The association between Addison’s disease and other endocrinopathies was probably first described in 1886. In 1926, Schmidt presented two cases of Addison’s disease with cortical atrophy and lymphocytic infiltration of the adrenal, as well as lymphoid infiltration in the thyroid [
4]. APS2 is rare, because it necessarily requires the presence of Addison’s disease. Considering that the prevalence of idiopathic Addison’s disease has been suspected to be 30 to 60 cases/million inhabitants and that about 50% to 75% of Addisonian patients may be affected by thyroid autoimmune disease and insulin dependent diabetes or both, it may be estimated that APS2 occurs in 15 to 45 cases per million inhabitants in the general population. The syndrome may occur at all ages and in both sexes but is most commonly found in middle-aged women. Inheritance is consistent with autosomal dominance with incomplete penetrance. These patients have an increased frequency of the HLA A1, B8 and DR3 haplotypes [
5]. An unexpected fall in insulin requirement in patients with T1DM may be the earliest sign of adrenal failure. Our index case developed recurrent hypoglycemia attacks without any change in his treatment or physical activity. Hypoglycemic attacks are considered to be caused by enhanced insulin sensitivity secondary to glucocorticoid deficiency [
6]. Hashimoto’s thyroiditis was diagnosed in our case on findings of seropositivity for Tg and TPO autoantibodies, and slightly high TSH accompanied by morphological changes seen on thyroid ultrasound [
7]. Symptoms and signs of hypothyroidism and hypoadrenalism are often non-specific. Since early diagnosis and treatment of these hormonal insufficiencies are vital, it is essential to always consider an association. Adrenal insufficiency should be considered in patients with autoimmune thyroid disease or T1DM who develop non-specific illness or become seriously ill, or in diabetic patients whose insulin requirements fall inexplicably [
8]. The hyperpigmention of the skin and mucous membranes was not obvious in our case. The absence or presence of hyperpigmentation in Addison’s disease is related to the duration of the illness and the time taken to stimulate the pituitary to produce ACTH. Although pigmentation is a very useful sign in Addison’s disease, its absence by no means excludes the diagnosis. It seems that only an awareness of the possibility of the disease will lead to an early diagnosis [
9]. Our case showed vitiligo over the chest and abdomen which is a chronic disorder that causes patchy hypopigmentation of the skin. It occurs when the melanocytes, which are derived from the neural crest, die or are unable to function. The precise pathogenesis of vitiligo is not yet fully understood but an autoimmune etiology is the most widely accepted. It is mandatory to actively look for, and if necessary, investigate patients with vitiligo for other autoimmune diseases [
10]. In Egypt, HCV infection in diabetic children is considered a health-related infection; with a prevalence of anti-HCV among diabetic children of 3.5%, it may be attributed to repeated hospitalization, insulin injections, shared insulin vials and shared spring-triggered devices for capillary blood glucose monitoring [
3]. Our case was diagnosed with chronic hepatitis C. We suggest that the risk factors for contraction of hepatitis C in our case were frequent hospital admissions and circumcision by a barber which is a common practice in villages in Upper Egypt. These suggestions are supported by Kalil
et al.[
11] and Medhat
et al.[
12] in their study regarding risk factors of acquisition of hepatitis C in children in Upper Egypt. HCV seems to be the virus usually associated with the appearance of autoimmune diseases, and the relationship between chronic HCV infection and some autoimmune disease has been studied. For some of these disorders their association with HCV infection is well recognized while for others it remains probable or weak [
13]. HCV infection has been associated with Type 2 diabetes mellitus; however, Chen
et al.[
14] reported T1DM one year after a blood transfusion-related HCV infection. The exact mechanisms underlying HCV-mediated T1DM still are not well understood and several investigators have proposed that cross reactive mechanisms are operating in the generation of autoimmunity in HCV infection. This hypothesis is supported by the discovery of remarkable amino acid similarities between HCV and glutamic acid decarboxylase 65 (GAD65), protein tyrosine phosphatase islet cell antigen-2 and phogrin [
15]. Identification of the type and extent of autoimmune disorders in children with HCV infection is important for the following reasons: First, this awareness can result in rapid diagnosis and treatment of these diseases. Second, the existence of an autoimmune disorder in patients with HCV infection requires clinicians with good experience in the management of such cases. Third, patients presenting with these disorders can be targeted for HCV testing [
13]. Our case presents three very interesting and unusual aspects. First, given that APS2 occurs most often in middle-aged women, its presentation in a boy during childhood is uncommon. In this communication, we report the case of a 14-year-old boy with APS2 with HCV infection. Second, the association of APS2 with chronic hepatitis C in our case would suggest adding APS2 to the list of autoimmune diseases apparently associated with chronic hepatitis C. Finally, hepatic dysfunction in Egyptian children with APS2 is not necessarily due to autoimmune hepatitis but can be attributed to HCV infection.