Disorders of the Anterior Pituitary and Hypothalamus

DISORDERS OF THE ANTERIOR PITUITARY AND

HYPOTHALAMUS

DR. JUAN CARLOS BECERRA MARTÍNEZ

CÁTEDRA DE MEDICINA INTERNA-MC3087

Tecnológico de MonterreyCampus Guadalajara

Anterior Pituitary Hormone Expression and Regulation

Harrison’s 18th Edition.

Harrison’s 18th Edition.

(GnRH) pulses induce secretory pulses of (LH).

Harrison’s 18th Edition.

Etiology of Hypopituitarism

Harrison’s 18th Edition.

Development/structural Pituitary dysplasia/aplasia Congenital CNS mass, encephalocele Primary empty sella

Congenital hypothalamic disorders (septo-optic dysplasia: dysgenesis of the corpus callosum)

Prader-Willi syndrome:○ Hypogonadotropic hypogonadism, hyperphagia-obesity, chronic muscle

hypotonia, mental retardation, and adult-onset diabetes mellitus Laurence-Moon-Biedl syndrome:

○ Mental retardation, renal abnormalities, obesity, and hexadactyly, brachydactyly, or syndactyly. GnRH deficiency occurs in 75%

Kallmann syndrome:○ Defective (GnRH) synthesis and is associated with anosmia or hyposmia

due to olfactory bulb agenesis.

Etiology of Hypopituitarism

Harrison’s 18th Edition.

Traumatic Surgical resection Radiation damage Head injuries

Etiology of Hypopituitarism

Harrison’s 18th Edition.

Neoplastic Pituitary adenoma Parasellar mass (germinoma, ependymoma, glioma) Rathke's cyst:  pars intermedia benign cystsCraniopharyngioma Hypothalamic hamartoma, gangliocytoma Pituitary metastases (breast, lung, colon carcinoma) Lymphoma and leukemia Meningioma

Etiology of Hypopituitarism

Harrison’s 18th Edition.

Infiltrative/inflammatoryLymphocytic hypophysitis:

○ Postpartum ○ MRI resembles an adenoma○ Resolves after several months of glucocorticoid

treatmentHemochromatosis: hereditary, (liver, pancreatic, heart)SarcoidosisHistiocytosis X: clonal proliferation of Langerhans cells

Etiology of Hypopituitarism

Harrison’s 18th Edition.

Vascular Pituitary apoplexy Pregnancy-related (infarction with diabetes;

postpartum necrosis) Sickle cell disease Arteritis

Etiology of Hypopituitarism

Harrison’s 18th Edition.

Infections Fungal (histoplasmosis)Parasitic (toxoplasmosis) Tuberculosis Pneumocystis carinii

Etiology of Hypopituitarism

Harrison’s 18th Edition.

Trophic hormone failure associated with pituitary compression or destruction usually occurs sequentially: GH > FSH > LH > TSH > ACTH.

During childhood, growth retardation is often the presenting feature, and in adults, hypogonadism is the earliest symptom.

Tests of Pituitary Sufficiency

Harrison’s 18th Edition.

Tests of Pituitary Sufficiency

Harrison’s 18th Edition.

Tests of Pituitary Sufficiency

Harrison’s 18th Edition.

Treatment: Hypopituitarism

Harrison’s 18th Edition.

Hypothalamic, Pituitary, and Other Sellar Masses

Harrison’s 18th Edition.

Hypothalamic, Pituitary, and Other Sellar Masses

Harrison’s 18th Edition.

Features of Sellar Mass Lesions

Harrison’s 18th Edition.

Features of Sellar Mass Lesions

Harrison’s 18th Edition.

Features of Sellar Mass Lesions

Harrison’s 18th Edition.

Features of Sellar Mass Lesions

Harrison’s 18th Edition.

Screening Tests for Functional Pituitary Adenomas

Harrison’s 18th Edition.

Treatment: Transsphenoidal Surgery

Harrison’s 18th Edition.

Treatment: Transsphenoidal Surgery

Harrison’s 18th Edition.

Treatment: Prolactinoma

Harrison’s 18th Edition.

Treatment: Prolactinoma

Harrison’s 18th Edition.

Oral dopamine agonists (cabergoline and bromocriptine) are the mainstay of therapy for patients with micro- or macroprolactinomas.

Dopamine agonists suppress PRL secretion and synthesis as well as lactotrope cell proliferation.

Treatment: Growth Hormone

Harrison’s 18th Edition.

Causes of Acromegaly

Harrison’s 18th Edition.

Causes of Acromegaly

Harrison’s 18th Edition.

Management of Acromegaly

Harrison’s 18th Edition.

Management of Acromegaly

Harrison’s 18th Edition.

Somatostatin AnaloguesOctreotideLanreotide,Sandostatin-LAR is a sustained-release, long-

acting formulation of octreotide incorporated into microspheres that sustain drug levels for several weeks after intramuscular injection.

Management of Acromegaly

Harrison’s 18th Edition.

GH Receptor AntagonistPegvisomant antagonizes endogenous GH

action by blocking peripheral GH binding to its receptor.

ACTH Deficiency

Harrison’s 18th Edition.

The total daily dose of hydrocortisone replacement preferably should not exceed 25 mg daily, divided into two or three doses.

Prednisone (5 mg each morning) is longer-acting and has fewer mineralocorticoid effects than hydrocortisone.

Cushing's Syndrome (ACTH-Producing Adenoma)

Harrison’s 18th Edition.

Cushing's Syndrome (ACTH-Producing Adenoma)

Harrison’s 18th Edition.

Cushing's Syndrome (ACTH-Producing Adenoma)

Harrison’s 18th Edition.

Ketoconazole, an imidazole derivative antimycotic agent, inhibits several P450 enzymes and effectively lowers cortisol in most patients with Cushing's disease when administered twice daily (600–1200 mg/d).

Metyrapone (2–4 g/d) inhibits 11-hydroxylase activity and normalizes plasma cortisol in up to 75% of patients.

Mitotane (o,p′-DDD; 3–6 g/d orally in four divided doses) suppresses cortisol hypersecretion by inhibiting 11-hydroxylase

Other agents include aminoglutethimide (250 mg tid), trilostane (200–1000 mg/d), cyproheptadine (24 mg/d), and IV etomidate (0.3 mg/kg per hour).