9 year-old Boy with Precocious Puberty. Katie O Sullivan, M.D. Fellow, Med/Peds Endocrinology University of Chicago Thursday, September 12 th, 2013
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1 9 year-old Boy with Precocious Puberty Katie O Sullivan, M.D. Fellow, Med/Peds Endocrinology University of Chicago Thursday, September 12 th, 2013
2 Chief Complaint 9 year and 2 month-old boy who presents with pubertal changes since 8 years 0 months of age This is a second opinion.
3 History of Present Illness 8 yrs: Patient developed pubic hair 8 yrs 6 mos: Parents noted penile enlargement 8 yrs 10 mos: Deepening of voice is noted -> Pediatrician Visit: Physical Exam: No acne, facial hair, axillary hair or body odor Tanner 3 pubic hair Accelerated linear growth
4 More History Birth History: Mother received routine prenatal care Uncomplicated pregnancy and delivery Full-term Birth Weight 8 lbs, 4 oz (AGA) Past Medical/Surgical History: None Developmental History: No delayed milestones Medications: None No herbs/supplements No exogenous steroid exposure No lavender/tea-tree oil Allergies: None Immunizations: Up-To-Date
5 Social History: Entering 4th grade this fall, good student Hobbies: Excels in gymnastics and karate Lives with Mother, Father, brother (10y) and sister (2y) Mother is an obstetrics nurse, Father is a paramedic Family History: No family history of precocious puberty. Mother with menarche at 12 years old. Father started shaving after high school. Great-great grandparents with DM. Grandparents with CAD.
6 Review of Systems Constitutional: Negative for fever, diaphoresis. +increased appetite, +weight gain, +fatigue. HENT: Negative for congestion, rhinorrhea, sore throat, neck swelling or difficulty swallowing. +deepening of voice. Eyes: Negative for visual disturbance. Respiratory: Negative for cough or shortness of breath. Cardiovascular: Negative for palpitations or chest pain. Gastrointestinal: Negative for abdominal pain, nausea, vomiting, diarrhea. +intermittent constipation.
7 Review of Systems Continued Genitourinary: Negative for urgency, frequency and enuresis. +enlarged phallus. +pubic hair. Musculoskeletal: Negative for arthralgias, edema. Skin: Negative for acne, rash. +dry skin. Neurological: Negative for headaches. +intermittent light-headedness with gymnastics. Psychiatric/Behavioral: Negative for behavioral problems. +some anxiety, +nail-biter
8 Physical Exam Vitals: T 35.8C, P 72, BP 85/50 Weight: 35.7 kg (85.1%) Length: cm (67.5%) BMI 18.9 kg/m2 (85.6%)
9 Growth Chart: Length for Age Height Age 10 yo
10 Growth Chart: Weight for Age
11 Growth Velocity
12 Constitutional: Appears well-developed and well-nourished. Active. No distress. Head/Face: No dysmorphic features. No facial hair. No acne. Mouth/Throat: Mucous membranes are moist. Dentition is normal. Oropharynx is clear. Eyes: Conjunctivae and EOM are normal. Pupils are equal, round, and reactive to light. Neck: Neck supple. No adenopathy. No thyromegaly. Cardiovascular: Normal rate and regular rhythm. Pulses are strong. No murmur heard. Pulmonary/Chest: Effort normal. There is normal air entry. No wheezes. Minimal breast tissue. No provoked discharge from nipples.
13 Axilla: Tanner 2 axillary hair. Abdominal: Soft, no distension. No hepatosplenomegaly. No masses. No tenderness. Normal bowel sounds, Genitourinary: Tanner 3 pubic hair. circumcised adult-appearing phallus, pigmented scrotum, testes descended bilaterally, left 4 cm and right 4.5 cm in long diameter (Tanner 4 genitalia). No testicular masses. Musculoskeletal: Normal range of motion. There is no edema and no tenderness. Neurological: Exhibits normal muscle tone. No motor weakness. 2+ Patellar DTRs. No tremor on outstretched hands. Balance and gait in tact. Coordination in tact. Skin: Skin is warm. No acanthosis nigricans. +eczematous skin. +hypo-pigmented patches on face.
