The endocrine system and its associated hormones influence the body’s cells and organs to orchestrate physiological functions properly. Issues related to growth, puberty, and sexual development in children are frequently linked to disruptions in this system. The thyroid and adrenal glands stand out as key players in overseeing these hormonal processes. Therefore, optimizing adrenal and thyroid function in children is of paramount importance in ensuring proper growth and development, resilience, and sustained well-being throughout their formative years. Functional medicine provides a holistic approach to pediatric endocrinology, considering the many factors that influence endocrine function and creating individualized treatment plans that address the unique root causes of imbalances in each child. Emphasizing sustained lifestyle modifications and prevention, it provides the tools children and families need for long-term well-being.

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Overview of Pediatric Thyroid and Adrenal Health 

The endocrine system is a complex network of multiple glands and hormones, with each component relying on the others for harmonious signaling and function. Imbalances in thyroid and adrenal function can reverberate across the entire endocrine system, disrupting the delicate equilibrium of hormonal interactions responsible for various physiological processes involved in growth, development, metabolism, and overall well-being. 

The thyroid gland is a butterfly-shaped gland located in the front of the neck. It produces hormones, including thyroxine (T4) and triiodothyronine (T3), whose key role is in regulating metabolism, which is how cells turn our food into energy. All of our cells require thyroid hormones to function correctly, so the thyroid’s function impacts almost every organ system in your body, impacting crucial functions such as heart rate, breathing, digestion, body temperature, brain development, cognition, skin, and bone maintenance, as well as sexual development and fertility. Thyroid hormone communication begins in the brain, specifically in the hypothalamus and pituitary, which regulate the thyroid’s production and secretion of hormones. The hypothalamus and pituitary glands secrete hormones called thyroid-releasing hormones (TRH) and thyroid-stimulating hormones (TSH) that tightly control the amount of thyroid hormones produced. The system is designed as a feedback loop where the hypothalamus and pituitary glands sense how much thyroid hormone is being released by the thyroid and adjust the amount by making more or less TRH and TSH. An elevated TSH is used to diagnose hypothyroidism (too little thyroid hormone), and a low or suppressed TSH is used to diagnose hyperthyroidism (too much thyroid hormone).

Thyroid disorders are among the most prevalent pediatric endocrine illnesses worldwide. They can vary in severity and, due to the many functions of thyroid hormones, can have a significant impact on children’s growth, brain function, and neuronal, musculoskeletal, and sexual development. Hypothyroidism occurs when the thyroid gland does not produce enough thyroid hormone and can cause symptoms like fatigue, weight gain, constipation, and decreased growth. Conditions causing hypothyroidism can be congenital, present at birth, or acquired, developing later in childhood or adolescence. Congenital hypothyroidism (CH) is a leading preventable cause of intellectual disability worldwide. Diagnosis, typically through newborn screening, allows for the timely initiation of life-long treatment with synthetic thyroid hormones to maintain brain and body organs' appropriate growth and functions. Autoimmune conditions, like Hashimoto’s thyroiditis, occur when the immune system damages the thyroid gland, causing hypothyroidism. Although less common in the United States, iodine deficiency is also a common cause of hypothyroidism worldwide (3, 7). The most common cause of hyperthyroidism in children is an autoimmune condition called Graves’ disease. Hyperthyroidism in children can present with goiter, palpitations, weight loss, headache, sleep disturbances, anxiety, and heat intolerance (3). 

The adrenal glands are triangular-shaped glands located on top of the kidneys. They release hormones such as cortisol, DHEA, aldosterone, and adrenaline that play a role in functions such as blood pressure, metabolism, stress response, immunity, and sexual development. Similar to the thyroid, adrenal activity is regulated by the hypothalamus and pituitary in the brain, which release corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH). 

Untreated adrenal disorders in children pose severe risks to their development. Metabolic imbalances may result in weight fluctuations and energy deficits, while cognitive impairments can affect memory and intellectual abilities. Adrenal disorders can also cause other hormonal imbalances, influencing sexual development and reproductive health. The symptoms of adrenal disorders will vary depending upon whether too little or too much hormone is being produced. Adrenal insufficiency can be primary, arising from a dysfunction in the adrenal glands themselves, or central, arising from deficiencies in hypothalamic or pituitary hormones. 

Primary adrenal insufficiency, known as Addison’s disease, can occur due to autoimmune disease, infections, tumors, or bleeding in the adrenal gland. Symptoms of adrenal insufficiency include slow weight gain, fatigue, generalized weakness, low blood pressure, and salt cravings. Cushing’s syndrome, characterized by overproduction of cortisol, is a common disorder of adrenal overactivity. It can result from prolonged use of corticosteroid medications or adrenal tumors. Congenital adrenal hyperplasia (CAH) is an inherited deficiency of adrenal hormone enzymes that causes too little cortisol and aldosterone production and an excess of androgen hormones. Adrenal tumors, such as adrenal adenomas or pheochromocytoma, may also cause adrenal overactivity (58). 

