Diagnostic algorithm for delayed puberty and primary amenorrhea in females based on gonadotropins and growth pattern.
Delay in onset of secondary sexual development after 13.5 years in boys → Serum gonadotropins
Elevated → Karyotype
Low → Growth pattern
Elevated gonadotropins — Karyotype
Absence or abnormality of one X chromosome or mosaicism with 45,X cell line → Turner syndrome (may or may not have somatic stigmata of Turner syndrome but short stature is extremely common)
Normal 46,XY → Primary ovarian failure–autoimmune or other etiology
Low gonadotropins — Growth pattern
Consistently short for chronologic age but appropriate for bone age → Bone age delayed → Constitutional delay in growth and puberty
Late-onset growth failure especially with concurrent diabetes insipidus → Signs of increased intracranial pressure or visual abnormalities → MRI → Mass → CNS tumor
Normal without growth spurt → Sense of smell
Sense of smell pathway
Anosmia or hyposmia → MRI → Absence of olfactory bulb and/or sulcus → Kallmann syndrome
Normal sense of smell → Normal MRI → Isolated gonadotropin deficiency
Normal secondary sexual development with primary amenorrhea — Karyotype
Normal → Anatomic defect or abnormality in LH pulsatility
46,XY → Syndrome of androgen resistance
Source: From Styne DM, Grumbach MM: Physiology and disorders of puberty. In Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, editors: Williams textbook of endocrinology, ed 13, Philadelphia, 2016, Elsevier, Fig. 25.49, p 1157.
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