Yegappan Lakshmanan, MD, (FRCS Ed)

• Chief, Department of Pediatric Urology,
• Children? Hospital of Michigan,
• Detroit, Michigan

This drug may be required for several months and should then be withdrawn gradually menstrual cycle 50 days discount female cialis. Drug-Associated Thyroiditis Thyroiditis is an uncommon complication of pharmacotherapy breast cancer medication buy female cialis 20mg with mastercard. Most of the thyroiditis associated with various therapeutic agents appears to be due to drug-induced exacerbation of underlying autoimmune disease menopause pain order female cialis cheap online. This effect is understandable with agents that are specifically administered to modify the immune system pregnancy early signs cheap 10mg female cialis with mastercard. Although imatinib has been associated with an increase in levothyroxine requirements in hypothyroid patients (analogous to the effects of phenytoin menopause cream buy female cialis 20 mg without a prescription, carbamazepine women's healthy eating plan discount female cialis 20mg on-line, and rifampin), those changes are independent of thyroid function. In other instances, large doses of thyroid hormone or other thyroactive material may be given without the knowledge of the patient, usually as part of a regimen for weight reduction. Some "natural" products for weight reduction stated not to contain thyroid hormone nonetheless do. In the absence of preexisting disease of the thyroid, the diagnosis is made from the combination of typical thyrotoxic manifestations, together with thyroid atrophy and hypofunction. Serum T4 concentrations are increased unless the patient is taking T3, in which case they will be subnormal. The presence of low, rather than elevated, values of serum Tg is a clear indication that the thyrotoxicosis results from exogenous hormone rather than thyroid hyperfunction. Evidence for the two latter disorders can be obtained by demonstration of the ectopic focus or foci by external radioiodine scanning or the presence of normal to elevated serum Tg concentrations. Treatment of thyrotoxicosis factitia consists of withdrawing the offending medication. Hamburger Thyrotoxicosis An unusual form of exogenous thyrotoxicosis occurred in the midwestern portion of the United States in 1984 and 1985. The source was the inclusion of large quantities of bovine thyroid in ground beef preparations. Such a possibility, although remote, should be considered, especially if one is confronted with epidemic exogenous thyrotoxicosis. Thyrotoxicosis Due to Extrathyroidal Tissue Struma Ovarii Thyroid tissue may be present in 5% to 10% of ovarian teratomas, and occasionally such foci are hyperfunctional. Although thyrotoxicosis is unusual, it may occur in as many as 8% to 10% of patients. The Tg may be elevated, particularly if the teratoma is malignant and has metastasized to the peritoneum. Thyrotoxicosis Factitia Thyrotoxicosis that arises from the ingestion, usually chronic, of excessive quantities of thyroid hormone usually occurs in individuals with a background of underlying psychiatric disease, especially in paramedical personnel who have access to thyroid hormone or in patients for whom thyroid hormone medication has been prescribed in the past. Generally the patient is aware of taking Chapter 12 Hyperthyroid Disorders 403 Treatment the patient should be rendered euthyroid if thyrotoxicosis is significant, followed by removal of the involved ovary or ovaries. Therapeutic radioiodine will be required for metastatic disease after ablation of the normal thyroid gland. Thyrotoxicosis Due to Metastatic Thyroid Carcinoma In general, thyroid carcinomas are made up of poorly functioning tissue. Treatment of this condition is typical for that of thyroid carcinoma and is described in Chapter 14. In patients with thyrotoxicosis due to metastatic tumor, serum Tg is quite elevated, indicating that the thyrotoxicosis is caused by thyroidal tissue that is not located in the neck. Prevalence of mitral valve prolapse in chronic lymphocytic thyroiditis and nongoitrous hypothyroidism. Autoantibodies of beta-adrenergic and M2 cholinergic receptors: atrial fibrillation in hyperthyroidism. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. Embolic risk in atrial fibrillation that arises from hyperthyroidism: review of the medical literature. Myocardial contractility and total arterial stiffness in patients with overt hyperthyroidism: acute effects of beta1-adrenergic blockade. Chronic cardiacspecific thyrotoxicosis increases myocardial beta-adrenergic responsiveness. Changes in adenylyl cyclase isoforms as a mechanism for thyroid hormone modulation of cardiac beta-adrenergic receptor responsiveness. Expression of uncoupling protein 1 in mouse brown adipose tissue is thyroid hormone receptor-beta isoform specific and required for adaptive thermogenesis. Thyroid hormone and parathyroid hormone competing to maintain calcium levels in the presence of vitamin D deficiency. Extraocular muscles have fundamentally distinct properties that make them selectively vulnerable to certain disorders. Change in bone mineral density in patients with hyperthyroidism after attainment of euthyroidism by dual energy X-ray absorptiometry. Bone mineral density in patients with hyperthyroidism measured by dual energy X-ray absorptiometry. Thyroid hormone excess rather than thyrotropin deficiency induces osteoporosis in hyperthyroidism. Changes in bone mass during prolonged subclinical hyperthyroidism due to L-thyroxine treatment: a metaanalysis. Anemia in patients with resistance to thyroid hormone: a role for thyroid hormone receptor in human erythropoiesis. Complex drug-drug-disease interactions between amiodarone, warfarin, and the thyroid gland. Urinary cortisol metabolites in the assessment of peripheral thyroid hormone action: application for diagnosis of resistance to thyroid hormone. A novel population of inner cortical cells in the adrenal gland that displays sexually dimorphic expression of thyroid hormone receptor-1. Detection of atrisk pregnancy by means of highly sensitive assays for thyroid autoantibodies. The interrelationships