Indications for Testing

Endocrinology: Indications for Testing

Syndrome	Indications for Testing

Autoimmune Polyglandular Syndrome	Presence of at least one of the three characteristic component diseases of autoimmune polyglandular syndrome type 1 (APS1) in children age ten or younger Suspicion of APS1 in individuals of any age Family history of APS1

Bardet-Biedl Syndrome	Postaxial polydactyly in infants Diagnosis of Bardet-Biedl Syndrome based on clinical criteria Family history of Bardet-Biedl Syndrome

Combined Pituitary Hormone Deficiency	Combined deficiencies in growth hormone and TSH or prolactin Family history of CPHD

Congenital Adrenal Hyperplasia	CYP21A2, CYPB11B1 (CAH) Ambiguous genitalia in infants Premature adrenarche Hirsutism and/or oligomenorrhea in women Family history of congenital adrenal hyperplasia CYP21A2 (CAH) Elevated 17-hydroxypregesterone levels Primary Adrenal Insufficiency in infants Family history of 21-hydroxylase deficiency CYP11B1 (CAH) Elevated levels of deoxycorticosterone or 11-deoxycortisol Ambiguous genitalia in infants with hypertension Family history of 11β-hydroxylase deficiency CYP17A1 (CAH) Ambiguous genitalia in 46XY infants, after exclusion of androgen insensitivity syndrome Lack of pubertal progression and primary amenorrhea in phenotypic females Low-renin hypertension and/or elevated deoxycorticosterone and corticosterone levels in children with a personal or family history of ambiguous genitalia, 46XY DSD, or lack of pubertal progression and primary amenorrhea in phenotypic females Family history of 17α-hydroxylase deficiency STAR (Lipoid CAH) Primary Adrenal Insufficiency in phenotypically female infants Family history of congenital lipoid adrenal hyperplasia

Congenital Hyperinsulinism	Severe, persistent hypoglycemia in newborns or infants Family history of severe, persistent hypoglycemia

Early-Onset Obesity	Severe obesity in children (BMI above 97.5 precentile for age and sex), in absence of developmental delay and/or dysmorphic features Family history of severe early-onset obesity

Endocrine Hypertension	Persistent low-renin hypertension in young children Family history of apparent mineralocorticoid excess

Familial Hypocalciuric Hypercalcemia	Asymptomatic persistent hypercalcemia and normal or mildly elevated blood levels of parathyroid hormone Family history of hypercalcemia

Familial Male-Limited Precocious Puberty	Gonadotropin-independent precocious puberty in boys Male-limited family history of precocious puberty

Hypercholesterolemia	Elevated plasma cholesterol levels Family history of premature coronary heart disease Family history of hypercholesterolemia

Hypophosphatemic Rickets	Progressive bowing of legs in a child more than 18 months of age with normal vitamin D levels and marked hypophosphatemia Hypophosphatemia and hyperphosphaturia in the presence of inappropriately normal vitamin D level at any age Family history of hypophosphatemic rickets or hypophosphatemic osteomalacia

Idiopathic Osteoporosis	Unusual bone fragility in otherwise healthy individuals, especially in children and in adult males Family history of idiopathic osteoporosis or of OPPG

Maturity-Onset Diabetes of the Young (MODY)	Non-ketotic insulin-sensitive hyperglycemia in individuals of any age Family history of MODY

Multiple Endocrine Neoplasia Type 1	Tumors in at least two of three target tissues (parathyroid glands, anterior pituitary, duodenum/pancreas) Multiple parathyroid tumors before age 30 Familial idiopathic hyperparathyroidism Zollinger Ellison syndrome Family history of MEN1 or FIHPT

Multiple Endocrine Neoplasia Type 2	Medullary thyroid cancer Pheochromocytoma Family history of MEN2

Neonatal Diabetes Mellitus	Insulin-sensitive hyperglycemia in newborns or infants Family history of neonatal diabetes mellitus

Nephrogenic Diabetes Insipidus	Severe polyuria and polydipsia in infants or children (in male infants and children, AVPR2 testing is recommended first) Family history of nephrogenic diabetes insipidus (if family history is male-limited, AVPR2 testing is recommended first)

Noonan Syndrome	Suspicion or diagnosis of Noonan Syndrome on clinical grounds Family history of Noonan Syndrome

Osteogenesis Imperfecta	One or more non-traumatic fractures in infants or young children Family history of multiple non-traumatic fractures

Osteoporosis-Pseudoglioma Syndrome	Ocular manifestations indicative of OPPG Unusual bone fragility in otherwise healthy individuals, especially in children and in adult males Family history of OPPG or of idiopathic osteoporosis

Pheochromocytoma Evaluation	Sporadic pheochromocytoma

Primary Adrenal Insufficiency	Primary Adrenal Insufficiency (ABCD1, NROB1, AIRE) Primary adrenal insufficiency in boys Family history of primary adrenal insufficiency in males ABCD1 (ALD) Primary adrenal insufficiency in boys Family history of X-linked Adrenoleukodystrophy NROB1 (AHC) Primary adrenal insufficiency in boys Family history of X-linked adrenal hypoplasia congenital AIRE (APS1) Presence of at least one fo the three characteristic component diseases of autoimmune polyglandular Syndrome type 1 (APS1) in children age ten or younger Suspicion of APS1 in individuals of any age Family history of APS1 CYP21A2 (CAH) Elevated 17-hydroxyprogesterone levels Primary adrenal insufficiency in infants Family history of 21-hydroxylase deficiency HSD3B2 (CAH) Undervirilization on 446XY or ambiguous genitalia in 46XX infants Primary adrenal insufficiency in infants, after exclusion of 21-hydroxylase deficiency Premature adrenarche, after exclusion of 21-hydroxylase and 11β-hydroxylase deficiency Elevated pregnenolone, 17OH-pregnenolone and/or dehydroepiandrosterone levels Family history of 3β-HSD deficiency

Short Stature	Growth Hormone Deficiency (GHD) Short stature (<2 SD below population average for age) and reduced growth rate, with low plasma growth-hormone levels and reduced growth-hormone release during provocative testing in children Family history of idiopathic growth hormone deficiency Growth Hormone Insensitivity (GHI) Short stature (<2 SD below population average for age) and reduced growth rate, with normal or high plasma levels of growth hormone and low plasma levels of IGF-1 Family history of growth hormone insensitivity Idiopathic Short Stature, Leri-Weill Dyschondrosteosis Short stature (<2 SD below population average for age) in presence of reduced extremities-to-trunk ratio Presence of Madelung wrist deformity Family history of Leri-Weill dyschondrosteosis or of Madelung wrist deformity

von Hippel-Lindau Syndrome	Cerebellar hemangioblastoma Retinal hemangioblastoma Pheochromocytoma Family history of VHL