case presentation in kallmann syndrome

1. CASE
PRESENTATION
PRESENTED BY:
GROUP 3B
APRICIO,REINA ARIANNE
COBSIN,KEVIN
KARUVAKODE, RANJIMA
PICORRO,PAUL
SABU, SACHIN
TORIO, KRISELDA MAY

2. FLOW OF
PRESENTATION
SALIENT FEATURES
PHYSICAL EXAMINATION
LABORATORY DIAGNOSTICS
WORKING DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
TREATMENT AND MANAGEMENT

3. A 15-year-old girl is brought to the pediatrician’s office because of
concern about her development. She has not gone through puberty as
have other girls her age. She reports never having had a period or
breast development. She also reports that she cannot smell things. She
has difficulty recognizing pungent odors such as trash and sweet
fragrances such as perfume and flowers. On physical examination,
she is sexually infantile without development of axillary or pubic hair
or breast tissue and is unable to perceive odors. The remainder of her
examination is normal. She has a cervix and uterus on pelvic
examination.

4. NO MENSTRUAL PERIOD
NO BREAST DEVELOPMENT
REDUCED OR ABSENT SENSE OF SMELL
CANNOT SMELL THINGS
not gone through puberty

5. PHYSICAL EXAMINATION
• RESULT • remarks
PATIENT
HISTORY
• 15years old
• not gone through
puberty as have
other girls her age
• difficulty
recognizing pungent
odors
• Abnormal for her
age
• ABNORMAL
Physical
appearance
No breast development
No pubic hairs or
axillary hairs(sexually
infantile)-
• ABNORMAL FOR HER
AGE
Pelvic
examination
Presence of cervix and
uterus
(normal)

7. DIFFERENTIAL
DIAGNOSIS

10. Klinefelter Syndrome
RULE IN RULE OUT
• No breast development • Speech and language
deficits (especially
expressive language)
• osteoporosis

11. Prader-Willi Syndrome
RULE IN Rule out
• hypogonadotropic
hypogonadism
• Obesity
• Mental retardation
• hypotonia
• Strabismus
• small hands and feet.
• short stature
Magnetic resonance imaging
(MRI) of the head (to
evaluate for hypopituitarism)

12. Turner Syndrome
RULE IN RULE OUT
• no breast development by
age 12 years or who have
not started menses by age
14 years
Elevated levels of luteinizing
hormone (LH) and FSH
confirm ovarian failure
osteoporosis
*Karyotyping-45,X cell line
or a cell line with deletion of
the short arm of the X
chromosome (Xp deletion)

14. ANATOMY
OF THE
CRIBIFORM
PLATE AND
CRANIAL
PLACODE
Normally during fetal development, there was a region of the brain called
olfactory placode.
There are 2 groups of neuron in the olfactory placode:
1.Olfactory neuron
2. Neuron that releases Gonadotropin releasing hormone.

15. Structure of
olfactory bulb

16. OLFACTORY PLACODE
1. Olfactory neurons
- responsible for the sense of smell.
- migrate from the olfactory placode and get embedded in the
cribiform plate.
- separates the nasal cavity from the brain forming the
olfactory bulb
2. Gonadotropin releasing hormone (GnRH) neurons
- migrate from the cribiform plate and settle in the hypothalamus.
- hypothalamic pituitary gonadal axis
- sytem of hormone signaling between the
hypothalamus, pituitary glands or gonads.
- controls sexual development and reproduction.
- released into the hypophyseal portal system
- network of capillaries connecting the hypothalamus to
the pituitary.
- stimulates the cells in the anterior pituitary called gonadotrophs
- releases: Gonadotropin, LH and FSH into the blood.
- stimulates the gonads to produce sex specific
hormones.

