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Chapter 49
Disorders of Endocrine
Control of Growth and
Metabolism
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Categories of Disturbances of Endocrine
Function
• Hypofunction: underproduction of hormone
• Causes
– Congenital defects
– Disruption in blood flow, infection, inflammation,
autoimmune responses, or neoplastic growth
– Decline in function with aging
– Atrophy as the result of drug therapy or unknown reasons
– Receptor defects
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Categories of Disturbances of Endocrine
Function (cont.)
• Hyperfunction: excessive hormone production
• Causes
– Excessive stimulation and hyperplasia of the
endocrine gland
– Hormone-producing tumor of the gland
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Categories of Endocrine Disorders
• Primary disorders
– Originate in the target gland responsible for
producing the hormone
• Secondary disorders
– The target gland is essentially normal, but its
function is altered by defective levels of stimulating
hormones or releasing factors from the pituitary
system.
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Categories of Endocrine Disorders (cont.)
• Tertiary disorders
– Result from hypothalamic dysfunction
– Both the pituitary and target organ are
understimulated.
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Categories of Pituitary Tumors
• Primary tumors
• Secondary tumors
– Metastatic lesions
• Functional tumors
– Secrete pituitary hormones
• Nonfunctional tumors
– Do not secrete hormones
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Manifestations of Hypopituitarism
• Usually occur gradually
• Can present as an acute and life-threatening condition
• Symptoms:
– Being chronically unfit
– Weakness and fatigue
– Loss of appetite
– Impairment of sexual function
– Cold intolerance
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Measurement of Hypothalamic–Pituitary
Target Cell Hormones
• Serum cortisol
• Serum prolactin
• Serum thyroxine and TSH
• Serum testosterone (male)/serum estrogen (female) and
serum LH/FSH
• Serum GH/insulin-like growth factor-1
• Plasma osmolality and urine osmolality
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Question
• A ______________ disorder results from lesions or
damage at the gland.
– A. primary
– B. secondary
– C. tertiary
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Answer
• A. primary
• Rationale: Primary disorders arise directly from damage
or disturbance at the gland.
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Hormones Essential for Normal Body
Growth and Maturation
• Growth hormone (GH)
• Insulin
• Thyroid hormone
• Androgens
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Growth Hormone
• Produced by somatotropes in the anterior pituitary
• Necessary for linear bone growth in children
• Stimulates cells to increase in size and divide more
rapidly
• Enhances amino acid transport across cell membranes
• Increases the rate at which cells use fatty acids
• Decreases the rate at which cells use carbohydrates
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Growth Hormone in Children
• GH deficiency
– Interferes with linear bone growth
– Results in short stature or dwarfism
• GH excess
– Results in increased linear bone growth
– Gigantism
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Causes of Short Stature
• Variants of normal
• Low birth weight
• Chronic illness and
malnutrition
• Functional endocrine
disorders
• Chromosomal disorders
• Skeletal abnormalities
• Unusual syndromes
• Genetic short stature
– Be well proportioned
and to have a height
close to the midparental
height of their parents
• Constitutional short stature
– Have moderately short
stature, thin build,
delayed skeletal and
sexual maturation, and
absence of other causes
of decreased growth
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Causes of Short Stature (cont.)
• Protein–calorie malnutrition
• Chronic diseases
– End-stage renal disease
– Poorly controlled diabetes mellitus
• Malabsorption syndromes
• Excessive glucocorticoid administration
• Emotional disturbances
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Tall Stature
• Constitutional tall stature
– A child who is taller than his or her peers and is
growing at a velocity that is within the normal range
for bone age
• Genetically tall
• Others
– Marfan syndrome
– Endocrine causes
• Sexual precocity
– Early onset of estrogen and androgen secretion
and excessive GH
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Effects of Growth Hormone Excess
in Adults
• Overgrowth of the cartilaginous parts of the skeleton
• Enlargement of the heart and other organs of the body
• Metabolic disturbances resulting in altered fat
metabolism and impaired glucose tolerance
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Causes of Acromegaly
• Most common cause (95%)
– Somatotrope adenoma
• Other causes (<5%)
– Excess secretion of GHRH by hypothalamic tumors
– Ectopic GHRH secretion by nonendocrine tumors such
as carcinoid tumors or small cell lung cancers
– Ectopic secretion of GH by nonendocrine tumors
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Treatment Goals for Acromegaly
• Normalization of the GH response to an oral glucose load
• Normalization of IGF-1 levels to age- and sex-matched
control levels
• Removal or reduction of the tumor mass
• Relieving the central pressure effects
• Improvement of adverse clinical features
• Normalization of the mortality rate
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Question
• Which of the following is cause of tall stature?
− A. Malabsorption syndromes
− B. Marfan syndrome
− C. Excessive glucocorticoid administration
− D. Emotional disturbances
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Answer
• B. Marfan syndrome
• Rationale: Marfan syndrome is a genetic condition that
results in rapid bone growth and late/absence of
epiphyseal capping.
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Precocious Puberty
• Isosexual precocious puberty is early activation of the
hypothalamic–pituitary–gonadal axis.
– Resulting in the development of appropriate sexual
characteristics and fertility
• Persons with precocious puberty usually are tall for their
age as children but short as adults because of the early
closure of the epiphyses.
