Alterations of Hormonal Regulation

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Alterations of Hormonal Regulation

• Chapter 18

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• Dysfunction
• Initially described
• Excessive hypersecretion
• Insufficient - hyposecretion
• Today
• Abnormal receptor function
• Altered intracellular response
• Circulating inhibitors
• water-soluble hormones (not steroids
  lipid-soluble)

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• Alterations of the Hypothalamic Pituitary
  System
• interruption of the pituitary stalk
• Destructive lesions
• Rupture after head injury
• Surgical transaction
• Stem tumor

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Loss of Hypothalamic Hormones
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• Diseases of the Posterior Pituitary
• Syndrome of inappropriate anti-diuretic hormone
  secretion (SIADH)
• Hypersecretion of ADH
• Ectopically produced (small cell carcinoma)
• Brain injury or infection (pulmonary disease)
• Psychiatric/drugs
• Water intoxication ( ?Na, hypo-osmolality)

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• Diseases of the Posterior Pituitary
• Diabetes insipidus
• Insufficiency of ADH
• Polyuria and polydipsia
• Partial or total inability to concentrate urine
• Neurogenic
• Insufficient amounts of ADH
• Nephrogenic
• Inadequate response to ADH
• Psychogenic

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• Diseases of the Anterior Pituitary
• Hypopituitarism spectrum
• Pituitary infarction
• Sheehan syndrome ( pituitary necrosis)
• Hemorrhage
• Shock
• Other head trauma, infections and tumors

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• Diseases of the Anterior Pituitary
• Hypopituitarism
• Panhypopituitarism
• ACTH deficiency
• TSH deficiency
• FSH LH deficiency
• GH deficiency

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Dwarfism
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• Diseases of the Anterior Pituitary
• Hyperpituitarism
• Commonly caused by a benign slow- growing
  pituitary adenoma
• Manifestation
• Headache and fatigue
• Visual changes
• Hyposecretion of neighboring anterior pituitary
  hormones

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• Diseases of the Anterior Pituitary
• Hypersecretion of growth hormone (GH)
• Acromegaly
• Hypersecretion of GH during adulthood
• Gigantism
• Hypersecretion of GH in children and adolescents

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Diseases of the Anterior Pituitary

• Hypersecretion of growth hormone (GH)

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Gigantism
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Barry Bonds HGH Steroids
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• Diseases of the Anterior Pituitary
• Hypersecretion of prolactin (most common)
• Caused by prolactinoma
• In females amenorrhea, galactorrhea, hirsutism
  and osteopenia
• In males hypogonodism, erectile dysfunction,
  impaired libido, oligospermia and ? ejaculate
  volume

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• Alterations of Thyroid Function
• Hyperthyroidism
• Thyrotoxicosis
• Graves disease
• Hyperthyroidism resulting from nodular thyroid
  disease
• Goiter
• Thyrotoxic crisis

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• Common Causes of
• Hyperthyroidism

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• Alterations of Thyroid Function
• Hypothyroidism (most common)
• Primary
• Subacute thyroiditis
• Autoimmune thyroiditis (Hashimoto disease)
• Painless thyroiditis
• Postpartum thyroiditis
• Myxedema coma
• Congenital
• Thyroid carcinoma

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Thyrotoxicosis Graves Disease
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Mechanism for Primary Secondary
Hypothyroidism
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Myxedema

• Orbital Edema, Facial Puffiness,
• Dry Skin

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Hypothyroidism

• Congenital Hypothyroidism
• cretin

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• Alterations of Parathyroid Function
• Hyperparathyroidism
• Primary
• Excess secretion of PTH from one or more
  parathyroid gland
• Secondary
• ? PTH 2 to a chronic disease

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• Alterations of Parathyroid Function
• Hypopararthyroidism
• Abnormally low PTH levels
• Usually caused by parathyroid damage in thyroid
  surgery

