Double-Crossed!

A Case of Craniopharyngioma
Grand Rounds Presentation

January 28, 2021

PRESENTER: Dr. Patrick Balamiento REACTORS:

Dr. Wilson Cua
Dr. John Mark Carabeo
MODERATOR: Dr. Joanna Biag
Opening Prayer
INTRODUCTION
INTRODUCTION
INTRODUCTION
 OBJECTIVES

• To present a case of craniopharyngioma.

• To discuss how craniopharyngioma leads to various
neuroendocrine complications
• To discuss how neuroendocrine complications were anticipated,
diagnosed, and managed.
• To discuss the general epidemiology, pathophysiology, clinical
manifestations, diagnosis and management, and prognosis of a
patient with craniopharyngioma.
GENERAL DATA
SM
• 13 years old
• Female
• Filipino, Roman Catholic
• from Rodriguez
• Father, self: good reliability
BLURRY VISION
for 2 years
Chief complaint
 HISTORY OF PRESENT ILLNESS

Interim 4 days prior to consult

• Recurrent headache • headache 7/10- 10/10, still intermittent.

• progressive blurring of vision • Double vision; postprandial vomiting

• Unquantified weight gain • Worse early in the morning, often waking patient up
• No fever, no stiff neck, no rash, no cough, or coryza.

2 YEARS PRIOR 1 year prior to consult On the day

• blurring of vision • Seen at NCH ophthalmology ophthalmology clinic:

• frontal non-throbbing • Treated as error of refraction, given papilledema
headache graded 3/10 which corrective lenses, with improvement referred to the neurology clinic.
spontaneously resolves after in symptoms
several hours
 HISTORY OF PRESENT ILLNESS

Interim 4 days prior to consult

• Recurrent headache • headache 7/10- 10/10, still intermittent.

• progressive blurring of vision • Double vision; postprandial vomiting

• Unquantified weight gain • Worse early in the morning, often waking patient up
• No fever, no stiff neck, no rash, no cough, or coryza.

2 YEARS PRIOR 1 year prior to consult On the day

• blurring of vision • Seen at NCH ophthalmology ophthalmology clinic:

• frontal non-throbbing • Treated as error of refraction, given papilledema
headache graded 3/10 which corrective lenses, with improvement referred to the neurology clinic.
spontaneously resolves after in symptoms
several hours
 HISTORY OF PRESENT ILLNESS

Interim 4 days prior to consult

• Recurrent headache • headache 7/10- 10/10, still intermittent.

• progressive blurring of vision • Double vision; postprandial vomiting

• Unquantified weight gain • Worse early in the morning, often waking patient up
• No fever, no stiff neck, no rash, no cough, or coryza.

2 YEARS PRIOR 1 year prior to consult On the day

• blurring of vision • Seen at NCH ophthalmology ophthalmology clinic:

• frontal non-throbbing • Treated as error of refraction, given papilledema
headache graded 3/10 which corrective lenses, with improvement referred to the neurology clinic.
spontaneously resolves after in symptoms
several hours
 HISTORY OF PRESENT ILLNESS

Interim 4 days prior to consult

• Recurrent headache • headache 7/10- 10/10, still intermittent.

• progressive blurring of vision • Double vision; postprandial vomiting

• Unquantified weight gain • Worse early in the morning, often waking patient up
• No fever, no stiff neck, no rash, no cough, or coryza.

2 YEARS PRIOR 1 year prior to consult On the day

• blurring of vision • Seen at NCH ophthalmology ophthalmology clinic:

• frontal non-throbbing • Treated as error of refraction, given papilledema
headache graded 3/10 which corrective lenses, with improvement referred to the neurology clinic.
spontaneously resolves after in symptoms
several hours
 Gastrointestinal Tract
REVIEW OF SYS- (-) jaundice
(-) vomiting

TEMS
General
(+) weight gain
(-) loose stools
(-) constipation
Genitourinary Tract
(-) rash (-) hematuria
(-) fever (-) oliguria
Head and Neck Endocrine
(-) eye discharge (-) polydipsia
(-) ear discharge (-) epistaxis (-) polyphagia
(-) gum bleeding Nervous
(-) seizures
(-) cervical lymphadenopathy
(-) weakness
Cardiovascular (-) numbness
(-) cyanosis Hematopoietic
Respiratory (-) active bleeding
(-) cough, difficulty breathing (-) easy bruisability
 PAST MEDICAL HIS-
TORY
• No prior hospitalization, no surgery, and no known allergy
• No menarche.
 IMMUNIZATION HIS-
TORY
• Completed health center vaccines up to 1 year of age
 FAMILY HISTORY