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Causes of Precocious Sexual Development
• Idiopathic
• Gonadal disease
• Adrenal disease
• Hypothalamic disease
• Benign and malignant tumors of the central nervous
system
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Major Functions of Thyroid Hormone
• Increases metabolism and protein synthesis
• Influence growth and development in children
– Mental development and attainment of sexual
maturity
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Three Major Thyroid-Binding Proteins
• Thyroid hormone–binding globulin (TBG)
– Carries approximately 70% of T4 and T3
• Thyroxine-binding prealbumin (TBPA)
– Binds approximately 10% of circulating T4 and lesser
amounts of T3
• Albumin
– Binds approximately 15% of circulating T4 and T3
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Measures Used to Diagnose Thyroid
Disorders
• Measures of T3, T4, and TSH
• Resin uptake test
• Assessment of thyroid autoantibodies
• Radioiodine (123I) uptake test
• Thyroid scans (i.e.,
123I, 99mTc-pertechnetate)
• Ultrasonography
• CT and MRI scans
• Fine-needle aspiration (FNA) biopsy of a thyroid nodule
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Alterations of Thyroid Function
• Hypothyroidism
– Decreased metabolic rate
– Accumulation of hydrophilic mucopolysaccharide substance
(myxedema) in the connective tissues
– Elevated serum cholesterol
• Hyperthyroidism
– Increased metabolic rate and oxygen consumption
– Increased use of metabolic fuels
– Increased sympathetic nervous system responsiveness
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Manifestations of Hyperthyroidism
• Thyroid storm
• Restlessness, irritability, anxiety
• Wakefulness
• Increased cardiac output
• Tachycardia and palpitations
• Diarrhea, increased appetite
• Dyspnea
• Heat intolerance, increased sweating
• Thin and silky skin and hair
• Weight loss
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Manifestations of Hypothyroidism
• Mental and physical sluggishness
• Myxedema
• Somnolence
• Decreased cardiac output, bradycardia
• Constipation
• Decreased appetite
• Hypoventilation
• Cold intolerance
• Coarse dry skin and hair
• Weight gain
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Congenital Hypothyroidism
• Thyroid hormone is essential for normal growth and brain
development, almost half of which occurs during the first
6 months of life.
• If untreated, congenital hypothyroidism causes mental
retardation and impairs physical growth.
• The manifestations of untreated congenital
hypothyroidism are referred to as cretinism.
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Graves Disease
• State of hyperthyroidism, goiter and ophthalmopathy
(less commonly, dermopathy)
• An autoimmune disorder characterized by abnormal
stimulation of the thyroid gland by thyroid-stimulating
antibodies (thyroid-stimulating immunoglobulins [TSI])
that act through the normal TSH receptors
• Is associated with human leukocyte antigen (HLA)-DR3
and HLA-B8
• Familial tendency is evident.
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Manifestations of Thyroid Storm
• Very high fever
• Extreme cardiovascular effects
– Tachycardia, congestive failure, and angina
• Severe CNS effects
– Agitation, restlessness, and delirium
• High mortality rate
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Question
• Is the following statement True or False?
• Thyroid storm results in delayed puberty.
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Answer
• False
• Rationale: Thyroid storm is a sever condition that results
in dangerously high temperatures.
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Stages of Adrenal Cortical Insufficiency
• Primary adrenal cortical insufficiency (Addison
disease)
– ACTH levels are elevated because of lack of feedback
inhibition.
• Secondary adrenal cortical insufficiency
– Occurs as a result of hypopituitarism or because
pituitary gland has been surgically removed
• Acute adrenal crisis
– Life-threatening situation occurs
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Clinical Findings of Adrenal Insufficiency
• Anorexia and weight loss
• Fatigue and weakness
• Gastrointestinal symptoms, nausea, diarrhea
• Myalgia, arthralgia, abdominal pain
• Orthostatic hypotension
• Hyponatremia
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Clinical Findings of Adrenal Insufficiency
(cont.)
• Hyperkalemia
• Hyper pigmentation
• Secondary deficiency of select hormones
• Associated autoimmune conditions
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Steroid Hormones Produced
by the Adrenal Cortex
• Mineralocorticoids (aldosterone)
– Function in sodium, potassium, and water balance
• Glucocorticoids (cortisol)
– Aid in regulating the metabolic functions of the body
and in controlling the inflammatory
– Essential for survival in stress situations
• Adrenal sex hormones (androgens)
– Serve mainly as source of androgens for women
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Actions of Cortisol
• Glucose metabolism
• Protein metabolism
• Fat metabolism
• Anti-inflammatory action
• Psychic effect
• Permissive effect
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Common Enzyme Deficiencies
• Congenital adrenal hyperplasia
– Increased levels of ACTH over stimulate production
of adrenal androgens, mineral corticoids
• 21-hydroxylase (accounting for >90% of cases)
• 11-β-hydroxylase deficiency
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Glucocorticoid Hormone Excess
• Cushing syndrome
(hypercortisolism)
– Pituitary form, which
results from excessive
production of ACTH by a
tumor of the pituitary
gland
– Adrenal form, caused by
a benign or malignant
adrenal tumor
– Ectopic form,
nonpituitary ACTHsecreting tumor
• Altered fat metabolism
• Muscle weakness
• Muscle wasting
• Purple striae
• Osteoporosis
• Derangements in glucose
metabolism
• Hypokalemia
• Gastric acid secretion
• Hirsutism, mild acne, and
menstrual irregularities
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Addison and Cushing Syndromes
• Addison disease is caused by destruction of the adrenal
gland and glucocorticoid insufficiency.
• In contrast, Cushing syndrome refers to the
manifestations of hypercortisolism from any cause.
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