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Anatomy, Pathology/ disorders and Management / pharmacological
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Pituitary and Hypothalamus
Oriba Dan Langoya
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)
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
Hypothalamic & Ant Pit Insufficiency
• 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)
Etiology of Hypopituitarism
• Traumatic • Surgical resection • Radiation damage • Head injuries • Infections • Fungal (histoplasmosis) • Parasitic (toxoplasmosis) • Tuberculosis • Pneumocystis carinii
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
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
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
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
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.
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
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
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
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
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
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