BCS III - EXAM 2 Tuberculosis PDF

KARLIE E BCS III - EXAM 2 TUBERCULOSIS DEFINITION o Chronic pulmonary and systemic disease caused most often by Mycobacterium tuberculosis, and the leading infectious cause of death worldwide o The source of transmission: § humans with...

KARLIE E BCS III - EXAM 2 TUBERCULOSIS DEFINITION o Chronic pulmonary and systemic disease caused most often by Mycobacterium tuberculosis, and the leading infectious cause of death worldwide o The source of transmission: § humans with active tuberculosis who release mycobacteria into the sputum droplets o Other types: § Oropharyngeal and intestinal tuberculosis contracted by ingesting milk contaminated with Mycobacterium bovis § It is rare in countries where milk is routinely pasteurized, but it is still seen in countries that have tuberculous dairy cows and unpasteurized milk. EPIDEMIOLOGY o A total of 1.3 million people died from TB in 2022 (including 167 000 people with HIV) - TB is the leading cause of death in patients with HIV. o Worldwide, TB is the second leading infectious killer after COVID-19 (above HIV and AIDS). o Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health security threat. Only about 2 in 5 people with drug resistant TB accessed treatment in 2022. o Ending the TB epidemic by 2030 is among the health targets of the United Nations Sustainable Development Goals (SDGs) KARLIE E REGIONS WITH HIGHEST INCIDENCE o SE Asia o Africa o The Western Pacific TB IN THE USA o 8,331: reported TB cases in the United States in 2022 (an incidence rate of 2.5 cases per 100,000 persons) o Up to 13 million: estimated number of people in the United States living with latent TB infection o 602 people died of TB-related causes in 2021 RISK FACTORS o PATHOPHYSIOLOGY o Mycobacterium tuberculosis à § MTB. is a slow-growing obligate aerobe and a facultative intracellular parasite. § They are rod-shaped; 0.2-0.5 µm by 2-4 µm § MTB. are non-spore-forming and nonmotile. KARLIE E § The mycolic acid component of the cell wall retain red basic fuchsin dye after acid rinsing - the basis of the acid-fast stains used for pathologic identification. § Gram stain can not penetrate MTB waxy well wall – no stain o Virulence factors à § Cell wall: Their cell walls contain mycolic acid-rich, long-chain glycolipids and phosphoglycolipids (mycocides) that protect mycobacteria from cell lysosomal attack. Lipoarabinomannan (LAM), a cell wall glycolipid found induces cytokines Sulfatides and trehalose dimycolate: triggers toxicity § Enzyme: Catalase-peroxidase: resists host cell oxidative response § Transmission: Exclusively airborne From patients with active TB o Pathogenesis à § 1st step is inhalation of aerosol droplets § Droplets are deposited in the lungs § 3 possible outcomes: Clearance of bacteria Primary active disease Latent infection (clinical disease may occur many years later) o Entry into macrophages § M. tuberculosis enters macrophages by phagocytosis mediated by several receptors expressed on the phagocyte, including mannose-binding lectin and the type 3 complement receptor (CR3) KARLIE E o Replication in macrophages § M. tuberculosis inhibits maturation of the phagosome and blocks formation of the phagolysosome, allowing the bacterium to replicate unchecked within the vesicle, protected from the microbicidal mechanisms of lysosomes. § During the earliest stage of primary tuberculosis ( 35 § Contraindicated in positive tuberculin reactions, AIDS, or immunosuppression § Vaccine administration will result in a positive TST. KARLIE E PROGNOSIS o Treatment with anti-mycobacterial drugs is 85% successful worldwide. o 15% mortality rate worldwide o 2.5%–5% rate of treatment failure or relapse in the United States DIFFERENTIAL DIAGNOSIS o Chronic bronchitis o Atypical pneumonia o M. avium complex (MAC) infection o Lung mycoses o Bronchial carcinoma o Granulomatous diseases § Sarcoidosis § Pneumoconiosis § Histoplasmosis DENTAL MANAGEMENT o Many patients with infectious disease, including TB, cannot be clinically or historically identified; therefore, all patients should be treated as though they are potentially infectious, and the CDC’s standard precautions for infection control should be strictly followed. o The CDC places most dental facilities in the low-risk category for potential occupational exposure to TB. In keeping with this risk category, it recommends that each dental facility have a written