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TYPE
Original Research
PAGE NO.
48-54
10.37547/tajmspr/Volume07Issue06-05
OPEN ACCESS
SUBMITED
17 April 2025
ACCEPTED
24 May 2025
PUBLISHED
24 June 2025
VOLUME
Vol.07 Issue 06 2025
CITATION
Laiba Razaq, Muhammad Saqib Mian, Muhammad Faizan, Muhammad
Arsalaan Awais, Syed Shayan Gilani, Rizwan Uppal, Muhammad Rehan
Uppal, Umar Saeed, Zahra Zahid Piracha, & Muhammad Nouman Tariq
Nouman Tariq. (2025). Precocious Puberty Induced by Chronic
Rhinosinusitis. The American Journal of Medical Sciences and
Pharmaceutical Research, 7(06), 48
–
54.
https://doi.org/10.37547/tajmspr/Volume07Issue06-05
COPYRIGHT
© 2025 Original content from this work may be used under the terms
of the creative commons attributes 4.0 License.
Precocious Puberty
Induced by Chronic
Rhinosinusitis
Laiba Razaq
International Centre of Medical Sciences Research (ICMSR),
Islamabad PAKISTAN.
Akhtar Saeed Medical and Dental College, Lahore PAKISTAN
Muhammad Saqib Mian
Akhtar Saeed Medical and Dental College, Lahore PAKISTAN
Muhammad Faizan
International Centre of Medical Sciences Research (ICMSR),
Islamabad PAKISTAN.
Muhammad Arsalaan Awais
International Centre of Medical Sciences Research (ICMSR),
Islamabad PAKISTAN.
Atlanticare Regional Medical Center, Pomona, New Jersey, USA
Omar Hospital & Cardiac Centre Johar Town, Lahore PAKISTAN
Syed Shayan Gilani
International Centre of Medical Sciences Research (ICMSR),
Islamabad PAKISTAN.
Omar Hospital & Cardiac Centre Johar Town, Lahore PAKISTAN
Sheikh Zayed Hospital Lahore PAKISTAN
Rizwan Uppal
Islamabad Diagnostic Center (IDC), F8 Markaz, Islamabad
PAKISTAN
Muhammad Rehan Uppal
Islamabad Diagnostic Center (IDC), F8 Markaz, Islamabad
PAKISTAN
Umar Saeed
Foundation University Islamabad (FUI), Islamabad PAKISTAN
Zahra Zahid Piracha
International Centre of Medical Sciences Research (ICMSR),
Islamabad PAKISTAN.
International Center of Medical Sciences Research (ICMSR),
Austin, TX, United States of America
International Center of Medical Sciences Research (ICMSR),
Chadwell Heath, United Kingdom
Acknowledgement:
Muhammad Nouman Tariq
Akhtar Saeed trust hospital
Abstract: Background:
Precocious puberty is the early
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onset of secondary sexual characteristics before age 8 in
girls and 9 in boys. It is classified into central precocious
puberty (CPP), which is GnRH-dependent, and
peripheral precocious puberty (PPP), which is GnRH-
independent. Hypothalamic hamartomas are a well-
documented cause of CPP, while chronic rhinosinusitis
has not been commonly associated with early puberty.
Case Presentation:
We report a 6.5-year-old boy who
presented with increased penile length, deepened
voice, and axillary and pubic hair growth for six months.
Additionally, he had a history of nasal obstruction,
rhinorrhea, blurred vision, and mild headaches.
Examination revealed signs of precocious puberty,
including Tanner stage III pubic and axillary hair and an
advanced bone age of 12 years. MRI revealed a
hypothalamic hamartoma, while a CT scan showed
chronic rhinosinusitis. Histopathology confirmed
chronic inflammatory changes without fungal infection.
The patient was initially considered for neurosurgical
intervention, but after ENT evaluation, he was treated
with intravenous antibiotics for chronic sinusitis. He
showed clinical improvement, and surgery was no
longer required.
