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JKM > Volume 36(4); 2015 > Article
Nam, Lee, Tang, Liu, Kim, Chun, Yeom, Kim, and Lee: A Case Report of Efficacy of Growth Height and Peak-Luteinizing Hormone Level Suppression on Idiopathic Gonadotropin-Dependent Precocious Puberty Patient Using Herbal Remedy, Aesopjiyoun-tang

Abstract

The purpose of this report is to evaluate effect of Korean medical treatment on idiopathic gonadotropin-dependent precocious puberty (G-DPP) patient received herbal medicine. We administered Aesopjiyoun-tang remedy to idiopathic G-DPP and analyzed the delay effect by hormonal value and radiographs; the height growth effect by measurement of height. After Korean medical treatment, suppression effect to peak- Luteinizing Hormone level (LHL) is 14.39IU/L to 10.9IU/L for 13month, growth effect to height value is 11cm/13month; and change of mean growth velocity (MGV) is 6.08cm/year to 10.06cm/year. The gain in height by treatment is 3.98cm/year. The result suggests Aesopjiyoun-tang can be an effective treatment for G-DPP. Herbal medicine can be used as an alternative treatment in place of the GnRH treatment.

Introduction

Precocious puberty (PP) is defined as the onset of secondary sexual characteristics development more than 2.5 to 3 standard deviations earlier than their same-age cohort1,2). Thus the puberty development begins younger than the age of eight years in girls or nine years in boys3). The etiology of PP is classified by the underlying pathogenesis into three categories: G-DPP, gonadotropin-independent PP (G-IPP), and incomplete PP. Although more than 80 percent of PP patients are idiopathic G-DPP4). G-DPP can be distinguished from G-IPP by measuring LHL5). In G-DPP, the peak-LHL has over 5IU/L diagnostic limit responded to gonadotropin releasing hormone (GnRH) stimulation6).
As the latest trend of earlier and growing, more and more patients with PP visit hospitals and clinics for treatment4). GnRH agonist is most commonly used for PP in order to lower sex hormone level. However, some patients were hesitant about GnRH treatment for adverse effects7,8).
Several researches reported that herbal medicine prescribed for those children suffering from PP has a certain effect on their symptoms9,10). However, reports are problematic in that there were no peak-LHL evaluation and made a simple comparison with breast buds or estradiol values of before and after taking the medicine. Serum estradiol values are highly variable and have a low sensitivity for the diagnosis of PP in girls. The criterion for diagnosis is the peak-LHL after stimulation by GnRH1).
This case study evaluated LHL, MGV duration of both herbal treatment and after cessation of treatment. It was to report to obtain significant results through the patient with G-DPP who were visited hospital of Korean Medicine for herbal treatment.

Case presentation

An 8-year-old girl was diagnosed with GDPP on Sep. 2014 in OO hospital near home. The pediatrician recommended GnRH treatment, but guardian refused due to anxiety about the adverse effect. They moved to our hospital right after diagnosis and wanted to get Korean Medicine treatment. Her medical history is unremarkable and pulse pattern is sunken with rough. The parents are below average height, and at physical examination, the girl is 135.2cm tall (in the 90~97th percentile for her age), weight 25kg, and has a body-mass index 13.7. On set of breast development is 7.7 years and at time of the clinic breast development is classified as Tanner stage 2. Her peak-LHL was 14.39IU/L and bone age (BA) was 9.7 years. Her Korean medicinal pattern of identification was syndrome of stagnant of qi (氣鬱). The general features and distribution of the subject are listed on Table 1.
As they desired to get herbal treatment, Aesopjiyoun-tang was prescribed for delay sexual development and growth height. Remedy has been made with ten or so herbal medicine ingredients including Cyperus rotundus (20%), Angelica gigas (15%), Paeonia japonica (15%), Atractylodes japonica (7%), Astragalus membranaceus (7%), Paeonia suffruticosa Andrews (7%), Cnidium officinale Makin (7%), Citrus unshiu Markovich (7%), Cinnamomum cassia (7%), Glycyrrhiza uralensis (5%), Zingiber officinale, Zizyphus jujuba. The medicines were prescribed every 15 days for three months (Sep. 13th, 2014 ~ Dec. 20th, 2014). The dose is two times a day(morning and evening) with 80cc.
Due to her clinical improvement, breast buds were not palpable (Nov. 2014) and peak-LHL was suppressed 14.39 to 13.8 (Dec. 2014) (Tab. 2). Height value has increased by 2.5cm for the same period. The MGV increase was from 6.08 to 10.43 (Tab. 3). So we decided to discontinue the herbal treatment and recommend a follow-up evaluation every three months. Suppression effective on LHL was maintained, as a result 10.9 IU/L was shown at the latest test (Oct. 2015) (Tab. 2). Follow-up radiographs of patient dated on Oct. 2015 (BA 10.8year) showed no time interval change compared to the initial radiograph in Sep. 2014 and ⊿BA/⊿ CA value was less than 1 (Fig 1). And her prediction height calculated by RUS is increased 164.4cm to 168.2cm (Tab 4)11.

