GANGGUAN PUBERTAS

Dr Eka Agustia Rini Sp AK Sub Bagian Endokrinologi Ilmu Kesehatan Anak FK-UNAND / RS Dr M. Djamil Padang

PRECOCIOUS PUBERTY

Hypothalamus - Pituitary – Gonad axis

INTRODUCTION
Epidemiology

– Frequency : girls > boys – Girls: most have a benign central cause – Boys: 50% pathologic peripheral cause.  all boys with precocious puberty should undergo detailed investigation, but in girls additional investigation can be based on the clinical impression

Profiles of Girls with Precocious Puberty (N=438)

Age of onset between 7-7.9 year olds 6 year olds < 6 years old. Etiology Gonadotropin Dependent Gonadotropin independent Neurogenic abnormalities (MR/CT skull)

59.6% 22.4% 18%
97.7% 2.3% 18.4%

Cisternino M, Arrigo T, Pasquino AM, et al. Etiology and Age Incidence of Precocious Puberty in Girls:

Precocious Puberty Definition – Appearance of secondary sexual characteristics : boys < 9 years and girls < 8 years old (.2SD) Sex steroid  – Estrogen: female – Testosterone:male .

Effect of sex steroid Estrogen  –Accelerated bone maturation and early epiphyseal fusion (tall child but short adult) –Uterus. aggressiveness . mammary gland Testosterone –Genital. acne. male habitus General:sexual behavior. Hirsutism.

 depressing the hypothalamus-pituitary-gonad axis .Classification GnRH dependent (central) : – premature reactivation hypothalamuspituitary-gonad axis  increased gonadotropin  increased sex steroids (dependent) – Usually idiopathic GnRH independent (peripheral): – autonomous sex steroid secretion.

Classification Variant –premature thelarche –premature adrenarche –gynecomastia .

trauma.Etiology GDPP idiopathic CNS – tumor – non-tumor: post infection. radiation. congenital iatrogenic Delayed diagnosis of GIPP .

Clinical manifestation GDPP Always isosexual Normal sequence of puberty Hormonal profile: increased gonadotropin and sex steroid .

germinoma. familial testotoxicosis – gonadotropin-secreting tumor: non CNS: hepatoma. CAH – testes : cell Leydig tumor.male Isosexual – adrenal: tumor. adenoma (LH secreting) heterosexual Increased peripheral aromatization .Etiology GIPP . teratoma CNS: germinoma.

female Isosexual) – McCune Albright – Severe hypothyroid heterosexual – adrenal: tumor. CAH – tumor ovarium: arrhenoblastoma .Etiology GIPP .

Mc Cune Albright Syndrome Trias – Precocious puberty / endocrine hyperactivity – Fibrodysplasia – Café au lait .

smaller) Low or normal gonadotropin and increased sex steroid .Clinical manifestation GIPP Isosexual or heterosexual (late onset CAH. tumor adrenal) Disconcordant of sexual characteristics (testes volume inappropriate with pubertal stage .

Benign Premature Adrenarche self-limited condition occurring before six years of age characterized by the appearance of pubic and no further secondary sexual development. normal growth patterns .

Benign Premature Adrenarche Normal bone age Slight elevation of serum DHEA Normal adrenal steroid hormone levels Normal sex hormone levels ACTH stimulation test: to exclude lateonset CAH GnRH test: prepubertal pattern Normal imaging studies No specific treatment required .

Premature Adrenarche Excude virilization – clitoral enlargement. and voice change. acne. rapid growth. advanced bone age. – rapid progression If virilization present – measure testosterone. 17-OHP and DHEA – USG: adrenal or ovarian tumor – 17-OHP or DHEA: CAH .

