HYPERTHYROIDISM,HYPOTHYROIDISM AND PARATHYROID

DISEASEPRESENTER: KINARA S KENYORU MED/18/11

FACILITATOR: DR. GARDNER

INTRODUCTION/ANATOMY•Thyroid gland located in the neck,ant to trachea btn cricoid cartilage and the suprasternal notch. (C5 and T1)•12-20g

THYROID GLAND DISORDERS Thyroid hormones:

T4: (Thyroxine) is made exclusively in thyroid glandT3: (Triiodothyronine) main source is peripheral deiodination:

Ratio of T4 to T3 ; 5:1 Potency of T4 to T3; 1:10 T4 is the most important source of T3 by peripheral tissue

deiodination “ T4 to T3 “T3 is the most important because more than 90% of

the thyroid hormones physiological effects are due to the binding of T3 to Thyroid receptors in peripheral tissues.

THYROID HORMONE EFFECTS CALORIGENESIS GROWTH & MATURATION RATE C.N.S. DEVELOPMENT & FUNCTION CHO, FAT & PROTEIN METABOLISM MUSCLE METABOLISM ELECTROLYTE BALANCE VITAMIN METABOLISM CARDIOVASCULAR SYSTEM HEMATOPOIETIC SYSTEM GASTROINTESTINAL SYSTEM ENDOCRINE SYSTEM PREGNANCY

HYPERTHYROIDISM

DEFINITION Excess thyroid hormone Most common forms;

diffuse toxic goitre(Graves dse) 80% toxic multinodular goiter 5% toxic adenoma – younger patients & in iodine-

deficient areas Thyroiditis (transient <8mo, symptomatic

treatment)

Epidemiology M<F 1:5 . Prevalence, which is approximately 1.3

percent, increases to 4 to 5 percent in older women.

Hyperthyroidism is also more common in smokers.

Graves' disease is seen most often in younger women, while toxic nodular goiter is more common in older women.

Etiology 1. Graves disease2. Multinodular goitre3. Solitary thyroid adenoma4. Thyroiditis

1. Sub acute (de Quervain’s)2. Post-partum

5. Iodide-induced1. Drugs (e.g. amiodarone)2. Radiographic contrast media3. Iodine prophylaxis programme

6. Extrathyroidal source of thyroid hormone1. Factitious thyrotoxicosis2. Struma ovarii

7. TSH-induced1. TSH-secreting pituitary adenoma2. Choriocarcinoma and hydatidiform mole (HCG)

8. Follicular carcinoma ± metastases

Pathogenesis ct’d In Graves dse, circulating autoantibodies against

thyrotropin receptor cause release of thyroid hormones and thyroglobulin, stimulate iodine uptake, protein synthesis and thyroid gland growth.

Ophthalmopathy is due to Ab reaction against the TSH receptor that results in activation of T cells against tissues in the retro orbital space that share antigenic epitopes with thyroid follicular cells.

THYROTOXICOSIS Symptoms:

Hyperactivity Irritability Dysphoria Heat intolerance &

sweating Palpitations Fatigue & weakness Weight loss with

increased appetite Diarrhea Polyuria Sexual dysfunction

Signs: Tachycardia Atrial fibrillation Tremor Goiter Warm, moist skin Muscle weakness,

myopathy Lid retraction or lag Gynecomastia * Exophthalmos * Pretibial myxedema

Clinical manifestationsSKIN  The skin is warm due to increased blood flow; it is also smooth

because of a decrease in the keratin layer. Palms are warm,moist and hyperemic and Plummer’s nails are seen.

Other changes include: Sweating-due to increased calorigenesis; often ass with heat

intolerance Onycholysis (loosening of the nails from the nail bed,)&

softening of the nails Hyperpigmentation; mediated by accelerated cortisol

metabolism Pruritus and hives, primarily in Graves' hyperthyroidism Vitiligo and alopecia areata Thinning of the hair Infiltrative dermopathy in patients with Graves'

hyperthyroidism.

