Chapter 21
Alterations of Hormonal Regulation
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
Elevated or Depressed
Hormone Levels


Failure of feedback systems
Dysfunction of an endocrine gland



Excessive/inadequate hormone production
Altered hormone inactivation/degradation
Ectopic hormone release


Nonendocrine
Autonomous production, no feedback mechanisms
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
2
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
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
3
Intracellular Disorders

Inadequate synthesis of a second messenger


Cyclic adenosine monophosphate (cAMP)
Failure of the target cell to produce anticipated
hormonal response

Faulty response to hormone-receptor binding
• Failure to generate required second messenger
• Abnormal response to the second messenger
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
4
Alterations of the
Hypothalamic-Pituitary System
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
5
Diseases of the Posterior
Pituitary

Syndrome of inappropriate antidiuretic hormone
(SIADH) secretion

Ectopic secretion of ADH most common cause; also
common after surgery
 For diagnosis, normal adrenal and thyroid function
must exist
 Clinical manifestations
• Related to enhanced renal water retention
• Hyponatremia
• Hypoosmolarity
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
6
Diseases of the Posterior
Pituitary

Diabetes insipidus

Insufficiency of ADH
 Polyuria and polydipsia
 Partial/total inability to concentrate the urine
 Neurogenic
• Insufficient amounts of ADH
 Nephrogenic
• Inadequate response to ADH
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
7
Diseases of the Anterior Pituitary


Pituitary is vascular and therefore vulnerable
to ischemia and infarction
Hypopituitarism


Pituitary infarction
• Sheehan syndrome
• Hemorrhage
• Shock
Others: head trauma, infections, and tumors
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
8
Diseases of the Anterior Pituitary

Hypopituitarism

Panhypopituitarism (all hormones absent)
• ACTH deficiency
• TSH deficiency
• FSH and LH deficiency
• GH deficiency

Glucose intolerance
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
9
Diseases of the Anterior Pituitary

Hyperpituitarism


Commonly due to a benign, slow-growing pituitary
adenoma
Manifestations
• Headache and fatigue
• Visual changes
• Hyposecretion of neighboring anterior pituitary hormones
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
10
Diseases of the Anterior Pituitary

Hypersecretion of growth hormone (GH)

Acromegaly
• Hypersecretion of GH during adulthood
• Slowly progressive



Mortality: cardiac hypertrophy, hypertension,
atherosclerosis, type 2 diabetes mellitus lead to coronary
artery disease
Malignancies common
Giantism
• GH hypersecretion in children and adolescents
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
11
Clinical Manifestations of
Acromegaly

Connective tissue proliferation


Enlarged tongue, interstitial edema, increase in the
size and function of sebaceous and sweat glands,
coarse skin and body hair
Bony proliferation



Large joint arthropathy
Periosteal vertebral growth
• Kyphosis
Enlargement of facial bones and hands and feet
• Protrusion of the lower jaw and forehead
• Need for increasingly larger sizes of shoes, hats, rings, and
gloves
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
12
Hypersecretion of GH
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
13
Diseases of the Anterior Pituitary

Hypersecretion of prolactin

Caused by prolactinomas
• Most common hormonally active pituitary tumor
• In females, increased levels of prolactin cause amenorrhea,
galactorrhea, hirsutism, and osteopenia
• In males, increased levels of prolactin cause hypogonadism,
erectile dysfunction, impaired libido, oligospermia, and
diminished ejaculate volume
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
14
Alterations of Thyroid Function

Primary


Dysfunction or disease of thyroid gland
• TH production
Secondary

Alteration of pituitary TSH production
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
15
Alteration in Thyroid Function

Primary





Hyperthyroidism, hypothyroidism
Thyrotoxicosis
Graves' disease
• Pretibial myxedema
Hyperthyroidism resulting from nodular thyroid
disease
• Goiter
Thyrotoxic crisis
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
16
Thyrotoxicosis (Graves' Disease)
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
17
Alterations of Thyroid Function

Hypothyroidism



Primary hypothyroidism
• Subacute thyroiditis
• Autoimmune thyroiditis (Hashimoto disease)
• Painless thyroiditis
• Postpartum thyroiditis
• Myxedema coma
Congenital hypothyroidism
Thyroid carcinoma
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
18
Hypothyroidism
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
19
Alterations of Parathyroid
Function

Hyperparathyroidism

Primary hyperparathyroidism
• Excess secretion of PTH from one or more parathyroid
glands
• 85% caused by parathyroid adenomas

