Jeffrey A Brinker, M.D.
- Professor of Medicine
- Joint Appointment in Radiology and Radiological Science
In other words buy cheap breast success 90caps line herbs used for healing, under this interpretation of wrongful life order 90 caps breast success visa empowered herbals, the notion of 57 self-authorship takes on the form of a right not to buy breast success once a day top 10 herbs be born. The question is, of course, whether one can one ever have such a right or legal interest. Protection of the child’s right would, paradoxically, cause the child not to come into existence in the rst place. The philosophical riddles under lying the supposed right not to be born are well rehearsed in academia as 58 part of what Derek Par t famously calls the nonidentity problem. One of the more practical aspects of the nonidentity problem, with which judges in wrongful life cases are confronted, is how to assess the damages owed to the child. The traditional logic underlying the law of damages would require judges to compare the child’s current situation with the situation in which the harm would not have taken place. However, in this case that would amount to comparing existence with nonexistence, which seems logically impossible. At the root of this practical problem is the more fundamental question whether one can ever legally argue that nonexistence is preferable to 57 the Dutch Supreme Court explicitly denied that it had recognised a right not to be born (see Baby Kelly, paragraph 4. In the legal reasoning underlying the ruling, Kelly’s claim is interpreted as derived from her parents’ right to self-determination. Therefore, within this speci c interpretation of wrongful life, children would not be able to sue their parents for wrongful life. However, given the fact that Kelly was awarded damages for her entire life, the conclusion seems inevitable that, if Kelly did not have a right not to be born, she at least had a legal interest in her own abortion, as I have argued elsewhere (Van Beers, Persoon en Lichaam, pp. Indeed, in many legal systems, recogni tion of wrongful life claims is deemed to be at odds with the legal principle of human dignity, because it implicitly depicts the child’s 59 disabled life as not worth living. A possible objection against arguments based on human dignity or fears of eugenics, is that wrongful life actions do not rely on other people’s value judgement about the child’s life or some objective standard of worthwhile life (objective interpretation). Instead, the child’s own judgement and experiences can be said to be the starting point of these actions (subjective interpretation). However, even leaving aside the fact that it is often the parents who sue for wrongful life on behalf of their child, this argument does not convince. In order to apply tort law to this situation, the child’ssu ering has to be legally quali ed under the exist ing system of the law of damages. In Hensel’s words, ‘a line will have to be 60 drawn somewhere between actionable and non-actionable disabilities’. This makes the question inevitable what kind and which degree of su ering is enough to be able to conclude that the child’s life is not worth living and can be legally regarded as a source of damages. In other words, some objective standard is inevitably needed to measure the child’s life and to argue that it falls below the threshold of worthwhile life. Additionally, most defenders of wrongful life claims agree that the child’s congenital disabilities need to be severe enough in order to justify 61 this legal claim, though it is beyond doubt that discussions on the 62 question what we exactly owe to future children will continue. These discussions will undoubtedly become even more complex with the prospect of further developments in the eld of ‘fetal personalised 63 medicine’. For example, fetal whole genome sequencing makes it pos sible to uncover enormous volumes of genomic data already before birth. Hensel, ‘The disabling impact of wrongful birth and wrongful life actions’ (2005) 40 Harvard Civil Rights – Civil Liberties Law Review 141–95, p. Jonathan Glover, Choosing Children: Genes, Disability, Design (Oxford: Clarendon Press, 2006); David DeGrazia, Creation Ethics: Reproduction, Genetics, and Quality of Life (Oxford: Oxford University Press, 2012). Bianchi, ‘From prenatal genomic diagnosis to fetal personalized medicine: progress and challenges’ (2012) 18 Nature Medicine 1041–51. Even from a tort law perspective, it is clear that the Me Medicine values of self-authorship and autonomy will not be able to provide answers to these vexing questions. More generally, it could be said with Hensel that ‘once the nondisabled are given authority to judge