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Chapter 21
Alterations of Hormonal Regulation
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Elevated or Depressed
Hormone Levels
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
Failure of feedback systems
Dysfunction of an endocrine gland
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

Excessive/inadequate hormone production
Altered hormone inactivation/degradation
Ectopic hormone release


Nonendocrine
Autonomous production, no feedback mechanisms
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Target Cell Failure
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Receptor-associated disorders
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
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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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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
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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
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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
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Alterations of the
Hypothalamic-Pituitary System
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Diseases of the Anterior Pituitary
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
Pituitary is vascular and therefore vulnerable
to ischemia and infarction
Hypopituitarism


Pituitary infarction
• Sheehan syndrome
• Hemorrhage
• Shock
Others: head trauma, infections, and tumors
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Diseases of the Anterior Pituitary

Hypopituitarism

Panhypopituitarism (all hormones absent)
• ACTH deficiency
• TSH deficiency
• FSH and LH deficiency
• GH deficiency

Glucose intolerance
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Diseases of the Anterior Pituitary
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Hyperpituitarism
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
Commonly due to a benign, slow-growing pituitary
adenoma
Manifestations
• Headache and fatigue
• Visual changes
• Hyposecretion of neighboring anterior pituitary hormones
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Diseases of the Anterior Pituitary
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Hypersecretion of growth hormone (GH)
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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
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Clinical Manifestations of
Acromegaly
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Connective tissue proliferation
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Enlarged tongue, interstitial edema, increase in the
size and function of sebaceous and sweat glands,
coarse skin and body hair
Bony proliferation
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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
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Hypersecretion of GH
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Diseases of the Anterior Pituitary
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Hypersecretion of prolactin
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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
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Alterations of Thyroid Function

Primary


Dysfunction or disease of thyroid gland
• TH production
Secondary

Alteration of pituitary TSH production
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Alteration in Thyroid Function
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Primary
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Hyperthyroidism, hypothyroidism
Thyrotoxicosis
Graves' disease
• Pretibial myxedema
Hyperthyroidism resulting from nodular thyroid
disease
• Goiter
Thyrotoxic crisis
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Thyrotoxicosis (Graves' Disease)
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Alterations of Thyroid Function
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Hypothyroidism
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Primary hypothyroidism
• Subacute thyroiditis
• Autoimmune thyroiditis (Hashimoto disease)
• Painless thyroiditis
• Postpartum thyroiditis
• Myxedema coma
Congenital hypothyroidism
Thyroid carcinoma
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Hypothyroidism
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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
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Alterations of Parathyroid
Function
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Hyperparathyroidism
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Hypercalciuria
Alkaline urine
Hyperphosphaturia
• Predisposes to the formation of calcium stones
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Alterations of Parathyroid
Function
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Hypoparathyroidism
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
Abnormally low PTH levels
• Depressed serum calcium level
• Increased serum phosphate level
Usually caused by parathyroid damage in thyroid
surgery
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Alterations of Parathyroid
Function
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Hypoparathyroidism clinical signs
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Hypocalcemia
• Lowering of the threshold for nerve and muscle excitation
• Muscle spasms; hyperreflexia; tonic-clonic convulsions;
laryngeal spasms; death from asphyxiation

Phosphate retention
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Diabetes Mellitus
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Type 1
Type 2
Gestational diabetes
Glucose intolerance
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Fasting, 2 hour post glucose load, A1C
Other types
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Type 1 Diabetes Mellitus
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

Demonstrates pancreatic atrophy and loss of
beta cells
Macrophages, T and B lymphocytes, and
natural killer cells are present
Two types


Immune
Nonimmune
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Type 1 Diabetes Mellitus
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

Genetic susceptibility
Environmental factors
Immunologically mediated destruction of beta
cells
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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
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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
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Diabetes Mellitus
Maturity onset diabetes of youth
(MODY)
 Gestational diabetes

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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
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Acute Complications of
Diabetes Mellitus

Hyperosmolar hyperglycemic nonketotic
syndrome (HHNKS)
 Usually associated with Type 2
 Higher glucose
 Less ketosis
 Severe dehydration and potassium
deficit
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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
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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
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Diabetic Nephropathy
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Complications of Diabetes Mellitus
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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
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Diabetic Neuropathy
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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
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Cushing Disease
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Alterations of Adrenal Function

Disorders of the adrenal cortex
Hyperaldosteronism
• Primary hyperaldosteronism
(Conn disease)
• Secondary hyperaldosteronism
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Primary Hyperaldosteronism
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Alterations of Adrenal Function

Disorders of the adrenal cortex
Adrenocortical hypofunction
• Primary adrenal insufficiency
(Addison disease)
Idiopathic Addison disease
• Secondary hypocortisolism
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Alterations of Adrenal Function

Disorders of the adrenal cortex
Hypersecretion of adrenal
androgens and estrogens
• Feminization
• Virilization
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Virilization
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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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Pheochromocytoma
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