14 Initial Assessment and Work-Up
15 Precocious Puberty Definition: Premature beginning of sexual characteristics before 9 years in boys and before 8 years in girls 1 (age still debated) 2 Prevalence 3 : Girls: 0.2% Boys: <0.05% 1. Rosenfield and Ghai. Disorders of Pubertal Development Walvoord EC. Journal of Adolescent Health Teilmann G et al. Pediatrics
16 Differential Diagnosis of Precocious Puberty Central Precocious Puberty premature reactivation of the GnRH pulse generation and the pituitary-gonadotropin axis = GnRH-dependent GnRH-Independent Puberty Increase in sex steroids outside of the HPG axis Isosexual vs. contrasexual
17 Central Precocious Puberty Idiopathic Neurogenic Etiology: CNS Disorders Chronic exposure to sex steroids Kisspeptin/Kisspeptin receptor gain-offunction mutation Lifshitz. Pediatric Endocrinology. 2007
18 Bone Age Chronologic Age: 9 years and 1 months > Bone Age ~ 12 years and 6 months old > Beyond 2 standard deviations from mean for a patient with chronologic age 9 years
19 Laboratory Studies at 9 yrs 0 mos LH FSH Value 4.9 IU/L 6.2 IU/L Range T II: ; T III: Tanner IV-V: T II: ; T III: Tanner IV-V: Total Testosterone 640 ng/dl Tanner IV: ng/dl Tanner V: mgdl SHBG 52 nmol/l nmol/l Free Testosterone 96 pg/ml Tanner IV: ng/dl Tanner V: ng/dl DHEA 17-OH Progesterone ng/ml 63 ng/dl T II: ng/ml; T III: ng/ml; T IV-V: ng/ml Male 7-9yr: <63 ng/dl Male 10-12yr: <79 ng/dl Male 13-15yr: ng/dl
20 What Study Would you Like Next?
21 MRI Brain: Sagittal Imaging
22 MRI Brain: T2 Axial Imaging 12.5 x 7.8 x 10.6 cm
23 Summary 9 yr 2 mo boy with central precocious puberty due to suprasellar arachnoid cyst. Evaluated by ophthalmology Has normal vision, including peripheral fields, and normal optic discs Evaluated by 3 neurosurgeons Consensus: No surgical intervention at this time Pituitary hormones were evaluated and determined to be normal Initiated Lupron
24 Clinical Questions 1. What are the most common causes of central precocious puberty in boys? 2. What is the mechanism of precocious puberty in patients with large arachnoid cysts? 3. What is the appropriate treatment of patients with large arachnoid cysts presenting with precocious puberty?