TB control protocol that includes instrument reprocessing and operatory cleanup, as well as protocols for identifying, managing, and referring patients with active TB and educating and training staff o The CDC also recommends that baseline and periodic screening of dental care workers with PPD be provided to document any recent KARLIE E exposure and that protocols be available that explain how the office assesses, manages, and investigates dental staff members with a positive result on PPD testing. CDC & PREVENTION GUIDELINES: TB PRECAUTIONS FOR USE IN OUTPATIENT DENTAL SETTINGS o These guidelines address administrative, environmental, and respiratory protection controls for outpatient health care settings such as dental offices ADMINISTRATIVE CONTROLS o Assign responsibility for managing TB infection control program. o Conduct annual risk assessments. o Develop written TB infection control policies for promptly identifying and isolating patients with suspected or confirmed TB for medical evaluation or urgent treatment. o Ensure dental health care personnel are educated regarding the signs and symptoms of TB. o Instruct patient to cover mouth when coughing and to wear a surgical mask. o Screen newly hired personnel for latent TB infection and disease. o Postpone urgent dental treatment if TB is suspected or active. ENVIRONMENTAL CONTROLS o Use airborne infection isolation room to provide urgent treatment to patients with suspected or confirmed TB. o Use high-efficiency particulate air filters or UV-germicidal irradiation in settings with a high volume of patients with suspected or confirmed TB. o Cover and clean and disinfect exposed patient area surfaces. KARLIE E o Sterilize patient care items RESPIRATORY PROTECTION CONTROLS o Use respiratory protection (at least an N95 filtering face piece [disposable], N99 or N100 respirators) for exposed personnel when they are providing urgent dental treatment to patients with suspected or confirmed TB. o Instruct TB patients to cover their mouth when coughing and to wear a surgical mask DENTAL MANAGEMENT FOR PATIENTS WITH A HX OF TB o Patients with clinically active sputum-positive TB à § Consult with a physician before treatment. § Perform urgent care only; palliate urgent problems with medication if contained facility in a hospital environment is not available. § Perform urgent care that requires the use of a handpiece (in patients older than 6 years) only in a hospital setting with isolation, sterilization (gloves, mask, gown), and special respiratory protection. § Treat those less than 6 years of age as a normal patient (noninfectious after consultation with physician to verify status). § Treat patients who consistently produce negative sputum as normal (noninfectious—verify with physician) o Patients with a past history of TB à § Approach with caution; obtain thorough history of disease and its treatment duration, with appropriate review of systems. § Obtain from patient a history of periodic chest radiographs and physical examination to rule out reactivation or relapse. KARLIE E § Consult with physician and postpone treatment with identification of any of the following: § Questionable adequacy of treatment time § Lack of appropriate medical follow-up evaluation since recovery § Sign or symptom of relapse § Treat as for normal patient if present status is “free of clinically active disease.” o Patients with a (+) tuberculin test or (+) IGRA à § Verify evaluation by physician to rule out active disease. § Verify completion of drug therapy with isoniazid for 9 months. § Treat as normal patient. o Patients w/ S/S suggestive of TB à § Refer to a physician and postpone treatment. § Treat as for a patient with sputum-positive status if treatment is necessary. DRUG CONSIDERATIONS o Several anti-TB drugs have notable adverse effects and drug interactions in which dentists should be knowledgeable. o KARLIE E ORAL COMPLICATIONS & MANIFESTATIONS OF TB o Tuberculosis manifests infrequently in the oral cavity o Oral lesions can occur at any age but most frequently are seen in men about 30 years of age and in children o The classic mucosal lesion is a painful, deep, irregular ulcer on the dorsum of the tongue o The palate, lips, buccal mucosa, and gingiva also may be affected - Mucosal lesions have been reported to be granular, nodular, or leukoplakic and sometimes painless o Extension into the jaws can result in osteomyelitis