scholarly journals Sex Steroids, Precursors, and Metabolite Deficiencies in Men With Isolated Hypogonadotropic Hypogonadism and Panhypopituitarism: A GCMS-Based Comparative Study

2015 ◽  
Vol 100 (2) ◽  
pp. E292-E296 ◽  
Author(s):  
Frank Giton ◽  
Séverine Trabado ◽  
Luigi Maione ◽  
Julie Sarfati ◽  
Yves Le Bouc ◽  
...  
Keyword(s):  
Sex Steroids ◽  
Hypogonadotropic Hypogonadism ◽  
Serum Levels ◽  
Dehydroepiandrosterone Sulfate ◽  
Kallmann Syndrome ◽  
Gas Chromatography Mass Spectrometry ◽  
Adrenal Steroid ◽  
Estrone Sulfate ◽  
Congenital Hypogonadotropic Hypogonadism ◽  
17 Hydroxyprogesterone

Abstract Context: Both testicular and adrenal steroid secretions are impaired in men with panhypopituitarism (Hypo-Pit), whereas only testicular steroid secretion is impaired in men with isolated gonadotropin deficiency (IHH) caused by normosmic congenital hypogonadotropic hypogonadism or Kallmann syndrome. Objective: The objective of the study was to compare the serum levels of sex steroids, precursors, and metabolites between men with complete IHH and those with Hypo-Pit. Patients: We studied 42 healthy men, 16 untreated men with IHH (normosmic congenital hypogonadotropic hypogonadism/Kallmann syndrome) and 23 men with Hypo-Pit (14 with craniopharyngioma, 9 with congenital hypopituitarism) receiving hydrocortisone, thyroxine, and GH replacement therapy but not T. Methods: Gas chromatography/mass spectrometry (GCMS) was used to measure the serum levels of sex steroids [T, dihydrotestosterone (DHT), and estradiol (E2)], their precursors (pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, androstenediol, progesterone, 17-hydroxyprogesterone, and androstenedione), and their metabolites (androsterone, estrone, and estrone sulfate) as well as pregnenolone and dehydroepiandrosterone sulfate esters. Results: All the above-mentioned steroids, and notably T, DHT, and E2, were significantly lower in IHH patients than in controls but remained well above the detection limit of the relevant assays. In Hypo-Pit men, all these steroids were dramatically and significantly lower than in IHH. Interestingly, T, DHT, and E2, as well as pregnenolone and dehydroepiandrosterone sulfate esters, were undetectable or barely detectable in the Hypo-Pit men. Conclusions: Steroid deficiencies are marked but partial in men with complete IHH. In contrast, men with Hypo-Pit have a very severe overall steroid deficiency. These deficiencies could affect health and quality of life.

Altered adrenal steroid production in term infants having respiratory acidosis

1993 ◽  
Vol 128 (2) ◽  
pp. 136-139 ◽  
Author(s):  
Cindy A Harlin ◽  
James M Tucker ◽  
Cary L Winkler ◽  
Brenda Henson ◽  
Charles R Parker
Keyword(s):  
Gestational Age ◽  
Pregnancy Complications ◽  
Respiratory Acidosis ◽  
Serum Levels ◽  
Dehydroepiandrosterone Sulfate ◽  
Delivery Method ◽  
Term Infants ◽  
Adrenal Steroid ◽  
Adrenal Steroidogenesis ◽  
The Status

Prior studies have provided evidence for reduced fetal adrenal production of dehydroepiandrosterone sulfate and normal or increased production of cortisol in association with pregnancy complications believed to result in fetal stress. In the present study, we sought to determine the status of adrenal steroidogenesis in 36 term infants having respiratory acidosis and to compare acidotic infants to (i) non-acidotic infants matched for pregnancy complications, gestational age, and method and indications for delivery (control infants), and (ii) non-acidotic infants of non-complicated pregnancies who were also matched for gestational age and delivery method (normal infants). Umbilical cord serum levels of dehydroepiandrosterone sulfate were lowest in acidotic infants, intermediate in the condition matched control infants and highest in the non-acidotic infants of normal pregnancies. On the other hand, cortisol levels were highest in acidotic infants, intermediate in control infants and lowest in the normal infants. These data suggest that various pregnancy complications give rise to significant alterations in adrenal steroidogenesis (decreased dehydroepiandrosterone sulfate and increased cortisol). Intrauterine deterioration during labor with resultant respiratory acidosis has an additional effect on fetal adrenal function.

