Endocrinopathies in Rubinstein Taybi Syndrome (RTS)

Introduction:
Rubinstein-Taybi syndrome (RTS) is a rare genetic disorder with a constellation of physical characteristic features, including a high-arched palate, broad thumbs, and microcephaly. It is associated with many endocrinopathies that need to be identified and treated. We present a case of RTS with associated hypogonadism, obesity, and type 2 diabetes Mellitus (DM).

Case Description:
The patient is a 47 y/o man with a history of Rubinstein-Taybi syndrome, diagnosed at 3, presented to our clinic at age 33 for continued management of hypogonadism. He had been treated with IM testosterone injection but was not compliant. His past medical history was significant for a seizure disorder, recurrent respiratory infection, and undescended testes for which he had surgery at age 5 and 11. Family history was positive for type 2 DM. He denied smoking and illicit drug use; however, he reported occasional alcohol use. Upon initial evaluation, VS: BP 109/63, HR 71, Ht 67.1 inches, Wt 265 lbs with a BMI 41.5. A physical exam showed an obese man with facial dysmorphism of microcephaly, up-slanted palpebral fissure, overcrowded teeth, broad bilateral thumbs, fifth fingers, and first toes. A wide space between the 1st and 2nd toe was noted, with sparse pubic and axillary hair, a small testis on the right, and an empty scrotum on the left. Labs were pertinent for total testosterone 134 ng/dl (264-916 ng/dl), FSH <0.3 mIU/ml (1.6-8.0 mIU/mL), LH <0.1 mIU/ml (1.5-9.3 mIU/mL), and WBCs 17.3 x 10E3/uL. Initial HbA1c 6.3%. Scrotal US revealed an empty left scrotum and hypovascular small right testis. Persistent leukocytosis was noted, ranging between 17.3-12.4 x 10E3/uL, for which he was sent to hematology; subsequent evaluation was unremarkable. Over the years, he progressed to type 2 DM, for which he is receiving glucagon-like peptide-1 receptor agonist (GLP-1) and metformin. With the addition of the GLP-1, his BMI decreased from 41 to 31, and his most recent HbA1c was 6.2%. For hypogonadism, he continues on IM testosterone injections.

Discussion:
RTS is a rare congenital condition linked to abnormalities in the CREBBP or EP300 genes as a result of microdeletion of chromosomes 16. 90% of cases survive to adulthood. Common endocrine conditions associated with RTS are congenital hypothyroidism, thyroid hypoplasia, growth hormone deficiency, and pituitary hypoplasia. Obesity is common, especially in adulthood; however, DM was not reported in the literature. Cryptorchidism is noted in over 70% of the cases. Of note, leukemia and lymphoma have also been linked to this syndrome; however, our patient's workup so far has been negative. The medical care for RTS patients is not standardized due to its incredibly rare nature. Our case is unique as there are no reported RTS patients with diabetes. These patients are at increased risk of obesity which will increase the risk of type 2 DM.