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Premature pubarche as a first presentation of pituitary macroprolactinoma
Fatemeh Tabatabaei1, Mohammad Reza Sharif2, Hossein Nasr Esfahani3, Razieh Yazdi Zahrani4, Abolfazl Taheri5, Rokhsareh Meamar4
1 Clinical Research Development Research Centre, Najafabad Branch, Islamic Azad University, Najafabad, Iran
2 Infectious Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran
3 Depatment of Ophthalmology, School of Medicine, Najafabad University, Shariati Hospital, Isfahan, Iran
4 Isfahan Clinical Toxicology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
5 Health Information Technology Research Center, Clinical Information's Research Group, Isfahan University of Medical Sciences, Isfahan, Iran
| Date of Submission | 02-Feb-2020 |
| Date of Decision | 15-Mar-2020 |
| Date of Acceptance | 27-Jul-2020 |
| Date of Web Publication | 26-Nov-2020 |
Correspondence Address:
Dr. Rokhsareh Meamar
Isfahan Clinical Toxicology Research Center, Isfahan University of Medical Sciences, Isfahan
Iran
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jrms.JRMS_118_20
Prolactinoma is a rare tumor of childhood. Clinical presentations of prolactinoma include amenorrhea, delayed puberty, and galactorrhea. For the first time, in this case, elevated prolactin levels were associated with unexpected premature pubarche. We describe an 8-year, 7-month-old boy with acne and gradual appearance of pubic hair, corresponding to tanner stage 2. Hormonal tests showed severe hyperprolactinemia (prolactin = 246.8 μg/L and pooled prolactin = 175 μg/L and macroprolactin = 5 μg/L) and mildly elevated level of dehdroepiandrostenedion sulfate (DHEAS) and testosterone. Magnetic resonance imaging (MRI) findings confirmed the presence of a pituitary macroprolactinoma, measuring 14 mm × 12 mm × 8 mm on the right side of the pituitary gland. Cabergoline therapy was commenced (0.5 mg/week) and after 3 months, no evidence of pubarche progression was observed. Prolactin level and tumor size markedly reduced. At the 9-month follow-up visit, a normal MRI was reported. This case highlights that even when facing premature pubarche, careful examination is mandatory, and if no obvious etiology is found for premature pubarche, clinicians should consider prolactinoma.
Keywords: Adrenarche, child, child/growth and development, dehdroepiandrostenedion sulfate (DHEAS), precocious puberty, prolactinoma, puberty
How to cite this article:
Tabatabaei F, Sharif MR, Nasr Esfahani H, Yazdi Zahrani R, Taheri A, Meamar R. Premature pubarche as a first presentation of pituitary macroprolactinoma. J Res Med Sci 2020;25:108 |
How to cite this URL:
Tabatabaei F, Sharif MR, Nasr Esfahani H, Yazdi Zahrani R, Taheri A, Meamar R. Premature pubarche as a first presentation of pituitary macroprolactinoma. J Res Med Sci [serial online] 2020 [cited 2021 Jan 23];25:108. Available from: https://www.jmsjournal.net/text.asp?2020/25/1/108/301546 |
| Introduction | |  |
Pediatric prolactinoma, a benign pituitary adenoma secreting prolactin, typically occurs at the age when puberty begins.[1],[2] There are no distinctive clinical symptoms, headache is the most prevalent complaint at diagnosis, and a large tumor mass can also present with visual disturbance. Galactorrhea and delayed pubertal development are other symptoms. Incidence rate shows that it is infrequent (<0.1/1000,000 persons),[1] yet it accounts for 50% of all pituitary adenomas and 2% of intracranial tumors.[3],[4]
The term macroprolactinoma is used when the size of these tumors are 1 cm or more.[5],[6]
Most symptoms of these tumors are due to the extreme production of prolactin and problems caused by the compressive effects of the tumor on adjacent neural structures. Macroprolactinoma is diagnosed and managed according to the serum prolactin levels and the appearances of the pituitary gland on magnetic resonance imaging (MRI).[6] The best recommended medical treatment is dopamine agonists.[5]
The majority of tumors are brought to attention clinically during puberty, with females incidence rate 5 times more than males.[6],[7] The most common presentation in girls is primary and secondary amenorrhea. Growth arrest, delayed puberty, and galactorrhea are more encountered in boys.[7],[8] Tütüncüler et al. presented six patients with macroprolactinemia with elevated levels of PRL. One of whom was asymptomatic and the other five either had headache, menstrual disturbance, short stature, increased hair growth, or premature puberty.[8]
The presence and development of the genital/axillary hair before the age of 8 years in girls and 9 years in boys is the most imperative symptom of premature pubarche. However, other symptoms of puberty or virilization did not progress.[9] Early pubertal changes do not necessarily mean precocious puberty. In our case for the first time, elevated PRL levels were accompanied with unexpected premature pubarche.
| Case Report | | |
An 8-year, 7-month-old boy with nonconsanguineous parents was seen in the endocrinology clinic for acne and gradual appearance of the pubic hair during the past 2 months. He had no history of headache, vomiting, convulsion, galactorrhea, or any other past medical or drug history.