Discussion
:
This case highlights a rare association
between chronic rhinosinusitis and CPP. While
hypothalamic hamartoma is a recognized cause of early
puberty, chronic inflammation might contribute to HPG
axis activation. Persistent sinonasal inflammation could
induce systemic inflammatory responses affecting
neuroendocrine regulation. This raises questions about
the potential role of chronic infections in puberty onset.
Conclusion:
Chronic rhinosinusitis may be an
underrecognized factor influencing early puberty.
Multidisciplinary evaluation, including endocrinology,
neurosurgery, and ENT, is crucial in such cases to ensure
accurate diagnosis and management. Further research is
needed to explore the possible link between chronic
inflammation and hypothalamic activation leading to
precocious puberty.
Keywords:
Precocious puberty, chronic rhinosinusitis,
hypothalamic hamartoma, invasive sinusitis
INTRODUCTION
Precocious puberty is defined as the early onset of
puberty and secondary sexual characteristics before the
age of 8 in girls and 9 in boys, with an estimated
incidence of 1:5,000 to 1:10,000 children. The female-
to-male ratio is approximately 10:1 (1).
Based on etiology, precocious puberty is classified into
two major types:
1.
Central Precocious Puberty (CPP)
–
GnRH-
dependent
2.
Peripheral Precocious Puberty (PPP)
–
GnRH-
independent
CPP results from early activation of the hypothalamic-
pituitary-gonadal (HPG) axis, commonly caused by CNS
tumors such as hypothalamic hamartoma, optic glioma,
and astrocytoma. Among these, hypothalamic
hamartoma is the most frequent cause (3). Other
contributing factors include CNS injury, cerebral palsy,
tuberculosis, neurofibromatosis type 1, and genetic
mutations, particularly loss-of-function mutations in the
MKRN3 gene (2). The activation of the HPG axis leads to
the development of secondary sexual characteristics,
accelerated growth, and behavioral changes due to
pulsatile GnRH secretion (6). Kisspeptin, a critical
regulatory peptide, influences GnRH production through
interactions with neurokinin B and dynorphin in the
hypothalamus (7).
PPP, on the other hand, results from increased secretion
of sex steroid hormones (androgens, estrogens, and
progestogens) independent of GnRH stimulation.
Conditions such as congenital adrenal hyperplasia
(CAH), McCune-Albright syndrome, and gonadal or
adrenal tumors are common causes. Clinical features
include breast enlargement and early menarche
(thelarche), accelerated growth (total height increase of
20
–
25 cm from the onset to completion of puberty),
pubic and axillary hair growth, acne, adult div odor,
deepened voice, and facial hair in boys (7). Neurological
symptoms such as headaches, increased head
circumference, seizures, and visual or cognitive changes
may also occur.
Diagnostic evaluation includes bone age assessment,
BMI measurement, serum LH, FSH, TFTs, and
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testosterone levels. In PPP, pelvic ultrasonography is
recommended for girls to detect ovarian cysts, and
testicular ultrasonography for boys. MRI is essential in
all cases of CPP to rule out hypothalamic lesions (5).
The primary goal of CPP treatment is to preserve adult
height and alleviate psychological distress. GnRH
agonists, available in intranasal, subcutaneous, and
intramuscular forms, are the treatment of choice (8). In
the United States, depot leuprolide acetate is the most
commonly used option, effectively suppressing the
GnRH axis (5). Treatment for PPP focuses on eliminating
the source of sex steroids
—
CAH is managed with
glucocorticoids, while McCune-Albright syndrome
benefits from aromatase inhibitors such as anastrozole
or tamoxifen. Early initiation of treatment improves
outcomes, but long-term endocrine, metabolic,
reproductive, and psychological consequences remain
uncertain (4).
