question Flashcards
What are the available options for the treatment of diabetes?
The available options for the treatment of diabetes include sulfonylureas, DPP4 inhibitors/GLP1 analogues, SGLT2 inhibitors, and α-glucosidase inhibitors.
Why is pioglitazone contraindicated in heart failure patients?
Pioglitazone is contraindicated in heart failure patients as it worsens heart failure by stimulating sodium reabsorption from the collecting duct, leading to fluid retention.
Which DPP4 inhibitor has been shown to increase the risk of heart failure?
Saxagliptin has been shown to increase the risk of heart failure.
Do GLP1 analogues have a cardiovascular benefit?
GLP1 analogues have been shown to have a cardiovascular benefit, but limited data exists.
What is the dosing schedule and time of administration of sulfonylureas?
The dosing schedule and time of administration of sulfonylureas are as follows: Glibenclamide - 10-20 mg once or twice daily, 30 minutes prior to a meal; Glipizide - 20-40 mg twice daily, 30 minutes prior to a meal; Gliclazide - 160-320 mg twice daily, 30 minutes prior to a meal; Glimepiride - 4-8 mg once or twice daily, 30 minutes prior to a meal.
What is the time of administration for oral antidiabetic drugs?
The time of administration for oral antidiabetic drugs is as follows: Sulfonylureas - 30 minutes prior to a meal; Metformin - with or after meals; Acarbose/voglibose - just before major meals; Pioglitazone - before meals but at a fixed time; DPP4 inhibitors - prior to a meal; GLP1 agonists - prior to a meal.
What is the HbA1c-reducing efficacy of various treatment modalities in the management of diabetes?
The HbA1c-reducing efficacy of various treatment modalities in the management of diabetes is as follows: Lifestyle modification - 1-2%; Sulfonylureas (SU) - 1-1.5%; Metformin - 1-1.5%; SU+metformin - 1-1.5%; Pioglitazone - 1-1.2%; DPP4 inhibitors - 0.6-0.8%; GLP1 agonists - 1-1.3%; Insulin - unlimited.
What are the probabilities associated with sudden worsening of vision in a patient on metformin, sulfonylurea, and pioglitazone?
The sudden worsening of vision in a patient on metformin, sulfonylurea, and pioglitazone may be due to macular edema caused by pioglitazone. Other possibilities include retinal detachment, vitreous hemorrhage, and central retinal artery/vein occlusion.
Is there a real risk for bladder cancer with pioglitazone?
There is a possible association between bladder cancer and the use of pioglitazone. The risk of bladder cancer is higher with a cumulative dose >28g and duration of use >2 years. However, some studies did not reveal an increased risk with pioglitazone use.
What are some of the drugs available for the management of osteoporosis?
The available drugs for the management of osteoporosis are anabolic drugs (rPTH1-34 or rPTH1-84), calcilytics (CaSR), romosozumab (sclerostin), abaloparatide (rPTHrP1-34 analogue), estrogen and SERM, bisphosphonates, denosumab (RANKL antibody), odanacatib (cathepsin K inhibitor), and saracatinib (c-Src kinase inhibitor).
How do bisphosphonates act?
Bisphosphonates (BPs) bind to calcium hydroxyapatite at active bone remodeling sites to exert their antiresorptive effects. They inhibit crystal dissolution and suppress bone resorption by blocking osteoclast action. BPs are classified into non-nitrogen-containing BPs and nitrogen-containing BPs, with each having different mechanisms of action.
What is the mechanism of action of non-nitrogen-containing bisphosphonates?
Non-nitrogen-containing bisphosphonates, such as etidronate and clodronate analogues, are metabolically incorporated into non-hydrolyzable ATP analogues within osteoclasts, resulting in osteoclast apoptosis.
What is the mechanism of action of nitrogen-containing bisphosphonates?
Nitrogen-containing bisphosphonates (amino-BPs), like pamidronate, alendronate, risedronate, ibandronate, and zoledronate, inhibit the mevalonate pathway by blocking farnesyl diphosphate synthase (FDPS). This leads to cytoskeletal abnormalities and disruption of prenylation of small GTPases in osteoclasts, causing osteoclast apoptosis.
What are the precautions to be taken before administering bisphosphonates?
Before administering bisphosphonates, a detailed history, examination, and appropriate investigations should be conducted to rule out secondary causes of osteoporosis and establish a definite indication for bisphosphonate use. Vitamin D levels should be assessed and supplemented if deficient. Renal function should be assessed, and bisphosphonates should preferably be avoided if eGFR is <30 ml/min. Oral cavity should be examined for periodontal diseases/caries and treated before bisphosphonate therapy. Oral bisphosphonates should be avoided in those with upper gastrointestinal disease.
Which bisphosphonate is preferred for the management of osteoporosis?
Zoledronate is the most potent bisphosphonate and is administered once a year, making it convenient for patients in clinical practice. However, all newer generation bisphosphonates are equally effective in preventing both hip and spine fractures.
What adverse events are associated with bisphosphonate therapy?
The adverse events associated with bisphosphonate use include acute flu-like syndrome, GI intolerance (nausea, vomiting, diarrhea, esophagitis), hypocalcemia, hypophosphatemia, occasional atrial fibrillation, renal failure, severe suppression of bone turnover, atypical fractures, impaired bone remodeling, osteonecrosis of jaw, and rare cases of esophageal carcinoma.
How do bisphosphonates cause hypocalcemia and hypophosphatemia?
The exact mechanism of how bisphosphonates cause hypocalcemia and hypophosphatemia is not described in the course notes.
When is discontinuation of therapy mandated in the case of a rise in serum creatinine?
Discontinuation of therapy is mandated if the rise in serum creatinine is more than 30% or is associated with hyperkalemia.
What are the causes of worsening renal function after initiation of ACEIs/ARBs?
The causes of worsening renal function after initiation of ACEIs/ARBs include bilateral renal artery stenosis, overzealous use of diuretics, accelerated hypertension, and uncontrolled hyperglycemia.
How do ACEIs or ARBs prevent diabetes?
ACEIs/ARBs prevent new-onset diabetes by increasing skeletal muscle blood flow, upregulating IRS-2 mRNA expression, and inhibiting adipocyte RAAS. This leads to skeletal muscle vasodilatation, improved insulin delivery to muscle, increased IRS-2 mRNA expression, enhanced insulin signaling pathway, and differentiation of preadipocytes to smaller, more insulin-sensitive adipocytes.
What is the likely diagnosis for a 60-year-old male with T2DM presenting with acute-onset lumbar pain, haematuria, and history of passage of flakes in urine?
The likely diagnosis is acute papillary necrosis, which is indicated by the presence of necrosed papilla and the passage of flakes in urine. Common precipitating factors include urinary tract infections and drugs like NSAIDs. In patients with diabetes, factors such as accelerated atherosclerosis, increased angiotensin II, and vulnerability to urinary tract infections can predispose to papillary necrosis.
