Adrenal Gland Disorders in Children in India
1. Yaman Hasan
2. Bugubaeva Makhabat Mitalipovna
(1. Student, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic
2. HOD Clinical Disciplines-2, Associate Professor, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.)
Abstract
Adrenal gland disorders in childhood represent a diverse group of endocrine conditions with significant implications for growth, metabolism, and survival. In India, the burden of congenital adrenal hyperplasia, adrenal insufficiency, adrenal tumors, and functional abnormalities reflects both global patterns and unique region-specific determinants such as consanguinity, limited newborn screening, variable access to endocrine testing, and delays in specialist referral. This review adopts an IMRAD framework to synthesize current knowledge on the epidemiology, pathophysiology, clinical manifestations, diagnostic approaches, and therapeutic considerations of pediatric adrenal disorders within the Indian context. Findings highlight substantial gaps in early detection and emphasize the ongoing challenges posed by resource constraints, cultural practices, and disparities in healthcare access between urban and rural regions. The discussion underscores the need for improved awareness, strengthened pediatric endocrine services, and wider implementation of newborn screening to ensure timely diagnosis and long-term follow-up. While scientific understanding of adrenal diseases continues to advance, achieving better outcomes in India depends on integrating these insights into practical, equitable healthcare strategies for children nationwide.
Introduction
Contextualizing Adrenal Pathophysiology
The adrenal glands, consisting of the outer cortex and inner medulla, serve as critical components of the neuroendocrine system, responsible for synthesizing essential steroid hormones (cortisol, aldosterone, androgens) and catecholamines (epinephrine and norepinephrine). These hormones are paramount for regulating metabolism, electrolyte balance, blood pressure, and the body's acute and chronic stress response.
In the pediatric population, dysfunction of these glands can lead to profound and often life-threatening imbalances. The spectrum of adrenal disorders in children ranges from congenital enzymatic defects, such as Congenital Adrenal Hyperplasia (CAH), which presents shortly after birth, to acquired conditions like primary adrenal insufficiency (Addison's disease) or hormone-secreting tumors (pheochromocytomas and adrenocortical carcinomas), which may manifest later in childhood or adolescence. Given the critical role of adrenal hormones in growth and pubertal development, timely diagnosis and initiation of appropriate management are non-negotiable determinants of long-term health outcomes. Failure to recognize these conditions promptly, particularly in the context of an acute adrenal crisis, carries significant morbidity and mortality risks, necessitating a high index of clinical suspicion across all pediatric care settings.
The Indian Epidemiological Landscape
The study of adrenal disorders in the Indian pediatric cohort presents unique challenges and epidemiological considerations. India's vast and heterogeneous population, combined with variability in public health infrastructure and screening practices across states, influences the reported incidence and prevalence figures. For instance, while CAH is a globally recognized disorder, the true incidence in India remains obscured due to the lack of a standardized, nationwide Newborn Screening (NBS) program, unlike in many Western countries. The available data are often derived from tertiary care centers and regional cohort studies, potentially introducing selection bias and underestimating the true burden of the disease in the general population.
Furthermore, the clinical presentation and management of these disorders are frequently complicated by coexisting conditions prevalent in the Indian setting, such as infectious diseases (e.g., tuberculosis as a cause of adrenal destruction), nutritional deficiencies, and delayed presentation to specialized care. An estimated 12,000 cases of CAH are born annually in India, according to extrapolated global incidence rates, yet only a fraction receive timely diagnosis and care. This necessitates a focused review to collate the existing literature, identify key epidemiological patterns, discuss diagnostic challenges, and critique current management practices within the Indian healthcare context. This article aims to provide a comprehensive, evidence-based overview of the prevalent adrenal gland disorders affecting children in India, thereby informing clinical practice, guiding public health policy regarding screening, and highlighting critical areas for future research.