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• Dysfunction of the Endocrine Pancreas
• Diabetes Mellitus (Table 18-4)
• group of disorders characterized by glucose
  intolerance
• Diagnosis
• Random glucose gt 200 mg/dl
• FBS gt 126 mg/dl (8 fast)
• 2 hour plasma glucose gt 200 mg/dl
• (75 gram OGTT)
• Pre-diabetes
• IGT impaired glucose tolerance - ? insulin
• IFG impaired fasting glucose - ? hepatic
  glucose output
• Glycosylated hemoglobin HbA1c
• Goals
• Maintain euglycemia, avoid hypoglycemia
• Prevent severe cardiovascular and neurologic
  complications

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International Diabetes Foundation

• 366 million people worldwide have this disease
• 4.6 million death per year due to diabetes
• 465 billion dollars per year
• Association for the Study of Diabetes Annual
  Meeting, Lisbon Portugal, Sept. 2011

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• Dysfunction of the Endocrine Pancreas
• Diabetes Mellitus
• Type 1
• Pancreatic atrophy and specific loss of beta
  cells
• Macrophages, T and B lymphocytes, and natural
  killer (NK) cells are present
• Two types
• Immune
• Non-immune

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Type 1 Diabetes Mellitus
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• Type 1 Diabetes Mellitus
• Genetic susceptibility HLA-DR3 DR 4
• Environmental Factors
• Drugs
• Nutritional intake
• Viruses
• Mumps, coxsackie, rubella, cytomegalovirus
• Immunologically mediated destruction of beta
  cells
• Beta cell autoantibodies
• Antibodies to insulin
• Manifestations
• Hyperglycemia, polydipsia, polyuria, polyphagia,
  weight loss, and fatigue Table 18.5

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• Type 2 Diabetes Mellitus
• Non-insulin dependent
• More common (90)
• Risk factors obesity, family history, ethnic
  minority, puberty, female and metabolic syndrome
• Cause
• Unknown
• Genetic susceptibility
• Environmental factors
• Cellular resistance to insulin
• Obesity
• ?Beta cell response to plasma glucose
• Abnormal glucagon secretion

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• Type 2 Diabetes Mellitus
• Pathophysiology
• Combination
• Excess nutrients (glucose/fat) ? beta cell
  apoptosis
• Obesity
• Inflammatory cytokines
• Obesity related (intra-abdominal fat) cytokines
  (adipokines) and ? FFA release
• Major factors insulin resistance and beta cell
  death

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• Gestational Diabetes
• glucose intolerance appears during pregnancy
• Risk factors
• Family history
• High-risk ethnic group
• Advanced maternal age (gt 25 years old)
• Prior history
• PCO syndrome
• BMI gt 25 kg/m2
• Past obstetrical complications - GD

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• Acute Complications of Diabetes Mellitus (Table
  18-7)
• Hypoglycemia (45 to 50 mg/dl)
• 90 Type 1
• Insulin shock or reaction
• Diabetic ketoacidosis
• Serious
• ?Insulin ? ? counter regulatory hormones
• Catecholamines, cortisol, glucagon, growth
  hormone
• Peaks in adolescence

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DKA HHNKS
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• Acute Complications of Diabetes Mellitus
• Hyperosmolar Hyperglycemic Nonketotic Syndrome
• Type 2 elderly
• Elevated serum glucose (500 mg/dl)
• Severe dehydration (?? serum osmotic pressure) ?
  low blood volume ? BP
• Ketosis less common ? insulin to lipolysis
  and protein catabolism
• Somogyi effect counter regulatory hormone
• Rebound hyperglycemia
• Dawn phenomenon GH
• Early AM rise blood glucose

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• Chronic Complications of Diabetes Mellitus (Table
  18-8)
• Hyperglycemia and non-enzymatic glycosylation
• Hyperglycemia and the polyol pathway
• Protein kinase C
• Microvascular disease
• Retinopathy
• Diabetic nephropathy

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• Chronic Complications of Diabetes Mellitus
• Macrovascular disease (Type 2)
• Coronary artery disease
• Stroke
• Peripheral artery disease
• Diabetic neuropathies
• Infection

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• Diabetes Mellitus
• Atherosclerosis

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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 Conn disease
• Secondary

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• Alterations of Adrenal Function
• Disorders of the adrenal cortex
• Adrenocortical hypofunction
• Primary (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
• Hyperfunction
• Chromaffin cell tumor
• Pheochromocytoma
• Secretions of catecholamines on a continuous or
  episodic basis (norepinephrine)