between thyroid dysfunction and hypogonadism in men and boys. Serum concentration of androstenediol and androstenediol sulfate in patients with hyperthyroidism and hypothyroidism. The presence of an abnormal thyroid-stimulating hormone in the serum of some thyrotoxic patients. Thyrotrophin receptor blocking antibodies: incidence, characterization and in-vitro synthesis. Influences of age, gender, smoking, and family history on autoimmune thyroid disease phenotype. Breaking tolerance to thyroid antigens: changing concepts in thyroid autoimmunity. Regulation of orbital fibrosis and adipogenesis by pathogenic Th17 cells in Graves orbitopathy. Thyroid-stimulating antibody activity between different immunoglobulin G subclasses. Engraftment of human lymphocytes and thyroid tissue into scid and rag2-deficient mice: absent progression of lymphocytic infiltration. Childbirths and risk of female predominant and other autoimmune diseases in a population-based Danish cohort. Lack of association between thyroid autoantibodies and parity in a population study argues against microchimerism as a trigger of thyroid autoimmunity. High frequency of skewed X-chromosome inactivation in females with autoimmune thyroid disease: a possible explanation for the female predisposition to thyroid autoimmunity. Skewed X chromosome inactivation and female preponderance in autoimmune thyroid disease: an association study and meta-analysis. Iodine contributes to thyroid autoimmunity in humans by unmasking a cryptic epitope on thyroglobulin. Decrease of incidence of toxic nodular goitre in a region of Switzerland after full correction of mild iodine deficiency. Low population selenium status is associated with increased prevalence of thyroid disease. No causal relationship between Yersinia enterocolitica infection and autoimmune thyroid disease: evidence from a prospective study. Hepatitis C virus infection of a thyroid cell line: implications for pathogenesis of hepatitis C virus and thyroiditis. Risk factors for and prevalence of thyroid disorders in a cross-sectional study among healthy female relatives of patients with autoimmune thyroid disease. Alemtuzumab-induced thyroid dysfunction exhibits distinctive clinical and immunological features. Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma. Survey of clinical practice patterns in the management of 992 hyperthyroid patients in France. Prevalence of thyrotropin receptor germline mutations and clinical courses in 89 hyperthyroid patients with diffuse goiter and negative anti-thyrotropin receptor antibodies. All-cause and cardiovascular mortality risk after surgery versus radioiodine treatment for hyperthyroidism. Propylthiouracil blocks extrathyroidal conversion of thyroxine to triiodothyronine and augments thyrotropin secretion in man. Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study. Genetic variants associated with antithyroid drug-induced agranulocytosis: a genome-wide association study in a European population. Expression of the thyroid-stimulating hormone receptor in the folliculo-stellate cells of the human anterior pituitary. Serum thyroxine and triiodothyronine concentrations during iodide treatment of hyperthyroidism. Double-blind, placebo-controlled, randomized trial of selenium in Graves hyperthyroidism. Role of cholestyramine in refractory hyperthyroidism: a case report and literature review. Is there a minimum number of thyroidectomies a surgeon should perform to optimize patient outcomes Radioiodine therapy in benign thyroid diseases: effects, side effects, and factors affecting therapeutic outcome. Euthyroid and primarily hypothyroid patients develop milder and significantly more asymmetrical Graves ophthalmopathy. Smoking and thyroid-associated ophthalmopathy: a novel explanation of the biological link. Risk factors for developing thyroid-associated ophthalmopathy among individuals with Graves disease. The patient experience of services for thyroid eye disease in the United Kingdom: results of a nationwide survey. Assessment of urinary thyrotropin-competing activity in choriocarcinoma and thyroid disease: further evidence for human chorionic gonadotropin interacting at the thyroid cell membrane. The role of chorionic gonadotropin in transient hyperthyroidism of hyperemesis gravidarum. Thyroid dysfunction associated with administration of the long-acting gonadotropin-releasing hormone agonist. Changes of serum anti-thyroid antibodies during and after pregnancy in autoimmune thyroid diseases. Thyroid autoantibodies in pregnancy: their role, regulation and clinical relevance. Predictive value of maternal second-generation thyroid-binding inhibitory immunoglobulin assay for neonatal autoimmune hyperthyroidism. Human chorionic gonadotropin and the thyroid: hyperemesis gravidarum and trophoblastic tumors. Reference intervals for thyroid markers in early pregnancy determined by 7 different analytical systems. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. Methimazole and propylthiouracil equally cross the perfused human term placental lobule. Scalp defects in infants of mothers treated for hyperthyroidism with methimazole or carbimazole during pregnancy. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Birth defects after early pregnancy use of antithyroid drugs: a Danish nationwide study. Embryonic exposure to propylthiouracil disrupts left-right patterning in Xenopus embryos. Therapy of endocrine disease: antithyroid drug use in early pregnancy and birth defects: time windows of relative safety and high risk Maternal thyrotropin receptor antibody concentration and the risk of fetal and neonatal thyrotoxicosis: a systematic review. Failure of rituximab treatment in a case of severe thyroid ophthalmopathy unresponsive to steroids. Treatment of maternal hyperthyroidism with antithyroid agents and changes in thyrotrophin and thyroxine in the newborn. Pharmacological treatment of hyperthyroidism during lactation: review of the literature and novel data. Thyroid function and intellectual development of infants nursed by mothers taking methimazole. Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism.