Benign Premature Thelarche Isolated appearance of unilateral or bilateral breast aged 6 months to 3 years No other signs of puberty or evidence of excessive estrogen effect (thickening of the vaginal secretions or bone age acceleration). Ingestion or application of estrogencontaining compounds must be excluded as etiology .

prepubertal uterus Usually resolves spontaneously and requires no treatment re-evaluation at intervals of 6-12 months to ensure that premaure thelarche is not the beginning of isosexual precocious puberty .Benign Premature Thelarche Normal growth rate and bone age Normal levels of gonadotropins and estradiol USG: normal ovaries.

lasting 2 years differentiate with obese boys – lipomastia – no mammae disk Pathological causes must be sought .Gynecomastia Breast enlargement in males common in teenage years.

including palpation of the testicles. Most cases resolve in one to two years.Pubertal Gynecomastia Incidence: 50-60% of boys during early adolescence breast tissue usually asymmetric and often tender. are unremarkable. If history and physical examination. . reassurance and periodic reevaluation are all that is necessary.

hCG. adrenal. spironolactone) Malnutrition Idiopathic (most common) Tumor producing disease – hepatoma.Gynecomastia Drugs – sex steroids. testosterone antagonist (ketoconazole. psychoactive (phenotiazine). cimetidine. testes. LH and hCG producing tumors . antituberculosis.

gynecomastia  cosmetic surgery. Pathologic gynecomastia – Klinefelter's syndrome: high risk for breast cancer – prolactin-secreting adenomata .Pubertal Gynecomastia Familial gynecomastia – X-linked recessive trait or a sex-limited dominant trait – unless associated with hypogonadism no further evaluation in an otherwise normal boy – If severe.

phenothiazines. – Drug induced (marijuana. opiates.Pubertal Gynecomastia Pathologic gynecomastia – hormone-secreting tumors (testes. cirrhosis. isoniazid. tricyclic antidepressants. ketoconazole. digitalis. cimetidine.and hyperthyroidism. spironolactone. hepatoma). tamoxifen reduction mammoplasty rarely indicated. hypo. etc). . estrogens. amphetamines. If worsens and associated with psychologic morbidity  bromocriptine.

Diagnostic work up Gonadotropin dependent or independent? Etiology? .

Hypothalamus GnRH (-) Pituitary LH/FSH Gonad E2 or T H-P-G axis .

Hypothalamus GnRH Primary (-) Pituitary LH/FSH Gonad Sex steroid  H-P-G axis in GDPP .

Hypothalamus GnRH (-) Pituitary LH/FSH Gonad Extra Gonadal Sex steroid  H-P-G axis in GIPP .

signs of virilisation. gelactic laughter (hamartoma). . CNS signs. meningitis TB Physical examination pubertal stage. symptoms extragonadal cause (adrenal). skin (acne. CNS complaints.Diagnostic work up History age of onset. café au lait). testes size (small indicative of perpheral cause). progressivity. growth. previous history: encephalitis. height. family history.

Diagnostic work up Laboratory gonadotropin. bone survey (McCune Albright). . bHCG. 17-OHProgesterone (CAH). CT/MRI. cortisol (Cushing syndrome. skull x-ray. pelvic ultrasound. adrenal tumor) Imaging Bone age.

dll Variant: observation . ketoconazole.Therapy According to the etiology GDPP idiopathic: GnRH agonis GIPP : medroxy-progesteron.

Prognosis According to etiology GDPP idiopathic: GnRH agonis – Final height = potential genetic height – Preserved fertility – Psychosocial minimal. regression of secondary sex GIPP : medical – Potential genetic height  – Regression of secondary sex   .

Conclusion Not all pubertal disorders are pathologic Early increase of sex steroid should be thoroughly investigated GnRH agonist = drug of choice for GDPP .

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DELAYED PUBERTY .

Definisi Pubertas terlambat bila tidak adanya tanda-tanda pubertas – laki-laki pada usia 14 tahun – perempuan pada usia 13 tahun Klasifikasi – hipergonadotropik hipogonadism – hipogonadotropik hipogonadism Ammenorrhoe primer Ammenorrhoe sekunder .

Hipergonadotropik hipogonadism Hipotalamus LHRH Hipofisis LH/FSH (-) Target Organ (gonad) Sex Steroid Primary defect .

Hipergonadotropik hipogonadism Dengan kelainan kromosom – Dysgenesis gonad Sindrom Turner Pure gonadal dysgenesis – Sindrom Klinefelter – Androgen Insensitivity Syndrome * .