from a “reasonable person” perspective whether or not the disabled life is worse than no life, the power of individuals with disabilities over their own identity and self 64 worth is seriously diminished’. This interpretation is also at the root of the Cour de 65 Cassation’s Perruche decision (2000). It presupposes that children such as Nicolas Perruche are wronged, not by the fact of being born, but by their genetic de ciencies. A major advantage of this approach is that no value judgements have to be made about the child’s life, only about his genetic disabilities. The child’s legal situation no longer needs to be explained in terms of a supposed right not be born or to be aborted. In other words, under the current possibilities of reproductive technologies, it would not have been possible for the child to be born without the genetic de ciencies. Therefore, holding medical professionals liable solely for the genetic impairments implies going against the laws of causality, and even the laws of nature. As French legal historian Yan Thomas demonstrates in his fascinating analysis of the Perruche case, these counterfactual elements go back to a novel legal ction that is introduced by this interpretation of wrongful life. This legal ction entails that the child could have been born in adi erent body and with a di erent genetic make-up and still be the same person. Of course, the law mobilises legal ctions more generally, 64 Hensel, ‘The disabling impact of wrongful birth and wrongful life actions’, p. However, what makes the wrongful life claim’s legal ction historically unprecedented is that it calls into exis 67 tence a completely ctional legal subject. By treating the child’s genetic disabilities as a source of damages, even if he could not have been born without them, the child is implicitly allowed to exercise a form of self-authorship that presupposes a right to 68 be born in a di erent body.
The claim of categorical exclusion from the environmental assessment was accepted and the quality reviewer determined that the investigational pembrolizumab drug product used in these studies was comparable for to order breast success 90caps with mastercard herbals for weight loss the marketed product generic 90 caps breast success amex herbs collinsville il. Using this criterion purchase breast success 90caps overnight delivery herbals books, the College of American Pathology stated that the “correct” result was obtained in >95% of cases. Despite this, there remains uncertainty regarding the performance characteristics across all laboratories which may be performing these tests, including whether performance characteristics may differ by primary cancer. Clinical Pharmacology/Pharmacogenomics I concur with the conclusions reached by the clinical pharmacology reviewers that there are no outstanding clinical pharmacology issues that preclude approval. The supplement contained following clinical pharmacology information: A pooled comparative analysis of pembrolizumab exposure and clearance across multiple tumor types was conducted. The population exposure of 200 mg Q3W was numerically higher than 2 mg/kg Q3W dose, but significantly lower than 10 mg/kg Q2W and Q3W doses. Based on this difference, the pharmacology reviewers also reviewed prior submissions in which the effects on survival among randomized, dose-ranging studies were noted to favor the higher dose. In their response, Merck noted that the duration of follow-up was unequal across studies. Since no baseline patient-specific factors are identified to determine which starting regimen should be recommended. The clinical review team did not concur with this recommendation for the reasons discussed in Section 7 of this review. No significant deviations were noted and the data were deemed reliable in support of this efficacy supplement. With regard to underlying primary cancer, 60% of the population had colorectal cancer. Of the remaining 40% (59 patients) with non-colorectal cancers, the most common primary cancers in descending order were: endometrial cancer (24%), biliary tract cancer (19%), gastric or gastroesophageal cancers (15%), small intestinal cancers (13%), and pancreatic cancers (10%). The median number of prior lines of therapies administered for the treatment of metastatic or unresectable disease was 2; 84% of patients with metastatic colorectal cancer and 53% of patients with other solid tumors 2 prior lines of therapy. For example, the primary cancers first identified as responsive to checkpoint inhibitors, melanoma and non-small cell lung cancer, are also cancers with the highest mutational burdens. I also concur that dose-related differences in response may be present but cannot be addressed