Download clinical disorders of pituitary

CLINICAL DISORDERS OF PITUITARY
LEARNING OBJECTIVES
• Be able to identify the parts of the pituitary gland
• Be able to identify hormones secreted by each lobe and their main
actions
• Understand the common diseases caused by excess or deficiency
of pituitary hormones
• Understand the common clinical presentation of these disorders
Anatomy of pituitary gland
• Was first called “Hypophysis “ by Thomas in 1778.
• Pea-sized gland located at middle cranial fossa within a recess of
the sphenoid bone called “Sella Turcica”.
• Suspended from hypothalamus by a stalk (infandibulum)
• Has mainly 2 lobes:
– Anterior gland:
– Posterior gland:
Adenohypophysis
Neurohypophysis
Anatomy of pituitary gland
Anatomy of pituitary gland
Development of Human Anterior Pituitary
Anterior Pituitary Function
Corticotroph Gonadotr Thyrotrop Lactotro
oph
h
ph
Hormone ACTH
FSH, LH TSH
Prolacti
n
Stimulat CRH, gp-130 GnRH,
TRH
Estroge
ors
cytokines
Estrogen
n, TRH
Inhibitor Glucocortic Sex
T3, T4,
Dopami
s
oids
steroids, Dopamine, ne
inhibin
Somatosta
tin, GH
Target Adrenals
Ovary,
Thyroid
Breast
Gland
Testes
and
other
tissues
Somatotro
ph
GH
GHRH,
GHS
Somatosta
tin, IGF-1,
Activins
Liver,
bone and
other
tissues
Trophic Steroid &
Sex
Effects androgens Steroid,
production Follicular
growth,
Germ Cell
maturatio
n
T4
Milk
IGF-1
synthesis Producti production
and
on
, Growth
secretion
induction,
Insulin
antagonis
m
Etiology of Hyper/Hypo Pituitary-Hypothalamic Lesions
• Non-Functioning Pituitary Adenomas
• Endocrine active pituitary adenomas
–
–
Prolactinoma
-Somatotropinoma
-Corticotropinoma
Thyrotropinoma -Mixed endocrine adenomas
• Malignant pituitary tumors
• Metastases in the pituitary (breast, lung, stomach, kidney)
• Pituitary cysts: Rathke's cleft cyst
Mucocoeles, Others
• Empty sella syndrome
Etiology of Hyper/Hypo Pituitary-Hypothalamic Lesions…cont
• Developmental abnormalities:
Craniopharyngioma, Germinoma, Others
• Primary CNS Tumors:
Perisellar meningioma
Hemangioblastoma
Optic glioma
Others
• Malignant systemic diseases:
Hodgkin'slymphoma
Leukemic infiltration
Eosinophilic granuloma
Non-Hodgkin lymphoma
Histiocystosis X
Giant cell granuloma
• Granulomatous diseases:
Neurosarcoidosis
Syphilis
PITUIOTARY ADENOMA
Wegner's granulomatosis, Tuberculosis,
CRANIOPHARYNGIOMA
PITUITARY ADENOMA
LYMPHOCYTIC
HYPOPHYSITIS
INFILTRATIVE DISORDER: SARCOIDOSIS
CLINICAL DISORDERS OF PITUITARY FUNCTION
• Due to Hypo-secretion of Pituitary Hormones
- Central Hypoadrenalism - Hypogonadism,
- Hypothyroidism
- GH deficiency
- Pan-Hypopituitarism
- Diabetes Insipidus
• Due to Hyper-secretion of Pituitary Hormones
- Hyperprolactinemia
- Acromegaly
- Cushing’s Disease
- SIADH
ANTERIOR PITUITARY CLINICAL
DISORDERS
EXCESS GROWTH HORMONE
• GIGANTISM IN CHILDREN:
• ACROMEGALY IN ADULTS
•
•
•
•
ESSENTIALS OF DIAGNOSIS
ACROMEGALY/GIGANTISM
Clinical features plus;
Elevated serum levels of IGF-1 (screening).
