o Goiter is almost always present and may be diffuse or multinodular. Since many of these patients have Graves’ disease, the goiter is more often diffuse and nontender. Patients often have marked muscle weakness owing to proximal myopathy and generalized cachexia. Tremor is present. The skin is warm, moist, flushed, soft, and “velvety.” Laboratory tests of thyroid function confirm the presence of hyperthyroidism, that is, high total and free thyroxine (T4) and triiodothyronine (T3) and a reduced and nearly undetectable thyrotropin (TSH) level. However, T3 and T4 levels may be decreased by concurrent nonthyroidal illness.
o The management of thyroid storm can be discussed under three broad categories: (1) control of hyperthyroidism, (2) treatment of the precipitating illness, and (3) other supportive measures.1. Several therapeutic agents that act by different mechanisms to block the synthesis, secretion, activation, or action of thyroid hormones can be used together for rapid control of hyperthyroidism-Thioureas,Ipodate sodium,Lithium, Iodide (Iodide blocks the release of thyroid hormones from the gland. Iodide also has an inhibitory effect on thyroid hormone synthesis. High doses of inorganic iodide decrease the yield of organic iodine within the thyroid gland-a phenomenon referred to as the Wolff-Chaikoff effect.Iodide should be administered only after synthesis of thyroid hormones has been inhibited by prior administration of thioureas. Intravenous sodium iodide can be administered at a dosage of 0.25 g every 6 hours. Alternatively, if the patient is able to take medication orally, Lugol’s solution at a dosage of 5–10 drops three times a day or saturated potassium iodide solution at a dose of 3 drops three times daily can be used), Propranolol, Glucocorticoids, Exchange transfusion and plasmapheresis have been advocated as ways of removing large amounts of thyroid hormones from the circulation. Salicylates should be avoided because these drugs can inhibit T4 and T3 binding to the binding proteins and increase the concentrations of the free T4 and T3.
o Myxedema coma represents a breakdown of the body’s compensatory mechanisms during the course of long-standing severe hypothyroidism. While laboratory tests confirm hypothyroidism, the diagnosis is based on the constellation of clinical findings of myxedema, altered mental status, and hypothermia.
o Patients with myxedema most often have a history of hypothyroidism, but the precipitating condition is almost always a combination of failure to take an adequate amount of thyroid replacement therapy and the presence of some comorbid condition. Because the serum half-life of T4 is quite long, hypothyroidism is a subacute condition characterized by decreased metabolic rate, accumulation of edema fluid, deterioration of cardiac function from structural and physiologic changes, hyperlipidemia, and inability to manifest an appropriate response to hypothermia. Ventilatory drive is diminished from central mechanisms and, because of respiratory muscle weakness and pleural effusions and ascites, can result in hypercapnia. Hyponatremia is common and results from the inability to dilute urine maximally.
o Most patients with myxedema are elderly women. The classic signs of myxedema are present, including puffy, expressionless face; dry, rough, and cold skin; nonpitting, doughy edema; loss of eyebrows and scalp hair; delayed relaxation phase of the tendon reflexes; and enlarged tongue. Hypothermia is a hallmark of myxedema coma, with core body temperatures as low as 21°C but more often in the range of 32–35°C. Severe hypothermia (temperature <32°C) is associated with a poor prognosis.
o Hyponatremia is often present. Arterial blood gases may reveal respiratory acidosis, hypercapnia, and hypoxemia. Hypoglycemia may occur, particularly if there is deficiency of pituitary hormones as well. Chest x-ray may reveal an enlarged cardiac silhouette and pleural and pericardial effusions. The ECG may demonstrate low voltage, sinus bradycardia, diffuse T-wave depression, nonspecific ST-segment changes, and prolonged QT and PR intervals. There may be conduction blocks as well. Cerebrospinal fluid (CSF) pressure and protein concentrations may be increased.
o Very high serum TSH levels (>20 μU/mL) favor the diagnosis of primary hypothyroidism. Moderately elevated TSH levels (up to 20 μU/mL) may be seen occasionally in the course of sick euthyroid syndrome. Severe nonthyroidal illness decreases the TSH response, and inappropriately low TSH is seen in secondary hypothyroidism owing to hypothalamic or pituitary disorders.
