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