• Neoplasia - results in hypersection
• hyperplasia  - results in hypersection
• Hemodynamic alterations
  • hemorrhage, necrosis 
  •  results in hyposection
• Congenital disorders
  • e.g., aplasia, hypoplasia
  • results in hyposection 
• Inflammation 
  • results in hyposection
• Pressure from adjacent 
  • tumors results in hyposection

• Functional tumors
  • most common reason for hyperfuction
  • usually benign
• Hyperplasia 
• Increased sensitivity/activity of the hypothalamus

• Most frequently seen BENIGN tumor in pituitary
• Produces prolactin and inhibits gonadal sex hormone production 
• Female: Amenorrhea, galactorrhea, infertility 
• Male: Decreased libido, impotence

pituitary tumor

• Acromegaly more common gigantism 
• Growth hormone antagonizes insulin 
  • 20% of patients have diabetes 
  • 1/3 have decreased glucose tolerance 
  • 1/3 have hypertension: leads to hypertrophy of the left ventricle and congestive heart failure

pituitary tumor

• Hypersecretion of ACTH 
• Stimulates the adrenal to produce cortisol: 
  • Cushing’s disease (Pituitary Cushing Syndrome)

Hypofunction (Hypopituitarism)

Craniopharyngioma:

• In children and young adults
• tumors are large and destroy the gland and/or hypothalamus
• impinge on the optic chiasma
• Diabetes insipidus (ADH- AntiDiuretic- deficiency) is also common.

• Impairment of iodine utilization 
• Exaggerated response to TSH 
• Autoantibodies
• Dietary goitrogens 

Non-toxic goiter bc hormone levels are ALL normal

• Dysphagia
•  Hoarseness
•  Congestion of the head and neck veins 
• T4 and T3 levels are normal 
• TSH levels are usually normal

• Abnormally high levels of T3 and T4 
• Hypermetabolism: increased metabolic rate; both anabolic and catabolic functions upregulated 
• Hyperactivity of the cardiovascular and neuromuscular systems

• Elevated body temperature, heat intolerance, perspiration 
• Increased cardiac contractility: direct effect on fibers 
• Increased blood volume via renin/angiotensin pathway 
• Elevated heart rate and systolic pressure; increased cardiac output

• Irritability 
• Tremor of hands 
• Weight loss 
• Muscle weakness

• hyperthyroidism
• Solitary, “hot nodule” 
• Not dependent on TSH - 
• Symptoms milder than Graves
• no exophthalmos

HYPOTHYROIDISM

- due to what 3 things?

• Defective synthesis of the thyroid hormones 
• Inadequate functioning of the gland due to inflammation (thyroiditis) or surgical resection
• Inadequate secretion of TSH (from pituitary gland)

Severe Deficiency of T4 and T3 in children

• due to?
• clinical?
• hormone levels?

• Cretinism: In childhood 
• Due to: errors of hormone synthesis, thyroid dysgenesis, unresponsiveness to TSH 
• Clinical: Dwarfs; low body temperature; pale cold skin; mental retardation; enlarged tongue and abdomen; 
• TSH elevated (pituitary works fine), T3 and T4 low (thyroid isn't working)

• Autoimmune pathogenesis 
• Gland is enlarged and rubbery 
• Lymphocytic infiltrates 
• Euthyroid but eventually hypothyroid
• Mild deficiency in T3 and T4

Due to bacterial or viral infections from the pharynx or upper respiratory tract

Transient hypothyroidism

Primary Hyperparathyroidism

- what is it?

- What does it result in?

Excessive production of PTH

Hypercalcemia and hypophosphatemia

• chronic renal failure 
• Inability of kidney to secrete out phosphate (leads to phosphate retention and loss of Ca to the urine)
• Hypocalcemia (initially) and hyperphosphatemia
• Compensatory hypersecretion of PTH and hyperplasia of the parathyroid glands 
• Renal osteodystrophy and osteitis fibrosa cystica

Hypoparathyroidism

- likely due to?

- what does it result in?

• Most commonly due to removal of glands during surgery, e.g., thyroidectomy
• Decreased levels of PTH result in: 
  • Depressed serum calcium and elevated serum phosphate
  • Tetany, neuromuscular irritability, is the hallmark of hypocalcemia
  • May lead to life-threatening laryngospasm and seizures.

