Transcript Hypopituitarism - University of Yeditepe Faculty of Medicine, 2011

Hasan AYDIN, MD
Endocrinology and Metabolism
Yeditepe University Medical Faculty
 The
deficiency (hypo) of one or more hormones
of the pituitary gland
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Deficiency of one or multiple hormones of the
anterior pituitary …….-hypopituitarism
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Deficiency of the posterior lobe …..-central
diabetes insipitus
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Deficiency of all pituitary hormones….panhypopituitarism
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Either result from hypothalamus or pituitary
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Symptoms and signs frequently protean and
nonspecific
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Abnormalities in electrolyte levels,
Altered mental status,
Abnormal glucose levels,
Altered body temperature,
Increased heart rate
Patients at risk of developing hypopituitarism
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Traumatic brain injury (TBI),
Cocaine use,
Subarachnoid hemorrhage,
Postpartum hypotension (Sheehan syndrome).
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76% tumor or treatment of tumor
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Mass effect of adenoma on other hormones
Surgical resection of non-adenomatous tissue
Radiation of pituitary
13% extrapituitary tumor
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Craniopharyngioma
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8% unknown
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1% sarcoidosis
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0.5% Sheehan’s syndrome
 In
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US
Prevelance of pituitary adenoma 10-20%
Hypopituitarism 2-8/100,000 persons/year
 World
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Incidence of 4.2 cases per 100,000 per year
Prevalence of 45.5 per 100,000 without gender
difference
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Missed or delayed diagnosis could potentially lead to
permanent disability or death
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Female patients with hypopituitarism have more
than a 2-fold increase in cardiovascular mortality
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Cardiovascular disease is significantly higher among
hypopituitary patients (incidence ratio, 3.7; 95%
confidence interval)
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Hypopituitary patients have lower high-density
lipoprotein cholesterol and higher low-density/highdensity lipoprotein ratio
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Primary pituitary disease
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Tumors
Pituitary surgery
Radiation treatment
Hypothalamic disease
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Functional suppression of axis
Exogenous steroid use
 Extreme weight loss
 Exercise
 Systemic Illness
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Interruption of the
pituitary stalk
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Extrasellar disorders
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Craniopharyngioma
Rathke pouch
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Developmental and
genetic causes
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Dysplasia
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Septo-Optic dysplasia
Developmental
hypothalamic dysfunction
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Kallman Syndrome
Laurence-Moon-BardetBiedl Syndrome
Frohlich Syndrome (Adipose
Genital Dystrophy)
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Acquired causes:
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Infiltrative disorders
Cranial irradiation
Lymphocytic hypophysitis
Pituitary Apoplexy
Empty Sella syndrome
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Hypothalamic dysfunction and hypopituitarism
 may result from dysgenesis of the septum pellucidum or
corpus callosum
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Affected children have mutations in the HESX1 gene
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These children exhibit variable combinations of:
 cleft palate
 syndactyly
 ear deformities
 optic atrophy
 micropenis
 anosmia
Pituitary dysfunction
 Diabetes insipidus
 GH deficiency and short stature
 Occasionally TSH deficiency
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Defective hypothalamic gonadotropin-releasing
hormone (GnRH) synthesis
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Associated with anosmia or hyposmia due to olfactory
bulb agenesis or hypoplasia
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May also be associated with: color blindness,
optic atrophy, nerve deafness, cleft palate,
renal abnormalities, cryptorchidism
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GnRH deficiency prevents progression
through puberty
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Characterized by
 low LH and FSH levels
 low concentrations of sex steroids
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Males patients
 Delayed puberty and hypogonadism, including micropenis
 Long-term treatment:
 human chorionic gonadotropin (hCG) or testosterone
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Female patients
 Primary amenorrhea and failure of secondary sexual
development
 Long-term treatment:
 cyclic estrogen and progestin
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Repetitive GnRH administration restores normal puberty
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Fertility may also be restored by the administration of
gonadotropins or by using a portable infusion pump to
deliver subcutaneous, pulsatile GnRH
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Rare autosomal recessive disorder
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Characterized by mental retardation; obesity;
hexadactyly, brachydactyly, or syndactyly
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Central diabetes insipidus may or may not be
associated
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GnRH deficiency occurs in 75% of males and half of
affected females
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Retinal degeneration begins in early childhood
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most patients are blind by age 30
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A broad spectrum of hypothalamic lesions
 hyperphagia, obesity, and central hypogonadism
Decreased GnRH production in these patients results in
 attenuated pituitary FSH and LH synthesis and release
Deficiencies of leptin, or its receptor, cause these clinical
features
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Infiltrative disorders
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Cranial irradiation
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Lymphocytic hypophysitis
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Pituitary Apoplexy
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Empty Sella syndrome
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Etiology
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Presumed to be autoimmune
Clinical Presentation
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Women, during postpartum period
Mass effect (sellar mass)
Deficiency of one or more anterior pituitary hormones
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Diagnosis
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ACTH deficiency is the most common
MRI - may be indistinguishable from pituitary adenoma
Treatment
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Corticosteroids – often not effective
Hormone replacement
Patoloji
Radyoloji
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Hemorrhagic infarction of a pituitary
adenoma/tumor
Considered a neurosurgical emergency
Presentation:
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Variable onset of severe headache
Nausea and vomiting
Meningismus
Vertigo
+/ - Visual defects
+/ - Altered consciousness
Symptoms may occur immediately or may develop
over 1-2 days
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Risk factors:
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Usually resolve completely
Transient or permanent hypopituitarism is possible
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Diabetes
Radiation treatment
Warfarin use
undiagnosed acute adrenal insufficiency
Diagnose with CT/MRI
Differentiate from leaking aneurysm
Treatment:
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Surgical - Transsphenoid decompression
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Visual defects and altered consciousness
Medical therapy – if symptoms are mild
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Corticosteroids
Radiology
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Infarction of pituitary after substantial blood loss
during childbirth
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Incidence: 3.6%
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No correlation between severity of hemorrhage and
symptoms
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Severe: recognised days to weeks PP
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Lethargy, anorexia, weight loss, unable to breast feeding
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Typically long interval between obstetric event and
diagnosis
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Of 25 cases studied:
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50% permanent amenorrhea
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The rest had scanty-rare menses
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Most lactation was poor to absent
Dx: MRI empty sella turcica
Often an incidental MRI finding
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Usually have normal pituitary function
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Implying that the surrounding rim of pituitary tissue is fully
functional
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Hypopituitarism may develop insidiously
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Pituitary masses may undergo clinically silent infarction
with development of a partial or totally empty sella by
cerebrospinal fluid (CSF) filling the dural herniation.