Symptoms of overactive adrenal glands depend on which hormones are being overproduced. Overproduction of androgen hormones can cause excess hair growth on the face and body, acne, a deeper voice, changes to height growth in boys, and genitals that don’t usually form in girls. Excess cortisol can cause delays in development, upper body obesity, high blood pressure, fatigue, high blood sugar, and irregular menstrual cycles in girls. Excess aldosterone can cause high blood pressure as well as muscle weakness and spasms. 

Challenges in Pediatric Endocrinology 

Diagnosing and managing thyroid and adrenal disorders in children presents unique challenges due to the complexities and subtleties inherent in pediatric endocrine disorders. One of the primary challenges is the dynamic nature of growth and development during childhood. Distinguishing between normal fluctuations and pathological conditions can be difficult and requires careful interpretation of symptoms and age-specific reference ranges. Moreover, symptoms of thyroid and adrenal disorders in children can be subtle and nonspecific, making early detection challenging, and children may not express their symptoms clearly (50, 51).

The intricacies extend to the management phase, as treatment plans often require careful consideration of a child's growth trajectory, developmental stage, and long-term implications. 

Medication dosages must be meticulously adjusted to accommodate the child's changing needs. Additionally, factors like adherence to treatment and potential impacts on pubertal development need thoughtful consideration. Collaboration between multiple providers, like pediatricians, is necessary for comprehensive care. The psychological impact of chronic diseases, especially during formative years, must also be considered in treatment to address not only physical but also emotional well-being. 

Functional Medicine Approach to Pediatric Thyroid and Adrenal Health 

Unlike traditional approaches that often concentrate solely on symptom management, functional medicine aims to identify and address the root causes of imbalances within the endocrine system. Central to this approach is the recognition that thyroid and adrenal health are intimately tied to one another, as well as the endocrine system as a whole. Furthermore, it recognizes the vital influence that genetics, environment, and lifestyle factors have on their function. This is an individualized approach that empowers patients and families to create a foundation for optimal endocrine health and sustained well-being.

Functional Medicine Testing for Children

Diagnosing thyroid conditions involves blood tests like Precision Point’s Comprehensive Thyroid Panel, which analyzes levels of thyroid hormones, including TSH, T4, and T3 in the blood. Antibodies, such as anti-thyroid peroxidase (TPO) and anti-thyroglobulin antibodies, diagnose autoimmune thyroid disorders like Hashimoto's thyroiditis. If hyperthyroidism is suspected, thyroid-stimulating immunoglobulin (TSI) antibodies can be ordered to assess for possible Graves’ disease (21, 45).

Which tests are ordered in diagnosing adrenal disorders depends upon the suspected condition and the presentation of the patient. Adrenal hormones like cortisol, DHEA, and aldosterone can be measured using blood tests. A 24-hour urinary-free cortisol test measures the amount of cortisol excreted over 24 hours. In some cases, imaging, like MRI or CT, can be used to visualize the adrenal glands to identify any structural abnormalities like tumors. In the case of low cortisol levels, an ACTH stimulation test helps to distinguish between primary and central adrenal insufficiency. In the case of elevated cortisol levels, a dexamethasone suppression test is used to diagnose Cushing’s syndrome. 

Advanced functional medicine tests can also be considered to provide additional insight into thyroid and adrenal function as well as the underlying factors that can influence their process.  

Adrenal Testing

The DUTCH Plus test by Precision Analytical serves as an advanced tool for assessing adrenal function, combining dried urine and salivary samples. The assessment of cortisol metabolites in dried urine offers a unique perspective on the body's handling of cortisol. Additionally, salivary measurements of cortisol and cortisone contribute crucial information about bioavailable cortisol levels, its conversion processes, and the diurnal rhythm of cortisol secretion. The inclusion of DHEA-S measurement adds further depth by examining the balance of adrenal hormones. Other markers, including melatonin, a hormone crucial for the sleep-wake cycle, reproductive hormone metabolites, and 8-Hydroxy-2-deoxyguanosine (8-OHdG), a feature of cellular stress, provide additional information about endocrine health as a whole.

Comprehensive Stool Analysis

The gut microbiome refers to the diverse community of microorganisms that inhabit the gastrointestinal tract. In a healthy state, the microbiome maintains a harmonious equilibrium, promoting beneficial interactions between different microbial species. Dysbiosis occurs when this balance is disturbed, leading to an overgrowth or underrepresentation of certain microorganisms. This imbalance can result from various factors, including the use of antibiotics, diet, stress, infections, and other environmental influences. Under ideal circumstances, the intestinal barrier prevents unwanted substances from entering the bloodstream. When there is dysbiosis, the intestinal wall can become more permeable, a condition known as leaky gut, allowing the importance to be absorbed and cause inflammation in the body. 

