Thyroid& Parathyroid

ENDOCRINE Thyroid & Parathyroid Dr. Hiwa Omer Ahmed Assistant Professor in grneral Surgery

Thyroid

Embryology • The thyroid gland develops from the median bud of the pharynx (the thyroglossal duct) which passes from the foramen caecum at the base of the tongue to the isthmus of the thyroid.

• Parafollicular cells (C-cells) are derived from the neural crest and reach the thyroid via the ultimobranchial body • The ultimobranchial body which arises from a diverticulum of the fourth pharyngeal pouch.

Surgical anatomy The normal gland weighs 20— 25 g. The functioning unit is the lobule supplied by a single arteriole and consisting of 24—40 follicles which are lined by cuboidal epithelium. The resting follicle contains colloid in which thyroglobulin is stored.

• Some residual thyroid tissue along the course of the thyrogbossal tract is not uncommon, and may be lingual, cervical or intrathoracic. Very rarely the whole gland is ectopic.

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Lingual thyroid at the foramen caecum and it may represent the only thyroid tissue present. It may cause dysphagia, impairment of speech, respiratory obstruction or hemorrhage. It is best treated by full replacement with thyroxine when it should get smaller, but excision or ablation with radioiodine is sometimes necessary.

Thyroglossalcyst The common situations, in order of frequency, are beneath the hyoid, in the region of the thyroid cartilage, and above the hyoid bone. Such a cyst occupies the midline, except in the region of the thyroid cartilage, where the thyroglossal tract is pushed to one side, usually to the left. It is to be remembered that the swelling moves upwards on protrusion of the tongue as well as on swallowing because of the attachment of the tract to the foramen caecum. A thyroglossal cyst should be excised because infection is inevitable

Thyroglossal fistula • Thyroglossal flstula is never congenital: Characteristically the fistula is drawn upwards on protrusion of the tongue. • discharges mucus, and is the seat of recurrent attacks of inflammation. • Treatment. Surgery

Physiology • • • • •

Steps of thyroid hormone formation: •trapping of inorganic iodide from the blood; •oxidation of iodide to iodine; •binding of iodine with tyrosine to form iodotyrosines; •coupling of mono-iodotyrosines and di-iodotyrosines to form 13 and T4 • when hormones are required the complex is resorbed into the cell and thyroglobulin broken down; T3 and T4 are liberated and enter the blood where they are bound to serum proteins: albumin and thyroxine binding globulin (TBG) and prealbumin (TBPA). A small amount of hormone remains free in the serum

INVESTIGATION OF THYROID • T3 • T4 • TSH • Thyroid autoantibodies , against thyroid peroxidase and thyroglobulin are useful in determining the cause of thyroid dysfunction and swellings. Titres of greater than 1:100 are considered significant

Isotope scan • radiolabelled iodine (123I) or technetium-99m (99”m’Tc, • This test is inappropriate for distinguishing benign from malignant lesions because the majority (80 per cent) of cold swellings is benign and some (5 per cent) functioning or warm swellings will be malignant. Its principal value is in the toxic patient with a nodule or nodularity of the thyroid

HYPOTHYROIDISM

Cretinism (foetal or infantile hypothyroidism) • Hypothyroidism occurs in I in 4000 live births 1.Sporadic is due to complete or near complete failure of thyroid development • the parents and other children may be perfectly normal. 2.In endemic areas, goitrous cretinism is common, and is due to maternal and foetal iodine deficiency.

Immediate diagnosis and treatment with thyroxine within a few days of birth are essential if physical and mental development are to be normal, Women under treatment with antithyroid drugs may give birth to a hypothyroid infant.

Adult hypothyroidism • •

The term myxoedema should be reserved for severe thyroid failure and not applied to the much commoner mild thyroid deficiency. The signs of thyroid deficiency are:

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bradycardia; cold extremities; dry skin and hair; periorbital puffiness; hoarse voice; bradykinesis —slow movements; delayed relaxation phase of ankle jerks

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The symptoms are: • tiredness; • mental lethargy; • cold intolerance; • weight gain; • constipation; • menstrual disturbance; • carpal tunnel syndrome. Comparison of the facial appearance with a previous photo-graph may be helpful.

