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CASE REPORT
J Res Med Sci 2020,  25:108

Premature pubarche as a first presentation of pituitary macroprolactinoma


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 Submission02-Feb-2020
Date of Decision15-Mar-2020
Date of Acceptance27-Jul-2020
Date of Web Publication26-Nov-2020

Correspondence Address:
Dr. Rokhsareh Meamar
Isfahan Clinical Toxicology Research Center, Isfahan University of Medical Sciences, Isfahan
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrms.JRMS_118_20

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  Abstract 


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 Nov 27];25:108. Available from: https://www.jmsjournal.net/text.asp?2020/25/1/108/301546




  Introduction Top


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 Top


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].
Table 1: The results of the endocrine tests at baseline and follow-up

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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 Top


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.



 
  References Top

1.
Hoffmann A, Adelmann S, Lohle K, Claviez A, Müller HL. Pediatric prolactinoma: Initial presentation, treatment, and long-term prognosis. Eur J Pediatr 2018;177:125-32.  Back to cited text no. 1
    
2.
Acharya SV, Gopal RA, Bandgar TR, Joshi SR, Menon PS, Shah NS. Clinical profile and long term follow up of children and adolescents with prolactinomas. Pituitary 2009;12:186-9.  Back to cited text no. 2
    
3.
Müller HL. Childhood craniopharyngioma. Pituitary 2013;16:56-67.  Back to cited text no. 3
    
4.
Fideleff HL, Boquete HR, Suárez MG, Azaretzky M. Prolactinoma in children and adolescents. Horm Res 2009;72:197-205.  Back to cited text no. 4
    
5.
Guaraldi F, Storr HL, Ghizzoni L, Ghigo E, Savage MO. Paediatric pituitary adenomas: A decade of change. Horm Res Paediatr 2014;81:145-55.  Back to cited text no. 5
    
6.
Iglesias P, Díez JJ. Macroprolactinoma: A diagnostic and therapeutic update. QJM 2013;106:495-504.  Back to cited text no. 6
    
7.
Perry A, Graffeo CS, Marcellino C, Pollock BE, Wetjen NM, Meyer FB. Pediatric pituitary adenoma: Case series, review of the literature, and a skull base treatment paradigm. J Neurol Surg B Skull Base 2018;79:91-114.  Back to cited text no. 7
    
8.
Tütüncüler F, Darendeliler F, Aygün M, Hekim N. Macroprolactinemia in childhood and adolescence: A cause of hyperprolactinemia. Turk J Pediatr 2006;48:143-7.  Back to cited text no. 8
    
9.
Utriainen P, Laakso S, Liimatta J, Jääskeläinen J, Voutilainen R. Premature adrenarche—a common condition with variable presentation. Horm Res Paediatr 2015;83:221-31.  Back to cited text no. 9
    
10.
Melmed S, Macp M, Koenig R, Rosen C, Auchus R, Goldfine A. Williams Textbook of Endocrinology E-Book. Elsevier Health Sciences: Elsevier; 2020.  Back to cited text no. 10
    
11.
Rege J, Rainey WE. The steroid metabolome of adrenarche. J Endocrinol 2012;214:133-43.  Back to cited text no. 11
    
12.
Rosenfield RL, Rich BH, Lucky AW. Adrenarche as a cause of benign pseudopuberty in boys. J Pediatr 1982;101:1005-9.  Back to cited text no. 12
    
13.
Ibáñez L, Dimartino-Nardi J, Potau N, Saenger P. Premature adrenarche-normal variant or forerunner of adult disease? Endocr Rev 2000;21:671-96.  Back to cited text no. 13
    
14.
Fideleff HL, Boquete HR, Sequera A, Suárez M, Sobrado P, Giaccio A. Peripubertal prolactinomas: Clinical presentation and long-term outcome with different therapeutic approaches. J Pediatr Endocrinol Metab 2000;13:261-7.  Back to cited text no. 14
    
15.
Slonim AE, Glick AD, Island DP, Kasselberg AG. Hyperprolactinemia associated with advanced puberty in a male. J Pediatr 1982;101:236-9.  Back to cited text no. 15
    
16.
Ambrosi B, Bassetti M, Ferrario R, Medri G, Giannattasio G, Faglia G. Precocious puberty in a boy with a PRL-, LH- and FSH-secreting pituitary tumour: Hormonal and immunocytochemical studies. Acta Endocrinol (Copenh) 1990;122:569-76.  Back to cited text no. 16
    
17.
Ambrosi B, Travaglini P, Beck-Peccoz P, Bara R, Elli R, Paracchi A, et al. Effect of sulpiride-induced hyperprolactinemia on serum testosterone response to HCG in normal men. J Clin Endocrinol Metab 1976;43:700-3.  Back to cited text no. 17
    
18.
Lobo RA, Kletzky OA, Kaptein EM, Goebelsmann U. Prolactin modulation of dehydroepiandrosterone sulfate secretion. Am J Obstet Gynecol 1980;138:632-6.  Back to cited text no. 18
    
19.
Posner BI, Kelly PA, Shiu RP, Friesen HG. Studies of insulin, growth hormone and prolactin binding: Tissue distribution, species variation and characterization. Endocrinology 1974;95:521-31.  Back to cited text no. 19
    
20.
Higuchi K, Nawata H, Kato K, Ibayashi H. Ovine prolactin potentiates the action of adrenocorticotropic hormone on the secretion of dehydroepiandrosterone sulfate and dehydroepiandrosterone from cultured bovine adrenal cells. Horm Metab Res 1985;17:451-3.  Back to cited text no. 20
    


    Figures

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    Tables

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This article has been cited by
1 Delayed pubarche
Francesco Baldo,Egidio Barbi,Gianluca Tornese
Italian Journal of Pediatrics. 2021; 47(1)
[Pubmed] | [DOI]



 

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