Non-classical 21-hydroxylase deficiency: prevalence in males with unexplained abnormal sperm analysis.

OBJECTIVE: To evaluate the prevalence of nonclassical 21-hydroxylase deficiency (NC-21OHD) in men with abnormal sperm parameters of unexplained etiology compared with males with normal sperm analysis. DESIGN: Case control study. SETTING: Major tertiary medical center. PATIENT(S): Of 484 healthy men being followed at a fertility clinic, 222 (mean age 33.8 +/- 6.1 [+/-SD] years) presented with abnormal findings on sperm analysis (1999 WHO criteria) of unknown cause and 262 (mean age 34.8 +/- 6.5 [+/-SD] years) with a normal sperm analysis. INTERVENTION(S): Random mid-morning blood sampling to test for 17-hydroxyprogesterone (17-OHP) levels. Subjects with levels of >or= 6 nmol/L underwent a standard adrenocorticotropic hormone (ACTH) stimulation test. MAIN OUTCOME MEASURE(S): NC-21-OHD, defined as a stimulated ACTH level of >or=45 nmol/L. RESULT(S): A serum 17-OHP level of >or=6 nmol/L was detected in 11 study patients (5.0%) and 14 control subjects (5.3%). Seven study patients and 8 controls subsequently underwent ACTH stimulation test, and none had levels compatible with a diagnosis of NC-21OHD. Mean 17-OHP levels were similar in the two groups (3.3 +/- 1.4 [+/-SD] nmol/L and 3.3 +/- 1.5 [+/-SD] nmol/L, respectively). There was no correlation between sperm parameters and serum 17-OHP levels. CONCLUSION(S): Until larger studies are performed, the routine measurement of 17-OHP in the evaluation of male infertility is not recommended.

Childhood obesity complicating the differential diagnosis of maturity-onset diabetes of the young and type 2 diabetes.

OBJECTIVE: To describe a proband with features of type 2 diabetes who was found to have concomitant maturity-onset diabetes of the young (MODY) and the consequent multigeneration genetic analysis. DESIGN: Familial genetic analysis. SETTING: Tertiary university medical center. PARTICIPANTS: The proband was a 13.5-yr-old boy with marked non-ketotic hyperglycemia, obesity, systolic hypertension, and insulin resistance. His mother, maternal aunt, grandmother, and great grandmother had diabetes; his father was obese and had early ischemic heart disease. INTERVENTIONS: Clinical examination, laboratory work-up, and DNA study. OUTCOME MEASURES: Mutation in hepatocyte nuclear factor-1alpha gene, the most common cause of MODY. RESULTS: The proband showed elevated C-peptide level and was negative for beta-cell antibodies. On genetic analysis for MODY, the 291fsinsC mutation was identified in all affected family members. A younger sister who was obese but had no signs of impaired glucose tolerance was also tested on the basis of these findings and was found to have the same mutation. CONCLUSIONS: The patient, who presented with apparent type 2 diabetes, had concomitant MODY 3, inherited from his mother's side, and some features of type 2 diabetes secondary to marked obesity. This combination probably caused an earlier and more severe presentation of the disease and had significant implications for medical management. A search for MODY mutations should be considered in patients with a history of diabetes in three generations of one side of the family, even those in whom the clinical picture resembles type 2 diabetes.

Decreased growth during therapy with selective serotonin reuptake inhibitors.

BACKGROUND: There is no information on the effects of selective serotonin reuptake inhibitors (SSRIs) on growth and puberty in children. We examined growth and growth hormone secretion in 4 children treated with SSRIs for various psychiatric disorders. DESIGN: Case study. PARTICIPANTS: Four children (3 boys) aged 11.6 to 13.7 years with obsessive-compulsive disorder or Tourette syndrome. MAIN OUTCOME MEASURES: Growth, pubertal progression, and hypothalamic pituitary function. METHODS: The patients were treated with SSRIs for 6 months to 5 years (dosage, 20-100 mg/d). All were regularly examined for changes in height and bone age and for pubertal progression. They also underwent evaluation of somatotrophic axis and hypothalamic-pituitary axis function. RESULTS: All 4 patients had growth attenuation. Three of them exhibited growth retardation at a pubertal stage when a growth spurt was anticipated. Three had a decreased growth hormone response to clonidine hydrochloride stimulation and 2 to both clonidine and glucagon stimulation, and 1 had decreased 24-hour secretion of growth hormone that normalized when therapy was stopped. The rest of the endocrine evaluations were within reference ranges in all patients. At follow-up, 2 patients were being treated with somatropin while continuing SSRI therapy, and the other 2 resumed normal growth after discontinuation of therapy. CONCLUSIONS: A decrease in growth rate, possibly secondary to suppression of growth hormone secretion, may occur during SSRI therapy. As the use of this group of drugs is expected to increase in the young age groups, larger studies are warranted to investigate their effect on growth and growth hormone secretion.