Pocket ObGyn – Delayed Puberty
See Abbreviations
Definition (N Engl J Med 2012;366:443; Pediatr Clin North Am 2011;58:1181)
- Absence of secondary sexual characteristics by age 13 (³2 SD from mean age), or absence of menses by age
Etiology ( J Clin Endocrinol Metab 2002;87:1613)
- 30% const del, 26% hypergonadotropic hypogonadism, 20% permanent hypogonadotropic hypogonadism, 19% transient (functional) hypogonadotropic hypogonadism, 5% other
Clinical Manifestations
- Hx: Anorexia, bulimia, excessive exercise, chronic dzs (eg, celiac dz, Crohn dz), radiation, chemo, meds, nutritional status, psychosocial functioning
- Sx: Neurologic sx, inability to smell, weight gain or loss, chronic dz
- FHx: Relatives w/ delayed puberty, heights of relatives, age of menarche & fertility status of female relatives, relatives w/ genetic abnormalities (CAH, adenocarcinoma in situ (AIS), gonadal dysgenesis), relatives w/ autoimmune dz
Physical Exam
- Height & weight measurements, growth chart,Tanner staging, examine for stigmata of Turner syn, midline facial defects, scoliosis,
- Arm span greater than height >5 cm sugg delayed epiphyseal closure
- Neurologic exam: Optic fundi, cranial nerves, visual fields, sense of smell
- Pelvic exam: Clitoral enlargement, hymenal ring patency, degree of vaginal rugation, presence or absence of mucus (indicates degree of estrogen effect)
Workup
- Hx, physical exam, bone age, labs (LH, FSH)
Elevated FSH/LH = hypergonadotropic hypogonadism Low FSH/LH = hypogonadotropic hypogonadism
- Further w/u if LH, FSH nml:
PRL – screen for hyperprolactinemia TSH, FT4 – screen for thyroid dzs
MRI – when si/sx CNS lesion present or if indicated by other eval (hyperprolac- tinemia, Kallmann syn); otherwise may defer until age 15
CBC, ESR, LFTs – screen chronic dzs (IBD, liver dz, anorexia)
Pelvic US – determine presence/absence uterus if undetermined by physical exam
- Unusually no apparent alternate cause on initial eval – const del likely dx; no test can reliably differentiate const del from hypogonadotropic hypogonadism; therefore, observe, & diagnose isolated hypogonadotropic hypogonadism if endogenous puberty has not begun by age 18; eventual nml progression of puberty confirms const
Treatment Goals
- Induce appearance of secondary sexual characteristics or acceleration of growth to mitigate pubertal delay & short stature, & promote nml bone mass
- Predict adult height w/ Bayley-Pinneau tables, although overestimate adult height in const
Figure 6.3 Approach to delayed puberty
| Chronic | Identify | |
| disease | possible | |
| functional | ||
| causes |
(From Fritz MA, Speroff L. Clinical Gynecologic Endocrinology and Infertility. Philadelphia, PA: Lippincott Williams & Wilkins; 2011)
Hypergonadotropic (Primary) Hypogonadism
- Dx: Elevated LH & FSH due to lack of negative feedback from Additional w/u: Karyotype, autoimmune dz eval.
- Etiology: Primary ovarian insufficiency (idiopathic, resistant ovary syn, autoimmune oophoritis, 17a-hydroxylase deficiency, galactosemia, aromatase deficiency), Gonadal dysgenesis (45,X; 46,XX; 46,XY), radiation, chemo. Special cases: Turner syn: 45,X (Semin Reprod Med 2011;29:342) – phenotype: Female, short stature,
ptosis, low-set ears, micrognathia, short “webbed” neck, broad shield-like chest, hypoplastic areolae, short 4th &/or 5th metacarpals, renal abnormalities (eg, horseshoe kidney), cardiovascular abnormalities (eg, coarct of the aorta). Risk of aortic dissection & rupture (1.5%). “Streak” gonads consist of fibrous tissue w/o germ cells. External female genitalia, uterus, fallopian tubes develop normally until puberty when estrogen-induced maturation fails to occur. Menstruation & Preg may occur in mosaic karyotype (45,X/46,XX). Rx: Growth hormone prior to estrogen initiation.
Swyer syn: 46,XY complete gonadal dysgenesis. Phenotype: Female, w/ vagina, cervix, uterus, fallopian tubes, & external genitalia. Rx: Requires early gonadecto- my due to risk of gonadal tumors.
Primary ovarian insufficiency: See Chap. 8.
Permanent Hypogonadotropic (Secondary) Hypogonadism
- Dx: Low to nml LH & FSH due to hypothalamic or pituitary
- Etiology: GnRH deficiency, CAH, CNS tumors, combined pituitary hormone deficiency, chemo, radiation
Kallmann syn: Anosmia or hyposmia; 1/50000 females
• Further w/u: MRI
- Rx: Initial low-dose estrogen titrated to mimic nml puberty to initiate sexual maturation
After 6–9 mo, cyclic progesterone to induce endometrial shedding Transition to combination OCP when breast dev optimized for hormonal
replacement
If fertility desired, pulsatile GnRH or injectable gonadotropin
Transient (Functional) Hypogonadotropic Hypogonadism
- Dx: Low LH & FSH due to delayed maturation of HPO axis due to underlying condition
- Etiology: Systemic illness (IBD, celiac dz, anorexia nervosa or bulimia, hypothyroidism, hyperprolactinemia, DM, Cushing dz), CNS disorders (tumors
- Rx: Treat underlying cause (treat dz or modify behavior)
• Const Del:
Dx: Low LH & FSH, HA = bone age < chrono age.Adrenarche & gonadarche often later than avg; isolated hypogonadotropic hypogonadism has adrenarche at nml age.
Rx: Expectant observation. If puberty has started (clinically or biochemically) & stature not a major concern, reassurance w/ adult height prediction.
Hormone rx is controversial (goal of preventing developmental psychosocial stress). Use low-dose estrogen until puberty progresses, then stop.
Progesterone not needed as similar long period of unopposed estrogen in early puberty. Growth hormone, anabolic steroids, aromatase inhibs not recommended.