Endocrine pathology Flashcards
Discuss the hypothalamic-pituitary axis.
Responsible for the control of many functions.
Consists of:
-
Hypothalamus:
- Gonadotropin Releasing Hormone (GnRH)
- Corticotropin Releasing Hormone (CRH)
- Thyrotropin Releasing Hormone (TRH)
- Prolactin Inhibitory Factor (PIF)*
- Growth Hormone Releasing Hormone (GHRH)
Hypothalamus secretes its hormones into the hypothalamic-pituitary portal system IOT control the release of anterior pituitary hormones.
-
Anterior Pituitary: (FLAT PEG = FLAT: Tropic hormones; PEG: direct hormones)
- Follical Stimulating Hormone (FSH)
- Leutinising Hormone (LH)
- AdrenoCorticoTrophic Hormone (ACTH)
- Thyroid Stimulating Hormone (TSH)
- Prolactin
- Endorphins
- Growth Hormone (GH)
-
Posterior Pituitary:
- AntiDiuretic Hormone
- Oxytocin
The posterior pituitary hormones are produced by neurons in the hypothalamus but they are transported along the axons of these neurons to, and stored within, the posterior pituitary before they are released into the blood.
What is SIADH?
The Syndrome of Inappropriate secretion of ADH (SIADH) results in inappropiately high levels of ADH being secreted into the blood.
This can occur via two mechanisms:
- Posterior pituitary tumor -> excessive ADH secretion
- Lung Ca -> secretion of ADH-like substance that mimics ADH
Normal function of ADH is facilitate the incorporation of aquaporins into the collecting ducts of the kidneys to allow H2O to be resorbed along the high conc’n grad’t.
In SIADH, excessive H2O reabsorption -> :
- oliguria
- hyponatraemia -> neural dysfunction -> altered LOC, coma etc
- oedema
What is Diabetes Insipidus?
Inability to concentrate urine due to dysfunction of ADH.
Can be caused by:
- Neurogenic causes -> inability to produce ADH eg pituitary tumors, stroke, head injury
- Nephrogenic causes -> inability to repsond to ADH
Leads to:
- Dehydration
- Hypotension
- Electrolyte imbalances
Give examples of syndromes that arise from anterior pituitary dysfunction.
- Giagantism/acromegaly - over production of GH
- Cushing disease - over production of ACTH
- Hyperprolactinaemia - over production of prolactin
Discuss the control of thyroid levels in the body.
- Thyrotropin Releasing Hormone (TRH) is released by the hypothalamus into the hypothalamic-pituitary portal system
- TRH stimulates thyrotrophs in the anterior pituitary to release Thyroid Stimulating Hormone (TSH) into the blood stream
- TSH binds to G-protein coupled receptors on thyroid follicle cells -> inc’d cAMP -> thyroid growth and hormone release
- Follicular cells release T3 (thyroxine) and T4 (triiodothyronine) into the blood -> binds to proteins (eg thyroxine binding protein)
- T3 10x more active than T4 -> binds to thyroid hormone receptors -> inc’d metabolic rate.
List the disorders that are associated with hyperthyroidism.
Primary
- Grave’s Disease
- Toxic multi-nodular goitre
- Toxic adenoma
- Iodine-induced hyperthyroidism
- Neonatal thyrotoxicosis (maternal Grave’s)
Secondary
- TSH secreting pituitary adenoma (rare)
Not associated with hyperthyroidism (ie thyroid gland is not hyperfunctioning)
- De Quervians (painful) thyroiditis
- Subacute lymphocytic (painless) thyroiditis
- Factitious thyrotoxicosis (exogenous thyroxine)
What is cretinism?
Severe hypothyroidism in the foetus, neonate or young child, usually due to severe iodine deficiency.
Leads to abnormal development of skeletal system and brain:
- Short stature
- Mental retardation
- Coarse facial features
- Protruding tongue
What is myxedema?
Severe hypothyroidism in an older child or adult.
