Growth hormone deficiency differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Overview

Growth hormone deficiency in children must be differentiated from other diseases that cause short stature such as: Achondroplasia, constitutional growth delay, familial short stature, growth hormone resistance, Noonan Syndrome, Panhypopituitarism, pediatric hypothyroidism, short stature accompanying systemic disease, psychosocial short stature, Silver-Russell Syndrome, Turner Syndrome, and idiopathic short stature.

Differentiating Growth Hormone Deficiency from other Diseases

Growth hormone deficiency in children must be differentiated from other diseases that cause short stature. Short stature is defined as the height that is 2 standard deviations(SD) or more below the mean height for children of that sex and chronological age in a given population. Theses causes include:

• Achondroplasia
• Constitutional growth delay
• Familial short stature
• Growth hormone resistance
• Noonan syndrome
• Panhypopituitarism
• Pediatric hypothyroidism
• Short stature accompanying systemic disease
• Psychosocial short stature
• Silver-Russell syndrome
• Turner syndrome
• Idiopathic short stature

Diseases	History and symptoms	Physical Examination				Laboratory findings
		Puberty development	Height velocity	Parents height	Characteristic facies	Bone age	Genetic analysis	GH level
Growth hormone deficiency	Children: delayed developmental milestones and muscle weakness Adults: increased lean body mass, osteopenia, and dyslipidemia	Delayed	Decreased	Normal	Doll-like fat distribution pattern Immature face with under developed nasal bridge Infantile voice	Delayed	POU1F1 gene mutations  GH1 gene mutations	Low
Achondroplasia	Normal Intelligence quotient A trunk of average size Arms and legs of diminished length Spinal stenosis Kyphosis and lordosis	Normal	Decreased	Decreased	Large heads Prominent forehead Midface hypoplasia	Delayed	FGFR3 gene mutations	Normal
Familial short stature	A normal variant with normal signs, investigations. Positive family history	Normal	Decreased	Decreased	Normal	Normal	Heterozygous IGF1 Splicing mutation	Normal
Constitutional growth delay	Family history of delayed growth spurt and puberty Childhood short stature but relatively normal adult height Normal size at birth A delayed growth rate begins at three to six months of age A family history of delayed growth and puberty in one or both parents	Delayed .	Normal	Normal	Normal	Normal	Mutations in Variation in FGFR1, GNRHR, TAC3, and TACR3 genes	Normal
Growth Hormone Resistance	Growth hormone insensitivity is an absence of the biological effects of growth hormone despite a normal production of GH. Its severity correlates to IGF-I and insulin-like growth factor-binding protein 3 (IGFBP-3) levels.	Delayed	Decreased	Normal	Small face in relation to head circumference Delayed dentition	Delayed	Growth hormone receptor mutations IGF-I gene mutations	Normal
Pediatric hypothyroidism	Low muscle tone Cold intolerance Persistent constipation Fatigue and weaknessExcessive sleeping Exaggerated jaundice	Delayed	Decreased	Normal	Puffy face Macroglossia Large fontanels Micrognathia	Delayed	Mutations in: Paired box 8 (PAX8) Thyroid Transcription factor-2 (TTF2) Transcription factors NK2	Normal
Turner syndrome	Females only Infertility Webbed neck Widely spaced nipples Broad chest Genu valgum Short neck Ovarian failure	Absent	Decreased	Decreased	Low hairline Low-set ears Characteristic facial features	Normal	45 X0	Normal
Silver-Russell Syndrome	Hemihypertrophy Hypoglycemia Wide fontanelle Clinodactyly Precocious puberty	Delayed	Decreased	Decreased	Prominent forehead Triangular face Downturned corners of the mouth Small jaw Pointed chin	Normal	Methylation involving the H19 and IGF2 genes	Normal
Noonan syndrome	Bleeding tendency Webbed neck Cryptorchidism Intellectual disability	Delayed	Decreased	Decreased	Minor facial dysmorphism	Normal	PTPN11 and SOS1 genes abnormality	Normal
Psychosocial short stature	A disorder of short stature or growth that is observed in association with emotional deprivation A disturbed relationship between child and caregiver is usually noted. A history of abuse or neglect and emotional deprivation The relationship between the caregiver and the child appears to be abnormal.	Delayed	Decreased	Normal	Failure to thrive Poor dental hygiene Sad Affect	Normal	Normal	Maybe low
Short stature accompanying systemic disease	Growth failure is seen in children with systemic diseases such as chronic kidney disease, malignancy, Chron's disease, and Cushing disease. The primary causes of growth failure in children include metabolic acidosis, poor nutrition secondary to dietary restrictions, disturbances of growth hormone metabolism and its main mediator, insulin-like growth factor-I (IGF-I).	Delayed	Decreased	Normal	Failure to thrive	Delayed	Normal	Normal
Idiopathic short stature	A height below 2 standard deviations (SD) of the mean for age, in the absence of any endocrine, metabolic, or other diagnosis	Normal	Decreased	Normal	Normal	Delayed	SHOX gene mutations	Normal