True Precocious Puberty Following Removal of Virilizing Adrenal Tumor

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Group: 2003
Subgroup: Volume 1, Issue 2, Spring
Date: June 2003
Type: Original Article
Start Page: 97
End Page: 100

Authors:

  • A Rashaud
  • Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, IR.Iran
  • N Najafizadeh
  • Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, IR.Iran

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Abstract:


Adrenal tumors are rare in children. Most of these tumors are virilizing. We present here the report of a girl with childhood virilization due to adrenal tumor in early childhood. In this patient after tumor resection and regression of secondary male sex characteristics, signs of econdary female sex characteristics developed before the age of 8 years due to pituitary activation (true precocious puberty). Treatment was performed with a GnRH analogue. Virilizing adrenal tumors have not been included in the etiology of true precocious puberty. It is suggested to consider these tumors as one of the causes of true precocious puberty.

Keywords: True precocious puberty;Virilizing;Adrenal tumor

Manuscript Body:


Introduction


True precocious puberty is defined as early initiation of GnRH production by the hypothalamus that leads to increased secretion of gonadotropins from the pituitary, resulting in increased activity of gonads and the appearance of secondary sexual characteristics in girls and boys before age of 8 and 9 years respectively.
Normal pubertal development is under the control of the gonads and adrenal glands. Maturation of gonads is defined as gonadarche and results in increased testicular cell number and volume followed by spermatogenesis and increased testosterone secretion in boys and increased number and volume of ovarian cells and formation of follicles and secretion of estrogen and progesterone in girls.
Maturation of adrenal cells, which is defined as adrenarche also, results in producing DHEA-S and androstendione in both sexes .1 Diagnosis of adrenal virilizing tumors is based on the clinical features and elevation of urinary 17-ketosteroids and also elevated serum levels of DHEA-S, androstendione and testosterone without significant decrease after administration of dexamethasone. Tumors are rarely palpable but the kidneys may be shifted downward by adrenal adenoma or carcinoma.' These tumors are often diagnosed by radiography especially intravenous pyelography (IVP). Adrenal ultrasound study is not valuable in diagnosis. CT scan is the best diagnostic tool.' These tumors must be resected with care without rupture of the capsule. Complete removal of the metastatic tumors increases the survival of the patient." In cases of advanced tumors, which cannot be totally removed, radiotherapy and chemotheraphy are performed. Aminoglutethimide, ketoconazole and O,P'-DDD are used for chemotherapy? For enhanced prognosis of virilizing localized adrenal tumors it is important to avoid abdominal radiotherapy, to prevent ovarian lesions? Long acting analogs of LHRH are effective for suppression of gonadotropin and sex steroid secretion in child   Wit 1 true precocious pu erty. ' Prognosis in adrenal carcinoma associated with Cushing's syndrome is poor and there is tendency to metastasis and recurrence of the tumor.r' Tumors with only virilism (no in- crease in cortisol secretion) generally have slow progression and recurrence is rarely observed and usually have very good progno. 2 SIS.
Following surgery clinical features and steroid levels must be evaluated frequently. Recurrence of signs or elevation in urinary 17 ketosteroids or plasma DHEA-S suggests local recurrence of the tumor?
The girl described in this report had signs of virilism in early childhood due to virilizing adrenal tumor. Following removal of the tumor and gradual disappearance of the abovementioned signs, she developed female secondary sex characteristics. In proceeding evaluations, unexpectedly true precocious puberty before the age of 8 years was confirmed.


Case Report


A 5 year, 10-month-old girl was admitted with complaints of growing coarse hair on pubis and axilla and appearance of fine black hair on the chest, the symptoms appearing just over one year prior to admission.
Family history: patient's father died from hepatic cancer and her brother also died from probable renal cancer.
Patient's weight and height were more than 90th percentile and 97th percentile for age respectively. Bone age was advanced and at the age of 7, was equivalent to 11 years of age. During physical examina tion, clitoromegaly was observed with no signs of breast devel As shown in Table I, high basal levels of gonadotropins and proportional elevated levels of these hormones after stimulation confirmed true precocious puberty.

Table 1: Results ofLHRH stimulation test

Serum hormone

Basal levels

after LHRH administration

 

 

30min

60min

FSH (lUlL)

7.0

 

9.0

LH (lUlL)

11.0

 


15.0


The patient with the above mentioned diagnosis was treated with LHRH analogs (Decapeptyle). During treatment breast diameter decreased (from 10x9 em to 8.5x8.0 ern) andserum estradiol concentrations declined (from 104 to 5.4 pg/mL) Considering the above mentioned findings true precocious puberty following virilizing adrenal tumor was confirmed and treatment was continued.


Discussion


Adrenal tumors are rare in children. Most of these tumors are virilizing although feminizing tumors have also been described.5,6 In extremely rare cases secondary activation of the hypothalamus - pituitary - adrenal axis following removal of a virilizing adrenal tumor has been reported.i'" Tumors may arise from ectopic adrenal tissues. Adrenocarcinoma in the liver of 3 years old boy has been reported.' It is assumed that reactivation of gonadarche in puberty is caused by:
I) Lack of inhibitory effect of central nervous system, which is independent of sex steroid hormone concentrations9 and 2) Decreased sensitivity of GnRH producing hypothalamic cells to increased concentrations of sex steroids."
It is also believed that long exposure of hypothalamus to androgens is one of the causes of reactivation of hypothalamus for pubertal maturation. 10 It has been suggested that a critical threshold level of body mass and skeletal maturation is required for hypothalamus stimulation and pubertal onset."
As described above in our patient, secondary male sex characteristics appeared in early childhood due to increased androgen secretion from the viril izing adrenal tumor. Following the removal of the tumor, serum androgen concentrations declined with regression of male sex characteristics. Several hypotheses are suggested for the mechanism of true recocious puberty in this case: a) Elevation in androgen concentrations prior to the removal of the tumor results in accelerated bone maturation and as described earlier this condition may cause the initiation of precocious puberty in these patients.
b) Considering the mechanisms mentioned in the physiology of pubertal maturation, it is assumed that long term increase in blood androgen concentrations in prepubertal period in children with virilizing tumors could result in hypothalamic stimulation for GnRH secretion and early pubertal maturation a mechanism similar to the mechanism of the development of true precocious puberty in girls after treatment of congenital adrenal hyperplasia (CAH). 10-12 Since virilizing adrenal tumors have not been included in the etiology of true precocious puberty, it is suggested these tumors be considered as one of the causes of true precocious puberty.

References: (13)

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