Extension of the infiltrate into epithelial (ductal) structures results in metaplasia and characteristic epimyoepithelial islands menstruation cup buy female cialis without prescription. Severe chronic inflammation and marked atrophy of the submandibular gland are present after irradiation of an adjacent oral cancer pregnancy mask buy female cialis 10mg visa. Late in the course of the disease menstrual gingivitis order 20mg female cialis free shipping, affected glands become atrophic women's health center elkhart indiana discount female cialis 10mg with visa, with fibrosis and fatty infiltration of the parenchyma menstruation synchronization buy cheap female cialis online. Salivary duct stricture or obstruction by stones may cause acute or chronic parotitis breast cancer 60 mile 3 day buy female cialis 20 mg on line. Epidemic parotitis (mumps) is an acute viral disease of the parotid glands that spreads via infected saliva. Involved glands have dense lymphocytic and macrophage infiltrates, epithelial degeneration and necrosis. Two thirds of major salivary gland tumors, and about half of those in the minor glands, are pleomorphic adenomas. These tumors occur nine times more often in the parotid than in the submandibular gland and usually arise in the superficial lobe of the former. Involvement of the lacrimal glands results in dry eyes (keratoconjunctivitis sicca). Initial periductal chronic inflammation gradually extends into the acini, until the glands are completely replaced by a sea of polyclonal lymphocytes, immunoblasts, germinal centers and plasma cells. Around ductal epithelial cells are smaller myoepithelial cells, which are the main cellular component. These tumor projections can be missed if a tumor is not carefully excised with its capsule intact, plus an adequate margin of gland parenchyma. Tumor implanted during surgery or tumor nodules left behind continue to grow and recur in scars from previous operations. Carcinomas may rarely arise in pleomorphic adenomas (carcinoma ex pleomorphic adenoma). In this case, the tumor that was present for many years then begins to grow rapidly or becomes painful. Such carcinomas are most frequently high-grade malignancies set in otherwise benign pleomorphic adenomas. However, virtually any type of salivary gland malignancy may occur in this setting, including mucoepidermoid or adenoid cystic carcinomas. If the malignancy is confined to the tumor capsule and does not invade the adjacent salivary gland, it is considered in situ or noninvasive carcinoma ex pleomorphic adenoma. Cellular components of pleomorphic adenomas include an admixture of glands and myoepithelial cells within a chondromyxoid stroma. The tumor is partly encapsulated, but a nodule protruding into the parotid gland lacks a capsule. Most (75%) arise in the parotid glands, 10% in the submandibular glands and 15% in the minor salivary glands of the upper aerodigestive tract. Warthin Tumor (Papillary Cystadenoma Lymphomatosum) Warthin tumors are the most common monomorphic adenomas. They are benign parotid gland neoplasms composed of cystic glandular spaces within dense lymphoid tissue. Clearly benign, they may be bilateral (15% of cases) or multifocal within one gland. These are the only salivary gland tumors that are more common in men than in women. Intermediate-grade tumors tend to grow in more solid patterns, with more epidermoid and intermediate cells and fewer mucussecreting cells. Lymph nodes are normally found in the parotid gland and its immediate vicinity and usually contain a few ducts or small islands of salivary gland tissue. Oncocytoma (Oxyphil Adenoma) Oncocytes are benign epithelial cells swollen with mitochondria, which impart a granular appearance to the cytoplasm. They are normally scattered or in small clusters among epithelial cells of various organs. Rare adenomas of nests or cords of oncocytes occur in parotid glands of the elderly. Mucoepidermoid carcinoma is characterized by an admixture of mucocytes (straight arrows), epidermoid cells (curved arrows) and intermediate cells. The mucocytes are clustered and have a clear cytoplasm with eccentrically situated nuclei. Epidermoid cells are squamous-like cells but lack keratinization and intercellular bridges. Adenoid cystic carcinoma showing cribriform growth in which cyst-like spaces are filled with basophilic material. Most do not metastasize for years, but they are often diagnosed late, are difficult to eradicate completely and have a poor longterm prognosis. Treatment is dictated by grade; low-grade tumors are treated surgically, but high-grade tumors require both surgery and radiation therapy. Acinic Cell Adenocarcinomas Arise from Secretory Cells these uncommon parotid tumors (10% of salivary gland tumors) arise occasionally in other salivary glands. Acinic cell carcinomas are encapsulated, round masses, usually under 3 cm, and may be cystic. They represent 5% of major salivary gland tumors and 20% of those of the minor salivary glands. The tumor cells are small, have scant cytoplasm and grow in solid sheets or as small groups, strands or columns. Tumor cells produce a homogeneous basement membrane material that gives them the characteristic "cylindromatous" appearance. This tumor demonstrates a solid growth pattern and is composed of basophilic cells with abundant cytoplasm filled with zymogen granules. Its outer surface is squamous epithelium, continuous with the skin of the external ear canal. They are composed of thick, hyalinized bundles of collagen in the deep dermis (see Chapter 3). Blows to the ears cause subperichondrial hematomas, which organize and deform the ears. The etiology of relapsing polychondritis is obscure; immune mechanisms are suspected. Relapsing polychondritis may occur alone or with other connective tissue diseases. Noncartilaginous tissues, such as the sclera and cardiac valves, also may be affected. The external auditory canal or meatus extends from the concha medially to the tympanic membrane (eardrum). The eardrum sits obliquely at the end of the external auditory canal, sloping medially from