LH resistance – didapat radiasi. proses autoimun .P450scc. P450 aromatase) anorchia.Hipergonadotropik hipogonadism Tanpa kelainan kromosom – kongenital gangguan biosintesis steroid adrenal (P450c17.3bHSD) dan gonad (17-KS. chemotherapy. ovary resistant syndrome.

Hipogonadotropik Hipotalamus LHRH hipogonadism Primary defect Hipofisis LH/FSH (-) Target Organ (gonad) Sex Steroid .

histiocytosis X) – Struktural (mid line defect) – Sindrom Kallmann – hipopituitarism idiopathic – pasca tindakan (radiasi. germinoma.Hipogonadotropik hipogonadism Constitutional delay Kelainan Susunan Syaraf Pusat – Tumor (craniopharyngioma. khemoterapi inflamasi.hemosiderosis) . optic glioma. infiltrasi .

Hipogonadotropik hipogonadism Penyakit kronis – endokrin. kelainan sistemik Aktivitas fisik berlebihan Sindrom-sindrom – Prader-Willi. malnutrisi/anorexia nervosa. Laurence-Moon-Biedl .

direct effects or following radiotherapy or surgery Haemochromatosis .Hypothalamic and pituitary causes of pubertal failure-low gonadotrophins Congenital defects – Kalmann syndrome – Congenital adrenal hypoplasia – Septoptic dysplasia – Development defect of pituitary Tumors.

1993 . A multicenter study (N=3092) 4% 3% 6% 7% 80% Delayed puberty IDDM Others Hypothyroidism Hypoparathyroidism Italian Working Group on Endocrine Complication in nonendocrine diseases.Thalassemia and endocrinopathy.

(29 centers). 3092 patients : Puberty failure: males 41 % females 39.Delayed puberty in Thalassamia patient Italian Multicenter Thalassemia study 1993.5 % All patient with hemachromatosis need periodic careful endocrine evaluation .

Tatalaksana Anamnesis Pemeriksaan fisik Pemeriksaan penunjang Terapi .

Anamnesis Riwayat perkembangan pubertas di dalam keluarga Data pertumbuhan & perkembangan Riwayat penyakit/pengobatan dahulu Fungsi penciuman .

Pemeriksaan fisik Pemeriksaan fisik secara umum Pemeriksaan neurologis (funduskopi) d Antropometri (TB. rentang lengan) Status pubertas Stigmata suatu sindrom (pendek. rasio segmen atas dan bawah. BB. webbed neck dll) . obese. retardasi mental.

CT scan/MRI kepala & USG genitalia interna (atas indikasi).Pemeriksaan Penunjang Pencitraan: – usia tulang. Estrogen atau testosterone Dan lain-lain – analisis kromosom (atas indikasi) – uji fungsi penciuman .Prolactin.FSH. Hormonal (basal/ uji GnRH) – LH.

FSH/LH. • Prolactin. T4/TSH.Pubertal Delay Any signs of puberty? YES NO Psychological distress? Check • height. Karyotype (girls) NO YES Low FSH/LH oxandrolone / sex steroids GnRh / sex steroids Monitor growth & pubertal progress sex steroids High FSH .

Hormonal replacement Discrepancies exist concerning – the age of initiation – dosage Some authors : postponing treatment until the age when arrested sexual maturation in easily diagnosed Early treatment supporters: Insist on the psychological benefits treatment Sexual development should be induce at an appropriate age .

Recommended hormone replacement When to wait watchfully and when to test and refer are part of the art of medicine – Female patients chronological age > 13-14 years bone age > 11 years – Male patients chronological age > 14-15 years bone age > 12 years .

25 mg daily (6-9 months) – after 9 MOs cyclic therapy ŵ estrogen for 1st 21 days Males: – testosterone enanthate 50 mg IM/ monthly – after 6-9 MOs.Hormonal replacement Females : – start ŵ estrogen 0. dose gradually increased to 200 mg/3 weeks (2-3 years) .

umur tertentu Pubertas harus selalu menjadi perhatian orangtua / tenaga kesehatan Setiap tenaga kesehatan dapat mendeteksi kelainan pubertas secara dini dan segera melakukan rujukan .KESIMPULAN Pubertas berlangsung menurut stadium.

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