Download Pituitary Physiology and Deficiencies

Pituitary Physiology and Deficiencies
Heidi Chamberlain Shea, MD
Endocrine Associates of Dallas
Pituitary
• Pituitary
– “Master” gland
– Most of the pituitary
hormones control
other endocrine glands
Goals of Discussion
• Review pituitary
anatomy
• Understand pituitary
physiology
• Discuss pituitary
hormone deficiencies
Nomenclature
• Pituitary
– Greek
• ptuo (to spit)
– Latin
• Pituita (mucus)
– Mucus was produced
by the brain and was
excreted through the
nose by the pituitary
Pituitary Development
• Evagination of the stromodeal ectoderm from buccal cavity
• Infundibulum, neural stalk and posterior lobe from diencephalon
• Development 3rd to the 15th week gestation
Pituitary Anatomy
Gross
• Sits in sella turcica
• Surrounded by dura
• Sphenoid
– Lateral and inferior
• Lateral
– Cavernous sinus
• Internal carotid artery
• CN III, IV, VI,
V1 and V2
Pituitary Anatomy
Gross
• Symmetrical bean
shaped
– Brownish red
•
•
•
•
13 mm transverse
9 mm AP
6 mm height
Adult
– 0.4-0.9 grams
– Larger in women
– Larger in multiparous
women
– During pregnancy
increases to 0.9-1 grams
Pituitary Anatomy
Microscopic
• Anterior lobe
– 80% of gland
– Brown color
• Posterior lobe
– Gray/brown color
Pituitary Anatomy
Microscopic
• Anterior lobe 3 divisions
– Pars distalis
• Largest
• Hormone producing cells
– Pars intermedia
• Poorly defined in the human
– Pars tuberalis
• Upward extension to the
anterior lobe and attached
to pituitary stalk
• Posterior lobe
– Pars nervosa
Pituitary Gland
Microscopic
• Pars distalis
– Pink acidophils
• Growth hormone
• Prolactin
– Dark purple basophils
• Corticotropin (ACTH)
• Thyroid stimulating
hormone (TSH)
• Follicle stimulating
hormone (FSH)
• Luteinizing hormone
(LH)
Pituitary
Portal System
• Hypophyseal arteries
– From carotid
– Superior
• 80-90% to adenophysis
– Inferior
• Posterior pituitary
• Posterior lobe
– Rich nerve supply
– Unmyelinated nerves
Goals of Discussion
• Review pituitary
anatomy
• Understand pituitary
physiology
• Discuss pituitary
hormone deficiencies
Hormones Of The Anterior Pituitary
• 6 main hormones
secreted by the
adenohypophysis:
– Growth hormone
• Somatotropin
– Thyroid-stimulating
hormone
• Thyrotropin
– Adrenocorticotropic
hormone
• Corticotropin
– Prolactin
– Follicle-stimulating
hormone
– Luteinizing hormone
Anterior pituitary
Hypothalamic
product
Pituitary
product
Target
organ
Hormone
product
CRH
ACTH
Adrenal
cortex
Cortisol
TRH
TSH
Thyroid
T4, T3
GHRH (+)
SRIH (-)
GH
Liver;
Tissues
IGF-I (systemic)
IGF-I (local)
PRIH
(dopamine)
PRL
Breast
[Lactation]
GnRH
LH,
FSH
Gonad
Sex hormones
(LHRH)
Hormone
Structure
Polypeptide/proteins
ACTH
Polypeptide
GH
Protein
PRL
Protein
Amino acids/Source
39
191
199
Corticotroph
Somatotroph
Lactotroph
Glycoproteins
TSH
Alpha* / TSH-beta 110
LH
Alpha / LH-beta 115
FSH
Alpha / FSH-beta 115
Thyrotroph
Gonadotroph
Gonadotroph
[hCG
Alpha / beta-hCG] 147
* 92 amino acids
[Placenta]
GH_AXIS_
HYPOTHALAMUS
(-)
HYPOTHALAMICPITUITARY
PORTAL SYSTEM
SRIH
(-)
POSTERIOR
PITUITARY
GHRH
(+)
ANTERIOR
PITUITARY
INCR. [FFA]
DIRECT
INSULIN RESISTANCE
EFFECTS
GH
TISSUES
IGF-I
IGFBP-3
GROWTH
HYPOTHALAMUS
(-)
HYPOTHALAMICPITUITARY
PORTAL SYSTEM
(-)
CRH
(+)
ANTERIOR
PITUITARY
POSTERIOR
PITUITARY
ACTH
ADRENAL Fasiculata
CORTISOL
HYPOTHALAMUS
(-)
HYPOTHALAMICPITUITARY
PORTAL SYSTEM
(-)
TRH
(+)
ANTERIOR
PITUITARY
POSTERIOR
PITUITARY
TSH
THYROID GLAND
T4, T3 (T4 --> T3)
HYPOTHALAMUS
PRIH
(DOPAMINE)
(-)
POSTERIOR
PITUITARY
ANTERIOR
PITUITARY
PRL
BREAST
HYPOTHALAMUS
(-)
HYPOTHALAMICPITUITARY
PORTAL SYSTEM
GnRH
(-)
(LHRH)
(+)
ANTERIOR
PITUITARY
POSTERIOR
PITUITARY
LH, FSH
GONAD
SEX HORMONES, INHIBIN
Posterior pituitary
Hypothalamic
source (cell body) Target
Effect
ADH
Collecting
duct
H2O retention
Oxytocin
Breast
Uterus
Milk let down
Smooth muscle
Contraction
Goals of Discussion
• Review pituitary
anatomy
• Understand pituitary