o Adrenal insufficiency can coexist with hypothyroidism in two clinical situations. First, in patients with autoimmune thyroid disease, there is a higher incidence of autoimmune adrenalitis and adrenal insufficiency than in the general population. Second, patients with panhypopituitarism may have absence of both TSH and adrenocorticotropin (ACTH). These patients with secondary adrenal insufficiency lack the skin and mucosal hyperpigmentation that is characteristic of primary adrenal insufficiency. A rapid ACTH stimulation test should be performed in patients with myxedema. However, it should be recognized that the cortisol response to ACTH may be attenuated by hypothyroidism.
o Treatment consists of thyroid hormone replacement, replacement of other necessary hormones, and supportive measures. Intravenous administration of T4 is considered safe and has been the standard for the past three decades. One traditional regimen consists of 500 μg of levothyroxine (T4) given slowly intravenously, followed by 100–150 μg every 24 hours. Recent literature has witnessed conflicting reports on the effectiveness of combined regimens of levothyroxine and triiodothyronine. Signs of adrenal insufficiency may be masked in hypothyroid patients. On the other hand, initiation of levothyroxine therapy without concomitant glucocorticoid replacement may precipitate adrenal crisis if the patient has adrenal insufficiency.
o Acute Adrenal Insufficiency→ Critical illness, whether from sepsis, trauma, surgery, or any condition associated with hemodynamic compromise, stimulates the hypothalamic-pituitary-adrenal axis causing an increased production of cortisol. This hormone, synthesized in the adrenal cortex under the influence of ACTH, maintains vascular integrity and tone, stimulates neoglucogenesis and free water clearance, and influences fluid and electrolyte balance. Lack of aldosterone, a mineralocorticoid is associated with inability to conserve sodium in the face of hypovolemia and hyperkalemia. Deficiency of cortisol , a glucocorticoid,on the other hand, is associated with inability to clear free water and with hemodynamic compromise mimicking hypovolemic or septic shock. Hyponatremia, a hallmark of adrenal insufficiency, is typically due to the inability of these patients to clear free water owing to cortisol deficiency and dysregulated antidiuretic hormone (ADH) secretion. Patients with adrenal insufficiency become hypotensive owing to a combination of factors, including hypovolemia and impaired vascular response to catecholamines and also to loss of a direct inotropic effect of cortisol. Cortisol stimulates hepatic neoglucogenesis, and it is therefore not surprising that patients with adrenal insufficiency may present with hypoglycemia. Serum cortisol levels in acutely ill patients are usually increased.
o Acute adrenal insufficiency is the result of inadequate cortisol production with life-threatening cardiovascular collapse and potentially severe electrolyte and fluid abnormalities. Acute insufficiency can occur as a result of an acute insult to the adrenal glands from infection or trauma or may be seen in a patient with chronic adrenal insufficiency who develops critical illness. Patients who receive corticosteroids for treatment of inflammatory diseases will have chronic suppression of pituitary-adrenal function, and abrupt cessation of therapy may precipitate acute adrenal insufficiency, especially if there is intercurrent illness. A high index of suspicion for the diagnosis of adrenal crisis is the key. Because delay in instituting treatment can be fatal, acute adrenal insufficiency should be suspected in any patient presenting with hypotension, fever, abdominal pain, hyponatremia, or hyperkalemia, especially if hyperpigmentation is present. In many clinical situations, empirical therapy may be appropriate, even before a definitive diagnosis has been made
o Tuberculosis used to be a major cause of adrenal insufficiency, but that disease is relatively uncommon now in developed countries. Other less common causes include adrenal hemorrhage; fungal infections such as histoplasmosis, coccidioidomycosis, blastomycosis, and candidiasis; hemochromatosis; irradiation; surgical removal of the adrenal glands; drug toxicity; and congenital disorders such as synthetic enzyme deficiencies. Patients with HIV infection often have abnormalities in the adrenal glands at autopsy but appear to have only a slightly increased incidence of adrenal insufficiency (about 5–10%). The impaired immune status resulting from HIV infection increases the likelihood of adrenal involvement with cytomegalovirus (the most common find-ing), fungi (eg, Cryptococcus and Histoplasma), or mycobacteria (both tuberculous and nontuberculous).