• Hypertension in father’s side of the family;

• Maternal aunt had breast cancer.
• No other family member with obesity.
• No known neurological disease in the family.
 DEVELOPMENTAL HISTORY

• Gross motor: Walking at 1 year, rode a bike at 6 years

• Fine motor: writing letters at 4 years
• Language: First word at 1 year old; Full sentences at 3 years.
• Cognitive: Consistent honor student since starting school.
• Psychosocial: Social smile starting at 2-3 months
 NUTRITIONAL HISTORY

• Exclusively breastfed: 6 months

• Solids: mashed vegetables and cere-
als at 6 months.
• Current diet: 3 meals and 2-3 snacks.
1-2 cups of rice with meat and
vegetable viands.
 PERSONAL/SOCIAL/HEADS
Home:
• lives in a household of 4,
• electricity and good ventilation.
• Generally harmonious relationships.
• Parents are both currently unemployed, currently relying on financial sup-
port from relatives.

Education
• consistent honor student and very diligent with her studies.

Environment:
• No known carcinogen exposure.

Activities:
• schoolwork, interacting with friends on social internet media.
 PERSONAL/SOCIAL/HEADS
Abuse
• Denies any form of abuse

Drugs:
• Denies any drug use or drug-exposed environment.

Depression:
• Denies depressed mood or anhedonia, denies any suicidal
thoughts.

Spirituality: Catholic

Sex: Heterosexual, female-identified. No sexual activity.

 PHYSICAL EXAMINA-
TION
General Anthropometrics
Awake, obese, Wt 82 kg
alert, not in distress
Ht 159 cm (z=0) average height

Vital Signs BMI 32.4 kg/m2 (z=3) obese

BP 120/80mmHg
(p90; p95 124/79) Abdominal circumference
109 cm
HR 90 bpm
(>90th percentile)
RR 17 cpm
T 36.8°C
O2 sats 99% at room air
 PHYSICAL EXAMINA-
TION

SKIN HEENT NECK

Normocephalic, anicteric sclera, No cervical lymphadenopathy,
Hyperpigmentation on
pink palpebral conjunctiva, no no neck vein distention, no pal-
the nape and axilla. No nasal congestion, intact tym- pable mass
jaundice, no rash. panic membranes; nonhyper-
emic pharynx
 PHYSICAL EXAMINA-
TION

CHEST AND LUNGS CARDIOVASCULAR ABDOMEN

Adynamic precordium, distinct Abdomen globular,
Symmetric chest extensive subcutaneous fat;
S1 and S2. Regular cardiac
expansion, no normoactive bowel sounds,
rhythm, no murmur
retraction, no crackles, no tenderness, liver and spleen
nonpalpable; no mass palpated
rales or wheezing.
 PHYSICAL EXAMINA-
TION

EXTREMITIES SPINE AND BACK

GENITALIA RECTUM AND ANUS
Full pulses, CRT<2sec, No deformity, spine
No mass on in- Patent anus, no skin tag
edema, no deformity midline
guinal area,
Tanner stage I
 PHYSICAL EXAMINATION: neurologic
Mental Status: Motor:
Awake, oriented to person, place, and time, follows 5/5 motor strength on bilateral upper and lower
Commands, intact short and long term recall, extremities; no rigidity or atrophy
calculations, attention
Sensory:
Cranial Nerves intact light touch truncal and extremity dermatomes
• I: Not assessed
• II: Pupils 3 mm, equal, round, and briskly reactive Cerebellar:
• to light and accomodation; Acuity 20/100 without No ataxia, no dysmetria, no dysdiadochokinesia
lenses; 20/20 with correction; grade 4 disc
edema, bilateral; intact visual fields Reflexes:
• III, IV, VI: EOM abduction deficit on the left 2+ deep tendon reflexes; no Babinski
• V: intact light touch V1, V2, V3; intact masseter
strength Meningeal:
• VII: Face symmetric no nasolabial fold flattening supple neck, no Kernig, no Brudzinski
• VIII: intact hearing
• IX, X: intact gag and phonation
• XI: strong shrug
• XII: tongue midline, no fasciculation
 SALIENT FEATURES
13 years old Obese
(early adolescent)
Female BP at p90

