Introduction
Primary generalized glucocorticoid resistance is an autosomal dominant disease in which tissue resistance toward glucocorticoids develops. It is a rare endocrinological condition. Tissues naturally develop resistance to cortisol. Glucocorticoids are steroid hormones that generally regulate inflammation and autoimmunity. Glucocorticoid regulates a broad spectrum of physiologic functions. It plays a very important role in various biological processes, such as growth, reproduction, intermediary metabolism, and the immune system. In this disease, patient tissue is exposed to elevated levels of adrenal androgens and mineralocorticoids, resulting in hyperandrogenism and hypermineralocorticoidism.
What Is Glucocorticoid?
Glucocorticoid is a steroid hormone secreted from the cortex of adrenal glands. It has a major role in glucose, protein, and fat metabolism in the body. They originate from steroid precursor cells. They act as anti-inflammatory, anti-allergic, and immunosuppressive agents. Cortisol is an essential glucocorticoid in the body.
What Is a Human Glucocorticoid Receptor?
The mechanism of action of glucocorticoid hormone is mediated by a protein 94-kDa protein, the glucocorticoid receptor. It is a nuclear receptor and functions as “a ligand -dependent”transcription factor. It regulates the expression of glucocorticoid responsive genes.
What Are the Causes of Primary Generalized Glucocorticoid Reactions?
Primary generalized glucocorticoid reactions are genetic diseases caused by mutation of a gene that encodes glucocorticoid receptors. Alteration of signal transduction leads to impaired sensitivity of glucocorticoid towards the tissue. Chrousos syndrome can be inherited in an autosomal recessive or dominant fashion or may be sporadic due to de novo genetic defects (point mutations, deletions, or insertions) in the NR3C1 gene. Due to this mutation, there is an alteration defect in glucocorticoid signal transduction.
What Are the Clinical Manifestations of Primary Generalized Glucocorticoid Reactions?
It is a genetic disease characterized by generalized partial insensitivity toward glucocorticoids. It is mainly associated with hypertension and hypokalemic alkalosis. In a young child, there is the presence of hypoglycemia. Generalized tonic-clonic seizures are reported in many cases. In a newborn baby, there is the presence of a febrile illness along with severe hypoglycemia. There is the presence of excessive fatigability during feeding. The child is more prone to infections, and retardation of growth is seen. There is the presence of precocious puberty in children of both genders. In males, there is acne hirsutism and decreased fertility, whereas in females, there is hair loss, menstrual irregularities, and oligo-anovulation is seen. Patients are predisposed to the development of adrenocorticotropic hormone-secreting pituitary adenoma. There is an increased level of anxiety and depression, and central nervous system dysfunction such as headaches, visual impairment, and seizures are also noted.
What Are the Complications of Primary Generalized Glucocorticoid Reactions?
Effects can range from mild to severe according to the severity of the disease.
It includes:
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Increased appetite leads to weight gain.
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Increased risk of infections.
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High blood pressure osteoporosis.
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Thinned skin that bruises easily.
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Withdrawal symptoms.
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Thinning of the skin, due to which skin is more prone to bruises.
How Can Primary Generalized Glucocorticoid Reaction Be Diagnosed?
Accurate and sensitive laboratory methods and proper clinical examination help in the diagnosis of primary glucocorticoid reactions. Pituitary magnetic resonance imaging, along with adrenal computed tomography, is advised. Complete personal and family history of a patient should be taken. Physical examination should include an assessment of signs of hyperandrogenism, acne, axillary hair development, and cilantro legally. An endocrinologic evaluation of the patient is advised. The concentrations of plasma corticotropin, plasma renin, aldosterone, serum cortisol, testosterone, androstenedione, total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting glucose insulin are evaluated.
What Is the Differential Diagnosis of Primary Generalized Glucocorticoid Reactions?
Following are the differential diagnosis of primary generalized glucocorticoid reactions.
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Adrenocortical Imaging.
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Congenital adrenal hyperplasia.
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Polycystic ovarian syndrome.
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Precocious Puberty.
What Is the Treatment for Primary Generalized Glucocorticoid Reactions?
As there is excessive secretion of adrenocorticotropic hormone and increased production of ‘’adrenal steroids,’’ there is an increase in androgenic activity. The major aim of treatment is to suppress the increased production of adrenal steroids. Administration of a high dose of synthetic glucocorticoid is given to activate the mutant gene and suppress the endogenous secretion of adrenocorticotropic hormone. A high dose of a synthetic glucocorticoid such as dexamethasone (1-3 mg given once daily at night) is given in a biochemically titrated dose. This helps in suppressing adrenocorticotropic hormone without stimulating mineralocorticoid receptors. Hyperandrogenism and hyper mineralocorticoids can be corrected while compensating for the glucocorticoid action on target tissues.
Conclusion
The glucocorticoid receptor is an intracellular transcription factor that mediates the action of glucocorticoids. It influences all the physiological functions which are essential for life. It has an important role in the regulation of crucial biological processes. There it is very important to diagnose this disease along the proper line of management.
