Sonography of abdominal organs in precocious puberty in girls.

Precocious puberty constitutes a significant clinical problem due to psychological implications and health concerns as well as consequences associated with girls' fertility. Self-acceptance, peer approval, early motherhood and future fertility - these are only a few issues associated with puberty, the disorders of which may have a negative influence on personality and health. The role of imaging is to determine the causes of early activation of the puberty process, to identify lesions responsible for abnormal sex hormone production and those which are the result of underlying hormonal disorders as well as to diagnose the processes which only mimic symptoms of precocious puberty. Out of all available imaging methods, sonography, thanks to its safety, availability and low cost, seems to be the best method to assess the breasts and internal organs of patients manifesting symptoms of precocious puberty both in early diagnosis and follow-up examinations. Apart from the technique of performing ultrasound examinations, the paper also explains its role in precocious puberty in girls, describes correct parameters of the organs which play the most significant role in the process of puberty as well as presents the features of changes responsible for or resulting from hormonal disorders.

Introduction

Precocious puberty (PP) is a development of secondary sex characteristics before the age of 8. Its incidence constitutes 1:5000–1:10 000 and occurs 2–23 times more frequently in girls than in boys(. This problem may appear due to too early activation of physiological mechanisms responsible for puberty, very often without known cause or because of the lesions in the central nervous system. It may be a reaction to an external hormonal stimulation (e.g. by food, drugs or cosmetics) or an internal one (e.g. ovarian or adrenal pathologies).

Early diagnosis and treatment of PP is essential due to emotional consequences (peer approval, problems of the puberty age, early fertility and motherhood) and effects on health (early termination of growing, decreased fertility in adulthood)(. The diagnostic algorithms of PP encompass hormonal, genetic and imaging examinations.

A standard imaging examination which extends the physical one is breast and abdominal ultrasound scan (US). Its aim is to visualize underlying changes that may be a cause (e.g. ovarian and adrenal tumor) and consequence (accelerated development of the reproductive organs – uterine and ovaries) of precocious puberty.

Technique of US examination in precocious puberty

In order to perform appropriate ultrasound examination in a child, one needs to have an ultrasound system which apart from standard 2D projection in gray scale also enables the assessment of vascular flow (color, power and spectral Doppler modes). Harmonic imaging is frequently used and improves the quality of the obtained image.

Moreover, the apparatus must enable size assessment of examined structures (length and volume) and documentation of the examination in the form of video printer printouts or storing digital photographs and films in the memory of the system (or coupled computer).

Lack of cooperation of the examined child, agitation and fretfulness frequently make the examination considerably more difficult. The “cine” review option, enabling going back to the previously obtained images after freezing the image, helps to overcome such inconveniences.

Transducers used in the abdominal ultrasound examination of a child, particularly in the assessment of the organs located in the lesser pelvis, should be of various sizes and have a broad frequency spectrum. As a rule, younger children require the usage of smaller transducers with higher frequencies than older children.

The small pelvis is a region to which US access is hindered mainly due to intestinal loops, whose contents frequently “conceal” the organs we wish to visualize. Therefore, appropriate preparation of the patient for US examination is recommended. A filled urinary bladder separates the intestinal loops and thus creates an acoustic window for the organs located behind it. However, in the youngest patients, maintaining the bladder filled for the entire duration of the examination is not feasible. The diet which reduces the amount of gas in the intestines also helps to visualize the pelvic organs.

Relevance of US examination in precocious puberty

The problems associated with precocious puberty change with the child's age. In the youngest girls, the most frequent indication for establishing a diagnosis are ovarian cysts as well as excessively stimulated and enlarged ovarian follicles that are sometimes visible in a prenatal examination. In infants fed with breast milk, unior bilateral breast enlargement may also be observed(. Isolated premature thelarche in older girls is associated with increased sensitivity of estradiol receptors in the glandular tissue, increased intraorganic or extracorporeal delivery of estrogens and early stimulation of the hypothalamic–pituitary axis leading to genuine precocious puberty(. In preschool girls, the development of secondar y sex characteristics and menarche should always be differentiated from early variant of normal puberty, changes in the central nervous system, secondary form of precocious puberty and isolated changes.

Assessment of mammary glands

Premature enlargement of the mammary glands may be a sign of PP or an isolated problem (isolated premature thelarche). Breast ultrasound examinations demonstrate the volume of the breast tissue, development of the lactiferous sinus as well as presence and diameter of milk ducts. Such data allow for categorization of the glands to individual stages of their development according to the Tanner scale(. Breast enlargement, especially asymmetrical, may result from the presence of focal lesions (frequently cysts, inflammatory infiltrations and abscesses) which only mimic a developing gland. What is more, it is believed that breast enlargement in infants, resulting from the effects of the mother's hormones, may persist for up to 12 months following birth and is not a pathological phenomenon(.

Assessment of the uterus

On US examination, the uterus is typically visualized posteriorly to the urinary bladder, usually in the medial line. When the urinary bladder is adequately filled, the organ is entirely seen in the examination. To assess the uterus, both transverse and sagittal images are used (similarly to the bladder assessment). The length and thickness of the uterus are measured in the sagittal plane whereas the largest width is taken in the transverse image. The obtained measurements are used to calculate approximate uterine volume. The broad ranges of normal values of the uterine length and volume changing with girls’ age are presented in tab. 1. According to some authors(, determining the limit volume at the level of 1.8 ml, which may not be exceeded before puberty, allows for obtaining 100% of sensitivity and specificity in PP diagnostics (tab. 1).

