Congenital hyperplasia

This rare form, which is inherited via a recessive autosomal route, was described in 1968 as a variant of BRIC. (1, 2) The genetic defect is located on chromosome 15 q. A specific feature of this disease in neonates is giant-cell hepatitis with cholestasis, (s. p. 417) From about the 6 year of life until puberty, pathogenetic hypoplasia or ectasia of the lymphatic vessels with oedema are found in the lower extremities. It is not clear whether (suspected) congenital hyperplasia of lymphatic vessels in the liver is the prime cause of cholestasis. Pronounced fibrosis is often in evidence, whereas cirrhosis only occurs rarely. 

Classical congenital hyperplasia 21-Hydroxylase deficiency 11-Hydroxylase deficiency 3P-Hydroxysteroid dehydrogenase deficiency Adult or attenuated adrenal hyperplasia Androgen-producing adrenal tumors... 

BIO. Birke, G., Diczfalusy, E., Plantin, L-0., Robbe, H., and Westman, A., Familial congenital hyperplasia of the adrenal cortex. Acta Endocrinol. 29, 55-69 (1958). 

Gas Chromatographic Estimation of Urinary Pregnanetriol, Pregnane-triolone, and Pregnanetetrol in Congenital Hyperplasia J. Clin. Endocrinol. Metab. 26(11) 1219-1226 (1966) CA 66 27221x... 

Primary or secondary adrenal cortical insufficiency, congenital adrenal hyperplasia, nonsuppressive thyroiditis, hypercalcemia associated with cancer... 

Congenital adrenal hyperplasia ° Familial glucocorticoid deficiency and hypoplasia... 

Hyperandrogenic anovulation (PCOS, congenital adrenal hyperplasia, androgen-producing tumors)... 

Congenital adrenal hyperplasia A rare inherited condition resulting from a deficiency in cortisol and aldosterone synthesis with resulting excess androgen production. The clinical presentation depends on the variant of the condition, but it typically manifests as abnormalities in sexual development and/or adrenal insufficiency. 

Caron, K. M., Soo, S. C., Wetsel, W. C., Stocco, D. M., Clark, B. J., and Parker, K. L. 1997. Targeted disruption of the mouse gene encoding steroidogenic acute regulatory protein provides insights into congenital lipoid adrenal hyperplasia. Proc. Natl. Acad. Sci. U.S.A., 94(21) 11540-11545. 

Mutations with similar outcomes have been identified in nonautoimmune autosomal dominant hyperthyroidism (toxic thyroid hyperplasia) (25,26,28,32,33). These variants are located in the third TM (Val509Ala), the seventh TM (Cys672Tyr), and the carboxyl tail (Asp727Glu) regions (34). These variants result in a form of congenital hyperthyroidism that is the germline counterpart of a hyperfunctioning thyroid adenoma, with similar functional characteristics (25,33). 

Amenorrhoea, which refers to the absence of menstruation, is associated with anorexia nervosa, polycystic ovary syndrome and congenital adrenal hyperplasia. The condition requires referral. 

Betamethasone, as with all steroids, is used to suppress inflammatory reactions. It can be used topically or systemically. Indications for its use include eczema, asthma and congenital adrenal hyperplasia. It is contraindicated in ocular herpes simplex and in the red eye syndrome since it may clear the symptoms while not addressing the infective component of the underlying condition. 

Endocrine disorders Primary or secondary adrenal cortical insufficiency (hydrocortisone or cortisone is the drug of choice synthetic analogs may be used in conjunction with mineralocorticoids in infancy, mineralocorticoid supplementation is important) congenital adrenal hyperplasia nonsuppurative thyroiditis hypercalcemia associated with cancer. 

Congenital adrenal hyperplasia Feds. Initial hydrocortisone 30-36 mg/mVd PO -5-1/3 dose qAM, 2/3 dose qPM maint 20-25 mg/mVd bid. 

As discussed above, in the case of phenylketonuria, early intervention can make the difference between mental retardation and a near normal life course for a newborn. Congenital adrenal hyperplasia and maple syrup urine disease are two examples of neonatal hereditary disorders where early diagnosis and medical intervention can make the difference between life and death for the newborn. In addition, in a number of genetic diseases, early diagnosis and treatment can help ameliorate symptoms these include fragile X syndrome, homocystinuria, sickle cell anemia, cystic fibrosis, and many /1-thalassemias. 

Dexamethasone Synthetic glucocorticoid, lacks mineralocorticoid activity Used to treat range of inflammatory diseases. Used to treat some forms of asthma, also cerebral oedema and congenital adrenal hyperplasia... 

Congenital enzymatic defects in the adrenal biosynthetic pathways lead to diminished cortisol and aldosterone production and release. In these conditions, corticotrophin secretion is increased, and adrenal hyperplasia occurs, accompanied by enhanced secretion of steroid intermediates, especially adrenal androgens. More than 90% of cases of congenital adrenal hyperplasia are due to 21-hydroxylase deficiency, which is cre-afed by mufafions in fhe CYP21 gene encoding fhe en-... 

