Hyperthyroidismclinical types:

diffuse toxic goitre( Graves’ disease ).

toxic nodular goitre.

toxic nodule.

rare causes.

Diffuse toxic goitreA diffuse vascular goitre usually occurs in younger women & is frequently associated with eye signs.

In 50% of primary thyrotoxicosis patients have a family history of autoimmune endocrine diseases.

The abnormality is due to abnormal thyroid-stimulating antibodies(TSH-RAb) that bind to TSH receptor sites & produce a disproportionate & prolonged

effects .

Toxic nodular goitreThe syndrome is that of secondary thyrotoxicosis, usually in the middle age or elderly who have a simple nodular goitre for a long time.

One or more nodules are overactive & sometimes the internodular tissue is overactive.

Toxic noduleA solitary overactive nodule, is autonomous & its hypertrophy & hyperplasia are not due to TSH-Rab.

Clinical features Thyrotoxicosis is eight times more common in women than in men.

It may occur at any age.

The most significant symptoms: loss of weight despite a good appetite.

a recent preference for cold. palpitations.

The most significant signs: tachycardia or cardiac arrhythmia.

agitation. exophthalmos.

goitre & bruit.

the goitre in primary thyrotoxicosis is diffuse & vascular, it may be large or small, firm or soft. The onset is abrupt.

In secondary thyrotoxicosis, the goitre is nodular. The onset is insidious & may present with cardiac failure or atrial fibrillation.

A fast heart rate ,which persists during sleep ,is characteristic.

Weakness of the proximal limb muscles is commonly found.

Pretibial myxoedema is a thickening of the skin by a mucin- like deposit always associated with true exophthalmos, past or present hyperthyroidism & high levels of TSH-Rab.

Diagnosis of thyrotoxicosisClinically.Thyroid function tests.T3 thyrotoxicosis is diagnosed by estimating the free T3.Thyroid scan.

TreatmentRest & sedation.Anti-thyroid drugs: carbimazole & propylthiouracil .

adrenergic blockers: propranolol & nadolol.Anti-thyroid drugs cannot cure a toxic nodule.Advantages: no surgery , no use of radioactive materials.Disadvantages: treatment is prolonged( from 6 months to 2 years ).

high failure rate ( 50 % ).Dose: 10 mg of carbimazole is given three or four times a day.

5 mg two or three times a day is given for 6 months – 2 years.Alternative technique: block & replacement treatment.

Side effects: agranulocytosis or aplastic anemia .

Surgery: in diffuse toxic goitre & toxic nodular goitre with overactive internodular tissue, surgery cures by reducing the mass of overactive tissue.

Advantages: removal of the goitre , rapid cure.

Disadvantages: recurrence occurs in 5% of cases.

thyroid insufficiency occurs in 20-45% of cases.

Radioiodine: it destroys thyroid cells so reduces the mass of functioning thyroid tissue to below a critical level .

Advantages: no surgery & no prolonged drug therapy.

Disadvantages: isotope facilities must be available.

thyroid insufficiency so indefinite follow up is essential

Choice of treatmentDiffuse toxic goitre:

Radioiodine if the patients over 45 years.

Surgery for the large goitre & anti-thyroid drugs or radioiodine for the small goitre if the patients under 45 years.

Toxic nodular goitre: should be treated surgically.

Toxic nodule: surgery radioiodine over the age of 45 years is an alternative.

Recurrent thyrotoxicosis after surgery: radioiodine is the treatment of choice.

Pregnancy: radioiodine is absolutely contraindicated because of the risk to the

fetus.

surgery in the second trimester.

careful administration of anti-thyroid drugs.

Children & adolescents treated with anti-thyroid drugs or total or near total thyroidectomy .

The thyrocardiac: beta blockers can assist rapid control of cardiac effects. radioiodine is the treatment of choice together with

anti-thyroid drugs.

Surgery for thyrotoxicosis:Preoperative preparation :

carbimazole 30-40 mg per day. Then reduce to 5 mg 8-hourly when euthyroid.

block & replace regime.

Alternative method: beta-blocking drugs: propranolol inhibits the peripheral

conversion of T4 to T3. propranolol 40 mg t.d.s. or nadolol 160 mg once daily.

Iodine may be given with carbimazole or beta- blocker for the 10 days before operation. it may reduce vascularity thereby improving safety.

Preoperative investigations

Thyroid function tests.

Indirect laryngoscopy.

Thyroid antibodies.

Serum calcium estimation.

An isotope scan.

Postoperative complications

Hemorrhage.Respiratory obstruction.

