Turner syndrome (TS) is defined as a genetic disorder among phenotypic females that manifests with characteristic physical features and partial or complete absence of the second sex chromosome¹⁾. Short stature and hypogonadism are principal signs of TS^2,3). TS affects approximately 1 individual in every 2,500 women^1,4). Nearly half of the individuals with TS have the typical 45,X karyotype while the rest have various types of chromosomal abnormalities including isochromosome and mosaicism^1,2,5).

TS may largely be diagnosed prenatally or during the neonatal, childhood, or adolescent period³⁾. Cystic hygroma on ultrasonography during pregnancy raises the possibility of TS. Diagnostic screening for TS may be performed with the use of prenatal triple screening tests (human chorionic gonadotropin, alpha fetoprotein, and unconjugated estriol levels). TS may be suspected in cases of clinical manifestations such as hygroma colli during the prenatal period, lymphedema of the extremities, broad chest with widely spaced nipples, webbed neck or cubitus valgus at birth or during infancy, and coarctation of the aorta detected later in childhood²⁾. TS may be suspected in persons with short stature and amenorrhea, as well as repeated abortion in adolescence or thereafter. The diagnosis of TS is confirmed through chromosomal analysis.

Growth hormone deficiency (GHD) is known to occur due to a lack of growth hormone (GH) secretion from the pituitary gland. Clinical manifestations of GHD are short stature, doll-like face, and truncal obesity⁶⁾. A diagnosis of GHD is made through a comprehensive combination of clinical phenotypes, GH provocation test, and imaging studies⁷⁾.

Although a differential diagnosis between TS and GHD must be made among female pediatric patients who are admitted to the hospital with the chief complaint of short stature, several cases with concomitant TS and GHD had been reported^8,9,10,11). Nevertheless, the concurrent development of these two disorders is rare and has not yet been reported in Korea. We report two cases of TS that was confirmed in patients with GHD.

Short stature is defined as height that is 2 standard deviations below the mean height for age and sex. The treatment, therapeutic effects, and prognosis may be different depending on the etiologies of the short stature. Thus, an accurate diagnosis is imperative. An accurate diagnosis necessitates meticulous physical examinations and appropriate tests⁶⁾. TS was confirmed through karyotyping in a female with typical phenotypes and GHD was diagnosed using a GH provocation test in a subject with short stature and other clinical findings^3,6).

The differences between TS and GHD included delayed bone age, the peak GH concentration after GH provocation, hypogonadism, and physical findings. Bone age is consistent with chrnological age in patients with TS. However, bone age is significantly lags behind chronological age in patients with GHD. In our cases, bone age was delayed in case 1, whereas bone age was advanced in case 2. In case 2, bone age advancement was mainly owing to spontaneous pubertal development. Up to 30% of TS patients are known to undergo spontaneous pubertal development¹²⁾.

TS could accompany endocrine disorders, including diabetes mellitus and autoimmune thyroid disease. TS patients are known to be GH sufficient. Twenty-four-hour GH secretory profiles and IGF-I levels in TS patients were similar to those in normal children¹³⁾. The causal relation between of TS and GHD has not been fully understood. The cause of short stature in TS is haploinsuffiency of short-stature homeobox-containing gene in chromosome X. A GH provocation test should be performed in patients whose growth pattern is abnormal compared to the growth reference for TS. Concomitant GHD has been reported in several TS cases. To our knowledge, the first reported case of TS with GHD was in a 9.1-year-old girl, by Brook in 1978¹⁴⁾. The girl's height was 109.2 cm (−3.6 SDS), and growth velocity was 2.5 cm/yr (Table 1). The peak GH concentration in a provocation test was 6.1 mIU/L after hypoglycemia. Efstathiadou and Tsatsoulis¹⁰⁾ reported a 30-year-old woman with TS who was previously diagnosed with multiple pituitary hormone deficiency. Gallicchio et al.⁹⁾ reported a case of TS with the 45,X/46,XX karyotype and multiple pituitary hormone deficiency. Jin et al.⁸⁾ reported an 11-year-old girl with TS, GHD, and hypothyroidism.

In our study, case 1 was initially diagnosed as GHD. Karyotyping was performed due to the typical phenotype and poor response to rhGH therapy, which revealed 45,X/45,X+mar. In case 2, the GH provocation test and karyotyping were performed simultaneously because of decreased growth velocity and TS phenotype. In the case reported by Brook¹⁴⁾, the patient was diagnosed with TS and then GHD according to the decreased growth velocity. The case reported by Efstathiadou and Tsatsoulis¹⁰⁾ was confirmed as TS 13 years after the GHD diagnosis. The case reported by Jin et al.⁸⁾ was diagnosed simultaneously as TS and multiple pituitary hormone deficiency.

In TS patients, rhGH therapy is indicated to attain normal adult height. The recommended rhGH dose is higher in TS than in GHD. Therefore, growth response could be poor in patients with TS who had been initially diagnosed with GHD. In prepubertal TS patients growth velocity was 4.7±1.9 cm/yr before rhGH therapy and 7.6±1.9 cm after 1 year of administration with a rhGH dose of 0.3 mg/kg/wk¹⁵⁾. In this study, growth velocity increased from 5.7 to 7.8 cm/yr after the rhGH therapy in case 1. However, our second case did not show a significant increase in growth velocity from 3.7 to 3.8 cm/yr because of the advanced bone age. Hence, early diagnosis is important.

In conclusion, to our knowledge this is the first report of TS and GHD in Korea. TS and GHD are important differential diagnoses in girls with short stature. Though a TS or GHD diagnosis may have been made, a throughout physical examination and further diagnostic tests are important when concomitant TS and GHD are clinically suspected.