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Tiredness
STUDENT: Serena Kay
MEDICAL SCIENCE 110
ASSIGNMENT ONE
LECTURER: Dr Sarath Jayawardana
STUDENT: Serena Kay
STUDENT NO: 2001 . 32M
a.
- Five common causes of tiredness:
- Hypothyroidism
- Anaemia: iron-deficiency anaemia; pernicious anaemia; haemorrhagic anaemia; haemolytic anaemia; thalassemia; aplastic anaemia
- Insomnia: sleep-onset insomnia; sleep-maintenance insomnia
- Depression
- Chronic Fatigue Syndrome / Fibromyalgia
b.
HYPOTHYROIDISM
- A condition characterised by decreased activity of the thyroid gland with decreased production of thyroid hormones.
- Severity ranges from mild and undiagnosed sub-clinical hypothyroidism to potentially fatal myxoedema in adults, and cretinism in infants
Thyroid hormones are involved in the regulation of:
- Oxygen use and basal metabolic rate – increases basal metabolic rate by stimulating the use of oxygen in the production of ATP by increasing the production of enzymes that drive the Na+/K+ pumps. As cells utilize more oxygen, heat is emitted leading to a rise in body temperature = calorigenic effect. Therefore plays a role in maintenance of body temperature.
- Cellular metabolism: stimulates enzymes for protein synthesis; increases utilization of glucose for ATP production; increases lipolysis
- Growth and development
Aetiology:
- Primary hypothyroidism = disease of the thyroid gland (about 95% of cases)
- Secondary hypothyroidism = due to anterior pituitary dysfunction.
- Surgical resection of all or part of the thyroid
- Dysfunction of the thyroid gland (eg. due to radiation; Hashimoto’s thyroiditis, an autoimmune disease – most common cause in USA)
- Poor conversion of thyroxin (T4) to triiodothyronine (T3), the metabolically active form of thyroid hormone
- Severe iodine deficiency (leads to goitre and/or hypothyroidism)
- Over-dosage of anti-thyroid medications used in the treatment of hyperthyroidism (eg. radio-iodine)
- Disease of the hypothalamus ® low TRH (thyrotropin-releasing hormone)
- Disease of the anterior pituitary (eg. tumour) / hypopituitarism
- Reduced secretion of TSH (thyroid-stimulating hormone) by anterior pituitary gland
- Reduced effect of TSH
- Dopamine, dopamine agonists (eg. levodopa) and phenothiazines (anti-psychotics, tranquillizers) can cause secondary hypothyroidism
- Nutrient deficiencies and effects of anti-nutrients as described in biochemical pathways below (Source: Tabrizian):
- Vitamin & mineral deficiencies: Vit A, Vit B2, Vit C, Vit E, selenium, vanadium
- Lack of proteins:
- tyrosine which binds to iodine in thyroid gland to from T1, T2,T3,T4
- for formation of TBG (thyroxine-binding globulin) – transports T3 & T4 in blood
- hormonal deficiencies (progesterone) – required for conversion of T4 to T3
- enzyme deficiency (peroxidase which catalyses 2I- ® I2) – generally due to genetic abnormality
Hypothalamus
¯
TRH (thyrotropin-releasing hormone)
¯
Anterior pituitary
¯ Vit A, Vit E
TSH
¯
Thyroid
¯ peroxidase, tyrosine, iodide, selenium, vanadium, Vit B2, Vit C
T1 (monoiodotyrosine) and T2 (diiodotyrosine)
¯
T4 = (T2 + T2)
¯ (peripheral iodination), selenium, progesterone
T3 = (T2 + T1)
Anti-nutrients:
- high/toxic levels copper – blocks Vit E, tyrosine, Vit C, activity of T3 within the mitochondria and increases back-conversion of T3 to T4.
- Consumption of > 30 mg cobolt/day
- Excessive consumption of fluoride (as it blocks iodine)
- Excessive consumption of goitrogenous foods (eg. uncooked cabbage, soya beans, peanuts, mustard)
- Some types of isothiocynates (phytochemicals found in cruciferous vegetables) can block iodine
Copper sources: eg.
- xenoestrogens and oestrogen dominance block detoxification of copper by the liver;
- low levels of molybdenum, zinc, manganese in soils and food increases absorption of copper;
- increased cadmium in soil and foods increases copper retention;
- water (copper pipes);
- many foods;
- anti-fungal sprays used on vegetables
Clinical Features:
More commonly seen in females of middle age. Female : Male ratio » 5:1
Early signs and symptoms:
- Reduced basal metabolic rate
- Low body temperature, intolerance to cold, cold hands & feet
- Weight gain and constipation due to sluggish digestive system
- Fatigue, tiredness
- Weakness
- Dry, thickened skin
- Coarseness and dryness of scalp hair, alopecia
- Thin, brittle nails
- Arthralgias and/or myalgias
- Increased allergies (as hypothyroidism results in decreased levels of cortisol binding globulin - CBG)
- Headache
- Menorrhagia
- Reduced libido
Myxoedema: (includes the above signs and symptoms, plus):
- Oedema / lymphoedema due to sluggish circulation, increase in capillary permeability and accumulation of interstitial hydrophilic mucopolysaccharides
(ie. swelling of hands, face, tongue, feet and periorbital tissue, pitting oedema, cardiac enlargement).