o Involvement of the salivary glands or temporomandibular joint is rare o Scrofula à § Infection of the cervical and submandibular lymph nodes with TB. § The nodes become enlarged and painful, and abscesses may form with subsequent drainage. § Resolution of the infectious oral lesion may result from treatment of TB with antituberculosis drugs. § OSHA o Continues to issue guidance policy to protect workers against exposure to M. tuberculosis and continues to mandate directives as public policy KARLIE E DIABETES MELLITUS ENDOCRINE SYSTEM CONTENTS o Hypothalamus o Pituitary o Pineal gland o Thyroid o Parathyroid o Thymus o Adrenal Gland o Pancreas o Ovaries/Testes HYPOTHALAMUS o Location à § Base of brain near optic chiasm o Function à § Links nervous system to endocrine system via the pituitary § Controls body temperature § Controls hunger § Controls important aspects of parenting and maternal attachment behaviors § Controls thirst § Controls fatigue § Controls sleep § Controls circadian rhythms § Controls certain social behaviors, such as § Sexual and aggressive behaviors KARLIE E o PITUITARY GLAND o Location à § At the base of the brain, protruding from hypothalamus o Function à § Controls growth § Controls blood pressure § Controls energy management § Controls all functions of the sex organs, § Controls thyroid gland § Controls metabolism § Controls some aspects of pregnancy, childbirth, and breastfeeding § Controls water/salt concentration at kidneys § Controls temperature regulation § Controls pain relief § KARLIE E PINEAL GLAND o Location à § Inferior to the corpus callosum in the middle of brain o Function à § Secretes melatonin, which helps the body know when it is time to sleep o THYROID GLAND o Location à § Anterior of the neck, inferior to the larynx o Functions à § Influences metabolic rate § Influences protein synthesis and growth in children o PARATHYROID GLANDS o Location à § Located on posterior thyroid gland o Function à § Regulate the amount of calcium in the blood and in the bones KARLIE E § Activates Vitamin D THYMUS o Location à § Superior ventral portion of chest, in the anterior superior mediastinum, dorsal to the sternum, and ventral to the heart o Function à § Produces white blood cells that fight infections and destroy abnormal cells o ADRENAL GLANDS o Location à § At the top of each kidney o Function à § Regulation of blood pressure § Regulation of electrolyte balance § Regulation of metabolism § Suppression of immune system § Steroidogenesis § Production of catecholamines, which produce a rapid response throughout the body in stress situations PANCREAS o Location à § Across the posterior abdomen, dorsal to the stomach o Function à § Hormone production, especially those that regulate levels of blood sugar § Aids in digestion (exocrine function) KARLIE E OVARIES o Location à § Alongside the lateral walls of the uterus in the ovarian fossa o Function à § Regulation of secondary sex characteristics in women § Maturation and maintenance of female reproductive organs in their mature functional state § Regulate hormones, playing an important role in pregnancy and fertility § Production and release of egg cells § Regulation of menstrual cycle TESTES o Location à § Inside the scrotum, inferior to the bulb of the penis o Function à § Regulation of secondary sex characteristics in men § Production of testosterone § Production of sperm § Regulation of reproductive function HORMONES o A chemical factor that is released at one site to travel via the circulation to a target cell some distance away for the purpose of regulating physiology or behavior PANCREAS o 99% exocrine à § Enzymes aid in the digestion of food § Trypsin - proteins KARLIE E § Chymotrypsin - proteins § Amylase - carbohydrates § Lipase - fats § Acini release iso-osmotic, alkaline pancreatic juices into a system of ducts that ultimately culminates in the pancreatic duct, which joins the common bile duct and releases into the duodenum via the ampulla of Vater. o 1% endocrine à § Islets of Langerhans Synthesizes and releases hormones, not enzymes Does not release into pancreatic duct system…releases directly into blood stream Main function of pancreatic hormones is to regulate levels of glucose in the blood § KARLIE E PANCREATIC HORMONES o INSULIN à 51 AA hormone consisting of two dimers (Chain A and Chain B) joined by a disulfide bond Main anabolic hormone in the human body