This is a protocol aimed at standardizing clinical care and the diagnostic approach in a carrier of a pathogenic IGSF1 mutation referred for hormonal analysis to the outpatient clinic.
ID
Source
Brief title
Condition
- Hypothalamus and pituitary gland disorders
- Testicular and epididymal disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Medical history.
2. Physical examination.
3. DEXA or bioelectrical impedance analysis for body composition.
4a. Fasting blood sample for FT4, FT3, T3, TSH, prolactin, LH, FSH,
testosterone, SHBG, inhibin B, antimüllerian hormone, oestradiol, DHEAS, DHEA,
androstenedione, IGF-I, IGFBP-3, cholesterol, LDL-cholesterol, HDL-cholesterol,
triglycerides, glucose, insulin, C-peptide, cortisol, ACTH, GH, leptin.
4b. TRH-induced response of TSH, prolactin and growth hormone at 0*, 20*, 60*,
90*, 120*, 180*. Free T4, Free T3 and thyroglobulin will be determined at 0,
120 and 180 minutes. TSH bioactivity will be assessed at 0, 20 and 60 minutes.
4c. If clinically indicated: GnRH-induced response of LH and FSH; GH response
to GH stimulation test; and assessment of corticotrope axis.
5. Ultrasound examination of the thyroid gland, and testis or ovaries.
6. Echocardiography
Secondary outcome
1. Ring size
2. X-ray of hand
3. Photograph with conventional camera
4. Questionnaire assessing complaints related to growth hormone overproduction
5. Neuropsychological tests
For participation in these measurements, the patient will receive a financial
compensation.
Background summary
Recently a novel X-linked syndrome caused by loss of function of IGSF1 was
discovered (Sun et al., Nature Genetics 2012). In IGSF1 deficient males, the
syndrome is characterized by central hypothyroidism in all patients (26 in 11
families), macroorchidism in all males (from late adolescence),
hypoprolactinaemia in 18/26 patients, partial and transient growth hormone (GH)
deficiency in 4/26 patients, disharmonious pubertal development, obesity, and
elevated serum IGF-I in late adulthood. Out of 20 female heterozygous carriers
of an IGSF1 mutation, five were hypothyroid, and in at least two female
carriers ovarian cysts were observed. Serum IGF-I was elevated in the majority
of these females.
The clinical significance of the syndrome, particularly the clinical
consequences of untreated hypothyroidism and elevated serum IGF-I, justifies to
screen family members of patients with an IGSF1 mutation for carriership, and
to study potential carriers of IGSF1 mutations, including patients with central
hypothyroidism, combined GH and TSH deficiency, macroorchidism, or delayed
puberty. If found positive, the clinical assessment should be performed in a
standardized fashion, and the results should be communicated to the medical
community. It is not unlikely that the clinical, laboratory and radiologic
characteristics are more diverse than suggested by the findings in the first
set of patients.
Study objective
This is a protocol aimed at standardizing clinical care and the diagnostic
approach in a carrier of a pathogenic IGSF1 mutation referred for hormonal
analysis to the outpatient clinic.
Study design
Prospective descriptive study
Study burden and risks
The small risk of minor side-effects related to the endocrine function tests
are largely outweighed by the fact that these tests are part of standard
clinical care, and they are directly aimed at assessing what treatment the
patient requires.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
Documented pathogenic mutation in the IGSF1 gene
Informed consent
Exclusion criteria
None
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL42991.058.13 |