Routine Laboratory Findings

Electrolyte disturbances are found in 92 of patients, with hyponatremia the most common (88 ). Without aldosterone there is salt wasting, so urine sodium is inappropriately high combined with the finding of hyponatremia, this may be misdiagnosed as the syndrome of inappropriate antidiuretic hormone (SIADH). The combination of hyponatremia and hyperkalemia owing to loss of mineralo-corticoid effect on sodium potassium exchange should strongly suggest adrenal Early Findings in Adrenal...

Primary Disorders of LDL Metabolism

Familial hypercholesterolemia (FH) is a common disorder occurring in 1 in every 500 people in the United States (2). The clinical manifestations include tendinous xanthomatosis most commonly involving the Achilles, the patellar, and the extensor tendons of the hands. Subjects may also have xanthelasma, arcus corneae, and premature coronary artery disease. The defect in FH involves the LDL receptor. A variety of mutations can occur that lead to the absence of or a functional defect in the LDL...

Adrenal physiology

Each adrenal gland is composed of cortical and medullary areas. The cortex is divided histologically and functionally into three concentric zones the zona glomerulosa, which secretes aldosterone, the fasiculata, which secretes cortisol, and the reticularis, which secretes adrenal androgens. The adrenal medulla secretes catecholamines, principally epinephrine. Cortisol secretion is closely regulated by a negative feedback mechanism, as shown in Fig. 1. Pituitary adrenocorticotropic hormone...

Primary Hypertriglyceridemia

Familial combined hyperlipidemia (FCH) is a common disorder probably inherited in an autosomal dominant fashion. Epidemiologic studies have shown that 1-2 of the general population suffer from this genetic defect and that it accounts for one-half of all cases of familial coronary artery disease (5). Unfortunately, these subjects present with no overt physical manifestations of hyperlipidemia such as xanthomata. The mechanism of this disorder involves the overproduction of apo B-100 with...

Treatment of Hypercalcemia

When deciding on time of therapy initiation for hypercalcemia one needs to consider the underlying cause and the patient's symptoms (43). When the serum calcium is greater than 14 mg dL, therapy should be initiated regardless of symptoms. Moderate hypercalcemia (12-14 mg dL) is treated aggressively if the patient is having clinical signs or symptoms consistent with hypercalcemia. Initially general measures should be instituted, consisting of rehydration with normal saline. Hypercalcemia impairs...

Miscellaneous Causes of Hypercalcemia

Sarcoidosis and Other Granulomatous Diseases Hypercalcemia occurs in about 10 of patients with sarcoidosis, and hypercalciuria is about three times more frequent (41). Kidney stones develop in about 10 of patients and are usually pure calcium oxalate stones (42). Pulmonary macrophages from affected individuals contain 25(OH)D 1-a-hydroxylase activity that is not readily inhibited by calcium or 1,25(OH)2D. Glucocorticoids suppress the 1-a-hydroxylase activity and provide effective treatment for...

Secondary Adrenocorticol Insufficiency

The presentation of secondary adrenal insufficiency is similar to that of primary adrenal insufficiency except that the adrenal glands remain intact and it is either hypothalamic CRH or pituitary ACTH secretion that is deficient. Clinically, this difference is seen as the lack of hyperpigmentation (owing to excess ACTH and MSH secretion in Addison's disease) and absent features of miner-alocorticoid deficiency, since the adrenal glands can still directly respond to Initial testing to rule out...

Endocrine Complications

Thirty percent of acromegalic patients have concomitant elevated serum PRL levels, with or without galactorrhea (15) owing to functional pituitary stalk compression by the adenoma, with interruption of tonic hypothalamic dopamine inhibition (36) or concomitant GH and PRL hypersecretion from mixed GH-cell and PRL-cell plurihormonal adenomas, monomorphous, mammosomatotroph adenomas, and acidophilic stem cell adenomas (9). Because most patients harbor macroadenomas, hypopituitarism develops from...

Cellular response to insulin

In both IGT and type 2 diabetes, defect (s) exist in insulin action and or insulin secretion from the pancreatic P-cell (21,55-60). Although the specific cellular and molecular defects have not yet been defined, the evolving delineation of the complex molecular events in insulin signaling and insulin synthesis secretion has given increasing information on the polygenic diseases that manifest as IGT and type 2 diabetes. The cellular effects of insulin have been generally agreed on for type 2...

Specific Disorders

Vitamin D3 is synthesized in the human skin by photoconversion of 7-dehy-drocholesterol to previtamin D3, which is isomerized to vitamin D3 (100). This form of vitamin D accounts for most vitamin D in a healthy person. Populations that do not have adequate sunlight exposure, such as housebound elderly, inner city children without adequate sunlight exposure, institutionalized patients, and people who wear clothing covering their entire bodies, are at increased risk for vitamin D deficiency. In...

