Referral Guidelines are peer reviewed guidelines developed to assist referring providers in their approach to a patient presenting with common signs or symptoms suggestive of an endocrine condition, and when to refer to Pediatric Endocrinology.
Symptoms/Signs:
Tall stature (0.7 SDS > midparental target height) with decreased upper to lower segment ratio (~ height – arm span > 2 cm)
Small testes for age
Learning disabilities
Delayed speech development
Reduced penile length
Delayed/ stalled out puberty
Gynecomastia
Hypertelorism
High arched palate
Hypotonia
BMI above mean
Blood tests:
Karyotype
FSH, LH
Testosterone (may be normal in boys < 10 years old and some older boys)
Other tests to consider after consultation with Pediatric Endocrinologist:
Bone Age x-ray
TSH, FT4
Estradiol, Sex Hormone Binding Globulin
Fasting glucose, lipids, HgbA1c
Hct/hgb
25-OH Vitamin D
Routine:
Nearly always
- Previous growth data/growth charts
- Pertinent medical records
- Recent laboratory and radiologic studies including the bone age film (not just the report)
Delayed Puberty/ small genitalia for age:
Constitutional delay of growth and puberty: Usually height is < target height %
Primary gonadal failure: typically no syndromic features
Hypogonadotropic hypogonadism
o Possible associations: sensorineural hearing loss; anosmia/hyposomia; cleft palate; renal abnormalities
Tall Stature:
Genetic tall stature
Marfan syndrome: +/- Family history, ectopia lentis (upward subluxation), aortic root dilatation, dural ectasia, long slender limbs and arachnodactyly (thumb sign and wrist sign) pectus carinatum, scoliosis, dolichocephaly, myopia
Homocystinuria: Similar skeletal findings to Marfan syndrome, downward subluxation of lens, osteoporosis, mental impairment, thromboembolic episodes
Sotos syndrome: Developmental delay, advanced bone age, macrocephaly, frontal bossing, high anterior hairline, frontotemporal hair scarcity, prominent mandible and pointed chin
Beals syndrome: Similar to Marfan but joint contractures, folded ear helixes, micrognathia
Beckwith-Wiedemann syndrome: Prenatal and postnatal overgrowth with omphalocele, macroglossia, visceromegaly, developmental delay
Simpson-Golabi-Behmel syndrome: X-linked R, similar to BWS but upturned nasal tip, broad nose, high arched/ cleft palate, hypoplastic or absent index fingernails, relatively normal cognitive development.
Weaver syndrome: Developmental delay, camptodactyly, advanced bone age, broad face, hypertelorism, flat occiput, depressed nasal bridge, hypertonia
Fragile X
Endocrine abnormalities
o Pituitary gigantism
o Lipodystrophy
o Precocious puberty
o Hyperthyroidism
o Aromatase deficiency
o Estrogen resistance
o Familial Glucocorticoid deficiency
More common than suspected: 150/100,000 live born males
Less than 10% diagnosed before puberty
More than 75% have learning disabilities
Gynecomastia is present in less than 50% of pubertal boys with Klinefelter syndrome and is usually very mild until adulthood
Increased risk for breast and mediastinal malignancies
Multi-disciplinary care is critical: primary care, speech pathologists, psychologists, endocrinologists, urologists and fertility specialists.
Some patients may require testosterone supplementation. They will also be referred to reproductive endocrinologists for discussion regarding infertility.
Gies, I., et al. (2014). "Management of Klinefelter syndrome during transition." Eur J Endocrinol 171(2): R67-77.
De Sanctis, V., et al. (2013). "Klinefelter syndrome and cancer: from childhood to adulthood." Pediatr Endocrinol Rev 11(1): 44-50.
Aksglaede, L., et al. (2013). "47,XXY Klinefelter syndrome: clinical characteristics and age-specific recommendations for medical management." Am J Med Genet C Semin Med Genet 163C(1): 55-63.
Groth, K. A., et al. (2013). "Clinical review: Klinefelter syndrome--a clinical update." J Clin Endocrinol Metab 98(1): 20-30.
Zeger, M. P., A. R. Zinn, et al. (2008). "Effect of ascertainment and genetic features on the phenotype of Klinefelter syndrome." J Pediatr 152(5): 716-722.
Emily Walvoord
May 1, 2020