o Other causes of adrenal insufficiency include metastatic cancer and hemorrhage. Although metastases to the adrenal gland are relatively common, adrenal insufficiency as a result of metastatic disease is uncommon. Adrenal hemorrhage may occur during the course of sepsis, excessive anticoagulation, trauma, pregnancy, or surgery. Adrenal infarction may occur as a result of thrombosis, embolism, or arteritis
o Patients with chronic adrenal insufficiency may not come to medical attention for some time because of the nonspecific nature of symptoms, such as fatigue, anorexia, weight loss, nausea, and vomiting. Other manifestations include weakness, salt craving, and postural dizziness. Patients with primary adrenal insufficiency usually have hyperpigmentation of the skin and mucous membranes because of increased ACTH production by the pituitary. Patients often develop a “tan” in both sun-exposed and non-exposed parts, especially in areas that suffer chronic friction and trauma, such as elbows, knees, knuckles, and the belt-line. The buccal mucosa may show hyperpigmentation, especially along sites of dental occlusion. The “tan” appearance of these patients often conveys a misleading impression of good health. Scars acquired during the course of adrenal insufficiency also become hyperpigmented, whereas those acquired before or after remain unpigmented.
o Laboratory data may reveal hyponatremia, hyperkalemia, and azotemia. Corticosteroids play an important role in regulating gluconeogenesis and have potent anti-insulin actions. Diagnosis can be made rapidly and reliably by an ACTH stimulation test. In addition, a random serum cortisol level greater than 20 μg/dL makes the diagnosis of adrenal insufficiency unlikely.
o Corticosteroid replacement can be given as hydrocortisone sodium succinate, 75–100 mg intravenously every 6–8 hours. If the patient is hypotensive, performance of the diagnostic ACTH stimulation test may unduly delay institution of therapy. Under these circumstances, an equivalent dose of dexamethasone (3–4 mg every 6–8 hours) can be given intravenously contemporaneously with ACTH administration. The dose of hydro-cortisone sodium succinate can be reduced to the replacement level (10–20 mg in the morning and 5–10 mg in the evening) as the patient’s condition improves. Empirical recommendations for glucocorticoid administration in surgical patients are to estimate the degree of stress and give 25 mg/day of hydrocortisone for mild stress, 50–75 mg/day for 2–3 days for moderate stress, and 100–150 mg/day for 2–3 days for severe stress. After recovery from acute illness, patients with adrenal insufficiency should be placed on chronic replacement therapy with hydrocortisone. Traditionally, a dose of 30 mg hydrocortisone administered in two divided doses-20 mg in the morning and 10 mg in the evening-has been used widely.
o Most patients with primary adrenal insufficiency require mineralocorticoid replacement. In chronic adrenal insufficiency, this can be administered as fludrocortisone acetate. The usual starting dosage is 0.05–0.1 mg by mouth daily. Some patients may develop leg edema on initiation of therapy. This usually will abate if the dose is reduced. Hydrocortisone by itself has some mineralocorticoid activity, so when patients are receiv-ing more than 50–60 mg/day of hydrocortisone, no additional mineralocorticoid replacement is necessary. However, if dexamethasone, which has little or no mineralocorticoid activity, is used instead of hydrocortisone, a mineralocorticoid should be added.
o Patients with adrenal insufficiency often have an enormous salt and water deficit. It is important to correct these deficits aggressively by administration of 0.9% NaCl solution intravenously. Patients who have been vomiting for a few days may present with hypoglycemia or develop hypoglycemia during the course of evaluation or treatment. Therefore, plasma glucose levels should be monitored and glucose given intravenously to correct or prevent hypoglycaemia.
o Another controversial issue has been the use of corticosteroids in patients with septic shock. Some studies suggest that hydrocortisone at dosages similar to replacement for adrenal insufficiency improves outcome in septic shock. Benefit was seen almost exclusively in those with an increase in serum cortisol level of less than 9 μg/dL in response to corticotrophin, despite some patients having supraphysiologic baseline serum cortisol levels.
o Sick Euthyroid Syndrome→ A number of nonthyroidal illnesses produce alterations in thyroid function in patients in whom no intrinsic thyroid disease is present and the patient is judged to be euthyroid. These low T3 and low T3-T4 syndromes seen with nonthyroidal illness represent a continuum probably reflecting severity of the disease process rather than discrete conditions. The syndromes must be distinguished from hypothyroidism because their treatment requires correction of the underlying disorder rather than thyroid hormone replacement.