The signs •

The facial appearance) is typical, and there isoften 1. supraclavicular puffiness, 2. a malar flush and a yellow tinge to the skin.

Myxoedema coma occurs in neglected cases and carries a high mortality; the body temperature is low and the patient must be warmed slowly:1 g of intravenous hydrocortisone (in divided doses) should be given daily, and intravenous tri-iodothyronine in slowly increasing doses

The classic symptoms • Severe progression of disease can result in cardiovascular symptoms, including hypertension, • pericardial effusion, • bradycardia, and • pleural effusions. • Abdominal distention with bowel edema and constipation is a sign of severe hypothyroidism. • Anemia may occur in 12% of cases.

Aetiology • In many underdeveloped countries, lack of sufficient iodine intake explains a large proportion of hypothyroid conditions. • In more developed countries, most cases of adult hypothyroidism are caused by • Hashimoto's thyroiditis, • radioactive iodine therapy • surgical removal. • antiarrhythmic drug amiodarone.

Other rarer causes • of hypothyroidism include 1.inherited defects in thyroid hormone synthesis, 2.congenital aberrant thyroid development can occur in children, including thyroid agenesis and thyroid hypoplasia. 3.Central nervous system abnormalities resulting in either anterior pituitary gland disease or hypothalamic disorders 4.Finally, peripheral tissue resistance to the action of thyroid hormone, possibly through an altered receptor mechanism, has been described

Dx. & Rx. • • • •

Thyroid function tests show low T4 and T3 levels high TSH High serum titres of antithyroid antibodies Treatment Oral thyroxine (0.10—0.20 mg) as a single daily dose is curative. • Caution is required in the elderly or those with cardiac disease and the replacement dose is then commenced at 0.05 mg daily and cautiously increased. • If a rapid response is required, tri-iodothyronine (20 mg three times a day) may be used

THYROIDITIS

Acute Suppurative Thyroiditis • Acute suppurative thyroiditis is extremely rare and usually the result of a severe pyogenic infection of the upper airway. The process results in severe localized pain and is generally unilateral. Abscess drainage followed by the administration of antibiotics is effective, and long-term deleterious effects on thyroid function rarely result.

Hashimoto's Thyroiditis This leads to alterations in thyroid cell function that impair T3 and T4 production. These cellular reactions ultimately result in infiltration of lymphocytes and resultant fibrosis, which decreases the number and efficiency of individual follicles. Ultimately, a clinical hypothyroid state can occur in patients with persistent TSHblocking antibodies

Subacute Thyroiditis • • • • • • • •

Subacute thyroiditis occurs predominantly in females (2:1) The mean age of patients is in the 40s in most series. The exact cause is not known, Patients have diffuse swelling in the cervical area and a sudden increase in pain. Approximately two thirds of patients demonstrate fever, weight loss, and severe fatigue. Fine-needle aspiration (FNA) can be diagnostic if it demonstrates giant cells of an epithelioid foreign body type, which characterizes the lesion. Treatment with corticosteroids or nonsteroidal anti-inflammatory drugs is effective in relieving symptoms. However, the disease process generally continues, unaffected by these medications.

Riedel's thyroiditis (struma) rare characterized by a firm thyroid secondary to a chronic inflammatory process involving the entire gland. Symptoms of severe discomfort can occur and are due to extension into the trachea, esophagus, and laryngeal nerve. As a result, patients may have impending airway obstruction or dysphagia. Unilateral involvement of symptoms may suggest a malignancy and lead to surgical intervention. • •

Treatment with thyroid hormone replacement is effective. Immediate tracheal or esophageal obstruction may require a surgical approach to relieve symptoms. Only the constricting portion of the thyroid is removed.

Hyperthyroidism

Hyperthyroidism • increased thyroid secretion result in a predictable hypermetabolic state. • primary alterations within the gland (Graves' disease, toxic nodular goiter, toxic thyroid adenoma) or central nervous system disorders and increased TSH-produced stimulation of the thyroid. Most hyperthyroid states occur because of primary malfunction. • Even more unusual hyperthyroid states can result from mismanaged exogenous thyroid ingestion, molar pregnancy with increased release of human chorionic gonadotropin, and unusually, thyroid malignancy with overproduction of thyroid hormone.

