The document discusses various ways that hormonal regulation can become altered, leading to either elevated or depressed hormone levels. It focuses on alterations within the hypothalamic-pituitary system and diseases of the posterior and anterior pituitary. Specific conditions covered include SIADH, diabetes insipidus, hypopituitarism, hyperpituitarism, acromegaly, hyperprolactinemia, hyperthyroidism, and Graves' disease. The clinical manifestations and diagnostic testing for some of these conditions are also outlined.

1. Alterations of Hormonal Regulation
Reference: Pathophysiology by Kathryn
McCance
Mindy Milton, MPA, PA-C
July 29, 2010
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2. Elevated or Depressed Hormone Levels
 Failure of feedback systems
 Dysfunction of an endocrine gland
 Secretory cells are unable to produce, obtain,
or convert hormone precursors
 The endocrine gland synthesizes or releases
excessive amounts of hormone
 Increased hormone degradation or
inactivation
 Ectopic hormone release
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3. Target Cell Failure
 Receptor-associated disorders
 Decrease in number of receptors
 Impaired receptor function
 Presence of antibodies against specific receptors
 Antibodies that mimic hormone action
 Unusual expression of receptor function
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4. Alterations of the Hypothalamic-
Pituitary System
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5. Diseases of the Posterior Pituitary
 Syndrome of inappropriate antidiuretic hormone
secretion (SIADH)
 Hypersecretion of ADH
 Without physiologic stimulus
 Most common etiology ectopically produced ADH
 Malignant tumors
 For diagnosis, normal adrenal and thyroid function must
exist
 Clinical manifestations are related to enhanced renal
water retention, hyponatremia, and hypoosmolarity
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6. Diseases of the Posterior Pituitary
 Diabetes insipidus
 Insufficiency of ADH
 Partial or total inability to concentrate the urine
 Neurogenic - MOST COMMON cause
 Destruction of stalk
 Insufficient amounts of ADH
 Nephrogenic
 Inadequate response to ADH
 Clinical manifestations
 Polyuria and polydipsia
 Low urine sp gravity
 Hypernatremia (loss of fluid)
 Increased plasma osmolarity
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7. Diseases of the Anterior Pituitary
 Hypopituitarism
 Pituitary infarction
 Sheehan syndrome - post-partum hemorrhage.
 Hemorrhage
 Shock
 Others: head trauma, infections, and tumors
 Decrease secretion of all or some hormones
 Clinical manifestations
 Depends on severity of each individual hormone deficiency
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8. Diseases of the Anterior Pituitary
 Hypopituitarism
 Panhypopituitarism
 ACTH deficiency
 TSH deficiency
 FSH and LH deficiency
 GH deficiency
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9. Diseases of the Anterior Pituitary
 Hyperpituitarism
 Commonly due to a benign, slow-growing
pituitary adenoma
 Adenoma secretes the hormone of the origin cell type
without physiological need or control of negative
feedback
 Manifestations due to local expansion of tissue
 Headache and fatigue
 Visual changes (optic chiasm or cavernous sinus)
 Hyposecretion of neighboring anterior pituitary
hormones
 GH, LH, and FSH-secreting cells most sensitive to pressure
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10. Diseases of the Anterior Pituitary
 Hypersecretion of growth hormone (GH)
 Acromegaly
 Hypersecretion of GH during adulthood
 Gigantism
 Hypersecretion of GH in children and adolescents
 Most common etiology is due to primary pituitary
adenoma
 Also see increased release of insulin-like growth factor 1
with increase GH
 Both lead to increase growth of bone and connective tissue
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11. Diseases of the Anterior Pituitary
 Acromegaly
 Pathophysiology
 Increased reabsorption of phosphate at the kidney
tubule
 Increased metabolic rate
 Impaired glucose metabolism
 Inhibition of peripheral glucose uptake
 Increased glucose production
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12. Acromegaly
 Clinical manifestation
 Enlarged tongue
 Coarse skin and body hair
 Enlarged bones of the face, hands, and feet
 Elongation of the ribs – barrel chest
 Elevated blood glucose
 Signs of tumor expansion
 Visual changes
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13. Hypersecretion of Growth
Hormone (GH)
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14. Diseases of the Anterior Pituitary
 Hypersecretion of prolactin- 30% of tumors
 Caused by prolactinomas
 In females, increased levels of prolactin cause
amenorrhea, galactorrhea, hirsutism, and osteopenia
 In males, increased levels of prolactin cause
hypogonadism, erectile dysfunction, impaired libido,
galactorrhea, oligospermia, and diminished ejaculate
volume
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15. Alterations of Thyroid Function
 Hyperthyroidism - Thyrotoxicosis
 Graves disease – most common
 Autoimmune
 Goiter
 Exophthalmos - infiltration of smooth
muscle around eye.