above downward and from behind forward, separating the external ear and the middle ear. The auricle is composed of keratinizing, stratified squamous epithelium with associated adnexa (hair follicles, sebaceous glands, eccrine sweat glands). The outer third of the external auditory canal also has ceruminal glands, modified apocrine glands that replace the eccrine glands of the auricular dermis. They produce cerumen and contain clusters of cuboidal cells with eosinophilic cytoplasm, often with granular, golden yellow pigment and secretory droplets by their luminal border. Ultimately, the cartilage is destroyed and replaced by granulation tissue and fibrosis. The perichondrium and elastic cartilage are infiltrated and partially destroyed by inflammatory cells and replaced by fibrosis. Infection may spread through the skin and cartilage to cause mastoiditis or osteomyelitis of the skull, venous sinus thrombosis, meningitis and death. Malignant otitis externa occurs mainly in elderly diabetics but also in patients with blood dyscrasias. This effect is particularly severe if there is an upper respiratory tract infection, acute allergic reaction or viral or bacterial infection at the eustachian tube orifice. Over half of children in the United States have at least one bout of serous otitis media before their third birthday. Repeated otitis media in early childhood often leads to residual (usually sterile) fluid in the middle ear, which contributes to unsuspected hearing loss. Carcinoma of the nasopharynx may cause chronic serous otitis media in adults and should be suspected if a unilateral middle ear effusion occurs in an adult. Together with the mastoid air sinuses, it forms a closed mucosal compartment, also called the middle ear cleft. This air passage allows air pressure on both sides of the tympanic membrane to equalize. The three auditory ossicles-the malleus, incus and stapes-are a chain that connects the tympanic membrane with the oval window located at the medial wall of the tympanic cavity. Free motion of the ossicles, mainly the stapes in the oval window, is more important for hearing than is an intact tympanic membrane. The middle ear opens posteriorly into the mastoid antrum, a honeycomb of small, aerated, bony compartments (air cells) lined by a thin mucous membrane continuous with that of the middle ear. Otitis Media Often Follows Obstruction of the Eustachian Tube Otitis media is inflammation of the middle ear. It usually results from upper respiratory tract infections that spread from the nasopharynx. Obstruction of the eustachian tube is important in production of middle ear effusions. When the pharyngeal end of the eustachian tube is swollen, air cannot enter the tube. Air in the middle ear is absorbed through the mucosa, and negative pressure causes transudation of plasma and occasional bleeding. Viral otitis media may resolve without suppuration or lead to secondary invasion by pusforming bacteria. Microorganisms ascend from the nasopharynx, through the eustachian tube, to the middle ear. Cholesterol crystals stimulate a foreign body response and granulation tissue, called a cholesterol granuloma. If they are allowed to persist for many months, the granulation tissue may become fibrotic, which may eventually lead to complete obliteration of the middle ear and mastoid by fibrous tissue. An accumulating purulent exudate in the middle ear may rupture the eardrum, causing a purulent discharge. Mastoid air cells are filled with pus, and their thin osseous intercellular walls are destroyed. Chronic otitis media occurs much more commonly in people who have had ear disease in early childhood, which may have arrested normal development of the air cells in the mastoid. Destruction of the facial nerve Deep cervical or subperiosteal abscess, if cortical bone of the mastoid process is eroded Petrositis, when infection spreads to the petrous temporal bone through the chain of air cells Suppurative labyrinthitis, due to infection of the internal ear Epidural, subdural or cerebral abscess, when infection extends through the inner table of the mastoid bone Meningitis, when infection reaches the meninges Sigmoid sinus thrombophlebitis, if infection traverses the dura to the posterior cranial fossa loss are constant symptoms. Exuberant granulation tissue may form polyps, which can extend through the perforated eardrum into the external ear canal. A cholesteatoma is a mass of accumulated keratin and squamous mucosa due to growth of squamous epithelium from the external ear canal through a perforated eardrum into the middle ear. The main dangers of cholesteatoma arise from bony erosion, which may destroy important contiguous structures. Jugulotympanic Paragangliomas Arise from Middle Ear Paraganglia Jugulotympanic paragangliomas are the most common benign tumors of the middle ear. They grow slowly but, over years, may destroy the middle ear and extend into the internal ear and cranial cavity. Paraganglial cells are of neural crest origin and contain varying amounts of catecholamines, mostly epinephrine and norepinephrine. The complex cavities of the osseous labyrinth contain the membranous labyrinth, a series of communicating membranous sacs and ducts. The osseous labyrinth connects to the subarachnoid space via the cochlear aqueduct. The entire mucosa (curved arrow) is thickened by chronic inflammation and granulation tissue. Tumor cell nests are composed of cells with ill-defined cell borders and prominent eosinophilic cytoplasm (chief cells). The membranous labyrinth contains a different fluid, the endolymph, which circulates in a closed system. Because there are no barriers between the cochlear and vestibular labyrinths, injury or disease of the inner ear frequently affects both hearing and equilibrium. It has three compartments: two that contain perilymph and a third (the cochlear duct) with endolymph. The cochlear duct encompasses the end organ of hearing, the organ of Corti, which rests on the basement membrane and is arranged as a spiral, with three rows of outer hair cells and a row of inner hair cells.