o The syndrome may be divided into three patterns: low T3, low T3 and T4, and low thyroid-stimulating hormone (TSH). 1.Low T3- most common presentation, state results in part from decreased conversion of T4 to T3.. a TSH level greater than 20 μU/mL is suggestive of primary hypothyroidism. 2. Low T3 and T4 .3.Low TSH- The availability of more sensitive third-generation TSH assays has made it possible to distinguish between marginally depressed TSH concentrations in euthyroid patients and the highly suppressed levels seen with hyperthyroidism (<0.01 μU/mL). If necessary, a TRH stimulation test can be used to confirm the result. Euthyroid patients with nonthyroidal illness and depressed TSH will show detectable responses of TSH (>0.1 μU/mL) to TRH stimulation, whereas hyperthyroid patients will show the expected absence of response to TRH stimulation.
o A number of conditions can produce alterations in thyroid function tests suggesting thyroid hormone deficiency→ Malnutrition, caloric deprivation, Chronic liver disease, Renal disease, Diabetes mellitus, Infection, Acute myocardial infarction, Cancer, Surgery, Medications, AIDS. Studies show that treating patients with the low T3-T4 syndromes with T4 was not beneficial and had no effect on mortality rates. In fact, there was no increase in T3 levels, suggesting that peripheral conversion was not enhanced. Some investigators have administered T3, but once again these studies have not demonstrated a beneficial effect on outcome. Supportive measures such as adequate nutrition and specific and successful treatment of the underlying illness should result in eventual normalization of the thyroid function alterations.
o Diabetic ketoacidosis→ (Acute illness in a patient with known type 1 (insulin-dependent) diabetes mellitus, especially if the patient is vomiting, Evidence of precipitating illness, including infection. Clinical symptoms and signs of volume depletion. Clinical features of metabolic acidosis, Laboratory features: hyperglycemia, anion gap acidosis, ketonemia, and academia) The pathophysiology of diabetic ketoacidosis is based primarily on an abnormal hormonal setting: insulin deficiency combined with an excess of hormones that increase the blood glucose level. This situation is similar to the physiologic state seen during normal fasting. This change in the insulin:glucagon ratio permits the liver to become the major source for glucose during fasting. At the same time, decreased insulin concentrations lead to lipolysis in fat depots, providing a source of free fatty acids as a fuel for muscle and thus sparing glucose for use by the brain. Furthermore, free fatty acids are converted by the liver to ketones under the influence of glucagon. Ketones constitute another alternative (nonglucose) energy source for brain and muscle tissues. Glycerol released by lipolysis and alanine from protein catabolism in muscle provide substrates for gluconeogenesis in the liver.
o In contrast to the low levels of insulin, glucagon concentration is markedly elevated, with a high glucagon:insulin ratio more striking than that seen during fasting. In addition, diabetic ketoacidosis is characterized by large increases in the levels of stress hormones, including the glucose counterregulatory hormones cortisol, growth hormone, and cate-cholamines. These hormones help to define diabetic ketoacidosis and are responsible for its two major features: hyperglycemia and ketonemia.
o An important factor that determines the degree of hyperglycemia in diabetic ketoacidosis is the extent of renal glucose losses. As long as the kidneys are well perfused, they act as a continuing source of glucose leak from the extracellular space and thereby prevent severe hyperglycemia. Ketosis is the second major manifestation of diabetic ketoacidosis and results from the accumulation of keto acids generated by the liver. Recognition of hyperchloremic acidosis is important because hyperchloremic acidosis takes longer to resolve during treatment than ketoacidosis. Another cause of acidosis in diabetic ketoacidosis is lactic acidosis. Fluid and electrolytes are lost in the osmotic diuresis caused by glycosuria that occurs as a result of marked hyperglycemia in diabetic ketoacidosis. most patients with mental impairment have been found to have serum osmolality greater than 350 mOsm/Kg.
o Most patients present with a history of polyuria and polydipsia, weakness, and weight loss. Duration is often as short as 24 hours, but the history usually extends over several days, and in newly diagnosed diabetes, symptoms often go on for weeks. Patients are usually anorexic and may have vomiting and abdominal pain. Abdominal pain associated with ketosis is most common in children, although it may occur in adults as well, and occasionally has features of an acute abdomen. Fatigue and muscle cramps are also presenting features of diabetic ketoacidosis.
