Endo

Diabetes Mellitus

• Cataracts are a key presentation, showing clouding of the lens and trouble with both near and far sightedness in poorly controlled diabetes.
• Hyperglycemia increases sorbitol production via aldose reductase, leading to cellular damage through osmotic principles.

Insulin

• Insulin is cleared renally and hepatically.
• Decreased renal clearance of insulin because of CKD may result in hypoglycemia if dosages aren't adjusted.
• Type 2 diabetes treatment should mimic insulin release by using rapid-acting insulin after meals, with a long-acting dose daily for baseline secretion.
• Visceral obesity (increased waist circumference) indicates insulin resistance.

Pancreatic Beta Cell Receptors

• Muscarinic M3, glucagon, Beta-2 adrenergic, and glucagon-like peptide-1 receptors stimulate insulin release.
• Alpha-2 adrenergic receptors and somatostatin 2 inhibit insulin release.
• Alpha-2 adrenergic receptors modulate sympathetic activation, but only decrease insulin secretion without fully stopping the sympathetic nervous system.

Glucose Transporter Protein

• GLUT4 is the only insulin-dependent glucose transporter.
• GLUT4 is found in skeletal myocytes and adipocytes.

Diabetic Kidney Disease

• Early screening involves checking for albumin because glucose is expected in urine due to hyperglycemia.
• ACE inhibitors and ARBs are the preferred treatments for BP control because of their antiproteinuric effects, which prevent kidney disease.

Diabetes Treatments

• Metformin inhibits mitochondrial glycerol-3-phosphate dehydrogenase, reducing available substrates for gluconeogenesis, with lactic acidosis as a complication for individuals with renal insufficiency.
• Sulfonylureas close K+ channels in pancreatic beta cells to increase insulin secretion by causing cell depolarization that releases calcium.
  • Examples of first generation sulfonylureas are chlorpropamide and tolbutamide.
  • Examples of second generation sulfonylureas are glipizide and glyburide.
  • Meglitinides (nateglinide, repaglinide) share the same mechanism of action and commonly cause hypoglycemia.
• Alpha-Glucosidase Inhibitors
  • They inhibit alpha-glucosidase, a brush border enzyme that hydrolyzes carbohydrates, facilitating glucose absorption.
  • Examples include acarbose and miglitol.
• Pioglitazone stimulates PPAR-gamma.
• Dipeptidyl peptidase-4 (DPP-4) inhibitors
  • Examples include medications ending in "-gliptin."
  • They inhibit the DPP-4 enzyme that deactivates GLP-1 and promote the release of endogenous insulin.

Weight-Favorable Antidiabetic Medications

• GLP-1 agonists and SGLT-2 inhibitors are weight-loss medications.
• DPP-4 inhibitors and metformin are weight-neutral.

Type 1 Diabetes

• Type 1 Diabetes Presentation shows polyuria, polydipsia, and weight loss.
• An A1c test is used to diagnose Type 1 Diabetes.

Hypothyroidism

• Congenital goiter presentation exhibits increased TSH, low T4, and an enlarged thyroid gland.
• Transplacental passage of antithyroid medications & thyroxine (T4) causes congenital goiter as the baby uses the mother's T4.
• In Graves' disease, TSH levels won't be elevated because of feedback inhibition.
• A pituitary tumor is indicated by high T3, T4, and TSH levels.

Congenital Hypothyroidism

• The presentation includes a "floppy" baby, hypotonia, large anterior fontanelle, large tongue (macroglossia), and reducible umbilical hernia.

Hyperprolactinemia

• Decreased GnRH causes vaginal dryness, atrophy, hypogonadism, anovulation, and amenorrhea

Parathyroid Hormone (PTH)

• PTH increases calcium and vitamin D levels while reducing phosphorus levels.
  • Intermittent exposure to PTH results in bone formation (increased osteoblasts).
  • Chronic exposure to PTH triggers bone resorption (osteoblast transformation into osteoclasts).

Glucagon

• Glucagon rapidly induces glycogenolysis (primary) and slowly induces gluconeogenesis (secondary).

Thyrotropin-Releasing Hormone (TRH)

• TRH originates from the hypothalamus.
• TRH stimulates the anterior pituitary to release TSH and prolactin.

SGLT-2 Inhibitors Pharmacology

• SGLT-2 inhibitors have names ending in "-flozin".
• SGLT-2 inhibitors block SGLT-2, a sodium-glucose cotransporter in the nephron's proximal tubule.
• Before starting SGLT-2 inhibitors, kidney function (creatinine) should be tested.
• SGLT-2 inhibitors' mechanism relies on proper kidney function for filtration in the PCT to work, resulting in less glucose.
• SGLT-2 inhibitors result in increased urinary glucose excretion, decreased total body sodium, and decreased extracellular fluid volume.

Dopamine Agonists

• Cabergoline is an example of a dopamine agonist.
• Dopamine agonists are used for prolactinoma to decrease prolactin levels and improve related symptoms.

Insulin Types

• Rapid-acting insulins (no lag): Lispro, Aspart, Glulisine
• Short-acting insulins: Regular
• Intermediate-acting insulins: NPH
• Long-acting insulins: Detemir, Glargine
• Very long-acting insulins: Degludec

Stress Hyperglycemia

• Stress Hyperglycemia is hyperglycemia following a severe illness in individuals without pre-existing diabetes.
• Stress-induced cortisol and catecholamine release causes the liver to increase glucose production through glycogenolysis and gluconeogenesis.

