Lecture 4 - Repro Endo Disease 2023-3 (Student Update) PDF

Reproductive and Endocrine Disease Shuo Xiao, PhD Office: EOHSI, 406 Tel: 848-445-3729 Email: [email protected] The whole picture of the Reproductive and Endocrine System • Lecture 1: Male and female reproductive diseases • Lecture 2: Diseases in pituitary, thyroid, and parathyroid • Lecture 3:...

Reproductive and Endocrine Disease Shuo Xiao, PhD Office: EOHSI, 406 Tel: 848-445-3729 Email: [email protected] The whole picture of the Reproductive and Endocrine System • Lecture 1: Male and female reproductive diseases • Lecture 2: Diseases in pituitary, thyroid, and parathyroid • Lecture 3: Diseases in adrenal gland, pancreas, and others https://anatomy-medicine.com/endocrine-system/ Adrenal gland physiology (Mineralocorticoid) • • A pair of glands sitting on the top of kidneys, two embryologically distinct tissues merged during development; The adrenal medulla secretes catecholamines (epinephrine), and the cortex secretes steroid hormones: aldosterone (mineralocorticoid), glucocorticoids, and sex hormones; Steroidogenesis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365799/ The HPA axis Adrenal pathology (Mineralocorticoid) • Hyperadrenalism o Hypercortisolism (Cushing syndrome) o Hyperaldosteronism o Adrenogenital or virilizing syndrome • Hypoadrenalism o Primary hypoadrenalism o ACTH deficiency Adrenal pathology – Hyperadrenalism (hypercortisolism) Corticotroph adenoma Adrenal pathology – Hyperadrenalism (hypercortisolism) • Morphologic changes in adrenal gland o Cortical atrophy o Diffuse hyperplasia o Micro- or macro-nodular hyperplasia o Adenoma (carcinoma causes virilization) ACTH dependent ACTH independent Adrenocortical adenoma Adrenocortical carcinoma Adrenal pathology – Hyperadrenalism (hyperaldosteronism) • Primary hyperaldosteronism o o o o ACTH dependent ACTH independent Renin-angiotensin independent Bilateral idiopathic hyperaldosteronism Adrenocortical neoplasm (adenoma is common) Familial hyperaldosteronism (CYP11B2) • Secondary hyperaldosteronism o Renin-angiotensin dependent o Decreased renal perfusion (arteriolar nephrosclerosis, renal artery stenosis) o Pregnancy (E2 increases the plasma renin) • Hypertension (the most important clinical symptom) o Cause 5-10% hypertensive individuals o Associated with risks of heart failure, stroke Adrenal pathology – Hyperadrenalism (adrenogenital syndrome) Congenital adrenal hyperplasia (CAH) Increase or decrease? • Also termed virilization, caused by the androgen excess in the gonad or adrenal gland; • Adrenal androgen is regulated by ACTH (gonad?), so usually together with the Cushing syndrome; • Androgen excess can be caused by adrenocortical neoplasms and congenital adrenal hyperplasia (CAH); • Adrenocortical neoplasm with high androgen usually indicate a higher chance of carcinoma; • Congenital adrenal hyperplasia (CAH) is caused by 21-hydroxylase (CYP21A2) deficiency (>90%); • • Female: masculinization (clitoral hypertrophy, pseudohermaphroditism in infants, oligomenorrhea, hirsutism, and acne in adults) Male: fertile but enlargement of the external genitalia • Treatments: surgery, cortisol ACTH dependent ACTH independent Aldosterone Adrenal pathology (Mineralocorticoid) • Hyperadrenalism o Hypercortisolism (Cushing syndrome) o Hyperaldosteronism o Adrenogenital or virilizing syndrome • Hypoadrenalism o Primary hypoadrenalism o ACTH deficiency (surgery, radiation, infection, tumor in hypothalamus or pituitary) Adrenal pathology – Acute/chronic adrenocortical insufficiency • Acute adrenocortical insufficiency o Massive adrenal hemorrhage caused extensive cortical destruction, during post-operative patients receiving anticoagulant therapy or in patients experiencing sepsis (Waterhouse Friderichsen syndrome, more common in children) ACTH dependent Acute adrenocortical insufficiency in patients with COVID19 • Chronic adrenocortical insufficiency (Addison disease) o Autoimmune adrenalitis (70-90%): AIRE mutation causes autoimmune polyglandular syndromes (APS); ACTH independent o Infections: TB, AIDS o Metastatic cancer AIRE: Autoimmune regulator https://www.ajtmh.org/view/journals/tpmd/103/4/article-p1604.xml Multiple endocrine neoplasia (MEN) syndromes • Major glands affected o o o o o Pituitary Thyroid Parathyroid Adrenal Pancreas • MEN1 o Mutation of MEN1 (Menin 1) gene o Parathyroid: the first affected gland, hyperparathyroidism, high calcium, kidney stones/damage o Pituitary: prolactinoma (phenotype?) o Pancreas: gastrinomas, insulinoma, leading cause of death • MEN2A/B o Medulla thyroid cancer (MTC) with or without parathyroid adenoma and neuromas o Mutation of RET (Ret Proto-Oncogene) gene is share by type 2A and 2B https://anatomy-medicine.com/endocrine-system/ The whole picture of the Reproductive and Endocrine System • Lecture 1: Male and female reproductive diseases • Lecture 2: Diseases in pituitary, thyroid, and parathyroid • Lecture 3: Diseases in adrenal gland, pancreas, and others https://anatomy-medicine.com/endocrine-system/ Pancreas and diabetes Prediabetes Diabetes Fasting plasma glucose 100-125 mg/dL >126 mg/dL Random plasma glucose 140-199 mg/dL >200 mg/dL Glycated hemoglobin (HbA1c) 5.7-6.4% >6.5% • Type I: 5-10%, < 20 years, immunological destruction of b cells, insulin deficiency; • Type II: > 95%, with overweight/obesity, insulin resistance and insulin deficiency • 11% of the population in the US; ¼ are unaware of the hyperglycemia; 1.4 million new cases per year; Pancreas and diabetes Obesity and type II diabetes Learning Objectives/Outline • Male and female reproductive system anatomy and biology • Male reproductive diseases o Cryptorchidism o Testicular tumor • Female reproductive diseases o Premature ovarian insufficiency / failure (POI/POF) o Polycystic ovarian syndrome (PCOS) o Ovarian tumor o Endometriosis o Endometrial hyperplasia and neoplasia Female – Polycystic Ovarian Syndrome (PCOS) • 10 - 15% incidence in adolescent and reproductive aged women • Symptoms: hyperandrogenism, anovulation, polycystic ovary (infertility, irregular period, obesity, diabetes …) https://www.nejm.org/doi/full/10.1056/NEJMcp1514916 Female – Polycystic Ovarian Syndrome (PCOS) Luteinized or hyperplasia of theca cells https://www.nejm.org/doi/full/10.1056/NEJMcp1514916 PCOS Etiology • Unknown • Defective HPG control • Genetic mechanisms • Environmental exposure (gestational exposure to high androgen) • …… https://www.thelancet.com/journals/lancet/article/PIIS0140673607613452 The whole picture of the Reproductive and Endocrine System • Lecture 1: Male and female reproductive diseases • Lecture 2: Diseases in pituitary, thyroid, and parathyroid • Lecture 3: Diseases in adrenal gland, pancreas, and others https://anatomy-medicine.com/endocrine-system/