Case Report
A 6.5-year-old boy presented to the outpatient
department of Farooq Hospital, Lahore, with a six-
month history of increased penile length, deepened
voice, and axillary and pubic hair growth. His parents
also
reported
intermittent
nasal
obstruction,
rhinorrhea, and blurred vision. The child occasionally
experienced mild headaches, primarily during episodes
of flu. There was no history of radiation therapy, trauma,
polyuria, fever, gelastic seizures, cachexia, or
medication use. The parents had a normal pubertal
history.
Physical Examination
The child appeared thin and moody, measuring 112 cm
in height and weighing 25 kg. He exhibited grade III pubic
and axillary hair growth, with normal neurological
findings. Testicular volume was 8
–
10 mL, and stretched
penile length was 7 cm. The abdomen was soft and non-
tender with no palpable masses. While there were no
visual field defects, his visual acuity was reduced.
Fundoscopy showed no evidence of papilledema. No
café-au-lait spots, rashes, or pigmentation were
observed.
Laboratory and Imaging Findings
•
Hormonal analysis: Elevated FSH, LH, and
testosterone within the upper normal range
•
Renal function tests: Normal, excluding
aldosterone deficiency
•
Thyroid function tests: Normal, ruling out
hypothyroidism
•
Bone age assessment (X-ray wrist): Advanced
bone age of approximately 12 years, showing
complete ossification of carpal bones, including
the pisiform, with an enlarged distal ulna and
radius epiphysis (Figure 1)
•
Ultrasound of the abdomen, pelvis, and testes:
No abnormalities detected
MRI
Brain
with
Contrast
(Figure
2):
A well-defined, midline rounded lesion was identified in
the hypothalamic region, projecting inferiorly behind
the infundibulum of the pituitary gland, measuring 11.7
× 9 × 8.3 mm (TR × AP × CC). The lesion demonstrated
iso-signal intensity on T1-weighted images and
heterogeneous high-signal intensity on T2-weighted and
FLAIR images, with mild post-contrast enhancement,
suggestive of a hypothalamic hamartoma. Other brain
structures, including parenchyma, ventricular system,
and extra-axial CSF spaces, were normal. However, fluid
signals were observed in all sinuses and bilateral
mastoid air cells.
Given the radiological diagnosis of hypothalamic
hamartoma
—
a benign mass consisting of disorganized
neurons and glial cells that may function as an accessory
GnRH pulse generator
—
the patient was referred to a
pediatric neurosurgeon. Surgical intervention was
initially considered; however, an ENT consultation was
sought to rule out fungal or invasive sinusitis before
proceeding.
Further Evaluation and Diagnosis
Unenhanced CT Paranasal Sinuses (Figure 3):
The FESS protocol CT scan showed polypoid mucosal
thickening and soft tissue opacification of nearly all
sinuses (maxillary, ethmoid, and sphenoid bilaterally).
There was partial opacification of bilateral mastoid air
cells, more pronounced on the right side, suggestive of
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mastoiditis.
Endoscopic
Nasal
Biopsy
and
Histopathology:
Biopsy from both nasal cavities revealed polypoidal
masses covered by benign columnar epithelium with
severe chronic inflammation, predominantly involving
mononuclear eosinophils. No fungal elements,
granulomas, dysplasia, or malignant cells were
observed.
Treatment and Outcome
With a confirmed diagnosis of chronic sinusitis, the
patient was started on:
•
Injection Co-amoxiclav 750 mg IV TDS for 4
weeks
•
Injection Ceftazidime 750 mg IV BD for 4 weeks
The patient showed significant improvement with
antibiotics, negating the need for surgery.
DISCUSSION
Hypothalamic Hamartoma and Central Precocious
Puberty (CPP)
The patient's clinical presentation, characterized by a
deepened voice, increased penile length, and the
development of axillary and pubic hair, strongly
suggested central precocious puberty (CPP). The MRI
findings confirmed the presence of a hypothalamic
hamartoma, a well-documented cause of CPP (10).