What are the modalities to preserve renal function in patients with DKD?
The modalities to preserve renal function in patients with DKD include good glycemic control (HbA1c <7%), optimal blood pressure control, use of ACEIs or ARBs, use of statins, correction of anemia, correction of metabolic acidosis, correction of secondary hyperparathyroidism, prevention of urinary tract infections, and the use of additional drugs like pioglitazone, linagliptin, and statins to reduce proteinuria.
What are the causes of hypertension in diabetes?
The causes of hypertension in diabetes include essential hypertension (in the majority of patients with T2DM), hyperinsulinemia/insulin resistance, diabetic kidney disease, renal artery stenosis, and autonomic neuropathy. Almost 50% of patients with T2DM are hypertensive at the time of diabetes diagnosis, and 80-90% of diabetics become hypertensive with the development of proteinuria.
How does insulin resistance cause hypertension?
Insulin resistance/hyperinsulinemia plays a role in the development of essential hypertension and T2DM. It increases blood pressure by promoting sodium and water reabsorption, enhancing intracellular movement of calcium, causing endothelial dysfunction, and reducing the vasodilatory effect of insulin in an insulin-resistant state.
What is the drug of choice for the management of hypertension?
The drug of choice for the management of hypertension is not specified in the provided course notes.
What is the recommended treatment for TIO?
Complete surgical excision of a well-localized tumor with wide margins is curative. If the tumor is inaccessible, radiofrequency ablation and lutetium-based therapies are other alternatives. In situations where the tumor is not localized, phosphate supplementation along with calcitriol is useful in the management of osteomalacia. Calcitriol helps in maintaining serum phosphate level by stimulating intestinal phosphate absorption and inhibiting renal phosphate wasting, which occurs as a result of phosphate therapy-induced rise in PTH. Calcimimetic agents like cinacalcet have been tried with limited success. Recently, a case report showed resolution of hypophosphatemia after total parathyroidectomy, and this opens new vistas in the management of TIO. Anti-FGF23 antibodies have been found to be effective in mouse models of hypophosphatemic osteomalacia and may be a promising alternative in the future.
What are the endocrine disorders associated with McCune–Albright syndrome?
McCune–Albright syndrome is associated with fibrous dysplasia, cafe-au-lait macules, and endocrinopathies. The common endocrine disorders include gonadotropin-independent precocious puberty, toxic nodular goiter, acrogigantism, and hypophosphatemic rickets/osteomalacia.
How does vitamin D deficiency impact fracture risk?
Vitamin D deficiency is an independent risk factor for fracture.
When should universal screening for vitamin D deficiency be recommended?
Ideally, screening for vitamin D deficiency should be done prior to vitamin D replacement. However, due to the rampant prevalence of vitamin D deficiency and its association with fracture risk, in routine clinical practice, supplementation without screening is recommended. Estimation of 25(OH)D is indicated in specific patient populations.
What are the indications for calcitriol therapy?
Calcitriol therapy is indicated in disorders associated with impaired 1α-hydroxylase activity or deficient secretion/action of PTH or increased FGF23. These include chronic kidney disease, hypoparathyroidism, pseudohypoparathyroidism, hypophosphatemic osteomalacia, renal tubular acidosis, hungry bone syndrome, and vitamin D-dependent rickets (type 1 and type 2). Elderly subjects may require calcitriol supplementation for bone health.
What is the role of PTH and FGF23 in regulating 1α-hydroxylase activity?
PTH and FGF23 are the prime regulators of 1α-hydroxylase activity. Impaired 1α-hydroxylase activity or deficient secretion/action of PTH or increased FGF23 can lead to disorders that require calcitriol therapy.
What are the alternate treatment options for TIO when the tumor is inaccessible?
When the tumor is inaccessible, radiofrequency ablation and lutetium-based therapies are other alternative treatment options for TIO.
What is the significance of hyperphosphatemia in a patient with McCune–Albright syndrome?
Hyperphosphatemia in a patient with McCune–Albright syndrome should prompt evaluation for hypersomatotropism.
What are the advantages of using HbA1c for the diagnosis of diabetes?
HbA1c has numerous advantages over blood glucose for the diagnosis of diabetes. It is a marker of chronic hyperglycemia, has greater pre-analytical stability, does not require fasting or administration of glucose load, and can be taken at any time of day.
What are the disadvantages of using HbA1c for the diagnosis of diabetes?
The disadvantages of HbA1c for the diagnosis of diabetes include lower diagnostic sensitivity, increased cost, limited utility in the presence of certain medical conditions (such as hemoglobinopathies, anemia, azotemia, and pregnancy), ethnic variability, and the need for standardization according to the DCCT/UKPDS standards.
In which patients should HbA1c not be used for the diagnosis of diabetes?
HbA1c is less reliable for the diagnosis of diabetes in patients with short duration of hyperglycemia, anemia, azotemia, hemoglobinopathies, and pregnant women.
What is considered the reference standard for the diagnosis of diabetes?
The 2-h PG post-glucose load >200mg/dl is considered the reference standard for the diagnosis of diabetes, as it best correlates with diabetic retinopathy, macrovascular disease, and HbA1c. However, it is cumbersome, has poor reproducibility, and is mainly used for research purposes.
What are the sensitivity and specificity of fasting plasma glucose compared to the reference standard for the diagnosis of diabetes?
The sensitivity of fasting plasma glucose is 50% and the specificity is 95% compared to the reference standard (2-h plasma glucose post-glucose load) for the diagnosis of diabetes.
What are the sensitivity and specificity of HbA1c (cutoff ≥6.5%) compared to the reference standard for the diagnosis of diabetes?
The sensitivity of HbA1c (cutoff ≥6.5%) is 44% and the specificity is 79% compared to the reference standard (2-h plasma glucose post-glucose load) for the diagnosis of diabetes.
How should an HbA1c of 6.2% and an FPG of 128 mg/dl be interpreted?
An HbA1c cutoff of 6.5% has a sensitivity of 44% to establish the diagnosis of diabetes, while FPG has a sensitivity of 50% in relation to the standard reference test. In this case, a repeat FPG and HbA1c should be performed. The repeat FPG was 130 mg/dl and the HbA1c was 6.3%. Therefore, the diagnosis of diabetes should be considered as 2 values of FPG are >126 mg/dl.
Who should be screened for diabetes?
Screening for type 2 diabetes is recommended in all adults who are overweight and have one additional risk factor, such as sedentary lifestyle, dyslipidemia, hypertension, cardiovascular disease, and family history of diabetes. It is also recommended in women with previous history of gestational diabetes, macrosomia, or polycystic ovarian disease. Screening is also indicated in all adults >45 years of age, irrespective of risk factors.
