hypothyroidism due to Hashimoto thyroiditis may lead to rapid pubertal progression and compromised adult height after initiation of levothyroxine (LT4) therapy. There are no reports of aromatase inhibitor use to augment height in these patients. We describe a patient with severe hypothyroidism and growth failure who experienced rapid pubertal and bone age maturation on initiation of LT4 therapy. Anastrozole was added after 2 years to delay epiphyseal fusion.

          A boy aged 12 years and 1 month presented to the endocrine clinic with short stature and a markedly delayed bone age of 6 years. Brain magnetic resonance imaging showed a 1.5 × 1.0 × 1.2-cm enlarged lobular anterior pituitary. On examination, his height was –3.5 SD score (SDS) and weight was –2.87 SDS. Laboratory studies showed elevated thyrotropin (TSH) 850.6 μIU/mL, low free thyroxine 0.25 ng/dL, and elevated antithyroid antibodies. LT4 was initiated with normalization of TSH after 6 months. After 2 years of treatment he demonstrated catch-up growth with rapid bone age maturation, and his predicted adult height was compromised at 164.6 cm vs a midparental target height of 175.4 cm. Anastrozole 1 mg once daily was initiated. After 1.5 years of anastrozole treatment, the rate of his bone age advancement had slowed and his linear growth remained robust. The patient’s near-final height (167 cm) was 2.4 cm taller than his height prediction prior to starting anastrozole.

          Anastrozole slowed the rate of bone age advancement in a patient with severe hypothyroidism and rapidly progressive puberty during treatment with LT4, leading to improvement in near-final height.

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          Most cited references24

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          Tables for predicting adult height from skeletal age: revised for use with the Greulich-Pyle hand standards.

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            Endocrine Regulation of the Growth Plate

            Longitudinal bone growth occurs at the growth plate by endochondral ossification. Within the growth plate, chondrocyte proliferation, hypertrophy, and cartilage matrix secretion result in chondrogenesis. The newly formed cartilage is invaded by blood vessels and bone cells that remodel the newly formed cartilage into bone tissue. This process of longitudinal bone growth is governed by a complex network of endocrine signals, including growth hormone, insulin-like growth factor I, glucocorticoid, thyroid hormone, estrogen, androgen, vitamin D, and leptin. Many of these signals regulate growth plate function, both by acting locally on growth plate chondrocytes and also indirectly by modulating other endocrine signals in the network. Some of the local effects of hormones are mediated by changes in paracrine factors that control chondrocyte proliferation and differentiation. Many human skeletal growth disorders are caused by abnormalities in the endocrine regulation of the growth plate. This review provides an overview of the endocrine signals that regulate longitudinal bone growth, their interactions, and the mechanisms by which they affect growth plate chondrogenesis.
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              Inhibition of estrogen biosynthesis with a potent aromatase inhibitor increases predicted adult height in boys with idiopathic short stature: a randomized controlled trial.

              In males as well as in females, estrogen is an essential regulator of bone maturation, growth plate fusion, and cessation of longitudinal growth. Therefore, an increase in predicted adult height (PAH) may be achieved in short boys by blocking estrogen biosynthesis. We tested the hypothesis that a decrease in the rate of bone maturation and an increase in PAH can be achieved in boys with idiopathic short stature (ISS) by the method of blocking estrogen biosynthesis with an aromatase inhibitor. Secondarily, we investigated the effects of aromatase inhibition on bone mineralization. This was a prospective, double-blind, randomized, placebo (Pl)-controlled clinical study. The study was performed at a university hospital out-patient clinic. Thirty-one boys, aged 9.0-14.5 yr, with ISS were studied. The boys were treated with the aromatase inhibitor letrozole (Lz; 2.5 mg/d) or Pl for 2 yr. The main outcome measure was the change in PAH after 24 months of treatment. PAH increased by 5.9 cm (P < 0.0001), and height SD score for bone age increased by 0.7 SD score (P < 0.0001) in the Lz-treated boys, whereas no changes occurred in the respective measures in Pl-treated boys. Areal bone mineral density of the lumbar spine and femoral neck, assessed by dual-energy x-ray absorptiometry, increased in a similar fashion in both groups during the treatment, whereas bone mineral apparent density increased only in those taking Lz (median increase, 4.3%; P = 0.009). Treatment with the aromatase inhibitor Lz delays bone maturation and improves PAH in boys with ISS. No adverse effects on bone mineralization were evident after 2 yr of treatment.
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                Author and article information

                Contributors
                Journal
                J Endocr Soc
                J Endocr Soc
                jes
                Journal of the Endocrine Society
                Oxford University Press (US )
                2472-1972
                01 May 2021
                20 February 2021
                20 February 2021
                : 5
                : 5
                : bvab025
                Affiliations
                [1 ] Division of Pediatric Endocrinology, Seattle Children’s Hospital, University of Washington , Seattle, Washington 98105, USA
                [2 ] Division of Pediatric Endocrinology, Rhode Island Hospital and Warren Alpert Medical School of Brown University , Providence, Rhode Island 02903, USA
                [3 ] Division of Pediatric Endocrinology, Nemours/A.I. duPont Hospital for Children and Sidney Kimmel Medical College of Thomas Jefferson University , Wilmington, Delaware 19803, USA
                Author notes
                Correspondence: Juanita K. Hodax, MD, Division of Pediatric Endocrinology, Seattle Children’s Hospital, 4800 Sand Point Way NE, Seattle, WA 98105, USA. Email: juanita.hodax@ 123456seattlechildrens.org .
                Author information
                https://orcid.org/0000-0003-3441-3877
                https://orcid.org/0000-0003-1691-2293
                Article
                bvab025
                10.1210/jendso/bvab025
                8064049
                4ec960be-41d4-43a1-a71f-6ed3da7fabc1
                © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 13 November 2020
                : 12 February 2021
                : 23 April 2021
                Page count
                Pages: 6
                Categories
                Case Reports
                AcademicSubjects/MED00250

                hypothyroidism,short stature,aromatase inhibitor,bone age

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