Anatomy, Pathology/ disorders and Management / pharmacological

1. Pituitary and
Hypothalamus
Oriba Dan Langoya

2. Disorders of the Anterior Pituitary
and Hypothalamus
• Ant pit often is referred to
as the "master gland“
• Produces 6 major
hormones:
1. Prolactin (PRL)
2. Growth hormone (GH),
3. Adrenocorticotropic
hormone (ACTH)
4. Luteinizing hormone (LH)
5. Follicle-stimulating
hormone (FSH)
6. Thyroid-stimulating
hormone (TSH)

4. Anatomy and Development
• Pit gland weighs 600mg located in sellar turcica
• Pit dev’t from Rathke's pouch involves a cplx
interplay of lineage-specific transcription factors
• Transcription factor Prop-1 induces pit dev’t of Pit-
1-specific lineages as well as gonadotropes
• Pit-1 determines cell-specific expression of GH, PRL,
and TSH in somatotropes, lactotropes, and
thyrotropes.
• High levels of ER in cells that contain Pit-1 favors
PRL expression, whereas thyrotrope embryonic
factor (TEF) induces TSH expression

5. Hypothalamic & Ant Pit Insufficiency
Etiology of Hypopituitarism
• Development/structural
• Transcription factor
• Pituitary dysplasia/aplasia
• Congenital CNS mass,
encephalocele
• Primary empty sella
• Congenital hypothalamic
disorders (septo-optic
dysplasia,
• Prader-Willi synd
• Kallmann syndrome)
• Traumatic
• Surgical resection
• Radiation damage
• Head injuries
• Infections
• Fungal (histoplasmosis)
• Parasitic (toxoplasmosis)
• Tuberculosis
• Pneumocystis carinii

6. Etiology of Hypopituitarism
• Neoplastic
• Pituitary adenoma
• Parasellar mass (germinoma,
ependymoma, glioma)
• Rathke's cyst
• Craniopharyngioma
• Pituitary metastases (breast,
lung, colon carcinoma)
• Lymphoma and leukemia
• Meningioma
• Infiltrative/inflammatory
• Lymphocytic hypophysitis
• Hemochromatosis
• Sarcoidosis
• Histiocytosis X
• Granulomatous hypophysitis
• Vascular
• Pituitary apoplexy
• Infarction with diabetes;
postpartum necrosis)
• Sickle cell disease
• Arteritis

7. Dev’tal and Genetic Causes of Hypopituitarism
Pituitary Dysplasia
 Result in aplastic, hypoplastic, or
ectopic pituitary gland dev’t
Septo-Optic Dysplasia
 Pit dysfunction leads to diabetes
insipidus, GH def and short stature,
and, TSH def.
 Mutations in the HESX1 gene
Tissue-Specific Factor
Mutations
 Pit-1 mutations cause combined
GH, PRL, and TSH deficiencies
 Prop-1 is appears to be required for
Pit-1 function
 PROP1 mutations result in combined
GH, PRL, TSH, and gonadotropin
deficiency
 Over 80% of these patients have
growth retardation

8. Developmental Hypothalamic Dysfunction
Kallmann Syndrome
Defective hypothalamic GnRH
syn & is assoc with anosmia or
hyposmia due to olfactory bulb
agenesis
Xterized by low LH and FSH levels
and low conc of sex steroids
(testosterone or estradiol)
Repetitive GnRH admin restores
normal pit gonadotropin responses,
pointing to a hypothalamic defect
Bardet-Biedl
Syndrome
Rare genetical disorder xterized
by mental retardation, renal
abnormalities, obesity, and
polydactle. Central diabetes
insipidus may or may not be
associated.
• GnRH deficiency occurs, Retinal
degeneration begins in early
childhood, and most patients are
blind by age 30

