Keywords: Chapter 21, Endocrine Pathology

Addison disease
Chronic adrenal cortical insufficiency, characterized by weight loss, hyperpigmentation of the skin, hypotension and loss of body hair. Addison disease is usually caused by an autoimmune condition, but can result from any destructive process affecting the adrenal cortex, e.g., metastatic carcinoma, amyloidosis, or tuberculosis.
Adenohypophysis
The anterior lobe of the pituitary, whose cells are true glandular cells, producing as they do, anterior lobe hormones.
Adrenocorticotroph hormone (ACTH)
A product of basophilic anterior lobe cells of the pituitary. Stimulates the adrenal cortex, in particular the zona fasciculata which produces glucocorticoids. Overproduction of ACTH causes Cushing disease.
Antidiuretic hormone/vasopressin
This hormone targets renal tubules and facilitates retention of water. Loss of the hormone results in polyuria, polydipsia (diabetes insipidus). Inappropriate overproduction of the hormone results in water retention. The vasopressin function of the hormone raises blood pressure through vasoconstriction.
Catecholamines
Epinephrine and norepinephrine, synthesized and secreted by cells of the adrenal medulla and their neoplastic counterparts. Catecholamines are derived from tryptophan which is converted to a metabolic intermediate, dihydroxyphenylalanine (DOPA).
Chief cell
The primary parathyroid hormone (PTH)-secreting cells of the parathyroid.
Chromaffin cells
The cells of pheochromocytomas or paragangliomas are chromaffin cells, meaning that they selectively stain brown with chromate salts.
Chvostek, Trousseau and Erbs signs
These are all physical signs of tetany, due to hypocalcemia. For details, consult your physical diagnosis text.
Cold nodule
A non-functional nodule in the thyroid that does not take up radioactive iodine.
Colloid goiter
a euthyroid form of nodular enlargement of the thyroid characterized microscopically by follicular enlargement and accumulation of intrafollicular colloid.
Congenital adrenal hyperplasia
An autosomal recessive deficiency of cortical hydroxylating enzyme(s) (usually 21-hydroxylase) leading to overproduction of androgenic steroids with subsequent virilization.
Conn syndrome
Primary hyperaldosteronism, usually due to a functional cortical adenoma that secretes aldosterone or other mineralocorticoids. Clinical features include hypernatremia, hypokalemia, alkalosis and hypertension.
Craniopharyngioma
A usually benign squamous epithelial tumor in a suprasellar location. Mostly seen in children and adolescents, they interfere with somatic and sexual development, but a second peak occurs in the 40s. They may be solid or cystic and are often calcified.
Cretinism
Hypothyroidism occurring at birth or in infancy. Clinical features include growth inhibition, round face, protruding tongue, narrow palpebral fissures, and mental retardation.
Cushing disease
Overproduction of adrenal cortical glucocorticoids secondary to overstimulation by ACTH. The latter may be due to an ACTH producing basophilic adenoma or adenomas of the pituitary gland, hyperplasia of same, or increased release of Corticotroph Release Factor (CRF) from hypothalamic neurons, reaching the pituitary through the portal venous system.
Cushing syndrome
Clinically similar to Cushing disease, but is caused by primary overproduction of adrenal cortical glucocorticoid hormones, due to adenoma, hyperplasia or carcinoma of the adrenal cortex. Ectopic production of ACTH e.g., in pulmonary carcinoids may play a role, and very often iatrogenic Cushing syndrome comes from prolonged treatment with corticosteroids, particularly treatment of autoimmune diseases.In both Cushing disease and Cushing syndrome, one may see moon face, buffalo hump, muscle atrophy, hyperglycemia, elevated red blood cell count (hyperglobulia) as well as hypernatremia and hypokalemia.
De Quervain thyroiditis
Subacute, granulomatous thyroiditis, suspected to be of viral etiology; it is usually a self-limited disease that remits spontaneously.
