Ectopic syndrome

With the introduction and use of monoclonal antibodies, the measurement of hormones is now accurate and precise. The production of hormones in cancer involves two separate routes. First, the endocrine tissue that normally produces it can produce excess amounts of a hormone. Second, a hormone may be produced at a distant site by a non-endocrine tissue that normally does not produce the hormone. The latter condition is called ectopic syndrome. For example, the production of adrenocorticotropic hormone (ACTH) is norraotopic by the pituitary and is ectopic by the small cell of the lung. Consequently, elevation of a given hormone is not diagnostic of a specific tumor, because a hormone may be produced by a variety of cancers. 

Antiepileptics are used in neuropathic pain resulting from lesions to the peripheral (e.g., diabetes, heipes) or central nervous system (e.g., stroke). Such syndromes have been attributed to ectopic activity in sensitized nociceptors from regenerating nerve sprouts, recruitment of previously silent nociceptors, and/or spontaneous neuronal activity. This may result in sensitization... 

Causalgia is burning pain evoked by the activation of sympathetic efferent fibres. The likely mechanism underlying this syndrome involves ectopic expression of a-adrenoceptors on nociceptive afferents following peripheral injury or disease. 

Syndrome of inappropriate antidiuretic hormone is defined by water retention, dilutional hyponatraemia and decreased volume of highly concentrated urine. There are several causes which can result in SIADH, neoplasms ectopic secreting AVP, ectopic release of AVP by various diseases or drugs, exogenous administration of AVP, desmopressin, lysipressin or large doses of OT (iatrogenic SLADH). 

In addition, several other organs, like the heart, ovaty, amnion, chorion, decidua, testis, epididymis and prostate, have been reported to synthesize OT, suggesting a paracrine role for this hormone in these tissues. Ectopic AVP production by lung cancer cells or other neoplasms has been described in humans, leading to the syndrome of inappropriate antidiuretic hormone secretion. 

ACTH-secreting non-pituitary tumors (ectopic ACTH syndrome)—15% of cases of endogenous Cushing s syndrome usually from small cell lung carcinoma, bronchial carcinoids, pheochromocytoma, or thymus, pancreatic, ovarian, or thyroid tumor. The tumor is usually disseminated (difficult to localize). 

CRH-secreting non-pituitary tumors (ectopic CRH syndrome)— rare... 

ACTH-dependent Cushing s syndrome is usually caused by overproduction of ACTH by the pituitary gland, causing adrenal hyperplasia (Cushing s disease). Pituitary adenomas account for about 80% of these cases. Ectopic ACTH-secreting tumors and nonneoplastic corticotropin hypersecretion are responsible for the remaining 20% of cases. 

Ectopic ACTH syndrome refers to excessive ACTH production resulting from an endocrine or nonendocrine tumor, usually of the pancreas, thyroid, or lung (e.g., small-cell lung cancer). 

Ectopic ACTH syndrome Surgery, chemotherapy. Metyrapone (Metopirone) 250-mg capsules 0.5-1 g/day, divided eveiy 4-6 hours 1-2 g/day, divided every 4-6 6 g/day... 

For some syndromes, clinical manifestations may be minimal or absent. Recurrent herpes infection may manifest as a single lesion. cMost cases of pharyngeal gonococci infection are asymptomatic. Salpingitis increases the risk of subsequent ectopic pregnancy and infertility. 

Complications Epididymitis, Reiter s syndrome (rare) Pelvic inflammatory disease and associated complications (i.e., ectopic pregnancy, infertility) Reiter s syndrome (rare)... 

Hypersensitivity or idiosyncrasy to quinidine or other cinchona derivatives manifested by thrombocytopenia, skin eruption or febrile reactions myasthenia gravis history of thrombocytopenic purpura associated with quinidine administration digitalis intoxication manifested by arrhythmias or AV conduction disorders complete heart block left bundle branch block or other severe intraventricular conduction defects exhibiting marked QRS widening or bizarre complexes complete AV block with an AV nodal or idioventricular pacemaker aberrant ectopic impulses and abnormal rhythms due to escape mechanisms history of drug-induced torsade de pointes history of long QT syndrome. 

Carboxyhemoglobinaemia Chronic obstructive airways disease Pulmonary hypoventilation syndrome Right-to-left cardiac shunt Absolute - physiologically inappropriate Ectopic erythropoietin production Renal carcinoma and cysts Hepatoma... 

Cushing s disease (caused by a pituitary ACTH-secreting adenoma) or Cushing s syndrome from an adrenal tumour is normally treated by surgical removal of the primary lesion where possible. Cases of ectopic ACTH syndrome associated with carcinoma of the bronchus cannot be treated surgically, and often benefit from medical therapy to control adrenal steroid excess. 