Secondary hyperparathyroidism
• Increase in PTH secondary to a chronic disease


Renal failure
Dietary deficiency of vitamin D, calcium
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
20
Alterations of Parathyroid
Function

Hyperparathyroidism



Hypercalciuria
Alkaline urine
Hyperphosphaturia
• Predisposes to the formation of calcium stones
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
21
Alterations of Parathyroid
Function

Hypoparathyroidism


Abnormally low PTH levels
• Depressed serum calcium level
• Increased serum phosphate level
Usually caused by parathyroid damage in thyroid
surgery
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
22
Alterations of Parathyroid
Function

Hypoparathyroidism clinical signs

Hypocalcemia
• Lowering of the threshold for nerve and muscle excitation
• Muscle spasms; hyperreflexia; tonic-clonic convulsions;
laryngeal spasms; death from asphyxiation

Phosphate retention
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
23
Diabetes Mellitus




Type 1
Type 2
Gestational diabetes
Glucose intolerance


Fasting, 2 hour post glucose load, A1C
Other types
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
24
Type 1 Diabetes Mellitus



Demonstrates pancreatic atrophy and loss of
beta cells
Macrophages, T and B lymphocytes, and
natural killer cells are present
Two types


Immune
Nonimmune
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
25
Type 1 Diabetes Mellitus



Genetic susceptibility
Environmental factors
Immunologically mediated destruction of beta
cells
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
26
Type 1 Diabetes Mellitus

Clinical manifestations

Hyperglycemia
• 80% to 90% of the function of the insulin-secreting beta cells
in the islet of Langerhans is lost

Polydipsia, polyuria, polyphagia, weight loss, and
fatigue
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
27
Dysfunction of the Pancreas

Type 2 diabetes mellitus





Affects adults and children
Genetic environmental interaction
Metabolic syndrome
Treatment
• Exercise, treatment of obesity, medication
Clinical manifestations
• Recurrent infections, vision problems, neuropathy
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
28
Diabetes Mellitus


Maturity onset diabetes of youth (MODY)
Gestational diabetes
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
29
Acute Complications of
Diabetes Mellitus


Hypoglycemia
Diabetic ketoacidosis

Usually associated with Type 1
 Illness, trauma, surgery, emotions
 Total body (not serum) potassium deficiency
 Cerebral edema, especially in children
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
30
Acute Complications of
Diabetes Mellitus

Hyperosmolar hyperglycemic nonketotic
syndrome (HHNKS)




Usually associated with Type 2
Higher glucose
Less ketosis
Severe dehydration and potassium deficit
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
31
Acute Complications of
Diabetes Mellitus

Somogyi effect




Usually associated with Type 1
Hypoglycemia with rebound hyperglycemia
Not as common as once thought
Dawn phenomenon

Early morning glucose elevation without nocturnal
hypoglycemia
 Related to nocturnal growth hormone elevation
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
32
Chronic Complications of
Diabetes Mellitus


Hyperglycemia and nonenzymatic glycosylation
Hyperglycemia and the polyol pathway




Sorbitol and fructose increase intracellular osmotic
pressure (attracts water, leading to cell injury)
Evident in the eye lens, nerves, RBCs
Protein kinase C
• Enzyme inappropriately activated by hyperglycemia
Microvascular disease


Retinopathy
Diabetic nephropathy
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
33
Diabetic Nephropathy
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
34
Complications of Diabetes Mellitus

Macrovascular disease





Coronary artery disease
• Most common cause of death in persons with type 2
• Prevalence increases with duration of disease
Stroke
Peripheral arterial disease
Diabetic neuropathies
Infection
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
35
Diabetic Neuropathy
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
36
Alterations of Adrenal Function

Disorders of the adrenal cortex


Cushing disease
• Excessive anterior pituitary secretion of ACTH
Cushing syndrome
• Excessive level of cortisol, regardless of cause
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
37
Cushing Disease
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
38
Alterations of Adrenal Function

Disorders of the adrenal cortex

Hyperaldosteronism
• Primary hyperaldosteronism (Conn disease)
• Secondary hyperaldosteronism
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
39
Primary Hyperaldosteronism
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
40
Alterations of Adrenal Function

Disorders of the adrenal cortex

Adrenocortical hypofunction
• Primary adrenal insufficiency (Addison disease)

Idiopathic Addison disease
• Secondary hypocortisolism
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
41
Alterations of Adrenal Function

Disorders of the adrenal cortex

Hypersecretion of adrenal androgens and
estrogens
• Feminization
• Virilization
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
42
Virilization
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
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
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
44
Pheochromocytoma
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.
45