Graves' Disease • Grave's disease is the most common cause of hyperthyroidism (diffuse toxic goiter). • Women between the ages of 20 and 40 years are most commonly affected. • The hyperthyroidism in Grave's disease is caused by stimulatory autoantibodies to TSH-R.

Clinical Features A patient with classic Graves' disease usually has triad 1.a visibly enlarged neck mass consistent with a goiter that may demonstrate an audible bruit secondary to increased vascular flow. 2.Clinical thyrotoxicosis 3 exophthalmos Hair loss, myxedema, gynecomastia, and splenomegaly can accompany the clinical findings. Tracheal compression

Clinical features The symptoms are: • • • • • •

• tiredness; • emotional lability; •heat intolerance; • weight loss; • excessive appetite; •palpitations.

The signs of thyrotoxicosis are: • tachycardia; • hot, moist palms; • exophthalmos; •lid lag/retraction; •agitation; •thyroid goitre and bruit.

The ocular consequences • proptosis, supraorbital and infraorbital swelling, and conjunctival swelling and edema, can be severe. • The ophthalmopathy is thought to be due to stimulation of the overexpressed TSH-R in the retro-orbital tissues of Grave's patients

WYNE CRITERIA

Dx 1.Thyroid Function test • T3 • T4 • TSH 2.US 3.CT & MRI ?

Rx 1.Medical a.betablockers b. antithyroid c.iodine 2. Radioisotope I131 3. Surgery; indicated – – – – –

obstructive goiter have a fear of radioactivit are noncompliant have had an adverse effect with antithyroid drugs pregnant patients or those with a suspicious nodule.

PO complications • • • •

Haematoma RLN Paralysis i3% mostly temp for 3 monthes Hypothyroidism <0.5% HypoparathyroidismRates of postprocedure hypocalcemia are about 5%, and it resolves in 80% of cases in about 12 months • Thyrotoxic crisis (storm) is an acute exacerbation of hyperthyroidism

• Superir LN palsy • The external branch can run closely adherent to the superior thyroid artery, and care must be exercised during dissection in this area. Injury to the branch causes voice changes, huskiness, poor volume voice fatigue, and inability to sing at higher ranges • RLN Palsy A wide spectrum of injuries to the voice or swallowing mechanisms, or to both, can occur because of the mixed fibers contained within the nerve.Temporary or permanent voice change can result and is extremely distressing to the patient.

The hypermetabolic state • of hyperthyroidism is clinically manifested as sweating, weight loss, heat intolerance, and thirst. Cardiovascular stress can be demonstrated by high-output cardiac failure, congestive heart failure with peripheral edema, and arrhythmias such as ventricular tachycardia or atrial fibrillation. Gastrointestinal signs may include diarrhea and electrolyte wasting. The menstrual cycle can be altered to the point of amenorrhea. Psychiatric signs may include altered sleep patterns, emotional mood swings, fatigue, excitability, and agitation.

LECTURE 2

SOLITARY THYROID NODULE

WORKUP AND DIAGNOSIS OF A SOLITARY THYROID NODULE • Management and the ultimate decision to proceed to surgical intervention after detection of a solitary nodule depend on the findings of a cost-effective workup and the prognosis . • The majority of patients with a solitary thyroid nodule will have a benign lesion; however, thyroid cancer is a definite possibility in all patients. Deciding between conservative management or surgical therapy relies on careful analysis of the clinical findings, assessment of images, and interventional diagnostic methods

Clinical Features • Increasing numbers of thyroid nodules are being found incidentally, possibly because of the increasing availability and sophistication of imaging techniques. The frequency of palpable and nonpalpable thyroid nodules rises with age. Solitary palpable nodules are about four times more prevalent in women than in men. Several different disorders can cause a thyroid nodule. It is important to exclude thyroid cancer in any clinical setting. Rapid growth and signs of possible invasion, such as pain or hoarseness, are most suggestive, but not conclusive of malignancy

On physical examination • it is important to include thorough palpation of the thyroid, as well as the anterior and posterior cervical triangles. Determining the size and consistency of the nodule is important. Multiple nodules or diffuse nodularity is associated with a more benign diagnosis. A firm solitary nodule, particularly in older men, is suggestive of a malignant diagnosis.