Secondary prevention of hypothyroidism Early Diagnosis And Treatment

Hypothyroidism fulfills the criteria for early detection, either through testing prompted by clinical suspicion (case finding) or by routine testing of all individuals in a defined group (screening). First, hypothyroidism is highly prevalent, particularly in clinically identifiable subsets of the population, such as older women. Second, its consequences can be clinically significant whether one considers the morbidity of subsequent myxedema or the long-term vascular effects of associated...

Arna Gudmundsdottir md and Gregory Doelle md

Ninety-nine percent of total body calcium is within bone 1 of this is rapidly exchangeable with extracellular calcium. Extracellular calcium is a substrate for bone mineralization. In the circulation, calcium is bound to proteins, principally albumin however, 50 circulates as ionized calcium. Ionized calcium is biologically active, and its concentration is tightly regulated. Interactions of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D 1,25(OH)2D precisely regulate ionized calcium...

Tertiary prevention of hypothyroidism Avoiding Complications

Potential complications of recognized hypothyroidism and its treatment are preventable with sustained thyroxine therapy and appropriate clinical and laboratory monitoring. Myxedema coma is a life-threatening syndrome of multisystem organ failure resulting from prolonged profound thyroid hormone deficiency, usually with superimposed sepsis, drug intoxication, or an ischemic vascular event (52). Anecdotally, the hypothyroid patient who is elderly or has a history of previous noncompliance, other...

Diabetes is an atherosclerosis risk equivalent

In contrast to the microvascular complications of diabetes, such as nephropathy and retinopathy, atherosclerosis occurs early in the process of type 2 diabetes. Based on the observation that patients with diabetes without known atherosclerosis have the same 7-yr incidence rate of fatal or nonfatal myocardial infarction (MI) as nondiabetic patients with documented coronary artery disease, the National Cholesterol Education Program (NCEP) has defined diabetes as an atherosclerosis risk equivalent...

Sporadic MTC

Ranging from large bulky tumors to microscopic lesions, sporadic and familial tumors are histologically similar except sporadic MTC is typically unilateral and not associated with other somatic lesions. A wider spectrum of abnormalities is encountered in familial cases, ranging from isolated hypertrophied C-cells to large bilateral multicentric tumors in the superior portions of the thyroid lobes. MTC is typically composed of fusiform or polygonal cells surrounded by irregular masses of amyloid...

Primary prevention of hypothyroidism

Primary prevention of disease focuses on risk factor identification and modification. Risk factors may stem from genetic predispositions and environmental exposures. There is a genetic predisposition to the most common cause of hypothyroidism, autoimmune thyroiditis, which occurs approximately tenfold more frequently in women than men and affects approximately one in seven female children of affected women. However, autoimmune thyroiditis appears to be a polygenic disorder (8) for which there...

Effects of thyrotoxicosis Bone Effects

Postmenopausal women are at high risk for losing bone density. Up to 3 of bone mass is commonly lost within each of the first 5 yr after menopause (37). It is estimated that 30 of Caucasian women in the United States have osteoporosis (38). Concomitant thyrotoxicosis, whether subclinical or overt, has been shown to exacerbate this risk for postmenopausal osteoporosis. In thyrotoxicosis there is an increase in both osteoblast and osteoclast activity. This results in increased bone turnover, as...

Men1 3ps parathyroid pancreas and pituitary tumors

MEN-1 is a rare disorder with an estimated prevalence of 2 in 100,000 persons (4). It is defined by the presence of hypercalcemia secondary to parathyroid hyperplasia, gastrointestinal and pancreatic islet cell tumors, and anterior pituitary tumors. Primary hyperparathyroidism is the most common component of MEN-1 hypercalcemia is the most common initial presentation of the disorder, occurring in 80-100 of patients by age 40 (5). Four-gland parathyroid hyperplasia and or adenomatous tumors...

Pathophysiology

Schematic depiction of factors regulating the production of androgens by the theca cell of the ovary. The conversion of cholesterol into androstenedione and testosterone within the theca cell is regulated by cytochrome p45017a enzymes (17a-hydroxylase and 17,20-lyase). These are further regulated by factors such as hyperinsulinemia and increased free insulin-like growth factor (IGF)-1. Elevated androgens within the theca cell inhibit the actions of aromatase and hence formation of...

Rapid ACTH Stimulation Test

In most patients dynamic testing is recommended, and the rapid ACTH stimulation test is the procedure of choice (14,15). This test should be the initial diagnostic test in either primary or secondary adrenal insufficiency. Corticotropin (250 g) is given intravenously or intramuscularly, and plasma cortisol is measured before and 30 (or preferably) 60 min after the injection. If the patient is hypotensive and possibly not perfusing peripheral tissue, the intravenous route is preferred. Because...