o Signs of volume depletion are characteristic. Decreased skin turgor, dry mucous membranes, sunken eyeballs, tachycardia, orthostatic hypotension, and even supine hypotension may be present. If severe acidosis is present, deep and slow Kussmaul respirations may be noted as well as the characteristic odor of ketones on the breath
o The most commonly recognized causes fall into three groups: (1) undiagnosed type 1 diabetes mellitus (2) reduction of insulin dose in association with intercurrent illness (particularly patients who have anorexia and vomiting and reduce the insulin dose for fear of hypoglycemia) or noncompliance (in recent times, interruption of nonconven-tional, nondepot insulin delivery,for example, insulin infusion pumps,also may be responsible for an unintended reduction in insulin dose), and (3) infection. Absence of acidemia or only mild acidemia in diabetic ketoacidosis may occur if the patient has had vomiting severe enough to result in a mixed metabolic alkalosis and acidosis.
o Mild hyponatremia is the most common abnormal finding and is due to a shift of water from the intracellular compartment into the hypertonic extracellular fluid. The patient with diabetic ketoacidosis is volume-depleted and may be acidotic, whereas the hypo-glycemic patient is usually cold and clammy
o The principles of management of diabetic ketoacidosis are to replace losses of water and electrolytes, give sufficient insulin (ie, stop ketogenesis, lipolysis, and gluconeogenesis), correct blood pH, closely monitor the patient through all stages of management, and eliminate or treat precipitating causes.
o Correction of hyperglycemia occurs by four different mechanisms. First, the concentration of the extracellular glucose is diluted by fluid replacement, expanding the extracellular space. The second is by continuing, and usually increased urinary loss of glucose that occurs with improved renal perfusion following expansion of the intravascular space. Third is the effect of insulin to diminish the hepatic glucose production rate. Considering that this is one of the important pathophysiologic mechanisms producing hyperglycemia in diabetic ketoacidosis- inhibition of this process must be one of the management goals. Indeed, it has been demonstrated that insulin infused at the routine doses is very effective in reducing glucose production by the liver during recovery from diabetic ketoacidosis. Increased glucose utilization is the fourth mechanism and is also an insulin-dependent process.
o Ketosis is corrected more slowly than hyperglycemia, so while serum glucose levels usually will reach 250–300 mg/dL within an average of 6–8 hours, it can take up to 12 hours or more for ketosis to clear. It is particularly important to continue insulin infusion during this period despite the fact that one major goal of therapy (reduction of hyperglycemia) has been attained. Intravenous insulin therefore should be stopped only when ketosis has cleared.
o Monitoring the anion gap is a better way of determining when ketosis has cleared. Serum bicarbonate concentrations are useful for monitoring progress of therapy but less useful when used alone. Fluid therapy is begun with intravenous 0.9% NaCl solution. A rough guide to volume replacement is as follows: (1) 2 L can be given over the first 2 hours, (2) this can be followed by 2 L over the next 4 hours using 0.9% or 0.45% NaCl solution, and (3) over the next 8 hours, another 2 L can be given using either 0.9% or 0.45% NaCl. This schedule should be modified according to ongoing assessment of volume replacement needs and serum sodium levels. In hemodynamically compromised patients and the elderly, close monitoring of volume status may be necessary, and consideration should be given to use of a central venous pressure or pulmonary artery catheter. If severe hypotension is present, maintaining intravascular volume with albumin or other plasma expanders also should be considered.
o When the plasma glucose concentration reaches 250–300 mg/dL, 5% dextrose solution should be started with an appropriate amount of NaCl according to the needs of the patient at that time. if serum glu-cose concentrations have not begun to fall after the first hour, the rate of insulin infusion should be doubled—and doubled once again if the same should happen during continuing ther-apy. The insulin infusion should cause blood glucose to fall at a rate of about 75 mg/dL per hour.