 Pretibial myxedema
 Toxic multinodular Goiter
 Pregnancy
 Increased TSH
 Puberty
 Iodine deficiency - stimmulation
 Toxic adenoma of thyroid
 Goiter with one hyperfunctioning nodule
 Mutation of TSH receptor
 TSH secreting pituitary adenoma
 Thyroid Storm
 Medical emergency 15
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16. Hyperthyroidism
Clinical Manifestations
 Subjective  Objective
 Heat intolerance  Muscle wasting
 Wt loss  Wt loss
 Fatigue  Diaphoresis
 Diarrhea  Flushed warm skin
 Irritability  Tachycardia
 Tremors  Atrial dysrhythmias
 Dyspnea  Hyperreflexia
 Anxiety
 Exophthalmos
 Menstrual irregularities
 Goiter
 Soft fine hair
 incresed sensitivity to
catacholamines.
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17. Hyperthyroidism – Lab Dx
 Pituitary  Thyroid
 Elevated TSH  Decreased TSH
 Elevated T3  Elevated T3
 Elevated T4  Elevated T4
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18. Alterations of Thyroid Function
 Hypothyroidism
 Primary hypothyroidism
 Subacute thyroiditis - can follow
viral infection. Tender neck.
 Autoimmune thyroiditis
(Hashimoto disease - opposite of
Graves, both #1.)
 Postpartum thyroiditis
 Myxedema
 Severe or long-standing
 Congenital hypothyroidism
 Cretinism
 Post therapy for hyperthyroidism
 Myxedema coma
 Medical emergency
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19. Hypothyroidism
Clinical Manifestations
 Subjective  Objective
 Weakness  Decreased cardia output
 Tiredness  Decreased bp
 Cold intolerance  Increased blood cholesterol
 Dry, flaky skin  Anemia
 Brittle nails
 Bradycardia
 Goiter
 Amenorrhea
 Slightly lower temp
 Confusion/dementia
 Reflex delayed return
 Constipation  Wt gain
 Wt gain  Cool skin
 Dyspnea
 Memory loss
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20. Hypothyroidism – Lab Dx
 Pituitary  Thyroid
 TSH  Elevated TSH
 Decreased T3  Decreased T3
 Decreased T4  Decreased T4
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21. Alterations of Parathyroid Function
 Hyperparathyroidism
 Primary
hyperparathyroidism
 Excess secretion of PTH
from one or more
parathyroid glands -
etiology unknown.
 Secondary
hyperparathyroidism
 Increase in PTH secondary
to a chronic disease - think
renal failure
 Hypoparathyroidism
 Abnormally low PTH levels
 Usually caused by
parathyroid damage in
thyroid surgery 21
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22. Alterations of Parathyroid Function
 Hyperparathyroidism  Hypoparathyroidism
 Increased bone resorption  Decreased bone resorption
by osteoclasts by osteoclast
 Pathologic fractures  Decreased calcium
 Kyphosis reabsorption from renal
 Hypercalcemia tubules
 Hypophosphatemia
 Hypocalcemia
 Hyperphosphatemia
 Alkaline urine,
Hypercalciuria, and  Lower threshold for nerve
hyperphosphaturia and muscle irritability
 Renal stones
 Calcium moves out of
cells
 Decrease response to ADH  Muscle spasms
 Mild insulin resistance  Hyperreflexia
 NV - direct stimulation to  seizure
CNS.  Must give Vit D.
