Issue #31 – Down Syndrome and the Endocrine System

Posted on Posted in All Articles, Down Syndrome and Congenital Heart Defects


The current publication focuses on Endocrine Disorders in children and young adults with Down Syndrome. Parents often ask: what is an endocrinologist, and why would any child be referred to a pediatric endocrinologist?

To answer briefly, a pediatric endocrinologist is a physician with specific expertise in normal growth and puberty as well as in disorders of growth and puberty. This includes expertise in thyroid disorders, bone density and bone strength, Vitamin D and calcium metabolism, weight management and obesity, cholesterol and lipids, and diabetes.

Infants, children, and adolescents with Down syndrome are carefully monitored for endocrine concerns that might occur in any child, however, for reasons not completely understood, the genetic alteration on chromosome 21, places children with Down Syndrome, at increased risk for some of these endocrine disorders. Endocrine disorders such as thyroid dysfunction (congenital hypothyroidism; autoimmune), low bone mass and low bone density, short stature, overweight/obesity; and diabetes (Both Type I “auto-immune juvenile diabetes” and type II, often familial and obesity-related) are more prevalent than in the general population. Specific normative growth curves (height and weight) exist for children with Down syndrome.

Autoimmune Endocrine Disorders:

Preliminary results suggest that abnormal AIRE expression (the AIRE gene regulates T-cell function) on chromosome 21 may have important implications for autoimmunity in Down syndrome, resulting in the greater prevalence of autoimmune disorders in Down syndrome, although more research is needed.


Thyroid dysfunction is prevalent in Down syndrome. The most common abnormalities include:

1- Congenital hypothyroidism. The American Academy of Pediatrics recommends thyroid screening (with TSH) at birth, at 6 months, then yearly beginning at one year of age.

2- Autoimmune thyroid disease – both Hashimoto’s Disease (associated with hypothyroidism-a low T4 and elevated TSH) and Graves’ Hyperthyroidism (suppressed TSH and high T3 and T4).

The American Academy of Pediatrics (AAP) recommends that thyroid screening be performed at birth, 6 months, and then once each year beginning at 1 year old. Patients with Down syndrome  have a higher prevalence of congenital hypothyroidism with some cases identified on thyroid tests performed within the first 6 months of life that were not discovered on newborn screening. Although transient mild TSH elevation may be seen in patients with Down syndrome, patients with TSH >10 mIU/L should be treated with L-thyroxine and are more likely to have evidence of thyroid autoimmunity.

Hypothyroidism converts to Graves’ Hyperthyroidism more frequently in Down syndrome compared to the general population. Most often, the hyperthyroidism is mild, with clinical stability on low dose oral methimazole. Proptosis (prominence of the globe of the eye) and opthalmopathy may occur with Graves’ hyperthyroidism and warrant monitoring by an ophthalmologist.

Other autoimmune associations: Scalp alopecia and skin vitiligo may occur. The prevalence of celiac disease (gluten intolerance) is increased in patients with Down syndrome. Each patient should be screened in childhood for gluten intolerance even in the absence of gastrointestinal symptoms. Causes for unexplained short stature or poor weight gain should be sought and may include celiac disease (gluten allergy), thyroid disease, diabetes, or colitis (eg crohn’s).

Type I Diabetes Mellitus: Autoimmune pancreatic beta cell destruction.

There is an increased risk of Type 1 Diabetes (T1D) in individuals with Down Syndrome, occurring early in childhood and in adolescence. Type I Diabetes Mellitus results from autoimmune destruction of the pancreatic beta cells (the beta cells are responsible for secreting insulin). Increasing thirst and urination, an increase in bed-wetting, or unexplained weight loss warrant an immediate urine test for glucose.

Type II Diabetes Mellitus:

Individuals with Down syndrome are at risk of developing type II Diabetes Mellitus, especially in patients who are overweight (BMI >85%) or obese (BMI>90%). Although familial and genetic inheritance are factors, weight management and adequate physical activity are life-style factors that can avoid (or treat) type II Diabetes. As in all individuals, the co-morbidities of obesity, including fatty liver, elevated cholesterol and other lipids, and the effect of excessive weight on physical mobility and on the joints emphasize the importance of a healthy weight and life style.

Growth and Puberty:

Updated growth charts for children with Down syndrome in the United States (US) were published in 2015, which showed improvement in weight gain and nutrition for infants <36 months of age, compared to 1988 data. While males 2–20 years old are taller overall than on previous charts, this effect did not exist for females. There is an increased prevalence of obesity and overweight in youth with Down syndrome, however there has been no further increase in the prevalence of obesity in children with Down syndrome over the past 30-40 years. Compared to other children, children with Down syndrome have a lower lean body mass and higher fat mass. While the Down Syndrome BMI charts are ideal for comparison with peers, the Center for Disease Control (CDC) 2000 growth chart can be used to identify excess adiposity

(> 85%) in children with Down syndrome. In addition, Down syndrome specific growth charts were recently published (2015) and provide a better assessment of growth and pubertal development.


Puberty in patients with Down syndrome can be expected to occur on time and progress at a rate similar to other children. Although dysfunction of the gonads (high FSH and LH) is occasionally reported in boys, concentrations of pubertal hormones are in the normal range in both males and females. Although gonadal dysfunction may occur, both men and women with Down syndrome can be fertile and produce children.

Bone Health:

Current research regarding bone health in Down syndrome describes an increased prevalence of low bone mass. Recent studies have shown lower bone mineral density (BMD) in individuals with Down syndrome than in controls. BMD in the femoral neck decreased with aging after early adulthood for both adults with and without Down syndrome, but the rate of change is greater in individuals with Down syndrome. BMD is a measure of bone density, but is not a measure of bone quality or function. The underlying etiology of low bone density is an area of active research. Further studies are needed to address whether patients with Down syndrome have abnormalities of their bone microarchitecture that can predispose them to fracture. Data is lacking on whether low BMD in Down syndrome is due to excessive bone turnover/resorption or inadequate bone formation.

Preventive measures focus on adequate Vitamin D and calcium intake, as well on an active lifestyle, and an exercise program with weight-bearing exercises. With increasing life expectancy, bone health in patients with Down syndrome is an area of growing importance. More research is needed to determine the specific mechanism of low BMD in this population as well as their fracture risk prior to recommending pharmacologic interventions.


Brenda Kohn,M.D
Chief, Division Pediatric Endocrinology  and Diabetes
NYU-Langone Health
Professor of Pediatrics
NYU-Grossman School of Medicine