Methods
i. Study Design and Scope of Review
This academic review employs a comprehensive, non-systematic approach, synthesizing primary research, clinical case series, consensus guidelines, and review articles pertinent to pediatric adrenal disorders within the context of the Indian subcontinent. The objective was to characterize the spectrum of adrenal pathology in this specific demographic, focusing on the most prevalent congenital, autoimmune, and oncologic conditions.
ii. Search Strategy and Data Sources
A multi-database literature search was conducted utilizing electronic databases including PubMed, Scopus, and the Cochrane Library. The search was further augmented by scrutinizing local Indian medical journals and grey literature where appropriate. Key search terms, both used individually and in combination with Boolean operators (AND, OR), included: "Adrenal gland disorders," "pediatric endocrinology," "children," "India," "Congenital Adrenal Hyperplasia (CAH)," "Addison's disease," "primary adrenal insufficiency," "Cushing's syndrome," "pheochromocytoma," "adrenocortical carcinoma," and "newborn screening." The search was restricted to articles published primarily between 2000 and 2024 to ensure contemporary relevance, although seminal papers of historical significance were included where necessary to establish foundational clinical concepts. Articles were screened based on title and abstract for relevance to the pediatric population (defined as individuals aged 0 to 18 years) and a clear focus on, or data derived from, studies conducted in India.
iii. Inclusion and Exclusion Criteria
Articles were selected for inclusion if they provided original epidemiological data, clinical descriptions, diagnostic algorithms, or therapeutic outcomes specific to adrenal disorders in Indian children. Studies that exclusively focused on the adult population, articles providing only a generalized global review without specific Indian data, or those not published in peer-reviewed forums were excluded. Preference was given to studies from large, specialized tertiary care centers that often serve as regional referral points, as these centers typically manage the most complex and statistically significant patient volumes.
iv. Data Synthesis and Analysis
The extracted data were organized and analyzed thematically according to specific disease entities: Congenital Adrenal Hyperplasia (the most common group), Autoimmune Adrenalitis (Addison's disease), Iatrogenic/Endogenous Hypercortisolism (Cushing's syndrome), and Adrenal Tumors. For each condition, the review focused on summarizing the reported prevalence, highlighting unique clinical phenotypes observed in the Indian setting, discussing prevalent diagnostic modalities (e.g., use of the ACTH stimulation test, genetic sequencing), and evaluating the challenges related to chronic management compliance, which is a known socio-economic factor influencing outcomes in India. The synthesis aimed to move beyond mere documentation of cases and to generate a cohesive narrative that identifies critical gaps between recommended global standards of care and current clinical practice within the nation. The findings were not subjected to meta-analysis due to the heterogeneity in study designs and reporting methodologies but were interpreted qualitatively to draw robust clinical and public health inferences.
Results
i. Congenital Adrenal Hyperplasia (CAH)
Congenital Adrenal Hyperplasia, overwhelmingly caused by a deficiency in the 21-hydroxylase enzyme (21-OHD), constitutes the most frequently encountered group of adrenal disorders in pediatric endocrinology across India. The true incidence, as noted, remains challenging to definitively ascertain. However, based on tertiary care center data, the incidence is often cited to range between 1 in 15,000 to 1 in 20,000 live births. This figure is highly variable and likely underestimates the total prevalence, particularly the milder non-classical forms, which may go undiagnosed until later childhood or even adulthood.
A significant finding recurrently documented in Indian cohorts is the high proportion of patients presenting with the severe classic salt-wasting (SW) form. This phenotype, resulting from severe cortisol and aldosterone deficiency, presents as an adrenal crisis in the neonatal period, characterized by vomiting, dehydration, failure to thrive, and life-threatening hyponatremia and hyperkalemia. Delayed or missed diagnoses, particularly in rural or peripheral hospitals lacking advanced biochemical facilities, directly contribute to the high reported mortality rates in this subset. In genetic terms, studies have noted a spectrum of common CYP21A2 gene mutations, though a complete, nationwide profile is still evolving. The clinical presentation is further complicated by the high incidence of ambiguous genitalia in genetically female infants (46,XX), necessitating the involvement of multi-disciplinary teams for sex assignment and surgical correction, which is often culturally sensitive and fraught with ethical complexities in the Indian social structure. The absence of a mandatory, robust National Newborn Screening (NBS) program is a critical barrier; pilot programs have demonstrated high efficacy, yet widespread implementation faces significant logistical and financial hurdles.