SERUM LEVELS OF TESTICULAR AND ADRENAL STEROIDS AFTER DEXAMETHASONE AND HCG-ADMINISTRATION IN THE LABORATORY-MAINTAINED RHESUS MONKEY

1978 ◽  
Vol 87 (3) ◽  
pp. 650-658 ◽  
Author(s):  
E. J. Wickings ◽  
E. Nieschlag
Keyword(s):  
Rhesus Monkey ◽  
Rhesus Monkeys ◽  
Dynamic Testing ◽  
Serum Levels ◽  
Adrenal Steroid ◽  
Human Situation ◽  
17 Hydroxyprogesterone ◽  
Very High ◽  
Male Rhesus

ABSTRACT In order to evaluate the endocrine testicular and adrenal function of rhesus monkeys in vivo, and to compare this with the human situation, the effect of dexamethasone (Dxm), HCG and combined Dxm/HCG administration on the steroid levels was investigated in 8 adult male rhesus monkeys in November/December (= season of high testicular activity). Serum levels of cortisol, testosterone (T), androstenedione (A), 17-hydroxyprogesterone (17-OHP), oestradiol (Oe2), dehydroepiandrosterone (DHA) and its sulphate (DHA-S) were measured radioimmunologically. Basal T and DHA serum levels were similar to those found in man, whilst A levels amounted to 1/10 and DHA-S to 1/30 of human values. Oe2 and 17-OHP levels were higher than in man. T and A levels were not suppressed by Dxm and very high degrees of stimulation were reached after HCG. The HCG-induced increment in T was smaller under Dxm/HCG than under HCG alone. 17-OHP levels were reduced to 25% of basal levels under Dxm, but the incremental response to Dxm/HCG was the same as that without Dxm. DHA and DHA-S were 60 and 75% lower under Dxm, and the increment in DHA after Dxm/HCG was less than that after HCG. DHA-S did not respond to HCG. In conclusion, several important differences in basal steroid levels and in the response to dynamic testing were found in the rhesus monkey, as compared to man. The adrenal contributes 75% to circulating 17-OHP levels, and 60 and 75% respectively to DHA and DHA-S levels. A is produced solely by the testis in the rhesus monkey. As compared to man, the rhesus monkey testis in vivo synthesises T via both the Δ4 and Δ5 pathways. The Δ5 pathway appears to be dependent on adrenal steroid precursors.

scholarly journals GENETICS IN ENDOCRINOLOGY: Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing

2018 ◽  
Vol 178 (3) ◽  
pp. R55-R80 ◽  
Author(s):  
Luigi Maione ◽  
Andrew A Dwyer ◽  
Bruno Francou ◽  
Anne Guiochon-Mantel ◽  
Nadine Binart ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Next Generation Sequencing ◽  
Pubertal Development ◽  
Hypogonadotropic Hypogonadism ◽  
Kallmann Syndrome ◽  
Incomplete Penetrance ◽  
Next Generation ◽  
Congenital Hypogonadotropic Hypogonadism ◽  
Main Challenge ◽  
Generation Sequencing

Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are rare, related diseases that prevent normal pubertal development and cause infertility in affected men and women. However, the infertility carries a good prognosis as increasing numbers of patients with CHH/KS are now able to have children through medically assisted procreation. These are genetic diseases that can be transmitted to patients’ offspring. Importantly, patients and their families should be informed of this risk and given genetic counseling. CHH and KS are phenotypically and genetically heterogeneous diseases in which the risk of transmission largely depends on the gene(s) responsible(s). Inheritance may be classically Mendelian yet more complex; oligogenic modes of transmission have also been described. The prevalence of oligogenicity has risen dramatically since the advent of massively parallel next-generation sequencing (NGS) in which tens, hundreds or thousands of genes are sequenced at the same time. NGS is medically and economically more efficient and more rapid than traditional Sanger sequencing and is increasingly being used in medical practice. Thus, it seems plausible that oligogenic forms of CHH/KS will be increasingly identified making genetic counseling even more complex. In this context, the main challenge will be to differentiate true oligogenism from situations when several rare variants that do not have a clear phenotypic effect are identified by chance. This review aims to summarize the genetics of CHH/KS and to discuss the challenges of oligogenic transmission and also its role in incomplete penetrance and variable expressivity in a perspective of genetic counseling.