Substitution therapy for deficiency states acute or chronic adrenal insufficiency, congenital adrenal hyperplasia, and adrenal insufficiency secondary to pituitary insufficiency, nonendocrine disorders arthritis rheumatic carditis allergic, collagen, intestinal tract, liver, ocular, renal, shin diseases bronchial asthma cerebral edema malignancies PO 5-60 mg/day in divided doses. Intra-articular, Intralesional (acetate) 4-100 mg, repeated as needed. Intra-articular, Intralesional (sodium phosphate) 2-30 mg, repeated at 3-day to 3-week intervals, as needed. IM (acetate, sodium phosphate) 4-60 mg a day. 

Substitution therapy in deficiency states acute or chronic adrenai insufficiency, congenital adrenal hyperplasia, and adrenal insufficiency secondary to pituitary insufficiency nonendocrine disorders arthritis rheumatic carditis aiiergic, coiiagen, intestinai tract, liver, ocular, renal, shin diseases bronchiai asthma cerebrai edema maiignancies PO... 

Chronic Addison s disease congenital adrenal hyperplasia (genetic disorder due to deficiency of steroidogenic enzymes). 

In patients suspected of congenital adrenal hyperplasia, to identify 21-hydroxylase deficiency, 11- hydroxylase deficiency, and 3l3-hydroxy-A5 steroid dehydrogenase deficiency, based on the steroids that accumulate in response to ACTH administration (see Figure 39-1 and Chapter 39)... 

Adrenocortical Hypo- and Hyperfunction CONGENITAL ADRENAL HYPERPLASIA... 

This group of disorders is characterized by specific defects in the synthesis of cortisol. In pregnancies at high risk for congenital adrenal hyperplasia, fetuses can be protected from genital abnormalities by administration of dexamethasone to the mother. The most common defect is a decrease in or lack of P450c21 (2ll3-hydroxylase) activity. ... 

When first seen, the infant with congenital adrenal hyperplasia may be in acute adrenal crisis and should be treated as described above, using appropriate electrolyte solutions and an intravenous preparation of hydrocortisone in stress doses. 

DOC, which also serves as a precursor of aldosterone (Figure 39-1), is normally secreted in amounts of about 200 mcg/d. Its half-life when injected into the human circulation is about 70 minutes. Preliminary estimates of its concentration in plasma are approximately 0.03 mcg/dL. The control of its secretion differs from that of aldosterone in that the secretion of DOC is primarily under the control of ACTH. Although the response to ACTH is enhanced by dietary sodium restriction, a low-salt diet does not increase DOC secretion. The secretion of DOC may be markedly increased in abnormal conditions such as adrenocortical carcinoma and congenital adrenal hyperplasia with reduced P450cll or P450cl7 activity. 

Merke DP et al Future directions in the study and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Ann Intern Med 2002 136 320. [PMID 11848730]... 

Arlt W, Walker EA, Draper N, Ivison HE, Ride JP, Hammer F, Chalder SM, Borucka-Ankie-wicz M, Hauffa BP, Malunowicz EM, Stewart PM, Shackleton CH (2004) Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis analytical study. Lancet 363 2128-2135... 

Caulfield MP, Lynn T, Gottschalk ME, Jones KL, Taylor NF, Malunowicz EM, Shackleton CH, Reitz RE, Fisher DA (2002) The diagnosis of congenital adrenal hyperplasia in the newborn by gas chromatography/mass spectrometry analysis of random urine specimens. J Clin Endocrinol Metab 87 3682-3690... 

Cristoni S, Cuccato D, Sciannamblo M, Bernardi LR, Biunno I, Gerthoux P, Russo G, Weber G, Mora S (2004) Analysis of 21 deoxycortisol, a marker of congenital adrenal hyperplasia, in blood by atmospheric pressure chemical ionization and electrospray ionization using multiple reaction monitoring. Rapid Commun Mass Spectrom 18 77-82... 

Honour JW, Anderson, JM, Shackleton, CH (1983) Difficulties in the diagnosis of congenital adrenal hyperplasia in early infancy the 1 l/ -hydroxylase defect. Acta Endocrinol (Copenh) 103 101-109... 

Joannou GE (1981) Identification of 15/5-hydroxylated C21 Steroids in the neo-natal period the role of 3a,15/),17a-trihydroxy-5/ -pregnan-20-one in the perinatal diagnosis of congenital adrenal hyperplasia (CAH) due to a 21-hydroxylase deficiency. J Steroid Biochem 14 901-912... 

Lacey JM, Minutti CZ, Magera MJ, Tauscher AL, Casetta B, McCann M, Lymp J, Hahn SH, Rinaldo P, Matern D (2004) Improved specificity of newborn screening for congenital adrenal hyperplasia by second-tier steroid profiling using tandem mass spectrometry. Clin Chem 50 621-625... 

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