Zaburzenia lękowe i depresyjne u dzieci i młodzieży z wybranymi chorobami układu wydzielania wewnętrznego

Introduction

Depressive and anxiety disorders are among the most common mental health problems in the child and adolescent population, and their consequences can permanently affect psychosocial development, school functioning and quality of life. According to a review of the literature by Rapee et al. [1], the estimated prevalence of anxiety disorders in individuals under the age of 18 is 5–10% per year and 15–20% across childhood and adolescence. The presence of anxiety disorders in childhood is associated with a high risk of their chronicity, co-occurrence with other psychiatric disorders (depression, attention-deficit hyperactivity disorder [ADHD], conduct disorders), and the occurrence of serious consequences in adulthood, including an increased risk of depression, addiction, and difficulties in social relationships [1].

At the same time, data from a meta-analysis by Lu et al. [2], including 96 studies from 29 countries and more than 500,000 participants, show an alarmingly high prevalence of depression or depressive symptoms among children and adolescents – 21.3% for mild to severe depression, 18.9% for moderate to severe symptoms, and 3.7% for major depression. According to the analysis, depression is four times more common in adolescents than in children under the age of 10 [2].

In the context of the growing body of scientific evidence supporting the importance of mental disorders in children and adolescents, an in-depth analysis of their prevalence in specific clinical populations becomes warranted. One group at particular risk for depressive and anxiety symptoms is patients with chronic endocrine diseases. They are exposed to multiple factors that may increase their vulnerability to mental health problems. These include the long-term burden of disease management, such as adherence to medical, dietary, and lifestyle recommendations, frequent medical appointments, and the potential side effects of treatment. Moreover, some endocrine disorders may impact physical development, growth, or sexual maturation, which can negatively influence self-image and social functioning. From a biological perspective, hormonal imbalances inherent to endocrine diseases may directly affect mood regulation and emotional stability, through the interactions between endocrine and neuropsychiatric systems. Together, these psychosocial and physiological factors may contribute to an increased risk of developing depressive and anxiety disorders in this population.

The purpose of this paper is to review available studies on the prevalence and characteristics of depressive and anxiety disorders among pediatric patients with selected endocrine diseases. Data on children with thyroid disease (Hashimoto’s, autoimmune thyroid diseases [AITD] and Graves' disease), growth hormone deficiency (GHD), congenital adrenal hyperplasia (CAH) and precocious puberty (CPP) were analyzed.

Material and methods

A search of the PubMed database was conducted to identify relevant publications. The search was performed in March and April 2025 and included papers published within the last 10 years. Only original publications that analyzed the prevalence of anxiety and/or depressive disorders in children and adolescents with the listed endocrine disorders were included. Papers written in English that focused on patients aged 0–18 years were included. The search was based on a standardized strategy, combining Medical Subject Headings (MeSH) keywords and free terms. Titles and abstracts were independently screened for relevance, and potentially eligible studies underwent full-text review. Reference lists of included articles were also examined to identify additional relevant publications.

A total of 14 studies were included in the review that met the search criteria and underwent critical appraisal by the authors (one study was outside the accepted publication period). These studies were grouped thematically according to the disease entity analyzed.

The identified papers were qualitatively assessed and organized in a table according to PICO (Population, Intervention, Comparison, Outcomes) principles. Included were: a description of the population (including age, location and method of recruitment), the mental symptom assessment tools used (with information on who completed each questionnaire), the control group (if present), the results (including numerical values and statistical significance), and the authors’ conclusions. In addition, the inclusion and exclusion criteria for each study are included in the table (Table I).

Growth hormone deficiency

Growth hormone deficiency (GHD) is an important endocrine cause of short stature in children and adolescents. In addition to somatic effects, GHD may also be associated with psychiatric disorders, particularly depression and anxiety disorders. A literature review considering three studies – Gizli Çoban et al. [4], Akaltun et al. [4], and Abe et al. [5] – indicates a clear association between GHD and the risk of emotional symptoms in pediatric patients.

All studies analyzed reported an increased incidence of psychiatric disorders in children with GHD. In the study by Gizli Çoban et al. [3], which included 61 patients aged 6–18, as many as 45.9% of participants were diagnosed with at least one psychiatric disorder, with social phobia (18.3%) predominating. A study by Akaltun et al. [4], which compared 122 children with GHD (87 treated, 35 pre-treatment) and 122 healthy peers, found a significantly higher prevalence of generalized anxiety disorder (GAD) and social anxiety (SAD) in the GHD group, particularly in those who had not yet been treated with growth hormone (GAD: 34.2%; SAD: 28.5%). On the other hand, in a study by Abe et al. [5], conducted in Japan, 15% of children with GHD had depressive tendencies as assessed by the Depression Self-Rating Scale for Children (DSRSC) scale, which was higher than the level reported in the general population (9.6%) [3–5].

Of particular note is the fact that the implementation of growth hormone treatment is associated with improvements in patients’ psychological functioning. In a study by Abe et al. [5] after an average of 19 months of therapy, the percentage of children with depressive tendencies decreased from 15% to 5%. Similar results were obtained by Akaltun et al. [4] who showed a significant reduction in scores on depression and anxiety scales (Children’s Depression Inventory [CDI], State-Trait Anxiety Scale for Children [STAIC], Social Anxiety Scale for Children-Revised [SASC-R]) in the group of children treated with GH compared to the untreated group [5].

Peer violence was also an important aspect discussed by Gizli Çoban et al. [3]. In the study group, 27.9% of children reported being a victim of bullying, which was associated with lower standard deviation score (SDS) of growth and increased depressive and anxiety symptoms. The risk of experiencing violence was higher in patients in the early stages of growth hormone (GH) treatment (< 1 year). The authors noted that younger children (6–12 years old) showed lower quality of life and higher levels of anxiety than older children (13–18 years old), suggesting a particular vulnerability of this age group to the psychosocial effects associated with the disease [3].

All the studies analyzed used standardized and accurate mental assessment tools, such as the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version (K-SADS-PL), CDI, STAIC, Screen for Child Anxiety-Related Emotional Disorders (SCARED), SASC-R, Strengths and Difficulties Questionnaire (SDQ), Pediatric Quality of Life Inventory (PedsQL) or Depression Self-Rating Scale for Children (DSRSC). Most of the questionnaires were completed by children, and some were also completed by parents (e.g. SDQ, K-SADS-PL).

The accumulated data clearly indicate that children with idiopathic growth hormone deficiency are a group at significant risk of mental disorders, and GH treatment can positively affect not only somatic growth, but also mental health. For this reason, it is recommended that these patients be cared for in a multidisciplinary model, including both an endocrinologist specialist and a psychiatrist/child psychologist. Early identification of depressive and anxiety symptoms and appropriate psychological support can significantly improve the quality of life of children with GHD.

In the context of the etiology of depressive and anxiety disorders observed in children with GHD, both psychosocial and biological mechanisms should be considered. Existing research suggests that growth hormone deficiency may affect emotional functioning not only indirectly – through short stature and related adaptive difficulties – but also directly, via the effects of the GH/IGF-1 axis on the brain. This axis plays a key role in neurogenesis, particularly within the hippocampus and frontal cortex – regions strongly implicated in mood regulation.

Neuroimaging studies have demonstrated altered activity in brain areas responsible for emotional control in children with GHD. Notably, improvements in depressive and anxiety symptoms have been reported within just a few months of GH therapy, suggesting a neurobiological effect beyond the psychosocial benefits of increased height. Moreover, children with idiopathic short stature (ISS), but without GH deficiency, have shown lower severity of psychiatric symptoms than peers with GHD, despite comparable final stature. These findings further support the hypothesis of a primary, somatotropic-axis-related mechanism influencing mental health outcomes [6].

Graves’ disease

Graves’ disease (GD) is the most common cause of hyperthyroidism in children and adolescents, and its impact is not limited to somatic disorders. In recent years, increasing attention has been paid to the neuropsychiatric aspects associated with the course of GD. Symptoms such as irritability, difficulty concentrating, anxiety, depressed mood or behavioral disturbances are sometimes present both during the active phase of the disease and after euthyroidism has been achieved.

In a retrospective population-based study conducted by Zader et al. [7] using the Military Health System (USA) database, 2480 children diagnosed with hyperthyroidism were evaluated. They were found to have a significantly higher prevalence of psychiatric diagnoses than controls, including depression (prevalence ratio [PR] 3.4), anxiety disorders (PR 2.3), adjustment disorders (PR 3.3), bipolar affective disorder (PR 4.9) and self-injurious behavior (PR 4.8). Importantly, in the majority of patients, the psychiatric diagnosis preceded the detection of thyroid disease, suggesting the possibility of earlier symptomatic manifestation of endocrine disorders in psychiatric form [7].

Hamed et al. [8] conducted a prospective case-control study involving 35 children with newly diagnosed GD and 40 healthy peers. Using the CBCL tool, the authors demonstrated the presence of behavioral and emotional problems in 74.3% of children in the active phase of the disease. After 12 months of thyreostatic treatment, despite achieving euthyroidism, symptoms persisted in 31.4% of patients. The most common symptoms were anxiety, depression, social withdrawal, attention problems and somatization symptoms. The severity of symptoms correlated significantly with thyroid-stimulating hormone (TSH) levels (negatively) and free triiodothyronine (fT3), free thyroxine (fT4) and TRAb levels (positively), suggesting a biological basis for the psychiatric disorders associated with hormonal hyperthyroidism [8].

A recent study by Akgül and Köprülü [9] assessed quality of life and psychiatric symptoms in euthyroid children with GD. Although there were no significant differences in anxiety and depression (Revised Children’s Anxiety and Depression Scale – Child Version – RCADS-CV) and quality of life (PedsQL) relative to the control group, children with GD had higher levels of irritability (ARI-P: p = 0.039) and severity of oppositional defiant and conduct disorder symptoms (T-DSM-IV-S, SDQ-A and SDQ-P). The results indicate that even after normalization of hormonal parameters, patients with GD may still experience emotional and behavioral disturbances requiring psychological intervention [9].

In summary, children and adolescents with GD show an increased risk of psychiatric disorders, including depressive, anxiety and oppositional-rebel symptoms. These symptoms may already be present before the disease is diagnosed and do not always resolve after the implementation of thyreostatic treatment. For this reason, it is recommended that the care of pediatric patients with GD should be interdisciplinary and include psychiatric and psychological evaluation – regardless of current hormonal status.

Hypothyroidism

Autoimmune thyroid diseases, including Hashimoto’s disease, are a significant health problem in the pediatric population. In recent years, there has been increasing research into their potential impact on the mental health of children and adolescents.

A cross-sectional population-based study by Hirtz et al. [10] assessed the quality of life and mental status of 8052 children and adolescents participating in the nationwide German KiGGS study. Participants with hypothyroidism and hyperthyroidism, autoimmune thyroiditis (Hashimoto’s), as well as healthy subjects were evaluated. The KINDL-R questionnaire was used to measure quality of life, and the Strengths and Difficulties Questionnaire (SDQ) was used to measure mental health. The results showed no significant differences in quality of life and mental health between children with thyroid disease and healthy controls. Only the group with overt hypothyroidism had slightly higher SDQ scores, but these values were still within normal limits. The authors suggest that thyroid disease in childhood does not significantly affect mental health, in contrast to observations in the adult population [10].

Different results were obtained by Aydin et al. [11] in a case-control study involving 82 girls aged 12–18 years. They compared 41 euthyroid female patients with Hashimoto’s disease with 41 healthy female peers. Three diagnostic tools were used: the CDI questionnaire, SCARED and the K-SADS-PL semi-structured psychiatric interview administered by a psychiatrist. The study found no differences in self-reported depression, but female patients with Hashimoto’s disease scored significantly higher on the anxiety scale. Moreover, a history of K-SADS-PL diagnoses of depression (29.3% vs. 4.9%), generalized anxiety disorder (24.4% vs. 2.4%) and social phobia (31.7% vs. 9.8%) were more common in the Hashimoto’s group compared to the control group. Multivariate analysis showed that elevated levels of anti-TPO antibodies were an independent risk factor for the development of depression, suggesting that autoimmune activation itself – rather than thyroid hormone levels – may contribute to the onset of psychiatric symptoms. This finding supports the neuroinflammatory hypothesis, which implicates immune-mediated processes in the pathogenesis of mood and anxiety disorders [11].

In summary, the findings are inconclusive. A population-based study by Hirtz et al. [10] suggested no association between thyroid disease and psychiatric disorders in childhood, while a clinical study by Aydin et al. [11] showed a markedly increased risk of anxiety and depressive disorders in girls with Hashimoto’s disease. The differences may be due to the methodology, population characteristics, and deeper clinical profile of the subjects in the study by Aydin et al. [11]. Further well-designed prospective studies are needed considering the available data.

Congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is a chronic endocrine disease requiring long-term treatment and monitoring that can significantly affect not only the physical but also the mental health of children and adolescents. In recent years, there has been growing interest in assessing the risk of depressive and anxiety disorders in this population.

A retrospective case-control study by Shafaay et al. [12] analyzed the quality of life of 146 children and adolescents with classic CAH in Saudi Arabia. Five domains of quality of life, including emotional health, were assessed using the EQ-5D-5L questionnaire. They found that 42.9% of children with CAH reported problems with anxiety and depression, and 38% experienced pain or discomfort. The results showed a significant reduction in the quality of life of CAH patients compared to healthy peers [12].

In contrast, a large retrospective cohort study by Harasymiw et al. [13] assessed the risk of depressive and anxiety disorders in a pediatric population with CAH in the United States, using administrative data from 2015–2019. The analysis included children (4–11 years) and adolescents (12–17 years) with CAH, whose outcomes were compared to healthy peers. The study found that children and adolescents with CAH had a significantly higher risk of depression (PR = 1.9–3.5) and anxiety disorders (PR = 1.8–2.0) compared to the general population. Additionally, they were more likely to be prescribed antidepressants [13].

Both studies clearly indicate an increased risk of psychiatric disorders in children and adolescents with CAH. The different methodological approaches – the subjective assessment of quality of life in the Shafaay et al.’s study [12] and the analysis of administrative data in Harasymiw’s work [13] – complement each other, revealing a comprehensive picture of the problem. The results underscore the need for holistic care for pediatric patients with CAH, including not only endocrinological aspects, but also emotional and psychosocial health.

Precocious puberty

Central precocious puberty (CPP) poses significant clinical challenges not only somatically, but also psychologically. Faster physical development relative to peers can lead to adaptive difficulties, impaired emotional well-being and an increased risk of depressive and anxiety disorders. An analysis of available studies indicates the complex effects of CPP on children’s mental health.

A prospective study by Yu et al. [14] assessed the impact of GnRH agonist treatment on the emotional state of girls with CPP. In a group of 66 girls aged about 8 years, treated for 12 months, significant improvements in mental parameters were observed: the mean CDI score decreased from 6.5 to 4.9 points, and the percentage of patients with clinical behavioral problems decreased from 30.3% to 10.6% in K-CBCL. The results suggest that gonadotropin-releasing hormone agonist (GnRHa) treatment may be beneficial in reducing depressive symptoms and behavioral disorders [14].

In contrast, a cross-sectional study by Gizli Çoban et al. [15] compared 71 girls with CPP to a group of 50 healthy female peers. In the CPP group, the frequency of psychiatric disorders was slightly higher (28% vs. 22%), with anxiety disorders such as social anxiety being the most diagnosed. A significant difference was shown in the frequency of experiencing peer violence, with 28% of CPP girls reporting being a victim of violence, compared to 12% in the control group (p = 0.033). These findings underscore the need to include social aspects in the psychological assessment of children with CPP.

The study by Kardaş et al. [16] included 92 girls presenting to an endocrinology clinic, divided into three groups: diagnosed CPP, suspected CPP and healthy controls. Both girls with CPP and those with suspected precocious puberty showed significantly higher levels of anxiety and lower quality of life compared to the control group. The highest levels of anxiety were in the group of girls whose concerns about precocious puberty were not clinically confirmed. In the CPP and suspicion groups, the frequency of diagnoses of disorders such as ADHD and anxiety disorders was 27.4%. The authors also noted the negative impact of mothers’ anxiety levels on their children’s mental state, emphasizing the need for parent education.

Changes in the mental status of girls with idiopathic CPP (iCPP) were also assessed by Uthayo et al. [17] in a cohort study involving 85 participants. At the beginning of the study, girls with iCPP had significantly higher scores on the CDI (8.1 vs. 3.7 points; p = 0.007) and a higher risk of emotional problems according to the SDQ compared to the prepubertal group. After six months, the differences between the groups were no longer statistically significant, which may suggest partial emotional adaptation or the influence of therapeutic support. Nevertheless, the authors stressed that children with iCPP should remain under constant observation for depressive and anxiety disorders [17].

In conclusion, the available studies indicate that children with precocious puberty are at higher risk for depressive disorders, anxiety disorders and social difficulties. This problem affects both children affected by CPP and those in whom the mere suspicion of faster development causes anxiety and stress. The findings underscore the need for regular psychological evaluation of pediatric patients with CPP and the integration of psychological support into the endocrine care model.

Conclusions

The results of this review indicate that children and adolescents with selected endocrine diseases – such as growth hormone deficiency, thyroid disease (Hashimoto’s and Graves' disease), congenital adrenal hyperplasia (CAH) and precocious puberty – are a population at particular risk for depressive and anxiety symptoms. Routine screening for psychiatric disorders should be integrated into standard endocrine follow-up. Such an approach would support early identification and timely psychological intervention as part of holistic patient care.

Although many studies confirm the existence of such an association, the scientific literature in this area remains limited, both in terms of the number of publications and methodological quality. The papers reviewed are dominated by studies conducted in single centers, often with small groups of patients. The diagnostic tools used were heterogeneous: depressive symptoms were often assessed with standardized scales such as the CDI, whereas anxiety symptoms were usually assessed using non-specific tools or general quality-of-life questionnaires. Only a few studies have used tools that are validated and dedicated to measuring anxiety in the pediatric population. In addition, none of the included studies analyzed the impact of psychiatric symptoms on treatment adherence or the effectiveness of endocrine treatment.

A noticeable and recurring theme, especially in studies of thyroid diseases, is the potential association between the severity of depressive and anxiety symptoms and thyroid hormone levels and the presence of antithyroid antibodies. This may suggest a role for biological mechanisms in the development of psychiatric symptoms in patients with endocrine diseases. This observation may provide a starting point for further research into the pathophysiology of these disorders.

In conclusion, there is an urgent need for multicenter, prospective studies involving larger population samples, using standardized, validated diagnostic tools. It seems particularly important to include anxiety symptoms as a separate, precisely measured area and to analyze their impact on quality of life, psychosocial functioning and endocrine disease outcomes. Only through such research will it be possible to fully understand the interrelationships between endocrine diseases and mental health in the pediatric population.