outside of a randomized trial comparing dosage regimens. Further, the recommendation is not consistent with prior recommendations based on relatively flat exposure: response and exposure: toxicity relationships observed in other trials; however, a more comprehensive investigation of these effects involving multiple rather than within an individual randomized, dose-ranging trial may be more informative. Pending further elucidation of this relationship to determine if 10 mg/kg every 2 weeks is actually superior to 200 mg every 3 weeks, I concur with the decision of the clinical review team that the Merck’s proposed dosage regimen is both safe and effective. Safety Size of the database: the characterization of the most serious adverse drug reactions of pembrolizumab were evaluated in 2799 pembrolizumab-treated patients, of whom 41% were exposed to pembrolizumab for 6 months and 21% were exposed to pembrolizumab for 12 months, which was revised as part of previous supplemental approvals. The most common adverse reactions of pembrolizumab were evaluated in 5 randomized trials enrolling 2195 pembrolizumab-treated patients and 3 single arm trials enrolling 772 pembrolizumab-treated patients. This clinical experience in these supplements was adequate to characterize the safety for both dosage regimens (10 mg/kg every 3 weeks and 200 mg every 3 weeks) in randomized, controlled clinical trials. Thus, the limited size of the safety database in this supplement was not of concern as the adverse reaction profile of pembrolizumab is known. Major safety concerns related to labeling: the serious adverse reactions of pembrolizumab resulting from pembrolizumab are autoimmune reactions against healthy organs and tissues. The most commonly affected organs are the endocrine system, colon, lungs, and liver. With the exception of immune-related endocrinopathies, which are generally not reversible and require hormone replacement due to loss of endocrine function, immune-related adverse reactions of other organs can be reversed with termination of pembrolizumab if mild and high dose corticosteroids with or without additional immunosuppression if moderate or more severe. While activity was observed in two patients, a third experienced neurologic deterioration and death, possibly attributable to lymphocytic tumor infiltration. Given the very limited experience, and in light of the potential for benefit, additional studies were required to further assess the safe use of pembrolizumab in this setting. Advisory Committee Meeting this efficacy supplement was not referred to the Oncologic Drugs Advisory Committee since the safety profile is acceptable for the indicated population and the trial design and endpoint are similar to prior accelerated approvals. The potential risks of lymphocytic infiltration (the suspected cause of “tumor flare” with these immunologic agents) occurring in a closed space are likely to increase the risk of herniation. Recent published reports of both responses and patient death in three pediatric patients support the potential for this risk. Other Relevant Regulatory Issues There are no other unresolved relevant regulatory issues. It is anticipated that this limitation of use may be revised when additional data are obtained in this population in required postmarketing trials. Decision/Action/Risk Benefit Assessment Regulatory Action: Approval Risk Benefit Assessment Unresectable, locally advanced or metastatic cancers that have progressed following two or more available therapies have a poor prognosis, regardless of primary cancer and, with few exceptions, will have 5-year survival rates of less than 10%. In this supplement, 84% of patients with metastatic colorectal cancer and 53% of patients with other solid tumors had received two or more prior lines of therapy. With available treatment for the most common cancers in this population, overall response rates with available therapy are low (1% with regorafenib and 1. The point estimates for response rates and response durations far exceed that expected with available and commonly accepted third-line chemotherapeutic options. The risks of pembrolizumab are acceptable in light of the magnitude and durability of response. At this time, I concur with the clinical review team that there is insufficient evidence to state that the higher dosage regimen employed (10 mg/kg every 2 weeks) provides superior results to the lower dosage regimen (200 mg every 3 weeks) based on the differences across studies with regard to patient population. This question should be re-assessed across the totality of the randomized, dose-ranging trials in all cancers to determine the extent, if any, of a dose-response relationship.