This subset of tumors tends to be solid and less likely to be calcified or cystic menopause jealousy buy female cialis 10mg without prescription. Visual field defects women's health specialists zanesville ohio order cheap female cialis on-line, papilledema pregnancy foods to eat safe 20 mg female cialis, and optic atrophy can occur from compression of the optic chiasm or nerves menopause 55 proven 10 mg female cialis. Between 80% and 90% of affected children have signs and symptoms of endocrine dysfunction women's health center tucson az cheap 20 mg female cialis visa, although these are not usually the chief complaint womens health 9 diet purchase cheap female cialis line. The latter is almost universal in adolescents and adults and likely also present, but undetected, in prepubertal children with craniopharyngiomas. Even if not present at initial diagnosis, endocrine dysfunction often occurs subsequent to treatment that may also include obesity, imbalances in body temperature, autonomic dysfunction, Precocious Puberty the term precocious puberty is used when physiologically normal pituitary-gonadal function appears at an early age (see also Chapter 26). Central precocious puberty with neurogenic causes and pineal gland disease are discussed in this chapter. Idiopathic Sexual Precocity Familial occurrence of idiopathic sexual precocity is uncommon, but there is a hereditary form of idiopathic sexual precocity that is largely confined to boys. The pathogenesis may be related to the rate of hypothalamic development or other as yet undetermined nutritional, environmental, or psychosocial factors. Many cases previously thought to be idiopathic are caused by small hypothalamic hamartomas (see later discussion). The intrahypothalamic or sessile type is enveloped by the posterior hypothalamus, which can distort the third ventricle. These hamartomas tend to be larger than the pedunculated variety, grow in the interpeduncular cistern, and are frequently accompanied by seizures, mental retardation, and developmental delays. Before the development of high-resolution scanning techniques, harmatoma was considered rare, but small ones can now be visualized. Precocious puberty occurs when the hamartoma makes connections with the median eminence and thus serves as an accessory hypothalamus. Manifestations of premature puberty in patients with hamartomas are similar to those associated with other central causes of precocity. In the past, most cases were thought to be fatal by age 20 years, but many hamartomas cause no brain damage and need not be excised. Early in the course of illness, epilepsy manifested as "brief, repetitive, stereotyped attacks of laughter"644 may provide a clue to the disease. Late in the course, hypothalamic damage can cause severe neurologic defects and intractable seizures. Several discrete cytopathologic entities account for mass lesions in the pineal region (Table 7. True pinealomas can be relatively well-differentiated pineocytomas, intermediate mixed forms, or the less-differentiated pineoblastomas,646,647 which are essentially identical to medulloblastomas, neuroblastomas, and oat cell carcinomas of the lung. The most common tumors of the pineal gland are actually germinomas (a form of teratoma), so designated because of their presumed origin in germ cells. A third possibility is that hypothyroidism causes hypothalamic encephalopathy that impairs the normal tonic suppression of gonadotropin release by the hypothalamus. Tumors of the Pineal Gland Pineal Parenchymal Tumors Pinealocytes Pineocytoma Pineoblastoma Ganglioglioma and chemodectoma Mixed forms exhibiting transitions among these types Glia Astrocytoma Ependymoma Mixed forms and other less frequent gliomas. Parinaud syndrome, which consists of paralysis of upward gaze, pupillary areflexia (to light), paralysis of convergence, and a wide-based gait, occurs with about half of patients with pinealomas. Additional neurologic signs occurring Nonneoplastic Conditions of Neurosurgical Importance Degenerative cysts of pineal gland lined by fibrillary astrocytes Arachnoid cysts Cavernous hemangioma From DeGirolami U. Teratomas derived from two or more germ cell layers also occur in the pineal region. Rarely, pinealomas cause delayed puberty, raising speculation about the role of melatonin in inhibiting gonadotropin secretion in these cases. Stereotaxic biopsy of the pineal region provided diagnosis in 33 of 34 cases in one series, suggesting that this is a useful alternative to open surgical exploration for diagnostic purposes. Psychogenic Amenorrhea Menstrual cycles can cease in young nonpregnant women with no demonstrable abnormalities of the brain, pituitary, or ovary in several situations,658,659 including pseudocyesis (false pregnancy), anorexia nervosa, excessive exercise, psychogenic disorders, and hyperprolactinemic states (see Chapter 17). Psychogenic amenorrhea, the most common cause of secondary amenorrhea except for pregnancy, can occur with major psychopathology or minor psychic stress and is often temporary. Exercise-induced amenorrhea may be a variant of psychogenic amenorrhea or may result from loss of body fat. If the activity is begun before puberty, normal sexual maturation can be delayed for many years. Fat mass may be a regulator of gonadotropin secretion with adipocyte-derived leptin as the principal mediator between peripheral energy stores and hypothalamic regulatory centers. Several organic lesions of the hypothalamus can cause this syndrome, including tumors, encephalitis, microcephaly, Friedreich ataxia, and demyelinating diseases. Other important causes of hypogonadotropic hypogonadism are Kallmann syndrome and Prader-Willi syndrome. Furthermore, most obese boys with delayed sexual development have no structural damage to the hypothalamus but have constitutional delayed puberty, which is commonly associated with obesity. It is not known whether there is a functional disorder of the hypothalamus in this condition. It is thought that psychosexual development of brain maturation depends on the presence of androgens within a critical developmental window corresponding to puberty; therefore hypogonadism in boys (regardless of cause) should be treated by the middle teen years (15 years of age at the latest). Several groups have reviewed the diagnostic approach to suspected central precocious puberty (see Chapter 26). Prolonged physical stress and sleep and energy deficiency can also decrease testosterone and gonadotropin levels. Persistence of regulatory abnormalities may be due to incomplete removal of a tumor, abnormal function of the remaining part of the gland, or underlying hypothalamic abnormalities. Furthermore, the results of repeated tests in children show considerable variability. It has been suggested that specific genetic defects may underlie the pathogenesis of a subset of children with this heterogeneous syndrome of growth failure. Such disorders include optic nerve dysplasia and midline prosencephalic malformations (absence of the septum pellucidum, abnormal third ventricle, and abnormal lamina terminalis). Maternal Deprivation Syndrome and Psychosocial Dwarfism Infant neglect or abuse can impair growth and cause failure to thrive (the maternal deprivation syndrome). A striking feature is an alert appearance and seeming euphoria despite the profound emaciation. A variety of associated neurologic abnormalities may be present, including nystagmus, irritability, hydrocephalus, optic atrophy, tremor, and excessive sweating. Most cases are due to chiasmatic-hypothalamic gliomas, with the majority classified as astrocytomas. The patient had a recurring cyclic disorder characterized by high fever, paroxysms of glucocorticoid hypersecretion, and electroencephalographic