Chronic headache and Abdominal circumference

visual disturbance with above 90th percentile
progression in severity,
Worse in the morning Tanner stage I

Binocular diplopia Papilledema

Weight gain Abduction defect on left eye

Normal development Intact higher functions

 Admitting Impression:
Increased Intracranial Pressure,
Secondary to Intracranial Mass
vs
Pseudotumor Cerebri
Obese, No Stunting
HOSPITAL COURSE
ON ADMISSION
Ophtha: Papilledema
Neurology: Admission for
workup, stat cranial CT
with contrast
 HOSPITAL COURSE
ON ADMISSION
Medical decompression
• Mannitol 0.12 g/kg/dose
• Dexamethasone 5 mg od
• Acetazolamide 3mg/kg/day
Lactulose
Neurosurgery, endocrinology referral
Workup
CBG monitoring
Electrolytes monitoring
RBS, BUN, serum creatinine, CBC,
urinalysis, uric acid, FSH, LH, TSH,
fT3, fT4, serum AM and PM cortisol,
FBS, lipid profile, BHCG, AFP,
liver ultrasound

TUMOR MARKERS
AFP B-HCG
(IU/ml) (mIU/ml)
1.87 <0.10
(<10) (<15)
 HOSPITAL COURSE
ON ADMISSION Workup
Medical decompression CBG monitoring
• Mannitol Electrolytes monitoring
• Dexamethasone RBS, BUN, serum creatinine, CBC,
• Acetazolamide urinalysis, uric acid, FSH, LH, TSH,
fT3, fT4, serum AM and PM cortisol,
Lactulose FBS, lipid profile, BHCG, AFP,
Neurosurgery, endocrinology referral liver ultrasound
endocrine workup
LH FT3 FT4 TSH Fasting AM cortisol PM cortisol
FSH (mIU/ml) insulin
(mIU/mL) (pmol/L) (pmol/L) (uIU/ml) (nmol/L) (nmol/L)
(uU/ml)
2.18 0.26 4.34 16.4 2.78 70.4 168.4 182.6
(1-12) (1-13.4) (5.3-6.2) (1.5-1.9) (1.6-2.8) (<25) (82-551) (82-275)
 HOSPITAL COURSE
ON ADMISSION Workup
Medical decompression CBG monitoring
• Mannitol Electrolytes monitoring
• Dexamethasone RBS, BUN, serum creatinine, CBC,
• Acetazolamide urinalysis, uric acid, FSH, LH, TSH,
fT3, fT4, serum AM and PM cortisol,
Lactulose FBS, lipid profile, BHCG, AFP,
Neurosurgery, endocrinology referral liver ultrasound
Endocrine Workup
FBS Total cholesterol Triglyceride HDL LDL
(mmol/L) (mmol/L) (mmol/L) (mmol/L) (mmol/L)
4.68 5.56 1.51 0.9 3.97
(4.1-5.9) (3.3-4.8) (1-4.8) (1.3-2.1) (1.2-2.7)
 HOSPITAL COURSE
ON ADMISSION Workup
Medical decompression CBG monitoring
• Mannitol Electrolytes monitoring
• Dexamethasone RBS, BUN, serum creatinine, CBC,
• Acetazolamide urinalysis, uric acid, FSH, LH, TSH,
fT3, fT4, serum AM and PM cortisol,
Lactulose FBS, lipid profile, BHCG, AFP,
Neurosurgery, endocrinology referral liver ultrasound

Liver Ultrasound:
Normal-sized liver with mild fatty changes
 HOSPITAL COURSE
ON ADMISSION Workup
Medical decompression CBG monitoring
• Mannitol Electrolytes monitoring
• Dexamethasone RBS, BUN, serum creatinine, CBC,
• Acetazolamide urinalysis, uric acid, FSH, LH, TSH,
fT3, fT4, serum AM and PM cortisol,
Lactulose FBS, lipid profile, BHCG, AFP,
Neurosurgery, endocrinology referral liver ultrasound

