Kongenitalna adrenalna hiperplazija– lekcije o rastu, razvoju i glukokortikoidnoj terapiji

Introduction: Congenital adrenal hyperplasia (CAH) includes a group of autosomal recessive disorders of steroidogenesis caused by reduced or absent activity of enzymes involved in the synthesis of steroid hormones from cholesterol. The most common form of CAH, which accounts for 90–95% of cases, is the result of a deficiency of 21-hydroxylase, an enzyme essential for the synthesis of cortisol and aldosterone. The severity of the disease depends on the residual enzymatic activity associated with certain mutations of the CYP21A2 gene, and the main feature of the clinical picture is virilization of the child. We distinguish between the classic form of CAH, which is manifested at birth, and the milder, non-classical form, in which the clinical picture develops later during childhood or adolescence. Virilization in its most severe form in girls is manifested by ambiguous genitalia, while it is more difficult to recognize immediately after birth in boys, but it causes progressive development of the genitals and accelerated growth and physical development, which can lead to true precocious puberty and compromise final height. The most severe form of the disease, classic salt-wasting CAH, if untreated or treated inappropriately, can lead to life-threatening adrenal crisis. Using the example of a boy with precocious puberty, we would like to demonstrate the method and importance of early diagnosis, the modalities and challenges of hormone replacement therapy in these patients, the importance of monitoring growth and development, and the timely recognition of metabolic and endocrinological complications. Patient case: We present a boy who was referred to an endocrinologist at the age of three and a half years due to suspected precocious puberty. The boy had not previously suffered from any serious illness or condition that would indicate the development of an adrenal crisis. The clinical status includes signs of false precocious puberty: tall stature, blackheads on the nose and ears, a deeper voice, and inappropriately large genitalia for his age (Tanner II-III) with pubic hair (Tanner II), while the testicles are of prepubescent size (2 according to Prader). Laboratory workup revealed a diagnosis of classical CAH with markedly accelerated bone maturation (10 years), and replacement therapy with hydrocortisone was initiated. The diagnosis was also confirmed by evidence of a CYP21A2 gene mutation. During follow-up, the boy developed true precocious puberty at the age of 6, which is why treatment with luteinizing hormone-releasing hormone (LHRH) agonists was initiated. The challenges of treatment and monitoring are listed below: titration of the hydrocortisone dose - a dose that will suppress androgen secretion without compromising growth; dose adjustment in acute stressful situations; new hydrocortisone formulations; recognition of the risk and development of true precocious puberty and its timely treatment; recognition of growth patterns that indicate (in)appropriate treatment of the boy. Conclusion: Congenital adrenal hyperplasia requires early recognition, timely treatment, and monitoring to prevent acute and long-term complications of the disease and to enable the child's growth and development to be as appropriate as possible.