Gonadotropin responses to low dose pulsatile administration of GnRH in a case of anosmia with hypogonadotropic hypogonadism associated with gonadal dysgenesis 47 XXY

Abstract

A 25 year old man presented hypogonadotropic hypogonadism with complete anosmia (Kallman's syndrome). His chromosomic type was 47 XXY (Klinefelter's syndrome). Clinical findings were: height 183 cm, weight 62 kg, increased length of lower limbs, P2\p=n-\A2pilosity and micropenis. Only a left testis was present (1.5\p=n-\1.5cm). Bone age was 15. Testicular biopsy showed that the signs were more related to the gonadotropic deficit than to the gonadal dysgenesis; tubular hyalinization was not observed. Plasma levels of testosterone and oestradiol were very low. Plasma gonadotropin levels were below normal ranges and did not respond to an infusion test of GnRH. GnRH was administrated iv every 90 min for 3 weeks by an auto syringe infusion pump and induced a pulsatile response of FSH and LH. Plasma levels of testosterone and oestradiol were unaffected. It may be concluded that the results of pulsatile injection of GnRH confirmed in this patient a unique association of Kallmann's syndrome with complete 47 XXY Klinefelter's syndrome.Idiopathic hypogonadotropic hypogonadism re¬ sult in absent or incomplete puberal development. The disease is characterized by low plasma gona¬ dotropin and sexual steroid levels; it appears to be due to a deficiency in GnRH. This type of hypo¬ gonadism may be associated with other inherited abnormalities such as hypo-or complete anosmia, cleft palate or cranio-facial deformities and in rare cases gonadal dysgenesis.In the present study we observed the effects of pulsatile low doses GnRH administration in a male with hypogonadotropic hypogonadism and complete anosmia (Kallmann's syndrome) asso¬ ciated with a 47 XXY gonadal dysgenesis (Klinefelter's syndrome). Material and MethodsHormones assays FSH and LH were determined in vitro in human serum by the principle of competitive protein-binding analysis (RIA-gnost hFSH and RIA-gnost hLH Tachisorb kits from Hoechst-Behring Laboratories) normal male adult range: 0.3-2.3 ng/ml for FSH; 1 ng of hFSH was equivalent to 4 mU hFSH MRC 69/104; normal male adult range 1.1 -3.1 ng/ml for LH; 1 ng of hLH was equivalent to 3.5 mU hLH MRC 68/40. Plasma testosterone was measured by radio-immunoassay as previously described (Abraham et al. 1972) normal male adult range 12 to 41 nmol/1. Plasma oestradiol was measured by a radioimmunoassay; nor¬ mal male adult range 36 to 183 pmol/1.

The Depth of the Olfactory Sulcus Is an Indicator of Congenital Anosmia

“…A nosmia since birth or early childhood is a condition that can be divided into anosmias associated with chromosomal disorders (eg, Kallmann syndrome 1 and Klinefelter syndrome 2,3 ) or anosmias without evidence of other defects (IA since birth or early childhood, termed "IA" throughout this article). While the underlying pathophysiology is relatively well-investigated in Kallmann syndrome, 4,5 IA has received far less attention, though from the literature and our own clinical experience, IA appears to be more frequent than Kallmann syndrome.…”

Central hypogonadism in Klinefelter syndrome: report of two cases and review of the literature

“…Different karyotypes were associated with HH in KS, including homogeneous 47,XXY, different grades of mosaicism, and one case with an extra Xq isochromosome (Table 1), so that a clearly predisposing cytogenetic background cannot be identified for this condition. While neonatal bilateral cryptorchidism and micropenis were reported only in one patient [18], absent or incomplete pubertal maturation was evident in most previously described cases and in our 2 patients as well, indicating an early onset of hypogonadism, which is unusual in KS [8][9][10]. Among features associated with KS, diabetes was reported in one patient, overweight in 4, low-normal intelligence scores in 5 with behaviour problems and emotional lability in one, and venous insufficiency in lower limbs in one subject (Table 1).…”

“…In this article we describe two cases of HH in two patients with KS without any identifiable cause to explain the central defect. Only 14 other similar cases have been previously reported so far (Table 1) [12][13][14][15][16][17][18][19][20][21][22][23].…”

“…Kallmann syndrome is diagnosed when CHH is accompanied by olfaction defects due to a common development of GnRH (gonadotropin-releasing hormone) and olfactory neurons, but also other features, such as facial midline defects, have been associated to this syndrome [44][45][46]. Hazard and colleagues described a 25 year-old man with anosmia, bilateral cryptorchidism, micropenis and cleft palate at birth, absence of spontaneous puberty, and a 47,XXY karyotype [18] thus demonstrating the cooccurrence of KS and Kallmann syndrome. This may also be the case of the 57-year-old man we have described in the present series (case 1), as anosmia and a positive family history are present as well; negative genetic analysis cannot exclude the diagnosis of Kallmann syndrome and it is not surprising indeed, as a genetic defect can be found only in 40-50% of patients with CHH [47,48].…”

“…Nevertheless, 12 previously published reports have described 14 patients with Klinefelter syndrome and hypogonadotropic hypogonadism (HH), variably associated with other pituitary hormones deficiencies, and in whom no organic cause could be identified to explain the hypothalamus-pituitary-gonadal axis (HPG) central defect [12][13][14][15][16][17][18][19][20][21][22][23].…”