5/1/2015

PITUITARY
S2iriraj Board
Review 2014

APIRADEE SRIWIJITKAMOL
DIVISION OF ENDOCRINOLOGY AND METABOLISM
DEPARTMENT OF MEDICINE
FACULTY OF MEDICINE SIRIRAJ HOSPITAL

APPROACH TO
PITUITARY DISORDER

INVESTIGATION
S2iriraj Board
Review 2014

FEEDBACK LOOP OF
HYPOTHALAMIC-PITUITARY-AXIS
AND LABORATORY INTERPRETATION

CBC, UA, Electrolyte

Hormonal study
FSH, LH, E2 (testosterone)
(ACTH), cortisol (during stress, morning)
TSH, T4
PRL
Film lateral skull
MRI pituitary

CASE AM
S2iriraj Board
Review 2014

S2iriraj Board

Hypothalamus
Pituitary

Releasing hormone

Negative
feedback

Stimulating hormone

Thyroid hormone

Review 2014

abnormal thyroid function
test ICCU

70 ACS
ICCU tachyarrthymia TFT
TT3 58 (90-180), FT4 0.78 (0.9-1.9), TSH 2.4
(0.4-4.5)

....

Corticosteroid
Sex hormone

5/1/2015

HYPOTHALAMIC-PITUITARY AXIS CHANGE

FOLLOWING PITUITARY LESION

CASE AM
S2iriraj Board

Review 2014

abnormal thyroid function
test ICCU

70 ACS
ICCU tachyarrthymia TFT
TT3 58 (90-180), FT4 0.78 (0.9-1.9), TSH 2.4
(0.4-4.5)

PITUITARY VS.
NON-PITUITARY TUMOR

FILM LATERAL SKULL

S2iriraj Board
Review 2014

Anterior clinoid process

Posterior clinoid process

Floor of sella

SELLA ENLARGEMENT
S2iriraj Board
Review 2014

5/1/2015

APPROACH TO
PITUITARY DISORDER

TREATMENT

Hormone replacement
Glucocorticoid
Thyroid
Sex hormone
+GH
Treatment of underlying disease

S2iriraj Board
Review 2014

Advice
Glucocorticoid before thyroid replacement
Glucocorticoid during stress

ACROMEGALY

Vital signs: BP

Weight, Height
Typical face:

ACROMEGALY
S2iriraj Board
Review 2014

Frontal bossing
Prognathism
Macroglossia
Coarse faces
Thickening of the nose

S2iriraj Board
Review 2014

Cutis vertices gyrate

Thyroid gland: enlarged, MNG

Skin: skin tags, Oily skin,

acanthosis nigrican
Wide and spread hands.
Carpal tunnel syndrome
Heart: Cardiomegaly
Abd: Hepatomegaly
Nervous system:
VF
Osteoarthritis
Galactorrhea

FILM FOOT
Heel pad sign
distance between the
plantar aspect of the
calcaneus and skin
surface
normal distance is 21 mm

S2iriraj Board
Review 2014

S2iriraj Board
Review 2014

Lateral radiograph of
skull reveals
Enlarged sella with
double flooring
Dilatation of air
sinus
Prognathism
Thickened skull
vault

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FILM HAND

FILM SKULL
S2iriraj Board
Review 2014

S2iriraj Board
Review 2014

Ungal tufting
Widening of the bases of
distal phalanges
Metacarpal osteophytes on
radial aspect (metacarpal
hooks)
Soft tissue hypertrophy

TREATMENT

DIAGNOSIS
S2iriraj Board
Review 2014

IGF-1
Screening test
Higher than same age
75 g OGTT
GH > 1 ug/L

Goal
GH < 1ug/L
Normalized IGF-1
Modalities
Surgery
Medication
Dopamine agonist
Somatostatin analog

S2iriraj Board

Review 2014
Failed to control biochemical by surgery alone
Primary medical therapy

Patient refuse surgery

Severe cardio- or respiratory disease
Lack of experienced surgeon
Low probability of surgical cure (without
compressive symptoms)

Radiation

ADVERSE EVENTS OF SRL

INDICATION FOR MEDICATION

S2iriraj Board
Review 2014

S2iriraj Board
Review 2014

Increased incidence of gallbladder sludge and

gallstone formation,
Abdominal bloating and cramping or
constipation
Bradycardia
Worsening of glucose metabolism

5/1/2015

APPROACH TO
PITUITARY DISORDER

CASE PS
S2iriraj Board

Review 2014
A 23-year-old woman presented with secondary
amenorrhea for 7 months. She had no other
complaints. Physical examination revealed few
drops of milk discharge on squeezing. Otherwise
were within normal limit. Progressterone challenge
test -, FSH 1.0, LH 0.8, E2 <5.