What is the rationale behind weekly levothyroxine therapy?
The rationale behind weekly levothyroxine therapy is based on the fact that LT4 has a half-life of 7 days. In a weekly regimen, seven times higher dose than the daily dose of levothyroxine is administered as a single dose once per week.
What was observed in the recent study comparing weekly and daily regimens of levothyroxine?
In the recent study, there was no difference in serum TSH levels achieved with both the regimens, but free T4 levels were significantly higher in the initial 4 h after administration of LT4 with a weekly regimen. However, this increase in free T4 levels was not accompanied by any symptoms of thyrotoxicosis or cardiac dysfunction.
Why is weekly regimen of levothyroxine not recommended?
The long-term safety data, particularly in elderly individuals, are not available; therefore, the weekly regimen is currently not recommended.
What are anti-mouse antibodies?
Anti-mouse antibodies, specifically human anti-mouse antibodies (HAMA), are antibodies produced in humans due to contact with animals or vaccination containing animal immunoglobulins. They are IgG in nature and interfere with TSH assays, leading to falsely high TSH value in the absence of primary thyroid dysfunction.
Why do newer TSH assays include blocking reagents like polymerized murine IgG?
Newer TSH assays include blocking reagents like polymerized murine IgG to overcome the interference caused by anti-mouse antibodies (HAMA) in the assay, which can lead to falsely high TSH values in the absence of primary thyroid dysfunction.
What is the role of iodine supplementation in patients with hypothyroidism?
Iodine supplementation in patients with hypothyroidism on levothyroxine replacement has no added advantage in improving thyroid function. However, routine iodized salt intake should be continued as iodine has many extrathyroidal advantages, including improvement in pregnancy outcome, antioxidant and anticancer properties, and suppression of autoimmunity.
What is the treatment of choice for hypothyroidism due to iodine deficiency?
Levothyroxine is the treatment of choice for hypothyroidism due to iodine deficiency. Therapeutic doses of stable iodine should be avoided in these patients to prevent Jod–Basedow’s phenomenon, as long-standing iodine deficiency may harbor thyroid nodules. Iodine supplementation in the form of iodized salt should be continued.
What is the preferred medium to deliver recommended daily allowance for iodine?
Common salt is the preferred medium to deliver the recommended daily allowance for iodine. The usual concentration of iodide in salt is 15–20 ppm (1 ppm is equivalent to 1 mg per kg). To provide the RDA of 150 μg iodine with a strength of 20 ppm, an intake of 10 g salt per day is required, which will be approximately equivalent to 150 μg of elemental iodine.
What are the pleiotropic effects of statins?
Statins have numerous pleiotropic effects including stabilization of coronary plaques, reduction in proteinuria, resolution of retinal hard exudates, increase in bone mineral density, and antioxidant/anti-inflammatory effects.
What is statin-induced myopathy?
Statin-induced myopathy is a condition where patients who receive statins experience muscle-related symptoms, such as myalgia or myositis, with elevated levels of creatine phosphokinase (CPK). Rarely, rhabdomyolysis can occur with the use of statins, characterized by extremely high CPK levels and a rise in serum creatinine.
What are the mechanisms for statin-induced myopathy?
The mechanism of statin-induced myopathy is not completely understood. However, theories propose that statins may result in mitochondrial dysfunction, depletion of isoprenoids, decrease in myocyte membrane cholesterol content, and increased expression of atrogin1, which decreases MyoD critical for muscle protein synthesis.
Who are at risk for statin-induced myopathy?
Those at risk for statin-induced myopathy include individuals with vitamin D deficiency, hypothyroidism, chronic alcoholism, older age (>80 years), strenuous physical activity, liver and renal disease, and those taking drugs like fibrates, ketoconazole, or macrolide antibiotics.
How can statin-induced myopathy be managed?
In patients experiencing mild and tolerable symptoms with CPK elevation <10-fold, statin therapy can be continued. If symptoms are intolerable and CPK elevation is <10-fold, switching to hydrophilic statins is recommended. Adequate treatment for concurrent vitamin D deficiency and hypothyroidism should be given. Discontinuation of statin therapy is necessary in case of CPK elevation >10-fold or rhabdomyolysis.
Does the use of statins cause diabetes?
Yes, the use of statins is associated with an increased incidence of new-onset diabetes. The risk of developing diabetes is dose dependent, greater in elderly individuals, and is a class effect, although some studies with pravastatin have shown a decreased risk of diabetes.
What is the estimated relative risk of developing diabetes with the use of statins?
The estimated relative risk of developing diabetes with the use of statins is 9%.
How many patients need to be treated with statins for 4 years to cause one additional case of new-onset diabetes?
A recent meta-analysis showed that 255 patients need to be treated with statins for 4 years to cause one additional case of new-onset diabetes. However, this treatment also resulted in the prevention of 5.4 cardiovascular events.
What are the extra-thyroidal manifestations of autoimmune thyroid diseases?
The extra-thyroidal manifestations of autoimmune thyroid disease include thyroid-associated orbitopathy, infiltrative dermopathy, and thyroid acropachy.
What is thyroid-associated orbitopathy?
Thyroid-associated orbitopathy (TAO) is an autoimmune disorder characterized by immuno-inflammation of the extraocular muscles and retro-orbital tissue, and invariably occurs in the presence of autoimmune thyroid disease, irrespective of presence of hyper-, hypo-, or euthyroidism.
Is there any difference between Graves’ orbitopathy and thyroid-associated orbitopathy?
Yes. The term thyroid-associated orbitopathy denotes orbitopathy associated with autoimmune thyroid disease, either Graves’ or Hashimoto’s thyroiditis, while Graves’ orbitopathy is a specific term for orbitopathy associated with Graves’ disease.
Is Graves’ ophthalmopathy and Graves’ orbitopathy synonymous?
No. Although the terms Graves’ ophthalmopathy and Graves’ orbitopathy are used interchangeably, they are not synonymous. The ocular manifestation in patients with thyroid disorder is due to involvement of retro-orbital tissue and ocular muscles. Therefore, the term “Graves’ ophthalmopathy” is a misnomer as it does not address orbital involvement in the disease process. Hence, the appropriate term should be Graves’ orbitopathy.
Why is the onset of TAO not always synchronous with the development of hyperthyroidism?
Onset of TAO can precede, follow, or may occur concurrently with hyperthyroidism in patients with Graves’ disease. Therefore, TAO and hyperthyroidism were considered as different diseases in the past. However, patients with euthyroid TAO often have subtle thyroid function abnormalities, and there is a qualitative correlation between the presence of TRAbs and the occurrence of TAO and thyrotoxicosis. Hence, it has been reconciled that both TAO and hyperthyroidism are a spectrum of the same autoimmune thyroid disease. Differential responsiveness of orbital fibroblast
What imaging features are consistent with the diagnosis of TAO?