Manifestations …..ctdEYES  Stare and lid lag occur in all patients(Due to

sympathetic overactivity) Only in Graves' disease have ophthalmopathy-

inflammation of the extraocular muscles and orbital fat and connective tissue; proptosis (exophthalmos), impairment of eye-muscle function, diplopia periorbital and conjunctival edema. gritty feeling or pain in their eyes Corneal ulceration optic neuropathy and blindness from severe

proptosis

Manifestations….ctdCARDIOVASCULAR increase in cardiac output, due both to incr

peripheral oxygen needs and incr cardiac contractility. Heart rate is increased, pulse pressure is widened, and peripheral vascular resistance is decreased

Systolic hypertension High- or normal-output CHF. Atrial fibrillation 10 to 20 % more common in elderly

patients Other abnormalities; mitral valve prolapse, mitral

regurgitation, and an increase in left ventricular mass index.

Manifestations…ctdMETABOLIC / ENDOCRINE Serum lipids  — low serum total and high-density

lipoprotein (HDL) cholesterol concentrations Hyperglycemia  — due to antagonism to the peripheral

action of insulin leading to impaired glucose tolerance in untreated patients

RESPIRATORY Dyspnea and dyspnea on exertion may occur due to:

a) Oxygen consumption and CO2 production increase.b) Respiratory muscle weakness.c) Tracheal obstruction from a large goiter.d) Hyperthyroidism may exacerbate underlying asthma.e) Pulmonary arterial systolic pressure is increased

Manifestations…ctdGASTROINTESTINAL Weight loss- increased metabolic rate (hypermetabolism),

and secondarily to increased gut motility and the associated hyperdefecation and malabsorption;

Hyperphagia. Anorexia/Vomiting/abdominal pain Dysphagia due to goiter Deranged LFTs,esp high serum ALP. SteatorrheaHEMATOLOGIC  Normochromic, normocytic anemia. High Serum ferritin concentrations Graves' hyperthyroidism may be ass with ITP and

pernicious anemia and antineutrophil antibodies. Hyperthyroidism may also be prothrombotic

Manifestations…ctdGENITOURINARY   Urinary frequency and nocturia/ Enuresis is common in

children oligomenorrhea,/anovulatory infertility /Amenorrhea gynecomastia, reduced libido, and ED in men.BONE increased porosity of cortical bone and reduced volume of

trabecular bone.

NEUROPSYCHIATRIC Behavioral and personality changes, such as psychosis,

agitation, depression, anxiety, restlessness, irritability, and emotional lability and Insomnia.

Investigations TFTS: -Primary: <TSH, >T3 & T4 -Secondary: Normal or > TSH, Radioiodide scan 99mTc 131I ELISA for anti –TSH receptor/TSI, antimicrosomal ab LFTS – elevated CBC- mild normocytic anemia, mild neutropenia, <

Platelets Biopsy- FNA cytology Ultrasound CT/MRI – head/ chest

TREATMENTIncludes: 1. Symptom relief2. Antithyroid pharmacotherapy3. Radioactive iodine 131 therapy4. Thyroidectomy

1. Symptoms relief Propranolol 40mg/6h PO for CVS and CNS symptoms Hydration of pt key before b blocker therapy CCBs may also be used for symptom relief. These therapies must be tapered and stopped once TFTs

are within normal ranges.

2. Antithyroid pharmacotherapyThionamidesmethimazole and propylthiouracil (PTU) inhibit thyroid hormone synthesis, and PTU also inhibits conversion of T4 to T3, faster onset of action.Employed for long term control in children,adolescents and pregnant women.In adult men and non-pregnant women,they control hyperthyroidism before definitive mgt with radioactive iodine or surgery.A major serious S/E is agranulocytosis. Propylthiouracil-5-10mg/kg/24 hours. Methimazole 0.25-1mg/kg/24 hoursTitrate the antithyroid drug dose every 4 weeks until thyroid functions normalize, Duration 12 – 18 months.