- Dry, scaly, carotenemic (yellowing due to high levels of carotenoids in blood) skin and little perspiration
- Muscular weakness
- Somnolence
- Slurred speech, hoarseness, reduced auditory acuity
- Reduced sense of taste and smell
- Bradycardia (as thyroid hormones enhance some activities of norepinephrine and epinephrine by up-regulating beta-receptors – therefore, low thyroid hormone levels reduces heart rate and forcefulness of contractions).
- Low thyroxine leads to increased circulatory lipids (as thyroid hormones increase lipolysis and enhance cholesterol excretion in bile) and atherosclerosis.
- Amenorrhea or menorrhagia
- Mental & physical lethargy
- Depression
- Pallor
- Pituitary enlargement due to hyperplasia
- May lead to coma and death
Diagnostic Tests / Investigations:
- Primary hypothyroidism: TSH elevated // T3, T4 reduced
- Pituitary dysfunction: TSH reduced or normal // T3, T4 elevated
- In Hashimoto’s thyroiditis (autoimmune disease) – antibodies against thyroperoxidase & thyroglobulin
- Low to low-normal FT4 (Free Thyroxine immunoassay)
- (Note: serum T3 is not an accurate test for hypothyroidism)
- Sub-Clinical hypothyroidism: Basal body temperature test: take morning axillary temperature (£ 36.5°C is considered abnormal)
Other possible abnormalities:
- Raised serum cholesterol (particularly LDL cholesterol and lipoprotein (a); liver enzymes; creatine kinase; serum prolactin
- Hyponatraemia – due to reduced reabsorption of Na+ in the renal tubules
- Hypoglycaemia
- Anaemia
- Low level of transthyretrin = prealbumin: (thyroid hormone is transported in blood and brain by transthyretrin) – more sensitive than testing TSH, T4, T3 (source: Life Extension)
- In myxoedema: the contraction and relaxation phases of the tendon reflex may be prolonged.
Complications:
- Most commonly: cardiac problems (atherosclerosis, cardiac enlargement, congestive heart failure)
- Increased susceptibility to infection
- Megacolon due to long-standing constipation
- Depression and psychoses with paranoid delusions
- Infertility (rare)
- TSH-secreting tumours
- Myxoedema coma (with hypothermia, hypoventilation, hypoxia, hyponatraemia, hypercapnia, hypotension, convulsions)
Principles of Management:
Conventional Allopathic Treatment:
Oral synthetic thyroxine (beginning with low dose and increasing it until TSH levels are normal) – generally required for life, with ongoing analysis of hormone levels.
Dietary & Other Supplementation:
- Natural thyroid glandular concentrates
- If toxic levels of copper present – detoxification and supplementation with nutrients that may involved in the blockade of the biochemical pathway described above.
- Nutrient supplementation: where deficiency states are present. Possible deficiencies include: iodine, tyrosine, Vit A, Vit E, Vit B2 (riboflavin), Vit B3 (niacin), Vit B6 (pyridoxine), Vit C, selenium, vanadium, zinc and progesterone.
- Capsaicin (found in cayenne pepper, chillis) & Ginseng stimulates the thyroid
- Kelp (with high iodine content) stimulates the thyroid
- Moderate levels of sunlight stimulates the thyroid
Prognosis:
The condition responds well to treatment but relapses may occur if treatment ceases.
If the disease progresses to myxoedema coma, then mortality is high.
References:
- M. Swash, Hutchison’s Clinical Methods, 20th Edition, W.B. Saunders Co. Ltd, London, 1995
- G.J. Tortora & S.R. Grabowski, Principles of Anatomy and Physiology, 9th Edition, John Wiley & Sons, 2000
- Mosby’s Medical, Nursing & Allied Health Dictionary, Fifth edition, Harcourt Health
Sciences Co, 1998
- I. Tabrizian, Nutritional Medicine: Fact and Fiction, NRS Publishing, Perth, 2002
- P. Macfarlane, R. Reid, R. Callander, Pathology Illustrated, Fifth edition, Churchill Livingstone, Edinburgh, 2000
- M. Murray, J. Pizzorno, Encyclopaedia of Natural Medicine, 2nd edition, Little, Brown & Co., London, 1998
- L. Tierney, S. McPhee, M. Papadakis, Current Medical Diagnosis and Treatment, 39th Edition, McGraw-Hill, New York, 2000
- M. Mulvihill, M. Zelman, P. Holdaway, E. Tompary, J. Turchany, Human Diseases – A Systemic Approach, 5th Edition, Prentice Hall, New Jersey, 2001
- The Life Extension Foundation, Disease Prevention and Treatment, 3rd Edition, Life Extension Media, Florida, 2000
- Hyperhealth
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