19. MALE DEVELOPMENT
Testosterone
- helps the external sex organs to differentiate into male genitals
- causes the testis to descend from the abdomen to scrotal sac.
- Leydig cells
-responds to the LH by converting more cholesterol into
testosterone.
- leads to the development of primary sex characteristics.
- Sertoli cells
-responds to FSH produces more sperm.
- Further increase in testosterone leads to development of secondary
sex characteristics
NORMAL PHYSIOLOGY

20. FEMALE DEVELOPMENT
Theca cells
- responds to LH by producing progesterone and
androstenedione.
Granulosa cells
- responds to FSH by converting androstenedione into
estrogen.
Progesterone and Estrogen
- regulates primary sex characteristics
- direct secondary sex characteristic development
NORMAL PHYSIOLOGY

21. Congenital hormonal condition characterized by the
failure of an individual to enter puberty.
a form of Hypogonadotrophic Hypogonadism (HH).
occurs when the hypothalamic neurons that are
responsible for releasing gonadotropin-releasing
hormone (GnRH neurons) fail to migrate into the
hypothalamus during embryonic development.
Kallmann syndrome also features the additional
symptom of an altered sense of smell either
completely absent (anosmia) or highly reduced
(hyposmia).

22. PATHOPHYSIOLOGY OF KALLMANN SYNDROME
Predisposing factors:
Family history
Gene mutation
Pubertal age
More common in boys(X-linked
Idiopathic)
Etiology:
unknown
Precipitating factors:
NONE
Cranial placode generates cell types: migratory and sensory in nature
Development of Olfactory placode
defect in Migration of olfactory placode to
Cribiform plate
Defect in the development and migration of
Gonadotropin Releasing Hormone Neurons
Decrease in release of GnRH in hypophyseal
portal system
defect in the development of first group of
neurons: olfactory neurons
Forms groups of neurons: olfactory
neurons and GnRH releasing neurons
Failure of olfactory bulb to develop
ANOSMIAHYPOSMIA
Decrease stimulation of the gonadotrophs
in anterior pituitaryDecrease or loss of sensitivity to odors
Defect Olfactory placode migrate from
cribiform plate to anterior pituitary
Decrease in signaling of hypothalamic pituitary
gonadal axis to the hypothalamus, pituitary glands
or gonads

24. defect in the migration
of neurons from the
olfactory placodes.
•- HYPOSMIA(reduced sense
of smell) or
ANOSMIA(complete loss of
smell).
- affects the GnRH
neurons
•- results in a decrease in GnRH
•- low level of gonadotropin
hormones, LH, and FSH
•- low gonadal function
- decreased
testosterone in males
and estrogen and
progesterone in
females
- prevents puberty
from beginning or
completing.
- Hypogonadotropic
Hypogonaidsm
•- underdevelopment of
primary and secondary sex
characteristics.

25. MALES
Primary sex characterisctics dysfunctions
- small penis and testes
- improper testicular descent
- low sperm count
Secondary sex characteristics dysfunctions
- lack of facial Hair
- low muscle mass
- no deep voice development.

26. FEMALES
Primary sex characteristics dysfunctions
- amenorrhea
- oligomenorrhea
Secondary sex characteristics dysfunctions
- lack of breast development
- lack of pubic hair
Both males and females: INFERTILITY
Non-reproductive symptoms:
- osteoporosis/osteopenia

27. LABORATORY STUDIES

28. HYPERANDROGENIC
DISORDER
(POLYCYSTIC OVARIAN
SYNDROME)
KALLMANN
SYNDROME
SERUM
(TOTAL/FREE)TESTOS
TERONE
INCREASED VERY LOW
SERUM(TOTAL/ FREE) TESTOSTERONE
) TESTOSTERONE

29. KALLMANN SYNDROME
SERUM ESTRADIOL DECREASED POSTPUBERTY AGED
FEMALES
SERUM ESTRADIOL

30. Indication
To diagnose hypothalamic-pituitary disease in precocious and
delayed puberty in both sexes in those children with low
basal gonadotropins.
Contra-indications
This test may be performed simultaneously with TRH or
glucagon as part of triple pituitary test.
Principle
GnRH (gonadotropin releasing hormone) is a decapeptide
secreted by the hypothalamus which stimulates the
production and secretion of LH and FSH by the anterior
pituitary.
Gonadotropin
Releasing
Hormone
(GnRH) Test

