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Isolated gonadotropin-releasing hormone deficiency (idiopathic hypogonadotropic hypogonadism)

Nelly Pitteloud, MD
William F Crowley, Jr, MD
Ravikumar Balasubramanian, MBBS, PhD, MRCP(UK)
Section Editors
Peter J Snyder, MD
Alvin M Matsumoto, MD
Deputy Editor
Kathryn A Martin, MD


Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD), also referred to as idiopathic hypogonadotropic hypogonadism (IHH), is a family of genetic disorders that are associated with defects in the production and/or action of hypothalamic peptide that controls human reproduction, GnRH. IHH can occur either with normal olfaction (normosmic IHH) or with anosmia. This latter clinical presentation of IHH with anosmia is referred to as Kallmann syndrome (KS) [1]. The pathogenesis, genetics, clinical presentation, and management of isolated GnRH deficiency (IGD or IHH) will be discussed here [2,3]. Other causes of hypogonadotropic hypogonadism (HH) are reviewed separately. (See "Causes of secondary hypogonadism in males" and "Evaluation and management of secondary amenorrhea".)


Patients with IHH often have clinical features that are present at birth (cryptorchidism, microphallus, and/or biochemical evidence of low gonadotropins and sex steroids during the three to six months of the neonatal period referred to as "mini-puberty"). Some experts consider this to be a congenital disorder and refer to it in the literature as "congenital hypogonadotropic hypogonadism."

However, more often, these neonatal features are absent and the age of onset or its precise etiology cannot be determined, and thus, the term "idiopathic" is used. Regardless of the terminology, this disorder is characterized by hypogonadotropic hypogonadism (HH), eg low inappropriately low or normal serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the setting of prepubertal levels of gonadal steroids. IHH is difficult to distinguish from the more common constitutional delay of puberty or functional hypogonadotropic hypogonadism (FHH) prior to age 18 years. (See 'Diagnosis' below.)


The lack of endogenous hypothalamic gonadotropin-releasing hormone (GnRH) secretion/action in patients with IHH cannot be proven by direct assay of GnRH in the portal circulation but can be reasonably inferred by two findings:

The lack of any endogenous GnRH-induced luteinizing hormone (LH) pulses during frequent blood sampling (figure 1) [4].

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Literature review current through: Nov 2017. | This topic last updated: Nov 21, 2017.
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