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23. Type 1 Diabetes Mellitus
 Genetic susceptibility
 Environmental factors
 Demonstrates pancreatic atrophy and specific loss of
beta cells
 No insulin
 Two types
 Immune
 Cell mediated destruction of beta cells
 Macrophages, T and B lymphocytes, and natural killer cells are
present
 Production of auto-antibodies to islet cells or to insulin
 HLA-DR3 and DR4 associated with higher risk of disease
 Non-immune
 Pancreatitis 23
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24. Type 1 Diabetes Mellitus
 Diagnosis
 Fasting blood glucose > 126 on two occasions OR
 R(andom)BS > 200 on two occasions with AND
symptomatic.
 Tracking progression and treatment effectiveness
 HgbA1c – glycosylated hemoglobin (%)
 RBC 120 d life span
 Irreversible binding
 Goal is 7, normal < 6
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25. Type 1 Diabetes Mellitus
 Manifestations
 Hyperglycemia,
 polydipsia, polyuria, polyphagia,
 weight loss, and fatigue
 Ketoacidosis (metabolic acidosis)
 Secondary to increased lipolysis with by-product
formation of acetone bodies from FFA catabolism
 Acetoacetic acid, hydroxybutyric acid, and acetone
 Blood and urine
 Glycosuria when renal threshold met (180 mg/dl)
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26. Type 1 Diabetes Mellitus
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27. Type 1 Diabetes Mellitus
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28. Dysfunction of the Pancreas
 Type 2 diabetes mellitus
 Maturity-onset diabetes of youth (MODY)
 Mutation of gene for insulin secretion or action
 Gestational diabetes mellitus (GDM)
 During pregnancy
 Majority go on to have DMII later
 Common form of diabetes mellitus type 2
 Insulin resistance
 Less receptors
 Compensatory hyperinsulinemia until beta cell burn out
 Dyslipidemia
 hypertension
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29. Type 2 Diabetes Mellitus
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30. Acute Complications of DM
 Hypoglycemia - #1 complication of DMII
 Increased insulin or oral medications in the presence of decreased glucose
availability (too much insulin or no food or increased exercise)
 Glucose 45-60 mg/dl
 Result in SNS stimulation DANGEROUS!
 Diaphoresis To the brain.
 Tachycardia Self control is
 Palpitations dangerous, especially if
 Tremors, pallor too tight, for this
 Altered mental status
 Diabetic ketoacidosis
 No insulin and counter regulatory hormones: cortisol and catecholamines
 Triggered by infection, illness, surgery, or interruption of insulin therapy
 Gluconeogenesis and Ketogenesis = ketone bodies = metabolic acidosis
 Clinical manifestations
 Dehydration due to osmotic diuresis and hyperglycemia Total K stores are down,
 Glucosuria but may not be noticable,
 hypokalemia so have to be careful
 Kussmaul respirations treating.
 Ketonuria
Look at K!!!
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 ALOC - coma
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31. Diabetic Ketoacidosis
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32. Acute Complications of DM
 Somogyi effect
 Drop in blood sugar causes stimulation of body’s glucose counter
regulation measures
 Nocturnal hypoglycemia
 Nightmares
 Morning headache
 Glucagon, cortisol, GH, and epinephrine
 Gluconeogenesis
 glycogenolysis
 Result is rebound am hyperglycemia
 Too much insulin!!! Many will want to over treat.