Secreted as proinsulin, which is converted to insulin through the removal of C-peptide, folding of the A and B chains, and the formation of the disulfide bond § Insulin - location Produced by the 𝛽-cells in the pancreatic islets of Langerhans; 𝛽-cells represent about 50-75% of cells in each islet. Binds to insulin receptors on target cells; primary target cells include hepatocytes, adipocytes, and skeletal muscle myocytes § Insulin – when In normal physiology, 𝛽-cell insulin secretion is coupled immediately with changes in the plasma glucose level. The secretory response is rapid (within a minute or two), and because the half-life of insulin is about five minutes, there is little lag time in the glucose regulatory system § Insulin – why Controls blood sugar levels by helping glucose center cells Helps turn food into energy Regulates the metabolism of carbohydrates, fats, and proteins by promoting absorption of glucose from the blood into target cells § Insulin – how KARLIE E Binds to an insulin receptor, a transmembrane protein on target cells. Insulin receptors are in the tyrosine kinase (RTK) superfamily of receptors. In skeletal muscle, converts glucose into glycogen via glycogenesis In adipose tissue, converts glucose into triglycerides via lipogenesis In liver, converts glucose into both glycogen and triglycerides o AMYLIN à 37 AA peptide hormone helps regulate blood glucose levels and energy balance § Amylin – location Produced by and co-secreted with insulin by the 𝛽-cells in the pancreatic islets of Langerhans Works on nuclei in the hindbrain, the hypothalamus, and in the periphery § Amylin – when Co-secreted with insulin when nutrients enter the small intestine at a ratio of approximately 100:1 (insulin: amylin) § Amylin – why To regulate blood glucose To reduce food intake To affect energy homeostasis § Amylin – how Slows gastric emptying Inhibits the release of glucagon Induces satiety after meals Prevents post-prandial spikes in blood glucose levels KARLIE E Can form amyloid fibrils, thought to play a role in the decline of islet cell function that accompanies type 2 diabetes o C-PEPTIDE à Connecting peptide 31 AA link cleaved from between the Chain A and Chain B areas of proinsulin § C-peptide - location Cleaved from proinsulin in the Golgi apparatus of the 𝛽- cells § C-peptide - when Originally produced at a 1:1 ratio with insulin although the ratio approaches 1:5 to 1:15 (insulin: C-peptide) in the blood due to rapid use of insulin, the longer half-life of C- peptide (compared to insulin), and C-peptide’s clearance in the kidney § C-peptide – why Helps insulin fold correctly and form disulfide bond § C-peptide – how High levels of C-peptide indicate high levels of insulin…which can be caused by elevated blood sugar, insulin resistance, or other factors High insulin: C-peptide ratio can indicate an insulinoma (a tumor producing excess insulin) or administration of exogenous insulin Low levels of C-peptide indicate the body is not producing enough insulin. Causes might include type 1 diabetes mellitus, advanced type 2 diabetes, taking too much exogenous insulin, not eating recently KARLIE E o GLUCAGON à 29 AA hormone Main catabolic hormone in the human body Secreted as proglucagon, a 160 AA polypeptide precursor that gives rise to glucagon, glucagon-like peptide 1 (GLP- 1), and other peptides § Glucagon – location Produced by the 𝛼-cells in the islets of Langerhans; 𝛼-cells represent about 25-35% of cells in each islet § Glucagon – when Elevated under stress Released when blood glucose is too low, causing glycogenolysis in the liver § Glucagon – why Increases energy expenditure § Glucagon – how Raises the concentration of glucose and fatty acids in the bloodstream o SOMATOSTATIN à Polypeptide hormone with two active forms: one 14 AA, the other 28 AA § Somatostatin – location Produced by the δ-cells in the islets of Langerhans; δ-cells represent about 10% of cells in each islet Works on 𝛼- and 𝛽-cells in a paracrine manner Also produced by pyloric antrum and duodenum § Somatostatin – when Half-life is between 1-3 mins § Somatostatin – why KARLIE E Inhibits secretion of insulin and glucagon § Somatostatin – how Glucose stimulates δ-cells to fire action potentials and secrete somatostatin Produces predominantly neuroendocrine inhibitory effects o GHRELIN à 28 AA polypeptide hormone § Grehlin – location Produced by the ε-cells in the islets; ε-cells