ii. Adrenal Insufficiency: Beyond Autoimmunity
While Addison's disease, the primary form of chronic adrenal insufficiency, is typically attributable to autoimmune adrenalitis in Western populations, the etiology in the Indian pediatric setting shows a notable divergence. A substantial minority of cases are attributed to infectious causes, primarily adrenal tuberculosis (TB). Given India's significant burden of endemic tuberculosis, TB must always remain a differential diagnosis, even in children, presenting as bilateral adrenal calcification on imaging. Regardless of etiology, the presentation of chronic adrenal insufficiency often follows a pattern of non-specific symptoms, including insidious onset of generalized fatigue, progressive weight loss, gastrointestinal disturbances, and the pathognomonic sign of hyperpigmentation involving the palmar creases, buccal mucosa, and pressure points. The acute adrenal crisis, triggered by minor illnesses, dehydration, or surgical stress, remains the most frequent reason for emergency department presentation. The diagnostic confirmation involves demonstrating low baseline cortisol levels, which fail to rise appropriately following administration of synthetic ACTH (the Synacthen test). Challenges in the accurate diagnosis and management in remote settings often revolve around the availability of timely and accurate hormone assays, and the immediate accessibility of parenteral glucocorticoid and mineralocorticoid replacement therapy.
iii. Adrenocortical Tumors and Hypercortisolism (Cushing's Syndrome)
Cushing's syndrome in the Indian pediatric population is a rare but critically important diagnostic entity. Exogenous administration of glucocorticoids, often prescribed for chronic conditions like asthma or nephrotic syndrome, remains the most common cause of hypercortisolism. Endogenous Cushing's syndrome in children is predominantly ACTH-dependent, typically arising from a pituitary microadenoma (Cushing's disease). However, the rare but aggressive adrenocortical carcinoma (ACC) warrants immediate consideration, as its prognosis is severely guarded.
The clinical phenotype of hypercortisolism in children can be subtle initially, manifesting as growth attenuation and weight gain, followed by the more classical signs of truncal obesity, hypertension, easy bruising, and striae. The workup involves biochemical confirmation via 24-hour urinary free cortisol measurements, followed by advanced imaging (MRI or CT) of the pituitary and adrenal glands to locate the pathological source. In regions where access to high-resolution MRI is limited, the diagnostic path can be protracted, delaying curative intervention, which is often transsphenoidal surgery for Cushing's disease or adrenalectomy for ACC.
Discussion
The findings synthesized from the Indian pediatric literature underscore a distinct pattern of adrenal pathology, heavily skewed toward Congenital Adrenal Hyperplasia and complicated by a notable incidence of tuberculosis-related adrenal insufficiency. These observations necessitate a paradigm shift in pediatric endocrine practice, moving beyond Western-centric guidelines to address local epidemiological realities.
i. The Critical Imperative of Newborn Screening
The single most impactful public health intervention identified to mitigate the catastrophic consequences of CAH, particularly the SW-form, is the implementation of a universal, government-subsidized Newborn Screening (NBS) program. The current reliance on clinical suspicion and delayed biochemical confirmation often results in infants presenting in extremis, leading to irreversible neurological damage and death. While pilot studies have demonstrated technical feasibility, the challenge remains in scaling up the infrastructure for sample collection, transportation, centralized laboratory analysis using 17-hydroxyprogesterone (17-OHP) assays, and ensuring a robust recall mechanism for confirmed cases. Overcoming the financial and logistical barriers in a country with diverse geographical and social terrains requires a committed partnership between central policy-makers, state health departments, and private laboratory networks. Furthermore, the socio-cultural context of delayed presentation, especially for female infants with mild virilization, must be addressed through community education to ensure parental compliance with follow-up protocols.
ii. Challenges in Chronic Management and Adherence
Beyond the critical phase of diagnosis, the chronic management of all forms of adrenal insufficiency presents substantial difficulties, primarily revolving around medication adherence. Children with CAH require precise, life-long replacement of glucocorticoids (hydrocortisone), often supplemented with mineralocorticoids (fludrocortisone). Compliance issues are multifactorial, stemming from low health literacy, economic constraints hindering regular medication purchase, and the inherent difficulty in maintaining strict adherence to complex dosing schedules in school-age children. This sub-optimal adherence significantly increases the risk of recurrent adrenal crises and compromises long-term growth and reproductive health outcomes.