 Dawn phenomenon
 Morning hyperglycemia due to decreased available insulin
 No nocturnal hypoglycemia
 Nocturnal elevation of GH
 Hyperglycemia by decreasing peripheral tissue glucose uptake
 Faster insulin clearance 32
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33. Chronic Complications of Diabetes
Mellitus
 Microvascular disease = Glycosylation end-products
 Retinopathy
 Retinal ischemia and RBC aggregation
 Progression from non-proliferative to proliferative disease
 Neovascularization and fibrous tissue formation
 Macula and optic disk = vision loss
 Diabetic nephropathy
 Glomeruli damage – hypertension and hyperglycemia
 Basement membrane thickening, hypertrophy = decrease GFR
 Microalbuminuria – first sign 3300.
 Diabetic neuropathy
 “dying back” – effects distal portions of nerves significantly
 Toes, feet, ankles
 Axon degeneration
 Involves sensory, motor, autonomic
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34. Chronic Complications of DM
 Macrovascular disease = large vessel
 Damage due to elevated LDL, triglycerides, and
AGE
 Coronary artery disease
 Stroke
 Peripheral arterial disease
 Infection
 Hyperglycemia
 Poor circulation
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35. Alterations of Adrenal Function
 Disorders of the adrenal cortex
 Cushing disease - acth microadenoma.
 Excessive anterior pituitary secretion of ACTH
 Mineralocorticoids and glucocorticoids
 Cushing syndrome
 Excessive level of cortisol, regardless of cause
 Exogenous
 Steroid treatment for chronic inflammatory conditions
 Endogenous
 ATCH secreting pituitary microadenoma (C. disease)
 Adrenal cortex tumor
 Ectopic secretion of ACTH by Lung cancer
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36. Cushing Syndrome
 Subjective:  Objective:
 Sx of gastritis, ulcer disease  General – buffalo hump,
 Acne truncal obesity, moon facies
 Wt gain
 Wt changes/distribution
 Mental status – depressed
 Increased facial hair with mood swings
 Thinning of scalp hair  Skin- atrophy, poor wound
 Bruising healing, purple striae,
 Decreased muscle strength ecchymosis, increase facial
or body hair
 MSK- muscle wasting,
decreased strength and tone
 Hypertension
 Hyperglycemia
 Glycosuria
 Hypokalemia
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37. Cushing Disease
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38. Alterations of Adrenal Function
 Disorders of the adrenal cortex
 Hyperaldosteronism
 Primary hyperaldosteronism (Conn disease)
 Benign, single adrenal adenoma (80-90%)
 Hypertension
 Hypokalemia
 Secondary hyperaldosteronism
 Most common due to angiotensin II (Renin mechanism)
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39. Primary Hyperaldosteronism
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40. Alterations of Adrenal Function
 Disorders of the adrenal cortex
 Adrenocortical hypofunction
 Primary adrenal insufficiency (Addison disease)
 Idiopathic Addison disease - autoimmune
 Elevated ACTH with inadequate corticosteriod synthesis and output
 Decrease mineralocorticoids, glucocorticoids, and androgens
 Secondary hypocortisolism
 Low or absent ATCH and low cortisol
 Pituitary hypofunction
 Sheehan syndrome
 Panhypopituitarism
 Hypophysectomy
 Isolated ATCH deficiency
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41. Addison Disease
 Subjective:  Objective:
 Anxiety  Wt loss
 Restlessness  Postural hypotension
 Fatigue/weakness  Increased pigmentation
 Dizziness of skin
 Nausea/vomiting
 Hypoglycemia
 diarrhea
 Hyponatremia
 Hyperkalemia
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42. Adrenocortical Insufficiency:
Laboratory
 Pituitary  Cortex
 Low ACTH  High ACTH
 Low Cortisol  Low Cortisol
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43. Alterations of Adrenal Function
 Disorders of the
adrenal medulla
 Adrenal medulla
hyperfunction
 Caused by tumors
derived from the
chromaffin cells of the
adrenal medulla
 Pheochromocytomas
 Secrete catecholamines
on a continuous or
episodic basis
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44. Pheochromocytoma
 Clinical manifestations:
 Hypertension
 episodic
 Diaphoresis
 Palpitations
 Headache
 Heat intolerance
 Wt loss
 constipation
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45. The End
 Questions?
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