Ectopic ACTH secretion
Secretion of an ACTH like substance from a non-pituitary neoplasm, commonly from small cell (oat cell) carcinoma of the lungs, causes Cushing syndrome
Empty sella syndrome
The pituitary undergoes pressure atrophy, most often secondary to downward bulging of the CSF containing cistern at the suprasellar part of the brain, into the sella turcica. The pituitary may be completely flattened as a pancake at the bottom of the sella as a result. Clinical hypopituitarysm accompanies this. Adenomas nevertheless may develop from such compressed, atrophic pituitary glands.
Endemic goiter
Nodular enlargement of the thyroid due to low environmental dietary iodine.
Exophthalmus
Bulging optic globes seen in hyperthyroidism.
Extraadrenal paraganglioma (chemodectoma)
Usually a benign neoplasm arising in extra-adrenal, catecholamine secreting cells, e.g., in the carotid body, glomus jugulare or organs of Zuckerkandl.
Follicle stimulating hormone (FSH)
Promotes growth and development of ovarian follicles, thereby estrogen production.
Follicular carcinoma
The second most common form of thyroid carcinoma, characterized microscopically by the presence of neoplastic follicles.
Ganglioneuroma
Benign neoplasm of neural crest cells. It is the benign counterpart of neuroblastoma.
Goitrogen
An environmental factor that can cause thyroid enlargement, e.g., iodine deficiency, treatment with thiourea, and certain dietary plant products, including turnip, cabbage, kale and brussel sprouts.
Graves disease
Thyrotoxicosis associated with diffuse thyroid hyperplasia and non-nodular enlargement, i.e. toxic goiter.
Hashimoto thyroiditis (struma lymphomatosa)
An autoimmune disease in which there is diffuse, painless thyroid enlargement due to infiltration by lymphocytes.
Howeship lacuna
A microscopic focus of bone resorption in hyperparathyroidism. In these lesions osteoclasts excavate resorption pits into the surfaces of trabecular bone spicules. Adjacent bone surfaces are lined by fibroblastic marrow stromal cells, differentiating into osteoblasts. Osteoblasts secrete alkaline phosphatase causing a rise in serum alkaline phosphatase.
Human growth hormone (HGH)
Instead of stimulating endocrine glands, it acts directly on somatic tissues, promoting their growth. Deficiency of HGH results in pituitary dwarfism, overproduction (usually from an adenoma) results in gigantism before the epiphyseal lines close, and acromegaly afterwards. HGH also causes hyperglycemia and may aggravate existing diabetes mellitus.
Hurthle cell
End stage or damaged follicular cell characterized microscopically by the presence of abundant, eosinophilic, granular cytoplasm.
Hypercalcemia of malignancy
A variety if malignant tumors, especially carcinomas of breast, lung, squamous carcinomas of the head and neck, and renal cell carcinomas secrete a PTH-like substance which causes increased bone resorption and hypercalcemia. This is the most common of all paraneoplastic syndromes. Not infrequently hematologic malignancies, esp. multiple myeloma and high grade lymphoma, are associated with hypercalcemia. In most cases, the tumor is secreting "parathyroid hormone-related peptide" (PTHrp).
Hyperprolactinemia
This condition is the result of a prolactin producing adenoma (the most common functioning adenoma of the pituitary) or of stalk defect, (e.g., disruption of the pituitary stalk by surgery or disease pressure by a brain tumor, or basal meningitis) prevents inhibiting factors reaching prolactin-producing cells in the adenohypophysis, hence hyperprolactinemia. In women secretion from the nipples (galactorrhea with amenorrhea), in men impotence and testicular atrophy may be caused by hyperprolactinemia.
Hypoparathyroidism
Decreased PTH secretion due to parathyroid absence or agenesis. Hypocalcemia results from an inadequate release of Ca2+ from the bone. Aside from the accidental removal of the parathyroid during thyroidectomy, the most common cause of hypoparathyroidism is the developmental absence of the parathyroids. Because the parathyroids and thymus arise from the same embryonic anlagen, a condition known as DiGeorge syndrome, exhibiting not only hypoparathyroidism but also T-cell immunodeficiency, results from a failure of development both thymus and parathyroids.