Elevated serum GH levels, NOT suppressed following oral glucose
test.
MRI/CT brain.
Symptoms and signs at
presentation
Facial change, acral
enlargement, and soft-tissue
swelling
Excessive sweating
Acroparesthesiae/ carpal tunnel
syndrome
Tiredness and lethargy
Headaches
Oligo- or amenorrhea, infertility
Erectile dysfunction and/or
decreased libido
Arthropathy
Impaired glucose tolerance/
diabetes
Goiter
Ear, nose throat and dental
problems
Congestive cardiac failure/
arrythmia
Overall prevalence (%)
100
83
68
53
53
55
42
37
37
35
32
25
Hypertension
23
COMPLICATIONS OF ACROMEGALY
Cardiovascular
Ischemic heart disease
Cardiomyopathy
Heart failure
Arrhythmias
Hypertension
Respiratory
Kyphosis
Obstructive sleep apnea
Metabolic
Diabetes mellitus/IGT
Hyperlipidemia
Neurologic
Carpal Tunnel syndrome
Stroke
Neoplastic
Colorectal
(Breast and prostate - uncertain)
Musculoskeletal
Degenerative arthropathy
Calcific discopathy, pyrophosphate arthropathy
GROWTH HORMONE DEFICIENCY
CLINICAL FEATURES:
• Short stature
• Delayed tooth development
• Delayed puberty
• Low energy
• Decrease strength and exercise tolerance
• Decreased muscle mass
• Weight gain, especially around the waist
ESSENTIALS OF DIAGNSIS
GH-DEFICIENCY
Low serum GH & IGF-1 level.
Provocative GH-stimilation test:
• Intravenous GHRH/Arginine sulfhydryl test.
• Oral Clonidine/Levodopa (in pt’s pretreated with propranolol or
estrogen).
Note:
GH deficiency is present in 96% of patients with three or
more other pituitary hormone deficiencies.
CUSHING’S DISEASE (ACTH EXCESS)
CUSHING SYNDROME vs. CUSHING DISEASE
• CUSHING’S SYNDROME:
Is a syndrome due to excess cortisol from pituitary, adrenal or other
sources (exogenous glucocorticoids, ectopic ACTH, etc.)
• CUSHING’S DISEASE:
Is hypercortisolism due to excess pituitary secretion of ACTH
(about 70% of cases of endogenous Cushing’s syndrome)
CLINICAL PRESENTATIONS OF CUSHING DISEASE
• Moon facies
• Facial plethora
• Supraclavicular fat pads
• Buffalo hump
• Truncal obesity
• Weight gain
• Purple striae
• Proximal muscle weakness
• Easy bruising
• Hirsutism
• Hypertension
• Osteopenia
• Diabetes mellitus/IGT
• Impaired immune function/poor wound healing
Central Obesity in Cushing’s Disease
Progressive Obesity of Cushing’s Disease
AGE 6
AGE 7
AGE 8
9
AGE 11
Buffalo Hump & Striae in Cushing’s Disease
AGE
ESSENTIALS OF DIAGNSIS
CUSHING’S DISEASE
• Clinical features plus;
• Plasma ACTH level is elevated.
• Plasma cortisol levels are also high.
• MRI/CT brain.
CENTRAL HYPOADRENALISM
(ACTH DEFICIENCY)
• Acute ACTH deficiency is serious condition and can lead to death if
not recognized and treated properly
• CLINICAL FEATURES:
Lethargy
Malaise
Anorexia
Vomiting
Abdominal pain
Dizziness
Weight loss
Postural hypotension
Pale skin
Shock
Coma
HYPERPROLACTINEMIAS & PROLACTINOMAS
Causes:
• Prolactinoma
• Pituitary stalk compression by non pitiutary tumor
• Primary hypothyroidism
• Drugs
•
•
•
•
•
•
CRF
Liver cirrhosis
PCOS
Acromegaly
Pregnancy
Lactation
HYPERPROLACTINEMIAS & PROLACTINOMAS…cont
CLINICAL FEATURES:
• Women may present with oligomenorrhea, amenorrhea,
galactorrhea or infertility.