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Rarely, functional pituitary adenomas may arise within
the rim of pituitary tissue, and these are not always
visible on MRI
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Can present with features of deficiency of one or
more anterior pituitary hormones
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Clinical presentation depends on:
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Age at onset
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Hormone affected, extent
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Speed of onset
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Duration of the deficiency
Radiology
Women
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Oligomenorrhea or
amenorrhea
Men
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Loss of libido
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Erectile dysfunction
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Infertility
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Loss of secondary sex
characteristics
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Atrophy of the testes
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Gynecomastia (testosterone
deficiency)
Loss of libido
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Vaginal dryness or
dyspareunia
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Loss of secondary sex
characteristics (estrogen
deficiency)
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Results in hypocortisolism
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Pale complexion
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Malaise
Anorexia
Weight-loss
Gastrointestinal disturbances
Hyponatremia
Unable to tan or maintain a tan
No features of mineralocorticoid deficiency
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Aldosterone secretion unaffected
 Hypothyroidism
 Atrophic
thyroid gland
 Inability
 Often
to lactate postpartum
1st manifestation of Sheehan syndrome
 Adults
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Often asymptomatic
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May complain of
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Fatigue
Degrees exercise tolerance
Abdominal obesity
Loss of muscle mass
Children
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GH Deficiency
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Constitutional growth delay
 Biochemical
insufficiency
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diagnosis of pituitary
Demonstrating low levels of trophic hormones in
the setting of low target hormone levels
 Provocative
tests may be required to assess
pituitary reserve
 Basal
ACTH secretion
Cortisol < 3 μg/dL, cortisol deficiency
 Cortisol > 18μg/dL, sufficient ACTH
 Cortisol > 3 μd/dL but < 18 μg/dL - test ACTH reserve
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 ACTH
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Metyrapone test (750 mg q 4hr for 24 hrs)
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Cortisol < 7 μg/dL, 11-deoxycortisol > 10 μg/dL
ITT ( 0.1 U/kg BW)
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reserve
Cortisol > 18 μg/dL, normal
Cosyntropin stimulation test
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Cortisol > 18 μg/dL, normal
 Serum
 TSH
T4 should be measured
may not be helpful
 MEN
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Testosterone low, LH normal or low
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Sperm count
 WOMEN
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LH-FSH, E2, vaginal cytology, response to
medroxyprogesterone 10 mg qd for 10 days
 Peak
GH response < 5 ng/ml
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ITT
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Arginine ( 0.5 g/ kgBW i.v.)
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L-DOPA ( 0.5 g orally )
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Clonidine ( 0.15 mg orally )
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Glucagon ( 0.03 μg/kg BW s.c. + 40 mg propranolol )
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Cortisol deficiency ( 5 - 2.5 mg prednisone qd)
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Levothyroxine ( 0.075 -0.15 mg qd )
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Gonadal steroids (E2 ,P, Testosterone)
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Growth hormone
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Vasopressin (desmopressin 10 μg x 2)
 Hormone
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replacement therapy
usually free of complications
 Treatment
regimens that mimic physiologic
hormone production
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allow for maintenance of satisfactory clinical
homeostasis
Trophic Hormone Deficit
Hormone Replacement
ACTH
Hydrocortisone (10-20 mg A.M.; 10 mg P.M.)
Cortisone acetate (25 mg A.M.; 12.5 mg P.M.)
Prednisone (5 mg A.M.; 2.5 mg P.M.)
TSH
L-Thyroxine (0.075-0.15 mg daily)
FSH/LH
Males
Testosterone enanthate (200 mg IM every 2 wks)
Testosterone skin patch (5 mg/d)
Females
Conjugated estrogen (0.65-1.25 mg qd for 25days)
Progesterone (5-10 mg qd) on days 16-25
Estradiol skin patch (0.5 mg, every other day)
For fertility: Menopausal gonadotropins, human
chorionic gonadotropins
GH
Adults: Somatotropin (0.3-1.0 mg SC qd)
Children: Somatotropin [0.02-0.05 (mg/kg per
day)]
Vasopressin
Intranasal desmopressin (5-20 ug twice daily)
Oral 300-600 ug qd