Endocrine disorders in the infancy and childhood Éva Erhardt MD, PhD

- thyroid diseases - adrenal diseases - polycystic ovary syndrome (PCOS)

Most common thyroid conditions in childhood Hypothyroidism –Congenital –Aquired Hyperthyroidism Euthyroid goiter

Causes of cong. hypothyroidism Aplasia, hypoplasia or maldescent of thyroid (80-90 %) embryonic defect of development Defective synthesis of thyroid hormone Maternal ingestion of medication during pregnancy Iodine deficiency

Clinical manifestations constipation prolonged jaundice feeding difficulties lack of interest somnolence enlarged tongue muscle hypotonia umbilical hernia dry skin bradycardia mental retardation

Cong. hypothyroidism Screening !! -from blood spot -at 5 days of age -disadvantage: no differentiation of secunder and tertier hypothyroidism

Chronic lymphocytic thyroiditis

Adrenal

Adrenal hypofunction (HYPADRENIA I.) Causes –Addison’s disease –Waterhouse-Friderichsen-sy. –Sudden discontinuation of steroid treatment –Adrenal hemorrhage, cyst –Idiopathic congenital adrenal hypoplasia/aplasia Primary – adrenal Secondary – hypophyseal

HYPADRENIA II. Symptoms: weakness, orthostatic collapse, hyperpigmentation, hypoglycaemia, hyponatraemia, hyperkalaemia Addison-crisis: infusion and hidrocortisone injection Therapy –Hydrocortisone –Mineralocorticoids

Congenital adrenal hyperplasia (CAH)

21 hydroxilase defect 95-97% of the all CAH Prevalence: 1:14000 (3/4- salt losing) Short arm of the 6. chromosome CYP21gene (P450 c21 ) - 21 hydroxylase def. Production of androstendion Insufficient production of cortisol Insufficient production of aldosteron (not necessary)

21-hydroxilase deficiency Clinical manifestations Salt-losing 2-4 weeks of age: vomiting, dehydration seK ↑, seNa ↓ Simple virilizing abnormal virilization –girls: ambiguous genitalia (Prader 5), boys: from two years of age: pubarche praecox, accelerated linear growth Late-onset

21-hydroxilase deficiency. Therapy Glucocorticoid-substitution (8-12 mg/m 2 /day hydrocortisone) Mineralocortocoid substitution ( mg/day) NaCl ( till 2 yr of age: 0,5-1g/day) Feminizing genitoplastic surgery

Polycystic ovary syndrome

1935. Stein-Leventhal National Institutes of Health hyperandrogenism, chronic oligo-anovulation Rotterdam - Consensus Workshop

Criterias of PCOS oligo-amenorrhoea clinical and/or biochemical signs of hyperandrogenism (except e.g. hyperprolactinaemia, late onset CAH, Cushing sy, tumor) PC ovaries (more then 10 cysts, max. 10 mm)

Pathogenesis of PCOS it’s not known exactly main features: insulin resistance and intra-, extraovarial hyperandrogenism inzulin ↑, IGF-1 ↑, LH ↑ number and function of theca cells ↑, function of granulosa cells ↓ → size of ovary ↑, follicular atresia, androgene production ↑

PCOS in puberty irregular cycles ( < 6 cycles/year) hyperandrogenism resistance of insulin, hyperinsulinemia obesity (50%) psychosocial problem

Acne - severe hyperandrogenism in a girl

Lab tests testosteron ↑ DHEAS ↑ sex-hormone binding globulin (SHBG) ↓ insulin ↑ dyslipidaemia: cholesterol ↑, TG ↑, LDL- cholesterol ↑, HDL-cholesterol ↓ IGT (30-40% of obese PCOS), T2 DM

Therapy lifestyle changes (diet, physical activity) insulin sensitizers antiandrogenes

Therapeutical effect of metformin insulin ↓ androgene ↓, SHBG ↑, LH ↓, dyslipidaemia ↓ IGT, T2 DM, cardiovascular diseases metabolic sy ↓ ovulation ↑ fertility ↑ endometrium cc ↓