GALACTORRHEA

APPROACH TO GALACTORRHEA

Galactorrhea?
Cause of galactorrhea?
Need treatment?

S2iriraj Board
Review 2014

Microscopy shows fat

globules in discharge.

DEFINITION

A milk-like secretion from the

breast in the
absence of parturition or
beyond 6 months
postpartum in a
nonbreastfeeding woman

> 2 years from the last breast

feeding

(American family physician 2004;70:543-50)

(American family physician 2001;63:1763-70)

APPROACH TO GALACTORRHEA

CAUSES OF GALACTORRHEA
Etiology

S2iriraj Board
Review 2014

HISTORY
Identify Cause
Drug use
Pituitary function
VF and VA
Hypothyroidism
CKD

PHYSICAL EXAMINATION
Galactorhea?
Signs of hypothyroidism
Signs of hypopituitarism
VF and VA

Mechanism

Prolactin
level

Drugs

-Effects on dopamine level-function

Pituitary, stalk,
hypothalamic

-Production
-Prolactin inhibitory factor

Thyroid disease

-Hypo TRH
-Hyper free estrogen

CKD

-Renal clearance
-Medication: methyldopa

Neurologic
cause

-Nipple or breast stimuli

-Chest wall irritation intercostal N.
Post column Hypothalamus PIF

Idiopathic

-Sensitivity to prolactin levels

-More bioactivity, low immunoactivity

5/1/2015

DRUG-INDUCED GALACTORRHEA
MECHANISM

DRUGS

APPROACH TO GALACTORRHEA

S2iriraj Board
Review 2014

S2iriraj Board
Review 2014

HISTORY

Dopamine-receptor blockade

Metoclopramide
Phenothiazines
Risperidone
SSRI: fluoxitine, setraline
Tricyclic antidepressants

Dopamine-depleting agents

Methyldopa
Reserpine

Inhibition of dopamine release

Heroin
Morphine

Histamine-receptor blockade

Cimetidine

Stimulation of lactotrophs

Oral contraceptives
Verapamil

Identify Cause
Drug use
Pituitary function
VF and VA
Hypothyroidism
CKD
Assess need to treatment
Menstruation
Amount of galactorrhea

Hx and PE
In case, Hx of drug:
stop medication
for 3 days

PHYSICAL EXAMINATION
Galactorhea?
Signs of hypothyroidism
Signs of hypopituitarism
VF and VA

Hx and PE
S2iriraj Board
Review 2014

PROLACTIN MEASUREMENT
NPO 6 hours, no stress, no breast stimulation
When in doubt, sampling can be repeated on a different day
at 15- to 20-min intervals to account for possible prolactin
pulsatility
When there is a discrepancy between clinical and prolactin level,
serial dilution of serum samples to eliminate an artifact with some
immunoradiometric assays (hook effect)

S2iriraj Board
Review 2014

In case, Hx of drug:
stop medication
for 3 days

Kidney

Kidney

Kidney

Kidney

Thyroid

Thyroid

Thyroid

Thyroid

Prolactin

Prolactin

Prolactin

Prolactin

SERUM PROLACTIN LEVEL IN 226 PATIENTS WITH

HISTOLOGICALLY VERIFIED NONFUNCTIONING
PITUITARY MACROADENOMA

CASE PS
S2iriraj Board

Review 2014
A 23-year-old woman presented with secondary
amenorrhea for 7 months. She had no other
complaints. Physical examination revealed few
drops of milk discharge on squeezing. Otherwise
were within normal limit. Progressterone challenge
test -, FSH 1.0, LH 0.8, E2 <5. Her serum prolactin
is 104 ng/mL, serum TSH 1.0 mIu/L. MRI of pituitary
gland showed pituitary tumor size 0.8 cm.

DIAGNOSIS: .