Simultaneous pancreas and kidney transplantation units A simultaneous pancreas and kidney transplant unit is defned as a clinical service of a state public hospital that actually performs the relevant transplant procedure order cheap breast success on-line herbs native to outland. The recommendations below should be used in conjunction with the detailed explanations of these recommendations provided in Chapter 2 order breast success visa herbals nature. Utilisation of lungs population (although prospective results are should be considered on a case-by not essential) purchase breast success in india herbs mopar. Post-transplant influenza treatment for 5-10 days is suggested for all recipients of organs from a donor infected with influenza. West Nile virus Variable; seasonal Screening of asymptomatic donors If a donor is suspected or known to epidemics during late is not recommended. Zika virus Widespread; outbreaks Screening of asymptomatic donors In the event that a donor tests positive possible wherever there for Zika virus is not recommended. Discuss with an infectious disease specialist and, if donation proceeds, provide a full treatment course to the recipient. Other risk active or latent tuberculosis can factors include household/ be considered, taking into account occupational contact with completeness of treatment, antibiotic tuberculosis, incarceration, sensitivities and current evidence of residence in an aged care infection in the donor. Discussion facility, homelessness and with an infectious diseases physician immunosuppression close follow-up of the recipient, and consideration of tuberculosis prophylaxis for the recipient are recommended. Treponema Worldwide All donors should be screened for If primary, latent or tertiary syphilis is pallidum (syphilis) T. A donor using a treponemal-specific with secondary syphilis may be enzyme immunoassay, with bacteraemic with the involvement of confirmation of positive results by many organs, hence caution should a non-treponemal test. Trypanosoma Mexico, Central and South Donors who have spent >3 Donor with known T. Several forms of the disease have been described, and the most common is the sporadic type. The most chal lenging aspect of this disease is its diagnosis—the gold standard for defnitive diagnosis is considered to be histopatho logical confrmation—but newer tests are providing means for an antemortem diagnosis in ways less invasive than brain biopsy. The current diagnostic criteria are limited; test sensitivity and specifcity varies with the genetics of the disease as well as the clinical stage. Physicians may be unsure of all diagnostic testing available, and may order outdated tests or prematurely request a brain biopsy when the diagnostic workup is incomplete. Regardless of the type, the disease has with other disorders, and years later only 2 of the cases a rapid clinical course that is uniformly fatal. Surgeons target areas that appear the most ab and clinical presentation implies that the conformational normal on imaging studies, but this is most often in deep variant is what determines the phenotypic or molecular seated subcortical structures. In this paper we tein that are unmasked with progressive denaturation, and briefy review the disease, assess the current tools used in antibodies specifc to these areas bind and elicit a positive making the diagnosis, discuss when a brain biopsy should result. It is 100% specifc for the disease, and recent data be performed, propose changes to diagnostic criteria, and show sensitivity that is at least equal to other diagnostic provide an algorithm for the workup of the patient with a tests. There the subsequent multimerization accumulates, spreads are more than 50 mutations described, and the disease is throughout the brain parenchyma, and induces the clas transmitted in an autosomal dominant pattern with high sic spongiform change (vacuolation of gray matter) by mi penetrance, and with an incidence that increases with age. This associated with intracerebral electrodes, corneal trans is very important because the genotype imparts genetic plantation, dura mater grafts, and growth hormone injec susceptibility in all types of prion disease. Those with contaminated electrodes placed if the survival increase is due to the age differences, but directly in the brain had short incubation periods of 16–28 recent epidemiological studies do suggest that exposure months, whereas peripheral injections of growth hormone alone is not suffcient to