L7 Clinical Chemistry

🧠 Concepts Introduced

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Intro to Clinical Endocrinology

LEARNING OUTCOME: To understand the basics of endocrine system To outline some endocrine disorders, their diagnosis and treatments

Fundamentals & Clinical Importance

cuz two patients can have identical symptoms but have different diseases but some hormone levels will be different.

Definition

Clinical endocrinology is a branch of patient-centered medicine study that focuses on the diagnosis and treatment of distant hormone-related disorders

ENDOCRINE SYSTEM A network of glands and organs that produce, store, and secrete hormones chemical messengers that regulate essential functions of distant tissues

HORMONE A biochemical messenger molecule produced by specialized cells or glands in an organism, which is released into the bloodstream or other bodily fluids to regulate specific physiological processes

Modes of SecretionChemical Signaling

Autocrine hormones bind to receptors on the cell that produces them. Eg. IL-2, TNFalpha

Paracrine (close by) hormones are secreted into the interstitial space and generally have a very short half life. Eg. Prostaglandins, neurotransmitters

Endocrine (distant) hormones are secreted into the bloodstream, generally have a longer half life

L2 Human Physiology#Chemical signaling between cellls

Hormones in other bodily fluids

Cerebrospinal Fluid (CSF): Certain neurohormones produced by the hypothalamus, like corticotropin-releasing hormone, can be detected in CSF, where they play a role in brain signaling and regulation

Saliva: Some steroid hormones, such as cortisol and testosterone, can diffuse from the blood into saliva. Saliva testing is often used to measure these hormones for diagnostic purposes

Urine: Hormones or their metabolites, like estrogen, progesterone, and human chorionic gonadotropin (hCG), can be excreted in urine. Urine tests for hCG, for example, are commonly used for pregnancy testing

Amniotic Fluid: During pregnancy, various hormones, including hCG and progesterone, are found in amniotic fluid and play a role in fetal development

Classification of Endocrine Hormones

Protein Hormones: Composed of amino acids, water-soluble, bind on membrane receptors

• Insulin
• glucagon
• parathyroid hormone (PTH)
• growth hormone (GH)
• prolactin
• oxytocin
• antidiuretic hormone (ADH)
• follicle-stimulating hormone (FSH)
• luteinizing hormone (LH)

Steroid Hormones: Derived from cholesterol, lipid-soluble and can easily pass through cell membranes to bind intracellular receptors

• Cortisol
• aldosterone
• testosterone
• estrogen
• progesterone
• vitamin D

Amine Hormones: Derived from single amino acid, mainly tyrosine or tryptophan, binding on receptor site is dependent on types of amine hormones

Hypothalamic-Pituitary Axis & Feedback Mechanisms

Hypothalamus and Pituitary

Negative feedback

here the only positive feedback

Adrenal Gland Anatomy & Physiology

Adrenal Gland Anatomy

Steroid Biosynthesis Pathway

Conversion from cholesterol to mineralocorticoids, glucocorticoids, and androgens

Functions of Adrenal Hormones

Glucocorticoid functions

• Promotes appetite & good mood

• Promotes gluconeogenesis & glycogen synthesis

• Promotes centripetal fat redistribution

• Inhibits inflammation

• Increases LDL and decreases HDL

• Promotes insulin resistance

Mineralocorticoid functions

• Sodium retention

• Potassium excretion

• Hydrogen ion excretion

Renin-Angiotensin-Aldosterone System (RAAS)

Mineralocorticoid: Aldosterone

renin is an enzyme produced by the juxtaglomerular apparatus of the kidney

Juxtaglomerular cell

Hypothalamic-Pituitary-Adrenal (HPA) Axis Regulation

Cortisol synthesis and release is controlled by the hypothalamicpituitary-adrenal (HPA) axis

Hypothalamus:

• The paraventricular nucleus of the hypothalamus responds to stress, exercise, and low blood sugar (hypoglycemia) by releasing corticotropin-releasing hormone (CRH) into the hypothalamicpituitary portal system

Pituitary Gland

• CRH stimulates the anterior pituitary gland to release adrenocorticotropic hormone (ACTH)

Additional Stimuli for ACTH Release:

• Proinflammatory cytokines and antidiuretic hormone (ADH) can also promote ACTH release from the anterior pituitary, though to a lesser degree than CR

Adrenal Disorders

Adrenal Insufficiency & Hypocortisolism

​Etiology & Types: Primary (Addison Disease), Secondary, Tertiary

Glucocorticoid vs. Mineralocorticoid deficiency

Hypercortisolism (Cushing Syndrome)

​ACTH-dependent vs. ACTH-independent causes

​Clinical signs and complications

Medical Treatment Strategies

Management of Cushing Syndrome

​Hormone replacement therapy for Addison Disease

Endocrine Diagnostics & Dynamic Testing

Hormone Measurement Methods

Immunoassays

High-Performance Liquid Chromatography with UV (HPLC-UV)

​Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Diurnal Variation & Patient Preparation

​Cortisol and aldosterone diurnal rhythms

​Postural impacts on aldosterone blood collection

Dynamic Tests for Adrenal Function

​ACTH Stimulation Test

​CRH Stimulation Test

​Metyrapone Stimulation Test

Dexamethasone Suppression Test: