1. HYPOthalamic-pituitary dysfunction
Chapter 17 & 18

2. Hypothalamic-pituitary system
Neuroendocrine System
Contains the hypothalamus and Pituitary Gland
Controls thyroid, adrenal and reproductive function

6. Anterior pituitary TROPIC HORMONES
MSH: secretion of melanin (melanocyte stimulating hormone)
FSH: estrogen production and spermatogenesis (follicle stimulating hormone)
LH: ovulation, progesterone and testosterone production (luteinizing hormone)
ACTH: cortisol production and maintenance of adrenal gland (adrenocorticotropic hormone)
TSH: thyroid hormone production (thyroid stimulating hormone)
GH: skeletal muscle growth, regulates metabolism, necessary for stress adaptation (growth hormone)
Regulated by GHRH and Somatostatin
IGF-1 and IGF-2 (insulin-like growth factor)
Prolactin: milk production (lactation)

7. Posterior pituitary POLYPEPTIDE HORMONES
ADH (vasopressin): controls plasma osmolality (antidiuretic hormone)
Regulated by glutamate and GABA
Increased release with stress, trauma, decreased intravascular volume
Decreased release with decreased plasma osmolality and increased intravascular volume
Oxytocin: uterine contraction and milk ejection
Also has some antidiuretic effects

8. Adrenal glands

9. Adrenal Medulla
Catecholamine secretion
Epinephrine and norepinephrine

10. Adrenal Cortex Glucocorticoids
Carbohydrate metabolism, immune suppression, anti-inflammatory effects, suppress bone formation, suppress ADH secretion, stimulate gastric acid secretion
In high levels cause:
Increased appetite, fat deposits in face, abdomen, upper back, hypocalcemia, decreased ACTH synthesis

11. Cortisol CRH  ACTH  cortisol secretion
Potent naturally occurring glucocorticoid
Necessary for maintenance of life
Diurnal release of ACTH
Negative feedback loop associated with ACTH release
Increased release: low levels of circulating cortisol; stress reactions
Decreased release: high levels of circulating cortisol; synthetic glucocorticoid use

12. Mineralcorticoids Aldosterone Natural occurring mineralcorticoid
Promotes sodium retention and potassium excretion
Regulated by the renin-angiotensin system (primarily angiotensin II)
Sodium and water depletion
Hyperkalemia
Decreased blood volume

15. Hormonal alterations 1. Inadequate Synthesis
Precursor dysfunction
2. Failure of Feedback Systems
Too much or too little hormone synthesis
3. Inactive Hormones
Directly inhibited or degraded
4. Ineffective Hormone Delivery
Decreased blood supply
Inadequate carriers
5. Decreased Target-Cell Sensitivity
Too little receptors
Presence of antibodies on receptors

16. SIADH Increased ADH release regardless of plasma osmolality Causes:
Neoplasms
Pulmonary disorders
CNS disorders
Medications

17. Manifestations: HYPONATREMIA Thirst Dyspnea Fatigue Vomiting
Confusion (late)
Lethargy (late)
Convulsions (late)
Irreversible neurological damage (late)

18. Diagnostics: Treatment: Serum hypoosmolality Serum hyponatremia
Urine hyperosmolality
Normal adrenal, thyroid, and renal function
Resistant hyponatremia
Treatment:
Fluid restriction
Hypertonic solutions
Use of demeclocycline

19. demeclocycline Tetracycline drug class
Has unique side effect of stimulating urine flow
Used for SIADH

20. Diabetes insipidus Decreased ADH release Causes: Neurogenic
Insufficient secretion of ADH
Interference of ADH synthesis (brain tumors, aneurysm, infection, thrombosis)
Nephrogenic
Renal tubules do not respond appropriately to ADH
Acquired
Pyelonephritis, polycystic kidney disease, anesthetics, medications
Genetic

21. Manifestations: Polyuria Nocturia Thirst Polydipsia Dilute urine
Urine hypoosmolality
Serum hypernatremia
Serum hyperosmolality

22. Treatment:
Desmopressin
Treatment of underlying cause

23. desmopressin Vasopressin Antidiuretic hormone
Promotes renal conservation of water, increasing permeability of renal tubules
Used for Diabetes Insipidus
Given intranasally, SQ, IV, or PO
Adverse effects:
Excessive water retention
Limited side effects

24. Hypopituitarism Causes: Inadequate Hypothalamic Releasing Hormones
Inadequate anterior pituitary gland
Infarction
Adenoma
Damage to pituitary stalk
Meningitis
Tuberculosis
Autoimmune disorders

25. Manifestations: Deficient ACTH : anorexia, fatigue, hypoglycemia
Deficient TSH : cold intolerance, lethargy, decreased metabolism
Deficient FSH and LH : amenorrhea, testicular atrophy, decreased libido
Deficient GH : hypopituitary dwarfism (children)
Feeling of poor well-being, osteoporosis, fatigue (adult) generalized complaints
Panhypopituitarism (all anterior pituitary hormones are deficient)