Clinicians in India are frequently tasked with educating families on the crucial concept of stress-dosing—the immediate tripling of glucocorticoid dosage during periods of fever, trauma, or significant illness. The need for an injectable form of glucocorticoid (e.g., Solu-Cortef) for emergency use at home is an absolute safety requirement that is often not met due to cost or lack of parental training. Future clinical research must focus on developing India-specific intervention strategies, potentially leveraging digital health platforms or community health workers (CHWs) to improve patient and family education, medication access, and adherence monitoring.
iii. The Burden of Infectious Adrenalitis
The persistence of Tuberculosis as a major cause of adrenal destruction fundamentally distinguishes the Indian clinical scenario. While autoimmune Addison's disease involves a gradual, often irreversible process, TB adrenalitis may be reversible, or partially reversible, if caught early and treated aggressively with a multi-drug anti-tubercular regimen. This diagnostic possibility places a higher burden on clinicians to pursue appropriate diagnostic imaging and serology, particularly in cases presenting with systemic signs of infection or vague abdominal symptoms alongside adrenal insufficiency. A clinical algorithm must be instituted that mandates screening for TB in all non-autoimmune cases of primary adrenal failure until proven otherwise, reflecting the country's unique epidemiological burden.
iv. Advancing Care for Adrenal Tumors
The management of rare but malignant tumors like Adrenocortical Carcinoma (ACC) and Pheochromocytoma in children requires highly specialized expertise found only at apex tertiary care centers. The survival rate for ACC is directly linked to the stage at presentation and the completeness of surgical resection. The lack of standardized, high-volume surgical units equipped for complex retroperitoneal resections means that patient outcomes can be highly variable across the country. Furthermore, genetic screening for associated syndromes like Multiple Endocrine Neoplasia type 2 (MEN 2) or Von Hippel-Lindau (VHL) disease, particularly in cases of pheochromocytoma, remains inconsistently applied. Integrating genetic counseling and advanced molecular diagnostics into the standard care protocol for pediatric adrenal tumors is a necessary next step to improve early detection in at-risk family members.
v. Conclusion and Future Directions
The current overview reveals that pediatric adrenal gland disorders in India present as a complex interplay between globally common genetic conditions (CAH) and locally dominant environmental/infectious etiologies (TB). While significant strides have been made in clinical management at specialized centers, vast disparities persist in access to timely diagnosis, comprehensive genetic testing, and chronic care adherence in underserved communities. Future efforts must prioritize the swift, national rollout of the Newborn Screening program, establish standardized clinical care protocols that account for infectious etiologies, and invest in robust, low-cost educational interventions to empower families in the management of these life-long, potentially life-threatening conditions. Adrenal gland disorders in children represent a significant but often under-recognized component of pediatric endocrine disease in India. Conditions such as congenital adrenal hyperplasia, adrenal insufficiency, and adrenal tumors carry risks of severe morbidity and mortality when diagnosis is delayed. This review demonstrates that while scientific understanding of these disorders continues to advance, systemic barriers such as limited newborn screening, disparities in specialist access, resource constraints, and cultural perceptions continue to impact outcomes for Indian children.
A coordinated national strategy emphasizing early detection, expanded pediatric endocrine services, and increased awareness among healthcare providers is essential. Timely diagnosis, lifelong follow-up, and comprehensive family support have the potential to transform the prognosis for children with adrenal disorders. As India continues to enhance its pediatric care infrastructure, prioritizing adrenal health can contribute significantly to improving child survival and long-term developmental outcomes across the country.
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