Tab. 1

Length and volume of the uterus in individual age groups(

	Age group
	1–6 years	6–8 years	8–10 years	10–12 years
Uterine length (mm)	28 ± 4	33 ± 4	35 ± 7	42 ± 5
Uterine volume (ml)	1,9 ± 0,5	2,6 ± 0,9	3,4 ± 1,1	4,3 ± 1,6

Before puberty, the uterus is tubular or conic in shape and the thickness of its corpus is lower or equal to the cer vica l t hick ness(. A lterations in t hese propor tions (enlargement of the uterine body which becomes pearshaped) are a sign of uterine development, so they should occur in the peripubertal period.

In the prepubertal period, the endometrium is not visible in sagittal images or may be seen as a linear hyperechoic structure with maximum 1 mm in thickness. Measuring the thickness of the endometrium should be performed in the sagittal plane, at its thickest site by measuring two layers simultaneously. The normal thickness of the uterine endometrium in older girls varies and changes considerably in the course of the menstrual cycle (4–16 mm().

Another parameter used to determine the development of the internal reproductive organs is the analysis of blood flow in the uterine arteries. There are three types of flow. The most frequent type in the prepubertal period is the flow that is seen solely in the systolic phase, but not observed in the diastolic one. The period of puberty is characterized by gradual appearance of diastolic blood flow. Finally, in adult women, a continuous flow, seen in all phases, is noted in the uterine arteries(.

Assessment of the ovaries

The ovaries are typically located at two sides of the uterus but in practice, they may be found in various localizations. In order to visualize them, particularly when the conditions are unfavorable (insufficiently filled bladder, gas in the intestines), one should “search” for them in the pelvis repeatedly and in various planes. When the ovaries have been visualized, their measurements are taken in three perpendicular planes and their volume, approximate number of follicles as well as the diameter of the dominant follicle are calculated. The size of the ovaries and their internal echostructure change with age. The mean ovarian volume in various age groups is presented in table 2.

Tab. 2

Mean ovarian volume in girls at various ages(

Age	Mean ovarian volume
0–1 month	0,5 ± 0,4
1–3 months	0,4 ± 0,1
3 months - 1 year	0,5 ± 0,2
1–3 years	0,7 ± 0,4
3–5 years	0,7 ± 0,5
5–7 years	0,8 ± 0,6
7–9 years	0,6 ± 0,4
9–11 years	1,3 ± 1,0
11–13 years	3,7 ± 2,1
13–15 years	6,7 ± 4,8

The volume of both the uterus and the ovaries can be measured using applications of the US apparatus which make automatic volume calculations on the basis of a three dimensional image.

Depending on the stage of development, the internal structure of the ovary may be classified to one of four groups(:

type 1 – homogeneous – no follicles are detected;

type 2 – paucicystic – less than 6 follicles are visible with diameters not exceeding 10 mm;

type 3 – multicystic – more than 6 follicles are detected with diameters of up to 10 mm;

type 4 – macrocystic – at least one follicle is visible that is greater than or equal to 10 mm.

The mean ovarian volume in various age groups is presented in table 3.

Tab. 3

Frequency of occurrence of individual ovarian structure types in different age groups (based on()

	Type 1	Type 2	Type 3	Type 4
1–6 years	78%	13%	9%	–
6–8 years	65%	20%	15%	–
8–10 years	61%	16%	19%	4%
10–12 years	44%	11%	28%	17%

One of the reasons for peripheral precocious puberty in girls is a hormonally active ovarian cyst. It may be a classical, anechoic fluid area visibly adjoining the ovary. Sometimes, however, the image is not easy to interpret. Cysts may resemble solid lesions. They may be so large that their place of origin is impossible to be unequivocally determined since they remain in contact with the kidney, pancreas or even with the spleen or liver.

The reason for symptoms of precocious puberty may also be ovarian tumors (e.g. tumor made of granulosa cells, gonadoblastoma)( which may be solid, cystic or of mixed type and are usually visibly connected with the ovary.

To differentiate such lesions from a complicated cyst, it is helpful to visualize the internal vascular segments in a Doppler examination. No signs of flow may, however, result from torsion of the tumor which should be considered especially when examining a patient with acute abdominal symptoms.

Assessment of the adrenal glands

Another organ whose pathologies may lead to symptoms of precocious puberty is the adrenal gland. In infants and young children, adrenal glands are normally visible as bands with layered, harmonic structure. In older children, this structure becomes less and less visible. In adults, only suprarenal areas are assessed since the organ itself remains invisible. A physician ought to describe all focal lesions (e.g. cysts, tumors) as well as enlargement or excessive folding of adrenals (so-called, image of the cerebral cortex) and the patient should be referred to further diagnosis.

Assessment of other organs

Furthermore, there is a group of diseases which mimic symptoms of precocious puberty, for example, the aforementioned breast enlargement due to a focal lesion or vaginal bleeding which being suggestive of premature menarche may in fact result from the presence of neoplastic lesions in the vagina (e.g. rhabdomyosarcoma). Tumors localized in the region of the vaginal fornices are well visible in abdominal US examinations in the retrovesical region. To determine the presence of such lesions in other localizations a transperineal ultrasound examination may be necessary.

Conclusion

Breast and abdominal US examinations should constitute an element of standard diagnostic procedure in each child with symptoms of precocious puberty. It should include the assessment of structures that are essential for the referring endocrinologist, i.e. the degree of development and possible presence of pathological lesions within the mammary glands, determining uterine and ovarian volumes with respect to norms for a given age, assessment of the presence and thickness of the endometrium as well as description of the structure, size and possible presence of focal lesions in the adrenal glands.

Detection of any changes in a US image that are suggestive of PP in patients diagnosed for other pathologies must entail the referral to an endocrinologist issued in the physician's office and included in the conclusions from the examination.