The gut plays a crucial role in thyroid health, as nutrient absorption, conversion of thyroid hormones, and immune system regulation. Dysbiosis and intestinal permeability are associated with autoimmune conditions, including Hashimoto’s thyroiditis. The microbiota can also influence the absorption of minerals essential to thyroid function, such as iodine, selenium, zinc, and iron, and low levels of Lactobacilli and Bifidobacteria are seen in hypothyroidism and hyperthyroidism.

The gut-brain axis refers to the bidirectional communication between the gut and the central nervous system, involving intricate interactions between the gastrointestinal tract, the nervous system, and the endocrine system. One significant component of the gut-brain axis is the connection between the hypothalamic-pituitary-adrenal (HPA) axis and gut health. HPA axis dysregulation affects gut motility, increases intestinal permeability, and influences the composition of the gut microbiome. Conversely, the gut microbiome can influence the HPA axis. The microbiota produces various molecules that can signal to the brain and modulate stress responses. Imbalances in the gut microbiome, known as dysbiosis, may contribute to HPA axis dysfunction (49). 

Genova’s GI Effects test is designed to offer a comprehensive assessment of gastrointestinal health, encompassing key factors such as inflammation, digestion, and the composition of the microbiome. It uses PCR and culture to identify any dysbiosis. It also examines markers associated with inflammation, such as calprotectin and zonulin, which are associated with intestinal permeability. The analysis extends to digestive function, assessing levels of digestive enzymes and the gut's ability to absorb nutrients efficiently.

Food Sensitivities

In individuals with autoimmune thyroid disorders like Hashimoto's thyroiditis, certain foods may trigger an immune response, leading to inflammation and exacerbating thyroid dysfunction. Gluten, in particular, through a process called molecular mimicry, can trigger the body to mistakenly attack thyroid tissue due to similarities between gluten proteins and thyroid proteins. This immune response can further damage the thyroid gland and worsen symptoms. Moreover, gut inflammation resulting from food sensitivities can activate the HPA axis. The continuous activation of the stress response can disrupt the body's ability to respond to stress appropriately, further contributing to the progression or exacerbation of adrenal disorders.

Cyrex’s Array 10 - Multiple Food Immune Reactivity Screen measures IgG and IgA antibody responses to raw, cooked, and modified foods as well as food enzymes, lectins, and artificial food additives. Most food sensitivity tests only test against foods in their raw form, which can miss reactions to the food if it is cooked, modified, or combined with other ingredients.

Micronutrients

Nutrients such as iodine, iron, selenium, and zinc are crucial for thyroid hormone synthesis and conversion, and vitamin D assists in regulating the immune response. Furthermore, nutrients, including B vitamins, magnesium, and vitamin C, play a role in HPA axis function. The Micronutrient Test by Spectracell evaluates a comprehensive array of 31 vitamins, minerals, and other nutrients to provide a thorough assessment of nutrient status.

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Nutritional Interventions in Pediatric Endocrine Health

To support healthy endocrine function in children, a balanced and nutrient-rich diet is essential. Adrenal disorders and thyroid disorders can negatively impact blood sugar regulation. Limiting the intake of processed foods as well as refined carbohydrates and sugars while focusing on adequate amounts of fiber, protein, healthy fats, and complex carbohydrates will help to support optimal blood sugar balance. A diet abundant in fruits, vegetables, whole grains, and lean proteins provides essential vitamins and minerals that contribute to endocrine health. Vitamin C, for instance, supports adrenal hormone production. Omega-3 fatty acids, abundant in fatty fish, help manage inflammation and promote overall endocrine balance. Incorporating foods rich in iodine, selenium, and zinc is crucial for optimal thyroid function, as these minerals play critical roles in the synthesis and conversion of thyroid hormones. Additionally, a sufficient intake of vitamin D supports immune function and helps regulate the immune responses associated with thyroid health.

Food sensitivities can contribute to intestinal permeability and inflammation. Gluten sensitivity, in particular, can be problematic in Hashimoto’s thyroiditis. An elimination diet can be considered for diagnosing food sensitivities or intolerances that can sometimes be missed on serum testing. All potentially problematic foods are removed for several weeks. Individual foods are then reintroduced one at a time over a few days to see if any alarming symptoms arise. Any foods that provoke unwanted symptoms are then removed for a more extended period of time before any attempts for reintroduction are made again. The goal of an elimination diet with reintroduction is to temporarily remove foods that promote inflammation, thereby improving the gut and immune health of the patient. This enables patients to gradually transition back to a more nutritionally diverse diet.