9. Developmental Hypothalamic Dysfunction
Leptin and Leptin
Receptor Mutations
Lack causes broad spectrum
of hypothalamic
abnormalities,
• Including hyperphagia,
obesity, and central
hypogonadism.
• Decreased GnRH prodn in
these patients results in
attenuated pituitary FSH and
LH synthesis and release.
Prader-Willi Syndrome
Deletion of genes on
chromosome 15q.
• Xterised by
hypogonadotropic
hypogonadism, hyperphagia-obesity,
chronic muscle
hypotonia, mental retardation,
and adult-onset diabetes mellitus

10. Acquired Hypopituitarism
 Caused by
• Accidental or neurosurgical
trauma
• Vascular events such as
apoplexy
• Pituitary or hypothalamic
neoplasms,
• Craniopharyngioma,
lymphoma, or metastatic
tumors.
• Inflammatory disease such
as lymphocytic hypophysitis
• Infiltrative disorders such as
sarcoidosis,
hemochromatosis
• Tuberculosis; or irradiation.

11. Acquired Hypopituitarism
• Inflammatory Lesions
commonly infections by
• Tuberculosis
• Opportunistic Fungal infection
assoc with HIV
• Tertiary syphilis
• Other inflammatory processes,
such as granulomas and
sarcoidosis
• Lymphocytic
Hypophysitis
• Often in postpartum
women; it usually presents
with hyperprolactinemia,
• Mildly elevated PRL levels.
• patients manifest syms of
progressive mass effects
with headache and visual
disturbance. ESR often is
elevated

12. Pituitary Apoplexy
• Acute intrapituitary hemorrhagic
vascular events
• May occur spontaneously in a
preexisting
• Adenoma;
• Postpartum (sheehan's
syndrome); or in assoc with
diabetes
• Hypertension, sickle cell anemia,
or acute shock
• Apoplexy is an endocrine
emergency
• May result in severe
hypoglycemia, hypotension
and shock, central nervous
system (CNS) hemorrhage,
and death.
• Acute symps include severe
headache with signs of
meningeal irritation,
bilateral visual changes,
ophthalmoplegia, and, in
severe cases.
• Cardiovascular collapse and
loss of consciousness

13. Presentation and Diagnosis
• Clinical manifestations of
depend on which hormones
and the extent of hormone
deficiency
• GH def causes growth
disorders in children &
abnormal body composit in
adults
• Gonadotropin def causes
menstrual disorders and
infertility and decreased
sexual function, infertility,
and loss of secondary
sexual Xteristics in men.
• TSH def causes growth
retardation in children
and features of
hypothyroidism in
children and adults.
• ACTH def leads to
hypocortisolism
• PRL def causes failure of
lactation.
• When lesions involve the
posterior pituitary,
polyuria and polydipsia
reflect loss of vasopressin
secretion

14. Laboratory Investigation
• Biochemical diagnosis of pituitary insufficiency is
made by demonstrating low levels of trophic
hormones in the setting of low levels of target
hormones
• Test for
• ACTH
• TSH
• FSH/LH
• GH
• Vasopressin

15. Treatment: Hypopituitarism
ACTH, Hormone
Replacement
• Hydrocortisone (10–20
mg A.M.; 5–10 mg
P.M.)
• Cortisone acetate (25
mg A.M.; 12.5 mg P.M.)
• Prednisone (5 mg A.M.)
FSH/LH
• Males
• Testosterone enanthate (200 mg
IM every 2 weeks)
• Testosterone skin patch (5 mg/d)
• Females
• Conjugated estrogen (0.65–1.25
mg qd for 25 days)
• 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

16. Treatment: Hypopituitarism
TSH
L-Thyroxine (0.075–0.15 mg
daily)
• Generally hormone
replacement therapy,
including glucocorticoids,
thyroid hormone, sex
steroids, growth hormone,
and vasopressin
GH
• Adults: Somatotropin (0.1–
1.25 mg SC qd)
• Children: Somatotropin
[0.02–0.05 (mg/kg per day)]
• Vasopressin
• Intranasal desmopressin
(5–20 g twice daily)
• Oral 300–600 g qd