represent 12 mg/dL. o Mnemonic for PH: § STONES § BONES § GROANS § MOANS o STONES (renal): § Nephrolithiasis (calcium phosphate or calcium oxalate stones) § Can progress to nephrocalcinosis (deposition of Ca in renal tubules) o BONES (3 skeletal abnormalities seen in untreated disease): § Osteoporosis: KARLIE E Mostly in cortical bone of the phalanges, vertebrae, and proximal femur Overall increased risk of fractures § Brown tumors: masses of reactive fibrous tissue with macrophages Due to brisk osteoclast activity Producing microfractures Associated with increased vascularity, hemorrhage, and hemosiderin deposition § Osteitis fibrosa cystica: from severe hyperparathyroidism, due to cystic degeneration of many brown tumors o GROANS (GI tract): § Obstipation § Abdominal distention § Nausea § Loss of appetite § Weight loss § Gastric and duodenal ulcers § Pancreatitis o MOANS (neuropsychiatric symptoms): § Depression § Personality changes § Lethargy § Coma CLINICAL FEATURES - OTHER MANIFESTATIONS o General or proximal muscle weakness, rapid muscle fatigue o Cardiovascular à § Hypertension KARLIE E § Vascular and valvular calcification § Electrocardiogram changes (atrioventricular (AV) block, bradycardia, short QT interval, left ventricular hypertrophy) § Polyuria, polydipsia o Hyperparathyroid crisis (rare) à § Polyuria, polydipsia § Nausea/vomiting § Loss of consciousness, somnolence, and coma SECONDARY HYPERPARATHYROIDISM o No unique clinical presentation o Patients with CKD can present with bone pain o Cases associated with vitamin D deficiency present with related symptoms: § Osteomalacia, increased fractures § Myopathy TERTIARY HYPERPARATHYROIDISM o Bone pain o Pruritus o Fatigue/lethargy o Increased risk of fractures DIAGNOSTICS o Primary à § Consider pHPT in patients with hypercalcemia. § Obtain laboratory studies to confirm hypercalcemia and assess for elevated intact PTH levels. § Evaluate for features of hypercalcemia KARLIE E § Determine surgical eligibility using detailed patient history and laboratory and imaging findings. § Consider genetic counseling referral if there is suspicion for an inherited condition based on the patient's family history. § Lab studies Diagnostic confirmation: (both results must be present on two separate occasions, ≥ 2 weeks apart) o Serum calcium - ↑ Serum calcium o Serum PTH - ↑ Serum intact PTH (or inappropriately normal) Additional studies: for patients with confirmed pHPT o Serum creatinine and estimated GFR: to evaluate for renal dysfunction o 25-hydroxyvitamin D: to assess for deficiency o Phosphate: may be low o ALP (Alkaline phosphatase): high as a result of bone turnover o 24-hour urinary calcium and creatinine o ↑ Ca/Cr clearance ratio (> 0.02): suggests pHPT and it is a risk factor for nephrocalcinosis and nephrolithiasis. o ↓ Ca/Cr clearance ratio (< 0.01): suggests familial hypocalciuric hypercalcemia, which can mimic pHPT. § Routine imaging Obtained in all patients with confirmed pHPT to evaluate for renal and skeletal manifestations. Skeletal evaluation o Assess for osteoporosis, osteopenia, and fragility fractures. KARLIE E o Preferred modality: dual-energy x-ray absorptiometry (DXA) including vertebral fracture assessment (VFA) o Alternative: vertebral x-ray (to assess for spinal fragility fractures) Renal imaging o Assess for nephrolithiasis and/or nephrocalcinosis. o Options include abdominal CT without contrast, renal ultrasound, and abdominal x-ray. § Additional imaging Neck imaging o For surgical planning to determine the location of the abnormal glands and evaluate for concomitant thyroid disease. o Options include ultrasound neck and nuclear imaging, i.e., Tc-99m sestamibi scan. X-ray is not routinely indicated; potential findings include: o Decreased BMD o Cortical thinning: especially prominent in the phalanges of the hand; manifests as acroosteolysis (a subperiosteal pattern of bone resorption) o Salt and pepper skull: granular decalcification manifesting as diffusely distributed lytic foci on imaging of the calvarium o Features of osteitis fibrosa cystica KARLIE E Salt and pepper skull - X-ray head (lateral view) Brown tumors - X-ray left femur (AP view) in a patient with Numerous small well-defined lucent calvarial lesions correlate pHPT with trabecular bone resorption (examples indicated by green Multiple circumscribed, lytic lesions (brown tumors) are seen. overlay). The salt and pepper (or pepper-pot) appearance is a Cortical thinning accompanies some lesions, but there is no feature of primary hyperparathyroidism. © AMBOSS cortical penetration. o COLLEGE OF DENTAL MEDICINE o Secondary & Tertiary Hyperparathyroidism à § Approach Consider sHPT in patients with hypocalcemia and an associated underlying condition (e.g., CKD, vitamin D deficiency). Consider tHPT in patients with long-standing sHPT who develop hypercalcemia. Imaging studies are not routinely indicated. § Lab studies Diagnostic confirmation o ↑ PTH and ↓ calcium: sHPT o ↑ PTH (or inappropriately normal) and ↑ calcium: tHPT § Additional studies: to support the diagnosis and assess for modifiable factors Phosphate o ↓ Phosphate: sHPT not caused by CKD o Normal or ↑ phosphate: sHPT caused by CKD KARLIE E o ↑ Phosphate: tHPT ↑ ALP: sign of bone turnover ↑ Creatinine and ↓ vitamin D: signs of CKD-MBD (Chronic kidney disease–mineral and bone disorder) DISEASE MANAGEMENT PRIMARY o Management should be guided by a specialist. o Provide treatment for hypercalcemia. o Refer all symptomatic patients and eligible asymptomatic patients for surgical evaluation. o For patients who do not undergo surgery: o Start pharmacotherapy. KARLIE E o Monitor for complications. o Surgical Therapy § Indications: symptomatic patients, and asymptomatic patients who fulfill any of the following criteria Age < 50 years Hypercalcemia: serum calcium level > 1 mg/dL above the upper limit of normal o Renal involvement § Estimated GFR < 60 mL/minute § Hypercalciuria § Nephrolithiasis or nephrocalcinosis on imaging o Skeletal involvement § Reduced BMD (T-score ≤-2.5 at any site) § Vertebral fracture o Surgical procedures § Minimally invasive parathyroidectomy of the affected gland– for Solitary adenoma § Total parathyroidectomy removal of all four glands with reimplantation of half a gland in easily accessible muscle - for Hyperplasia § Tumor resection with removal of the ipsilateral thyroid lobe and enlarged lymph nodes in cases involving Carcinoma o Pharmacotherapy § Calcimimetics (e.g., cinacalcet) KARLIE E Mechanism of action: increases the sensitivity of calcium- sensing receptors in parathyroid glands to circulating Ca2+ → inhibition of PTH release § Bisphosphonates (e.g., alendronate): for patients with osteopenia or osteoporosis § Denosumab: alternative to bisphosphonates § Vitamin D supplementation For patients with vitamin D deficiency or insufficiency o Monitoring § Indication patients who do not undergo parathyroid surgery § Imaging studies every 1–2 years DXA with VFA to assess BMD Renal imaging (e.g., abdominal CT without contrast, renal ultrasound) to assess for nephrolithiasis and/or nephrocalcinosis § Laboratory studies yearly Serum calcium, 25-hydroxyvitamin D, creatinine, estimated GFR 24-hour urine calcium SECONDARY & TERTIARY o Treatment of the underlying condition § Manage chronic kidney disease” and “CKD-MBD § In patients with vitamin D deficiency: Supplement with vitamin D analogues (e.g., ergocalciferol). o Calcimimetics KARLIE E § For treatment of sHPT in patients with CKD who are on dialysis § Consider for patients with tHPT o Parathyroidectomy § Consider for sHPT refractory to medical therapy. § Mainstay of treatment for tHPT DIFFERENTIAL DIAGNOSIS o Primary à § Other causes of PTH-mediated hypercalcemia: i.e., tHPT, familial hypocalciuric hypercalcemia § Causes of non-PTH-mediated hypercalcemia: e.g., hypercalcemia of malignancy, granulomatous disorders. o Secondary & Tertiary à § Other causes of hypercalcemia § Other causes of hypocalcemia § Other causes of hyperphosphatemia DENTAL CONSIDERATIONS o Dental changes in hyperparathyroidism include; § loss of the lamina dura and generalized bone rarefaction, but giant cell lesions are late and uncommon. o Brown tumors are indistinguishable from central giant cell granulomas of the jaws – If giant cell lesion is found, particularly in a middle-aged patient or in a patient with CKD, parathyroid function should be investigated. o LA is the main means of pain control, especially if hypertension and arrhythmias are present. o Conscious sedation is preferably carried out with nitrous oxide and oxygen. KARLIE E o GA may be challenging because of cardiovascular complications and sensitivity to muscle relaxants. o Dental treatment in hyperparathyroidism may be complicated by renal disease, peptic ulceration, bone fragility or pluriglandular disease.