- Isolated (or Congenital) GnRH Deficiency (IGD) is a rare disease. People who have this go
through puberty late. Some never reach puberty or don t complete it without treatment. They
also may have an impaired sense of smell or other health problems. Research shows that
disorders like this can have a negative effect on a person s psychological profile.
- To understand the psychological outcomes in people with IGD. These can include depression,
anxiety, poor health, and poor social function.
- Adults age 18 and over with IGD. They must be currently on a full dose of hormone
replacement therapy for at least 3 months.
- Healthy adult volunteers.
- Participants will get a username and password. This will give them access to questions
online. They can do this from any computer connected to the Internet.
- Participants will log in and complete the questionnaires. There are 5 total, but they
will appear as 1 continuous set of questions. Answering them takes about 1 hour or less.
- The first set is about the participant s disorder. The rest ask about depression,
anxiety, global health, and social function.
- All answers will be used for research and to better understand reproductive disorders.
Only researchers from the NIH Unit on Genetics of Puberty and Reproduction and from this
study will know which answers belong to which participant.
Isolated GnRH Deficiency (IGD) is a rare disorder characterized by decreased secretion of
GnRH, resulting in impaired gonadotropin secretion and subsequent impaired sex-steroid
production. Patients with this rare clinical syndrome present with absent, delayed, or
stalled pubertal development by eighteen years of age. In addition, non-reproductive
phenotypes of this spectrum have been identified in some individuals, including anosmia,
auditory and ocular defects, and skeletal, neurological, and renal anomalies.
Due to the complex heterogeneity among affected individuals and the rarity of the disease
itself, the phenotypic spectrum has not been fully investigated. The relationship between
psychological disorders and IGD remains largely unexplored as a phenotypic association,
despite evidence that disorders of puberty and reproduction can have a negative impact on the
This study aims to conduct a preliminary investigation into the association between
psychological symptoms and IGD. We plan to recruit adult patients with a diagnosis of IGD to
complete online assessments that measure psychological health outcomes from the patient
perspective in order to gauge the prevalence of negative emotional states among affected
individuals, compared to healthy controls. This will determine whether further studies are
necessary to investigate psychiatric disease as part of the phenotypic spectrum of the
disorder, and will improve our understanding of this complex disorder as a whole. Greater
knowledge of the psychological impact of IGD may impact the current standards of evaluation
and treatment of patients with delayed pubertal maturation.
- ELIGIBILITY CRITERIA FOR IGD PATIENTS:
Males or females with clinical findings consistent with IGD who are greater than or equal
to 18 years old and treated with hormone replacement therapy for IGD at the full adult
replacement dose for at least 3 months. Clinical findings of IGD will be confirmed by a
nurse or physician associated with this protocol, and include: clinical presentation
consistent with a diagnosis of IGD, such as delayed, incomplete, or absent pubertal
development, and a record of serum hormone levels demonstrating low total testosterone
(males) or estradiol (females) in association with low or inappropriately normal
gonadotropin levels in a clinic note or history and physical, and individuals with records
demonstrating failure to undergo normal puberty. Anosmia may or may not be present. Since
IGD presents as a phenotypic spectrum, there are no specific exclusion criteria for this
study, except as noted below.
- Patients with a diagnosis of IGD who are <18 years old;
- Patients with a diagnosis of IGD who are not on a full adult replacement dose of sex
hormone therapy for at least 3 months;
- Patients who do not have a diagnosis of IGD as indicated by the inclusion criteria
- Patients without access to a computer connected to the internet;
- Patients who cannot read, write, and understand English at an eighth grade level or
ELIGIBILITY CRITERIA FOR HEALTHY CONTROLS:
Healthy males or females who are greater than or equal to 18 years old.
- Subjects with any chronic medical condition, other than seasonal/environmental
- Subjects with a BMI < 18.5 or > 29.9;
- Subjects with prior history of abnormal pubertal development, infertility, or anosmia;
- Subjects with a family history of IGD;
- Subjects without access to a computer connected to the internet;
- Subjects who cannot read, write, and understand English at an eighth grade level or