Liver Ultrasound:
Normal-sized liver with mild fatty changes
HOSPITAL COURSE

3RD HOSPITAL DAY

Resolution of headache

10th HOSPITAL DAY

Resolution of strabismus and dizziness
Mannitol discontinued
HOSPITAL COURSE
SIADH WORKUP
19th -21st HOSPITAL DAY 24H URINE 24H URINE SERUM
Decreased urine output was noted. OSMOLALITY SODIUM OSMOLALITY
SIADH considered (MMOL/kgH20) (MMOL/24H) (MMOL/KG H20)
328 168.84 281
(500-800) (109-136) (285-295)
24-hour urine osmolality, urine
sodium, serum osmolality.
2/12 2/20
SIADH was confirmed. Fluid Na
132 142
restriction was thus done at 1000 (MMOL/L)
ml/m2, with notable improvement in Cl
101 115
urine output and laboratory (MMOL/L)
parameters.
HOSPITAL COURSE
Monitored in intensive care for 3 days
30th HOSPITAL DAY
Dexamethasone was shifted to hydrocortisone Eventually was transferred to the regular
ward.

Right pterional craniotomy with near total

No sign of ensuing diabetes insipidus
excision of the tumor (No hypernatremia, no excessive urine
volume) or other endocrine complication
was noted.

HISTOPATHOLOGY
Adamantinomatous
craniopharyngioma
HOSPITAL COURSE

37th HOSPITAL DAY

Discharged uneventfully by the 7th postop day

Neuro and onco follow up

For OPD visual perimetry

For OPD scheduling of radiotherapy at Cardinal

Santos Medical Center
CASE DISCUSSION
 HEADACHE
AND DIPLOPIA:

DIFFERENTIAL
DIAGNOSIS

Kliegman, Robert. Nelson Textbook of Pediatrics. Edition 21. Philadelphia, PA: Elsevier, 2020.
 NEUROLOGIC COMPLICATIONS

Singh P, Yoon SS, Kuo B. Nausea: a review of pathophysiology and therapeutics. Therap Adv Gastroen-
terol. 2016 Jan;9(1):98-112. doi: 10.1177/1756283X15618131. PMID: 26770271; PMCID: PMC4699282
NEUROLOGIC COMPLICATIONS
NEUROLOGIC COMPLICATIONS
 NEUROLOGIC COMPLICATIONS

Why no visual field defect

detected?
- Confrontation testing fairly
insensitive (20% to 50% ) for
bitemporal hemianopsia.

Johnson LN, Baloh FG. The accuracy of confrontation visual field test in comparison with automated
perimetry. J Natl Med Assoc. 1991 Oct;83(10):895-8. PMID: 1800764; PMCID: PMC2571584.
 ENDOCRINE COMPLICATIONS:

OBESITY, POSSIBLE IIH

Paley GL, Sheldon CA, Burrows EK, Chilutti MR, Liu GT, McCormack SE. Overweight and obesity in
pediatric secondary pseudotumor cerebri syndrome. Am J Ophthalmol. 2015 Feb;159(2):344-52.e1. doi:
10.1016/j.ajo.2014.11.003. Epub 2014 Nov 7. PMID: 25447107; PMCID: PMC4643369.
 ENDOCRINE COMPLICATIONS:

CAUSE OF OBESITY?

Blüher, M., 2019. Obesity: global epidemiology and pathogenesis. Nature Reviews En-
docrinology, 15(5), pp.288-298.Robert L. Hypothalamic Obesity after Craniopharyngioma:
Mechanisms, Diagnosis, and Treatment. Frontiers in Endocrinology. VOLUME2; 2011.
 ENDOCRINE COMPLICATIONS:

CAUSE OF OBESITY?

Hypothalamic?

Blüher, M., 2019. Obesity: global epidemiology and pathogenesis. Nature Reviews En-
docrinology, 15(5), pp.288-298.Robert L. Hypothalamic Obesity after Craniopharyngioma:
Mechanisms, Diagnosis, and Treatment. Frontiers in Endocrinology. VOLUME2; 2011.
 ENDOCRINE COMPLICATIONS:

Metabolic Syndrome

Ford ES, Li C. Defining the metabolic syndrome in children and adolescents: will the real definition please
stand up? J Pediatr. 2008 Feb;152(2):160-4. doi: 10.1016/j.jpeds.2007.07.056. Epub 2007 Oct 31. PMID:
18206681.
 ENDOCRINE COMPLICATIONS:

Metabolic Syndrome

Miss SM

AC 109 (>90th percentile)

FBS 84.24 mg/dl

BP 120/80mmHg (p90)