explain the higher incidence, and took anywhere from 5 to 30 years for the symptoms to that age is an important risk factor for contracting the dis begin. The most se cortical signal in 25%, usually seen in the temporal lobe vere damage is in the pulvinar, which correlates with the and with little basal ganglia involvement. Also, numerous atypical neurologi myoclonus, an age of onset in the 7th decade of life, and a cal examination fndings are commonly seen: myoclonus, short mean disease duration of 4 months. The most com visual changes leading to cortical blindness, ataxia, and mon presentation is cognitive impairment, but prominent usually an akinetic mutism in the last stages of the dis visual signs (Heidenhain’s variant), cerebellar ataxia, and ease. Myoclonus is the most common sign, but there are psychiatric symptoms can be present as well. There is a mean age of onset at 60 years, but the duration of the disease is, on eeg Findings average, 18 months. This sub Now the anatomical areas of diagnosis have expanded sequently results in electronic coupling through synchro from the traditional basal ganglia/thalamic areas to fron nization in the corpus callosum. Shorter time between symptom onset and akinetic mary cerebral function are most common. This importantly, provide diagnostic criteria early in the dis is temporally limited by the fact that there is only a mean ease course. The highest proportion of cases were observed in disease or other disorders resulting in neuronal damage. Positive 14–3-3 results are seen in viral en found that costs were signifcantly higher than in those cephalitides, recent stroke, subarachnoid hemorrhage, hy without any surgical intervention (p < 0. The laboratory study of the disease also led to the de Thiofavin T binds to these fbrils, and emits fuorescence velopment of new research techniques. The samples used in the test are becoming easier to obtain Need for New diagnostic criteria. A physician sive results may be due to the suspicion that prions are faced with the challenging task of diagnosing a patient shed in the olfactory nerves. An diseases is to associate phenotype with genotype to aid updated diagnostic criteria and algorithm should provide diagnosis. If the most common imaging, clinical, and labo confdence in the diagnosis, while avoiding unnecessary ratory fndings are studied in the context of the genotype, costs, waste of resources, and the potential morbidity as the clinician will have less doubt about the diagnosis.
Importance of intercellular lipids in water-retention properties of the stratum corneum: Induction and recovery study of surfactant dry skin generic breast success 90caps amex herbals on deck review. Challenging the surfactant monomer skin penetration model: Penetration of sodium dodecyl sulfate micelles into the epidermis cheap 90caps breast success otc herbs parts. Penetration of mixed micelles into the epidermis: Effect of mixing sodium dodecyl sulfate with dodecyl hexa(ethylene oxide) purchase generic breast success pills jovees herbals. Hydrophobically modifed polymers can minimize skin irritation potential caused by surfactant-based cleansers. Attenuated total refection-Fourier transform infrared spectroscopy as a possible method to investigate biophysical parameters of stratum corneum in vivo. Automated depth-scanning confocal raman microspectrometer for rapid in-vivo determination of water concentration profles in human skin. Application of optical non-invasive methods in skin physiology: Comparison of laser scanning microscopy and optical coherence tomography with histological analysis. Molecular interactions of plant oil components with stratum corneum lipids correlate with clinical measures of skin barrier function. A randomized comparison of an emollient containing skin related lipids with a petrolatum-based emollient as adjunct in the treatment of chronic hand dermatitis. Skin permeability barrier and occlusion: No delay of repair in irritated human skin. Taylor Introduction Hyperpigmentation is a common complaint encountered by dermatologists. A study of 2000 dermatol ogy patients with darker skin tones revealed that pigmentary disorders were the third most common diagnosis, preceded only by acne and eczema. Melasma is an acquired pigmentary disorder which typically manifests as hyperpigmented macules and patches symmetrically distributed on the face, neck, and occasionally the upper extremities. Additional risk factors reported in the literature are antiepileptic