Diagnosis • The workup of a patient with a solitary nodule begins with a careful history and physical examination. Clinical groups with the highest risk for malignancy in a thyroid nodule are children, males, adults younger than 30 or older than 60 years, and those exposed to radiation therapy, especially during childhood. A careful history includes any exposure to radiation, either through occupational sources or through irradiation of the head or neck, particularly in childhood. Additionally, a thorough history of specific endocrine disorders, including medullary carcinoma, MEN 2, or papillary thyroid cancer (PTC), or a history of familial polyposis, including Gardner's syndrome, is warranted.

Radioisotope Scanning • •

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Whereas ultrasound allows anatomic evaluation, radionuclide scans allow assessment of thyroid function. Technetium pertechnetate (99mTc) is taken up rapidly by the normal activity of follicular cells. It is trapped by follicular cells, but not organified. 99mTc has a short half-life and low radiation dose. Its rapid absorption allows quick evaluation of increased uptake (socalled hot) or hypofunctioning (so-called cold) areas of the thyroid. Because screening with 99mTc shows uptake in the salivary glands and major vascular structures, interpretation of thyroid pathology requires a higher level of expertise. Malignancy has been shown to occur in 15% to 20% of cold nodules and, additionally, in 5% to 9% of nodules with uptake that is warm or hot, thus mandating a continued aggressive approach to clinically suspicious nodules, even if they are not cold.

Tumors & MALIGNANCY

Benign tumours • Follicular adenomas present as clinically solitary nodules and the distinction between a follicular carcinoma and an adenoma can only be made by histological examination: in the adenoma there is no invasion of the capsule or of pericapsular blood vessels. Treatment is, therefore, by wide excision —preferably a lobectomy. The remaining thyroid tissue is normal so that prolonged follow up is unnecessary. It is doubtful whether there is such an entity as a papillaryadenoma and all papillary tumours should be considered asmalignant even if encapsulated

Malignant • The vast majority of primary growths is carcinomas . Dunhill classified them histologically as differentiated and undifferentiated: and the differentiated carcinomas are now subdivided into follicular and papillary. Secondary growths are rare but bloodborne metastases occur Blood borne metastases more usually occur from primary carcinomas of breast, colon and kidney and from melanomas.

Aetiology • Differentiated thyroid carcinoma, particularly papillary, frequently follows accidental irradiation of the thyroid in childhood7. The incidence of follicular carcinoma is high in endemic goitrous areas, possibly owing to TSH stimulation. Malignant lymphomas can present in a patient known to have autoimmune thyroiditis, so that the lymphocytic infiltration in the autoimmune process may be an aetiological factor. Indeed, itis likely that all lymphomas of the thyroid arise in glands affected by such thyroiditis

Clinical features •

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The annual incidence is about 3.7 per 100 000 of the popu-lation and the sex ratio is three females to one male. The mortality should only be of the order of 2—3 per cent. The commonest presentingsymptom is a thyroid swelling (Fig. 44.36) and a 5-year history is far from uncommon indifferentiated growths. Enlarged cervical lymph nodes may be the presentation of papillary carcinoma. Recurrent laryngeal nerve paralysis may be a presenting feature of locally advanced disease. Anaplastic growths are usually hard, irregular and infiltrating. A differentiated carcinoma may be suspiciously firm and irregular, but is often indistinguishable from a benign swelling. Smallpapillary tumours may be impalpable (occult carcinoma) — even when lymphatic metastases are present (so-called lateral aberrant thyroid). Pain, often referred to the ear, is frequent in infiltrating growths.