Imaging features consistent with the diagnosis of TAO include extraocular muscle belly thickening with tendon sparing.
When is surgery indicated in patients with TAO?
Surgery is indicated only in patients with dysthyroid optic neuropathy, corneal breakdown, and globe subluxation who do not respond to glucocorticoids within 1-2 weeks.
What is the recommended duration of consistent inactivity of eye disease before rehabilitative surgeries are undertaken?
Rehabilitative surgeries are undertaken once the eye disease is consistently inactive for 6 months.
What are the criteria for using the turbo PTH assay?
The criteria for using the turbo PTH assay are young (<30 years), non-localization of an abnormal gland, and parathyroid malignancy.
How does the turbo PTH assay provide faster results compared to conventional assays?
The turbo PTH assay provides faster results by increasing the incubation temperature from 20°C to 45°C and shaking speed from 180 to 400 rpm, reducing the incubation time to 7 minutes instead of 1-2 hours.
What is the Miami criterion used for in parathyroidectomy?
The Miami criterion is used to define the success of parathyroidectomy. It requires a >50% reduction in serum PTH levels 10 minutes after excision of the suspected abnormal gland, compared to the highest pre-incision or pre-excision serum PTH level.
What is the accuracy of intraoperative PTH (IOPTH) in predicting cure for solitary adenoma and multiglandular disease?
The accuracy of IOPTH in predicting cure for solitary adenoma is 97%, while for multiglandular disease it is 58%.
What are the biochemical alterations that occur after parathyroid surgery?
After successful removal of an abnormal parathyroid gland, PTH levels decline by >50% intraoperatively and return to the reference range within 30 hours. Serum calcium decreases by 12 hours and reaches a nadir by 24-36 hours postoperatively. Serum phosphate may normalize or decline, depending on the severity of preexisting bone disease.
What is the effect of curative parathyroidectomy on bone mineral density (BMD)?
Curative parathyroidectomy results in a significant increase in BMD at the spine and hip, increasing by approximately 5-10% in the first year and continuing to increase by 12-15% over ten years. However, there is minimal or no change in BMD at the distal radius, which is predominantly composed of cortical bone.
What are the causes of hypocalcemia after parathyroidectomy?
Hypocalcemia after parathyroidectomy can occur due to hungry bone syndrome, transient hypoparathyroidism, hypomagnesemia, and permanent hypoparathyroidism. Hungry bone syndrome is the most common cause in patients with symptomatic primary hyperparathyroidism (PHPT).
What is hungry bone syndrome and how is it characterized?
Hungry bone syndrome (HBS) is characterized by the ‘increased appetite of bone’ for calcium and phosphorus, resulting from a sudden decrease in osteoclastic activity combined with continued osteoblast activity. Biochemically, it is characterized by hypocalcemia, hypophosphatemia, hypomagnesemia, raised alkaline phosphatase, and hypocalciuria.
What is diabetic embryopathy?
Diabetic embryopathy is a result of peri-conceptional uncontrolled hyperglycemia which influences organogenesis during the embryonic period.
What are some congenital anomalies associated with diabetic embryopathy?
The congenital anomalies associated with diabetic embryopathy include neural tube defects, caudal regression syndrome, transposition of great vessels, ventricular septal defect, hypoplastic left heart syndrome, renal agenesis, duodenal atresia, and hypoplastic femur.
What is the diabetes-specific defect in diabetic embryopathy?
The diabetes-specific defect in diabetic embryopathy is caudal regression syndrome (sacral agenesis).
What are the maternal risks associated with GDM?
Women with GDM have an increased risk of preeclampsia, fetal loss, difficult labor, and future risk of developing T2DM.
What are the immediate risks to the fetus associated with GDM?
The immediate risks to the fetus associated with GDM include macrosomia (>4 kg), intrauterine death (if FPG >105 mg/dl), neonatal hypoglycemia, polycythemia, hypocalcemia, and hyperbilirubinemia.
When should hyperglycemia screening be done in pregnancy?
Hyperglycemia screening should be done in every pregnant woman as early as possible (first contact visit or preferably <12 weeks) to avoid missing preexisting diabetes. Retesting is also recommended in all women between 24 and 28 weeks of gestation.
Who should be screened for hyperglycemia in the first trimester of pregnancy?
According to ADA guidelines, individuals with a high risk of having type 2 diabetes require screening at the first trimester of pregnancy. Therefore, all adult women with a prepregnant BMI >25 kg/m2 with one additional risk factor like hypertension or polycystic ovarian disease, ethnic group with high diabetes prevalence, the presence of family history of diabetes in the first-degree relatives, or personal history of abnormal glucose intolerance or bad obstetric outcome should be screened for hyperglycemia in the first trimester.
Who should be screened for hyperglycemia at 24–28 weeks of gestation?
All pregnant women require screening for hyperglycemia with an oral glucose challenge test at 24–28 weeks of gestation, except those who were diagnosed with overt diabetes (FPG ≥126 mg/dl, RPG ≥200 mg/dl, or HbA1c ≥6.5%) in the first trimester.
What are the emergencies in a patient with acromegaly?
Patients with acromegaly can present in emergency due to pituitary apoplexy, subarachnoid hemorrhage, status epilepticus, paraplegia, accelerated hypertension, diabetic ketoacidosis, gastrointestinal bleed, cardiac arrhythmias, and acromegalic cardiomyopathy.
What are the unusual signs in patients with acromegaly?
The unusual signs in patients with acromegaly include cutis verticis gyrata, facial asymmetry, tonsillomegaly, acromegalic rosary, orchidomegaly, gynecomastia, osteoma, and tarsal tunnel syndrome.
What are the causes of cutis verticis gyrata?
Cutis verticis gyrata is not a specific feature of acromegaly, but is also seen in patients with neurofibroma, pachydermoperiostitis, melanocytic nevi, myxedema, and amyloidosis.
What are the causes of headache in acromegaly?
Headache in acromegaly can be caused by increased intrasellar pressure in microadenomas, stretching of the dura in macroadenomas, calvarial thickening, osteomas, recurrent sinusitis, and secretion of putative algesic peptides by the tumor tissue.
What are the causes of macroglossia?
Causes of macroglossia include acromegaly, primary hypothyroidism, Down’s syndrome, amyloidosis, hemangioma, lymphangioma, and tongue neoplasms.
What are the oral manifestations of acromegaly?
Oral manifestations in a patient with acromegaly include prognathism, thick fleshy lips, increased spacing between teeth, malalignment of jaw, macroglossia, and tonsillomegaly.
What are the cutaneous manifestations of acromegaly?
The cutaneous manifestations in a patient with acromegaly include hyperhidrosis, seborrhea, hirsutism, acanthosis nigricans, skin tags, hyperpigmentation, and cutis verticis gyrata.