Hyperthyroidism

• Beta-blockers are used in hyperthyroidism to inhibit T4 to T3 conversion via 5'-deiodinase.

Thyroiditis

• Postpartum thyroiditis presents with thyroid problems within one year of childbirth.
• The disease course starts with hyperthyroidism, progresses to hypothyroidism, and eventually returns to a euthyroid state.
  • The hyperthyroid phase stems from the release of preformed thyroid hormones.
  • The hypothyroid phase stems from the depletion of thyroid hormone stores.
• De Quervain Thyroiditis (Subacute granulomatous thyroiditis) presents with painful thyroid enlargement, typically after a viral illness.
• A biopsy shows a mixed inflammatory infiltrate of macrophages and multinucleated giant cells.

Parathyroid Disease

• Primary Hyperparathyroidism is associated with high calcium and low phosphate levels, as well as a decreased reabsorption of phosphate in the proximal tubules, osteitis fibrosa cystica, and osteoporosis.
  • Main causes include parathyroid adenoma (most common), parathyroid hyperplasia, and parathyroid carcinoma.

Secondary Hyperparathyroidism

• Secondary Hyperparathyroidism is associated with high PTH, low calcium, and high phosphate, as kidney dysfunction impairs phosphate excretion.
  • Causes include vitamin D deficiency, decreased calcium intake, CKD, and osteomalacia (adults).
• A defective mineralization of osteoid, caused by vitamin D deficiency produces Rickets (children).
• Defective mineralization of cartilaginous growth plates, caused by vitamin D deficiency also produces Rickets (children).

Hypoparathyroidism

• Thyroid surgery is the most common cause.
• Hypocalcemia is the most significant lab finding because PTH is essential for maintaining calcium levels.
  • Signs: Chvostek's sign (facial muscle twitching upon tapping the cheek) and Trousseau's sign (hand/wrist contractions with BP cuff).

Hyperaldosteronism

• Lab findings include hypertension, high sodium, low potassium, metabolic alkalosis (due to H+ secretion), and decreased renin (negative feedback).

Obesity Hormones

• Ghrelin is secreted in the stomach and increases feelings of hunger.
• Leptin is secreted from adipose tissue and increases feelings of fullness.
• Insulin, secreted from the pancreas, regulates glucose metabolism and induces feelings of fullness.
• Losing body fat: Leptin and Insulin decrease, and Ghrelin increases.

Anterior Pituitary Cells

• Lactotrophs produce prolactin and can cause prolactinoma.
• Somatotrophs produce GH and can cause acromegaly or gigantism.

Adrenal Insufficiency

• Adrenal Crisis presentation includes abdominal pain, vomiting, shock (low BP, high HR), low blood sugar, autoimmune disease, and hyperpigmentation.
  • Adrenal Crisis treatment involves intravenous fluids and steroids (dexamethasone or hydrocortisone).
• Addison's Disease (Primary Adrenal Insufficiency)
  • Addison's Disease Presentation includes hyperpigmentation (due to increased ACTH and MSH) and weight loss.
  • Physiological stress can trigger adrenal crisis which can be fatal.
  • A lack of cortisol response to ACTH administration (when cortisol is not already high) indicates Addison's disease.

Gynecomastia

• Hormonal imbalance during puberty causes unilateral or bilateral gynecomastia in adolescent boys.
• This condition is benign and typically resolves within a year.

Maturity-Onset Diabetes in the Young (MODY)

• Maturity-Onset Diabetes in the Young (MODY) is a genetic form of diabetes with onset later in life.
• Glucokinase deficiency is the cause.

Acute Hyponatremia

• Too much fluid intake causes hypervolemic hyponatremia and may affect runners who gain weight during a race.

Multiple Endocrine Neoplasia

• Type 1: Mutation in the MEN1 gene on Chromosome 11.
  • This may lead to Pituitary, pancreatic, and parathyroid tumors
• Type 2: Mutation in the RET gene on Chromosome 10.
  • Type 2A may result in parathyroid tumor, medullary thyroid carcinoma, and pheochromocytoma
  • Type 2B may result in medullary thyroid carcinoma, pheochromocytoma, and mucosal neuromas

Pheochromocytoma

• Definition: Cancer of the medulla of the adrenal gland.
• Presentation: The 5 Ps: Pressure (increased BP), Pain (headache), Perspiration (sweating), Palpitations (tachycardia), Pallor (whiteness to the skin).
• Labs: Increased catecholamines and metanephrines.

Iodine Uptake

• Thyroid tissue is the only tissue that uptakes iodine during radioactive iodine administration.

Acromegaly

• Acromegaly involves metabolic changes, including increased GH and insulin-like growth factor-1 (IGF-1), which causes deranged glucose homeostasis.
  • GH opposes insulin, causing insulin resistance in fat and muscle tissues.
  • GH stimulates the liver to release more glucose (increased hepatic gluconeogenesis).

Changes in Hormones with Aging

• Testosterone decreases in men as they age, stimulating the hypothalamic-pituitary axis to increase GnRH, FSH, and LH secretion.