On physical examination, his height was 128 cm (on 25% percentile of height) and his weight was 31 kg (on 75% percentile of weight), body mass index was 18.92 kg/m2, axillary hair growth was at tanner stage 1, pubic hair was at tanner stage 2, testes were stage 1 tanner, and volume of both right and left testes was <4 mL.
In laboratory examinations, serum electrolytes (Na, K, Ca, and P) were all normal. Mildly elevated levels of dehdroepiandrostenedion sulfate (DHEAS) and testosterone were detected in accordance with second stage of tanner (DHEAS = 15–97 μg/dl, testosterone = 0.2–0.8 ng/mL). In addition, hyperprolactinemia (prolactin = 246.8 μg/L and pooled prolactin = 175 μg/L and macroprolactin = 5 μg/L) was detected [Table 1].
Pituitary MRI showed a pituitary macroadenoma, measuring 14 mm × 12 mm × 8 mm on the right side of the pituitary gland with thin ring enhancement on postcontrast images, with features consistent with macroprolactinoma [Figure 1]. Extrasellar extension was not present. The visual field examination and examinations of other systems were normal. Wrist X-ray revealed bone age of 9 years. | Figure 1: Brain magnetic resonance imaging, demonstrating a pituitary macroadenoma measuring 14 mm × 12 mm × 8 mm; (a) Coronal; white arrow refers to optic nerve without any pressure effect, black arrow shows adenoma and (b) sagittal planes; white arrow refers to basilar artery and black arrow shows empty sella torsica induced by pressure effects of adenoma
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The patient's parents were informed about his disease and cabergoline therapy (0.5 mg/week) was started for prolactinoma. After 3 months, no evidence of pubarche progression was observed and prolactin and tumor size markedly reduced. Level of serum prolactin reached 30 and 14.8 μg/L, on follow-up of 3 and 9 months later, respectively. In the second MRI report, a 10 mm × 5 mm simple cyst was seen on the right side. However, at the 9th month control visit, normal MRI was reported. The patient is still being followed at our clinic and continues cabergoline therapy.
| Discussion | | |
In this study, we presented an 8-year, 7-month-old boy with premature pubarche with prolactinoma and a little elevated level of DHEA and testosterone in accordance with stage 2 tanner.[10] We excluded any other etiology for pubarche.
The appearance of pubic hair (pubarche) occurs due to stimulation of androgen-sensitive hair follicles. Adrenarche is presented with rising in the adrenal production of the 17-ketosteroids DHEAS and DHEA-sulfate.[11] This can explain premature pubarche for most cases in girls, but in male development, the role of adrenal androgens is less clear.[12]
In the most of the cases in boys, clinical presentation of premature pubarche is not a major clinical issue. Previous reports claim that pubarche should not necessarily present true puberty in a considerable number of boys older than 10 years of age with normal development.[12] Indeed, it seems that in most cases, the presentation of isolated pubarche is to be the consequence of isolated adrenarche.[13] On the other hand, premature adrenarche is associated with adrenal hyperandrogenism[10] and elevation level of DHEAS, which is compatible with our case.
In addition, it has been reported that the prevalence of premature adrenarche is increased in central nervous system abnormalities.[10] Fideleff et al.'s study reported a more frequent occurrence of neuro-ophthalmologic signs and higher incidence of macroadenoma in boys when compared with girls. Some causes could be recognized such as delayed onset of symptoms in males and difference in tumoral biology behavior between two sexes.[14] Most clinical manifestations in males include delayed puberty, gynecomastia, and galactorrhea.[10] On the contrary, the appearance of precocious puberty has been reported.[15],[16] Tütüncüler et al.[8] introduced two cases of macroprolactinemia with increased hair growth or premature puberty. Whereas, we have a patient with premature pubarche. To our knowledge and based on an exhaustive literature search, we claim that this child is the first case of prolactinoma associated with premature pubarche. The atypical finding of premature pubarche development in our patient may be explained by the fact that low levels of prolactin could act as having a stimulatory effect and high levels having an inhibitory effect on male gonads.[17] In addition, there is evidence that prolactin may have a stimulatory effect on Leydig-cell function and secretion of adrenal androgens, especially DHEA and DHEAS.[18] Prolactin and insulin growth factor 1 have also been suggested to be stimulants in the secretion of cortisol.[10] Specific prolactin receptors presence has been confirmed in the adrenal gland.[19] In addition, the direct effect of prolactin on stimulation of adrenal androgen secretion was confirmed by a primary monolayer culture of bovine adrenal cells.[20] The synergistic mechanism of prolactin-ACTH may be a limited inhibition of adrenal 3-beta-hydroxysteroid dehydrogenase, resulting in a noteworthy surge of DHEA-S and DHEA, but not of androstenedione.[20]
With these considerations in mind, early pubertal changes do not necessarily mean precocious puberty. Based on our findings in this case, our suggestion is to include prolactinoma in the differential diagnosis of premature pubarche.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1]
[Table 1]
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