Why are hands warm and moist in patients with acromegaly?
GH promotes peripheral deiodinase activity and increases T4 to T3 neogenesis, which is responsible for the increased adrenergic sensitivity manifesting clinically as warm and moist hands. The direct effect of GH on sweat glands also contributes.
What are the causes of abdominal pain and vomiting in a patient with diabetes?
Abdominal pain and vomiting can occur in a patient with diabetes due to diabetic ketoacidosis, acute pancreatitis, acute cholecystitis, acute papillary necrosis, gastroparesis, and diabetic kidney disease. Drugs like metformin, gliptins, and GLP1 analogues may also cause abdominal pain, nausea, and vomiting in these patients.
What can mimic acute abdomen in a patient with diabetes?
Acute coronary syndrome may mimic acute abdomen in a patient with diabetes.
What are the potential causes of anemia in patients with Type 1 Diabetes Mellitus?
Patients with Type 1 Diabetes Mellitus are predisposed to various causes of anemia such as celiac disease, pernicious anemia, and autoimmune thyroid disorders.
What is the definition of gestational diabetes mellitus?
Gestational diabetes mellitus (GDM) is defined as glucose intolerance of any severity with onset or first recognition during pregnancy.
What are the limitations of the definition of GDM?
The definition of GDM, which entails glucose intolerance of any severity and first recognition during pregnancy, has limitations. It categorizes all women with hyperglycemia as GDM, even though hyperglycemia due to pregnancy is milder than hyperglycemia associated with preexisting diabetes. The differentiation between preexisting diabetes and hyperglycemia during pregnancy is important for monitoring and managing complications. Additionally, the definition does not consider the absolute numerical values of plasma glucose to define hyperglycemia during pregnancy.
What are the differences between a patient with preexisting diabetes and gestational diabetes?
Patients with preexisting diabetes have diabetes onset before conception, while gestational diabetes occurs after conception. Preexisting diabetes can be Type 2 Diabetes Mellitus or Type 1 Diabetes Mellitus, whereas gestational diabetes is characterized by transient hyperglycemia. Diabetic complications, such as microangiopathy and macroangiopathy, are more common in preexisting diabetes. Maternal and neonatal risks differ between the two conditions.
What is fuel-mediated teratogenesis?
Fuel-mediated teratogenesis refers to teratopathy occurring due to exposure of the embryo or fetus to high levels of glucose and ketones during pregnancy with diabetes. The type and severity of defects depend on the timing of exposure, with diabetic embryopathy occurring during embryogenesis and anthropometric and metabolic abnormalities occurring if the fetus is exposed to the abnormal metabolic milieu after 8 weeks of gestation.
What is the appropriate term for hyperglycemia during pregnancy instead of GDM?
The appropriate term for hyperglycemia during pregnancy is ‘hyperglycemia during pregnancy’ rather than GDM.
What is the role of bisphosphonates in the perioperative period?
Bisphosphonates should be administered, if indicated, in the perioperative period.
Why should incentive spirometry be advised in the perioperative period?
Incentive spirometry should be advised to reduce postoperative morbidity.
How should patients with Cushing’s disease be handled during shifting?
Gentle handling of the patient should be ensured during shifting to avoid fragility fracture.
Why should glucocorticoid not be administered preoperatively in patients with Cushing’s disease?
Glucocorticoid should not be administered preoperatively in patients with Cushing’s disease because it may interfere with postoperative monitoring of cortisol and may increase morbidity by exacerbating preexisting hypercortisolemia.
What is the prior medical therapy indicated for patients who are moribund and at high risk for surgery?
Prior medical therapy with ketoconazole/metyrapone/pasireotide is indicated in those who are moribund and are at high risk for surgery, to achieve rapid eucortisolemia.
Why are patients with Cushing’s syndrome predisposed to thromboembolic diseases?
Patients with Cushing’s syndrome are predisposed to thromboembolic diseases due to cortisol excess, which is associated with a procoagulant state.
What are the predictors of cure in Cushing’s disease?
The predictors of cure in Cushing’s disease are well-localized microadenoma without parasellar extension, postoperative 0800h cortisol between day 1 and 7 < 50 nmol/L (1.8 μg/dl), plasma ACTH <20 pg/ml within 24 h of surgery, histological documentation of pituitary adenoma, positive ACTH immunostaining, and prolonged requirement of glucocorticoid replacement.
Are remission and cure synonymous in Cushing’s disease?
No, remission and cure are not synonymous in Cushing’s disease. Remission refers to the resolution of signs and symptoms, while cure additionally requires restoration of diurnal rhythm of cortisol secretion, normalization of urine free cortisol (UFC), suppressibility of cortisol after overnight dexamethasone suppression test (ONDST), and stimulability with 250 μg/1 μg ACTH without the need for glucocorticoid replacement and no evidence of other pituitary hormone deficiencies.
What is the relationship between overt hypercalcemia and vitamin D deficiency in patients with PHPT?
Overt hypercalcemia occurs in patients of PHPT with concurrent vitamin D deficiency.
In patients with secondary hyperparathyroidism due to vitamin D deficiency, what happens to the PTH levels?
The PTH levels decrease/normalize without the development of hypercalcemia.
List the familial causes of PTH-dependent hypercalcemia.
The familial causes of PTH-dependent hypercalcemia are multiple endocrine neoplasia (MEN1, MEN2a, and MEN4), familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, hyperparathyroidism–jaw tumor syndrome, and familial isolated hyperparathyroidism.
What percentage of PTH-dependent hypercalcemia is contributed by familial causes?
Familial causes contribute to only 5% of PTH-dependent hypercalcemia.
What is the most common endocrine manifestation in patients with multiple endocrine neoplasia type 1 (MEN1)?
The most common endocrine manifestation in patients with MEN1 is primary hyperparathyroidism (PHPT).
What is the difference between PHPT in patients with MEN1 and sporadic PHPT?
PHPT in patients with MEN1 has an earlier age of onset (20-25 years), equal male-to-female ratio, phenotypic markers like facial angiofibromas, collagenomas, and a higher risk for hypoparathyroidism. Sporadic PHPT usually occurs after the age of 50, has a higher prevalence in females, no phenotypic markers, and a low risk for hypoparathyroidism.
When is surgery recommended for patients with PHPT and MEN1?
Surgery is recommended for symptomatic patients with PHPT and MEN1. Bilateral neck exploration is the preferred approach due to multiglandular involvement, and 3.5 gland excision is recommended.
What is hyperparathyroidism-jaw tumor syndrome (HPT-JT)?
Hyperparathyroidism-jaw tumor syndrome is an autosomal dominant disorder characterized by fibro-osseous tumors of the mandible and/or maxilla with primary hyperparathyroidism. It is associated with ossifying fibromas of the jaw, multiglandular involvement with cystic adenomas, and has a potential risk for malignancy.