Recurrent laryngeal nerve paralysis( transient paralysis in 3%).Thyroid insufficiency(20-45%).Parathyroid insufficiency(less than 0.5%).Recurrent thyrotoxicosis( 5% ).Thyrotoxic crisis.Wound infection.Hypertrophic or keloid scar.Stitch granuloma.

Neoplasms of the thyroid

Classification: benign- follicular adenoma

malignant- primary: follicular epithelium: differentiated

follicular papillary

follicular epithelium:undifferentiated anaplastic

parafollicular cells: medullary lymphoid cells: lymphoma

secondary- metastatic : local infiltration.

Incidence of primary malignant tumors

Papillary ca. 60%Follicular ca. 20%Anaplastic ca. 10%Medullary ca. 5%Malignant lymphoma 5%

etiology

Irradiation of the thyroid under 5 years of age.

ret/PTC 3 oncogene.

endemic goitrous areas( TSH stimulation ).

Autoimmune thyroiditis (lymphocytic infiltration ) .

Clinical features

Incidence is about 3.7 per 100 000 of the population.

Sex ratio is three females to one male.

The overall mortality should be low.

Older patients have a worse prognosis.

Thyroid swelling is the most common presentation.

Enlarged cervical lymph nodes---- papillary ca.

Recurrent laryngeal nerve paralysis---- locally advanced disease.

Hard ,irregular & infiltrating---- anaplastic growth.

Pain referred to the ear is frequent in infiltrating growths.

Lateral aberrant thyroid---- occult ca.

Diagnosis of thyroid neoplasms

Clinical examination in anaplastic ca. DDx Riedel’s thyroiditis.

- solitary nodule in the young male is suspect.

Failure to take up radioiodine is characteristic.

Elevated thyroid antibody titres.

FNAC.

Incisional biopsy is not advised .

Papillary ca.

Histologically the tumour shows papillary projections & characteristic pale empty nuclei ( Orphan Annie-eyed nuclei ).Are very seldom encapsulated.Are multifocal in the same lobe.

Spread to the lymph nodes is common, but blood-borne metastases are unusual unless the tumour is extrathyroidal .

Follicular ca.Macroscopically encapsulated.Microscopically , there is invasion of the capsule & vessels in the capsular region.Lymph node involvement is much less common than in papillary ca.Blood-borne metastases are twice as common.Mortality rate is twice as high.Hurthle cell tumours are a variant of follicular neoplasm.

Prognosis

The prognosis depends on age, the presence of extrathyroidal spread or major capsular transgression( in follicular ca.) & the size of the tumour.On these basis the patients are separated into low & high risk groups.Low risk group have 2% 25 year mortality rate.High risk group have 46% 25 year mortality rate.

Surgical treatmentTotal thyroidectomy & lymph nodes removal if they are involved.

Additional measuresThyroxine in a dose of 0.1-0.2 mg daily to suppress endogenous TSH production after operation for differentiated thyroid ca.Radioiodine to detect & treat metastases.

Thyroglobulin measurement in the serum is of value in the follow up & detection of metastatic disease.

Thyroiditis

Chronic lymphocytic thyroiditis:

Is usually associated with raised titres of thyroid antibodies.

It commonly presents as a goitre.

It commonly associated with other thyroid disease, notably toxic goitre.

Clinical features:

Insidious onset & asymptomatic or so sudden & painful.

Mild hyperthyroidism initially, but hypothyroidism is inevitable.

The goitre is usually lobulated & may be diffuse or localised to one lobe.

Is most common in women at the menopause.

Papillary ca. & malignant lymphoma are occasional association.

Diagnosis:

Raised serum levels of thyroid antibodies are present in over 85% of cases.

Thyroid function tests vary with the thyroid status.

FNAC.

Treatment:

Full replacement dose of thyroxin for hypothyroidism & if the goitre is large or symptomatic.

Steroid therapy.

Thyroidectomy.

Granulomatous thyroiditis(subacute thyroiditis , de Quervain’s thyroiditis):Is due to virus infection.

Subacute presentation : pain in the neck, fever, malaise & irregular enlargement of one or both lobes.Raised ESR ; absent thyroid antibodies ; T4 is high normal.

Acute presentation : the goitre very painful & tender ; symptoms of hyperthyroidism.

Diagnosis: FNAC; radioactive iodine uptake;

rapid response to prednisone.Treatment : prednisone 10-20 mg daily for 7 days .

Riedel’s thyroiditis:Thyroid tissue is replaced by cellular fibrous tissue.

It may occur in association with retroperitoneal & mediastinal fibrosis.

The goitre is very hard & fixed.

Biopsy can differentiate the condition from anaplastic ca.

Treatment is with high dose steroid & thyroxin replacement.

Parathyroid glandsMost individuals will have four glands.

10% of the population will have one or more supernumerary glands.

Function of the parathyroid glands: it secretes PTH which controls the level of calcium in the blood & extracellular fluid.

PTH stimulates calcium reabsorption in the kidney, inhibits phosphate reabsorption & stimulates the synthesis of vitamin D.

In bone, PTH stimulates resorption by increasing osteoclast activity & stimulates osteoblast activity.

Primary hyperparathyroidismA sporadic or familial disorder associated with hypercalcemia, elevated or inappropriately raised PTH levels & parathyroid gland enlargement.

Sporadic primary hyperparathyroidism: is more common in women than men incidence 1% of adults.

Familial hyperparathyroidism: occurs as part of the following genetic conditions. Multiple endocrine neoplasia type 1(MEN-1): the clinical features includes :

hyperparathyroidism; benign pituitary adenomas; multiple pancreatico-duodenal neuroendocrine tumours, functioning

gastrinoma, insulinoma, glucanoma.

Multiple endocrine neoplasia type 2(MEN-2):

MEN-2A hyperparathyroidism in 25% of patients; adrenal phaeochromocytoma ; medullary ca. of thyroid.

MEN-2B hyperparathyroidism rare; mucosal neuroma of the lips & tongue ; Marfanoid habitus .

Familial isolated hyperparathyroidism: this is a rare autosomal dominant disorder ; it has an associated risk of parathyroid ca.(20%).

Pathology:Sporadic primary hyperparathyroidism: adenoma( 85%), hyperplasia(14%) ,

& carcinoma(1%).Familial disease: multiple gland enlargement.

Clinical & biochemical features:Asymptomatic in mild hyperparathyroidism & in 30% is diagnosed as an incidental finding.Severe hyperparathyroidism: Bone disease( von Recklinghausen’s disease ).

bone pain, osteopenia, osteitis fibrosa cystica & path-

ological fractures. Renal disorders: nephrocalcinosis & urinary calculi.

GIT: peptic ulcer, pancreatitis & constipation muscle weakness & fatigue.

soft tissue calcification.

hypertension.

hyperuricemia & lipid abnormalities.

Biochemical diagnosis: hypercalcemia & increased PTH levels.

hypophosphatemia & high plasma chloride levels.

bone- specific alkaline phosphatase may be elevated.

Differential diagnosis

Causes of hypercalcaemia :Primary hyperparathyroidism.Tertiary hyperparathyroidism.Hypercalcaemia of malignancy.Myeloma.Thiazide diuretics.Vitamin D excess.Hyperthyroidism.Immobilization.Sarcoidosis.Familial hypocalciuric hypercalcaemia.Phaeochromocytoma .

Treatment

Non-surgical treatment of severe hypercalcaemia: rehydration with normal saline(4-6 litres in the first 24 hours).

intravenous bisphosphonate therapy( pamidronate 60-90mg i.v. over 4 hours.

Surgical treatment of primary hyperparathyroidism: surgery is curative.

indications: urinary tract calculi. markedly reduced bone density.

serum calcium more than 2.85mmol/l.Preoperative localization studies:

neck ultrasound. technetium-99m isotope scan.

single photon emission CT.

Secondary hyperparathyroidism

Causes :Chronic renal failure.Rickets.Osteomalacia.Malabsorption.Pseudohypoparathyroidism.

Clinical features of renal hyperparathyroidism:Bone pain, pruritus, muscle weakness, renal osteodystrophy & soft tissue calcification.

Serum calcium levels are low or normalPhosphate levels are high.Marked elevation of PTH.

Treatment

Dietary phosphate restriction.

Calcium & vitamin D supplementation.

Surgery is indicated in symptomatic secondary hyperparathyroidism & when there is an excessive rise in calcium &/or serum PTH.

Parathyroid carcinoma

The presentation is with symptomatic , severe hypercalcemia & very high PTH levels.

It is responsible for 1% of cases of hyperparathyroidism.

Surgery include excision of the tumour mass, ipsilateral thyroid lobectomy & node dissection if involved.

Hypoparathyroidism

Congenital causes: DiGeorge’s syndrome.

Autoimmune polyglandular syndrome.

Acquired causes: postoperative(thyroidectomy)

haemochromatosis,Wilson’s

disease.

Symptoms & signs

Symptoms of hypocalcaemia: perioral numbness & tingling, paraesthesiae of the fingers & toes.In severe cases, ventricular arrhythmia, laryngeal spasm & grand mal fits.

Chvostek’s sign.Trousseau’s sign.ECG changes : prolonged QT intervals & QRS complex changes.

Treatment In severe cases(calcium less than 1.95mmol/l) : 10 ml of 10% calcium gluconate solution by slow i.v. injection.Magnesium supplements.Milk & 1 alpha vitamin D can be used.