Table 4.

Recommendations for Clinical Management of IGSF1 Deficiency

Indications for Mutational Analysis of IGSF1
Central hypothyroidism of unknown cause, especially when accompanied by the following
X-linked inheritance pattern
Deficiency of prolactin or GH
Disharmonious pubertal development, macroorchidism, or delayed adrenarche
Screen appropriate family members after a mutation is discovered
Diagnosis and Follow-Up	Children		Transition	Adults
	Diagnosis	Follow-Up		Diagnosis	Follow-Up
Males
History, physical examination	Xa	Xa	X	Xb	Xb
FT4, TSH	X	Xc	X	X	Xc
T	X	Annual if testes ≥4 mL	X	X
Prolactin	X			X
Dynamic adrenal axis testing	Xd
Cortisol (early morning)				Xe
IGF-1	X	c		X
Cholesterol, TG, HDL, LDL, glucose	X	c	X	X	c
If growth failure or low IGF-1:
(Primed) GH stimulation test, hand x-ray	X	X	f
Females
History, physical examination	Xa			Xb
FT4, TSH	X	Xg		X	h
Cholesterol, TG, HDL, LDL, glucose	X	c		X	c
Treatment
Levothyroxine	In all male children. Trial course in male adults and in females with decreased FT4 or low-normal FT4 in combination with features suggestive of tissue hypothyroidism
Hydrocortisone	In neonates with impaired cortisol response in low-dose ACTH test (<0.550 μmol/L); reevaluate after 1 y
rhGH	In case of >1.0 SD deviation of growth, height <−2 SD or low growth velocity and impaired GH response in (primed) GH stimulation test
T	In case of a delay in pubertal development in males (pubic hair stage 1 and/or prepubertal T at 14.0 y)

Abbreviations: LT4, levothyroxine; TG, triglycerides.

^aHeight, weight, head circumference, pubic hair, testicular volume, heart rate. Periodic evaluation is done at the discretion of the treating physician.

^bBMI, waist circumference, signs and symptoms of hypothyroidism and, if treated with levothyroxine, of hyperthyroidism. Periodic evaluation is done at the discretion of the treating physician.

^cFollow-up at the discretion of the treating physician.

^dDynamic testing may be preceded by randomly measured plasma or serum cortisol concentrations. Sufficiently high concentrations make central adrenal insufficiency unlikely. However, low concentrations do not prove adrenal insufficiency. In case of a low random cortisol concentration in a neonate, we suggest performing a low-dose ACTH test. If abnormal (cortisol response <0.550 μmol/L), then treat with hydrocortisone. Reevaluate after 1 year.

^eSufficiently high concentrations make central adrenal insufficiency unlikely. A low concentration warrants dynamic adrenal axis testing.

^fRepeat GH stimulation test at transition in patients treated for GH deficiency.

^gAge 0–3 years, at least yearly and also if hypothyroidism is absent. Age 4–18 years: at discretion of treating physician.

^hPreconception and during pregnancy. If hypothyroid, follow-up is done at the discretion of the treating physician.