How is a mass localized in the left suprarenal region?
A SPECT/CT fusion image can localize the mass to the left suprarenal region.
What is the preferred choice for further investigation if the CT abdomen fails to localize the catecholamine-secreting tumor?
The preferred choice is a 123I-MIBG scan, which has a sensitivity of 80-90% to localize the source of catecholamine excess.
What are the causes of false-negative 123I-MIBG scan?
The causes of false-negative 123I-MIBG scan are metastatic pheochromocytoma, paraganglioma (especially SDHB related), and necrotic tumors. Certain drugs like calcium channel blockers, labetalol, tricyclic antidepressants, and sympathomimetics can also interfere with 123I-MIBG uptake and cause a false-negative scan.
What is the recommended preoperative management for pheochromocytoma/paraganglioma?
Preoperative management should focus on controlling blood pressure and appropriate volume expansion. Nonselective α-blocker, phenoxybenzamine, or selective α-1 blocker, prazosin, are used for preoperative α-blockade. After achieving adequate α-blockade, salt ad lib and β-blockers should be added. Calcium channel blockers may be required if blood pressure is not controlled with α-blockers and β-blockers. The target blood pressure prior to surgery is <130/80 mmHg (seated) and systolic blood pressure >90 mmHg on standing.
In which disorders is salt ad lib recommended despite the presence of hypertension?
Salt ad lib is advocated in patients with pheochromocytoma and primary aldosteronism, regardless of the presence of hypertension. In pheochromocytoma, salt ad lib diet is required to replete the intravascular volume. In primary aldosteronism, salt ad lib improves the sensitivity of the screening test and helps identify hypokalemia.
What are the preferred anesthetic agents in pheochromocytoma/paraganglioma?
Propofol, etomidate, or barbiturates in combination with synthetic opioids are preferred as anesthetic agents in pheochromocytoma/paraganglioma.
What are the typical locations where phosphaturic mesenchymal tumors are commonly found?
Phosphaturic mesenchymal tumors are commonly located in extremities and paranasal sinuses.
What is the histological grouping of phosphaturic mesenchymal tumors?
Phosphaturic mesenchymal tumors are grouped as ‘phosphaturic mesenchymal tumors - mixed connective tissue variant (PMT-MCT)’ and include hemangiopericytomas, hemangioma, sarcoma, ossifying fibroma, and rarely osteoblastoma.
What percentage of phosphaturic mesenchymal tumors are benign?
Approximately 90% of phosphaturic mesenchymal tumors are benign.
What are the clinical clues to suspect tumor-induced osteomalacia?
Clinical clues to suspect tumor-induced osteomalacia include osteomalacia with normocalcemia, severe hypophosphatemia, normal or mildly elevated alkaline phosphatase, normal PTH and 25(OH) D levels, failure to respond to cholecalciferol/calcitriol, and worsening of hypophosphatemia after rPTH therapy initiated for osteoporosis management.
Which phosphatonin is clinically most relevant in tumor-induced osteomalacia (TIO)?
FGF23 is the clinically most relevant phosphatonin in tumor-induced osteomalacia (TIO).
What is the hallmark biochemical abnormality in tumor-induced osteomalacia?
The hallmark biochemical abnormality in tumor-induced osteomalacia is severe hypophosphatemia due to renal phosphate wasting caused by the secretion of FGF23 from mesenchymal tumors.
What is the preferred functional imaging for localizing tumors in patients with tumor-induced osteomalacia (TIO)?
Octreotide-based scintigraphy (e.g., 68Ga-DOTATATE PET-CT) is the preferred functional imaging for localizing tumors in patients with tumor-induced osteomalacia (TIO).
Why is octreotide-based scintigraphy preferred over 18F-FDG-PET for tumor localization in TIO?
Octreotide-based scintigraphy is more sensitive and specific than 18F-FDG-PET scan for the localization of tumor in tumor-induced osteomalacia (TIO) due to the low proliferative indices of these tumors and FDG uptake by metabolically active fracture sites.
What are the surrogate laboratory evidences for primary aldosteronism?
The surrogate laboratory evidences for primary aldosteronism are hypokalemia, metabolic alkalosis, hypomagnesemia, mild hypernatremia, hyperglycemia, proteinuria, U waves in ECG, and left ventricular hypertrophy.
What are the biochemical abnormalities associated with primary aldosteronism?
The biochemical abnormalities associated with primary aldosteronism are hypokalemia, metabolic alkalosis, hypomagnesemia, mild hypernatremia, hyperglycemia, and proteinuria.
What are the causes of hypokalemia in primary aldosteronism?
The causes of hypokalemia in primary aldosteronism are increased cellular exchange with sodium and potassium wasting.
What causes metabolic alkalosis in primary aldosteronism?
Metabolic alkalosis in primary aldosteronism is caused by loss of H+ into urine, shift of H+ into potassium-depleted cells, and increased bicarbonate reabsorption.
What leads to hypomagnesemia in primary aldosteronism?
Hypomagnesemia in primary aldosteronism is caused by increased tubular secretion of magnesium.
What is the effect of aldosterone on sodium reabsorption?
Aldosterone increases sodium reabsorption, leading to mild hypernatremia in primary aldosteronism.
What are the precautions required prior to investigation in a patient with primary aldosteronism?
Prior to investigation, precautions include selecting appropriate antihypertensives, salt ad lib, normalizing serum potassium, and ensuring adequate measures for blood sampling.
Which antihypertensive drugs are preferred in patients with primary aldosteronism?
The preferred antihypertensive drugs are prazosin and verapamil as they do not interfere with the renin-angiotensin-aldosterone system (RAAS).
What are the target glucose levels for fasting and post-meal in women with gestational diabetes mellitus (GDM)?
The target glucose levels for fasting is 90–130 mg/dl and for post-meal is <180 mg/dl.
What should be done with glucose-lowering therapy (insulin/OADs) immediately after delivery in patients with GDM?
Glucose-lowering therapy should be discontinued immediately after delivery in patients with GDM.
How long should blood glucose (fasting and postprandial) be monitored after delivery in women with GDM?
Blood glucose should be monitored for 24-72 hours after delivery in women with GDM.
What should be done at 6-12 weeks postpartum in women who had GDM?
Women who had GDM should be subjected to a 75-g OGTT to categorize them as normal, prediabetes, or diabetes using the standard criteria for nonpregnant adults.
What is the suggested treatment option to manage diabetes during lactation?
The best treatment option is possibly insulin. However, metformin and second-generation sulfonylureas (glibenclamide and glipizide) have been safely used in lactating women.
What is the concentration of metformin in breast milk and its effect on infants?
