Download - Pituitary Disorders _ Parathyroid Disorders
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APIRADEE SRIWIJITKAMOL
DIVISION OF ENDOCRINOLOGY AND METABOLISM
DEPARTMENT OF MEDICINE
FACULTY OF MEDICINE SIRIRAJ HOSPITAL
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PITUITARY
APPROACH TO PITUITARY DISORDER
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INVESTIGATION
CBC, UA, Electrolyte
Hormonal study
FSH, LH, E2 (testosterone)
(ACTH), cortisol (during stress, morning)
TSH, T4
PRL
Film lateral skull
MRI pituitary
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FEEDBACK LOOP OF HYPOTHALAMIC-PITUITARY-AXIS AND LABORATORY INTERPRETATION
Hypothalamus
Pituitary Releasing hormone
Stimulating hormone
Thyroid hormone Corticosteroid
Sex hormone
Negative
feedback
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CASE AM
ทา่นไดร้ับปรกึษาเรือ่ง abnormal thyroid function
test จาก ICCU
ผูป่้วยหญงิอาย ุ70 ปี มาดว้ย ACS ระหวา่งอยูใ่น
ICCU ม ีtachyarrthymia เลยเจาะ TFT
TT3 58 (90-180), FT4 0.78 (0.9-1.9), TSH 2.4
(0.4-4.5)
แปลผลว่า ....
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HYPOTHALAMIC-PITUITARY AXIS CHANGE FOLLOWING PITUITARY LESION
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CASE AM
ทา่นไดร้ับปรกึษาเรือ่ง abnormal thyroid function
test จาก ICCU
ผูป่้วยหญงิอาย ุ70 ปี มาดว้ย ACS ระหวา่งอยูใ่น
ICCU ม ีtachyarrthymia เลยเจาะ TFT
TT3 58 (90-180), FT4 0.78 (0.9-1.9), TSH 2.4
(0.4-4.5)
แปลผลว่า
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PITUITARY VS. NON-PITUITARY TUMOR FILM LATERAL SKULL
Anterior clinoid process
Posterior clinoid process
Floor of sella
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SELLA ENLARGEMENT
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TREATMENT
Hormone replacement
Glucocorticoid
Thyroid
Sex hormone
+GH
Treatment of underlying disease
Advice
Glucocorticoid before thyroid replacement
Glucocorticoid during stress
APPROACH TO PITUITARY DISORDER
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ACROMEGALY
Vital signs: BP
Weight, Height
Typical face:
Frontal bossing
Prognathism
Macroglossia
Coarse faces
Thickening of the nose
Cutis vertices gyrate
Thyroid gland: enlarged, MNG
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Skin: skin tags, Oily skin,
acanthosis nigrican
Wide and spread hands.
Carpal tunnel syndrome
Heart: Cardiomegaly
Abd: Hepatomegaly
Nervous system:
VF
Osteoarthritis
Galactorrhea
ACROMEGALY
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FILM FOOT
Heel pad sign
distance between the
plantar aspect of the
calcaneus and skin
surface
normal distance is 21 mm
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Lateral radiograph of skull reveals
Enlarged sella with double flooring
Dilatation of air sinus
Prognathism
Thickened skull vault
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FILM SKULL
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FILM HAND
Ungal tufting
Widening of the bases of
distal phalanges
Metacarpal osteophytes on
radial aspect (metacarpal
hooks)
Soft tissue hypertrophy
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DIAGNOSIS
IGF-1
Screening test
Higher than same age
75 g OGTT
GH > 1 ug/L
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TREATMENT
Goal
GH < 1ug/L
Normalized IGF-1
Modalities
Surgery
Medication
Dopamine agonist
Somatostatin analog
Radiation
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INDICATION FOR MEDICATION
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)
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ADVERSE EVENTS OF SRL
Increased incidence of gallbladder sludge and
gallstone formation,
Abdominal bloating and cramping or
constipation
Bradycardia
Worsening of glucose metabolism
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APPROACH TO PITUITARY DISORDER
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CASE PS
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.
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Galactorrhea?
Cause of galactorrhea?
Need treatment?
APPROACH TO GALACTORRHEA GALACTORRHEA
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
(American family physician 2004;70:543-50)
> 2 years from the last breast
feeding
(American family physician 2001;63:1763-70)
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Identify Cause
Drug use
Pituitary function
VF and VA
Hypothyroidism
CKD
Galactorhea?
Signs of hypothyroidism
Signs of hypopituitarism
VF and VA
APPROACH TO GALACTORRHEA
HISTORY PHYSICAL EXAMINATION
Etiology 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
CAUSES OF GALACTORRHEA
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MECHANISM DRUGS
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
DRUG-INDUCED GALACTORRHEA
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Identify Cause
Drug use
Pituitary function
VF and VA
Hypothyroidism
CKD
Assess need to treatment Menstruation Amount of galactorrhea
Galactorhea?
Signs of hypothyroidism
Signs of hypopituitarism
VF and VA
APPROACH TO GALACTORRHEA
HISTORY PHYSICAL EXAMINATION
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Hx and PE
In case, Hx of drug:
stop medication
for 3 days
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”)
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Hx and PE
In case, Hx of drug:
stop medication
for 3 days
Kidney X
Thyroid ✓
Prolactin
Kidney ✓
Thyroid X
Prolactin
Kidney ✓
Thyroid ✓
Prolactin
Kidney ✓
Thyroid ✓
Prolactin ✓
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CASE PS
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 PROLACTIN LEVEL IN 226 PATIENTS WITH
HISTOLOGICALLY VERIFIED NON‐FUNCTIONING
PITUITARY MACROADENOMA
Karavitaki N. Clinical Endocrinology 2006;65; 524-529.