In summary, fostering healthy endocrine function in children involves a diet rich in nutrient-dense foods while being mindful of potential dietary triggers. Consulting with healthcare professionals or registered dietitians can provide personalized guidance, ensuring that nutritional modifications align with the unique needs of each child, supporting average growth and development, and promoting optimal thyroid and adrenal health from an early age.

Lifestyle and Behavioral Factors 

Encouraging a healthy and balanced lifestyle, including regular physical activity and sufficient sleep, is essential for regulating hormone balance. Additionally, promoting stress management techniques and providing emotional support is vital, as stress can exacerbate endocrine disorders.

Physical Activity

Regular physical activity is vital for maintaining optimal endocrine function in children. Research has shown that children with higher levels of physical activity show more adapted HPA axis responses to stress than children with low levels of physical activity. Exercise has also been shown to balance levels of thyroid hormones, including TSH, T4, and T3. The CDC recommends that children engage in 60 minutes or more of moderate-to-vigorous physical activity each day. This includes aerobic exercise, such as walking or running, as well as activities that strengthen muscles and bones.

Sleep

Sleep deprivation is associated with multiple hormone changes and increases in inflammation. The American Academy of Sleep Medicine developed recommendations for the amount of sleep needed to promote optimal health in children and adolescents:

• Infants should sleep 12-16 hours per day 
• Children 1 to 2 years of age should sleep 11 to 14 hours per day
• Children 3 to 5 years of age should sleep 10 to 13 hours per day
• Children 6 to 12 years of age should sleep 9 to 12 hours
• Teenagers 13 to 18 years of age should sleep 8 to 10 hours

Meeting the minimum sleep requirements is associated with not only better endocrine and physical health but also improved attention, behavior, learning, memory, emotional regulation, and quality of life.

Stress Management

About 35% of children in America experience stress-related health problems. Children and adolescents are exposed to a variety of stressors, including the absence of supportive caregivers, poverty, friendship, and interpersonal difficulties, heavy academic workloads, and bullying. Stress can significantly impact thyroid function and the HPA axis in children. Repeated or chronic stress can lead to dysregulation of the HPA axis, resulting in an imbalance in cortisol production. This, in turn, may influence thyroid function as cortisol interacts with the thyroid hormones. Stress management practices, such as meditation, acupuncture, and biofeedback, stimulate the body’s relaxation response to counteract the adverse neuroendocrine effects of stress. 

Integrating Conventional and Functional Treatments

Integrative medicine (IM) is a patient-centric, evidence-based approach that aims to incorporate both conventional and complementary treatments to achieve optimal patient outcomes. It emphasizes the patient-provider relationship, addresses the physiologic, psychosocial, spiritual, and environmental aspects of the patient’s health, and leans on lifestyle changes to optimize healing. In the pediatric population, IM practices have enormous potential to reduce healthcare costs and ensure a healthier, long-term future by emphasizing prevention and promoting wellness instead of just focusing on symptom relief. Research has confirmed that IM therapies are effective in improving patient outcomes, patient satisfaction, and improving overall quality of life.  

Integrative care in pediatric endocrinology recognizes that factors such as diet, stress, genetics, and environment can all influence hormone imbalance. Integrative endocrinologists will use thorough medical history and comprehensive laboratory testing to identify the root causes of hormone imbalances in each patient. Once the cause of the hormonal imbalance has been identified, an integrative endocrinologist may recommend a combination of dietary and lifestyle changes and supplements in combination with conventional treatments to optimize thyroid and adrenal function. 

Educating Families and Empowering Young Patients 

Educating families about thyroid and adrenal health in children is paramount for fostering proactive healthcare. A comprehensive understanding of these endocrine systems is crucial, as they play pivotal roles in growth, metabolism, and overall well-being during essential developmental stages. Families need to understand adrenal and thyroid disorders, the potential impact on a child's health, and the significance of early detection and proper management.

The family unit is an essential piece in maintaining health and preventing disease in children because family members support each other through multiple life stages. Each member of the household influences the choices of others in the family. Encouraging families to ask questions, seek clarification, and actively participate in discussions about their child's condition fosters a sense of collaboration and understanding. Secondly, providing accessible educational materials helps families comprehend the complexities of thyroid and adrenal health. Family-centered care can improve patient and family outcomes, improve the patient’s and family's experience, increase patient and family satisfaction, and decrease healthcare costs (6, 44).

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Functional Medicine in Pediatric Endocrinology: Final Thoughts

Incorporating functional medicine and integrative care into pediatric endocrinology ensures a comprehensive and personalized approach to thyroid and adrenal health. Emphasizing collaboration and individualized care, this holistic approach not only addresses immediate concerns but also supports long-term well-being in children by addressing the root cause of hormone imbalances and fostering foundational lifestyle practices.