Diagnosis of thyroid neoplasms • Diagnosis is obvious on clinical examination in most cases of anaplastic carcinoma, although Riedel’s thyroiditis (see later) is indistinguishable. The localised forms of granulomatous thyroiditis and lymphadenoid goitre may simulate carcinoma. It is not always easy to exclude a carcinoma in a multinodular goitre, and solitary nodules, particularly in the young male, are always suspect. Failure to take up radio-iodine is characteristic of almost all thyroid carcinomas [only very rarely will differentiated carcinoma (primary or secondary) take up 1231in the presence of normal thyroid tissue], but occurs also in degenerating nodules and all forms of thyroiditis. Thyroid antibody titres are often raised in carcinoma.

The role of FNAC • in preoperative diagnosis has already been discussed. No diagnostic test is absolutely certain, and exploration with excision in the form of lobec-tomy is essential when indoubt. Incisional biopsy may cause seeding of cells and local recurrence, and is most inadvisable ina resectable carcinoma. In an anaplastic and obviously irremovable carcinoma, however, incisional or needle biopsy is justified.

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papillary follicular carcinoma Hurthle cell tumours Undifferentiated (ana plastic) carcinoma Lymphoma

• 2ndaries

Surgical treatment • There is continuing disagreement on the most appropriate operation for differentiated thyroid carcinoma. The con-servative approach advocates lobectomy with isthmusectomy in most patients with total thyroidectomy reserved for specific indications (viz, those with bilateral disease or judged to be in a high-risk category). The more radical approach advocates routine total thyroidectomy often as a staged procedure depending on the pathological findings of the initial lobectomy

Additional measures • Thyroxine. It is standard practice to prescribe thyroxine in a dose of 0.1—0.2 mg daily, to suppress endogenous TSH production, for all patients after operation for differentiated thyroid carcinoma on the basis that some tumours are TSH dependent. Suppression of the TSH level should be con-firmed by measurement. Failure of suppression to a level of <0.1 i.t/litre may indicate an inadequate dose of thyroxine or more usually that the patient is noncompliant.

Radioiodine • If metastases take up radioiodine they may be detected by scanning and may be treated with large doses of radioiodine. For effective scanning, all thyroid tissue must have been ablated by either surgery or preliminary radioiodine and the patient must be hypothyroid to improve uptake

Medullary Carcinoma • MCT accounts for 5% to 10% of thyroid cancers. The malignancy involves the parafollicular cell, or C cell, derived from the neural crest. MCT is associated with the secretion of a biologic marker, calcitonin. Excess secretion of calcitonin has been demonstrated to be an effective marker for the presence of MCT. Calcitonin excess is not associated with hypocalcemia. • Medullary carcinoma can occur in a sporadic form or as part of MEN 2A or 2B. The MEN syndromes are covered in more detail in Chapter 40 . MEN 2A usually has a more favorable long-term outcome than MEN 2B or sporadic MCT does

Clinical Features •

A patient with a sporadic medullary carcinoma may have either of two manifestations: a palpable mass for which a diagnosis can be made with FNA or the finding of an elevated calcitonin level. In sporadic MCT, the tumors are usually single and have no familial predisposition. The presence of both a mass and an elevated calcitonin level is virtually diagnostic of MCT, whereas the finding of an elevated basal calcitonin level in the absence of a thyroid mass might require further workup, including repeat basal calcitonin measurement and a calcium-stimulated or gastrin-stimulated test. Family members of patients with MEN 2 ideally are screened for the RET proto-oncogene. The workup of these patients includes a detailed and in-depth family history to inquire about the characteristics of MEN 2 in the patient and family members ( Fig. 36-19 ). If MCT is suspected, serum calcium and urinary catecholamines must be determined to evaluate for hyperparathyroidism and possible pheochromocytoma

Treatment • • The surgical approach to sporadic medullary carcinoma involves at least total thyroidectomy with or without central lymph node dissection. Total thyroidectomy allows complete removal of the gland and a search for multicentricity. In sporadic MCT, the lesion is generally contained within one lobe, whereas in MEN 2, the malignancy involves the upper halves of both lobes. Dissection of the central lymph node compartment allows appropriate staging of this process. Any palpable lymph nodes in lateral areas require a modified radical neck dissection.