Pharmacotherapy…ctdSodium ipodate or iopanoic acid-lowers serum T 3 and T 4 levels and causes rapid improvement of hyperthyroidism; appropriate for acute management of severe hyperthyroidism that is not responding to conventional therapy

3. Radioactive iodine therapy. Radioiodine 131 (131I)Causes destruction of thyroid follicular cells Main complication is hypothyroidismIf the first dose does not control the hyperthyroidism within 6 to 12 months,then administer another dose.Contraindicated during pregnancy and breastfeeding due to risk of cretinism

4. Surgery Thyroidectomy

Exopthalmos: Corticosteroids. Tarsorrhaphy. Orbital decompression. Cardiac arrythmias: ß- blockers. In euthyroid state, cardioversion is done.

THYROID STORM Rare but life threatening sudden severe exarcerbation of

hyperthyroidism. Causes: Precipitated by stress or infection with either unrecognized thyrotoxicosis inadequately treated thyrotoxicosis Following subtotal thyroidectomy/radio active

iodine. Trauma. Pregnancy. Emotional stress.

Management Treatment started immediately with Propranolol 80mg/6hrs orally(dose of 1-5mg/6hrs given IV). Potassium iodide 60mg daily orally/ sodium iopodate 500mg daily orally.

Carbimazole 60-120mg daily

Dexamethasone 2mg/6hrs IV.

Fluid replacement. 150ml/hr

Antibiotics.

HYPOTHYROIDISM

Epidemiology Prevalence of overt hypothyroidism is 0.1-2%. The prevalence of subclinical hypothyroidism is 4-10%

percent of adults. F>M=5-8:1

Primary hypothyroidism   Autoimmune hypothyroidism: Hashimoto's

thyroiditis(TPO, thyroglobulin, TSH receptors), atrophic thyroiditis

  Iatrogenic: 131I treatment, subtotal or total thyroidectomy, external irradiation of neck for lymphoma or cancer

  Drugs: iodine excess (including iodine-containing contrast media and amiodarone), lithium, antithyroid drugs, p-aminosalicyclic acid, interferon- and other cytokines, aminoglutethimide

  Congenital hypothyroidism:1:3000-4000 absent or ectopic thyroid gland, dyshormonogenesis, TSH-R mutation.   

Iodine deficiency Infiltrative disorders: amyloidosis, sarcoidosis,

hemochromatosis, scleroderma, cystinosis, Riedel's thyroiditis

Etiology Secondary hypothyroidism Hypopituitarism: tumors, pituitary surgery or irradiation, infiltrative

disorders, Sheehan's syndrome, trauma, genetic forms of combined pituitary hormone deficiencies

Isolated TSH deficiency or inactivity Bexarotene treatment Hypothalamic disease: tumors, trauma, infiltrative

disorders, idiopathic

HYPOTHYROIDISM Symptoms:

Tiredness Cold intolerance Weakness Sexual dysfunction Dry skin Hair loss Difficulty

concentrating, forgetfulness

Heavy menses Constipation

Signs: Bradycardia Dry coarse skin Puffy face, hands and

feet Diffuse alopecia Peripheral edema Delayed tendon reflex

relaxation Carpal tunel

syndrome Serous cavity

effusions.

CLINICAL MANIFESTATIONSSkin   The skin is cool and pale in due to decreased blood flow. dry roughness of the skin . Sweating is decreased Skin discoloration may occur. A yellowish tinge may be present if the patient has carotenemia,

while hyperpigmentation may be seen if ass with primary adrenal failure.

Hair may be coarse, hair loss is common, and the nails become brittle.

Nonpitting edema (myxedema) occurs in from infiltration of the skin with glycosaminoglycans with associated water retention

Eyes  Periorbital edema. Graves' ophthalmopathy may persist when hypothyroidism develops

after treatment of Graves' hyperthyroidism.

Manifestations Hematologic  Increased risk of bleeding (hypothyroidism-associated

hypocoagulable state ) normochromic, normocytic hypoproliferative anemia Pernicious anemia in AI thyroiditis.(macrocytic anemia) iron deficiency anemia, secondary to menorrhagiaCardiovascular system   decrease in cardiac output mediated by reductions in heart rate

and contractility thus reduced exercise capacity and SOB during exercise.

