Case history: We present a 61-year-old male with a background history of 47 XYY syndrome who was referred to the endocrine outpatient service with abnormal thyroid function tests. He has mild learning disabilities, asthma, action tremor, erectile dysfunction, and type 2 diabetes. He was tall in stature with obvious clinodactyly. He had been evaluated for his tremor by our Neurology colleagues.
Investigations: His blood tests results were as follow- TSH 5.38 mIU/L (0.27-4.20), FT4 11.6 pmol/l (12.0-22-0), FT3 4.5 pmol/l (3.1-6.8), Testosterone 16.9nmol/l ( 6.3-26.5), LH 15.6 IU.L (1.7-8.6), FSH 7.7IU/L (1.5-12.4), Prolactin 200 mIU/L (86-324), Cortisol 309 nmol/l, IGF-1 16.3 nmol/l (3.5-32.0). His Anti TPO were negative.
Discussion of results: His testosterone levels were normal with mildly elevated LH and normal FSH. The Thyroid function tests were in keeping with primary hypothyroidism with negative antibodies.
Conclusions and points for discussion: 47 XYY Syndrome, also known as Jacobs syndrome (JS), is a rare genetic condition. Hallmark clinical features includes tall stature, clinodactyly, macrocephaly & hypertelorism. Recognized associated complications includes asthma, action tremor, seizure disorders, infertility, and psychological problems (1). An action tremor can be seen in JS and should be a clue to consideration of karyotyping. Also patients should be offered genetic testing to rule out Klinefelters syndrome (KS) 47 XXY where some patients sometimes share JS features including tall stature & infertility. In KS, the testes are likely to be small in volume with presence of gynecomastia. There are no previous studies to suggest any correlation between Hypothyroidism and JS, but one multicentre study showed that the prevalence of hypothyroidism in KS was similar to normal male population, showing absence of increased risk of hypothyroidism associated with the XXY karyotype (2).
References: 1. Sood B, Clemente Fuentes RW. Jacobs Syndrome. 2022 Sep 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. PMID: 32491631. 2. Balercia, G., Bonomi, M., Giagulli, V.A. et al. Thyroid function in Klinefelter syndrome: a multicentre study from KING group. J Endocrinol Invest 42, 11991204 (2019). https://doi.org/10.1007/s40618-019-01037-2