# Weight Loss Improved Hypothalamic GH Deficiency but not Hypogonadotropic Hypogonadism in a Man With Down Syndrome

**Authors:** Yukie Nakagawa, Katsumi Taki

PMC · DOI: 10.1210/jcemcr/luae114 · JCEM Case Reports · 2024-07-18

## TL;DR

A man with Down syndrome experienced improved GH deficiency after significant weight loss, but his hypogonadism remained unresolved.

## Contribution

This case study shows that weight loss can improve hypothalamic GH deficiency in Down syndrome without resolving hypogonadism.

## Key findings

- Weight loss improved IGF-1, TSH, and prolactin levels to normal ranges.
- LH and FSH levels remained low despite weight loss.
- Leptin decreased and ghrelin increased with weight loss, possibly influencing hormone changes.

## Abstract

Down syndrome (DS) is associated with several endocrine disorders, including diabetes, obesity, and primary hypogonadism. Here, we present a man with DS who manifested with atypical hypogonadotropic hypogonadism and in whom weight loss resulted in the improvement of hypothalamic GH deficiency. A 27-year-old man with DS and severe obesity was admitted for hypoxia resulting from obesity hypoventilation syndrome. Laboratory tests showed normal levels of LH and FSH despite low testosterone and free testosterone levels. Moreover, thyroid stimulating hormone and prolactin levels were slightly elevated, although a euthyroid function was observed, and GH and IGF-1 levels were low. Endocrinological stimulation tests revealed hypogonadotropic hypogonadism and hypothalamic GH deficiency. Reduction in body weight by 35.3% resulted in the improvement of the IGF-1, thyroid stimulating hormone, and prolactin levels to the reference range, whereas the LH and FSH levels remained low, despite slight elevation. Levels of leptin, which suppresses the hypothalamus–gonadotroph–gonadal axis and upregulates thyrotropin-releasing hormone expression, decreased with weight loss. Furthermore, ghrelin, whose levels increase with weight loss, stimulates GH secretion. Thus, leptin and ghrelin could have contributed to the observed changes in the pituitary hormone profile after weight loss.

## Linked entities

- **Proteins:** PLOD1 (procollagen-lysine,2-oxoglutarate 5-dioxygenase 1), BRD2 (bromodomain containing 2), PROLACTIN (PROLACTIN protein), GH1 (growth hormone 1), IGF1 (insulin like growth factor 1), lepa (leptin a), GHRL (ghrelin and obestatin prepropeptide)
- **Diseases:** Down syndrome (MONDO:0008608), diabetes (MONDO:0005015), obesity (MONDO:0011122), hypogonadotropic hypogonadism (MONDO:0018555), obesity hypoventilation syndrome (MONDO:0009763)

## Full-text entities

- **Genes:** IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, PRL (prolactin) [NCBI Gene 5617] {aka GHA1, pPRL}, GGH (gamma-glutamyl hydrolase) [NCBI Gene 8836] {aka GATD10, GH}, TRH (thyrotropin releasing hormone) [NCBI Gene 7200] {aka Pro-TRH, TRF}, LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}
- **Diseases:** obesity (MESH:D009765), Hypogonadotropic Hypogonadism (MESH:D007006), hypoxia (MESH:D000860), obesity hypoventilation syndrome (MESH:D010845), Hypothalamic (MESH:D007027), Man (MESH:D016750), endocrine disorders (MESH:D004700), DS (MESH:D004314), Weight Loss (MESH:D015431), diabetes (MESH:D003920), GH Deficiency (MESH:D006432)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11255480/full.md

## References

22 references — full list in the complete paper: https://tomesphere.com/paper/PMC11255480/full.md

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Source: https://tomesphere.com/paper/PMC11255480