Hypothalamic hamartomas are benign congenital
lesions composed of disorganized neurons and glial cells
that can function as ectopic GnRH pulse generators. This
results in the premature activation of the hypothalamic-
pituitary-gonadal (HPG) axis, triggering early puberty
(11).
Association with Chronic Rhinosinusitis
This case is unique due to the simultaneous diagnosis of
chronic rhinosinusitis alongside CPP. The patient
exhibited persistent nasal obstruction, rhinorrhea,
intermittent headaches, and blurred vision, all of which
suggested underlying chronic sinus inflammation. CT
and histopathology confirmed chronic rhinosinusitis,
which had not been previously associated with CPP in
medical literature. While hypothalamic lesions are a
well-known trigger for GnRH secretion and CPP, the
potential contribution of chronic sinus inflammation to
this process is less understood.
Inflammatory Factors and Endocrine Activation
Chronic rhinosinusitis is characterized by persistent
mucosal inflammation, with tissue histology revealing
severe
eosinophilic
infiltration.
The
prolonged
inflammatory state could have influenced the
neuroendocrine axis, potentially contributing to the
early activation of GnRH-secreting neurons (12).
Inflammatory mediators such as IL-6, TNF-
α, and
prostaglandins are known to impact the HPG axis,
potentially leading to premature puberty (12,14).
However, the exact mechanism linking chronic sinus
inflammation and early puberty remains speculative,
and further studies are needed.
Management and Handling
Initially, neurosurgical resection of the hypothalamic
hamartoma was considered as the primary treatment
option. However, given the unexpected MRI findings of
extensive sinus inflammation, consultation with an ENT
specialist was prioritized to rule out fungal or invasive
sinusitis before proceeding with surgery. Further
workup confirmed chronic bacterial sinusitis, leading to
a shift in management toward aggressive antibiotic
therapy with Co-amoxiclav and Ceftazidime for four
weeks. Remarkably, the patient responded well to
medical therapy alone, eliminating the need for
immediate surgery. This highlights the importance of a
multidisciplinary approach in managing atypical
presentations of CPP (13).
Clinical Practice Implications
This case underscores the importance of considering
chronic
inflammatory
conditions
as
potential
contributors to endocrine dysfunction. It also reinforces
the necessity of a multidisciplinary approach when
dealing with complex cases of precocious puberty.
Pediatric endocrinologists, neurosurgeons, and ENT
specialists must collaborate to ensure a thorough
diagnostic evaluation and an optimal, individualized
treatment plan.
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Limitations and Future Research
While this case presents a compelling clinical
association, it does not establish a definitive causal link
between chronic sinus inflammation and CPP. Future
research should explore the potential mechanisms by
which chronic inflammation affects GnRH secretion.
Long-term follow-up studies on patients with chronic
sinusitis and endocrine abnormalities may provide
valuable insights into whether persistent inflammatory
states influence pubertal timing (14).
CONCLUSION
This case highlights a novel association between chronic
rhinosinusitis and precocious puberty, emphasizing the
importance of considering underlying inflammatory
conditions when evaluating early-onset puberty. The
successful resolution of symptoms with antibiotic
therapy suggests that chronic inflammation may play a
role in endocrine dysregulation. Further studies are
needed to explore the connection between persistent
inflammation and early HPG axis activation. This case
also stresses the importance of an interdisciplinary
approach when managing atypical presentations of
precocious puberty.
Consent
The patient's express written permission to publish this
case report and the related photographs were acquired.
The Editor-in-Chief of this journal can examine a copy of
the written consent upon request.
REFERENCES
Partsch CJ, Sippell WG. Pathogenesis and epidemiology
of precocious puberty. Effects of exogenous
oestrogens. Hum Reprod Update. 2001 May-
Jun;7(3):292-302.
doi:
10.1093/humupd/7.3.292.
PMID: 11392376.
