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/high-
density lipoprotein ratio
 Primary pituitary disease  Interruption of the
 Tumors pituitary stalk
 Pituitary surgery
 Radiation treatment
 Extrasellar disorders
 Hypothalamic
 Craniopharyngioma
disease  Rathke pouch
 Functional suppression of axis
 Exogenous steroid use
 Extreme weight loss
 Exercise
 Systemic Illness
 Developmental and  Acquired causes:
genetic causes  Infiltrative disorders
 Dysplasia  Cranial irradiation
 Septo-Optic dysplasia  Lymphocytic hypophysitis
 Developmental  Pituitary Apoplexy
hypothalamic dysfunction  Empty Sella syndrome
 Kallman Syndrome
 Laurence-Moon-Bardet-
Biedl Syndrome
 Frohlich Syndrome (Adipose
Genital Dystrophy)
 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
 ACTH deficiency is the most common
 Diagnosis
 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:
 Diabetes
 Radiation treatment
 Warfarin use
 Usually resolve completely
 Transient or permanent hypopituitarism is possible
 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
 Loss of libido
 Vaginal dryness or
dyspareunia
 Loss of secondary sex
characteristics (estrogen
deficiency)
Men
 Loss of libido
 Erectile dysfunction
 Infertility
 Loss of secondary sex
characteristics
 Atrophy of the testes
 Gynecomastia (testosterone
deficiency)
 Results in hypocortisolism
 Malaise
 Anorexia
 Weight-loss
 Gastrointestinal disturbances
 Hyponatremia

 Pale complexion
 Unable to tan or maintain a tan

 No features of mineralocorticoid deficiency

 Aldosterone secretion unaffected
 Hypothyroidism

 Atrophic thyroid gland

 Inability to lactate postpartum

 Often 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 diagnosis of pituitary
insufficiency

 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 reserve
 Metyrapone test (750 mg q 4hr for 24 hrs)
 Cortisol < 7 μg/dL, 11-deoxycortisol > 10 μg/dL
 ITT ( 0.1 U/kg BW)
 Cortisol > 18 μg/dL, normal
 Cosyntropin stimulation test
 Cortisol > 18 μg/dL, normal
 Serum T4 should be measured

 TSH 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