Women Interested in Fertility

Most women with PCOS ovulate intermittently and can present with infertility. However, only a subset have infertility secondary to anovulation, and most respond to ovulation-inducing agents. The current medical treatment strategy for PCOS patients to regulate menstruation and treat infertility includes use of an estrogen receptor agonist antagonist such as clomiphene citrate. Clomiphene is typically administered in the follicular phase of the cycle, starting on d 3-5 for a total of 5 d. The...

Secondary Adrenal Insufficiency

The most common cause of secondary adrenocorticol insufficiency is iatrogenic, caused by withdrawal of therapy from patients who have been treated with pharmocologic doses of glucocorticoids (10). Clinical experience suggests that more than 30 d of supraphysiologic glucocorticoid treatment (e.g., prednisone at doses of > 7.5 mg d) may suppress CRH and ACTH for 3-6 mo an additional 36 mo may then be required for cortisol to respond to ACTH since ACTH is trophic for the adrenal glands. Both...

Approach to therapy

Several different treatment modalities are available to attain tight control of GH hypersecretion in order to improve morbidity and mortality in patients with acromegaly. Multiple treatment options may be required, and an individualized therapeutic approach is recommended for each patient Fig. 10 . In assessing the role of surgery as primary therapy, the likelihood of cure must be seriously considered. Surgery is the primary treatment for pituitary microadenomas or macroadenomas that have not...

Clinical presentation

Most of the clinical features of pheochromocytoma result from metabolic and hemodynamic actions of norepinephrine and epinephrine secreted by the tumor 1,5,13 . Hypertension is the most common clinical sign. Headache, excessive truncal sweating, and palpitations are the most common symptoms. Although pallor is found only in a small number of patients, the presence of this sign is highly suspicious for pheochromocytoma and, together with hypertension and excessive sweating, provides a high...

Vivien Bonert md and Shlomo Melmed md

Growth Hormone Releasing Factor

Introduction Clinical Features Diagnosis Treatment Approach to Therapy References Acromegaly is a chronic, insidious, disfiguring disorder of adulthood caused by excess circulating growth hormone GH secretion occurring after epiphyseal closure with protean clinical manifestations affecting almost every major organ system. GH hypersecretion stimulates increased hepatic insulin-like growth factor IGF-1 production, and both GH and IGF-1 contribute to the clinical features of hypersomatotrophism....

Udaya M Kabadi md frcpc facp face

Chylomicron Hdl Ldl

PRIMARY DISORDERS OF LIPID METABOLISM Cardiovascular disease has reached epidemic proportions in the United States and throughout the world and is the leading cause of death in both men and women in the United States. For this reason, intense and extensive research efforts have been carried out to identify risk factors for coronary artery disease in order to develop preventive and treatment strategies. These investigations have demonstrated that alterations in lipid metabolism adversely affect...

Biochemical diagnosis

Comt Metanephrines

Diagnosis of a pheochromocytoma depends on biochemical evidence of excessive catecholamine norepinephrine and epinephrine production by the tumor. This is usually achieved by measurements of catecholamines and catecholamine metabolites in plasma or urine. However, catecholamines are normally produced by the sympathetic nervous system and the adrenal medulla and are not specific to pheochromocytoma. Thus, a variety of physiologic conditions involving sympathoadrenomedullary activation cause...

Incidence and death rates of thyroid cancer and lymphoma

About 17,000 new cases of thyroid cancer are diagnosed annually in the United States, making it about 14th in incidence among malignancies 6 . It occurs at all ages but is most common among middle-aged and postmenopausal women Fig. 1 . The lifetime risk of developing thyroid cancer is about 1 0.65 for women and 0.25 for men 7 , and death rates are less than 10 1200 deaths occurred among 135,000 thyroid cancer patients in 1998 6 . However, both the incidence and mortality rates vary...

Polycystic Ovarian Syndrome and Insulin Resistance

The association between insulin resistance and PCOS has been well recognized for almost two decades. Insulin resistance refers to an impairment of insulin-stimulated glucose uptake largely in skeletal muscle and an impairment in insulin-mediated inhibition of hepatic glucose output. In skeletal muscle and fat, insulin initiates several intracellular signals culminating in GLUT 4-mediated glucose uptake. Insulin also has a vasodilator effect on the normal skeletal muscle vasculature mediated by...

Thyroid Lymphoma

The annual incidence of thyroid lymphoma in the United States is less than 1 in 2 million persons 29 . Thus the likelihood that a thyroid nodule is a primary thyroid lymphoma is less than 1 in 1000 it is much more likely to be a manifestation of systemic lymphoma, which affects the thyroid in about 10 of those who die of the disease 29 . However, the incidence of thyroid lymphoma has been rising significantly and now constitutes about 5 of all thyroid malignancies 29 . The reason for this is...