• Mineralocorticoid - hormones similar to aldosterone (thus, retain water and salt)
• Glucocorticoids - aka cortisol: inc sugar in blood, suppress immune system, dec bone formation
• Sex hormones

• Gluconeogenesis and glycogen deposition 
• Catabolism of fats 
• Gastric secretion 
• Bone resorption 
• Neural excitability 
• Suppress immune functions

• Resorption of sodium and chloride
• loss of potassium 
• Retention of water

• Adenoma of the cortex of adrenal gland(90%)
• Hyperaldosteronism

Acute form of hypofunction of the adrenal cortex

May be due to:

• Meningococcal septicemia
• Sudden stop of corticosteroid drug therapy
• Sudden hemorrhage into the gland
• Extensive burns

• Chronic form of Adrenal Cortical Hypofunction 
• Hypoaldosteronism
• Caused by:
  • Autoimmune destruction of tissues (loss of aldosterone)
  • Tuberculosis: most common cause worldwide
• Clincal
  • hypotension
  • hyperpigmentation
  • weakness, weight loss
  • GI symptoms

• Hyperfunction of the Adrenal medulla
• Benign tumor - episodes sporadically
• Catecholamine overproduction 
• Clinical
  • Paroxysmal hypertension 
  • Tachycardia Sweating, trembling, anxiety
  • severe throbbing headache
  • sudden death from MI or stroke
  • May be part of MEN 1 and 2 syndromes

1) functional tumors

2) hyperplasia; or

3) increased activity/sensitivity of the hypothalamus

• usually benign, like adenomas
• But significant for 3 reasons: 
  • 1) size- pressure on adjacent structures, 
  • 2) hypersecretion of hormones
  • 3) destruction of gland tissue.

• Benign tumor of pituitary gland
• Hyperpituiary - too much prolactin
• clinical: 
  • female — amenorrhea, galactorrhea, infertility;
  •  male— decreased libido and impotence
  • due to prolactin inhibiting gonadal sex hormones

• coarse facial features with broadening of the lower face
• overgrowth of the mandible (prognathism) and maxilla
• spaces between the upper incisors
• large hands and feet

• secondary (not primary) diabetes
• 1/3 of patients have decreased glucose tolerance. 
• 1/3 of patients have hypertension 
  • Can lead to increased left ventricular mass and congestive heart failure
• The thyroid, liver, and adrenals can also enlarge. 

• hyperfunction of the pituitary gland due to tumor
• hypersecretion of ACTH 
  • stimulates the adrenal to produce excess of cortisol (Cushing’s disease) 

• Suprasellar Hypofunction of the pituitary gland
• Seen in :children and young adults; older adults 
• due to destruction of pituitary proper or the hypothalamus due to large tumor size
• Clinical: 
  • impinging on the optic chiasma results in impaired vision
  • headaches
  • growth retardation
  • Diabetes insipidus (from posterior pituitary) results in ADH deficiency

• Hypofunction of the Pituitary gland
• Due to loss of blood to PG (causing necrosis) after woman gives birth
• AKA Sheehan SYNDROME
• Anterior PG more affected than Posterior PG

• Hypofunction of the Pituitary gland
• Due to congenital disease causing lack of GH (during time when epiphyses have not closed)

• Hypofunction of the Pituiary Gland/ Hypothalamus
• due to deficiency of ADH (secreted by the posterior pituitary; under the influence of the hypothalamus) 
• Clinical presentation: 
  • polyuria
  •  polydipsia
  • (no polyphagia as in DM)

• Originates from endoderm at root of tongue and descends to its normal position in the anterior neck
•  Remnants of tissue in the path of descent can result in thyroglossal (duct) cysts, or ectopic glands
• T 3 (major effector) + T 4 cause increased O2 consumption in tissues, affect all tissues, and increase both anabolic and catabolic functions
• C cells: secrete calcitonin (decreases Ca concentration).

• Non-toxic goiter
• Cause:
  • Impairment of iodine utilization
  • exaggerated response to TSH
  • autoantibodies
  • dietary goitogens
• T3 normal; T4 normal; TSH normal
• Clinical
  • dysphagia
  • dyspnea
  • hoarseness
  • congestion of the head and neck

•  Nontoxic or euthyroid (normal thyroid hormone levels)
• May induce thyrotoxicosis (toxic multinodular goiter with elevated thyroid hormone levels, or hyperthyroidism)
•  Extreme enlargement due in part to 
  • intermittent periods whereby dietary iodine increases
  • demand for thyroid hormone decreases
• the stimulated follicular epithelium and the thyroid follicle undergo involution and regression 
• Dental management issues arise with the use of epinephrine in dental anesthetic to patients with thyrotoxicosis. 

• Inc in T3 and T4; presence of toxic goiter
• state of hypermetabolism and hyperactivity
• All cases of hyperthyroidism present with:
  • elevated body temperature
  • increased cardiac output due to decreased systemic vascular resistance
  • increased blood volume through activation of the renin-angiotensin system
  • increased cardiac contractility
  • and elevated heart rate and systolic pressure
  • heat intolerance
  •  continuous perspiration
  •  marked irritability and tremor of the hands
  • weight loss but increased appetite
  • and muscle weakness.

• Hyperthyroidism with goiter
• due to Autoimmune antibodies activating TSH receptors in Thyroid; heredity, sex, emotional factors.
• Clinical:
  • goiter 
  • hyperthyroidism 
  • exophthalmos 
  • pretibial myxedema of the skin
  • thyroid follicles are filled with colloid
  • Histologically,  too many cells. 
  • increase uptake of iodine by the thyroid (reflective of increased thyroid hormone synthesis) 
  • elevated serum levels of T3 and T4

• Hyperfunction of the thyroid gland
• due to benign tumor causing enlargement of one solitary part of the gland
• clinical
  • hot nodule
  • milder than Graves 
  • symptoms do not present until the tumor is large
  • not dependent on TSH

Due to:

• defective synthesis of TH 
• inadequate functioning of thyroid parenchyma as a result of thyroiditis or surgical resection
• inadequate secretion of TSH 

Clinical symptoms depend on the degree of hypofunction of the gland.

• Hypothyroidism in childhood
• Lack of T3, T4 due to 
  • errors in hormone synthesis
  • unresponsiveness to TSH
  • thyroid dysgenesis

Myxedema

• Hypothyroidism in adults
• Lack of T3, T4 due to:
  • may be of autoimmune origin
  • end stage of Hashimoto’s disease (autoimmune hypothyroidism)
• Clinical
  • myxedema, e.g., boggy facies,  puffy eyelids, edema of hands and feet, enlarged tongue, hoarseness
  • decreased cardiac contractility, prolonged diastolic relaxation, decreased heart rate
  • Myxedema heart- results in decreased cardiac output; may lead to pericardial effusion
  • atherosclerosis
  • Cardiac tamponade apparently does not occur.

• Hypothyroidism 
• due to autoimmune
• Clinical: 
  • Initially - Euthyroid state
    • gland often diffusely enlarged, painless, symmetric, and rubbery
  • Eventually - Atrophied hypothyroid state
    • lymphocytic infiltrates, plasma cells, and well developed germinal centers
  • Women

• thyroid globulin
• This is subsequently iodinated and stored as thyroid hormone in the colloid containing follicles of the thyroid gland
• Sensitization of autoreactive CD4+ T cells to thyroid antigens appears to be the initiating event for thyroid cell death  
• In the usual clinical course of Hashimoto thyroiditis, the hypothyroidism develops gradually
• In some cases, may be preceded by transient thyrotoxicosis caused by disruption of thyroid follicles, with secondary release of thyroid hormones
• During this secondary phase, T3 and T4 levels are thus elevated, TSH is diminished, and radioactive iodine uptake is decreased. 
• As hypothyroidism supervenes, however, T3 and T4 levels progressively fall, accompanied by a compensatory increase in TSH—reflective of a decrease in the biosynthesis of thyroid hormone. 

• Hypothyroidism aka Granulomatous/De Quervain
• due to:
  • viral infections from pharynx and upper respiratory tract 
    • Coxsackievirus, mumps, measles, adenovirus
•  Clinical
  • transient (gone after 2-6 weeks)

• Hypothyroidism aka Papillary carcinoma
• due to non-functional carcinoma
  • possibly from exposure to ionizing radiation
• Clinical
  •  (“cold nodules”) 
  • form solitary nodules
  • can destroy the gland
  • usually slow growing and are slow to metastasize
  • women
  • Hoarseness, dysphagia, cough, or dyspnea suggests advanced disease
  • In a minority of patients, hematogenous metastases are present at the time of diagnosis, most commonly in the lung.

• consists typically of 4 glands on the posterior surface of the thyroid
• PTH regulates calcium and phosphate metabolism: 
  • bone-increases bone resorption; 
  • kidney-decreases phosphate reabsorption with resulting phosphaturia, enhances calcium reabsorption, and increases vitamin D production in the kidney; 
  • intestine- increased absorption of calcium due to enhanced vitamin D production. 
  • Vitamin D regulates serum calcium.

Primary

• usually due:
  • Adenoma- accounts for 85% to 95 % of cases. 
  • Hyperplasia--all glands are enlarged and hypercellular and occurs in 15% of cases. 
  • Carcinoma-rare

Secondary

• usually due to:
  • kidney failure
  • intestinal disease
  • renal cell carcinoma

Due to:

• Renal disease: 
  • inability of kidney to secrete out phosphate—leads to phosphate retention 
  • initially, hypocalcemia
• vitamin D deficiency
• malabsorption

Clinical of Secondary -  hyperplasia of all four parathyroid glands and compensatory hypersecretion of PTH