• Men often have less symptoms than women (sexual dysfunction,
visual problems, or headache) and are diagnosed later.
• In both sexes, tumor mass effects may cause visual-field defects or
headache
ESSENTIALS OF DIAGNSIS
PROLACTINEMIA
• Clinical features plus;
• Elevated serum Prolactin levels.
• MRI/CT brain.
CENTRAL/SECONDARY HYPERTHYROIDISM
CLINICAL FEATURES:
Skin warm & sweaty
Heat intolerance
Palmar erythma
Thinning of hair
Tachycardia
Dyspnea
High output heart failure
Weight loss
Atrial fibrillation
hyperdefecation
Malabsorption
Gynecomastia
Decrease libido
Erectile dysfunction
Osteoporosis/fractures
Anxiety
Insomnia
HYPERTHYROIDISM….cont
• Palmar erythema
• Clubbing (thyroid acropachy)
Atrial fibrillation
CENTRAL/SECONDARY HYPOTHYROIDISM
CLINICAL FEATURES:
Cold intolerance
Somnolence
Lethargy
Impaired memory
Cold pale dry skin
Bardycardia
Sluggishness
HYPOTHYROIDISM…cont
Weight gain
Constipation
Fatigue
Weight gain
Menstrual abnormalities
Dry fine hair
Hypothermia
Pretibial myxedema
Pretibial Myxedema
HYPOTHYROIDISM….cont
Hypothyroidism in chidren; Cretinism (meaning Christ like)
ESSENTIALS OF DIAGNSIS
TSH EXCESS OR DEFICIENCY
•
•
•
•
Clinical features plus;
Serum TSH level.
Serum T3 & T4 levels.
MRI/CT brain.
GONADOTROPHIN DEFICIENCY
(FSH/LH DEFICIENCY)
CLINICAL FEATURES:
• Male:
Erectile Dysfunction
Decreased libido
Fatigue
Loss of muscle mass
Small & soft testes
Infertility
Loss of facial, axillary & pubic hair
• Female:
Amenorrhea
Hot flushes
Failure to lactate
Breast atrophy
Decreased axillary and pubic hairs
Thin skin with fine wrinkling
ESSENTIALS OF DIAGNSIS
(FSH/LH DEFICIENCY)
Clinical features plus;
Low serum levels of FSH & LH.
MRI/CT brain.
POSTERIOR PITUITARY CLINICAL DISORDERS
POSTERIOR HYPER-PITUITARY DISORDERS
• Syndrome of inappropriate secretion of Anti-diuretic hormone,
SIADH (TOO MUCH ADH!!)
• CAUSES:
Lung cancer
Ca duodenum/pancreas
Lung disease
CNS disorders/infections/
Drugs
Trauma
CLINICAL FEATURES OF SIADH
• Weight gain.
• Decrease urine output
• Decrease serum Na levels.
– weakness
– muscle cramps
– Diarrhea
– Seizueres
POSTERIOR HYPO-PITUITARY DISORDERS
DIABETES INSIPIDUS (too little ADH)
• 50% idiopathic
– a. central -- i.e. brain tumors
– b. nephrogenic - inability of tubules to respond to ADH
CLINICAL FEATURES OF DIABETES INSIPIDUS
• Polydipsia
• Polyuria (10L in 24 hours)
• Severe fluid volume deficit
– wt loss
– tachycardia
– constipation
– shock
ESSENTIALS OF DIAGNSIS
DIABETES INSIPIDUS
•
• Clinical features plus;
• A supervised “vasopressin challenge test” (for central DI).
• Serum vasopressin measurement with modest fluid restriction (for
nephrogenic DI).
• Serum & urine osmolality.
THANK YOU ALL……..