Parathyroid

Parathyroid glands Anatomy •

The parathyroid glands, four in number, are small, oval in shape, commonly about 0.5 cm in size, soft, mobile, yellowish brown in colour and arranged in pairs — most often closely applied to the thyroid gland, either within or closely applied to its capsule. The upper pair is more constant in position than the lower: 80 per cent are found on the posterolateral aspect of the thyroid, immediately above the termination of the inferior thyroid artery, close to the cricothyroid articulation. Most of the remaining 20 per cent are posterolateral to the upper pole of the thyroid lobe. The lower pair is more variable in position: 40 per cent are found at the lower pole of the thyroid and 40 per cent are within the thymic tongue (Fig. 45.1). The remaining 20 per cent are variable in site, most often some distance lateral to the thyroid, and less often in the mediastinal thymus a few centimeters below the sternal notch or, very occasionally, ectopicallv situated near the carotid sheath, sometimes as high as the carotid bifurcation.

Physiology •

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The chief cells of the parathyroids produce parathormone, the hormone being released directly into the bloodstream. The circulating level of parathormone can be measured by radioimmuno-assay, which is sufficiently reliable to distinguish between high and low levels. Facilities for obtaining the estimation are widely available. Parathormone: •stimulates osteoclastic activity, thereby increasing bone resorption by mobilizing calcium and phosphate; •increases the reabsorption of calcium by the renal tubules, thus reducing the urinary excretion of calcium; •augments the absorption of calcium from the gut; •reduces the renal tubular reabsorption of phosphate, thus promoting phosphaturia. Parathyroid hormone is an 84 amino acid peptide which has a short half-life before degradation into amino-terminal and carboxy-terminal fragments, with the aminoterminal fragment having biological activity. The amino-terminal fragment retains biological activity with a half-life of minutes and the carboxy-terminal fragment a halflife of hours. Available assays measure either the intact hormone, the amino- or carboxy-terminal or ‘mid-portion’ fragments. Calcitonin(Copp) is secreted by the parafollicular cells of the thyroid (thyrocalcitonin). It lowers the serum calcium and affects calcium storage in bones; quite the opposite action of parathormone.

Parathyroid hormone-related protein (PTH-rP) • is a hypercalcaemic factor with similar bioactivity to that of parathyroid hormone. Since its isolation from cancer cell lines and carcinoma of the breast, strong evidence has emerged that it is an important hormonal mediator of cancerassociated hypercalcaemia in patients with solid tumours. Plasma PTH-rP 1—86 concentrations may be measured by a two-site immunoradiometric assay.

Hypoparathyroidism •

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Parathyroid tetany, due to hypocalcaemia, is a rare com-plication of subtotal thyroidectomy (less than 1 per cent) but a more common complication of total thyroidectomy. At these operations, some of the parathyroid glands may be removed or have their blood supply temporarily embar-rassed. It may also occur after surgery to the parathyroids themselves. Symptoms usually appear on the second or third postoperative day, and are temporary. Milder forms of hypoparathyroidism have been described in the follow-up of thyroidectomised patients. Permanent hypoparathyroidism, most commonly encountered following radical thyroidectomy for cancer, requires constant supervision and treatment. Tetany in the newborn may occur within the first few days of life in the child born of a mother with undiagnosed hypoparathyroidism. Spontaneous hypoparathyroidism is an unusual form of autoimmune disease.

Clinical features •

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The first symptoms are tingling and numbness in the face, fingers and toes. In extreme cases, cramps in the hands and feet are very painful; the extended fingers are flexed at their metacarpophalangeal joints, with the thumb strongly adducted (Fig. 45.3); the toes are plantar-flexed and the ankle joints extended — the so-called carpopedal spasm. Spasm of the muscles of respiration results in not only pain and stridor, but also dread of suffocation. In infancy, the symptoms of tetany may be mistaken for epilepsy, although there is no loss of consciousness. Latent tetany may be demonstrated by the following. • Chvostek’s sign. Tapping over the branches of the facial nerve at the angle of the jaw will produce twitching at the corner of the mouth, the ala of the nose and the eyelids. • Trousseau’s sign. A sphygmomanometer cuff applied to the arm and inflated above the systolic blood pressure for not more than 2 minutes will produce carpal spasm.

