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Isolated lutropin deficiency(HH23)

MedGen UID:
82881
Concept ID:
C0271582
Disease or Syndrome
Synonyms: FERTILE EUNUCH SYNDROME; HH23; Hypogonadotropic hypogonadism 23 with or without anosmia; HYPOGONADOTROPIC HYPOGONADISM 23 WITHOUT ANOSMIA; PASQUALINI SYNDROME
SNOMED CT: Isolated lutropin deficiency (8829008); Fertile eunuch syndrome (8829008); Fertile eunuch (8829008)
 
Gene (location): LHB (19q13.33)
 
Monarch Initiative: MONDO:0009223
OMIM®: 228300
Orphanet: ORPHA325448

Definition

Male patients with hypogonadotropic hypogonadism due to isolated luteinizing hormone (LH) deficiency have normal sexual differentiation but fail to develop spontaneous puberty. Absence of LH alters Leydig cell proliferation and maturation and impairs the onset of normal spermatogenesis, which requires high levels of intratesticular testosterone. Infertility and very low levels of spermatogenesis generally persist in affected men despite long-term exposure to gonadotropin therapy. Female patients exhibit normal pubertal development and menarche, followed by oligomenorrhea and anovulatory secondary amenorrhea (summary by Basciani et al., 2012). Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. Idiopathic hypogonadotropic hypogonadism can be caused by an isolated defect in gonadotropin-releasing hormone (GNRH; 152760) release, action, or both. Other associated nonreproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss, occur with variable frequency. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism has been called 'Kallmann syndrome (KS),' whereas in the presence of a normal sense of smell, it has been termed 'normosmic idiopathic hypogonadotropic hypogonadism (nIHH)' (summary by Raivio et al., 2007). Because families have been found to segregate both KS and nIHH, the disorder is here referred to as 'hypogonadotropic hypogonadism with or without anosmia (HH).' For a general phenotypic description and discussion of genetic heterogeneity of hypogonadotropic hypogonadism, see 147950. Reviews Arnhold et al. (2009) noted that the clinical manifestations of female patients with hypogonadotropic hypogonadism due to mutations in LHB are very similar to those of women with hypergonadotropic hypogonadism due to inactivating mutations of the LH receptor (see 238320): all have female external genitalia, spontaneous development of normal pubic hair and breasts at puberty, and normal to late menarche followed by oligoamenorrhea and infertility. Pelvic ultrasound shows a small or normal uterus and normal or enlarged ovaries with cysts. However, women with LHB mutations can be treated with luteinizing hormone or chorionic gonadotropin (CG; 118860) replacement therapy; women with LH receptor mutations are resistant to LH, and no treatment is effective in recovering their fertility. [from OMIM]

Clinical features

From HPO
Azoospermia
MedGen UID:
2150
Concept ID:
C0004509
Disease or Syndrome
Absence of any measurable level of sperm,whereby spermatozoa cannot be observed even after centrifugation of the semen pellet.
Oligomenorrhea
MedGen UID:
18159
Concept ID:
C0028949
Pathologic Function
Infrequent menses (less than 6 per year or more than 35 days between cycles).
Ovarian cyst
MedGen UID:
14540
Concept ID:
C0029927
Disease or Syndrome
The presence of one or more cysts of the ovary.
Secondary amenorrhea
MedGen UID:
115919
Concept ID:
C0232940
Disease or Syndrome
The cessation of menstruation for six months or more in a female that is not pregnant, breastfeeding or menopausal.
Abnormal spermatogenesis
MedGen UID:
488909
Concept ID:
C0520933
Finding
Incomplete maturation or aberrant formation of the male gametes.
Testicular microlithiasis
MedGen UID:
355854
Concept ID:
C1864873
Disease or Syndrome
Testicular microlithiasis, the deposition of calcium phosphate microliths within the seminiferous tubules, has a population prevalence of 0.6 to 9% (Kim et al., 2003). Middleton et al. (2002) found that it was associated with a majority of primary testicular malignancies. Miller and Sidhu (2002) found that it was present in 1% of male idiopathic infertility cases.
Abnormality of the Leydig cells
MedGen UID:
869277
Concept ID:
C4023703
Anatomical Abnormality
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Abnormality of the sense of smell
MedGen UID:
867293
Concept ID:
C4021655
Finding
An anomaly in the ability to perceive and distinguish scents (odors).
Sparse pubic hair
MedGen UID:
388095
Concept ID:
C1858573
Finding
Reduced number or density of pubic hair.
Sparse axillary hair
MedGen UID:
348975
Concept ID:
C1858574
Finding
Reduced number or density of axillary hair.
Delayed puberty
MedGen UID:
46203
Concept ID:
C0034012
Pathologic Function
Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty.
Male hypogonadism
MedGen UID:
57480
Concept ID:
C0151721
Disease or Syndrome
Familial male hypogonadism is a highly heterogeneous category from which some disorders such as Reifenstein syndrome (312300), Kallmann syndrome (see 308700), isolated gonadotropin deficiency, and some other entities can be separated. The presence of an autosomal recessive form is suggested by the occurrence of parental consanguinity (Nowakowski and Lenz, 1961).
Hypogonadotropic hypogonadism
MedGen UID:
82883
Concept ID:
C0271623
Disease or Syndrome
Hypogonadotropic hypogonadism is characterized by reduced function of the gonads (testes in males or ovaries in females) and results from the absence of the gonadal stimulating pituitary hormones
Androgen insufficiency
MedGen UID:
488853
Concept ID:
C0342527
Disease or Syndrome
Insufficient amount of androgenic activity.
Elevated circulating follicle stimulating hormone level
MedGen UID:
867192
Concept ID:
C4021550
Finding
An elevated concentration of follicle-stimulating hormone in the blood.
Decreased circulating luteinizing hormone level
MedGen UID:
893008
Concept ID:
C4072890
Finding
A reduction in the circulating level of luteinizing hormone (LH).
Decreased serum testosterone concentration
MedGen UID:
892974
Concept ID:
C4073137
Finding
Decreased circulating dihydrotestosterone concentration
MedGen UID:
1784952
Concept ID:
C5539826
Finding
A reduced concentration of dihydrotestosterone in the blood circulation.
Gynecomastia
MedGen UID:
6694
Concept ID:
C0018418
Disease or Syndrome
Abnormal development of large mammary glands in males resulting in breast enlargement.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVIsolated lutropin deficiency

Professional guidelines

PubMed

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Recent clinical studies

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Therapy

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Prognosis

Namikawa T, Shimizu S, Yokota K, Tanioka N, Fukudome I, Munekage M, Uemura S, Maeda H, Kitagawa H, Hanazaki K
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Clinical prediction guides

Gomes AR, Souteiro P, Silva CG, Sousa-Pinto B, Almeida F, Sarmento A, Carvalho D, Freitas P
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