Results in slowing of physical and mental activity:
- Listless
- Cold intolerant
- Overweight
- Reduced sympathetic activity: ->
- Constipation
- Red’d sweating
- Cool pale skin
- Decreased cardiac output -> SOB and red’d exercise tolerance
Compare and contrast Hashimoto’s Thyroiditis and Grave’s Disease.
- Both result from a breakdown in self-tolerance to thyroid auto-antigens.
- Hashimoto’s -> immune destruction of thyrocytes -> reduction in production of T3 and T4 -> hypothyroidism
- **Grave’s **-> immune complex binding to TSH receptors -> inappropriate production of T3 and T4 -> thyrotoxicosis
Describe the functions of parathyroid hormone.
- Increases the renal tubular reabsorption of Ca++;
- Increases the activation of Vitamin D in the kidneys;
- Increases urinary phosphate excretion; and
- Augments GI Ca++ absorption.
Discuss the common abnormalities of parathyroidhormone function.
-
Hyperparathyroidism:
-
Primary:
- Parathyroid adenoma (85-95%);
- Parathyroid hyperplasia (5-10%); and
- Parathyroid Ca (1%).
-
Secondary:
- Chronic hypocalcaemia -> compensatory hyperparathyroidism
- Usually the result of renal failiure or Ca def’y
-
Primary:
-
Hypoparathyroidism:
- Usually the result of accidental surgical resection during thyroidectomy.
- Genetic causes
What are the physical manifestations of hypercalcaemia?
- Cardiovascular
- Hypertension
- Arrhythmias - prolonged QTc
- Catecholamine resistance
- Urinary
- Renal calculi formation
- Polyuria/polydipsia
- Renal failure
- Neurologic
- Weakness
- Psychosis
- Seizures
- Coma
- GI
- Nausea
- Vomitting
- Constipation
- Pancreatitis
What are the clinical manifestations of Cushing Syndrome?
- Glucose impairment
- Skin
- Bones
- Immune suppression
- Sexual hormone dysfunction
- Hypertension
- Weight gain - truncal obesity, buffalo hump
- Muscle wasting - “stick limbs”, weakness
Discuss the effects of thyroxine on the body.
Both T3 and T4 are active at thyroxine receptors in cells - T3 approx 10x more active than T4:
- Proteins - increases protein synthesis
- Lipids - increases lypolysis
- **Glucose **- Increases effects of beta-adrenergic receptors on glucose metabolism -> inc’d glucose synthesis via gluconeogenesis and glycogenolysis
- **Cardiac **- Increases effects of beta-adrenergic receptors on cardiac muscle -> increase HR and contractility, inc’d sys BP and dec’d dias BP (bounding pulse)
- **Neurologic **- Reduction in serotinergic activity
- Development - Profound effects on neonatal development of bones, myelin and other neuron components and the lungs
Compare Type 1 and Type 2 DM.
Onset:
-
T1DM -
- childhood and adolescence
- associated with normal wt or wt loss preceding diagnosis
- circulating antibodies to islet cells
- diabetic ketoacidosis w/out insulin therapy
-
T2DM
- adulthood (adolescence inc’g)
- 80% obese
- Inc’d insulin (early), normal or moderate dec’d insulin (late)
- No islet cell antibodies
- Non-ketoic hyperosmolar coma mosre common
Genetics:
-
T1DM
- Major linkage to MHC I & II genes
-
T2DM
- No HLA linkage
- Linked to obesity-related genes
Pathogenesis:
-
T1DM
- Dysfunction in T cells -> breakdown in self-tolerance to islet cell auto-antigens
-
T2DM
- insulin resistance in peripheries. Failure of compensation by beta-cells
- Multiple obesity-related factors -> insulin resistance
Pathology:
-
T1DM
- Insulitits - (inflam’y infiltration of T-cells and macrohages)
- Beta-cell depletion, islet atrophy
- T2DM
- No insulitis, amyloid deposition in islets
- Mild beta-cell depletion
