|Year : 2014 | Volume
| Issue : 2 | Page : 89-94
Thyroid dysfunction in attention-deficit hyperactivity disorder and effect of comorbidity
Samia Abd El Rahman, Shereen M. Abd El Mawella, Hoda A. Hussein, Mohamed El Mosalmy
Department of Psychiatry, Faculty of Medicine, Cairo University, Cairo, Egypt
|Date of Submission||29-Oct-2013|
|Date of Acceptance||20-Nov-2013|
|Date of Web Publication||11-Jun-2014|
MD Shereen M. Abd El Mawella
Assistant Professor of Psychiatry, Department of Psychiatry, Faculty of Medicine, Cairo University, Cairo
Source of Support: None, Conflict of Interest: None
Attention-deficit hyperactivity disorder (ADHD) is considered to have a biologic basis, but the precise cause is unknown. It is one of the neurodevelopmental abnormalities observed frequently in children with generalized resistance to thyroid hormone, suggesting that thyroid abnormalities may be related to ADHD.
To assess thyroid dysfunction in children with ADHD and to detect the most common comorbidity.
Participants and methods
This was a case-control cross sectional study, in which 30 ADHD children were recruited from the Kasr Aini Pediatric Hospital (Abu-El Rish) outpatient psychiatry clinic and compared with 14 healthy control children, siblings of the patient group who participated in this research.
The Stanford Binet Intelligence Scale, the Arabic version of Conners' Parent Rating Scale-Revised-Long version, and social score were used to calculate social standards of families.
Serum total T3, total T4, and thyroid-stimulating hormone were assessed using the enzyme-linked immunosorbent assay.
About 80% of the participants were males and 20% were females. Diagnosis according to the Diagnostic and statistical manual of mental disorders, 4th ed. (DSM-IV) showed that 29 (96.7%) of the patients were diagnosed with ADHD combined type by DSM-IV and only one patient (3.3%) had ADHD inattentive type. Forty percent of the patients were from low socioeconomic class, followed by 26.7% from moderate socioeconomic, and a very low socioeconomic class; however, 6.6% were from a high socioeconomic class. There was a statistically significant difference between cases and control groups in all components of Conners' Parent Rating Scale; all cases had higher means than the control group (P = 0.001). There was no significant difference between both the study group and their siblings in serum total T3, thyroid-stimulating hormone, T4 (P > 0.05). Fifty percent of the patients had no or only one comorbidity and 15 (50%) had two or more comorbidities. On comparing the two subgroups (group with no or one comorbidity and the other group with two or more comorbidities), we found that there were no statistically significant differences between the two groups in the IQ components test. There were only statistically significant differences between two subgroups in the social problem subscale of Conners' scale, which showed higher scores in the subgroup of patients with two or more comorbidities. Also, there were no statistically significant differences in the thyroid profile of the two subgroups and the thyroid functions were within normal.
Oppositional defiant disorder was the most common comorbidity. Social problems are common in children with ADHD with comorbidity. Children with ADHD have no thyroid dysfunction.
Keywords: attention-deficit hyperactivity disorder, comorbidity, socioeconomic standard, thyroid dysfunction
|How to cite this article:|
Abd El Rahman S, Abd El Mawella SM, Hussein HA, El Mosalmy M. Thyroid dysfunction in attention-deficit hyperactivity disorder and effect of comorbidity. Egypt J Psychiatr 2014;35:89-94
|How to cite this URL:|
Abd El Rahman S, Abd El Mawella SM, Hussein HA, El Mosalmy M. Thyroid dysfunction in attention-deficit hyperactivity disorder and effect of comorbidity. Egypt J Psychiatr [serial online] 2014 [cited 2018 Apr 26];35:89-94. Available from: http://new.ejpsy.eg.net/text.asp?2014/35/2/89/134194
| Introduction|| |
Attention-deficit hyperactivity disorder (ADHD) is the diagnosis made in children and adults who show developmentally inappropriate levels of inattention, overactivity, and impulsivity; these symptoms cause significant impairment in the individual's functioning in both the home and school or work environment (American Psychiatric Association, 2000).
ADHD is considered to have a biologic basis, but the precise cause is unknown. It is one of the neurodevelopmental abnormalities observed frequently in children with generalized resistance to thyroid hormone (GRTH), suggesting that thyroid abnormalities may be related to ADHD (Weiss et al., 1993).
An association has been recognized between behavioral and psychological changes and thyroid dysfunction in humans since the 19th century. In a recent study, 66% of children with ADHD were found to be hypothyroid, and supplementation with thyroxine was largely curative (Aronson and Dodds, 2005; Beaver and Huang).
A study in India concluded that iodine deficiency can cause learning disabilities, poor academic motivation, and impairment of cognition; the same study reported that case reports of thyrotoxicosis in ADHD patients are rare. Symptoms may be subtle, leading to a missed diagnosis. In patients with no characteristic signs of hyperthyroidism, treatment resulted in control of hyperactivity, increased attention span, and improved language function in patients with no characteristic sign of hyperthyroidism (Suresh et al., 1999).
The similarity between symptoms of thyroid dysfunction and those of ADHD may attract attention to the possible etiological relationship between these disorders. The prevalence of thyroid dysfunction among patients with ADHD was significantly higher than that among the general population. Identification and treatment of thyroid dysfunction are important considerations when there is an exacerbation of ADHD symptoms in patients whose symptoms had been controlled previously (Weiss et al., 1993).
| Patients and methods|| |
The sample group
This study included 30 Egyptian children diagnosed with ADHD. All of them were selected from the Kasr Aini Pediatric Hospital (Abu-El Rish) outpatient psychiatry clinic (fixed 2 days/week in the hospital). Fourteen healthy control children were selected from among the siblings of the patients of this research. All the patients ranged in age from 4 to 14 years, both sexes, and fulfilled the Diagnostic and statistical manual of mental disorders, 4th ed., text revision (DSM-IV-TR) diagnostic criteria of ADHD (American Psychiatric Association, 2000). The control group was chosen from among the siblings of the patients; thus, both the patient and the control group had the same educational and socioeconomic level as well as the same genetic background. All patients had mental retardation (MR) (IQ below 70 as assessed by the Stanford Binet test), organic etiology. Children with congenital disorders, any chronic medical illness, or those receiving medical treatment for systemic disorders were excluded from the study.
A specially designed semistructural interview obtained from the Kasr Al Aini psychiatric sheet was used to determine demographic data, personal history (prenatal, natal, and childhood history), past history, family history, and mental state examination. The diagnosis was made according to the DSM-IV criteria (American Psychiatric Association, 2000).
Stanford Binet Intelligence Scale (Ahmad and Lewis, 1972)
This is the Arabic version of the Stanford Binet Intelligence Scale of general intelligence by Ahmad and Lewis (1972). It assesses the following abilities or cognitive areas: memory, comprehension, perception, language abilities, and performance abilities.
These abilities or areas are covered by a variety of subtests that differ according to the age group, ranging from board, picture and object identification at younger ages to memory, vocabulary, verbal absurdities, similarities, and reasoning in older ages.
The score of these subtests is then converted into a figure indicating 'mental age' (the average age of a child achieving that score). Then, mental age is divided by chronological age of the child and multiplied by 100 to arrive at the intelligence quotient or IQ. An IQ of 100 means that the child's chronological and mental ages match. Traditionally, IQ scores of 90-109 are considered average.
The Arabic version of Conners' Parent Rating Scale-Revised-Long version (El-Sheikh et al., 2002)
This was developed by Conners et al. (1997), translated by El-Sheikh et al. (2002), and validated by use in many subsequent researches. It is a paper-and-pencil screening questionnaire designed to be completed by parents to help determine whether children between the ages of 3 and 17 years might have ADHD. It consists of 80 questions, to be answered by parents, each followed by four choices: 0 (not at all), 1 (just a little), 2 (pretty much), or 3 (very much).
The following subscales are provided after scoring the test:
Oppositional, cognitive problems/Inattention, hyperactivity, anxious-shy, perfectionism, social problems, psychosomatic, Conners' ADHD index, Conners' global index restless/impulsive, Conners' global index emotional lability, Conners' global index total, DSM-IV inattentive, DSM-IV hyperactive-impulsive, DSM-IV total.
Social score to calculate social standards of families (Fahmy and El-Sherbini, 1983)
This is the type of social score used to correlate the social standard with the knowledge attitudes and practices of certain groups with certain health problems related to culture. The model is modified by certain additions of some social indices that include the presence or absence of audiovisual aids of information inside houses. Thus, the indices used were education of the father, education of the mother, per-capita income of family members, crowding index, sanitation in general, family size, and information tools in the house. The total score summed is 37. A total score of 20-25 indicates a low social standard. A middle social standard is determined by a total score of 26-30, whereas high social standard needs total score of 31-37 (Fahmy and El-Sherbini, 1983).
A volume of 3 ml of venous blood was withdrawn from every participant in our study (case and control). Blood was centrifuged, serum was separated and stored at 20°C until assay was performed. Laboratory assessments of serum total T3, total T4, and thyroid-stimulating hormone (TSH) were performed using the enzyme-linked immunosorbent assay.
Expected normal values are as follows: total T3 (71-207 ng/dl), total T4 (6.43-12.17 ng/dl), and TSH (0.35-5.5 μIU/ml).
Before assay, the reagents were allowed to stand at room temperature (18-26°C). All reagents were gently mixed before use. The desired number of coated strips was placed in the holder. A volume of 50 μl of TSH standards, control and patients, were pietted. A volume of 100 μl of ready-to-use enzyme conjugate was added to all wells. The plate was covered and incubated for 60 min at room temperature (18-26°C). Liquid was removed from all wells. The wells were washed three times with 300 μl. Of 1× wash buffer and blotted on absorbent paper towels. A volume of 100 μl of tetramethylbenzidine (TMB) substrate was added to all wells. Incubation was performed for 15 min at room temperature. A volume of 50 μl of stop solutions were added to all wells and the plate was shaken gently to mix the solution. The absorbance was read on an enzyme-linked immunosorbent assay reader at 450 nm within 15 min after the addition of the stopping solution. Expected references (0.35-5.5 μIU/ml).
The Wilcoxon signed-ranks test was used. The Spearman ρ method was used to test the correlation between numerical variables. Data were analyzed using SPSS win statistical package version 17 (SPSS Inc., Chicago, Illinois, USA). Numerical data were expressed as mean and SD or median, and range as appropriate. Qualitative data were expressed as frequency and percentage. The χ2 -test was used to examine the relation between qualitative variables (Surwillo, 1980). Comparison of categorical variables between the study group and their siblings was carried out using the McNemar test. For quantitative data, comparison between two groups was carried out using the Mann-Whitney U-test (nonparametric t-test). Different scores between the study group and their siblings were compared. A P-value less than 0.05 was considered significant.
| Results|| |
The sample included 30 children with ADHD (mean age 8.1 ± 2.2 years); 14 of their siblings were included in a control group (mean age 7.8 ± 2.7 years). About 80% of the cases were males and 20% were females. Diagnosis according to DSM-IV showed that 29 (96.7%) of the patients were diagnosed with ADHD combined type by DSM-IV and only one case (3.3%) had ADHD inattentive type.
[Table 1] shows the socioeconomic standard of the patient groups; about 40% were from a low socioeconomic level, followed by 26.7% from a moderate socioeconomic level and a very low socioeconomic level (26.7%); however, 6.6% were from a high socioeconomic level.
In terms of the Stanford Binet test, there were statistically significant differences between the cases and controls in the IQ (P < 0.05). The case group had significantly low IQ compared with the control group in all components and the total score [Table 2].
[Table 3] shows that all cases had higher means than the control group in all components of Conners' Parent Rating Scale with a statistically significant difference (P = 0.001).
|Table 3: Conners' parent rating scale-revised-long version in cases and controls|
Click here to view
There was no significant difference between the cases and the control group (patient's siblings) regarding serum total T3, TSH, T4 (P > 0.05) [Table 4].
[Table 5] shows that 15 (50%) of the patients had no or only one comorbidity and 15 (50%) had two or more comorbidities. On comparing between the two subgroups (group with no or one comorbidity and the group with two or more comorbidities), we found that there were no statistically significant differences between the two groups in the IQ components test. There were only statistically significant differences between the two subgroups in the social problem subscale of Conners' scale, for which the scores were higher in the subgroup of children with two or more comorbidities. Also, there were no statistically significant differences in the thyroid profile of the two subgroups and the thyroid functions were within normal.
| Discussion|| |
ADHD is considered to have a biologic basis, but the precise cause is unknown. It is one of the neurodevelopmental abnormalities observed frequently in children with GRTH, suggesting that thyroid abnormalities may be related to ADHD (Weiss et al., 1993).
The majority of affected children in our study group were males (80%). These findings are consistent with previous studies that show that children diagnosed with ADHD are predominantly males (Biederman and Faraone, 2004).
ADHD is much more common among males than females. It is estimated that boys are two to three times more likely to have ADHD than girls. They are up to nine times more likely than girls to be referred for evaluation and treatment.
This might be attributed to the fact that males with ADHD show more externalizing hyperactive disruptive behavior than their female counterparts.
Girls usually tend to cluster in the inattentive subtype. Because they are do not show a behavior problem, their difficulties are often overlooked. Boys diagnosed with ADHD are usually clinic-referred because of oppositional, aggressive, and conduct behaviors. They tend to be very disruptive in the classroom, drawing the attention of their teachers (Biederman et al., 2010).
Most of the children in our study were from a low socioeconomic level. Many authors have reported that children affected by psychological disorders tend to be of low socioeconomic status (Castellanos et al., 2002). Among the different possible indicators of socioeconomic status, lower family income alone has repeatedly been shown to be correlated with the risk of ADHD (Graetz et al., 2001).
Diagnosis depends on the presence of three diagnostic criteria: inattentions, hyperactivity, and impulsiveness. Our results showed that all three criteria were present in the 30 children studied, except one child, who did not show hyperactivity.
These findings are consistent with many previous studies that found that the combined type of ADHD is the most common subtype, followed by the predominantly inattentive subtype, followed by the predominantly hyperactive subtype (Biederman et al., 2000).
Our results showed that ADHD cases had lower means than control participants for all components of the Stanford Binet Intelligence Scale.
Recently, it has been reported frequently that children with ADHD have on average a lower IQ than children without ADHD.
ADHD symptoms may directly cause an individual to perform poorly on the standard test of intelligence (Barkley, 1997).
In terms of the thyroid profile (TSH, T3, T4), the levels of the three hormones in the study group with within normal; no thyroid dysfunction was detected. There was no statistically significant difference between the study group of ADHD patients and their siblings in the total T3, T4, and TSH levels.
These results are in agreement with many previous studies that have examined the association between thyroxin and TSH, psychiatric diagnosis, and neurocognitive functioning; most of these studies reported a low prevalence of thyroid concentration abnormalities in psychiatric clinic-referred children (Refetoff, 1994).
In addition, Spencer et al. (1999) reported that most ADHD patients do not show resistance to thyroid hormone (RTH); in addition, patients with ADHD usually have normal thyroid hormone levels.
Another study, in contrast, found that 60% of patients with RTH also have ADHD, pointing to thyroid dysfunction as a potential cause of ADHD (Davis et al., 1995).
Also, our results differed from those of the study of Hauser et al. (1993), who evaluated the presence and severity of ADHD in 18 families with a history of GRTH. They found that in the study sample, ADHD is associated strongly with GRTH. Symptoms suggestive of this disorder have been reported in patients with GRTH, a disease caused by mutations in the thyroid receptor-β gene and characterized by reduced responsiveness of peripheral and pituitary tissues to the actions of thyroid hormone.
In addition, a stronger relationship was evidenced between lower concentrations of free T4 and more frequent mood symptoms and more perhaps ADHD patients may have subtle abnormalities in the hypothalamic-pituitary-adrenal axis. Free T4 may contribute directly toward poor attention, as suggested by studies of children with hypothyroidism (Murphy et al., 1990).
These differences between our study and other studies may be because of the small sample size of our study compared with the previously mentioned studies; in addition, most of the children in the case group had the combined type not the predominate inattentive-type or hyperactive-type ADHD, which is reported more in children with thyroid dysfunction. It may also be because RTH is not a common disorder.
There were no statistically significant differences between patients with one comorbidity and those with more than one comorbidity in terms of IQ; this is in agreement with the study carried out by Faraone et al. (2003), who found that psychiatric comorbidity had limited influence on the IQ score. However, other studies have reported that patients with ADHD plus conduct problems have been reported to have lower verbal IQ than those with either disorder alone (Bradley et al., 2006).
Clinical examination and diagnostic interviewing of the ADHD patients in our sample showed no associated comorbidities in only four children (13.3%). Others had oppositional defiant disorder (ODD) (30%), conduct disorder, and tic disorders (3.3 for each). Two comorbidities were found in 13 children (43.3%).
This is in agreement with previous studies in the literature; 60-100% of patients with ADHD show one or more comorbid disorders. Around 42-90% of patients fulfill the criteria for ODD and conduct disorder (Gillberg et al., 2004).
The above studies are consistent with our study in terms of the increased comorbidities with ADHD in the form of externalizing, internalizing disorders, learning disabilities, and speech problems. However, the difference in the prevalence rates of those comorbidities can be attributed to our small sample size.
On comparing the two subgroups with and without comorbidity, we found that there was a statistically significant difference in only social problems, which can be attributed to high comorbidity with ODD that is usually associated with social problems.
The result also showed no significant differences between both groups in thyroid profile, which may be because we failed to detect any patient with thyroid dysfunction during our study. Finally, longitudinal studies are needed to detect the relation between maternal thyroid hormone levels and the appearance of ADHD symptoms later on.
Our results should be considered in light of several methodological limitations:
- Our study was carried out on a small sample size of clinic-referred ADHD children who might be nonrepresentative for all children with ADHD.
- Our assessments relied on indirect parental reports and direct interviews with children, but did not include information collected from teachers.
The number of children in the control group was limited to 14 siblings because of refusal of many parents to complete the test on their normal children.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]