Treatment • In acute cases the symptoms may be relieved speedily by the slow intravenous injection of 10—20 ml of a 10 per cent solution of calcium gluconate. This may be repeated until the patient’s circulating calcium level has been stabilised. For longer-term management, the absorption of calcium is enhanced by oral administration of the most active metabolite of vitamin D — 1,25dihydroxycholecalciferol [1,25(OH)2D3]. Its major action is on the gut, promoting active absorption of calcium and phosphorus, raising calcium levels to normal within a week. Magnesium supplements may occasionally be needed. Serum calcium levels must be estimated daily and the dosage adjusted as appropriate. •

Hyperparathyroidism • Hyperparathyroidism is a more common condition than had been previously believed • •The symptomatic presentation may vary but the increased use of auto analysers has resulted in ‘asymptomatic’ hypercalcaemic patients being the largest group. • A corrected serum calcium concentration above the upper limit of normal and a simultaneous elevation of serum parathyroid hormone level are mandatory for the diagnosis. • •

• Surgery should only be performed by an experienced parathyroid surgeon. • Long-term follow-up is essential as there is a significant increase in risk of death from cardiovascular disease. Hyperparathyroidism is associated with an increased secretion of parathyroid hormone. This occurs in: • •Primary hyperparathyroidism, which is an un stimulated and inappropriately high parathyroid hormone secretion for the concentration of plasma ionised calcium, and is due to adenoma or hyperplasia, and very rarely carcinoma.

• A single adenoma is the commonest finding (multiple in 6 per cent). The whole gland is usually considerably enlarged, darker in colour, firmer and more vascular than normal; in some a rim of normal parathyroid tissue may be seen surrounding the adenoma. The histological appearances are the same as in hyperplasia, with a predominance of chief and water-clear cells. Carcinoma of the parathyroids is extremely rare, less than 1 per cent. It tends to invade locally and recur after operation. Blood-borne metastases have been described.

others • Secondary hyperparathyroidism is associated with chronic renal failure or malabsorption syndromes. The stimulus for the hyperplasia is chronic hypocalcaemia. All four glands are involved. • •Tertiary hyperparathyroidism is a further stage in the development of reactive hyperplasia where autonomy occurs as the parathyroids no longer respond to physiological stimuli

Cinical features •

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Hyperparathyroidism, rarely found in the first decade of life, is commoner in women than men, and most commonly found between the ages of 20 and 60 years. The clinical features vary enormously, even when the biochemical changes are similar. Asymptomatic cases The most common presentation is the detection of unsuspected and asymptomatic hypercalcaemia by routine biochemical screening. Bones, stones, abdominal groans and psychic moans’ Only 50 per cent of patients suffer from any of these. Nonspecific symptoms Nonspecific symptoms include muscle weakness, thirst, polyuria, anorexia and weight loss — a challenge to the astute clinician!

Bones Stones Moans & Groans Bone disease • There may be generalised decalcification of the skeleton, as in osteitis fibrosa cystica (von Recklinghausen’s disease), single or multiple cysts, or pseudotumours of any bone. The latter are particularly common in the jaw bones. Early radiological changes first appear in the skull and in the phalanges (Fig. 45.4),with loss of density and subperiosteal erosions. Many patients presenting with vague pains in the bones and joints are mistakenly diagnosed as rheumatic

Renal stones • Hyperparathyroidism must be considered in every patient presenting with renal tract stone or nephrocalcinosis (Fig. 45.5),and even in those cases of renal colic where no stone can be demonstrated

Dyspeptic cases • Patients with nausea, vomiting and anorexia are relatively common. Peptic ulcer and pancreatitis are not infrequently found in association with hyperparathyroidism, but the relationship is not as yet fully understood.

Psychiatric cases • Psychiatric cases are not uncommon; women, complaining of tiredness, listlessness and with obvious personality changes, are often wrongly labelled ‘neurotic’ or ‘menopausal’. Patients have been admitted to mental institutions because of irrational behaviour.