Other abnormalities: Pericardial effusion/hypercholesterolemia/Hypertension

Manifestations Respiratory system   Fatigue, shortness of breath on exertion, rhinitis, and decreased exercise capacity

may result from impaired respiratory function Hypoventilation occurs because of respiratory muscle weakness and reduced

pulmonary responses to hypoxia and hypercapnia Sleep apnea mostly as a result of macroglossia.

Gastrointestinal disorders   Decreased gut motility results in constipation/marked ileus Decreased taste sensation. Gastric atrophy due to the presence of antiparietal cell antibodies. Pernicious anemia Celiac disease is four times more common in hypothyroid patients A modest weight gain due to decreased metabolic rate and accumulation of fluid Ascites is a rare finding.

Manifestations…ctd Reproductive abnormalities > (women) oligo- or amenorrhea

or hypermenorrhea-menorrhagia, decreased fertility. If pregnancy does occur, there is an increased likelihood for early abortion, Hyperprolactinemia may occur, and is occasionally sufficiently severe to cause amenorrhea or galactorrhea.

(men) Decreased libido, erectile dysfunction, and delayed ejaculation Neurological dysfunction — - Hashimoto's encephalopathy  - Myxedema coma - when severe hypothyroidism is complicated by trauma, infection, cold exposure, or inadvertent administration of hypnotics or should be suspected in comatose patients who are hypothermic, hypercapnic, and hyponatremic. Musculoskeletal symptoms — Joint pains, aches and stiffness

CRETINISM

Hypothyroidism dating from birth. Tyroxine is essential for growth and

development of brain during the first three years.

Earlier onset greater is the brain damage. Causes : - Congenital developmental

defects. - Radio iodine/surgery. - Post radiation. - Iodine deficiency. - Drug induced. - Hashimoto’s thyroiditis. - Recurrent hypothyroidism.

Investigations Relies heavily on lab tests. TFTs Primary: High TSH & low T4 Central (2˚ & 3˚): Low T4, TSH inappropriately normal for the low T4, coexisting hormone def. Lipid profiles – Fasting cholesterol and triglycerides may be

raised U/E/Cs < Na+ Muscle enzymes (CPK) – elevated CBC- anaemia (normocytic normochromic) CXR- Effusions CT head- sellar/ suprasellar region.

TreatmentGoals; Reverse clinical progression Correct metabolic derangements

Treatment STANDARD REPLACEMENT THERAPY   The treatment of choice is synthetic thyroxine (T4). Bioavailability 80% levothyroxine (T4) – 50-100µg/24h PO (1.6mcg/kg/day),

review at 12wks. Adjust 6wkly by clinical state and to normalise but not suppress TSH (keep TSH 0.35-5.5mIU/L) should be taken on an empty stomach, an hour before breakfast not with other meds that interfere with absorption, such as bile acid resins, proton pump inhibitors, calcium carbonate, and ferrous sulfate .

Older patients and pts with ischemic heart disease started at 25-50mcg levothyroxine daily

SPECIAL TREATMENT CONSIDERATIONSMyxedema coma

Reduced level of consciousness, seizures Hypotension/shock Hypothermia Hyponatremia

Usually in elderly hypothyroid pts. Usually precipitated by intercurrent illnesses that impairs

ventilation An Emergency with a high mortality rate Treatment: Lyotironine(T3) or T4, Hydrocortisone, external

warming, IV fluids

PARATHYROID DISEASE

INTRODUCTION

The 4 parathyroid glands are located posterior to the thyroid gland.

They produce parathyroid hormone (PTH), which is the primary regulator of calcium physiology.

PTH acts directly on bone,(induces calcium resorption), and on the kidney, where it stimulates calcium reabsorption and synthesis of 1,25-dihydroxyvitamin D [1,25(OH)2D], a hormone that stimulates gastrointestinal calcium absorption.

Calcium and vitamin D, inhibit PTH release and synthesis.

HYPERPARATHYROIDISM

Increased PTH secretion leading to hypercalcemia and hypophosphatemia.