• Due to renal failure
  • kidney can't excrete phosphate (hyperphosphatemia)
  • Pt becomes hypocalcemic initially 
  • Pt can't make active Vit D either 
• The Hypocalcemia:
  • Results in parathyroid starts to secrete PTH
• Inc of PTH:
  •  osteoclasts are recruited to resorb bone -osteoporosis in bone 
  • Cystic lesions due to  osteoclast-mediated resorption-  osteitis fibrosa cystica
• Calcium rises in blood. But phosphate still can't be excreted into urine.
  • Elevated levels of serum phosphate are “driving force” 
  • Serum phosphate directs the elevated levels of serum calcium  back into the bone 
    • osteosclerosis, or thickening of the bone
• Result of less active Vit D
  • osteomalacia
• renal osteodystrophy (changes in bone due to secondary hyperpara in renal failure)
  • Osteoporosis
  • osteitis fibrosa cystica 
  • osteomalacia
  • osteosclerosis 
  • Bone likely to fracture

• Due to accidental removal of glands during surgery

• The adrenals are located bilaterally above kidneys. 
• Cortex—produces 
  • (1) mineralocorticoid aldosterone which stimulates reabsorption of sodium and chloride and loss of potassium in kidney (controlled by renin-angiotensin system)
  • (2) glucocorticoids -- cortisol and corticosteroid (controlled by ACTH). The effects of glucocorticoids are many—stimulation of gluconeogenesis and glycogen deposition through acceleration of protein, carbohydrate and fat catabolism; stimulation of gastric secretion and bone resorption; increases neural excitability; suppress immune functions
  • (3) sex hormones involved in masculinization and some estrogen (controlled by ACTH). 
• Medulla-- produces epinephrine or adrenalin and norepinephrine (catecholamines). 
  • Epinephrine increases cardiac output and the basal metabolic rate; glycogenolysis; lipolysis; CNS excitability; bronchial and coronary artery dilation (and hence its use in asthma); and constriction of blood vessels of skin. 
  • Norepinephrine increases peripheral resistance by constricting blood vessels; stimulates lypolysis and increases slightly the basal metabolic rate.

• Hyperfunction of the Adrenal Cortex
• due to 
  • functional adenoma in pituitary gland; inc in ACTH
  • adenoma/carcinoma in the adrenal cortex; Inc of cortisol secretion
  • Paraendocrine tumors (cancer in lung that secretes ACTH)
  • Exogenous source: chronic glucocorticoid drug therapy

• Hyperaldosteronism in Adrenal Cortex
• due to excess of aldosterone produced by adenoma of the cortex (90%) but bilateral hyperplasia cases are increasing

• Hyperfunction of adrenal cortex that deals w/ sec hormones
• Get: excess of androgenic hormones
• May be seen with or without Cushing syndrome.

INC production of Ca2+

DEC production of Phosphate

• exophthalmos (enlargement of extraocular muscles within the orbit, due to mucinous edema [due to accumulation of proteoglycans or mucopolysaccharides], fibroblast, and lymphocytic accumulation); 

whereby the skin is thickened and scaly (due to infiltration with glycosaminoglycans or proteoglycans, and lymphocytes)

• hypercalcemia + hyophosphatemia
• Inc bone resporption
  • Osteoporosis
  • Osteitis Fibrosis Cystica w/ Brown tumors
  • Loss of lamina dura
• Metastatic calcifications
  • nephrocalcinosis = kidney stones
  • cataracts (calcium in eye)
• PTH stimulates secretion of Gastrin hormone
  • peptic ulcers

• Clinical: 
  • cretins are dwarfs
  • ossification, epiphyseal union, and dentition formation abnormal
  • enlarged protruded tongues
  • large abdomen
  • low body temperature; pale cold skin
  • mental retardation
  • serum levels of TSH elevated and low serum levels of T3 and T4.

• Decreased levels of PTH result in decreased calcium absorption from the gut and reabsorption of calcium by kidney
• increased phosphate reabsorption by kidneys; 
• decreased calcium mobilization from bone. 
• All produce depressed serum calcium and elevated serum phosphate. 
• tetany, laryngeal spasms, neuromuscular irritability, cataract formation
• Tetany, neuromuscular irritability, is the hallmark of hypocalcemia.

• Clinical--
  • hypertension -sodium reabsorption and water retention leads to 
  • hypokalemia leads to muscular weakness, cardiac arrhythmias, paresthesia (numbness); 
  • renal damage--polyuria due to lack of response to ADH due to tubular degeneration.

• Clinical
  • moon face, buffalo hump, 
  • edema, hypertension (due loss of Na)
  • muscular weakness (due to loss of K)
  • increased susceptibility to infection
  • diabetes mellitus due to increased gluconeogenesis and glucose intolerance
  • osteoporosis
  • violaceous striae (purple striae on skin)
  • easy bruising 
  • congestive heart failure
  • atherosclerosis (due to inc fat metabolism)
  • gastric ulcers (inc in gastric secretions)