Discussion

The primary purpose of treatment for G-DPP is to induce a child to grow to a normal adult height12,13, 14). Treatment effect of PP patient was evaluated by LH suppression effective15,16). In this case, basal-LHL was elevated 0.02 to 1.6 and peak-LHL was suppressed 14.39 to 10.9. After 2nd round treatment, it was seen that breast buds had been disappeared. Other previous report, “Kim et al.” gained almost identical clinical effect10). However, it is hard to acknowledge medicinal effect. Because it is very often for early adolescence that the breast buds had disappear without receiving any treatment.
The height growth value for subject was increased to 146.1cm, while that before herbal treatment was 135.2cm. Increment of height growth value has very important meaning to PP patient. Because in not all cases but most advanced bone age may reach short adult height17,18).
Patient with PP’s BA are more advanced than chronological age. Radiograph of the Sep. 2014, BA is more than 9.5 years old (Fig. 1A). Radiograph of the Mar. 2015, the main point of interest in this case is the sesamoid of thumb. The sesamoid bone was normal in more than 10 year old girls’ AP view of the hand but rarely to 8 year old girls (Fig. 1B). Radiograph of the Oct. 2015, it shows no specific change in carpal bone and radius, ulna for 13 months11) (⊿BA/⊿CA<1) (Fig. 1C). These represent the growth plate fusion was delayed.
In Korean medicine, there is no specific term or definition that refers to the current understanding of G-DPP. The pattern of identifications on G-DPP are follows: syndrome of stagnant of qi (氣鬱), syndrome of deficiency of yin (陰虛), syndrome of damp-heat (濕熱)19. In this case, the patient’s pattern of identification was syndrome of stagnant of qi (氣鬱). Therefore, we decided to administer Aesopjiyoun-tang which has been recommended for PP patients who have identified syndrome of stagnant of qi (氣鬱). The remedy consists of circulation meridian system (通經絡), adaptation of qi (順氣), releasement of stasis (解鬱) herb such as Cyperus rotundus, Citrus unshiu Markovich: healthy spleen (健脾) herb such as Atractylodes japonica: activation of blood (活血) herb such as Paeonia japonica, Angelica gigas, Cnidium officinale Makin.
This case demonstrates that herbal treatment can have beneficial effects on the symptom of idiopathic G-DPP, including height growth. Although these results cannot be extrapolated to patients with all of PP, this case study provides a basic data for the investigation of Korean herbal medicine as a alternative therapy. In future studies, we intend to confirm the efficacy of Aesopjiyoun-tang in detail and the underlying mechanisms with well-controlled clinical trials.

Fig. 1
Radiographs of the left hand were obtained.
(A) Radiograph of the left hand AP view (2014-09). BA of this radiograph is more than 9.7 years old. (B) Radiograph of the left hand AP view (2015-03). The main point of interest in this case is the sesamoid of thumb. The sesamoid bone was normal in more than 10 year old girls’ AP view of the hand but rarely to 8 year old girls. (C) Radiograph of the left hand AP view (2015-10). This radiograph shows no specific change in carpal bone and radius, ulna for 13 months (⊿BA/⊿CA<1). These represent the growth plate’s fusion was delayed.
jkm-36-4-150f1.gif
Table 1
Demographic Characteristic of Participant
Parameters
Gender Female
Chronological age (years) 8.2
Bone age (years) 9.7
Height (cm) 135.2
Contrast to same age group (cm) +7.8
Weight (kg) 25
Contrast to same age group (kg) −1.2
MPH (cm) 154
On set of breast development (years) 7.7
Date of the first visit Sep. 6th, 2014
breast stage 2
breast pain -
menstruation sign -

Bone age: Assessment according to TW3

MPH: Mid Parental Height

Breast stage: Rating according to Tanner Stage

Table 2
LH, FSH Level After GnRH Stimulation
DATE Item Basal 30min 60min 90min
2014-09 FSH 0.39 7.95 9.74 8.83
LH 0.02 14.39 14.18 9.82

2014-12 LH 0.4 13.8 11.0 8.5

2015-10 LH 1.6 10.9 7.9 5.8

Unit: mlU/ml

Table 3
Increment Height and Weight Value After Treatment
DATE Height (cm) Weight (kg) MGV (cm/year)
2014-09 135.2 25
2014-10 135.9 25.7 6.08
2014-12 137.7 26.8 10.43
2015-06 143.4 28.5 10.95
2015-10 146.1 30.2 10.06

MGV: Mean growth velocity. 365/days×height

All measurements were progressed 9:00AM~10:30AM

Table 4
Increment Predicted Height After Treatment
DATE Height (cm) BA Prediction Height(cm)
2014-09 135.2 9.74 164.4
2015-03 139.6 10.41 164.9
2015-10 146.1 10.81 168.2

PH: Prediction Height

BA, PH: Assessment according to TW3 method

References

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