abnormalities. Psychologic abnormalities in hypothalamic disease include antisocial behavior; attacks of rage, laughing, and crying; disturbed sleep patterns; excessive sexuality; and hallucinations. Both somnolence (with posterior lesions) and pathologic wakefulness (with anterior lesions) occur, as do bulimia and profound anorexia. A more complete discussion of imbalance in energy homeostasis (both obesity and cachexia) associated with hypothalamic dysfunction and neuropeptides is presented in Chapter 39. Patients with hypothalamic damage may experience hyperthermia, hypothermia, unexplained fluctuations in body temperature, and poikilothermy. Disturbances of sweating, acrocyanosis, loss of sphincter control, and diencephalic epilepsy are occasional manifestations. Hypothalamic damage also causes loss of recent memory, believed to be due to damage of the mammillothalamic pathways. Hypothalamic tumors grow slowly and may reach a large size while producing minimal disturbance of behavior or visceral homeostasis, whereas surgery of limited extent can produce striking functional abnormalities. Presumably this is because slowly growing lesions permit compensatory responses to develop. Adverse effects of treatment have led to more conservative surgical guidelines for the treatment of craniopharyngioma. A review from the University of Pittsburgh summarizes their individualized treatment program that includes microsurgical tumor resection, intracavitary 32P radiotherapy, and gamma knife stereotactic radiosurgery to produce maximal benefit with minimal morbidity. More generally, these recent discoveries suggest the possibility that other cryptic hypothalamic disorders could be caused by selective disturbances in other neuropeptidergic circuits. Paroxysmal Sympathetic Storms (Diencephalic Epilepsy) Diencephalic epilepsy is characterized by episodic, autonomic discharge that can include tachycardia, bradycardia, diaphoresis, pupillary dilation, flushing, elevations in blood pressure, tachypnea, hypothermia and hyperthermia, and abnormal extensor posturing. Therefore it has been proposed to better describe these episodes as paroxysmal sympathetic storms. Narcolepsy A convergence of functional genomics from two animal species, the dog and mouse, has dramatically refocused attention on neuropeptide circuits of the hypothalamus in the control of sleep and wakefulness. Positional cloning was used to identify mutations in the hypocretin-orexin receptor 2 as a cause of canine narcolepsy. Most cases of spontaneous narcolepsy with cataplexy result from a degenerative hypothalamic disorder, most likely autoimmune in pathogenesis, that produces a selective destruction of neuropeptidergic neurons. Future development of bioavailable, orexin-hypocretin receptorselective compounds may provide a specific treatment alternative Kleine-Levin Syndrome Kleine-Levin syndrome is a periodic sleep disorder, generally of male adolescents, characterized by relapsing episodes of hypersomnia that can last hours to days associated with cognitive and behavioral abnormalities, including hyperphagia and hypersexuality, but normal behavior between episodes. The etiology is unknown, although several hypotheses have been put forward and reviewed by Al Shareef and colleagues697 Evidence for abnormal perfusion by functional imaging studies in several brain regions, including the hypothalamus, thalamus, and cortex, has raised the possibility that Kleine-Levin syndrome may be an inflammatory disorder either due to viral or autoimmune encephalitis. However, there is evidence to suggest that the hypothalamus is also involved in the pathophysiology of a number of common neuropsychiatric disorders. Genome-wide pathway and functional analysis of susceptibility genes associated with schizophrenia, for example, identify the hypothalamus as one of five major regions in the brain where these genes are predominantly expressed. Enlargement of the third ventricle is also known to be associated with schizophrenia and major depressive illness and thought secondary to loss of periventricular gray matter (see Bernstein and colleagues701 for review). Dysregulation of the oxytocin and orexin systems has also been implicated in the pathophysiology of neuropsychiatric disorders, although the data have been somewhat inconsistent. Acknowledgments the author greatly appreciates the important contributions made to previous versions of this chapter by Drs. Seymour Reichlin for his teaching, guidance, and important work he has done to shape the direction of neuroendocrinology. Ancient views on the hypothalamic-pituitary-thyroid axis: an historical and epistemological perspective. Permeability of the hypophysis and hypothalamus to vital dyes, with study of hypophyseal blood supply. Leptin prevents fastinginduced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus. Multilevel interactions between the sympathetic and parasympathetic nervous systems: a minireview. Autonomic regulation of islet hormone secretion- implications for health and disease. Localization of vagal preganglionics that stimulate insulin and glucagon secretion. New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Selective pharmacogenetic activation of catecholamine subgroups in the ventrolateral medulla elicits key glucoregulatory responses. A gut-brain axis regulating glucose metabolism mediated by bile acids and competitive fibroblast growth factor actions at the hypothalamus. Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells. Anatomical variations in the pituitary gland and adjacent structures in 225 human autopsy cases. Alpha-melanocytestimulating hormone and N-acetyl-beta-endorphin immunoreactivities are localized in the human pituitary but are not restricted to the zona intermedia. A review of oxytocin and argininevasopressin receptors and their modulation of autism spectrum disorder. Hypothalamic tanycytes: potential roles in the control of feeding and energy balance. Hypothalamic tanycytes-masters and servants of metabolic, neuroendocrine, and neurogenic functions. Regulation of body weight and metabolism by tanycyte-derived neurogenesis in young adult mice. Semaphorin7A regulates neuroglial plasticity in the adult hypothalamic median eminence. Vasoactive intestinal polypeptide/peptide histidine isoleucine immunoreactive neuron systems in the basal hypothalamus of the rat with special reference to the portal vasculature: an immunohistochemical and in situ hybridization study. Signaling pathways to and from the hypophysial pars tuberalis, an important center for the control of seasonal rhythms. The role of hypothalamic tri-iodothyronine availability in seasonal regulation of energy balance and body weight. Identification of an endocannabinoid system in the rat pars tuberalis-a possible interface in the hypothalamic-pituitary-adrenal system Circumventricular organs: definition and role in the regulation of endocrine and autonomic function. Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ. Circumventricular organs: targets for integration of circulating fluid and energy balance signals Ghrelin receptors mediate ghrelininduced excitation of agouti-related protein/neuropeptide Y but not pro-opiomelanocortin neurons. Transient receptor potential vanilloid 1 is required for intrinsic osmoreception in organum vasculosum lamina terminalis neurons and for normal thirst responses to systemic hyperosmolality. Distribution of Fos immunoreactivity in the lamina terminalis and hypothalamus induced by centrally administered relaxin in conscious rats. Intravenous hypertonic saline induces Fos immunoreactivity in neurons throughout the lamina terminalis. Actions of angiotensin in the subfornical organ and area postrema: implications for long term control of autonomic output.