HDL 34.75 mg/dl

Triglycerides 133.63 mg/dl

Ford ES, Li C. Defining the metabolic syndrome in children and adolescents: will the real definition please
stand up? J Pediatr. 2008 Feb;152(2):160-4. doi: 10.1016/j.jpeds.2007.07.056. Epub 2007 Oct 31. PMID:
18206681.
 ENDOCRINE COMPLICATIONS:

Metabolic Syndrome

Fornari, E. and Maffeis, C., 2019. Treatment of Metabolic Syndrome in Children. Frontiers in
Endocrinology, 10.
 ENDOCRINE COMPLICATIONS:

Hypopituitarism/ Incomplete Hypopituitarism

hormonal deficiencies occur in about 65-92% of patients, most common complication of treatment for
craniopharyngioma

pathogenesis
• tumor mass effect
• surgical invasion,
• radiotherapy,
• pituitary fibrosis

• growth hormone deficiency is the most common deficit at 62%> thyroid axis> adrenal axis> vaso-
pressin>gonadal axis

Zhou, Z., Zhang, S. and Hu, F., 2021. Endocrine Disorder in Patients With Craniopharyngioma. Frontiers in
Neurology, 12
Honegger J, Tatagiba M. Craniopharyngioma surgery. Pituitary. (2008) 11:361–73. doi: 10.1007/s
11102-008-0137-z
Qi S, Peng J, Pan J, Fan J, Zhang S, Liu Y, et al. [Hypopituitarism mode in patients with
craniopharyngioma in relation to tumor growth pattern]. Zhonghua yi xue za zhi. (2018) 98:19–24.
 ENDOCRINE COMPLICATIONS:

Anticipating Diabetes Insipidus

• Most common postsurgical endocrinopathy in craniopharyngioma
• Most serious manifestations: within 1-2 weeks postop

• Polydipsia, polyuria, nocturia

• Central DI: treat with (responsive to) exogenous vasopressin

Dabrowski E, Kadakia R and Zimmerman D: Diabetes insipidus in infants and children. Best
Pract Res Clin Endocrinol Metab. 30:317–328. 2016.

Duicu C, Pitea AM, Săsăran OM, Cozea I, Man L and Bănescu C: Nephrogenic diabetes
insipidus in children (Review). Exp Ther Med 22: 746, 2021
 ENDOCRINE COMPLICATIONS:

SIADH

Hyponatremia with at least 2 of the following:

• No sign of hypovolemia
• No laboratory evidence of dehydration, (elevated hematocrit, hemoglobin, serum albumin, or blood
urea)
• Normal or positive fluid balance with absence of weight loss
• Central venous pressure (CVP) > 6 cm of water

Addressed with fluid restriction

Spasovski, G., Vanholder, R., Allolio, B., Annane, D., Ball, S., Bichet, D., et al. (2014).
Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol. Dial.
Transplant. 29 (Suppl. 2), i1–i39. doi: 10.1093/ndt/gfu040
 DIAGNOSIS

• MRI – imaging of choice

• HISTOPATHOLOGY
• Genetic Testing is available:
CTTNB1 gene, beta catenin

Prabhu VC, Brown HG. The pathogenesis of craniopharyngiomas. Childs Nerv Syst. 2005 Aug;21(8-9):622-7.
doi: 10.1007/s00381-005-1190-9. Epub 2005 Jun 18. PMID: 15965669
France A, Lakis NS. Craniopharyngioma-adamantinomatous. PathologyOutlines.com website. https://www.-
pathologyoutlines.com/topic/cnstumoradamcraniopharyngioma.html. Accessed January 17th, 2022.
Lubuulwa J, Lei T. Pathological and Topographical Classification of Craniopharyngiomas: A Literature Review.
J Neurol Surg Rep. 2016 Jul;77(3):e121-7. doi: 10.1055/s-0036-1588060. PMID: 27556005; PMCID:
MANAGEMENT

Neurosurgery
• total or near total excision depending
on hypothalamic incursion
• 10% mortality

Radiotherapy
• External beam radiotherapy
MANAGEMENT

Prognosis and Long Term Care

•80% 5-year survival rate
•5-year survival better in children (85%) than
in adults (40%)
•Recurrence rate postop: 15-20%
•rehabilitation and long-term neurology and

endocrinology follow up
SUMMARY
THANK YOU!