Metformin is secreted into breast milk in the range of 0.28-1.08%, but this concentration is too low to have any detrimental effects on the infant. The use of metformin had no adverse effect on infant growth and motor and social development during the first 6 months of life.
Which antidiabetic medications are extensively bound to circulating proteins and not secreted into breast milk?
Glibenclamide and glipizide are extensively bound to circulating proteins and hence not secreted into breast milk.
Is there data available regarding the use of glimepiride or gliclazide during lactation?
No, there is no data available regarding the use of glimepiride or gliclazide during lactation.
What is the suggested reading for Acromegaly: Diagnosis and Treatment?
Suggested Reading. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
What is the clinical round mentioned in the notes for Acromegaly?
Clinical Rounds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
What is the suggested reading for Hyperprolactinemia?
Suggested Reading. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
What is the case vignette mentioned in the notes for Hyperprolactinemia?
Case Vignette . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
What is the stepwise analysis mentioned in the notes for Hyperprolactinemia?
Stepwise Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
What is the clinical round mentioned in the notes for Hyperprolactinemia?
Clinical Rounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
What is the suggested reading for Cushing’s Syndrome: Clinical Perspectives?
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
What is the case vignette mentioned in the notes for Cushing’s Syndrome: Clinical Perspectives?
Case Vignette . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
What are the illicit stimulators in ACTH-independent macronodular adrenal hyperplasia?
The illicit stimulators in ACTH-independent macronodular adrenal hyperplasia include arginine vasopressin, glucose-dependent insulinotropic peptide, beta-adrenergic agonist, LH/hCG, serotonin, leptin, and angiotensin II.
What is the exact pathogenesis of ACTH-independent macronodular adrenal hyperplasia (AIMAH)?
The exact pathogenesis of ACTH-independent macronodular adrenal hyperplasia is not known, but it is believed to be a result of overexpression or ectopic expression of receptors for peptide hormones/amines on adrenocortical cells.
What has been reported to cause ACTH-independent macronodular adrenal hyperplasia?
Mutations of a putative tumor suppressor gene, armadillo repeat containing 5 (ARMC5), have been reported to cause ACTH-independent macronodular adrenal hyperplasia.
What are the alterations in cortisol dynamics during pregnancy?
During pregnancy, cortisol levels are high, dexamethasone test is non-suppressible, and UFC (urine free cortisol) and ACTH levels are mildly elevated. The circadian rhythm of cortisol secretion is preserved, with higher levels overall.
When should Cushing’s syndrome be suspected in pregnancy?
Cushing’s syndrome should be suspected in pregnancy when distinctive features such as proximal myopathy, maternal weight gain with fetal intrauterine growth retardation, worsening of glycemic control, and hypertension are present.
How is the diagnosis of Cushing’s syndrome in pregnancy established?
The diagnosis of Cushing’s syndrome in pregnancy is established by measuring urine free cortisol (UFC). A UFC value more than three times the upper limit of normal is diagnostic of Cushing’s syndrome.
What is the common cause of Cushing’s syndrome during pregnancy?
The common cause of Cushing’s syndrome during pregnancy is adrenal adenoma, followed by Cushing’s disease. Even in patients with adrenal adenoma, plasma ACTH levels are measurable due to the stimulatory effect of placental CRH on the maternal HPA axis.
What is an adrenal incidentaloma?
An adrenal incidentaloma is an adrenal mass larger than 1 cm that is incidentally detected on imaging during evaluation for a reason unrelated to adrenal disorder, excluding those detected during cancer staging.
What is persistent or recurrent PHPT?
Persistent PHPT is defined as hypercalcemia that either persists or recurs within 6 months of parathyroid surgery. Reappearance of hypercalcemia after 6 months of curative parathyroid surgery is termed as recurrent PHPT.
What are the causes of persistent/recurrent PHPT?
The causes of persistent/recurrent PHPT include failure to localize abnormal parathyroid gland intraoperatively, incomplete excision of adenoma, multiglandular disease (familial syndromes), ectopic parathyroid adenoma, and rarely parathyroid carcinoma.
What is the role of preoperative imaging in patients with recurrent/persistent PHPT?
Preoperative localization is mandatory prior to any surgical intervention. USG neck and 99mTc-sestamibi-SPECT scintigraphy are recommended as the initial imaging modalities. If the results are concordant, accuracy of this combined approach is 90%, and no further investigation is required.
Which imaging modalities are helpful in localizing ectopic lesion in the mediastinum?
CT and MRI are helpful in localizing ectopic lesion in the mediastinum with a sensitivity of 46–87%.
What is the sensitivity of USG-guided FNAC in the diagnosis of parathyroid lesion?
USG-guided FNAC of suspected lesion with assessment of tissue PTH level has a sensitivity of 87% in the diagnosis of parathyroid lesion.
When should patients with recurrent/persistent PHPT be treated surgically?
Indications for surgery are essentially the same as in surgically naive patients. All symptomatic patients should be subjected to surgery. Those with non-localization or discordant results on USG and MIBI should undergo further imaging, and failure to localize warrants bilateral neck exploration.
What is the surgical cure rate in patients with recurrent/persistent PHPT?
Surgical cure rate is 85–90% in patients with recurrent/persistent disease as compared to 95–97% in surgically naive patients.
Why should asymptomatic patients with recurrent/persistent hyperparathyroidism be kept under regular surveillance?
Patients with recurrent/persistent hyperparathyroidism who are asymptomatic or who have mild disease should be kept under regular surveillance. This is because of difficulties associated with redo surgery due to distorted neck anatomy, higher risk of recurrent laryngeal nerve injury, and hypocalcemia.
Who should be screened for osteoporosis?
Screening for osteoporosis is recommended in individuals who have a high risk for fragility fracture. The indications as recommended by the National Osteoporosis Foundation are summarized in the table given below.
What are the indications for BMD measurement in osteoporosis screening?
The indications for BMD measurement in osteoporosis screening are: all women ≥65 years or men ≥70 years, younger postmenopausal women, perimenopausal women, and men aged 50–69 with clinical risk factors for fracture, and adults with fracture after the age >50 years or disorders and/or drugs associated with osteoporosis.
Why is there a need for a fracture prediction tool?
The occurrence of fragility fracture is not solely dependent on decreased bone mineral density, but is rather a culmination of multiple risk factors. Hence, there is a need to devise a comprehensive tool to precisely predict the fracture risk in an individual.
What are some important risk factors for fragility fracture?
Some important risk factors for fragility fracture include advanced age, female sex, low body weight, past/family history of fracture, visual impairment, neuromuscular dysfunction, smoking, alcohol, and use of glucocorticoids.
What is the FRAX score used for?
The FRAX score is a web-based algorithm designed to calculate the 10-year probability of a major osteoporosis-related fracture or hip fractures alone. It is applicable for both men and women.