31. • Normal basal reference values in prepubertal
children are:
LH < 2.0 iu/L
FSH < 2.0 iu/L
• Following GnRH, the response may be considered
normal if the basal values are in the reference
range and there is at least a doubling at 20 min for
LH and FSH. The response varies throughout the
menstrual cycle: early (D4) < late follicular (D11) =
"luteal" (D21), max response occurs at the mid-
cycle (D14).
• An exaggerated response is seen in primary &
secondary gonadal failure.
• A flat response in gonadotropins (< 5 iu/L) occurs
in prepubertal children and with pituitary and/or
hypothalamic disease. However, a normal
response does NOT exclude pituitary or
hypothalamic disease since the response will be
affected by the exact anatomy of the disorder.
• The magnitude of the LH response is proportional
to the mean nocturnal LH and therefore the
evolution of puberty.
Interpretation

32. KALLMANN SYNDROME
SERUM LH AND FSH LOW NORMAL OR DECREASED
SERUM LH AND FSH

33. Magnetic
resonance
imaging

34. Mutations on the
following genes:
WDR11, FGF17, IL17RD,
DUSP6, SPRY4, FLRT3,
AXL, SOX10,SEMA3A,
and HS6ST11
Gene test

35. • The hypothalamus and the
pituitary gland are grossly normal.
Absence of olfactory bulbs and
abnormal (shallow, absent, or
medially oriented) olfactory sulci
are frequent findings in patients
with Kallmann syndrome
Histologic Findings

36. Management and Treatment

37. Hormone
Replacement
Therapy
Standard treatment for Kallmann
syndrome.
To normalize the sex hormone levels,
so as to induce and maintain sexual
development.
The dose usually needs to be tailored
to each individual, particularly during
certain life stages. Dosage adjustment
is necessary to induce fertility if the
individual desires to conceive.

38. IN FEMALE:
Estrogen and progestin therapy is usually needed to induce
secondary sex characteristics.
if the patient wishes to attempt conception, further treatment with
gonadotropins or pulsatile GnRH can stimulate folliculogenesis, and
the production of mature eggs cells.
Duration of treatment:
Continue sex hormone replacement therapy until the time of the
natural menopause- typically to age 50.

39. IN MALE:
Involve testosterone therapy.
There are various testosterone formulations available that may be
used in the treatment of kallmann syndrome, such as Intramuscular
injections, Tropical patches, Gels or Liquids.
The testosterone therapy usually continues even after puberty has
been initiated, to maintain secondary sex characteristics and normal
levels of testosterone in the body.
If the patient desires to start a family, further treatment with
gonadotropins may be required to stimulate testicular growth and
initiated sperm production.

40. Bone
Mineral
Density
Bone health can deteriorates
significantly over a period of
time in which the individual
experiences a low circulating
level of sex hormones.
It is important for the bone
mineral density to be
measured and, if needed,
treated appropriately, in order
to improve bone strenght and
prevent osteoporosis.

41. Sense of
Smell
Anosmia is evident in patients with kallman
syndrome.
This can also affect the sense of taste, and may
change the appetite of affected individuals.
Unfortunately, there is currently no treatment
available to improve the sense of smell. Instead,
affected individuals should be aware of the
situation and take measure to reduce associated
risk.
They should avoid eating foods that may have
expired, particularly if there is no one else available
to confirm the freshness of the food.

42. Follow-up
• Patients with kallmann syndrome require
regular consultations with an endocrinologist,
that is a doctor who specializes in hormone-
associated diseases.
• Regular checkups are needed, including tests
monitor serum concentrations of various
hormone levels. These are required to bring
about and maintain the proper hormonal
balance. Changes in dosage may be needed,
according to the concentration and the normal
range of the hormone in unaffected individuals.
In particular life stages, changes in the therapy
and closer support are usually required.

43. -THE END-
THANK YOU
FOR
LISTENING!