Luteinizing hormone (LH)
Promotes formation of the ovarian corpus luteum, and progesterone production.
MEN II syndrome
A syndrome in which there is concurrence of multiple endocrine neoplasias. In MEN II (also known as Sipple syndrome) there is usually medullary carcinoma of the thyroid plus pheochromocytoma of the adrenal.
Medullary carcinoma
Uncommon thyroid carcinoma derived from calcitonin-secreting parafollicular cells (C cells). Typically, deposits of endocrine-type amyloid are present, infiltrating this tumor.
Metastatic calcification
Pathologic calcification of soft tissues, especially lungs, stomach and kidneys, due to hypercalcemia, hyperphosphatemia or both. This is a serious complication of both primary and secondary hyperparathyroidism.
Myxedema
Hypothyroidism occurring in adulthood. Clinical features include lethargy, cold intolerance, decreased sweating, bradycardia, tongue enlargement, and non-pitting edema of the skin due to infiltration of the subcutaneous tissues by metachromatic proteoglycans.
Nelson syndrome
Surgical removal of the adrenal glands (sometimes for treatment of Cushing syndrome) reduces feedback to the hypothalamus resulting in hyperplasia of ACTH producing cells in conjunction with melanotrophic hormone production. The patient's face is round and hyperpigmented.
Neuroblastoma
A malignant neoplasm of childhood. This tumor of the adrenal medulla is derived from primitive neural crest cells.
Neurohypophysis
The posterior lobe of the pituitary, connected to the hypothalamus by a stalk. The neurohypophysis originates as a downgrowth of nervous tissue from the hypothalamus, it joins as pituitary posterior lobe the adenohypophysis within the sella turcica of the sphenoid bone. It is not a true gland, its glia-like constituent cells store and release rather than produce posterior lobe hormones.
Osteitis fibrosa cystica (von Recklinghausen disease of bone)
Osteoclastic bone resorption seen in hyperparathyroidism. X-ray changes include resorption of the distal phalanges and the lamina dura of the teeth. Gross lesions caused by hyperparathyroidism have a gelatinous, brown (anchovy paste) appearance and are often referred to as "brown tumors".
Oxyphil cell
An involutional chief cell with abundant granular eosinophilic cytoplasm. The number of oxyphil cells increases with age; their function is unknown. The cytoplasm is packed with mitochondria.
Oxytocin
This hormone helps contraction of the uterine smooth muscles (myometrium), most importantly during the birth process. It also helps to expel milk from mammary glands during nursing.
Papillary carcinoma
The most common form of thyroid carcinoma, is characterized microscopically by papillary proliferations and psammoma bodies. Papillary carcinomas are usually slow-growing and slow to metastasize, so the prognosis is generally good.
Pheochromocytoma
Usually benign catecholamine-secreting tumor of the adrenal medulla. Over-secretion of epinephrine and/or norepinephrine by the tumor cells is associated with paroxysmal hypertension.
Pituitary adenomas
Some produce hormones (one or more), others do not. They often compress within the narrow confines of the sella turcica the rest of the pituitary, thereby causing hypofunction of the gland. Small tumors (microadenomas) become symptomatic only if they produce hormones in excess. Large tumors (macroadenomas) in addition to compressing the rest of the pituitary, extend upward from the sella and press against the optic chiasm causing first bitemporal hemianopsia, but eventually possible total blindness. Rarely they may even kill the patient via increased intracranial pressure.
Pituitary carcinomas
These are rare malignant epithelial tumors, most often of the basophilic variety. They may metastasize widely to other organs.
Pituitary portal system
Hypothalamic hormones stimulating or inhibiting pituitary anterior lobe function reach the gland through veins coming from the hypothalamus. Since the hypophysis receives these rare afferent veins, they share this distinction with the portal vein system of the liver which brings blood to an organ rather than take out blood. (The latter is done by hepatic veins in the liver, and the hypophysis also has efferent veins).
Pituitary stalk
Nervous tissue connecting the hypothalamus with the posterior lobe of the hypophysis.