medications, phototoxic medications, thyroid dis ease, and genetic predisposition. Cosmeceuticals are now more commonly used to treat disorders of hyperpigmentation, including melasma. This chapter will review the role of cosmeceutical products in the treatment of melasma, including safety and effcacy. Clinical Presentation Melasma is an acquired disorder of hyperpigmentation, symmetrically distributed, with light to dark brown macules and patches located most often on the face. The centrofacial pattern involves the forehead, cheeks, nose, chin, and/or upper lip; the malar pattern characteristically involves the cheeks and nose. Additionally, the mandibular pattern involves the ramus of the mandible, but has been speculated to be a type of Poikiloderma of Civatte, as affected patients are often post-menopausal and biopsies demonstrate sig nifcant actinic damage. A study9 which evaluated biopsy specimens of lesional skin described two distinct histopatho logic patterns of melasma: an epidermal form with deposition of melanin primarily in the basal/ suprabasal layers, with highly dendritic melanocytes full of pigment; and a dermal type with superf cial and deep dermal perivascular melanophages and less prominent epidermal pigmentation. Furthermore, this group utilized Mel-5 staining to demonstrate that there was no increase in melanocyte number, but that the melanocytes in the lesional skin were larger in size and had more prominent dendritic processes10; data supported by electron microscopy. Therefore, melasma lesions that appear to be epidermal may, in actuality, have signifcant amounts of melanin in the dermis. Additionally, melanocytes in melasma lesions had more dendrites, rough endoplasmic reticulum, mitochondria, and Golgi, suggesting that they had increased biological activity compared to similar structures observed in normal skin. Melasma lesions are seen in photo-exposed skin and patients typically report exacerbation with sun exposure. Many patients report onset or worsening of melasma with oral contraceptive use or pregnancy. Additional, less commonly reported risk factors for melasma include the expression of stem cell factors,17 use of phototoxic medications and cosmetics,18 neural factors,19 vascular infuences,20 and the presence of thyroid disorders. Melasma and Depigmentation Agents 345 Differential Diagnosis Proper diagnosis of melasma is vital to effective treatment. Skin conditions that may mimic the clinical appearance of melasma include postinfammatory hyperpigmentation, drug-induced hyperpigmentation, ephelides, facial acanthosis nigricans, solar lentigines, nevus of Ota, acquired bilateral nevus of Ota-like macules (Hori’s nevus), actinic lichen planus, and frictional melanosis. Cosmeceutical Options for Melasma Treatment Patients frequently seek natural alternatives to address skin disorders including melasma in order to prevent potential adverse effects and decrease exposure to perceived harmful chemicals. Cosmeceuticals are perceived as milder but effective options for treatment of melasma. It competitively inhibits melanin synthesis through the inhibition of sulfhy dryl groups and by acting as a substrate for the enzyme tyrosinase. Semiquinone free radicals are then released, which subsequently damage melanocytes and melanosomes in treated skin. Less common manifestations of ochronosis include asymptomatic erythema, gray-blue colloid milia, and papulonodules on sun-exposed areas. These measures were proposed due to the potential for development of ochronosis and carcinogenicity. It functions as a substrate for tyrosinase, thus inhibiting the formation of melanin precursors. Using this formulation with sunscreen reduces the incidence and severity of these potential adverse reactions. While azelaic acid demonstrates cytotoxic and antiproliferative activ ity on abnormal melanocytes, it does not affect normal melanocytes. There are no randomized controlled trials comparing the effcacy of kojic acid to other cosmeceuticals. The other control side of the face was treated with the same combination without kojic acid. While visible improvement was noted on both sides of the face, 60% of lesions treated with kojic acid versus 47. Tretinoins (all-trans-retinoic acid), in addi tion to synthetic naphthalene derivatives such as tazarotene, bexarotene, and adapalene, are registered prescription retinoids. The prescription topical retinoids have been studied extensively and are indicated for photoaging, acne, and pigmentary disorders.
