Kallmann syndrome, one of the most common causes of congenital hypogonadotropic hypogonadism (accounting for approximately 50% of cases) is the result of deficient production and secretion of the GnRH neurohormone leading to a decreased activity of the gonads. The majority of patients also suffer from the lack or severe dysfunction of the sense of smell (hyposmia or anosmia). Kallmann syndrome is the result of abnormal development of GnRH neurons. During organogenesis of the hypothalamus and olfactory bulbs the migration of neurons differentiating into the olfactory bulb or GnRH-secreting cells is disordered (1, 2).

The prevalence of Kallmann syndrome is estimated to be 1: 10,000 in boys and very low, 1: 50,000 in girls (1). Kallmann syndrome is difficult to diagnose in girls in early life due to a significant variety of clinical, hormonal and genetic symptoms. The syndrome is usually diagnosed in adolescent girls or only in adulthood due to the difficulty in differentiating Kallmann syndrome from other causes of delayed puberty or absence thereof.

Classic Kallmann syndrome is inherited in an X-linked autosomal dominant pattern (mutation of the KAL 1 gene); however, autosomal recessive inheritance has also been confirmed. In addition, the rare occurrence of this syndrome has been reported (1, 2). According to the literature over 25 different genes correlated with Kallmann syndrome have been identified (FGFR1, FGF8, CHD7, SOX10) (2). A genetic link has been confirmed in only 20-30% of cases (3).

Main components of Kallmann syndrome in adolescent girls and young adult women:

1. Congenital hypogonadotropic hypogonadism, absence of or a decreased sense of smell in the majority of affected individuals, disordered secretion of gonadotropins and sex hormones by the gonads, clinical absence of or delayed puberty, no signs of puberty in girls after 13 years of age (child-like proportions of the body, absence of breast development – Tanner stage I).

2. Other concomitant dysfunctions:

– hearing impairment,

– cleft lip and/or palate, dental agenesis,

– kidney and heart defects,

– skeletal system anomalies,

– eunuchoid body proportions,

– malocclusion/gothic palate (1-5).

A 23-year-old woman was admitted to the Department of Endocrinology of the Centre of Postgraduate Medical Education (CKMP) in order to determine the cause of primary amenorrhoea. The patient had been under the care of a paediatric endocrinology ward and clinic by 19 years of age. She was born from a normal full-term pregnancy with normal body mass and length. She had a normal psychomotor development, although a severely decreased sense of smell was observed already in early childhood. At 14 years of age symptoms of adrenarche appeared, small acne lesions appeared on the face and pubic and axillary hair developed, without other signs of puberty. Olfactory dysfunction was found in the patient’s grandmother and brother. Hearing impairment was also diagnosed in the brother. Due to the lack of menses endocrinological assessment was conducted at 16 years of age. It revealed child-like body proportions, absence of breast development (Tanner stage I), the presence of axillary and pubic hair as well as normal body mass and height. Hormone tests demonstrated a very low estradiol level – 8.93 pg/ml and low levels of gonadotropins: FSH – 4.15 IU/l, LH – 2.56 IU/l. In an LHRH test an increase of the LH level from 2.31 up to 36.0 IU/l in 30 minutes and an increase of the FSH level from 3.52 up to 10.6 IU/l in 90 minutes were observed.

Delayed puberty was diagnosed and hormone replacement therapy was introduced (Estrofem, Estrofem mite). During the treatment regular menses occurred. Breast development took place around 19 years of age after 3 years of treatment. Hormone replacement therapy was discontinued after 6 years in 2015. No menstrual bleeding has appeared since then.