Serum PRL in all patients

Serum PRL in patients

not taking drugs

>141.5
94.3-141.5
<94.3
Karavitaki N. Clinical Endocrinology 2006;65; 524-529.

5/1/2015

CASE PS
S2iriraj Board

Review 2014
A 23-year-old woman presented with secondary
amenorrhea for 7 months. She had no other
complaints. Physical examination revealed few
drops of milk discharge on squeezing. Otherwise
were within normal limit. Progressterone challenge
test -, FSH 1.0, LH 0.8, E2 <5. Her serum prolactin
is 104 ng/mL, serum TSH 1.0 mIu/L. MRI of pituitary
gland showed pituitary tumor size 0.8 cm.

DIAGNOSIS: .
TREATMENT:

APPROACH TO PITUITARY INCIDENTALOMA

<6 mm

6-9 mm

APIRADEE SRIWIJITKAMOL
abnormal

normal

abnormal

DIVISION OF ENDOCRINOLOGY AND METABOLISM

DEPARTMENT OF MEDICINE
FACULTY OF MEDICINE SIRIRAJ HOSPITAL

Freda PU. J Clin Endocrinol Metab 96: 894904, 2011

CALCIUM
HOMEOSTASIS

VITAMIN D PATHWAY
S2iriraj Board
Review 2014

S2iriraj Board
Review 2014

5/1/2015

APPROACH TO HYPERCALCEMIA

TREATMENT OF HYPERCALCEMIA

S2iriraj Board
Review 2014

Mild
Symptom

-Hyper PTH
-Lithium
-Familial hypocalciuric
hypercalcemia

-Vitamin D intake
-Malignancy
-Granulomatous
- PTHrP:
disease
- Sq cell CA
- Breast, lymphoma
- Humoral: NHL
- LOF: MM, Breast
-Endocrine dis.
-Drugs: vit A, thiazide
-Others

APPROACH TO HYPOCALCEMIA

-/+

Identify cause

Supportive

IV fluid*
I/O > 3L/D

IV Furosemide

Bisphosphanate**

Calcitonin***

Hemodialysis

* Be careful in elderly and heart disease patients

** Do not use in patient with acute kidney injury
*** A few days of treatment

-Vit D def.
-Low PTH:
-Critical illness
- Malabsorption
- Hypoparathyroidism
- Hyperphos.
- Liver and renal
-Low Mg
- Rhabodmyolysis
- Anticonvulsant
-PTH resistance
- Tumor lysis synd
- Elderly
- Pseudohypo PTH
- Phosphate Rx
-Vit D resistance
- Others:
- Ricket type II
-Drugs:
- Phenytoin Rx
- P450: INH, rifam, anticonvulsant
,gllucocorticoid
- Citrate

OSTEOMALACIA

Mineralization
Osteomalacia/rickets
Low bone mineral content
Osteoporosis
High bone turnover
Hyperparathyroidism

S2iriraj Board
Review 2014

OSTEOMALACIA
S2iriraj Board
Review 2014

Inadequate MINERALIZATION of normal

osteoid tissue
Different expressions of the same disease
Rickets
Areas of endochondral growth
Osteomalacia
All skeleton is incompletely calcified

Severe

METABOLIC BONE DISEASES

S2iriraj Board
Review 2014

S2iriraj Board
Review 2014

Moderate

S2iriraj Board
Review 2014

Symptoms and Signs

Bone pain, backache
Muscle weakness
Vertebral collapse
Kyphosis
loss of height
Deformities & stress fractures

5/1/2015

Bone pain
Pathological fracture

Bone pain
Pathological fracture

Generalized muscle weakness

Disability

Generalized muscle weakness

Disability

Others
Metastasis bone

Metabolic Bone Disease

Metastasis bone

Rheumato

Hematologic:
MM

Clinical
Lab
X-ray
BMD

Others

Osteoporosis

Pagets

Osteoporosos
Osteopenia
Decrease

OSTEOMALACIA

Vit D def.