Incidence 27 cases annually per 100,000 Prevalence HPT general population 0.1%-0.3% Prevalence women >60 years more than 1%

Causes

Primary hyperparathyroidism Solitary adenoma-80% Hyperplasia of all glands Parathyroid cancer Associated with hereditary syns MEN I (hyperparathyroidism, pituitary tumors,

pancreatic tumors) MEN II – hyperparathyroidism,

pheochromocytoma, medullary carcinoma of thyroid.

Causes…ctd

Secondary hyperparathyroidism Decreased vit D intake Chronic renal failureTertiary hyperparathyroidism Occurs after prolonged secondary

hyperparathyroidism

Clinical features and complicationsSymptom and signs: >1/2 asymptomatic Symptomatic: Stones, Bones, Groans, Thrones and

Psychiatric Overtones - weakness and fatigue, depression, bone pain, myalgias, decreased appetite, joint pain, cognitive impairement - decreased appetite, nausea and vomiting, constipation, polyuria, polydipsiaComplications Nephrocalcinosis, Recurrent nephrolithiasis, Urinary

obstruction, infection, loss of renal function Osteitis fibrosa cystica: > giant multinucleated osteoclasts in

scalloped areas on bone surface (Howship’s lacunae)

Parathyroid immunoassay PTH levels Serum calcium levels Serum phosphate - 1˚ (low), 2˚ (elevated) Alkaline phosphatase – elevated Bone densitometry decreased Radioisotope studies

Management SURGERY VERSUS MEDICAL MANAGEMENT   Symptomatic primary hyperparathyroidism -parathyroid

surgery. Parathyroidectomy is an effective therapy that : cures the disease, decreases the risk of kidney stones, improves bone mineral density/and may decrease fracture

risk and modestly improve some quality of life measurements.

Alternatives to surgeryPreventive measures  Avoid factors that can aggravate hypercalcemia, including thiazide

diuretic and lithium carbonate therapy, volume depletion, prolonged bed rest or inactivity, and a high calcium diet (>1000 mg/day).

Encourage physical activity to minimize bone resorption. Adequate hydration (at least 8 glasses of water per day) to

minimize the risk of nephrolithiasis. Maintain a moderate calcium intake (1000 mg/day).  A low calcium diet may lead to further increases in PTH secretion

and could aggravate bone disease Maintain moderate vitamin D intake (400 to 600 International Units

daily). Vitamin D deficiency stimulates PTH secretion and bone resorption and, therefore, is deleterious in patients with primary hyperparathyroidism.

Drug therapyBisphosphonates and estrogen plus progestininhibit bone resorption and can increase bone density and

possibly lower serum calcium concentrations in patients with hyperparathyroidism

Other medications,Eg calcimimetics or vitamin D analogues, suppress parathyroid hormone release or counteract the effects of hyperparathyroidism at the level of the PTH receptor.

HYPOPARATHYROIDISM

Hypoparathyroidism is a condition of parathyroid hormone deficiency

Primary hypoparathyroidism is a state of inadequate PTH activity

Secondary hypoparathyroidism is a physiologic state in which PTH levels are low in response to a primary process that causes hypercalcemia

EtiologyPrimary Hereditary/genetic: Idiopathic- isolated autoimmune Ass’ with other abnormalities- thymus, thyroid,

adrenal, ovary.Secondary Surgery(thyroidectomy and parathyroidectomy) Radiation Hemochromatosis

Clinical manifestations Paresthesias Muscle aches and cramps Twitching and spasms of muscles Fatigue or weakness Painful menstruation patchy hair loss Dry, coarse skin Brittle nails Anxiety and nervousness, headaches, depression,

mood swings, memory problems Hypocalcemia: Chvostek, trousseau sign

Diagnosis

Measurement of calcium, serum albumin (used to correct serum calcium levels) and PTH in blood

Treatment

Medical treatmentCalcium supplementsCalcitriolSurgery parathyroidectomyPatients at a higher risk of permanent primary

hypoparathyroidism