26. HYperpituitarism Acromegaly
Prolonged exposure to increased GH and IGF-1
Middle aged adults
Rare
Slowly progressive
Cause:
Pituitary adenoma

27. Manifestations: Enlarged tongue Enlarged sweat glands Coarse skin
Excessive body hair
Enlargement of facial bones (protrusion of forehead and jaw)
Enlargement of hands and feet

28. Treatment: Surgical removal of GH secreting adenoma Radiation
Octreotide
Lanreotide
Pegvisomant

29. Somatostatin analogs Ocreotide Lanreotide IM injection
Indicated for acromegaly
Adverse effects:
GI symptoms
gallstones
Lanreotide
Prefilled SQ syringe
Diarrhea

30. Growth hormone receptor antagonist
Pegvisomant
Most effective drug option for acromegaly
SQ injection
Expensive
Adverse effects:
GI upset
Chest pain
Flu-like symptoms
Monitor hepatic function

31. Prolactinoma Sustained, elevated release of prolactin Manifestations:
Galactorrhea
Amenorrhea
Treatment:
Bromocriptine
Cabergoline
Causes:
Pituitary tumor

32. Dopamine agonists
Ergot derivatives Cabergoline -PO with or without food -can be used to correct amenorrhea, infertility and galactorrhea associated with a prolactinoma -can also cause tumor regression -immediate effects of decreased prolactin secretion -should monitor prolactin monthly until normal, treatment can stop after 6 months of normal levels -adverse effects: nausea, headache, dizziness Bromocriptine Similar, except is not tolerated as well as cabergoline

33. Alterations of adrenal function
HYPERCORTISOLISM
Cushing Syndrome
Chronic exposure to excessive cortisol
Cushing Disease
Excessive secretion of ACTH
Cushing-Like Syndrome
Administration of synthetic glucocorticoids

34. Manifestations: Weight gain
Fat deposits in face, trunk and cervical area (moon face, buffalo hump)
Glucose intolerance (hyperglycemia)
Protein wasting (thin extremities)
Osteoporosis
Collagen loss (thin, weak skin, striae, bruising)
Increased catecholamine activity (hypertension)
Increased mineralcorticoid activity (edema, potassium loss)
Cushing Disease in Females (increased androgen levels)
Increased hair growth
Acne
amenorrhea

35. Diagnostics: Urine cortisol Dexamethasone suppression test
Measurement of ACTH and cortisol levels

36. Treatment:
treat underlying cause
tumor removal
radiation therapy
Ketoconazole
antifungal, but also blocks glucocorticoid synthesis
mg/day (high doses)
must monitor liver enzymes at this high dose

37. Secondary Adrenal Insufficiency : decreased ACTH
HYPOCORTISOLISM
Addison’s Disease (Primary Adrenal Insufficiency) : increased ACTH, decreased cortisol and aldosterone
Secondary Adrenal Insufficiency : decreased ACTH
Causes:
Autoimmune attack of the adrenal cortex (Primary Adrenal Insufficiency)
Prolonged administration of glucocorticoids (Secondary Adrenal Insufficiency)
Pituitary tumors (Secondary Adrenal Insufficiency)
Infections (tuberculosis)

38. Manifestations: Weakness Fatigue
Hyperpigmentation of the skin (only in Addison’s disease)
Weight loss
Hypotension
Hypoglycemia
Syncope

39. Diagnostics: Hyperkalemia Hyponatremia Hypoglycemia
Decreased serum and urine cortisol
Increased ACTH (Addison’s Disease)

40. Treatment:
Lifelong glucocorticoid supplementations (higher doses during acute stressors)
Hydrocortisone
Mineralcorticoid supplementation
Fludrocortisone

41. Hydrocortisone
For use in Addison’s Disease
Take entire dose in am or 2/3 in am and remainder in afternoon
Lifelong supplementation
Increased dose at times of stress
Excessive doses can produce symptoms of Cushing’s Syndrome

42. Mineralcorticoid replacement 0.1 mg PO daily
Fludricortisone
Mineralcorticoid replacement
0.1 mg PO daily
Used in combination with glucocorticoid
Adverse effects:
With high doses
Hypertension
Hypokalemia
Weight gain
Edema

43. Hypersecretion of androgens and estrogens
Caused by adrenal adenomas or carcinomas
Feminization: development of female secondary sex characteristics
Gynecomastia, testicular atrophy, decreased libido, early development of sex characteristics
Virilization: development of male secondary sex characteristics
Excessive face/body hair growth, clitoral enlargement, amenorrhea, acne, breast atrophy

44. Tumor of adrenal medulla
PHEOCHROMOCYTOMA
Causes continuous, excessive secretion of catecholamines
Rare and can be malignant
Manifestations:
Hypertension, tachycardia, diaphoresis, palpitations, headaches, hypermetabolism
Treatment:
Check for excessive catecholamines in blood and urine
Surgical removal of tumor
Alpha and beta blockers