25 Distribution of Diagnoses of Patients with Central Precocious Puberty Pescovitz et al. Journal of Pediatrics
26 Arachnoid Cyst Abnormality of the arachnoid membrane caused by accumulation of CSF Typically congenital, but not always Rare, account for only 1% of intracranial mass lesions Sellar/Suprasellar Cysts 9-15% of all Arachnoid Cysts Wide range of endocrine dysfunction 33% present with CPP Chung et al. RadioGraphics Huang et al. Pediatric Neurology Mohn et al. Pediatric Neurosurgery
27 Exact Mechanism of CPP is Unknown Endocrinopathies correlate with proximity of the cyst to the H-P area Proposed Mechanisms: 1. Disruption of the neural pathway that normally inhibits the GnRH pulse generator Direct physical compression of portions of H-P axis Pressure effects on the pressure-sensitive hypothalamus 2. Direct release of hormones into the pituitary portal circulation Adan et al. European Journal of Pediatrics Chung et al. RadioGraphics
28 Management: Medical vs. Surgical GnRH Agonist successfully halts pubertal development in this patient population Surgical Management is controversial for arachnoid cysts, in general Complication Rate 15-58% Recurrence Rate 15-30% Outcomes after surgical management for CPP is mixed: At least 6 Case Reports suggest cessation of puberty after surgery 10-40% endocrine disorders persist despite surgery Boutarbouch et al. Clinical Neurology and Neurosurgery Ozek MO and Urgun K. World Neurosurgery
29 Works Cited 1. Boutarbouch et al. Management of intracranial arachnoid cysts: institutional experience with intial 32 cases and review of the literature. Clinical Neurology and Neurosurgery (1): Chung et al. From the Radiologic Pathology Archives: Precocious Puberty: Radiologic-Pathologic Correlation. RadioGraphics : Gangemi et al. Suprasellar arachnoid cysts: endoscopy versus microsurgical cyst excision and shunting. British Journal of Neurosurgery. 207; 21(3): Guzel et al. Suprasellar Arachnoid Cyst: A 20-year Follow-Up after Stereotactic Internal Drainage: Case Report and Review of the Literature. Turkish Neurosurgery (3): Huang et al. Arachnoid Cyst with Gn-RH-dependent sexual precocity and growth hormone deficiency. Pediatric Neurology (30)2: Lifshitz. Puberty and its Disorders. Pediatric Endocrinology, 5 th Edition. Informa Healthcare INC. New York, NY. 2007, p Mohn et al. The Endocrine Spectrum of Arachnoid Cysts in Childhood. Pediatric Neurosurgery : Ozek MO and Urgun K. Neuroendoscopic Management of Suprasellar Arachnoid Cysts. World Neurosurgery (2S):S19.13-S19.e Pescovitz et al. The NIH Experience with precocious puberty: Diagnostic subgroups and response to short-term luteinizing hormone releasing hormone analogue therapy Journal of Pediatrics. 108(1): Rosenfield and Ghai. Disorders of Pubertal Development: Too Early, Too Much, Too Late, or Too Little. Adolescent Medicine: State of the Art Reviews Hanley & Belfus, INC. Philadelphia, PA. 1994, p Teilmann G et al. Prevalence and incidence of precocious pubertal development in Denmark: an epidemiologic study based on national registries. Pediatrics : Walvoord EC. The Timing of Puberty: is it changing? Does it matter? Journal of Adolescent Health. 47:
30 Case Report year-old female with precocious puberty 35 x 25 mm suprasellar arachnoid cyst s/p cystoventriculography Breast tissue disappeared in 1 year Guzel et al. Turkish Neurosurgery
31 Additional Laboratory Studies Value Range Cortisol* 2.7 mcg/dl 3-23 Prolactin 10.8 ng/ml IGF-1 IGFBP ng/ml 3690 ng/ml Tanner I: Tanner II, III: Tanner IV, V: Tanner I: Tanner II: Tanner III: Tanner IV, V: obtained at 5:30pm from ARUP Laboratories
32 Additional Laboratory Studies Calcium
33 Mohn et al. Pediatric Neurosurgery
34 CNS lesions causing CPP and more
35 Mohn et al. Pediatric Neurosurgery
36
37 CNS Disorders Acquired: Abscess/Encephalitis/Meningitis Inflammation Chemo/Radiation Surgical/Trauma Congenital anomalies: Hypothalamic harmartoma Arachnoid cysts Hydrocephalus SOD Suprasellar cyst Myelomeningocele Tuberous Sclerosis CNS Tumors: Craniopharyngiomas Astrocytomas Pinealomas Ependymomas Gliomas Optic-Pathway (NF-1) LH-secreting adenoma
Childhood. Unknown. Minimal gonadotrophin stimulation. Signal that dampens GNRH stimulation? Signal that dampens GNRH stimulation?
Normal Pubertal Development Childhood Minimal gonadotrophin stimulation Due to dampening of GNRH stimulation Signal that dampens GNRH stimulation? Signal that dampens GNRH stimulation? Unknown Any interference
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