Isolated hypogonadotropic hypogonadism (IHH) |
Anosmic form of IHH (Kallmann syndrome [KS]) | Mutated Gene |
ANOS1 formerly KAL1 (X-linked recessive) |
SEMA3A (Autosomal Dominant) |
SOX10 (Autosomal Dominant) |
IL17RD (Autosomal Dominant) |
FEZF1 (Autosomal Recessive) |
Normosmic form of IHH | Mutated Gene |
KISS1R (Autosomal Recessive) |
KISS1 (Autosomal Recessive) |
GNRHR (Autosomal Recessive) |
GNRH1 (Autosomal Recessive) |
TAC3 and TAC3R (Autosomal Recessive) |
Anosmic and Normosmic forms of IHH | Mutated Gene |
PROK2 and PROKR2 (Autosomal Recessive) |
FGF8 (Autosomal Dominant) |
FGFR1 (Autosomal Dominant) |
CHD7 (Autosomal Dominant) |
HS6ST1 (Oligogenic Inheritance together with FGFR1 and NSMF) |
FGF17 (Oligogenic Inheritance together with IL17RD, DUSP6, SPRY4, and FLRT3) |
NSMF (Oligogenic Inheritance together with FGFR1 and HS6ST1) |
DUSP6 (Oligogenic inheritance) |
SPRY4 (Oligogenic inheritance with DUSP6 and FGFR1) |
RFLT3 (Oligogenic inheritance with FGF17, HS6ST1, and FGFR1) |
WDR11(Oligogenic inheritance) |
AXL (Oligogenic inheritance) |
Digenic Anosmic forms of IHH | Mutated genes |
Heterozygous mutation FGFR1 and Heterozygous deletion NSMF |
Digenic Normosmic forms of IHH | Mutated genes |
Compound heterozygous mutation of GNRHR and heterozygous mutation FGFR1 |
IHH associated with obesity | Mutated genes |
Leptin or leptin receptor mutations | LEP, LEPR |
IHH associated with Mental Retardation | Genetic Abnormality |
Prader Willi Syndrome (PWS) | Loss of paternal copy of the PWS "critical region” on chromosome 15q11.2-13 |
IHH associated with ß-subunit mutations | Genetic Abnormality |
ß-subunit of LH |
ß-subunit of FSH |
Deficiencies of multiple pituitary hormones | Pituitary gland differentiation genes |
LHX3, LHX4, HESX1, and PROP-1 |
Acquired causes of secondary hypogonadism |
Suppression of gonadotropins release | Conditions leading to suppression of gonadotropin release |
Hyperprolactinemia |
Exogenous sex steroids |
Opioid induced hypogonadism |
Therapeutic use of GnRH agonists |
Acute critical illness |
Chronic illness (COPD, CHF, cirrhosis, AIDS, ESRD) |
T2DM |
Obesity |
Anorexia nervosa |
Chronic glucocorticoid treatment |
Damage to gonadotrophs | Conditions leading to damage of gonadotrophs |
Pituitary adenoma/cyst/carcinoma |
Infiltrative diseases: Langerhans cell histiocytosis, hemochromatosis, sarcoidosis |
Infectious: meningitis, tubercolosis |
Pituitary apoplexy |
Head trauma, traumatic brain injury |
Idiopathic |