Format

Send to

Choose Destination
J Clin Endocrinol Metab. 2010 Sep;95(9):4235-43. doi: 10.1210/jc.2010-0245. Epub 2010 Jun 30.

The long-term clinical follow-up and natural history of men with adult-onset idiopathic hypogonadotropic hypogonadism.

Author information

1
Harvard Reproductive Endocrine Sciences Center and Reproductive Endocrine Unit of Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

Abstract

CONTEXT AND OBJECTIVE:

Adult-onset idiopathic hypogonadotropic hypogonadism (AHH) is a rare disorder characterized by an isolated failure of gonadotropin secretion occurring after an otherwise normal sexual maturation in men. This study aims to examine the etiology and long-term natural history of this disorder.

DESIGN AND SETTING:

Long-term follow up, including detailed clinical, biochemical, and genetic examinations, were performed and compared with those at diagnosis.

PATIENTS:

Patients included 10 men with AHH [serum testosterone (T) <125 ng/dl].

INTERVENTIONS:

Overnight neuroendocrine studies, semen fluid analyses, and genetic screening were performed (KAL1, FGFR1, PROK2, PROKR2, NELF, TAC3, TACR3, and GNRH1) over a decade of longitudinal follow up.

RESULTS:

Follow-up evaluations were conducted 10.6 +/- 5.9 yr after initial studies and revealed that the clinical characteristics and seminal fluid analyses of AHH men (body mass index, 28.8 +/- 4.1 vs. 27.0 +/- 4.3 kg/m(2); testicular volume, 18 +/- 6 vs. 19 +/- 6 ml) do not change over a decade with no spontaneous reversals. Several men exhibited some variability in their endogenous GnRH-induced LH secretory patterns, including emergence of endogenous pulsatility in three individuals. However, all remained hypogonadal (T < or =130 ng/dl). A single heterozygous DNA sequence change in PROKR2 (V317L) was identified, although this rare sequence variant did not prove to be functionally abnormal in vitro. Seven days of pulsatile GnRH therapy in this subject nearly normalized his serum T, supporting that the site of the defect is hypothalamic and not pituitary.

CONCLUSIONS:

1) AHH in men appears to be a long-lasting condition. 2) Although minor changes in the abnormal pattern of endogenous GnRH-induced LH secretion occurred in some AHH patients, all remained frankly hypogonadal.

PMID:
20591981
PMCID:
PMC2936052
DOI:
10.1210/jc.2010-0245
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center