Osteoporosis

Pagets

Osteomalacia

Fanconis
-RTA
-Glycosuria
-hypophosphatemia

Hereditary
Hypophosphatemia

TIO

OSTEOMALACIA
S2iriraj Board
Review 2014

Defect in Vitamin D metabolism

Nutritional
Underexposure to sunlight
Intestinal malabsorption
Liver & kidney diseases
Anticonvulsant use
Hypophosphataemia with renal phosphate wasting
RTA
Tumor-induced ostemalacia
Hereditary hypophosphatemic osteomalacia

Rheumato

Hematologic:
MM

Osteomalacia

Osteomalacia
Pain, muscle weakness
Ca , P , Alk
Osteopenia, looser zone
Decrease

Metabolic Bone Disease

PSEUDOFRACTURE

Investigation
Blood chemistries
Calcium, Phosphate, Albumin, Alkaline
phosphatase
Renal function and Elyte
25-OH vitamin D
iPTH
Urine calcium/phosphate
Film bone survey
Bone biopsy

S2iriraj Board
Review 2014

PSEUDOFRACTURE
S2iriraj Board
Review 2014

S2iriraj Board
Review 2014

5/1/2015

HYPOPHOSPHATEMIA VS.
VITAMIN D DEFICEINCY

PSEUDOFRACTURE
S2iriraj Board
Review 2014

S2iriraj Board

Hypophosphatemic
Osteomalacia

Review 2014
Vit. D Deficiency
Osteomalacia

Normal

Normal. (Low)

Calcium
Phosphate

Low

Low

ALP

High

High

Elyte

In RTA

25-OH vitamin D

Normal

Low

iPTH

Normal,

Nornal, (High)

High

Normal

Urine phosphate

*Urine phosphate > 100 mg/D , FE phosphate > 5% = high

PRIMARY HYPERPARATHYROIDISM
History
Asymptomatic
50% of symptomatic:
Renal calculi
Bone pain or fracture
Other symptoms
PU, Pancreatitis
Neuromuscular and
Neuropsychiatric
Endocrine syndrome:
MEN I or MEN IIa

Film HAND
S2iriraj Board
Review 2014

Physical examination
Neck mass
Basic lab
CBC, UA
Ca, P, Alk, Alb
Electrolyte, BUN, Cr
Special test

Bone survey
BMD
MIBI scan

FILM BONE SURVEY

A: Subperiosteal distal clavicular resorption
B: Brown tumor, the osseous expansion
and lucency of the proximal humerus

Acro-osteolysis
Generalized
osteopenia
Subperiosteal
resorption of the radial
aspect of the middle
phalanges of index and
middle fingers

FILM SKULL
S2iriraj Board
Review 2014

Trabecular bone
resorption resulting in
the salt-and-pepper
appearance

10

5/1/2015

FILM SKULL

RENAL OSTEODYSTROPHY
S2iriraj Board

Brown tumor Review 2014

Loss of lamina dura

Characteristic endplate
sclerosis
Rugger-jersey spine

RECOMMENDATIONS FOR THE

EVALUATION OF ASYMPTOMATIC PHPT

RENAL OSTEODYSTROPHY
S2iriraj Board
Review 2014

Multifocal, large, amorphous

calcific deposits
Tumoral calcinosis

S2iriraj Board

Review 2014
Biochemistry panel
Ca, P, ALP, BUN, Cr, 25(OH)D
PTH level
BMD by DXA
Lumbar spine, hip, and distal 1/3 radius
Vertebral spine X-ray or VFA by DXA
24-h urine for:
Ca, Cr, CCr
Stone risk profile esp. Ur Ca >400 mg/D
Abdominal imaging by x-ray, ultrasound, or CT scan

Bilezikian et al,. J Clin Endocrinol Metab, October 2014, 99(10):35613569

PRIMARY HYPERPARATHYROIDISM

Symptomatic: surgery
Asymptomatic: ?Indication

Measurement

S2iriraj Board
Review 2014

1990

2002

2008

2013

1-1.6 mg/dl

1 mg/dl

1 mg/dl

1 mg/dl

24-h Ur Ca

>400 mg/D

>400 mg/D

Ccr

by 30%

by 30%

< 60 mL/min

Serum Ca
(>upper NL)
Renal

< 60 mL/min
Ca-stone
risk

Others
Skeletal
BMD

Z-score <-2.0 in T-score <-2.5 at T-score <-2.0 at T-score <-2.5 at

forearm
any site
any site*
any site*

Others
Age

Vertebral #
<50

<50

<50

<50

*Z-score in premenopausal women and in men under 50

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