physiology
• Discuss pituitary
hormone deficiencies
History
• 15yr old WF presents with secondary
amenorrhea, polydipsia and polyuria
• Normal growth and development
• Menarche at 11 years of age
– Qmonth menses until 12 years of age
– Withdrawal bleeding only with OCP’s
History
• Drinks 32 oz water Q34hrs during the day
• Drinks and urinates Q23hrs at night
• ROS: occasional
headaches, fatigue and
difficulty losing weight
Physical Exam
•
•
•
•
•
Wt 62.9kg (75%)
Ht 5ft 3.5in (50%)
BMI 24.2 kg/m2
HR 80
B/P 117/86
• General:
nondysmorphic, wellnourished
• HEENT: visual fields
intact, no thyromegaly
• Breast: no discharge,
Tanner V
• GU: Tanner V
Differential Diagnosis
Hypopituitarism
• Isolated hormone
deficiencies
– Acquired or congenital
• Tumors
–
–
–
–
Pituitary adenomas
Pituitary apoplexy
Hypothalamic tumors
Metastatic carcinoma
• Inflammatory
– Granulomatous
disease
• Sarcoidosis, TB and
syphilis
– Eosinophilic
granuloma
– Lymphocytic
hypophysitis
Differential Diagnosis
Hypopituitarism
• Vascular disease
– Sheehan’s postpartum
necrosis
– Carotid aneurysm
• Destructive
– Surgery
– Radiation
– Trauma
• Infiltration
– Hemochromatosis
– Amyloidosis
Hypopituitary
Presentation
• Growth hormone
production
– First hormone to be
disrupted
• Gonadotropin
deficiency
– Easily disrupted
• Corticotropin
– Less frequently
affected
• Thyrotropin
– Rarely affected
• Anti-diuretic hormone
– Deficiency usually due
to tumor
– Craniopharyngioma
Hypopituitary
Presentation
• Growth hormone
deficiency
– Children
• Short stature
– Adults
• Non specific
• Fine wrinkling around the
face
• Improved insulin sensitivity
Hypopituitary
Presentation
• Gonadotropin deficiency
– Women
• Amenorrhea
– Primary or secondary
• Infertility
– Men
• Decreased libido
• Decreased beard and body
hair
Hypopituitary
Presentation
• Corticotropin deficiency
–
–
–
–
–
Fatigue
Decreased appetite
Weight loss
Decreased pigmentation
Abnormal response to
stress
• Hypotension
• Hyponatremia
• Fever
• Primary Adrenal
Insufficiency
–
–
–
–
–
–
–
Addison’s disease
Fatigue
Decreased appetite
Weight loss
Increased pigmentation
Hyperkalemia
Abnormal response to
stress
• Hypotension
• Hyponatremia
• Fever
Hypopituitary
Presentation
• Hypothryoidism
–
–
–
–
Fatigue
Cold intolerance
Puffy skin
Absence of goiter
• Diabetes Insipidus
– Polyuria
– Polydipsia
Evaluation
• What testing?
– Polydipsia and
polyuria
• Water deprivation test
– Secondary
amenorrhea
• Prolactin
• Gonadotropins
• Thyroid function
Laboratory
• Water deprivation test reveals diabetes
insipidus
• MRI – pituitary seen, no masses, subtle
thickening of 3rd ventricle floor and no
hyperintense neurohypophysis in sella
noted
• TSH 1.61 ug/dl (0.35-5.54)
• T4 8.4 uIU/ml (4.0-12.8)
Laboratory
•
•
•
•
•
•
Cortisol 0800 15.5 ug/dl (5-25)
ACTH 14 pg/ml
BHCG <5 mIU/ml
Prolactin 5 ng/ml (3-27)
Estradiol 1.3 ng/dl (3.4-17)
ESR 101
Laboratory
•
•
•
•
FSH 6.9 mIU/ml (Tanner V 1.0-9.2)
LH 7.1 mIU/ml (Tanner V 0.4-11.7)
IGF-1 207 ng/ml (217-589)
Skeletal Xray: no lesions and
epiphyses closed.
• Dopamine arginine GH stimulation test
<5ng/ml
Treatment
• Growth hormone therapy
• Estrogen and progesterone
– Birth control pills
• Testosterone
– Cypianate or enanthate
• 200 mg IM Q2 weeks
– Gels 5-10 gram per day
• Fertility
– Refer to Reproductive
Endocrinologist
• Thyroid
–
–
–
–
Levothyroxine (generic)
Synthroid
Levoxyl
Unithroid
• Dose ranges 75-150 mcg per
day
Treatment
• Cortisol
– Hydrocortisone
• 10mg AM and 5 mg PM
• 6-8 mg/m2/day
• Stress dosing
–
–
–
–
Fever, illness, surgery
20 mg/m2/day
Double or triple daily dose
100 mg x1 then 25-50 mg
Q6-8hrs
• All hypopituitary patients
need a medic alert
bracelet
Treatment
• Desmopressin
(DDAVP)
– Nasal spray
• 10 mcg QD-BID
– Tablets
• 0.1 to 0.2 mg QD-BID
– SQ injection
• 1-2 ug QD-BID
Treatment
• DDAVP nasal spray 10mcg QD
• Ortho-novum 777
• Growth hormone therapy