In long-standing womens health 78501 generic female cialis 20mg overnight delivery, chronic osteomyelitis menstruation on depo provera purchase female cialis 20mg with visa, antibiotics alone are not curative and extensive surgical debridement of necrotic bone is often required define women's health issues generic female cialis 20mg otc. Syphilis causes a slowly progressive women's health diet plan cheap female cialis 20 mg with amex, chronic women's health center fountain valley generic 20mg female cialis free shipping, inflammatory disease of bone pregnancy 7 months symptoms discount female cialis 10mg with mastercard, characterized by granulomas, necrosis and marked reactive bone formation. It may be acquired through sexual contact or transmitted transplacentally from mother to fetus (see Chapter 9). Tuberculosis of Bone Represents Spread from a Primary Focus Elsewhere Tuberculosis of bone usually originates in the lungs or lymph nodes (see Chapter 9). When the bone infection is caused by the rare bovine type of tubercle bacillus, the initial focus is often in the gut or tonsils. The mycobacteria spread to the bone hematogenously, and only rarely is there direct spread from the lungs or lymph nodes. In severe disease, an epiphysis may Tuberculous Spondylitis (Pott Disease) Tuberculous spondylitis. As a result of currently available effective antibiotic treatment, Pott disease is now rare. The granulomas first produce caseous necrosis of the bone marrow, which leads to slow resorption of bony trabeculae and, occasionally, to cystic spaces in the bone. Since there is little or no reactive bone formation, affected vertebrae tend to collapse, leading to kyphosis and scoliosis. The intervertebral disk is crushed and destroyed by the compression fracture, rather than by invasion of organisms. If the infection ruptures into the soft tissue anteriorly, pus and necrotic debris drain along the spinal ligaments and form a cold abscess. A cross-section of a tubular bone infected by syphilis shows marked periosteal new bone formation. The medullary cavity is filled with a lymphoplasmacytic infiltrate that replaces the normal marrow fat. The cortex is irregularly destroyed by osteoclastic resorption, a process that stimulates periosteal new bone formation. After the zone of calcified cartilage is destroyed, a sea of lymphocytes, plasma cells and spirochetes fills the marrow spaces. Because the periosteum is stimulated to produce reactive new bone, the thickness of the cortex may actually be doubled. The inflammatory infiltrate permeates the cortex through the Volkmann and Haversian canals and settles in the elevated periosteum. Tibial lesions are marked by periostitis, with deposition of new bone on the medial and anterior aspects of the shaft, which leads to the saber shin deformity. The markedly irregular, thickened periosteal surfaces, which are perforated by pits and serpiginous ulcerations, are characteristic of syphilis. Lysis and collapse of nasal and palatal bones produce the classic saddle nose-perforation, destruction and collapse of the nasal septum (see Chapter 29). It is usually seen in the first two decades of life but occasionally occurs in older individuals. These lesions may cause mild pain or may be incidental findings on routine chest radiographs. Foci of disease in the lower thoracic or upper lumbar vertebrae may lead to collapse and pathologic fractures. There are many eosinophils throughout these lesions, occasionally forming collections called "eosinophilic abscesses. Radiolucent bony lesions characterize the disorder, most frequently in the calvaria, ribs, pelvis and scapulae. Involvement of the jaw bone results in loss of teeth, evident radiologically as "floating teeth. Crusty, red, weepy skin lesions occur at the hairline and on the extensor surfaces of the extremities, the abdomen and occasionally the soles of the feet. Deafness results from involvement of the external auditory canal and mastoid air cells. Multiple organ involvement culminates in massive hepatosplenomegaly, lymphadenopathy, anemia, leukopenia and thrombocytopenia. Widely scattered, seborrheic skin lesions, which are often hemorrhagic, are usual. Bone lesions are not prominent initially, but progressive marrow replacement and pulmonary infiltration occasionally cause death. Diabetes insipidus seems to be irreversible, despite irradiation of the pituitary region. Bone mass normally peaks between the ages of 25 and 35 and begins to decline in the fifth or sixth decade. Bone loss with age occurs in all races, but because of higher peak bone mass, blacks are less prone to osteoporosis than are Asians and whites. Bone loss during normal aging in women has been divided into two phases: menopause and aging. At a certain point, the loss of bone suffices to justify the label osteoporosis and renders weight-bearing bones susceptible to fractures. In whites in the United States, 15% of people have had a hip fracture by the age of 80 years and 25% by age 90. Women have twice the risk of hip fracture as men, although among blacks and some Asian populations, the incidence is equal among the sexes. Compared with other osteoporotic fractures, hip fractures incur the greatest morbidity, mortality (up to 20% within a year) and direct medical costs. A subset of women in the early postmenopausal years is at particular risk of vertebral fractures, which are rare in middle-aged men. The propensity of men to sustain hip fractures as opposed to vertebral ones also reflects factors other than bone mass, such as loss of proprioception. Although osteoporosis reflects a number of causes, it is always characterized by loss of skeletal mass. The etiology for bone loss is diverse but includes menopause, smoking, vitamin D deficiency, low body mass index, hypogonadism, a sedentary lifestyle and glucocorticoid therapy. Regardless of the cause of osteoporosis, it always reflects enhanced bone resorption relative to formation. Thus, this family of diseases should be viewed in the context of the remodeling cycle. Individuals younger than 35 or 40 years completely replace bone resorbed during the remodeling