o Potassium replacement is started by the addition of potassium chloride 20–40 meq/L to the fluid replacement solution. Potassium phosphate also may be given (alternating with potassium chloride) if phosphate repletion is necessary. American Diabetes Association (ADA) recommends that 100 mmol of sodium bicarbonate should be added to 400 mL of sterile water and given at a rate of 200 mL/h in severe acidosis (pH <6.9). In patients with a pH of 6.9–7.0, 50 mmol of sodium bicarbonate should be diluted in 200 mL of sterile water and infused at a rate of 200 mL/h. Patients with hypophosphatemia should be given supplemental phosphorus in the form of potassium phosphate. A concern about phosphate administration in patients with diabetic ketoacidosis is hypocalcemic tetany, which has been described in some patients who receive phosphate therapy.
o One of the rare but significant conditions that should be kept in mind in the management of diabetic ketoacidosis is mucormycosis. This rare condition associated with ketoaci-dosis is a treatable yet severe infection by the fungus Rhizopus.
o Hyperglycemic Hyperosmolar Nonketotic Coma→This disorder is probably not a distinct entity but rather a variant of the diabetic ketoacidosis syndrome because a large overlap exists in the clinical presentation and pathogenesis of diabetic ketoacidosis and nonketotic coma. Biochemically, the typical patient with hyperglycemic hyperosmolar nonketotic coma has more severe hyperglycemia (eg, serum glucose often > 1000 mg/dL) and hyperosmolarity, more pronounced elec-trolyte abnormalities, and no ketosis.
o Ketoacidosis makes the patients feel more ill and thus prevents the syndrome from going undiagnosed for prolonged periods. The lack of ketosis in hyperglycemic hyperosmolar nonketotic coma may delay presentation, resulting in ongoing osmotic diuresis that results in more severe volume depletion. Plasma glucose concentrations should be allowed to decrease at a rate of about 100 mg/dL per hour, and fluid replacement should begin with normal saline
o Increased concentrations of cortisol, catecholamines, growth hormone, and glucagon lead to increased hepatic glucose production by gluconeogenesis and glycogenolysis, as well as insulin resistance at the level of muscle and adipose tissue. Some diabetic patients appear to have decreased insulin requirements or a decreasing need for oral hypoglycemic agents when acute illness supervenes. Small decreases in weight often are sufficient to produce a substantially decreased requirement for insulin or other hypoglycemic agents. Decreased growth hormone or cortisol can diminish the need for hypoglycemic agents by enhancing peripheral insulin sensitivity and decreasing gluconeogenesis. Because the liver and the kidneys are the primary organs involved in metabolism of insulin and the sulfonylurea drugs, development of renal or hepatic failure may delay drug clearance and result in hypoglycaemia. A relatively common cause of unexpected hypoglycemia occurs during acute episodes of congestive heart failure in insulin-treated patients. As a result of liver congestion and possibly decreased insulin clearance with reduced hepatic blood flow, insulin requirements are transiently diminished. If the insulin dose is not reduced, hypoglycemia may occur.
o Even in the absence of an exogenous source of glucose, such as total parenteral nutrition, it is important to recognize that hyperglycemia in patients with diabetes is the result of a continuous delivery of large amounts of glucose from an endogenous source, that is, the liver.
o Some of the complications of DM are clinically obvious renal failure or nephrotic syndrome with hypoalbuminemia, defects in vision, orthostatic hypotension, gastroparesis, recurrent urinary tract infections, syndrome of hyporeninemic hypoaldosteronism, Hyperkalemia.
o Medical conditions requiring hospitalisation→ Medical management of Pyelonephritis in uncontrolled Diabetes mellitus, Medical management of Lower Respiratoy Tract Infection, Medical management of Fungal Sinusitis, Medical management of Cholecystitis, Medical management of Cavernous Sinus Thrombosis in uncontrolled Diabetes mellitus, Medical management of Rhinocerebral Mucormycosis. Initial evaluation and management of Hypopituitarism with growth harmone, Hormonal therapy for Pituitary – Acromegaly, Medical Management of Cushings Syndrome, Hormonal therapy for Delayed Puberty Hypogonadism-Turners Syndrome/Kleinfelter Syndrome, Hypopiturasim Initial Evaluation And Management With Growth Hormone, Medical Management of Graves Disease.
o Surgical conditions & procedures requiring hospitalisation- Bilateral Adrenalectomy in nonmalignant conditions, Unilateral Adrenelectopmy in nonmalignant conditions
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