Primary hyperparathyroidism
Hypersecretion of PTH due to an intraparathyroid cause. Causes of primary hyperparathyroidism, in order of descending frequency, are parathyroid adenoma, parathyroid hyperplasia and parathyroid carcinoma. Clinical findings include high serum and urine Ca, low serum and high urine phosphate, and high serum alkaline phosphatase, localized bone loss on x-ray especially in the phalanges and lamina dura of the teeth, and renal stones.
Prolactin
Promotes milk production in mammary glands.
Pseudohypoparathyroidism
A condition in which clinical findings are similar to those seen in true hypoparathyroidism, but the hypocalcemia is uncorrectible by giving PTH. In this case there is "end-organ resistance" to PTH, especially in the kidneys and bone. Also, there is a characteristic body habitus including short stature, round face and short fingers (brachydactly).
Rathke pouch
An extension of the primitive oral cavity (stomodeum) into the sphenoid bone. The pouch is lined by oral mucosal epithelium (it does not originate from the pharynx, the term craniopharyngioma notwithstanding). Eventually the lining cells differentiate into the hormone-producing anterior lobe cells of the pituitary gland. Remnants of Rathke pouch may form cysts.
Riedel thyroiditis
Invasive, fibrous thyroid infiltration of unknown etiology. Also known as "woody" thyroiditis, due to the texture of the involved gland.
Rosette
Circumferential arrangement of primitive neuroblast cells in a neuroblastoma.
Secondary hyperparathyroidism
Due to excess PTH secretion in response to the persistently low serum calcium levels that occur in chronic renal disease. Manifestations in the bones are clinically referred to as renal osteodystrophy.
Sheehan syndrome
Severe loss of function of the anterior lobe of the pituitary, classically due to infarction secondary to venous stasis in the late phase of pregnancy or at delivery. Loss of body hair, no lactation and no resumption of menstrual periods are common clinical signs. Hypofunction of thyroids and adrenal cortex also develop with loss of pituitary stimulating hormones.
Stridor
A harsh vibrating sound produced by respiration.
Supraoptic and paraventricular nuclei
Clusters of neurons above the optic tracts and next to the wall of the third ventricle, respectively. They are able to secrete the polypeptides antidiuretic hormone (vasopressin) and oxytocin. These substances travel through the axons of these neurons via the pituitary stalk into the posterior lobe of the hypophysis.
Thyroglossal duct cyst
Persistent, cystic thyroglossal duct. The latter is the anlagen of the thyroid, which arises as a midline invagination from the foramen cecum of the tongue.
Thyroid binding globulin (TBG)
The carrier protein in the blood for the thyroid hormones T3 and T4.
Thyroid stimulating hormone (TSH)
Stimulates thyroid growth and hormone output. Its absence brings about hypothyroidism, eventually atrophy of the gland.
Thyroid stimulating immunoglobulin (TSI)
A circulating autoimmune factor in Graves disease that binds and activates the thyroid hormone receptor on follicular cells.
Thyroid storm
A severe hyperthyroid state characterized by hyperpyrexia, dehydration due to G.I. disturbances, marked hypertension, tachycardia, arrhythmia, shock and ultimately death if not corrected.
Thyrotoxicosis
A hypermetabolic state, resulting from excessive secretion of thyroid hormone, characterized by nervousness, sweating, palpitation, tachycardia, tremor, loss of weight, heat intolerance, and high output cardiac failure.
Vanilylmandelic acid
Metabolic end-product of catecholamines, excreted into the urine.
Water-clear (German- wasserhelle) cell
A variant of chief cells with abundant, clear cytoplasm. They also are capable of secreting PTH.
Waterhouse-Friderichsen syndrome
Acute adrenal cortical insufficiency, often caused by septicemia and associated with disseminated intravascular coagulation. Clinical features include profound weakness, fever, shock, and petechial hemorrhages throughout the skin and mucous membranes.
Zona glomerulosa, fasciculata and reticularis
Microscopic and functional layers of the adrenal cortex.