scholarly journals Congenital hypogonadotropic hypogonadism/Kallmann syndrome is associated with statural gain in both men and women: a monocentric study

2020 ◽  
Vol 182 (2) ◽  
pp. 185 ◽  
Author(s):  
Luigi Maione ◽  
Giovanna Pala ◽  
Claire Bouvattier ◽  
Séverine Trabado ◽  
Georgios Papadakis ◽  
...  
Keyword(s):  
General Population ◽  
Hypogonadotropic Hypogonadism ◽  
Genetic Defect ◽  
Hormonal Treatment ◽  
Rare Condition ◽  
Kallmann Syndrome ◽  
Age At Diagnosis ◽  
Individual Growth ◽  
Men And Women ◽  
Congenital Hypogonadotropic Hypogonadism

Context Congenital hypogonadotropic hypogonadism/Kallmann syndrome (CHH/KS) is a rare condition characterized by gonadotropin deficiency and pubertal failure. Adult height (AH) in patients with CHH/KS has not been well studied. Objective To assess AH in a large cohort of patients with CHH/KS. Patients A total of 219 patients (165 males, 54 females). Parents and siblings were included. Methods AH was assessed in patients and family members. AH was compared to the general French population, mid parental target height (TH) and between patients and same-sex siblings. Delta height (∆H) was considered as the difference between AH and parental TH. ∆H was compared between patients and siblings, normosmic CHH and KS (CHH with anosmia/hyposmia), and according to underlying genetic defect. We examined the correlations between ∆H and age at diagnosis and therapeutically induced individual statural gain. Results Mean AH in men and women with CHH/KS was greater than that in the French general population. Patients of both sexes had AH > TH. Males with CHH/KS were significantly, albeit moderately, taller than their brothers. ∆H was higher in CHH/KS compared to unaffected siblings (+6.2 ± 7.2 cm vs +3.4 ± 5.2 cm, P < 0.0001). ∆H was positively correlated with age at diagnosis. Neither olfactory function (normosmic CHH vs KS) nor specific genetic cause impacted ∆H. Individual growth during replacement therapy inversely correlated with the age at initiation of hormonal treatment (P < 0.0001). Conclusions CHH/KS is associated with higher AH compared to the general population and mid-parental TH. Greater height in CHH/KS than siblings indicates that those differences are in part independent of an intergenerational effect.

HLA-Compatible Paternity in Two “Fertile Eunuchs” with Congenital Hypogonadotropic Hypogonadism and Anosmia (the Kallmann Syndrome)

1980 ◽  
Vol 51 (2) ◽  
pp. 275-279 ◽  
Author(s):  
ALAN D. ROGOL ◽  
KAMAL K. MITTAL ◽  
BEVERLY J. WHITE ◽  
MARY H. McGINNISS ◽  
JEFFREY M. LIEBLICH ◽  
...  
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Kallmann Syndrome ◽  
Congenital Hypogonadotropic Hypogonadism

Molecular genetic and clinical delineation of 22 patients with congenital hypogonadotropic hypogonadism

2017 ◽  
Vol 30 (10) ◽  
Author(s):  
Kohei Aoyama ◽  
Haruo Mizuno ◽  
Tatsushi Tanaka ◽  
Takao Togawa ◽  
Yutaka Negishi ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Hypogonadotropic Hypogonadism ◽  
Molecular Genetic ◽  
Japanese Patients ◽  
Kallmann Syndrome ◽  
Next Generation ◽  
Genetic Causes ◽  
Congenital Hypogonadotropic Hypogonadism ◽  
Pathogenic Mutations

AbstractBackground:Congenital hypogonadotropic hypogonadism (CHH) is classified as Kallmann syndrome (KS) with anosmia/hyposmia or normosmic (n)CHH. Here, we investigated the genetic causes and phenotype-genotype correlations in Japanese patients with CHH.Methods:We enrolled 22 Japanese patients with CHH from 21 families (18 patients with KS and 4 with nCHH) and analyzed 27 genes implicated in CHH by next-generation and Sanger sequencing.Results:We detected 12 potentially pathogenic mutations in 11 families, with three having a mutation inConclusions:The frequency of CHH genes in the Japanese was compatible with previous reports, except that

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