Serum PRL in all patients Serum PRL in patients not taking drugs
>141.5
94.3-141.5 <94.3
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CASE PS
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: ……………
abnormal
abnormal
<6 mm 6-9 mm
Freda PU. J Clin Endocrinol Metab 96: 894–904, 2011
normal
APPROACH TO PITUITARY INCIDENTALOMA
APIRADEE SRIWIJITKAMOL
DIVISION OF ENDOCRINOLOGY AND METABOLISM
DEPARTMENT OF MEDICINE
FACULTY OF MEDICINE SIRIRAJ HOSPITAL
S2iriraj Board Review 2014
CALCIUM
HOMEOSTASIS
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VITAMIN D PATHWAY
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APPROACH TO HYPERCALCEMIA
-Hyper PTH
-Lithium
-Familial hypocalciuric
hypercalcemia
-Vitamin D intake
-Granulomatous
disease
-Malignancy
- PTHrP:
- Sq cell CA
- Breast, lymphoma
- Humoral: NHL
- LOF: MM, Breast
-Endocrine dis.
-Drugs: vit A, thiazide
-Others
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TREATMENT OF HYPERCALCEMIA
Mild Moderate Severe
Symptom - - + -/+
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
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APPROACH TO HYPOCALCEMIA
-Low PTH:
- Hypoparathyroidism
-Low Mg
-PTH resistance
- Pseudohypo PTH
-Critical illness - Hyperphos.
- Rhabodmyolysis - Tumor lysis synd - Phosphate Rx
- Others: -Drugs:
- P450: INH, rifam, anticonvulsant ,gllucocorticoid
- Citrate
-Vit D def.
- Malabsorption
- Liver and renal
- Anticonvulsant - Elderly
-Vit D resistance
- Ricket type II
- Phenytoin Rx
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METABOLIC BONE DISEASES
Mineralization
Osteomalacia/rickets
Low bone mineral content
Osteoporosis
High bone turnover
Hyperparathyroidism
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Inadequate MINERALIZATION of normal
osteoid tissue
Different expressions of the same disease
Rickets
Areas of endochondral growth
Osteomalacia
All skeleton is incompletely calcified
OSTEOMALACIA
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Symptoms and Signs
Bone pain, backache
Muscle weakness
Vertebral collapse
Kyphosis
loss of height
Deformities & stress fractures
OSTEOMALACIA
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Bone pain Pathological fracture
•Generalized muscle weakness •Disability
Metabolic Bone Disease Others
Metastasis bone
Hematologic: MM
Rheumato
Osteoporosis
Osteomalacia
Paget’s
Osteomalacia
Pain, muscle weakness
Ca ↓, P ↓, Alk ↑
Osteopenia, looser zone
Decrease
Osteoporosos
-
-
Osteopenia
Decrease
Clinical
Lab
X-ray
BMD
Bone pain Pathological fracture
•Generalized muscle weakness •Disability
Metabolic Bone Disease Others
Metastasis bone
Hematologic: MM
Rheumato
Osteoporosis
Osteomalacia
Paget’s
Vit D def. Fanconi’s
-RTA
-Glycosuria -hypophosphatemia
Hereditary Hypophosphatemia
TIO
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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
OSTEOMALACIA
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Investigation
Blood chemistries
Calcium, Phosphate, Albumin, Alkaline
phosphatase
Renal function and E’lyte
25-OH vitamin D
iPTH
Urine calcium/phosphate
Film bone survey
Bone biopsy
OSTEOMALACIA
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PSEUDOFRACTURE
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PSEUDOFRACTURE
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PSEUDOFRACTURE
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HYPOPHOSPHATEMIA VS. VITAMIN D DEFICEINCY
*Urine phosphate > 100 mg/D , FE phosphate > 5% = high
Hypophosphatemic
Osteomalacia
Vit. D Deficiency
Osteomalacia
Calcium Normal Normal. (Low)
Phosphate Low Low
ALP High High
E’lyte In RTA -
25-OH vitamin D Normal Low
iPTH Normal, Nornal, (High)
Urine phosphate High Normal
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
Physical examination
Neck mass
Basic lab
CBC, UA
Ca, P, Alk, Alb
Electrolyte, BUN, Cr
Special test
Bone survey
BMD
MIBI scan
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Film HAND
Acro-osteolysis
Generalized
osteopenia
Subperiosteal
resorption of the radial
aspect of the middle
phalanges of index and
middle fingers
A: Subperiosteal distal clavicular resorption
B: Brown tumor, the osseous expansion
and lucency of the proximal humerus
FILM BONE SURVEY
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FILM SKULL
Trabecular bone resorption resulting in the salt-and-pepper appearance
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Brown tumor
Loss of lamina dura
FILM SKULL
Characteristic endplate
sclerosis
Rugger-jersey spine
RENAL OSTEODYSTROPHY
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Multifocal, large, amorphous
calcific deposits
Tumoral calcinosis
RENAL OSTEODYSTROPHY
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RECOMMENDATIONS FOR THE
EVALUATION OF ASYMPTOMATIC PHPT
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):3561–3569
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Symptomatic: surgery
Asymptomatic: ?Indication
PRIMARY HYPERPARATHYROIDISM
Measurement 1990 2002 2008 2013
Serum Ca
(>upper NL)
1-1.6 mg/dl 1 mg/dl 1 mg/dl 1 mg/dl
Renal
24-h Ur Ca >400 mg/D >400 mg/D -
Ccr by 30% by 30% < 60 mL/min < 60 mL/min
Others Ca-stone
risk
Skeletal
BMD Z-score <-2.0 in
forearm
T-score <-2.5 at
any site
T-score <-2.0 at
any site*
T-score <-2.5 at
any site*
Others Vertebral #
Age <50 <50 <50 <50
*Z-score in premenopausal women and in men under 50