Abreu AP, Macedo DB, Brito VN, Kaiser UB, Latronico
AC. A new pathway in the control of the initiation of
puberty: the MKRN3 gene. Journal of molecular
endocrinology. 2015 Jun 1;54(3):R131-9.
Harrison VS, Oatman O, Kerrigan JF. Hypothalamic
hamartoma with epilepsy: Review of endocrine
comorbidity. Epilepsia. 2017 Jun;58:50-9.
Fuqua JS. Treatment and outcomes of precocious
puberty: an update. J Clin Endocrinol Metab. 2013
Jun;98(6):2198-207. doi: 10.1210/jc.2013-1024. Epub
2013 Mar 20. PMID: 23515450.
Lee PA, Klein K, Mauras N, Neely EK, Bloch CA, Larsen
L, Mattia-Goldberg C, Chwalisz K. Efficacy and safety of
leuprolide acetate 3-month depot 11.25 milligrams or
30 milligrams for the treatment of central precocious
puberty. The Journal of Clinical Endocrinology. 2012
Feb 16;97(5):1572-80.
Maione L, Bouvattier C, Kaiser UB. Central precocious
puberty: Recent advances in understanding the
aetiology and in the clinical approach. Clin Endocrinol
(Oxf).
2021
Oct;95(4):542-555.
doi:
10.1111/cen.14475. Epub 2021 Apr 20. PMID:
33797780; PMCID: PMC8586890.
Soriano-Guillén L, Argente J. Central precocious
puberty, functional and tumor-related. Best Pract Res
Clin Endocrinol Metab. 2019 Jun;33(3):101262. doi:
10.1016/j.beem.2019.01.003. Epub 2019 Jan 22.
PMID: 30733078.
Bereket A. A Critical Appraisal of the Effect of
Gonadotropin-Releasing Hormon Analog Treatment
on Adult Height of Girls with Central Precocious
Puberty. J Clin Res Pediatr Endocrinol. 2017 Dec
30;9(Suppl 2):33-48. doi: 10.4274/jcrpe.2017.S004.
Epub 2017 Dec 27. PMID: 29280737; PMCID:
PMC5790330.
Lee PA, Houk CP, Ahmed SF, Hughes IA, participants in
the International Consensus Conference on Intersex
organized by the Lawson Wilkins Pediatric Endocrine
Society and the European Society for Paediatric
Endocrinology. Consensus statement on management
of intersex disorders. Pediatrics. 2006 Aug
1;118(2):e488-500.
Abreu AP, Dauber A, Macedo DB, Noel SD, Brito VN,
Gill JC, Cukier P, Thompson IR, Navarro VM, Gagliardi
PC, Rodrigues T. Central precocious puberty caused by
mutations in the imprinted gene MKRN3. New England
Journal of Medicine. 2013 Jun 27;368(26):2467-75.
The American Journal of Medical Sciences and Pharmaceutical Research
53
https://www.theamericanjournals.com/index.php/tajmspr
The American Journal of Medical Sciences and Pharmaceutical Research
Batsakis JG, Regezi JA. The pathology of head and neck
tumors: Salivary glands, part 1. Head & Neck Surgery.
1978 Sep;1(1):59
–
68.
Schaefer F, Stanhope R, Scheil H, Schönberg D, Preece
MA, Schärer K. Pulsatile gonadotropin secretion in
pubertal children with chronic renal failure. European
Journal of Endocrinology. 1989 Jan 1;120(1):14-9.
Carel JC, Eugster EA, Rogol A, Ghizzoni L, Palmert MR,
members of the ESPE-LWPES GnRH Analogs Consensus
Conference Group. Consensus statement on the use of
gonadotropin-releasing hormone analogs in children.
Pediatrics. 2009 Apr 1;123(4):e752-62.
Marshall WA, Tanner JM. Variations in the pattern of
pubertal changes in boys. Archives of disease in
childhood. 1970 Feb 1;45(239):13-23.
Figure 1
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Figure 2
Figure 3