cycle. With age, less bone is replaced in resorption bays than is removed, leading to a small deficit at each remodeling site. Given the thousands of remodeling sites in the skeleton, net bone loss, even in a short time, can be substantial. Primary osteoporosis, by far the more common variety, is of uncertain origin and occurs principally in postmenopausal women (type 1) and elderly people of both sexes (type 2). Secondary osteoporosis is a disorder associated with a defined cause, including a variety of endocrine and genetic abnormalities. Type 1 primary osteoporosis is due to an absolute increase in osteoclast activity. Since osteoclasts initiate bone remodeling, the number of remodeling sites increases in this state of enhanced osteoclast formation, a phenomenon known as increased activation frequency. The increase in osteoclasts in the early postmenopausal skeleton is a direct result of estrogen withdrawal. The effects of lack of estrogen are not, however, targeted directly to the osteoclast, but rather to cells derived from marrow stroma, which secrete cytokines that recruit osteoclasts. Type 2 primary osteoporosis, also called senile osteoporosis, has a more complex pathogenesis than type 1. The lamellar bone trabeculae have abnormal amounts of nonmineralized bone (osteoid). These osteoid seams are thickened and cover a larger than normal area of the trabecular bone surface. The lamellar bone trabeculae are actively resorbed by numerous osteoclasts that bore into each trabecula. The appearance of osteoclasts dissecting into the trabeculae, a process termed dissecting osteitis, is diagnostic of hyperparathyroidism. The morphologic appearance is similar to that of primary hyperparathyroidism, except that prominent osteoid covers the trabeculae. Osteoclasts do not resorb unmineralized bone, and wherever an osteoid seam is lacking, osteoclasts bore into the trabeculae. Thus, although osteoclast activity is no longer increased, the number of osteoblasts and amount of bone produced per cell are insufficient to replace bone removed in the resorptive phase of the remodeling cycle. The development of clinically significant osteoporosis is related, in largest part, to the maximal amount of bone in a given person, referred to as the peak bone mass. In general, peak bone mass is greater in men than in women and in blacks than in whites or Asians. There is a higher concordance of peak bone mass in monozygotic than in dizygotic twins. Femoral head of an 82-year-old female with osteoporosis and a femoral neck fracture (right) compared with a normal control cut to the same thickness (left). Microscopically, there is reduction in the size and thickness of bone trabeculae and loss of connectivity. Calcium intake: the average calcium intake of postmenopausal women in the United States is below the recommended value of 800 mg/day. However, whether this apparent shortfall contributes to development of osteoporosis is controversial, in view of a number of studies to the contrary. Nevertheless, it has been recommended that both premenopausal and postmenopausal women increase the intake of calcium and vitamin D. Calcium absorption and vitamin D: Calcium absorption by the intestine decreases with age. Because calcium absorption is largely under the control of vitamin D, attention has been directed to the role of this steroid hormone in osteoporosis. Exercise: Physical activity is necessary to maintain bone mass, and athletes often have increased bone mass. The weightlessness of space flight results in severe bone loss (33% of trabecular bone mass in 25 weeks). Yet vigorous exercise in this setting does not seem to increase bone mass substantially or prevent osteoporosis. Environmental factors: Cigarette smoking in women has been correlated with an increased incidence of osteoporosis. It is possible that the decreased level of active estrogens produced by smoking is responsible for this effect. In summary, the two major determinants of primary osteoporosis are estrogen deficiency in postmenopausal women and the aging process in both sexes. Until recently, most patients were unaware of their disease until they had a fracture of a vertebra, hip or other bone. Because of the abundance of cancellous bone in the spine, osteoporotic changes are generally most conspicuous there. In vertebral body fractures caused by osteoporosis, the vertebra is deformed, with anterior wedging and collapse. If the vertebral body is not fractured, there is a general outline of both endplates, with a virtual absence of cancellous bone. Although senile osteoporosis tends to feature reduced trabecular thickness, postmenopausal osteoporosis exhibits disrupted connections between trabeculae. The loss of trabecular connectivity, which is attended by diminished biomechanical strength and ultimately provokes fracture, is due to perforation of trabeculae by resorbing osteoclasts in remodeling sites. Vertebral body compression fractures often occur after trivial trauma or may even follow lifting a heavy object. Estrogen therapy is an effective yet controversial means of preventing postmenopausal osteoporosis. Because hormone treatment carries with it increased risks of breast and endometrial cancers, other bone-specific antiosteoporotic drugs have been developed. All successful antiosteoporotic agents thus far developed block or slow the rate of bone resorption but do not stimulate bone formation. Thus, the drugs may prevent disease progression but cannot cure a patient who already has osteoporosis. Dietary calcium supplementation in elderly patients reduces the risk of osteoporotic fractures by half. Endocrine conditions: the most common form of secondary osteoporosis is iatrogenic and results from corticosteroid administration. Bone loss may also result from an excess of endogenous glucocorticoids, as in Cushing disease (see Chapter 27). Estrogen is a key hormone for maintaining bone mass, and its deficiency is the major cause of age-related bone loss in both sexes; estrogen deficiency or a low level of bioavailable estrogen decreases bone mass in elderly males.

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