What are the risk factors used for fracture prediction in the FRAX score?
The risk factors used for fracture prediction in the FRAX score include body weight, previous history of fracture, history of hip fracture in parents, current smoking, use of glucocorticoids, rheumatoid arthritis, alcohol use, and secondary osteoporosis.
What are the advantages of the FRAX score?
The advantages of the FRAX score include being inexpensive, convenient, easy to use, and comprehensive. It also takes into account the effect of race and ethnicity for the assessment of fracture risk.
What are the limitations of the FRAX score?
The limitations of the FRAX score include not considering independent risk factors like number of falls, visual impairment, neuromuscular dysfunction, vitamin D deficiency, and physical inactivity. It also cannot assess fracture risk in individuals aged <40 or >90 years and is not validated for monitoring therapeutic response.
What are some causes of bilateral pheochromocytoma?
The causes of bilateral pheochromocytoma are MEN2A, MEN2B, von Hippel–Lindau disease, and familial paraganglioma syndrome like SDHB and SDHD mutations.
Do bilateral pheochromocytomas occur in all familial syndromes?
No, some familial syndromes like NF1-related pheochromocytoma are usually unilateral and not associated with bilateral pheochromocytoma.
What is the hormone secretory pattern of pheochromocytomas?
Catecholamine-secreting tumors originating from the adrenal gland can secrete both epinephrine and norepinephrine.
Can functional paragangliomas secrete epinephrine?
No, functional paragangliomas can only secrete norepinephrine. They lack the enzyme PNMT required for the conversion of norepinephrine to epinephrine.
What are the characteristic features of pheochromocytoma associated with multiple endocrine neoplasia type 2 (MEN2)?
MEN2-related pheochromocytomas are always adrenal, predominantly secrete epinephrine, and are almost never malignant.
What is von Hippel–Lindau disease?
Von Hippel–Lindau disease is an autosomal dominant disorder characterized by bilateral pheochromocytoma and/or paraganglioma, nonfunctioning pancreatic islet cell tumor, hemangioblastomas of cerebellum, brainstem or spinal cord, retinal angiomas, and clear cell renal cell carcinoma.
Why does pheochromocytoma associated with VHL predominantly produce norepinephrine?
Patients with VHL having bilateral pheochromocytomas predominantly produce norepinephrine due to the under-expression of the enzyme PNMT.
What are the characteristics of TMEM127 and MAX mutation-associated PPGL?
TMEM127 and MAX mutation-related catecholamine-secreting tumors are familial in origin, present at a later age (40–50 years), and have mutations in the TMEM127 and MAX genes.
What are the potential causes of the increase in the incidence of T1DM?
The increase in the incidence of T1DM may be partially attributed to the hygiene hypothesis and the accelerator hypothesis.
What is the hygiene hypothesis?
The hygiene hypothesis proposes that improvements in living conditions result in a lack of early exposure to pathogens, leading to inadequate maturation of the immune system and increased predisposition to autoimmune disorders, including T1DM.
What is the accelerator hypothesis?
The accelerator hypothesis suggests that there is an enhanced immuno-inflammatory destruction of β-cells in response to increased insulin resistance associated with obesity.
Which HLA loci are protective for T1DM?
The HLA loci DRB11501, DQA10102, DQ6, and DRB1*1401 are protective for T1DM, although their presence may not confer protection in all cases.
How does obesity predispose to T1DM?
Obesity increases the risk of developing T1DM by accelerating the immuno-inflammatory destruction of β-cells through insulin resistance and the release of adipocytokines (IL6 and TNFα).
What is the term used to describe the combination of type 1 diabetes with insulin resistance?
The combination of type 1 diabetes with insulin resistance is known as ‘double diabetes’.
What are some animal models of T1DM?
Some animal models of T1DM include the Nonobese diabetic (NOD) mouse, BioBreeding (BB) rat, Long–Evans Tokushima Lean (LETL) rat (spontaneous models), and streptozotocin- or alloxan-induced diabetic Wistar rat (induced models).
What is a ‘pseudoatrophic’ islet?
In patients with long-standing T1DM, the selective destruction of β-cells eventually leads to the disappearance of β-cells and the infiltrates, leaving behind clumps of islet containing α-cells, which are termed as ‘pseudoatrophic’ islets.
What are the distinctive features of T1DM?
The distinctive features of T1DM are young age of onset, absolute insulin deficiency, and presence of islet autoimmunity.
What are the causes of PHPT?
A single parathyroid adenoma accounts for approximately 80–85% of patients with PHPT, and double adenomas are found in 4–5%. Multiple gland hyperplasia contributes to approximately 10% of patients with PHPT, while parathyroid carcinoma is rare (<1%).
Is there any correlation between clinical phenotype and histology of parathyroid adenoma in patients with PHPT?
Most parathyroid adenomas or hyperplasia arise from chief cells. Rarely (3%) adenomas can arise from oxyphil cells which are usually larger than chief cell adenomas and have modestly elevated PTH. Clear cell adenomas are rare with anecdotal case reports.
Why is PHPT a disease of postmenopausal women?
Postmenopausal state is characterized by estrogen deficiency. Estrogen inhibits the action of PTH by interfering with post-receptor signaling (cAMP-dependent protein kinase) and antagonizes cytokine-mediated bone resorption. Hence, estrogen deficiency in postmenopausal state leads to unopposed PTH action, thereby unmasking PHPT. In addition, estrogen deficiency may have a role in parathyroid tumorigenesis.
What are the mechanisms implicated in parathyroid tumorigenesis?
The exact pathogenesis of parathyroid tumorigenesis is still elusive, but it seems to be multifactorial in origin, except in familial syndromes where exact mutation can be detected. Sporadic PHPT accounts for 95% of patients and harbors single or double adenoma, while the rest are contributed by familial syndromes and usually have parathyroid hyperplasia.
Why is inferior parathyroid gland more likely to be ectopic?
Parathyroid glands are endodermal in origin and develop from the pharyngeal pouch. Superior parathyroid glands originate from the fourth pharyngeal pouch, while inferior parathyroid glands from the third pharyngeal pouch. Because inferior parathyroid glands have to travel a longer distance as compared to superior parathyroid glands, they are more likely to be ectopic in location.
Why is there a differential effect of parathyroid hormone on cortical and cancellous bone?
The skeletal tissue is composed of cortical and cancellous bone in varying proportions. PTH has an anabolic effect on cancellous bone and resorptive effect on cortical bone.
What is the preferred insulin for CSII therapy?
The preferred insulin for CSII therapy is regular or rapid-acting analogues.
Why are rapid-acting analogues preferred for CSII therapy?
Rapid-acting analogues are preferred for CSII therapy because they are monomeric and have a favorable pharmacokinetic profile, resulting in better glycemic control.