Acute hyperparathyroidism •

This diagnosis is difficult and only too often made after death. Nausea and abdominal pain is followed by severe vomiting, dehydration, oliguria and finally coma. The serum calcium is very high. • Treatment is urgent after rehydration, which is vital. Biphosphonates (disodium etidronate and pamidronate) are specific inhibitors of bone resorption. • They are highly effective given parenterally and may also be used in the preoperative, short-term medical management of severe hypercalcaemia in primary hyperparathyroidism.

Finding • Corneal calcification • Less common is band keratopathy in which a transverse band of calcification forms across the front of the cornea, and conjunctival • Hypertension may be present in up to 50 per cent of cases. • There may be electrocardiographic changes with a shortened QT interval, primarily by an effect on the length of the S—T segment.

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A parathyroid adenoma is very seldom palpable in the neck. The diagnosis is confirmed with the following biochemical findings: •elevation of serum calcium (upper limit of normal 2.6 mmol/litre). corrected serum calcium (mmol/litre) = measured serum Ca (mmol/litre) + (40 —A) x 0.02, where A = serum albumin (g/litre); •diminution of serum phosphorus (lower limit of normal 0.8 mmol/litre); •increased excretion of calcium in the urine (upper limit of normal 62 mmol per 24 hours for females, 75 mmol for males); •elevation of the serum alkaline phosphatase in cases with bone disease; •elevation of serum parathormone concentration.

The simplest localisation test • • •

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is an ultrasonic scan but results vary according to the skill and experience of the investigator. • Computerised tomography is of most value in localising a lesion in the mediastinum rather than the neck. •Thallium—technetium isotope subtraction imaging may locate up to 90 per cent of parathyroid adenomas before surgery (Fig. 45.6).Like ultrasonography, subtraction scintigraphy is more accurate the larger the adenoma, and is inaccurate in parathyroid hyperplasia. •MRI is improving rapidly with some centres reporting up to 64 per cent detection prospectively. A low signal is obtained from the parathyroid glands on a T1-weighted image while a T2-weighted image appears in early studies to produce good contrast resolution from the surrounding tissues. •Invasive techniques such as selective angiography and selective venous sampling may be helpful in locating an abnormally situated gland after a failed initial exploration.

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Differential diagnosis Other causes of hypercalcaemia must be remembered and excluded. They are: •secondary cancer in bone (breast, prostate, bronchus, kidney and thyroid); •carcinoma with endocrine secretion (bronchus, kidney and ovary); •multiple myeloma; •vitamin D intoxication; •sarcoidosis; •thyrotoxicosis; •immobilisation; •medication: thiazide diuretics, lithium. The differential diagnosis presents no problem if the parathormone level is estimated. In none of the above-mentioned conditions will parathormone be detectable in the blood.

Treatment • The only corrective treatment is surgical removal of the overactive gland or glands. In symptomatic patients, the indications for operation are clearcut • Preoperative treatment is not usually necessary except in acute cases, when rapid correction of dehydration and electrolyte imbalance is necessary, with a careful daily check on the serum calcium

auto transplantation • Parathyroid tissue can be successfully auto transplanted into the arm, a useful technique to avoid repeated potentially difficult explorations of the neck. The indications are tertiary hyperparathyroidism in patients undergoing chronic renal dialysis, and recurrent hyperparathyroidism. The technique is to excise all of the parathyroid tissue from the neck and to implant eight 1-mm3 fragments into a pocket in the forearm muscle mass, marking the site with nonabsorbable sutures.

Parathyroid carcinoma • Parathyroid carcinoma is a rare condition to be considered when a high serum calcium is associated with a palpable lump in the neck. At operation it has a characteristic grey—white colour and is adherent because of local invasion of adjacent soft tissue. The best results are obtained by early recognition, avoiding rupture of the tumour capsule, and aggressive surgical management including ipsilateral thyroid lobectomy. Surgical clips should be used to outline the tumour bed for postoperative radiotherapy. • Multiple endocrine neoplasia syndrome — APUD cells • Always consider that a patient with hyperparathyroidism may also have multiple endocrine adenomas.