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Therefore when glucose is given orally it induces more insulin secretion than when given intravenously purchase cheap breast success line herbals on demand shipping. Synthesis breast success 90 caps line wonder herbals, release of insulin is decreased when there is scarcity of dietary fuels cheap breast success amex herbals and liver damage. Metabolic Role of Insulin Carbohydrate metabolism: Insulin produces lowering of blood glucose and increases glycogen stores. It is due to increased translocation of glucose transporters from Golgi to plasma membrane. Paradoxycal action of insulin * Insulin stimulates protein phosphatase-1 which dephosphorylates and activates key enzyme glycogen synthase. Lipid metabolism: Insulin causes lowering of free fatty acids level in blood and increases the stores of triacylglycerol. It also induces the synthesis of lipoprotein lipase 208 which releases more fatty acids from the circulating lipoproteins. Protein Metabolism: Insulin promotes protein synthesis by: • Increased uptake of amino acids through increased synthesis of amino acid transporters in the membrane. Diabetes mellitus -cells of islets of Langerhans fail to secrete adequate amounts of insulin or producing absolute or relatively low amounts of insulin. Secondary changes in the protein, lipid, water and electrolytes metabolism may also occur. Though exact cause is not known, but an insufficient level of insulin is found in the patient. Initially patients B-cells respond normally however there is Produce more insulin than normal Relative deficiency of insulin Soon the -cells gets exhausted, due to insulin antagonism. Plasma insulin is almost absent, Plasma insulin levels may be raised or normal 8. Insulin antagonism is found in maturity onset diabetes, the secretion of hormone is normal or more. The antagonism could be due to antibodies to insulin or the insulin molecule may be abnormal, less active or altered. It may also be due to insulin receptor deficiency; there can be lack of cellular response to insulin. Secondary diabetes Mellitus is due to other diseases like pancreatitis, malignancy of pancreas, hemocromatosis. Hypothyroidism, Cushing syndrome, hyper pituitarism, and increased glucagon activity. Patient may also present classical symptoms like polyuria, polydypsia, and polyphasia, accompanied by loss of weight. Patient suffers from increased break down of tissue proteins, which accounts for loss of weight. Increased breakdown of fatty acids lead to ketosis, Diabetic Keto acidosis and hyperventilation. Chronic complications of diabetes: • Uncontrolled diabetic patients develop cataract. There is glycosylation of lense proteins or Glucose gets metabolized to sorbitol in the lense. The associated osmotic changes ultimately result in fibrosis and cataract formation. Since hypoglycemia is a serious possibility in these patients, they are protected by giving orally more than 1000gms of glucose/day. It acts as a hormone and is required to mobilize metabolic substrates from the storage depots. Carboxy peptidase B, trypsin like peptidase in the lysosomes of -cells, hydrolyze it to produce active glucagon and some inactive peptides. Role of glucagon: * Carbohydrate metabolism: * It increases glucose by Glycogenolysis in liver. Effect on mineral metabolism: • It increases potassium, and calcitonin release which in turn causes calcium lowering effect. T3, T4 are iodinated amino acids of tyrosine, and are synthesized from thyroglobulin and iodine. A large part (70%) of iodine in thyroglobulin exists as inactive monoiodotyrosine, diiodotyrosine and rest is in the form of T3, T4. Synthesis of Thyroglobulin: * the acinar cells of thyroid synthesize and store thyroglobulin as colloid in follicles. The required transporter pump is located on the plasma membrane which works along with sodium pump. The iodine pool in acinar cells exists as exchangeable iodide in blood and unused iodine as iodotyrosine. Mechanism of action of thyroid hormone: Targets are liver, kidneys, adipose, cardiac, neurons, and lymphocytes. Thus in hypothyroidism, there is accumulation carotene in blood which is responsible for the yellowish tint of the skin. Hyperthyroidism: There is excess of T3, T4 due to enlarged thyroid, toxic goiter, thyrotoxicosis. Symptoms: • Patient has protrusion of eye balls; in a condition called exophthalmoses. Hyperthyroidism is treated with radioactive isotope like 131 I or anti thyroid drugs improve the condition of the patient. Hypothyroidism: Occurs due to insufficient free T3 or T4, mainly because of thyroid failure. It can be due to congenital absence of thyroid gland or from lack of iodine in the diet. Iodine deficiency prevents the production of T3, T4 but does not stop production of thyroglobulin.