Disorders of the Anterior Pituitary and Hypothalamus, review of Harrison's Principles of Internal Medicine.

1. DR. JUAN CARLOS BECERRA MARTÍNEZ
CÁTEDRA DE MEDICINA INTERNA-MC3087
Tecnológico de Monterrey
Campus Guadalajara

2. Anterior Pituitary Hormone
Expression and Regulation
Harrison’s 18th Edition.

3. Harrison’s 18th Edition.

4. (GnRH) pulses induce secretory
pulses of (LH).
Harrison’s 18th Edition.

5. 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.

6. Etiology of Hypopituitarism
Harrison’s 18th Edition.
 Traumatic
 Surgical resection
 Radiation damage
 Head injuries

7. Etiology of Hypopituitarism
Harrison’s 18th Edition.
 Neoplastic
 Pituitary adenoma
 Parasellar mass (germinoma, ependymoma, glioma)
 Rathke's cyst: pars intermedia benign cysts
 Craniopharyngioma
 Hypothalamic hamartoma, gangliocytoma
 Pituitary metastases (breast, lung, colon carcinoma)
 Lymphoma and leukemia
 Meningioma

8. Etiology of Hypopituitarism
Harrison’s 18th Edition.
 Infiltrative/inflammatory
 Lymphocytic hypophysitis:
○ Postpartum
○ MRI resembles an adenoma
○ Resolves after several months of glucocorticoid
treatment
 Hemochromatosis: hereditary, (liver, pancreatic,
heart)
 Sarcoidosis
 Histiocytosis X: clonal proliferation of Langerhans
cells

9. Etiology of Hypopituitarism
Harrison’s 18th Edition.
 Vascular
 Pituitary apoplexy
 Pregnancy-related (infarction with diabetes;
postpartum necrosis)
 Sickle cell disease
 Arteritis

10. Etiology of Hypopituitarism
Harrison’s 18th Edition.
 Infections
 Fungal (histoplasmosis)
 Parasitic (toxoplasmosis)
 Tuberculosis
 Pneumocystis carinii

11. 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.

12. Tests of Pituitary Sufficiency
Harrison’s 18th Edition.

13. Tests of Pituitary Sufficiency
Harrison’s 18th Edition.

14. Tests of Pituitary Sufficiency
Harrison’s 18th Edition.

15. Treatment: Hypopituitarism
Harrison’s 18th Edition.

16. Hypothalamic, Pituitary, and Other
Sellar Masses
Harrison’s 18th Edition.

17. Hypothalamic, Pituitary, and Other
Sellar Masses
Harrison’s 18th Edition.

18. Features of Sellar Mass Lesions
Harrison’s 18th Edition.

19. Features of Sellar Mass Lesions
Harrison’s 18th Edition.

20. Features of Sellar Mass Lesions
Harrison’s 18th Edition.

21. Features of Sellar Mass Lesions
Harrison’s 18th Edition.

22. Screening Tests for Functional
Pituitary Adenomas
Harrison’s 18th Edition.

23. Treatment: Transsphenoidal
Surgery
Harrison’s 18th Edition.

24. Treatment: Transsphenoidal
Surgery
Harrison’s 18th Edition.

25. Treatment: Prolactinoma
Harrison’s 18th Edition.

26. 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.

27. Treatment: Growth Hormone
Harrison’s 18th Edition.

28. Causes of Acromegaly
Harrison’s 18th Edition.

29. Causes of Acromegaly
Harrison’s 18th Edition.

30. Management of Acromegaly
Harrison’s 18th Edition.

31. Management of Acromegaly
Harrison’s 18th Edition.
 Somatostatin Analogues
 Octreotide
 Lanreotide,
 Sandostatin-LAR is a sustained-release, long-
acting formulation of octreotide incorporated into
microspheres that sustain drug levels for several
weeks after intramuscular injection.

32. Management of Acromegaly
Harrison’s 18th Edition.
 GH Receptor Antagonist
 Pegvisomant antagonizes endogenous GH
action by blocking peripheral GH binding to its
receptor.

33. 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.

34. Cushing's Syndrome (ACTH-
Producing Adenoma)
Harrison’s 18th Edition.

35. Cushing's Syndrome (ACTH-
Producing Adenoma)
Harrison’s 18th Edition.

36. 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).