Amiodarone is effective in maintaining sinus rhythm in most patients with paroxysmal atrial hbrillation and in many patients with persistent atrial hbrillation. It is also effective in preventing recurrences of A-V nodal reentry and atrial tachyarrhythmias and in the prevention of reentrant rhythms and atrial hbrillation in patients with Wohf-Parkinson-White syndrome. Also, it is the most efficacious therapy for postoperative junctional ectopic tachycardia. 

The syndrome of inappropriate antidiuretic hormone (SIADH) secretion is a condition in which secretion of ADH continues despite serum hypo-osmolarity. This results in fluid retention and hyponatremia that can lead to brain oedema, mental confusion and coma. The causes are hypothalamic-pituitary tumours or an ectopic vasopressin-secreting tumour. 

See Table 15-6. Potassium-sparing diuretics are most useful in states of mineralocorticoid excess or hyperaldosteronism (also called aldosteronism), due either to primary hypersecretion (Conn s syndrome, ectopic adrenocorticotropic hormone production) or secondary hyperaldosteronism (evoked by heart failure, hepatic cirrhosis, nephrotic syndrome, or other conditions associated with diminished effective intravascular volume). Use of diuretics such as thiazides or loop agents can cause or exacerbate volume contraction and may cause secondary hyperaldosteronism. In the setting of enhanced mineralocorticoid secretion and excessive delivery of Na+ to distal nephron sites, renal K+ wasting occurs. Potassium-sparing diuretics of either type may be used in this setting to blunt the K+ secretory response. 

Fig. 5.1.2 Cholesterol biosynthesis branch of the isoprenoid biosynthetic pathway. Enzymes are numbered as follows 1 squalene synthase 2 squalene epoxidase 3 2,3-oxidosqua-lene sterol cyclase 4 sterol A24-reductase (desmosterolosis) 5 sterol C-14 demethylase 6 sterol A14-reductase (hydrops-ectopic calcification-moth-eaten, HEM, dysplasia) 7 sterol C-4 demethylase complex (including a 3/ -hydroxysteroid dehydrogenase defective in congenital hemidyspla-sia with ichthyosiform nevus and limb defects, CHILD, syndrome) 8 sterol A8-A7 isomerase (Conradi-Hunermann syndrome CDPX2) 9 sterol A5-desaturase (lathosterolosis) 10 sterol A7-reductase (Smith-Lemli-Opitz syndrome). Enzyme deficiencies are indicated by solid bars across the arrows...

Table 5.1.1 Inherited disorders of isoprenoid/cholesterol biosynthesis. CDPX2 Conradi-Hunermann syndrome, CHILD congenital hemidysplasia with ichthyosiform nevus and limb defects, HEM hydrops-ectopic calcification-moth-eaten, MA/HIDS mevalonic aciduria/ hyperimmunoglobulinemia D and periodic fever syndrome, MIM Mendelian Inheritance in Man... 

As an alternative, primary skin fibroblasts or lymphoblasts of patients suspected to be affected with a cholesterol biosynthesis defect can be cultured for 3-7 days in medium supplemented with fetal calf serum depleted of lipoproteins to induce cholesterol biosynthesis, whereupon the specific defect can be determined by sterol analysis using GC-MS as described above. This procedure will readily identify patients affected with Smith-Lemli-Opitz syndrome, desmosterolosis, lathosterolosis, hydrops-ectopic calcification-motheaten (HEM) skeletal dysplasia and most patients with Conradi-Hunermann syndrome (CDPX2). Patients with congenital hemidys-plasia with ichthyosiform nevus and limb defects (CHILD) syndrome may not be identified with this assay, but they can be readily diagnosed on the basis of their typical clinical presentation. 

First- and second-trimester abortion Cervical reopening Induction of labor Augmentation of labor Postpartum hemorrhage Ectopic pregnancy Lactation suppression In gastrointestinal disease Peptic ulceration Liver transplantation Chemotherapy-induced mucosal lesions In cardiovascular disease Congenital cardiac malformations Raynaud s syndrome Chronic obstructive pulmonary disease Adult respiratory distress syndrome Pulmonary hypertension Arterial occlusive disease Extracorporeal circulation In urology Erectile dysfunction... 

Any consideration of major issues relating to the balance of benefit and harm, such as cancer or mortality rates, should be supplemented by a consideration of less prominent ones, for example, a reduction in disorders of the menstrual cycle (such as dysmenorrhea, menorrhagia, and the premenstrual syndrome) and the reduced risks of iron deficiency anemia, functional ovarian cysts, uterine fibroids, benign breast disease, pelvic inflammatory disease, and ectopic pregnancy (10,11). 

In humans, mifepristone causes generalized glucocorticoid resistance. Given orally to several patients with Cushing s syndrome due to ectopic ACTH production or adrenal carcinoma, it was... 

ACTH-dependent Cushing s syndrome is driven by increased ACTH and includes exogenous ACTH administration as weU as pituitary and ectopic Cushing s. 

---