Disorders of the Adrenal Gland

70 Disorders of the Adrenal Gland



The adrenal gland is really two separate organs: the adrenal medulla secretes epinephrine and norepinephrine, and the adrenal cortex secretes glucocorticosteroids, mineralocorticoids, and androgenic steroids. Glucocorticoids and mineralocorticoids are essential for maintaining metabolic homeostasis, particularly during times of stress; deficiency of these hormones can be life threatening if not recognized and treated. Conversely, excess of any of these hormones, although unusual, can lead to severe and permanent consequences. Accordingly, it is critically important to recognize disordered adrenal function and to institute treatment expediently. This chapter focuses on the physiology and pathology of the adrenal cortex.



Adrenal Gland Physiology


The adrenal cortex consists of three distinct zones, the glomerulosa, the fasciculata, and the reticularis. The fasciculata is the principal component of the hypothalamic–pituitary–adrenal axis. Glucocorticoid (cortisol) secretion from the fasciculata is regulated by adrenocorticotropic hormone (ACTH). ACTH is synthesized from pre-pro-opiomelanocortin (pre-POMC). The removal of the signal peptide during translation produces the 267 amino acid polypeptide POMC, which undergoes a series of posttranslational modifications to yield various polypeptide fragments with varying physiological activity. These fragments include the 39 amino acid polypeptide ACTH, as well as β-lipotropin, γ-lipotropin, melanocyte-stimulating hormone (α-MSH), and β-endorphin. POMC, ACTH and β-lipotropin are secreted from corticotropes in the anterior lobe of the pituitary gland in response to the hormone corticotropin-releasing hormone (CRH) released by the hypothalamus (Figure 70-1).



A reduction in circulating cortisol levels activates this axis, leading to increased secretion of ACTH; high levels of cortisol or exogenous steroids downregulate the axis and reduce secretion of adrenal cortisol. Aldosterone is produced in the zona glomerulosa under independent control through the renin–angiotensin system. Low blood pressure and intravascular volume contraction lead to renin release from the kidney, activating this system.




Adrenal Insufficiency



Etiology and Pathogenesis



Primary Adrenal Insufficiency


Primary adrenal insufficiency is caused by congenital or acquired dysfunction of the adrenal cortex or the hormone-producing steroidogenic pathway (Table 70-1). The most common cause in the developed world is autoimmune adrenalitis, also known as Addison’s disease. In developing countries, tuberculosis remains the most prominent cause. Destruction of the gland leads to deficiencies in all adrenal cortex hormones, but this process may be metasynchronous, and not all hormones are lacking in all patients. Enzyme defects can cause cortisol deficiency with an excess of precursor hormones. Loss of negative feedback from low cortisol levels leads to high ACTH in these disorders.


Table 70-1 Causes of Primary Adrenal Insufficiency



























































Cause Associations or Pathogenesis Diagnosis
Acquired
Addison’s disease Other autoimmune disease Adrenal antibodies
Autoimmune polyglandular syndrome Type 1: hypoparathyroidism and mucocutaneous candidiasis
Type 2: type 1 diabetes, thyroiditis, other autoimmune
AIRE gene mutation in type 1
Infiltration or infection TB, fungal, cancer, amyloidosis, sarcoid, hemochromatosis, CMV (HIV patients) PPD, cultures, imaging, biopsy, ELISA or Western blot
Waterhouse-Friderichsen syndrome Meningococcemia leading to adrenal hemorrhage Cultures
Bilateral hemorrhage Trauma, anticoagulants Imaging
Medications: mitotane, ketoconazole Destruction of gland, enzyme blockage History
Congenital
CAH Autosomal recessive; mutation of 21-hydroxylase and others Adrenal steroid profiles, genetic testing CYP21
Adrenoleukodystrophy; adrenomyeloneuropathy X-linked; buildup of VLCFAs in adrenals and cerebral or spinal cord involvement; neuromuscular disease Serum VLCFAs; ALD gene
X-linked congenital adrenal hypoplasia Delayed puberty, contiguous gene mutations (Duchenne’s muscular dystrophy, glycerol kinase) DAX1 gene testing
Triple A syndrome Autosomal recessive; achalasia, alacrima, adrenal insufficiency AAAS gene at 12q13
Other syndromes: IMAGE, Smith-Lemli-Opitz Vary Genetic testing
ACTH resistance ACTH receptor or melanocortin 2 receptor accessory protein (MRAP) gene mutations Genotyping of receptor or MRAP genes

ACTH, adrenocorticotropic hormone; CAH, congenital adrenal hyper-plasia; CMV, cytomegalovirus; ELISA, enzyme-linked immunosorbent assay; HIV, human immunodeficiency virus; IMAGE, intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita, genital abnormalities; PPD, purified protein derivative; TB, tuberculosis; VLCFA, very long chain fatty acid.



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Jun 19, 2016 | Posted by in PEDIATRICS | Comments Off on Disorders of the Adrenal Gland

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